Podcasts about Transduction

Prof. Kevin Ellis and Dr. Zenna Tavares talk about making AI smarter, like humans. They want AI to learn from just a little bit of information by actively trying things out, not just by looking at tons of data.They discuss two main ways AI can "think": one way is like following specific rules or steps (like a computer program), and the other is more intuitive, like guessing based on patterns (like modern AI often does). They found combining both methods works well for solving complex puzzles like ARC.A key idea is "compositionality" - building big ideas from small ones, like LEGOs. This is powerful but can also be overwhelming. Another important idea is "abstraction" - understanding things simply, without getting lost in details, and knowing there are different levels of understanding.Ultimately, they believe the best AI will need to explore, experiment, and build models of the world, much like humans do when learning something new.SPONSOR MESSAGES:***Tufa AI Labs is a brand new research lab in Zurich started by Benjamin Crouzier focussed on o-series style reasoning and AGI. They are hiring a Chief Engineer and ML engineers. Events in Zurich. Goto https://tufalabs.ai/***TRANSCRIPT:https://www.dropbox.com/scl/fi/3ngggvhb3tnemw879er5y/BASIS.pdf?rlkey=lr2zbj3317mex1q5l0c2rsk0h&dl=0 Zenna Tavares:http://www.zenna.org/Kevin Ellis:https://www.cs.cornell.edu/~ellisk/TOC:1. Compositionality and Learning Foundations [00:00:00] 1.1 Compositional Search and Learning Challenges [00:03:55] 1.2 Bayesian Learning and World Models [00:12:05] 1.3 Programming Languages and Compositionality Trade-offs [00:15:35] 1.4 Inductive vs Transductive Approaches in AI Systems2. Neural-Symbolic Program Synthesis [00:27:20] 2.1 Integration of LLMs with Traditional Programming and Meta-Programming [00:30:43] 2.2 Wake-Sleep Learning and DreamCoder Architecture [00:38:26] 2.3 Program Synthesis from Interactions and Hidden State Inference [00:41:36] 2.4 Abstraction Mechanisms and Resource Rationality [00:48:38] 2.5 Inductive Biases and Causal Abstraction in AI Systems3. Abstract Reasoning Systems [00:52:10] 3.1 Abstract Concepts and Grid-Based Transformations in ARC [00:56:08] 3.2 Induction vs Transduction Approaches in Abstract Reasoning [00:59:12] 3.3 ARC Limitations and Interactive Learning Extensions [01:06:30] 3.4 Wake-Sleep Program Learning and Hybrid Approaches [01:11:37] 3.5 Project MARA and Future Research DirectionsREFS:[00:00:25] DreamCoder, Kevin Ellis et al.https://arxiv.org/abs/2006.08381[00:01:10] Mind Your Step, Ryan Liu et al.https://arxiv.org/abs/2410.21333[00:06:05] Bayesian inference, Griffiths, T. L., Kemp, C., & Tenenbaum, J. B.https://psycnet.apa.org/record/2008-06911-003[00:13:00] Induction and Transduction, Wen-Ding Li, Zenna Tavares, Yewen Pu, Kevin Ellishttps://arxiv.org/abs/2411.02272[00:23:15] Neurosymbolic AI, Garcez, Artur d'Avila et al.https://arxiv.org/abs/2012.05876[00:33:50] Induction and Transduction (II), Wen-Ding Li, Kevin Ellis et al.https://arxiv.org/abs/2411.02272[00:38:35] ARC, François Chollethttps://arxiv.org/abs/1911.01547[00:39:20] Causal Reactive Programs, Ria Das, Joshua B. Tenenbaum, Armando Solar-Lezama, Zenna Tavareshttp://www.zenna.org/publications/autumn2022.pdf[00:42:50] MuZero, Julian Schrittwieser et al.http://arxiv.org/pdf/1911.08265[00:43:20] VisualPredicator, Yichao Lianghttps://arxiv.org/abs/2410.23156[00:48:55] Bayesian models of cognition, Joshua B. Tenenbaumhttps://mitpress.mit.edu/9780262049412/bayesian-models-of-cognition/[00:49:30] The Bitter Lesson, Rich Suttonhttp://www.incompleteideas.net/IncIdeas/BitterLesson.html[01:06:35] Program induction, Kevin Ellis, Wen-Ding Lihttps://arxiv.org/pdf/2411.02272[01:06:50] DreamCoder (II), Kevin Ellis et al.https://arxiv.org/abs/2006.08381[01:11:55] Project MARA, Zenna Tavares, Kevin Ellishttps://www.basis.ai/blog/mara/

Mohamed Osman joins to discuss MindsAI's highest scoring entry to the ARC challenge 2024 and the paradigm of test-time fine-tuning. They explore how the team, now part of Tufa Labs in Zurich, achieved state-of-the-art results using a combination of pre-training techniques, a unique meta-learning strategy, and an ensemble voting mechanism. Mohamed emphasizes the importance of raw data input and flexibility of the network.SPONSOR MESSAGES:***Tufa AI Labs is a brand new research lab in Zurich started by Benjamin Crouzier focussed on o-series style reasoning and AGI. They are hiring a Chief Engineer and ML engineers. Events in Zurich. Goto https://tufalabs.ai/***TRANSCRIPT + REFS:https://www.dropbox.com/scl/fi/jeavyqidsjzjgjgd7ns7h/MoFInal.pdf?rlkey=cjjmo7rgtenxrr3b46nk6yq2e&dl=0Mohamed Osman (Tufa Labs)https://x.com/MohamedOsmanMLJack Cole (Tufa Labs)https://x.com/MindsAI_JackHow and why deep learning for ARC paper:https://github.com/MohamedOsman1998/deep-learning-for-arc/blob/main/deep_learning_for_arc.pdfTOC:1. Abstract Reasoning Foundations [00:00:00] 1.1 Test-Time Fine-Tuning and ARC Challenge Overview [00:10:20] 1.2 Neural Networks vs Programmatic Approaches to Reasoning [00:13:23] 1.3 Code-Based Learning and Meta-Model Architecture [00:20:26] 1.4 Technical Implementation with Long T5 Model2. ARC Solution Architectures [00:24:10] 2.1 Test-Time Tuning and Voting Methods for ARC Solutions [00:27:54] 2.2 Model Generalization and Function Generation Challenges [00:32:53] 2.3 Input Representation and VLM Limitations [00:36:21] 2.4 Architecture Innovation and Cross-Modal Integration [00:40:05] 2.5 Future of ARC Challenge and Program Synthesis Approaches3. Advanced Systems Integration [00:43:00] 3.1 DreamCoder Evolution and LLM Integration [00:50:07] 3.2 MindsAI Team Progress and Acquisition by Tufa Labs [00:54:15] 3.3 ARC v2 Development and Performance Scaling [00:58:22] 3.4 Intelligence Benchmarks and Transformer Limitations [01:01:50] 3.5 Neural Architecture Optimization and Processing DistributionREFS:[00:01:32] Original ARC challenge paper, François Chollethttps://arxiv.org/abs/1911.01547[00:06:55] DreamCoder, Kevin Ellis et al.https://arxiv.org/abs/2006.08381[00:12:50] Deep Learning with Python, François Chollethttps://www.amazon.com/Deep-Learning-Python-Francois-Chollet/dp/1617294438[00:13:35] Deep Learning with Python, François Chollethttps://www.amazon.com/Deep-Learning-Python-Francois-Chollet/dp/1617294438[00:13:35] Influence of pretraining data for reasoning, Laura Ruishttps://arxiv.org/abs/2411.12580[00:17:50] Latent Program Networks, Clement Bonnethttps://arxiv.org/html/2411.08706v1[00:20:50] T5, Colin Raffel et al.https://arxiv.org/abs/1910.10683[00:30:30] Combining Induction and Transduction for Abstract Reasoning, Wen-Ding Li, Kevin Ellis et al.https://arxiv.org/abs/2411.02272[00:34:15] Six finger problem, Chen et al.https://openaccess.thecvf.com/content/CVPR2024/papers/Chen_SpatialVLM_Endowing_Vision-Language_Models_with_Spatial_Reasoning_Capabilities_CVPR_2024_paper.pdf[00:38:15] DeepSeek-R1-Distill-Llama, DeepSeek AIhttps://huggingface.co/deepseek-ai/DeepSeek-R1-Distill-Llama-70B[00:40:10] ARC Prize 2024 Technical Report, François Chollet et al.https://arxiv.org/html/2412.04604v2[00:45:20] LLM-Guided Compositional Program Synthesis, Wen-Ding Li and Kevin Ellishttps://arxiv.org/html/2503.15540[00:54:25] Abstraction and Reasoning Corpus, François Chollethttps://github.com/fchollet/ARC-AGI[00:57:10] O3 breakthrough on ARC-AGI, OpenAIhttps://arcprize.org/[00:59:35] ConceptARC Benchmark, Arseny Moskvichev, Melanie Mitchellhttps://arxiv.org/abs/2305.07141[01:02:05] Mixtape: Breaking the Softmax Bottleneck Efficiently, Yang, Zhilin and Dai, Zihang and Salakhutdinov, Ruslan and Cohen, William W.http://papers.neurips.cc/paper/9723-mixtape-breaking-the-softmax-bottleneck-efficiently.pdf

Clement Bonnet discusses his novel approach to the ARC (Abstraction and Reasoning Corpus) challenge. Unlike approaches that rely on fine-tuning LLMs or generating samples at inference time, Clement's method encodes input-output pairs into a latent space, optimizes this representation with a search algorithm, and decodes outputs for new inputs. This end-to-end architecture uses a VAE loss, including reconstruction and prior losses. SPONSOR MESSAGES:***CentML offers competitive pricing for GenAI model deployment, with flexible options to suit a wide range of models, from small to large-scale deployments. Check out their super fast DeepSeek R1 hosting!https://centml.ai/pricing/Tufa AI Labs is a brand new research lab in Zurich started by Benjamin Crouzier focussed on o-series style reasoning and AGI. They are hiring a Chief Engineer and ML engineers. Events in Zurich. Goto https://tufalabs.ai/***TRANSCRIPT + RESEARCH OVERVIEW:https://www.dropbox.com/scl/fi/j7m0gaz1126y594gswtma/CLEMMLST.pdf?rlkey=y5qvwq2er5nchbcibm07rcfpq&dl=0Clem and Matthew-https://www.linkedin.com/in/clement-bonnet16/https://github.com/clement-bonnethttps://mvmacfarlane.github.io/TOC1. LPN Fundamentals [00:00:00] 1.1 Introduction to ARC Benchmark and LPN Overview [00:05:05] 1.2 Neural Networks' Challenges with ARC and Program Synthesis [00:06:55] 1.3 Induction vs Transduction in Machine Learning2. LPN Architecture and Latent Space [00:11:50] 2.1 LPN Architecture and Latent Space Implementation [00:16:25] 2.2 LPN Latent Space Encoding and VAE Architecture [00:20:25] 2.3 Gradient-Based Search Training Strategy [00:23:39] 2.4 LPN Model Architecture and Implementation Details3. Implementation and Scaling [00:27:34] 3.1 Training Data Generation and re-ARC Framework [00:31:28] 3.2 Limitations of Latent Space and Multi-Thread Search [00:34:43] 3.3 Program Composition and Computational Graph Architecture4. Advanced Concepts and Future Directions [00:45:09] 4.1 AI Creativity and Program Synthesis Approaches [00:49:47] 4.2 Scaling and Interpretability in Latent Space ModelsREFS[00:00:05] ARC benchmark, Chollethttps://arxiv.org/abs/2412.04604[00:02:10] Latent Program Spaces, Bonnet, Macfarlanehttps://arxiv.org/abs/2411.08706[00:07:45] Kevin Ellis work on program generationhttps://www.cs.cornell.edu/~ellisk/[00:08:45] Induction vs transduction in abstract reasoning, Li et al.https://arxiv.org/abs/2411.02272[00:17:40] VAEs, Kingma, Wellinghttps://arxiv.org/abs/1312.6114[00:27:50] re-ARC, Hodelhttps://github.com/michaelhodel/re-arc[00:29:40] Grid size in ARC tasks, Chollethttps://github.com/fchollet/ARC-AGI[00:33:00] Critique of deep learning, Marcushttps://arxiv.org/vc/arxiv/papers/2002/2002.06177v1.pdf

