Podcasts about correlative

Dr. John Sweetenham shares highlights from Day 4 of the 2024 ASCO Annual Meeting, including exciting new data from the IMROZ trial in multiple myeloma, adjuvant therapy for triple-negative breast cancer in A-BRAVE, and the front-line treatment of advanced renal cell carcinoma in JAVELIN Renal-101. TRANSCRIPT Dr. John Sweetenham: I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my top takeaways on selected abstracts from Day 4 of the 2024 ASCO Annual Meeting.   Today's selection features 3 randomized prospective trials in the first-line treatment of multiple myeloma, adjuvant therapy for triple negative breast cancer, and the frontline treatment of advanced renal cell carcinoma, all of which provide important new data.   My full disclosures are available in the transcript of this episode. The first of today's abstracts is number 7500. This abstract, presented by Dr. Thierry Facon from the Department of Hematology at the University of Lille in France, describes the results of the IMROZ study. This was a multicenter phase 3 study comparing a current standard first-line regimen for transplant ineligible patients with myeloma VRd with the same combination plus an additional agent, isatuximab.  The combination of bortezomib, lenalidomide and dexamethasone, known as VRd, is currently a standard first-line regimen for patients with multiple myeloma, both transplant eligible and ineligible