François Chollet discusses the outcomes of the ARC-AGI (Abstraction and Reasoning Corpus) Prize competition in 2024, where accuracy rose from 33% to 55.5% on a private evaluation set. SPONSOR MESSAGES: *** CentML offers competitive pricing for GenAI model deployment, with flexible options to suit a wide range of models, from small to large-scale deployments. https://centml.ai/pricing/ Tufa AI Labs is a brand new research lab in Zurich started by Benjamin Crouzier focussed on o-series style reasoning and AGI. Are you interested in working on reasoning, or getting involved in their events? They are hosting an event in Zurich on January 9th with the ARChitects, join if you can. Goto https://tufalabs.ai/ *** Read about the recent result on o3 with ARC here (Chollet knew about it at the time of the interview but wasn't allowed to say): https://arcprize.org/blog/oai-o3-pub-breakthrough TOC: 1. Introduction and Opening [00:00:00] 1.1 Deep Learning vs. Symbolic Reasoning: François's Long-Standing Hybrid View [00:00:48] 1.2 “Why Do They Call You a Symbolist?” – Addressing Misconceptions [00:01:31] 1.3 Defining Reasoning 3. ARC Competition 2024 Results and Evolution [00:07:26] 3.1 ARC Prize 2024: Reflecting on the Narrative Shift Toward System 2 [00:10:29] 3.2 Comparing Private Leaderboard vs. Public Leaderboard Solutions [00:13:17] 3.3 Two Winning Approaches: Deep Learning–Guided Program Synthesis and Test-Time Training 4. Transduction vs. Induction in ARC [00:16:04] 4.1 Test-Time Training, Overfitting Concerns, and Developer-Aware Generalization [00:19:35] 4.2 Gradient Descent Adaptation vs. Discrete Program Search 5. ARC-2 Development and Future Directions [00:23:51] 5.1 Ensemble Methods, Benchmark Flaws, and the Need for ARC-2 [00:25:35] 5.2 Human-Level Performance Metrics and Private Test Sets [00:29:44] 5.3 Task Diversity, Redundancy Issues, and Expanded Evaluation Methodology 6. Program Synthesis Approaches [00:30:18] 6.1 Induction vs. Transduction [00:32:11] 6.2 Challenges of Writing Algorithms for Perceptual vs. Algorithmic Tasks [00:34:23] 6.3 Combining Induction and Transduction [00:37:05] 6.4 Multi-View Insight and Overfitting Regulation 7. Latent Space and Graph-Based Synthesis [00:38:17] 7.1 Clément Bonnet's Latent Program Search Approach [00:40:10] 7.2 Decoding to Symbolic Form and Local Discrete Search [00:41:15] 7.3 Graph of Operators vs. Token-by-Token Code Generation [00:45:50] 7.4 Iterative Program Graph Modifications and Reusable Functions 8. Compute Efficiency and Lifelong Learning [00:48:05] 8.1 Symbolic Process for Architecture Generation [00:50:33] 8.2 Logarithmic Relationship of Compute and Accuracy [00:52:20] 8.3 Learning New Building Blocks for Future Tasks 9. AI Reasoning and Future Development [00:53:15] 9.1 Consciousness as a Self-Consistency Mechanism in Iterative Reasoning [00:56:30] 9.2 Reconciling Symbolic and Connectionist Views [01:00:13] 9.3 System 2 Reasoning - Awareness and Consistency [01:03:05] 9.4 Novel Problem Solving, Abstraction, and Reusability 10. Program Synthesis and Research Lab [01:05:53] 10.1 François Leaving Google to Focus on Program Synthesis [01:09:55] 10.2 Democratizing Programming and Natural Language Instruction 11. Frontier Models and O1 Architecture [01:14:38] 11.1 Search-Based Chain of Thought vs. Standard Forward Pass [01:16:55] 11.2 o1's Natural Language Program Generation and Test-Time Compute Scaling [01:19:35] 11.3 Logarithmic Gains with Deeper Search 12. ARC Evaluation and Human Intelligence [01:22:55] 12.1 LLMs as Guessing Machines and Agent Reliability Issues [01:25:02] 12.2 ARC-2 Human Testing and Correlation with g-Factor [01:26:16] 12.3 Closing Remarks and Future Directions SHOWNOTES PDF: https://www.dropbox.com/scl/fi/ujaai0ewpdnsosc5mc30k/CholletNeurips.pdf?rlkey=s68dp432vefpj2z0dp5wmzqz6&st=hazphyx5&dl=0

References Front Physiol. 2021; 12: 730829. Non-coding RNA Investig 2017. 1:5. Genome Biology 2011. volume 12, Article number: 236 RNA Biol . 2021 Nov 12;18(sup2):574-585. Hunter. R. 1975. "Cruel White Water" https://youtu.be/T-oBD3F74Nk?si=zsrEBN0JKan_FXdH --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Stuart Firestein, a professor of biological sciences at Columbia University, walks us through his study of the vertebrate olfactory system. Professor Firestein is a member of the American Association for the Advancement of Science. With a unique career trajectory, Professor Firestein shares his thoughts on the current state of science education and imparts valuable advice for aspiring scientists. Do not miss this thought-provoking discussion on the past, present, and future of the scientific field.

Genetic recombination --- Send in a voice message: https://podcasters.spotify.com/pod/show/biozenithacademy/message

In this episode, we review the high-yield topic of ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Signal Transduction⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠from the Biochemistry section. Follow ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Medbullets⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets --- Send in a voice message: https://podcasters.spotify.com/pod/show/medbulletsstep1/message

You can never be too prepared when it comes to CRNA school. So why not get a head start and begin learning the concepts you are expected to learn? In today's show, Jenny Finnell prepares for us a special Academic Series born from a conversation with a current student. RRNA David Bearden has observed gaps in nursing education knowledge, even when it comes to interviewing for CRNA schools. They are now bridging those gaps starting with this episode, where they dive deep into signal transduction. What is signal transduction and why does it matter? What role do G proteins play in signal transduction? Tune in to find out more key information that will help you stand out in interviews and support you in CRNA schools. Grab your free Study Notes For This Episode: https://www.cspaedu.com/bkfrtigjHead to YT to watch: https://www.youtube.com/@CRNASchoolPrepAcademyGet access to planning tools, mock interviews, valuable CRNA Faculty guidance, and mapped-out courses that have been proven to accelerate your CRNA success! Become a member of CRNA School Prep Academy here! https://www.crnaschoolprepacademy.com/join Book a mock interview, personal statement, resume and more at http://www.NursesTeachNurses.comBook a mock interview with David: https://app.nursesteachnurses.com/services/113 Join the CSPA email list here! https://www.cspaedu.com/podcast-emailSend Jenny an email or make a podcast request! * let us know what you think of these episodes! Hello@CRNASchoolPrepAcademy.com

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.13.536748v1?rss=1 Authors: Boileau, C., Deforges, S., Peret, A., Scavarda, D., Bartholomei, F., Giles, A., Partouche, N., Gautron, J., Viotti, J., Janowitz, H., Penchet, G., Marchal, C., Lagarde, S., Trebuchon, A., Villeneuve, N., Rumi, J., Marissal, T., Khazipov, R., Khalilov, I., Martineau, F., Marechal, M., Lepine, A., Milh, M., Figarella-Branger, D., Dougy, E., Tong, S., Appay, R., Baudouin, S., Mercer, A., Smith, J. B., Danos, O., Porter, R., Mulle, C., Crepel, V. Abstract: Objective: Temporal lobe epilepsy (TLE) is characterized by recurrent seizures generated in the limbic system, particularly in the hippocampus. In TLE, recurrent mossy fiber sprouting from dentate gyrus granule cells (DGCs) creates an aberrant epileptogenic network between DGCs which operates via ectopically expressed GluK2/GluK5-containing kainate receptors (KARs). TLE patients are often resistant to anti-seizure medications and suffer significant comorbidities; hence there is an urgent need for novel therapies. Previously we have shown that GluK2 knockout mice are protected from seizures. This study aims at providing evidence that downregulating KARs in the hippocampus using gene therapy reduces chronic epileptic discharges in TLE. Methods: We combined molecular biology and electrophysiology in rodent models of TLE and in hippocampal slices surgically resected from patients with drug-resistant TLE. Results: Here we confirmed the translational potential of KAR suppression using a non-selective KAR antagonist that markedly attenuated Interictal-like Epileptiform Discharges (IEDs) in TLE patient-derived hippocampal slices. An adeno-associated virus (AAV) serotype-9 vector expressing anti-grik2 miRNA was designed to specifically downregulate GluK2 expression. Direct delivery of AAV9-anti grik2 miRNA into the hippocampus of TLE mice led to a marked reduction in seizure activity. Transduction of TLE patient hippocampal slices reduced levels of GluK2 protein and, most importantly, significantly reduced IEDs. Interpretation: Our gene silencing strategy to knock down aberrant GluK2 expression demonstrates inhibition of chronic seizure in a mouse TLE model and IEDs in cultured slices derived from TLE patients. These results provide proof-of-concept for a gene therapy approach targeting GluK2 KARs for drug-resistant TLE patients. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.20.533502v1?rss=1 Authors: Metcalfe, M., Steward, O. Abstract: Spinal cord injuries (SCI) cause severe and long-lasting functional impairments due to compromised motor function and sensory signals. Regeneration of the damaged spinal cord is not possible due to intrinsic growth limitations of adult neurons and extrinsic inhibitory factors, especially at the injury site. Deletion of the phosphatase and tensin homolog (PTEN) can enable regeneration of central nervous system axons. AAV-retro is a retrogradely transported AAV variant that can deliver gene modifying cargos to the cells of origin of multiple pathways. In this study, we used AAV-retro to delete PTEN in multiple pathways after cervical SCI to promote regeneration of descending tracts and recovery of motor function. We injected different titers of AAV-retro/Cre into the cervical spinal cord at C5 in PTENf/f;RosatdTomato mice and control RosatdTomato mice at the time of a C5 dorsal hemisection injury. Our results revealed that PTENf/f;RosatdTomato mice injected with high and mid AAV-retro/Cre doses exhibited transient improvements in forelimb gripping ability in comparison to controls. There were major sex differences, with male mice exhibiting greater recovery than females. The values for male mice largely account for the overall differences between PTEN-deleted and controls. However, some PTEN-deleted mice began to exhibit pathophysiologies involving excessive scratching and hindlimb dystonia with persistent extension, which increased over time. Overall, although intra-spinal injections of AAV-retro/Cre in PTENf/f;RosatdTomato mice can lead to initial improvements in forelimb motor recovery after SCI, there are late-developing functional abnormalities with the experimental conditions used here. The mechanisms underlying these late-developing pathophysiologies remain to be defined. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.18.529042v1?rss=1 Authors: Li, X., Ren, M., Gu, Y., Zhu, T., Zhang, Y., Li, J., Li, C., Wang, G., Song, L., Bi, Z., Liu, Z. Abstract: Hearing loss is a major health problem worldwide. Numerous attempts at regenerating functional hair cells (HCs) have been unsuccessful, but little is known about the main barrier that prevents us from achieving it and improving the hearing ability after damage. Here, we developed an in vivo genetic mouse model, by which the inner HCs (IHCs), the primary sound receptors innervated by the auditory neurons, were specifically damaged and the neighboring nonsensory supporting cells (SCs) were transformed into IHCs by ectopic expression of transient Atoh1 and permanent Tbx2. Despite ~477 new IHCs were regenerated per cochlea and their differentiation status was more advanced than reported previously, no significant hearing improvement was achieved. By taking advantage of this unique model, we further found that the new IHCs expressed the functional marker vGlut3, harbored the similar transcriptomic profiles and electrophysiological properties as the endogenous IHCs. However, the mechanosensory transduction (MET) current could not be recorded in the new IHCs. Thus, our study indicated that the defective MET should be the main barrier that stops us from restoring the hearing capacity in the damaged cochlea and would pave the way for regenerating IHCs in vivo. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.12.523776v1?rss=1 Authors: Semesta, K. M., Garces, A., Tsvetanova, N. G. Abstract: RBM12 is a high-penetrance risk factor for familial schizophrenia and psychosis, yet its precise cellular functions and the pathways to which it belongs are not known. We utilize two complementary models, HEK293 cells and human iPSC-derived neurons, and delineate RBM12 as a novel repressor of the G protein-coupled receptor/cyclic AMP/protein kinase A (GPCR/cAMP/PKA) signaling axis. We establish that loss of RBM12 leads to hyperactive cAMP production and increased PKA activity as well as altered neuronal transcriptional responses to GPCR stimulation. Notably, the cAMP and transcriptional signaling steps are subject to discrete RBM12-dependent regulation. We further demonstrate that the two RBM12 truncating variants linked to familial psychosis impact this interplay, as the mutants fail to rescue GPCR/cAMP signaling hyperactivity in cells depleted of RBM12. Lastly, we present a mechanism underlying the impaired signaling phenotypes. In agreement with its activity as an RNA-binding protein, loss of RBM12 leads to altered gene expression, including that of multiple effectors of established significance within the receptor pathway. Specifically, the abundance of adenylyl cyclases, phosphodiesterase isoforms, and PKA regulatory and catalytic subunits is impacted by RBM12 depletion. We note that these expression changes are fully consistent with the entire gamut of hyperactive signaling outputs. In summary, the current study identifies a previously unappreciated role for RBM12 in the context of the GPCR/cAMP pathway that could be explored further as a tentative molecular mechanism underlying the functions of this factor in neuronal physiology and pathophysiology. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.28.522095v1?rss=1 Authors: Melo, M. R., Wykes, A. D., Connelly, A. A., Bassi, J. K., Cheung, S. D., McDougall, S. J., Menuet, C., Bathgate, R. A., Allen, A. M. Abstract: The preBotzinger Complex (preBotC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBotC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetised and conscious states. The population of 7n-projecting preBotC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBotC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviours. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviours have been associated with the development and progression of diseases. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.29.520757v1?rss=1 Authors: Basarrate, S., Monzel, A. S., Smith, J., Marsland, A. L., Trumpff, C., Picard, M. Abstract: Objective: Psychosocial stress is transduced into disease risk through energy-dependent release of hormones that affect target organs, tissues, and cells. The magnitude of the physiological stress responses reflects both systemic levels of these hormones and the sensitivity of target tissues to their effects. Thus, differential expression of receptors across organs likely contributes to stress transduction. Here we provide a quantitative whole-body map of glucocorticoid and adrenergic receptor expression. Methods: We systematically examined gene expression levels for the glucocorticoid receptor (GR), - and {beta}-adrenergic receptors (AR-1B, AR-2B AR-{beta}2, and AR-{beta}3), across 55 different organs using the Human Protein Atlas dataset. We also leveraged the Human Proteome Map and MitoCarta3.0 data to examine receptor protein levels and, given the energy-dependence of the stress response, the link between stress hormone receptor density and mitochondrial pathways. Finally, we tested the functional interplay between GR activation and AR expression in living human cells. Results: The GR was expressed ubiquitously across all investigated organ systems. Immune tissues and cells expressed the highest GR RNA and protein levels. In contrast, AR subtypes showed lower and more localized expression patterns. Co-regulation was found between GR and AR-1B, as well as between AR-1B and AR-2B. In human fibroblasts, activating the GR selectively increased AR-{beta}2 (3.6-fold) and AR-1B (2.2-fold) expression, confirming their interaction. Consistent with the energetic cost of stress responses, GR and AR expression were positively associated with the expression of key mitochondrial pathways. Conclusion: Our results provide a cartography of GR and AR expression across the human body. Tissue-specific stress hormone receptor expression patterns could make specific organ systems more responsive to the sustained, energetically expensive, neuroendocrine signaling pathways triggered by chronic psychosocial stress. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.12.520050v1?rss=1 Authors: Radoux-Mergault, A., Oberhauser, L., Aureli, S., Gervasio, F. L., Stoeber, M. Abstract: G protein-coupled receptors in intracellular organelles can be activated in response to membrane permeant ligands, which contributes to the diversity and specificity of agonist action. The opioid receptors (ORs) provide a striking example, where opioid drugs activate ORs in the Golgi apparatus within seconds of drug addition. Till date, our knowledge on the signaling of intracellular GPCRs remains incomplete and it is unknown if the downstream effects triggered by ORs in plasma membrane and Golgi apparatus differ. To address this gap, we first assess the recruitment of signal transducers to ORs in both compartments. We find that Golgi-localized ORs couple to Gai/o probes and are phosphorylated by GPCR kinases (GRK2/3), but unlike plasma membrane receptors, do not recruit b-arrestin or a specific Ga probe. Subsequent molecular dynamics simulations with OR-transducer complexes in model bilayers mimicking plasma membrane or Golgi composition reveal that the lipid environment promotes location selective coupling. Unbiased global analyses then show that OR activation in the plasma membrane and Golgi apparatus has strikingly different downstream effects on transcription and protein phosphorylation. Taken together, the study delineates OR signal transduction with unprecedented spatial resolution and reveals that the subcellular location defines the signaling effect of opioid drugs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Frontiers in Immunology November 2014. 21(578):1 Clin Epigenetics. 2017; 9: 94 Cancer Cell International September 2020. 20(1):429 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

From paper-thin speakers to DNA in space, it's the Weekly Scideshow! If you want to learn more about the topics we talked about today, check out the links below. The Future of Solar Energy NASA's 10-Year Plan Paper-thin Speakers Seawater to Drinking Water Mountain-Climbing Marine Dinosaurs DNA & RNA in Space

Dr. Lewis Cantley is the Director of the Meyer Cancer Center at Weill Cornell Medical College as well as the Stanton Clinical Cancer Program at New York-Presbyterian Hospital. In addition, he is Co-Founder of Petra Pharma and Agios Pharmaceuticals. His research investigates signal transduction. He has spent most of his career trying to improve our understanding of cell signaling pathways at a molecular level since many diseases, such as cancer, involve defects in signaling. Outside science, he is an avid reader of science fiction, mystery, and history books. He received his B.S. in Chemistry from West Virginia Wesleyan College and his Ph.D. in Biophysical Chemistry from Cornell University. Lewis conducted postdoctoral research at Harvard University, and served on the faculty at Harvard University, as well as Tufts University before joining the faculty at Cornell. Lewis has received many awards and honors during his career, including the 2005 Pezcoller Foundation-American Association for Cancer Research International Award for Cancer Research, the 2013 Breakthrough Prize in Life Sciences, the 2015 Ross Prize in Molecular Medicine, the 2015 Wolf Prize, the 2015 Association of American Cancer Institutes Distinguished Scientist Award, the 2015 Canada Cairdner award, and he was named one of “The World's Most Influential Scientific Minds” in 2015 by Thomson Reuter. Lewis is also a Fellow of the American Academy of Arts and Sciences, as well as a Member of the National Academy of Sciences, the Institute of Medicine of the National Academies, and the European Life Sciences Academy. Lewis is here with us today to tell us all about his journey through life and science.

Benjamin – found on social media as @antlerboy – has been in public service reform and organizational effectiveness for over 20 years, and is passionate about the systems | complexity | cybernetics field. He describes himself as business evolutionary and avid learner, all of which he traces back to science fiction, studying philosophy (with politics and economics at Oxford University), and being an outsider despite his privilege.He began in a frontline role and then became Adviser to Leader in a London borough council and a career in public service consultancy through PwC, Sector Projects (part of Capita). He set up Red Quadrant, a network consultancy, in 2009 with the goal of transforming public services and disrupting consulting. In 2016, Benjamin established the Public Service Transformation Academy, a not-for-profit social enterprise which builds the capacity of public services to transform themselves. Benjamin curates and shares everything to do with systems/complexity/cybernetics at the Systems Community of Inquiry, hosts and supports and engages with many social media groups and systems societies, and is a Fellow of the Cybernetics Society  and a Director of Systems and Complexity in Organisation, the systems practitioner professional body. In that capacity, he has supported the development of the UK's level seven (post-grad) systems thinking practitioner apprenticeship. He is writing two systems thinking books, one for Routledge and one for Triarchy Press, and recording two podcasts: Transduction, the systems, cybernetics, and complexity podcast (I have come to sing songs to your cat), and Joy and Work: leading service transformation.

Classic: The dominant sequence transduction models are based on complex recurrent or convolutional neural networks in an encoder-decoder configuration. The best performing models also connect the encoder and decoder through an attention mechanism. We propose a new simple network architecture, the Transformer, based solely on attention mechanisms, dispensing with recurrence and convolutions entirely. Experiments on two machine translation tasks show these models to be superior in quality while being more parallelizable and requiring significantly less time to train. Our model achieves 28.4 BLEU on the WMT 2014 English-to-German translation task, improving over the existing best results, including ensembles by over 2 BLEU. On the WMT 2014 English-to-French translation task, our model establishes a new single-model state-of-the-art BLEU score of 41.8 after training for 3.5 days on eight GPUs, a small fraction of the training costs of the best models from the literature. We show that the Transformer generalizes well to other tasks by applying it successfully to English constituency parsing both with large and limited training data. 2017: Ashish Vaswani, Noam M. Shazeer, Niki Parmar, Jakob Uszkoreit, Llion Jones, Aidan N. Gomez, Lukasz Kaiser, Illia Polosukhin BLEU, Transformer, Machine translation, Encoder, Convolution, Transduction (machine learning), Recurrent neural network, Image, Network architecture, Input/output, TensorFlow, Network Abstraction Layer, Artificial neural network https://arxiv.org/pdf/1706.03762.pdf

Dr. Jennifer Grandis is a Professor in the Department of Otolaryngology - Head and Neck Surgery, Director of the Clinical and Translational Science Institute, and Associate Vice Chancellor of Clinical and Translational Research at the University of California, San Francisco. She is also an American Cancer Society Professor. Jennifer is a Cancer Biologist as well as a head and neck surgeon. Her research revolves around understanding the key features of head and neck cancer that can be used to develop more effective treatments. Jennifer and her husband like to go running every morning with their dogs near their home in San Francisco. She makes sure to dedicate time in her day for reading, and she also listens to books on her phone when traveling. Reading and cooking are two activities that bring Jennifer great happiness. Jennifer received her B.A. in Biology and Art History at Swarthmore College and was awarded her M.D. from the University of Pittsburgh School of Medicine. She completed her residency and an Infectious Disease Fellowship at the University of Pittsburgh School of Medicine and went on to serve on the faculty there for over 20 years before accepting her current position at UCSF. Jennifer has received many honors and awards during her career, including the Peggy Wheelock Award for Excellence in Research, Mentoring, and Promotion of Women in Science from the University of Nebraska, as well as the University of Pittsburgh's Provost's Award for Excellence in Mentoring, Philip Hench Distinguished Alumnus Award, Chancellor's Distinguished Research Award, Scientific Leadership Award, promotion to Distinguished Professor of Otolaryngology, and more. Jennifer is also an Elected Member of the Association of American Physicians, the American Society for Clinical Investigation, and the Institute of Medicine of the National Academies. Jennifer joined us in this interview to tell us all about her journey through life and science.

This podcast provides an overview of G-protein coupled recertors (GPCRs) and Second messengers. This biochemistry content may be useful to premedical and medical students. --- Send in a voice message: https://anchor.fm/a-j-ghalayini/message

This podcast describes the activation of the alpha1-adrenergic receptor and the production of the second messengers DAG, IP3 and calcium. This biochemistry content may be useful to premedical and medical students. --- Send in a voice message: https://anchor.fm/a-j-ghalayini/message

This podcast describes the activation of the beta-adrenergic receptor and the generation of the second messenger, cAMP in detail. This biochemistry content may be useful to premedical and medical students. --- Send in a voice message: https://anchor.fm/a-j-ghalayini/message

This podcast describes the mechanism of action of steroid receptors and the types of cellular responses they ellicit. This biochemistry content may be useful to premedical and medical students. --- Send in a voice message: https://anchor.fm/a-j-ghalayini/message

This podcast describes the activation of receptors tyrosine kinase receptors. This biochemistry content may be useful to medical and premedical students. --- Send in a voice message: https://anchor.fm/a-j-ghalayini/message

This podcast describes the 4 types of receptors involved in cellular signaling. This biochemistry content may be useful to premedical and medical students. --- Send in a voice message: https://anchor.fm/a-j-ghalayini/message

This podcast covers thd mechanism of activation of two GPCRs: The beta- adrenergic and the alpha1-adrenergic receptors. This biochemistry content may be useful to premedical and medical students. --- Send in a voice message: https://anchor.fm/a-j-ghalayini/message

This podcast covers the four major classes of receptors and their mechanism of activation to generate a cellular response. This biochemistry content may be useful to premedical and medical students. --- Send in a voice message: https://anchor.fm/a-j-ghalayini/message

My AP Biology Thoughts  Unit 4 Cell Communication and Cell CycleWelcome to My AP Biology Thoughts podcast, my name is Corrinna and I am your host for episode #88. This is Unit 4 Cell Communication and Cell Cycle and today, we will be talking about transduction phosphorylation cascades Segment 1: Introduction to transduction: phosphorylation cascadesTransduction is the second step in cell signaling pathways. It comes after reception, where the signal (which is called the ligand) is received by the receptor.  In order for the signal to start a response in the protein, the receptor needs to be activated. For the cell to produce a response, the next proteins in the chain also need to be activated. These proteins can be activated and deactivated like an on/off switch.  One of the ways that the signaling molecules are activated is phosphorylation. For a molecule to be phosphorylated, phosphate is added to the molecule. Phosphate groups are typically linked to either tyrosine, threonine, or serine, since these amino acids have hydroxyl groups in their side chains.  Phosphorylation is what can activate or deactivate the signaling molecules. It can also make the proteins more active (like an enzyme) or cause it to be broken down. Additionally, phosphorylation generally isn't permanent. To de-phosphorylate a protein, cells have enzymes called phosphatases that remove the phosphate groups from the phosphorylated protein.  A phosphorylation cascade is when multiple signaling molecules in the cell signaling chain are phosphorylated, which transports the signal to another molecule to produce the end result.  Segment 2: examples of transduction: phosphorylation cascadesIn order to better understand phosphorylation cascades, let's look at an example.  One example of a phosphorylation cascade is the epidermal growth factor (EGF) pathway.  When growth factor ligands bind to the receptors, the receptors act as kinases and attach phosphate groups to each other's intracellular tails. These receptors are now activated, triggering a series of events. Since these events don't include phosphorylation, we won't cover them in detail and will instead talk about the parts after that series that do involve phosphorylation.  Those events activate kinase Raf. This activated Raf phosphorylates and activates MEK, which in turn phosphorylates and activates ERKs. The ERKs then phosphorylate and activate other target molecules that then promote cell growth and division.  This specific pathway is called a mitogen-activated protein kinase cascade.  Because this specific pathway used multiple phosphorylation events that triggered other phosphorylations, it can be classified as a phosphorylation cascade.  Segment 3: Connection to the Course Phosphorylation cascades are extremely important in cell signaling pathways because they allow the cell to respond to more than one cell signal. Phosphorylation cascades trigger multiple cellular responses, because the phosphorylation of one protein leads to the phosphorylation of another.  Additionally, if phosphorylation cascades become out of control, especially cascades that signal for growth factor, cancer can occur. This shows that being able to stop cell signaling is extremely important, since if cell growth and division goes unregulated, it becomes dangerous.  To stop cell growth and division, the cell may receive a signal to undergo apoptosis, or cell death. This usually happens if a cell doesn't pass a checkpoint in the cell cycle, which is explained in further detail in another episode.  Thank you for listening to this episode of My AP Biology Thoughts. For more student-run podcasts and digital content, make sure that you visit http://www.hvspn.com (www.hvspn.com). See you next time on My AP Biology thoughts Podcast! Music Credits: "Ice Flow" Kevin MacLeod (incompetech.com) Licensed under...

My AP Biology Thoughts  Unit 4 Cell Communication and Cell CycleWelcome to My AP Biology Thoughts podcast, my name is Helena Holley and I am your host for episode #91 called Unit 4 Cell Communication and Cell Cycle: Changes in signal transduction pathways. Today we will be discussing factors that affect signal transduction pathways and their consequences in the body.  Segment 1: Introduction to Changes in signal transduction pathwaysThe first thing to know is what are signal transduction pathways? This is a process in which extracellular ligands/signaling molecules bind to receptors, which could be located inside the cell or on it's surface, and triggers a series of events which results in a cellular response or multiple responses. Depending on the pathway this process could involve the use of a secondary messenger. This is typically an intracellular signaling molecule that amplifies the signal inside the cell in response to the presence of an extracellular signaling molecule in order to reach the target cell that will initiate cellular response. The signal transduction pathways can alter a lot of cell functions and that is why it is critical that all parts of the process function correctly. Changes in parts of the process can cause disorders and disease.  Segment 2: More About changes in signaling transduction pathwaysThe signaling transduction pathway is a complicated process that requires a lot of factors to work properly in order to reach the desired response, and because this process is so complicated there are a lot of chances for something to go wrong. First of all, mutations in signaling molecules could cause it to be unable to bind to the receptor and therefore the whole signaling transduction pathway will not be able to occur. This same situation can happen if the receptor was mutated, hence the signaling molecule won't be able to bind to the receptor. The next place where something in the pathway could be altered is during transduction. If one of the relay molecules is mutated this could stop the process from finishing or it could result in a different (potentially harmful) response to the initial signal. Certain chemicals can also affect signaling transduction pathways by either activated or deactivating a process and change the cellular response that happens.  Segment 3: Connection to the CourseAlteration in signaling transduction pathways can lead to diseases such as type 1 diabetes or cancers. This is why it is important to understand how the steps in the pathway works and where things can go awry. If we can understand where the issue is taking place that causes cancer or causes diabetes, we can help the individual by disrupting the cancer signaling pathway or giving the patient insulin. The signaling transduction pathway is used in the body all the time, whether it be during the cell cycle or after we eat some glucose and that's why it is crucial to understand the mechanisms by which it works so we can combat issues that may arise during it.  Thank you for listening to this episode of My AP Biology Thoughts. For more student-ran podcasts and digital content, make sure that you visit http://www.hvspn.com (www.hvspn.com). Eat a cookie you gotta make sure those insulin receptors still work from time to time!  Music Credits: "Ice Flow" Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 4.0 License http://creativecommons.org/licenses/by/4.0/ Subscribe to our Podcast https://podcasts.apple.com/us/podcast/my-ap-biology-thoughts/id1549942575 (Apple Podcasts) https://open.spotify.com/show/1nH8Ft9c9f6dmo75V9imCk (Spotify) https://podcasts.google.com/search/my%20ap%20biology%20thoughts (Google Podcasts )   https://www.youtube.com/channel/UC07e_nBHLyc_nyvjF6z-DVg (YouTube)  Connect with us on Social Media Twitterhttps://twitter.com/thehvspn ( @thehvspn)

My AP Biology Thoughts  Unit 4 Cell Communication and Cell CycleWelcome to My AP Biology Thoughts podcast, my name is Morgan and I am your host for episode #89 called Unit 4 Cell Communication and Cell Cycle: transduction; secondary receptors. Today we will be discussing secondary receptors and their role in the signal transduction Segment 1: Introduction to transduction pathwaysIn signal transduction, there are three things that are necessary for the cell to do.  First, the signal, or ligand, must bind to the receptor, either on the cell's surface or inside the membrane. This is the first component, which is known as reception.  From there, the transduction occurs, where proteins are activated, and it is the component that includes secondary messengers.  Lastly, the transduction pathway eventually elicits a response from the cell, which is the overall goal of cell signaling. This response can be anything from activating an enzyme to initiating apoptosis, which is programmed cell death.  After the ligand binds to its receptor and changes the shape, the cell sets off with a series of signaling events, all designed to amplify the signal and eventually reach a response. This chain of events is what we call the transduction pathway. The first way transduction occurs is through protein phosphorylation, where a series of proteins are activated by phosphorylases. The other way transduction can occur is by secondary messengers, so let's learn more about those! Segment 2: More About secondary messengersSecondary messengers are small molecules that are specifically not proteins, although proteins play a huge role in the cell cycle. These secondary messengers are the ones that receive the signal from the first ligand when it binds to its receptor. The signal, or ligand, is thought of as the first messenger, so these little molecules that pick up and carry along the signal are therefore secondary messengers. Two examples of secondary messengers are calcium ions and cyclic AMP. First, calcium in the form of Ca2+ ions are a very common secondary messenger in cells. They are stored in the endoplasmic reticulum, which is purposeful so they are isolated from the rest of the cell until they are needed and released. The pathway starts with a signal that binds to and opens one of the ligand-gated calcium ion channels in the cell. With an open ion channel, calcium ions from the extracellular space are able to flow freely into the cell and greatly increase the concentration of Ca2+ ions in the cytoplasm. From there, the abundance of calcium ions bind with various proteins in the cell, changing their shape and function to initiate a response. Secondary messengers are nonspecific, so the signals can lead to many types of responses based on the proteins present and type of cell. The next example of a secondary messenger is cyclic AMP. Cyclic AMP is made when an enzyme gets a specific signal and converts ATP into the new molecule of cyclic AMP, also referred to as cAMP. Once it is made from the ATP, cAMP activates protein kinase A, a molecule that phosphorylates other proteins and passes along the signal to produce different responses. Segment 3: Connection to the CourseSecondary messengers have many connections to this unit of cell communication and the cell cycle, as well as the overall biology course. To start, it is important to understand signal transduction pathways and the three components before diving deeper into secondary messengers. We must know the purpose of these signaling pathways, as well as how they are started and what happens, which would be our three components of reception, transduction, and response. Additionally, we know that the purpose of secondary messengers is to amplify a signal and achieve a response, which we can see physically by responses in our body. For example, one of the secondary messengers we talked about earlier was calcium, which has a specific signaling pathway in...

My AP Biology ThoughtsUnit 4 Cell Communication and Cell CycleWelcome to My AP Biology Thoughts podcast, my name is Nikki Evich and I am your host for episode #82 called Unit 4 Cell Communication and Cell Cycle: Intro to Signaling Transduction Pathway. Today we will be discussing the components that make up a pathway. Segment 1: Introduction to the signaling transduction pathway● Signal also call ligand binds to a receptor on target cell membrane ○ , starts the pathway, ○ had to fit receptor, ○ once bound, transduction is initiated ● Receptor- intracellular or extracellular ○ Binding domain recognizes specific chemical messengers ● transduction-lots of varian with transduction ○ Could activate inactive protein by phosphorylating ○ Amplifies with secondary messengers ● Response- what the end result is ○ Can be short or long ○ Activate enzyme or move cell-short ○ Alter gene expression levels or cell division (apoptosis)-long Segment 2: More About the signaling transduction pathway● Type 1 ● Once the food is broken down into glucose, these molecules are then absorbed into the bloodstream. The high glucose levels in the bloodstream activate the beta cells in the pancreas to start producing insulin. Insulin is a hormone created in the pancreas. In the pancreas, beta cells are present which are in charge of secreting the insulin into the bloodstream once they detect an increase in blood glucose. Insulin travels to three main destinations-muscle, fat, and liver cells. ● This is where the transduction pathway happens ● The insulin will then bind to the insulin receptors. The insulin receptors are made up of extracellular alpha subunits and transmembrane beta subunits. ● When the insulin binds to the extracellular alpha subunits, the beta subunits become activated and auto phosphorylate. This means that they phosphorylate themselves. ● This leads to the phosphorylation and activation of the IRS protein. The IRS protein is regulated and can be phosphorylated by PTEN. PTEN can regulate phosphorylation and activate IRS Isaforms by dephosphorylating IRS. Once IRS is activated, proteins including PI3K will bind to the IRS protein through their P85 subunit. ● The PI3K will then phosphorylate PIP2 to PIP3. When the PIP3 concentration increases, other proteins like PDK1 and AKT are recruited towards the plasma membrane. PIP3 activates PDK1 which then phosphorylates AKT. ● Cells have reservoirs of intracellular vesicles that contain GLUT4, a glucose transporter. So in order for glucose to be let into the cell the glucose transporters have to translocate to the plasma membrane. However, AS160 inhibits this process. ● Luckily, phosphorylated AKT inactivates AS160. So when AKT is phosphorylated by PDK1, AS160 is inactivated which in turn allows for the translocation of glut 4 so it can embed itself in the membrane. Now glucose can get into the cell for storage and other purposes. Segment 3: Connection to the Course● Involved in evolution-some cell transduction pathways stayed the same ○ Track common ancestors Interruptions in this pathway are serious like with the brain sending signals out ● Involved in negative feedback loops and homeostasis ● Body is constantly sending signals, though it may seem minute it makes you be able to do all you do ● In all walks of life ● Can be seen in all types of diseases and illness from Diabetes to cancer Thank you for listening to this episode of My AP Biology Thoughts. For more student-ran podcasts and digital content, make sure that you visit www.hvspn.com. Bye now! Music Credits: ● "Ice Flow" Kevin MacLeod (incompetech.com) ● Licensed under Creative Commons: By Attribution 4.0 License ● http://creativecommons.org/licenses/by/4.0/ Subscribe to our Podcast https://podcasts.apple.com/us/podcast/my-ap-biology-thoughts/id1549942575 (Apple Podcasts) https://open.spotify.com/show/1nH8Ft9c9f6dmo75V9imCk (Spotify)...

Recorded: November 24, 2020 About the podcast Antlerboy starts off the show with a confession; that he has been seeing other people – in fact quite a selection of other people.  Behind JP’s back but in broad daylight, he has been recording two other podcasts; “Joy and Work” for leading (public) service transformation, and “Transduction” for the systems, complexity, and cybernetics.  He also shares that his launch strategy is rather atypical in that he is purposefully limiting his audience to a “need to listen” basis with a tight circle of trust and with limited outreach.  JP thinks this is a rather odd launch strategy indeed.  But then again, JP got a bit lost (but not surprised) when Antlerboy started talking about the subject matter having socialist and liberal leanings and academic wonks being the source for many of his episodes. JP expresses concern that Antlerboy’s appetite for strange is insatiable and that he should seek help – this before confessing that he too has recently launched a new podcast himself entitled “Supercharged Supply Chain”.  But JP’s also shares that his new podcast is a bit of a struggle because he is not used to having a co-host who is so much smarter than he is, and it takes a lot of work on his part to be sure to be on his toes. Of course, both Antlerboy and JP wish each other much success with their new ventures. Our first guest is Sam Storm from Sweden.  JP has known Sam for some time and took notice of the complete personal transformation that Sam has undertaken in the past year; from hoodies and baggie-pants to custom tailored suits.  In the spirit of John T. Molloy, Sam is “dressed for success”.  Sam then shares that he has competed in the Swedish hip-hop cover competition several times and does a pretty good Dr. Dre cover.  It is near peak darkness in Sweden now with a maximum of seven hours of twilight and Sam is finding satisfaction in working with others; coaching and mentoring them on agile tools and techniques with an eye to professional and personal growth. This leads to a larger discussion on mentoring; and how we often don’t know we are mentoring others (and that others don’t know that we are being mentored by them).  Perhaps it is better this way in that each of us can be more genuine and have the real conversations without feeling the pressures associated with knowing we are examining or being examined. Our next guest to the bar is a regular, Stephane from Belgium and now in France.  The conversation starts with the renewed lockdown in France and the challenges that will be faced with holiday shopping.  It would appear that many people in France openly rail against Amazon whilst secretly clicking away.  Absurdly, the supermarkets are open for food, but aisles within the supermarket are closed because they sell “non-essential” items (whatever that means) even though they are in the same store.  This is to protect the small shops that sell these items, but are currently closed – even though you can buy these items online.  Government Rules Hurt. Our. Heads. JP shares with Stephane that he was concerned for Stephane’s well-being.  Usually, Stephane is responsive to eMails and LinkedIn messages, but there were a couple of weeks where Stephane did not respond – not even open a message on LinkedIn.  Stephane shared that he was on vacation, or rather a “stay-cation”.  He stayed in his apartment and unplugged from everything work-related.  How can a person do that for two weeks, couped up in an apartment with restrictions for movement, escaped JP (who would have had to escape). Lastly, we again call to center stage, Mandalyn, with another acapella rendition of one of her original songs.  This one is a personal favorite of her’s and is entitled “Breaking Up” about the end of one of her relationships a really long time ago. As usual, we sit around the table discussing what-not and such – mostly adding to the previous conversations of the evening, until the last call is shouted and the lights are turned up brighter letting us all know it’s time to go. Hosts: Joseph Paris, Founder of the OpEx Society & The XONITEK Group of Companies   Benjamin Taylor,  Managing Partner of RedQuadrant.

T cell agency initiates upon the stimulation of the TCR via presentation of cognate peptide-MHC complexes in associative ligand-mediated membrane co-receptor CD28 with co-stimulatory molecules presented on the surface of the APC: this event is called T cell licensure and essentially quits quiescence. The TCR signals through the ERK/MAPK pathways and calcium flux; where as CD28 signaling activates the PI3K-AKT-mTOR axis, and both pathways synergistically engage the NF-κB organon of pleitropic T lymphocyte agency. Merry Christmas from AUTHENTIC BIOCHEMISTRY! Please subscribe and help promote/produce the podcast by donating 10 dollars each this month! Thank You! --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.16.342899v1?rss=1 Authors: Zimmer, M. H., Niesen, M. J., Miller, T. F. Abstract: Force-sensitive arrest peptides regulate protein biosynthesis by stalling the ribosome as they are translated. Synthesis can be resumed when the nascent arrest peptide experiences a pulling force of sufficient magnitude to break the stall. Efficient stalling is dependent on the specific identity of a large number of amino acids, including amino acids which are tens of angstroms away from the peptidyl transferase center (PTC). The mechanism of force-induced restart and the role of these essential amino acids far from the PTC is currently unknown. We use hundreds of independent molecular dynamics trajectories spanning over 120 s in combination with kinetic analysis to characterize the barriers along the force-induced restarting pathway for the arrest peptide SecM. We find that the essential amino acids far from the PTC play a major role in controlling the transduction of applied force. In successive states along the stall-breaking pathway, the applied force propagates up the nascent chain until it reaches the C-terminus of SecM and the PTC, inducing conformational changes that allow for restart of translation. A similar mechanism of force propagation through multiple states is observed in the VemP stall-breaking pathway, but secondary structure in VemP allows for heterogeneity in the order of transitions through intermediate states. Results from both arrest peptides explain how residues that are tens of angstroms away from the catalytic center of the ribosome impact stalling efficiency by mediating the response to an applied force and shielding the amino acids responsible for maintaining the stalled state of the PTC. Copy rights belong to original authors. Visit the link for more info

Dr. Kathryn Medler is an Associate Professor in the Department of Biological Sciences at The State University of New York at Buffalo. Her lab is dedicated to understanding how the taste cells in our tongues are able to detect the chemicals in our food and send this information to the brain so that we can decide whether to eat something or spit it out. The sense of taste is critical for survival, and there are many complex signaling mechanisms involved. In addition to spending time with her family, one of Kathryn’s passions outside of work is travel. While she hasn’t been able to travel as much lately, she has managed to escape the city and spend some long weekends hiking and enjoying nature in the Finger Lakes Region of New York. Kathryn was awarded her B.S. in biology from Texas A&M University, her M.S. in physiology from San Diego State University, and her PhD in neuroscience from Louisiana State University. Afterwards, Kathryn conducted postdoctoral research at Louisiana State University and subsequently at Colorado State University before joining the faculty there at the University at Buffalo in 2004. In our interview, Kathryn shares more about her life and research.

next_generation 8.0 LIVE-CODING | Lecture [06.06.2019 - 09.06.2019] Als größtes biennales Treffen der Hochschulstudios für elektronische Musik bietet next_generation NachwuchskomponistInnen eine Plattform, ihre kompositorischen Neuentwicklungen zu präsentieren. Von Mittwoch, 5. Juni bis Sonntag, 9. Juni 2019 fand am ZKM die achte Ausgabe des biennalen Festivals next_generation statt. An fünf Tagen wurde ein spannendes und dichtes Programm über die neuesten Positionen zu den Themen »Fixed Media«, »Raummusik« und »Live-Elektronik« geboten. 2019 stand das Festival unter dem Schwerpunkt »Live-Coding«. Damit garantiert next_generation 8.0 eine repräsentative Übersicht über das aktuelle kreative Schaffen der kommenden Komponierendengeneration im Kontext von Technologie und Kunst. /// As the largest biennial gathering of university studios for electronic music, next_generation 8.0 offers young composers a platform to present their new compositional developments. The eighth edition of the next_generation biennial festival took place at ZKM from Wednesday, June 5 to Sunday, June 9, 2019. Over five days, an exciting and dense program was offered on the latest positions of the themes »fixed media«, »spatial music« and »live electronics«. 2019, the festival focus was on »live coding«. Thus, next_generation 8.0 guarantees a representative overview of the current creative work of the next generation of composers in the context of technology and art.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.28.271510v1?rss=1 Authors: Thomson, N. J., Vickery, O. N., Ives, C. M., Zachariae, U. Abstract: G-protein-coupled receptors (GPCRs) are membrane proteins that transmit signals across the cell membrane by activating intracellular G-proteins in response to extracellular ligand binding. A large majority of GPCRs are characterised by an evolutionarily conserved activation mechanism, involving the reorientation of helices and the conformation of key residue side chains, rearrangement of an internal hydrogen bonding network, and the expulsion of a sodium ion from a binding site in the transmembrane region. However, how sodium, internal water, and protein residues interplay to determine the overall receptor state remains elusive. Here, we develop and apply "State Specific Information" (SSI), a novel methodology based on information theory, to resolve signal transmission pathways through the proteins. Using all-atom molecular dynamics simulations of pharmaceutically important GPCRs, we find that sodium plays a causal role in the formation and regulation of a communication channel from the ion binding site to the G-protein binding region. Our analysis reveals that the reorientation of specific water molecules is essential to enable coupled conformational state changes of protein residues along this pathway, ultimately modulating the G-protein binding site. Furthermore, we show that protonation of the ion binding site creates a conformational coupling between two previously separate motifs, entirely controlled by the orientation of two water molecules, priming the receptor for activation. Taken together, our results demonstrate that sodium serves as a master switch, acting in conjunction with the network of internal water molecules, to determine the micro- and macrostates of GPCRs during the receptors' transition to activation. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.11.245753v1?rss=1 Authors: Gessara, I., Dittrich, F., Hertel, M., Hildebrand, S., Pfeifer, A., Frankl-Vilches, C., McGrew, M., Gahr, M. Abstract: SUMARYThe ability to genetically manipulate organisms has led to significant insights in functional genomics in many species. In birds, manipulation of the genome is hindered by the inaccessibility of the one-cell embryo. During embryonic development, avian primordial germ cells (PGCs) migrate through the blood stream and reach the gonadal anlage; where they develop into mature germ cells. Here, we explored the use of PGCs to produce transgenic offspring in the zebra finch, which is a major animal model for sexual brain differentiation, vocal learning and vocal communication. Zebra finch PGCs (zfPGCs) obtained from embryonic blood significantly proliferated when cultured in an optimized culture medium and conserved the expression of germ and stem cell markers. Transduction of cultured zfPGCs with lentiviral vectors was highly efficient leading to strong expression of the enhanced green fluorescent protein (eGFP). Transduced zfPGCs were injected into the host embryo and transgenic songbirds were successfully generated. Copy rights belong to original authors. Visit the link for more info

تختلف خلية البكتيرية بعض الشيء عن الخلايا المتواجدة في النباتات والحيوانات، فخلايا البكتيريا لا تضم نواة Nucleus كما ترتبط العضيات organelles معا بالغشاء باستثناء الريبوسومات. تمتلك البكتيريا أيضا شعرات Pili وأسواط flagella وكيس خلوي في بعض الأحيان، ما يميزها عن خلايا الحيوانات والنباتات، علماً أن الكائن الحي الذي لا يشمل على نواة يسمى بدائيات النوى Prokaryote. إذا فالخلية البكتيرية تضم: الجسم الأساسي: وهو يعقد قاعدة السوط التي تسمح له بالدوران والاستدارة. الكيس الخلوي: طبقة خارجية لجدار الخلية، علماً أن هذا الكيس لا يتواجد لدى جميع أنواع البكتيريا. جدار الخلية: طبقة رفيعة خارج الغشاء البلازمي، ويقع في حدود الكيس الخلوي إن وجد. الحمض النووي الريبي المنزوع الاكسجين DNA: هو الذي يضم جميع المكونات الجينية المستخدمة في تطور وعمل البكتيريا، وتتواجد في هيولي الخلية Cytoplasm. الهيولي: هو عبارة عن مادة هلامية داخل الغشاء البلازمي، حيث تتواجد المكونات الجينية والريبوسومات في داخله. السوط: وهو الذي تستخدمه البكتيريا في الحركة والدفع، علماً أن بعض أنواع البكتيريا تمتلك أكثر من سوط واحد.  شعرات: هي التي تمكن البكتيريا من الالتصاق على الأسطح وتحويل المركبات الجينية إلى الخلايا الأخرى، كما كشفت دراسة علمية نشرت في مجلة Proceedings of the National Academy of Sciences أن هذه الشعرات مسؤولة عن الإصابة بإسهال السفر. الغشاء البلازمي: يعمل على توليد الطاقة ونقل المواد الكيميائية، فهذه المواد تكون قادرة على العبور من خلال الغشاء. الريبوسومات: هو المكان الذي يتم تصنيع البروتينات فيه، وهي عبارة عن عضيات صغيرة مصنوعة من حمض نووي ريبي غني بالحبيبات. كيف تتغذى البكتيريا وتتكاثر؟ هناك عدة طرق تمكن البكتيريا من تغذية نفسها، وهي تشمل: غيري التغذية Heterotrophs: أي أنها تتغذى على كائنات حية أخرى، بعض أنواع البكتيريا تقتل الكائن الذي تتغذى عليه في حين أن بعضها الآخر يقوم بمساعدتها. ذاتي التغذية Autotrophs: أي أن هذا النوع من البكتيريا يقوم بصنع طعامه بنفسه، ويتم هذا على طريقتين: 1- البناء الضوئي Photosynthesis: حيث يتم استخدام أشعة الشمس وثاني أكسيد الكربون CO2 والماء لصناعة الغذاء للبكتيريا. 2- التمثيل الكيميائي Chemosynthesis: في هذه الطريقة تستخدم البكتيريا ثاني أكسيد الكربون والماء وبعض المواد الكيميائية مثل الأمونيا بهدف صنع غذائها. ولكن كيف تتكاثر هذه البكتيريا؟ هناك عدة طرق تستخدمها البكتيريا للتكاثر، وتشمل: الانقسام الثنائي Binary fission: وهي لا تتطلب وجود ذكر وأنثى، بل تتكاثر من تلقاء نفسها، حيث ينمو جدار الخلية من المركز ليشكل خليتين صغيرتين تنقسما فيما بعد. إعادة تركيب بكتيري Bacterial recombination: تأتي عملية التكاثر هذه لتحل مشكلة عملية الإنقسام الثنائي، إذ أنه في العملية الأولى تكون البكتيريا الجديدة مطابقة جداً للبكتيريا القديمة، بالتالي يكون من السهل القضاء عليها باستخدام المضادات البكتيرية، وتتم عملية التكاثر هذه عن طريق: 1- الاقتران: أي نقل بعض الجينات من خلية بكتيرية إلى أخرى عن الطريق اتصالهما معا 2- التحول: بعض الخلايا البكتيريا قادرة على انتزاع الحمض النووي من البيئة المحيطة. 3- التنبيغ Transduction:  تصاب البكتيريا بنوع من الفيروسات التي تسمى العاثية Bacteriophages التي تقوم بإدخال الجينات الخاصة بها إلى البكتيريا، لتتكاثر هذه الجينات مع جينات البكتيريا في داخلها. ادعموني على منصة patreon من خلال مساهماتكم على الرابط التالي:: www.patreon.com/microinmin تابعوا صفحتي على فيس بوك من خلال الرابط التالي :: www.facebook.com/microinmin #podcast #microbiology_in_aminute

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.08.139667v1?rss=1 Authors: gong, h., Yuan, N., Shen, Z., Tang, C., Shipp, S., Qian, L., Lu, Y., Andolina, I. M., Zhang, S., Wu, J., Yang, H., Wang, W. Abstract: Rapid and efficient gene transduction via recombinant adeno-associated viruses (rAAVs) is highly desirable across many basic and clinical research domains. Here we report vector co-infusion with doxorubicin, a clinical anti-cancer drug, markedly enhanced rAAV-mediated gene expression in cerebral cortex across mammalian species (cat, mouse, and macaque), acting throughout the time-period examined and detectable at just three days post-transfection. This enhancement showed serotype generality, being common to rAAV serotypes 2, 8, 9 and PHP.eB tested, and was observed both locally, and at remote locations consistent with doxorubicin undergoing retrograde axonal transport. All these effects were observed at doses matching human blood plasma levels in clinical therapy, and lacked detectable cytotoxicity as assessed by cell morphology, activity, apoptosis and behavioral testing. Altogether, this study identifies an effective means to improve the capability and scope of in vivo rAAV applications, accelerating and augmenting gene transduction at doxorubicin concentrations paralleling medical practice. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.19.104109v1?rss=1 Authors: Laprell, L., Brehme, M.-L., Oertner, T. G. Abstract: Microglia react to danger signals by rapid and targeted extension of cellular processes towards the source of the signal. This positive chemotactic response is accompanied by a hyperpolarization of the microglia membrane. Here we show that optogenetic depolarization of microglia has little effect on baseline motility, but significantly slows down the chemotactic response. Reducing the extracellular Ca2+ concentration mimics the effect of optogenetic depolarization. As the membrane potential sets the driving force for Ca2+ entry, hyperpolarization is an integral part of rapid stimulus-response coupling in microglia. Compared to other excitable cells, the sign of the activating response is inverted in microglia, leading to inhibition by depolarizing channelrhodopsins. Copy rights belong to original authors. Visit the link for more info

It’s all about maintaining homeostasis in Episode 36! Neurons are specialized cells for conducting electrical signals and releasing chemical neurotransmitters (2:02). Axons conduct an action potential through the movement of sodium and potassium ions (3:00). The message changes from electrical to chemical at a synapse (4:30). Neurotransmitters act as ligands, binding to the postsynaptic membrane (5:20).The Question of the Day asks (6:44) “Which autoimmune disorder degrades the myelin sheath of an axon? ”Thank you for listening to The APsolute RecAP: Biology Edition!(AP is a registered trademark of the College Board and is not affiliated with The APsolute RecAP. Copyright 2020 - The APsolute RecAP, LLC. All rights reserved.)Website:www.theapsoluterecap.comEMAIL:TheAPsoluteRecAP@gmail.comFollow Us:INSTAGRAMTWITTER

Topic: The episode starts off rather professional (read dry) with Antlerboy sharing some rather serious endeavors he is launching.  He introduces two new podcasts; “Joy in Work; The public service transformation” and “Transduction; the systems complexity and cybernetics” – neither of which pose any competition to The Outliers Inn (not even close).  And he also shares another project; Requisite Agility managing change and uncertainty (http://requisiteagility.org/), where “requisite” is required by the nature of things and “agility” being the ability to successfully adapt, cope, or exploit changing situations. That (thankfully) being done and dusted (read buried), the guests (mercifully) come to visit and breathe life back into the conversation with talks of; robot competitions, beer (again), heaps of cash for consultants in the UK, and the tragedy of a video being removed from YouTube causing one of our guests to actually do work. We welcome our first guest, David, who has been working with high school students design and build robots that have to complete a fixed series of tasks.  The robot that completes the tasks the most completely wins.  The team that David and five other mentors coach consists of 148 students.  And although they came in force, the take-away lesson was “don’t forget the ‘Loctite”. Don is still brewing beer and promises to share with the other visitors to The Outliers Inn.  He has been producing a bunch of lagers because the temperature has been cool.  And they just did two high gravity beers; a “Scottish Wee Heavy” which will take months to mature and come in at 10% and a “Barley Wine” coming in at 9%.  Made for sipping not for sessioning. John returns to visit us.  He is in much better spirits than his last visit – and we are sure it’s not because of Don’s concoctions.  Rather, he shares with us that the UK Government has a program with whole pots of money for helping smaller companies and the supply chain into aerospace – and that this will make consultants (including himself) very happy.  In the interim, he’s found a job to keep him busy in logistics – as a delivery driver. Our last guest is Stephane, who is rather desperate today.  He is working on team effectiveness and coming up with a brand new model.  He was disappointed that a YouTube video by Richard Hackman – which used to be there – was now longer there.  This meant he was going to have to actually do some work.  After it is complete, he will be rolling it out to his team, and perhaps further.  And the debate over the best beer continues; Belgian, German, or Don’s… Hosts: Joseph Paris, Founder of the OpEx Society & The XONITEK Group of Companies   Benjamin Taylor,  Managing Partner of RedQuadrant. Recorded: March 3, 2020

Kiss/kick/six

Can neuromodulation be used to change the sensory transduction of the ischemic ventricle? To answer this question, Editor-in-Chief Dr. Irving H. Zucker (University of Nebraska Medical Center) interviewed lead author Jeffrey Ardell ( University of California Los Angeles) and content expert Marc Kaufman (Pennsylvania State University) about the new work by Salavatian et al. Ardell and co-authors found that preemptive spinal cord stimulation can reduce the afferent signal coming from the ischemic ventricle. Was this a result of a change in substrate utilization in the heart or was this “silent ischemia”? Does this spinal cord stimulation work by Ardell and collaborators have the potential to translate to reducing pain for patients with angina? Don’t miss the extra “off the record” commentary at the end to find out.   Siamak Salavatian, Sarah M. Ardell, Mathew Hammer, David Gibbons, J. Andrew Armour, Jeffrey L. Ardell Thoracic spinal cord neuromodulation obtunds dorsal root ganglion afferent neuronal transduction of the ischemic ventricle Am J Physiol Heart Circ Physiol, published November 4, 2019. DOI: doi.org/10.1152/ajpheart.00257.2019

Sam Hughes chats to electronic duo, Nic AKA ROOM8 about their new album Transduction, their work on controversial movie, Cuck and more! ROOM8 is the Stockholm/Los Angeles based artist/producer duo Ezra Reich and Nic Johns. They make music which melds electro pop, dance and synth film soundtracks. They released their debut single EP "Visions of You (feat.Electric Youth)" on Sean Glass' Win Music (Duke Dumont, Flight Facilities, Tiga), as well as another production and co-write for Electric Youth's (From the Drive Soundtrack) debut album "Innerworld" out on Secretly Canadian and Last Gang called "Without You". The latter was singled out as the stand out on the album by the Idolator and NPR. As a live band ROOM8 have played tastemaker nights like Neon Gold's pop shop in Brooklyn and DC with Le Maitre and in LA with Xylo. They have also appeared at School Night with ASTR and supported Kitten (whose debut album they produced), Electric Youth, College, Gavin Turek, Holychild, Life is Beautiful festival and many more. Special thanks to Callum Tennick for editing. Want to sponsor an episode? E-mail Sam at sam@thesoundarchitect.co.uk for your sponsorship to be read out on the podcast. This episode and so much more at: www.thesoundarchitect.co.uk Twitter: @SoundDesignUK Facebook: facebook.com/thesoundarchitect.co.uk Instagram: thesoundarchitectofficial  Stay up to date via our Monthly Newsletter as well: www.thesoundarchitect.co.uk/newsletter --- Send in a voice message: https://anchor.fm/thesoundarchitect/message

Dr. Stephane Angers is a Professor at the University of Toronto. He is an expert in the field of signal transduction, working to understand the signaling mechanisms underlying the Wnt and Hedgehog families of growth factors and the large family of G protein-coupled receptors.

AI Insider and self-driving car industry guru, Dr. Lance Eliot, explains transduction vulnerabilities and self-driving cars. See www.ai-selfdriving-cars.guru for further information.

Podcast LGC TV Les ondes électromagnétiques pour agir sur la cellule Jean-Pierre CHAMODOT. Les ondes électromagnétiques pour agir sur la cellule - Jean-Pierre CHAMODOT et Gwennoline Avec quel signal Œuvrer ? Pourquoi renoncer à la réaction chimique ?Pourquoi renoncer au signal chimique ? Pourquoi choisir l'onde électromagnétique ?Les thérapies énergétiques utilisent des oem de toutes fréquences : Thérapies par résonance, et thérapies dites « quantiques » : Limites et inconvénients de la chimie.Le choix de l'onde électromagnétique repose sur des preuves scientifiques : Preuves d'une nouvelle médecine : Jacques Benveniste 1935-2004 (Onde électromagnétique, Mémoire de l'eau et l'action informationnelle de l'homéopathie). Le professeur Luc Montagnier prix Nobel de médecine (Expérience de Transduction d'ADN : reconstitution chimique d'une molécule d'ADN pilotée par des ondes électromagnétiques).Interprétation du Pr Marc Henry (physique quantique : eau métamorphique piège les ondes électromagnétiques). Preuves de l'épigénétique (Bruce Lipton), de la nouvelle biochimie biologie moléculaire et biophysique (Dr Tian Yow Tsong). L'onde électromagnétique, qu'est-ce que c'est ?L'onde n'est pas une sinusoïde mais un vortex (Nassim Haramein). La thérapie par résonance George Lakhovsky (1869-1942) (cellules reconnaissent et résonnent dans leur propre fréquence). Royal Rife (1888 – 1971) élimine les virus par la résonance. Thérapies « quantiques » : Découvertes de l'aérospatiale Russe, Banques de données de fréquences. Le principe de ces machines. Utilisation du terme « quantique » souvent abusive

Dr Guerra takes a deeper dive into the hormonal and subcellular dysfunctional arrays linking obesity to Non-alcoholic Steatohepatitis (NASH) and Hepatocellular Carcinoma --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

We're back at it -- inoculating your mind against ignorance! Check out the second episode of transduction where we talk about two completely different public health topics! Sources: Link 1; Link 2; Link 3 Viral is written and produced by Linsey Grove and Quinn Lundquist. Our theme is “Take Your Medicine” by the Quick and Easy Boys.Visit us at www.viral-pod.com for more information.

This episode: The bacterial immune system, CRISPR-Cas, can enhance gene transfer via transduction (phages carrying bacteria DNA) despite preventing it via conjugation! Download Episode (14.9 MB, 16.3 minutes) Show notes: Microbe of the episode: Human polyomavirus 8 Journal Paper: Watson BNJ, Staals RHJ, Fineran PC. 2018. CRISPR-Cas-Mediated Phage Resistance Enhances Horizontal Gene Transfer by Transduction. mBio 9:e02406-17. Other interesting stories: Using yeast in packets to measure exposure to radiation Light-controlled swimming bacteria can be shaped into complex patterns Special bacteria could help people lacking an enzyme avoid food toxicity   Email questions or comments to bacteriofiles at gmail dot com. Thanks for listening! Subscribe: Apple Podcasts, RSS, Google Play. Support the show at Patreon, or check out the show at Twitter or Facebook

SHR # 2225_A :: BluePrint Power Hour plus Mechano-transduction: Chew Yourself to a Younger Face :: First Hour: Listener questions are answered about training, nutrition, supplementation and more. PLUS Second Hour: What if chewing could give you the same effects as a face lift? Take years off your face? Well t can. Specific activation of the jaw and chewing can lead to a more aesthetic, more youthful looking face at any age. But you have to know how to do it. ::

SHR # 2225_A :: BluePrint Power Hour plus Mechano-transduction: Chew Yourself to a Younger Face :: First Hour: Listener questions are answered about training, nutrition, supplementation and more. PLUS Second Hour: What if chewing could give you the same effects as a face lift? Take years off your face? Well t can. Specific activation of the jaw and chewing can lead to a more aesthetic, more youthful looking face at any age. But you have to know how to do it. ::

Get ready to be inoculated with some surprising knowledge bits about interesting public health topics. We're not going to spoil the surprise, so sit back and enjoy the show!  Link to Final Forms Article: https://www.newyorker.com/magazine/2014/04/07/final-forms Viral is written and produced by Linsey Grove and Quinn Lundquist. Our theme is “Take Your Medicine” by the Quick and Easy Boys.Visit us at www.viral-pod.com for more information.

--- Support this podcast: https://anchor.fm/brad-richardson/support

--- Support this podcast: https://anchor.fm/brad-richardson/support

In today's podcast, we hear that hackers have looted cryptocurrency exchange Coincheck to the tune of about $530 million. Experty's ICO speculators get phished by crooks. Jackpotting hits American ATMs. The Dridex banking Trojan apparently has a ransomware sibling: FriedEx. Transduction attacks could hit IoT sensors. Steganographic app "Muslim Crypt" is designed for jihadist communication. North Korea tells Britain to mind its own business about WannaCry. Zulfikar Ramzan from RSA with his perspective on Spectre and Meltdown. Strava fitness app reveals locations of user activity. 

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler The TWiVsters explain how superspreader bacteriophages release intact DNA from infected cells, and the role of astrocytes in protecting the cerebellum from virus infection.   Become a patron of TWiV! Links for this episode Nido2017 Meeting Superspreader bacteriophages (mBio) Astrocytes, interferon, and viral infection (JCI) Viral disruption of blood brain barrier (Trends Micro) On Warts by Lewis Thomas (pdf) Letters read on TWiV 428 This episode is brought to you by Blue Apron. Blue Apron is the #1 fresh ingredient and recipe delivery service in the country. See what’s on the menu this week and get your first 3 meals free – WITH FREE SHIPPING – by going to blueapron.com/twiv Weekly Science Picks Alan - Skulls Unlimited Rich - Bernard Moss Reflection Kathy - Why vaccines don't cause autism Dickson - Honomobo Vincent - Trump vs FDA Send your virology questions and comments to twiv@microbe.tv

Dr. Lewis Cantley is the Director of the Meyer Cancer Center at Weill Cornell Medical College as well as the Stanton Clinical Cancer Program at NewYork-Presbyterian Hospital. He is also Professor of Cancer Biology in Medicine and Professor in Oncology Research at Weill Cornell Medical College. In addition, Lewis is Co-Founder of Petra Pharma and Agios Pharmaceuticals. He received his B.S. in Chemistry from West Virginia Wesleyan College and his Ph.D. in Biophysical Chemistry from Cornell University. Lewis conducted postdoctoral research at Harvard University, and served on the faculty at Harvard University, as well as Tufts University before joining the faculty at Cornell. Lewis has received many awards and honors during his career, including the 2005 Pezcoller Foundation-American Association for Cancer Research International Award for Cancer Research, the 2013 Breakthrough Prize in Life Sciences, the 2015 Ross Prize in Molecular Medicine, the 2015 Wolf Prize, the 2015 Association of American Cancer Institutes Distinguished Scientist Award, the 2015 Canada Cairdner award, and he was named one of “The World’s Most Influential Scientific Minds” in 2015 by Thomson Reuter. Lewis is also a Fellow of the American Academy of Arts and Sciences, as well as a Member of the National Academy of Sciences, the Institute of Medicine of the National Academies, and the European Life Sciences Academy. Lewis is here with us today to tell us all about his journey through life and science.

Tue, 22 Sep 2015 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/18720/ https://edoc.ub.uni-muenchen.de/18720/1/Fang_Chong.pdf Fang, Chong

Tue, 22 Sep 2015 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/18720/ https://edoc.ub.uni-muenchen.de/18720/1/Fang_Chong.pdf Fang, Chong

Dr. Jennifer Grandis is a Professor in the Department of Otolaryngology - Head and Neck Surgery, Director of the Clinical and Translational Science Institute, and Associate Vice Chancellor of Clinical and Translational Research at the University of California, San Francisco. She is also an American Cancer Society Professor. Jennifer received her B.A. in Biology and Art History at Swarthmore College and was awarded her M.D. from the University of Pittsburgh School of Medicine. She completed her residency and an Infectious Disease Fellowship at the University of Pittsburgh School of Medicine and went on to serve on the faculty there for over 20 years before accepting her current position at UCSF. Jennifer has received many honors and awards during her career, including the Peggy Wheelock Award for Excellence in Research, Mentoring, and Promotion of Women in Science from the University of Nebraska, as well as the University of Pittsburgh’s Provost’s Award for Excellence in Mentoring, Philip Hench Distinguished Alumnus Award, Chancellor’s Distinguished Research Award, Scientific Leadership Award, promotion to Distinguished Professor of Otolaryngology, and more. Jennifer is also an Elected Member of the Association of American Physicians, the American Society for Clinical Investigation, and the Institute of Medicine of the National Academies. Jennifer is with us today to tell us all about her journey through life and science.

Listen to Gregory Bigford discuss his latest ASN NEURO paper on Neuroendocrine and cardiac metabolic dysfunction and NLRP3 inflammasome activation in adipose tissue and pancreas following chronic spinal cord injury in the mouse.

Vincent, Michael, and Michele discuss how soil-dwelling bacteria induce the formation of root nodules on legumes via a protein called CYCLOPS. 

Thu, 11 Jul 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15943/ https://edoc.ub.uni-muenchen.de/15943/1/Vetter_Alexandra_Kerstin_Maria.pdf Vetter, Alexandra Kerstin Maria ddc:5

Fri, 26 Apr 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15677/ https://edoc.ub.uni-muenchen.de/15677/2/Faust_Thomas.pdf Faust, Thomas ddc:530, ddc:500, Fakultät f

Intracellular protein delivery is offering numerous possibilities in research and in therapy. Aside gene therapy, protein delivery into living cells is one of the most promising tools for the treatment of various so far immedicable diseases including cancer. To develop a practicable protein delivery platform, a test system which allows easy control of successful intracellular delivery is needed. Therefore a test system based on two model proteins was established. A nuclear localization signal tagged EGFP molecule is enabling fast control of cellular uptake and endosomal release. The second model protein ß-galactosidase is evidencing that protein conformation is not irreversible disturbed by modification with the carrier molecules. Protein transduction technology is opening the door for a promising alternative to gene therapy, as it is lacking of the potential malignant side effects of gene therapy. The most limiting step in the development of a therapeutic drug remains the delivery process. In the last decade, many techniques to deliver proteins into living cells were developed. Although great efforts were made, so far no all-purpose technique is available that addresses all critical steps, like efficient uptake, endo-lysosomal escape, low toxicity, while maintaining enzymatic activity. Each method has got its limitation, for example cell type dependence. Among the so far used carriers, the most effective ones are cationic polymers like polyethylenimine. These carriers are lacking of precise structure and often show high toxicity, dependent on the molecular weight of the used polymer. In this thesis the properties of the three arm cationic oligomer 386, which was previously designed for siRNA delivery was investigated in regard of being applicable as a transduction carrier for protein delivery. This carrier molecule, in contrast to other cationic polymers used for protein delivery, is of precise structure, of low molecular weight and potentially degradable by proteases. The transduction oligomer was covalently bound to the protein by a bioreversible bond. Our results reveal that covalent coupling of the structure defined cationic oligomer 386 to a protein leads to a high efficient, serum insensitive and low toxic alternative to established protein transduction technologies. For a general all-purpose delivery system covalent coupling of the carrier to the cargo protein is indispensable. Protein delivery requires special properties to the linker molecule. Therefore in this work a new pH sensitive linker was developed which combines the advantages of click reactions with the implementation of a traceless cleavable bond between two conjugated molecules. Three different click chemistries were performed which all are compatible with the acid labile properties. A traceless cleavage may be a particularly important feature in protein transduction strategies, to maintain full bioactivity of enzymes and other proteins. The current example of 386 carrier-mediated cytosolic delivery and subsequent nuclear import of released nls-EGFP demonstrates the advantage of the traceless linker. To demonstrate that the modification does not irreversibly affect structure and biological activity of proteins, 386-AzMMMan-ßgalactosidase was delivered as a model enzyme. It exhibited cytosolic activity in the transduced cells far higher than without shuttle. Aside from these encouraging options for protein delivery and modification, the linker might have broader use in the design of novel programmed, acid labile and biodegradable drug delivery systems. Targeted therapeutics could, after delivery into acidic tumor areas or upon cellular uptake into endosomes, be dismantled from their outer shell including targeting ligands. Besides drug delivery, the linker may also be of interest for other applications, such as reversible labeling of various biological and also chemical molecules. The developed linking strategy and the presented concepts for transduction shuttles may help to get a step closer in the design of an all-purpose protein delivery platform, applicable on bench as on bedside.

Das Forschungsgebiet nanomechanischer Systeme betrachtet die Bewegung von Strukturen, deren Länge in mindestens einer Richtung deutlich unter einem Mikrometer liegt. Meist werden dabei Auslenkungen untersucht, die in der Nähe einer mechanischen Resonanz angetrieben werden. Das wissenschaftliche Interesse an solchen Strukturen hat mehrere Gründe: aufgrund der kleinen Masse und oftmals geringen Dämpfung (d.h. hohe Güte) reagieren solche nanomechanischen Systeme sehr empfindlich auf Änderungen ihrer Umgebung oder ihrer eigenen Eigenschaften wie etwa ihrer Masse. Die große Vielfalt der nanomechanischen Systeme erlaubt die Kopplung an verschiedenste physikalische Größen wie (Umgebungs-)Druck, Licht, elektrische/magnitische Felder. Dies ermöglicht, die Wechselwirkung selbst zu untersuchen oder entsprechende Änderungen empfindlich zu detektieren. Im Rahmen der vorliegenden Arbeit wurde die Resonator Bewegung von doppelseitig eingespannten Balken untersucht; diese wurden mit konventioneller Mikrofabrikation aus verspanntem Silizium-Nitrid gefertigt. Die große Zugspannung in den Balken führt zu einer hohen mechanischen Stabilität und ebenso zu hohen mechanischen Güten. Ein Teil der Arbeit befasste sich mit der Entwicklung neuer Detektions- und Antriebsmechanismen. Unter Ausnutzung der Polarisierbarkeit des Resonators wurde ein lokaler Antrieb realisiert, der sich durch besondere Einfachkeit auszeichnet. Ebenso wurden Fortschritte in der optischen Detektion erzielt. Ein Photodetektor konnte innerhalb einer optischen Wellenlänge Abstand zum Resonator plaziert werden; dies ermöglicht die lokale Detektion seiner Bewegung. Hochempfindliche Messungen nutzen oft optische Resonanzen; bisherige Umsetzungen basieren auf Reflexionen und sind daher auf Objekte beschränkt, die größer als die verwendete Wellenlänge sind. In einer Zusammenarbeit mit Prof. Kippenberge konnte diese Beschränkung umgangen werden, indem geführtes Licht in einem Mikro-Toroiden verwendet wurde. Weiter wurde in der Arbeit die resonante Bewegung selbst untersucht. Im Bereich hoher Amplituden zeigt die rücktreibende Kraft nichtlineares Verhalten. Das sich dadurch ergebende bistabile Verhalten des Resonators wurde mit Hilfe von kurzen, resonanten Pulsen untersucht; schnelles Schalten wurde erreicht. Die mechanische Dämpfung der Siliziumnitrid Resonatoren wurde untersucht. Die hohen Güten von Systemen unter Zugspannung konnte erklärt werden durch die sich ergebende erhöhte gespeicherte elastische Energie; im Gegensatz zu einem veränderten Dämpfungsverhalten.

In the last decade there has been an impressive growth in research and development in the field of sensor technology. Danilo De Rossi discusses the sensing properties of redundant piezioresistive polymer arrays and the actuation properties of dielectric elastomers for new physical sensors and actuators.

This presentation discusses the various chemical signals and gradients that play a role in the swimming motion of E. coli cells.

Tue, 9 Dec 2008 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/10208/ https://edoc.ub.uni-muenchen.de/10208/1/Schlesner_Matthias.pdf Schlesner, Matthias ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Wed, 24 Sep 2008 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/9108/ https://edoc.ub.uni-muenchen.de/9108/1/Hanke_Stefan.pdf Hanke, Stefan ddc:500, ddc:540, Fakultät für Chemie

This thesis applies quantitative mass spectrometry to research topics in relation to cancer. Proteome-wide quantification at the protein expression level and phosphorylation level were achieved. The technologies developed and used here cover the latest improvements in instrumentation in mass spectrometry, strategies in phosphopeptide enrichment in large scale, algorithms in data analysis and their streamlined implementation, and data mining in downstream bioinformatics. For each of the projects described in this thesis, proteome mapping routinely resulted in identification and quantitation of around 4,000 proteins and phosphoproteome mapping often lead to quantitation of more than 5,000 phosphorylation sites. This ‘systems-wide’ quantitation of the proteome and phosphoproteome is a completely novel development, which has not been used in cancer related topics before. Three major biology topics are studied in this thesis. In the first project, the phosphoproteome of a mouse liver cancer cell line Hepa1-6 was analyzed in-depth, by using phosphatase inhibitors (calyculin A, deltamethrin, and Na-pervanadate) to boost phosphorylation. The characterization of the phosphoproteome revealed a broad spectrum of cellular compartmentalization and biological functions. Quantitation of phosphatase inhibitor treatment using the Stable Isotope Labeling by Amino Acids in Cell culture (SILAC) method revealed the quantitative effects of these inhibitor compounds on the whole phosphoproteome. To our surprise, these three broadband phosphatase inhibitors displayed very different efficiency, with tyrosine phosphorylation significantly boosted but serine/threonine phosphorylation much less affected. Additionally, a method to estimate an upper bound of the stoichiometry of phosphorylation was introduced by comparing phosphorylation in three SILAC conditions: non-treated cells, stimulated cells (e.g. with insulin), and only phosphatase inhibitor treated cells. The methods developed here can be used directly in development of drugs directed against kinases and phosphatases, key regulators in cancer and other diseases. The second project continues with the application of phosphoproteomics techniques. Kinase inhibitors influence cellular signal transduction processes and therefore are of great potential in rescuing aberrant cellular signaling in tumors. In fact they constitute a significant portion of drug developing programs in pharmaceutical industry. With the aim of quantifying the effect of kinase inhibitors over the entire signaling network, the second project first set out to study two very commonly used kinase inhibitor compounds for MAPKs: U0126 and SB202190. Their effect on epidermal growth factor (EGF) signal transduction was quantified and compared using the HeLa cell system. The study confirmed that the MAPK cascades are the predominant signaling branches for propagating the EGF signaling at early time points of stimulation. These large scale examinations also suggest that U0126 and SB202190 are quite specific inhibitors for MAPKs as the majority of regulated phosphopeptides appears to belong to the MAPK pathways. In the second part of the project, the effect on phosphoproteome changes of the chemical compound dasatinib, which was demonstrated to effectively inhibit the constitutively activated fusion protein BCR-ABL and was recently approved for chronic myelogenous leukemia (CML) therapy, was quantified in the human CML cell line K562. Bioinformatic analysis revealed that the most influenced signal transduction branch was the Erk1/2 cascade. Overall more than 500 phosphorylation sites were found to be regulated by dasatinib, the vast majority not described in the literature yet. The third project compared the proteomes of mouse hepatoma cell line Hepa1-6 with the non-transformed mouse primary hepatocytes. This was performed by combining the SILAC heavy labeled form of Hepa1-6 with the primary hepatocytes. To characterize the features of these two proteomes, quantitation information (i.e. protein ratios between the two cell types) was used to divide all proteins into five quantiles. Each quantile was clustered according to the Gene Ontology and KEGG pathway databases to assess their enriched functional groups and signaling pathways. To integrate this information at a higher level, hierarchical clustering based on the p-value from the first Gene Ontology and KEGG clustering was performed. Using this improved bioinformatic algorithm for data mining, the proteomic phenotypes of the primary cells and transformed cells are immediately apparent. Primary hepatocytes are enriched in mitochondrial functions such as metabolic regulation and detoxification, as well as liver functions with tissue context such as secretion of plasma and low-density lipoprotein (LDL). In contrast, the transformed cancer cell line Hepa1-6 is enriched in cell cycle and growth functions. Interestingly, several aspects of the molecular basis of the “Warburg effect” described in many cancer cells became apparent in Hepa1-6, such as increased expression of glycolysis markers and decreased expression of markers for tricarboxylic acid (TCA) cycle. Studies in this thesis only provide examples of the application of mass spectrometry-based quantitative proteomics and phosphoproteomics in cancer research. The connection to clinical research, especially the assessment of drug effects on a proteome wide scale, is a specific feature of this thesis. Although this development is only in its infancy, it reflects a trend in the quantitative mass spectrometry field. We believe that more and more clinical related topics can and will be studied by these powerful methods.

Guest: George I. Viamontes, MD, PhD Host: Leslie P. Lundt, MD Signal transduction is a key concept in cell and molecular biology. How can understanding this concept help us understand how psychotropics and psychotherapy works? Dr. George Viamontes, author of An Atlas of Neurobiology: How the Brain Creates the Self, joins host Dr. Leslie Lundt to discuss signal transduction.

Beverly Mitchell lectures on Leukemia. (September 19, 2007)

Lecture 28: The instructor reviews some major pathways dealing with signal transduction and an application of principles learned to cancerous cells.

Mon, 17 Mar 2008 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/9276/ https://edoc.ub.uni-muenchen.de/9276/1/Staudinger_Wilfried.pdf Staudinger, Wilfried ddc:500, ddc:540, Fakult

Lecture 27: Kaplan continues his discussion of signal transduction, the role of signals in cell migration, and the ability of cells to see which direction to move.

Lecture 26: Kaplan talks about properties of signaling modules and different kinds of membrane receptors that interpret signals from outside the cell.

Enhanced Audio PodcastAired date: 10/23/2006 12:00:00 PM Eastern Time

Enhanced Video PodcastAired date: 10/23/2006 12:00:00 PM Eastern Time Institute: NINDS

Enhanced Audio PodcastAired date: 10/23/2006 12:00:00 PM Eastern Time Institute: NINDS

Enhanced Video PodcastAired date: 10/23/2006 12:00:00 PM Eastern Time

Thu, 15 Apr 2004 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/2061/ https://edoc.ub.uni-muenchen.de/2061/1/Mueller_Irina_M.pdf Müller, Irina ddc:540, d

Tue, 14 Jan 2003 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/728/ https://edoc.ub.uni-muenchen.de/728/1/Kirschke_Stephanie_O.pdf Kirschke, Stephanie Olivia

The SIRPs are a recently discovered family of glycoproteins comprising more than 30 members belonging to the immunoglobulin superfamily. The two different structural subtypes, termed SIRP α and SIRP β, are distinguished by the presence or absence of a cytoplasmic domain, respectively. SIRP α1, the first member of the family to be purified, had been characterised as a negative regulator of signal transduction, and transformation assays had suggested that it also had tumour suppressive effects. Little or nothing is known about the possible function of either the other SIRP α homologues or the members of the SIRP β subtype. The Ig-like domains possessed in the extracellular domains of all SIRPs suggest they have binding partners outside the cell. Cell adhesion experiments using the extracellular domains of SIRP family members showed that SIRP α have adhesion molecule properties. This led to the identification of CD47 as one ligand for SIRP α, performed in collaboration with others21and confirmed here. Furthermore, these experiments suggested that SIRP α molecules have at least one further unknown ligand that is not CD47. The discovery that SIRP α was a cell adhesion molecule with a regulatory role in signal transduction was expanded by in vitro kinase experiments and experiments with inhibitors of tyrosine kinases. They showed that SIRP α associated with more than one kinase activity, and that cytosolic tyrosine kinases, probably of the srcfamily, were necessary for SIRP α to regulate tyrosine phosphorylation of a receptor. In contrast to SIRP α molecules, proteins belonging to the SIRP β subtype remain uncharacterised. Therefore a large part of this work concentrates on the SIRP β subtype, its associated proteins, localisation and possible function in a cell. In vitro association experiments revealed that SIRP β is part of a multiprotein complex at the cell membrane, where SIRP β1 interacted with DAP12, an adaptor protein with a transmembrane domain. DAP12 linked SIRP β to a cytosolic tyrosine kinase identified as Syk confirmed by western blot and PCR from cDNA preparations of the cell lines used in these experiments. The interaction of Syk with the complex required the tyrosine phosphorylation of DAP12. Coligating SIRP β molecules at the membrane with a SIRP β-specific monoclonal antibody recruited Syk to DAP12 where it could be activated by treatment with sodium pervanadate. In vitro kinase assays detected several unknown phosphorylated proteins associated with SIRP β/DAP12/Syk when Syk was activated that may represent signalling molecules operating downstream of the complex. Cotransfection experiments showed that SIRP α complexed with kinase activities that enabled it to inhibit both DAP12 tyrosine phosphorylation and Syk kinase activity. This suggested that both complexes at some point operated in close contact, so experiments were carried out to localise SIRP proteins in the cell. Fractionation experiments discovered that SIRP α and possibly SIRP β could be detected in fractions that contained GPI microdomains, or caveolae. Similar investigations with the SIRP β1/DAP12 complex revealed that DAP12 was dependent upon SIRP β for its direction to the plasma membrane where it was activated by tyrosine kinases. Membrane localisation of SIRP β was similarly reliant upon DAP12 expression, however, further experiments suggested that SIRP β may be secreted from the cell in the absence of DAP12. To address the potential role of SIRP β1/DAP12 complex in signal transduction, cell lines overexpressing SIRP β and DAP12 were analysed. Cell death assays suggested that the SIRP β1/DAP12 complex was a negative regulator of induced cell death, and that tyrosine kinases might be involved in this regulation. Cells overexpressing SIRP β and DAP12 showed an enhanced rate of acid production, corresponding to an enhanced rate of glucose metabolism. These observations suggests that, SIRP β1/DAP12 overexpression may be a factor that contributing to a transformed phenotype, works in opposition to SIRP α molecules. This work views the SIRPs as components of a cluster of different proteins at the cell membrane that recruit and use other cytosolic proteins, among them tyrosine kinases and phosphatases. It shows that SIRP α molecules may collaborate with SIRP β family members to modulate the signals generated by other receptors in signal transduction. This modulation may influence aberrant cellular processes that lead to disease.

The sugar units of glycan structures store information and establish an alphabet of life. The language of the oligosaccharide coding units is deciphered by receptors such as lectins and the decoded message can be transduced by multiple signaling pathways. Similar to glycoconjugates, these receptors can exhibit pronounced changes in quantitative and qualitative aspects of expression, as attested by a wealth of lectin and immunohistochemical studies. Since histochemistry provides a static picture, it is essential to shed light on the mechanisms of how a recognitive protein-carbohydrate interplay can be transduced into cellular responses. Their consequences for example for cell morphology will then be visible to the histochemist. Therefore, basic signaling routes will be graphically outlined and their trigger potential will be explained by selected examples from the realm of glycosciences.

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Recent studies have demonstrated that the CD3-ζ subunit of the T cell antigen receptor (TCR) complex is involved in signal transduction. However, the function of the remaining invariant subunits, CD3-γ, -δ, and , is still poorly understood. To examine their role in TCR function, we have constructed TCR/CD3 complexes devoid of functional ζ subunit and showed that they are still able to trigger the production of interleukin-2 in response to antigen or superantigen. These data, together with previous results, indicate that the TCR/CD3 complex is composed of at least two parallel transducing units, made of the γδ and ζ chains, respectively, Furthermore, the analysis of partially truncated ζ chains has led us to individualize a functional domain that may have constituted the building block of most of the transducing subunits associated with antigen receptors and some Fc receptors.

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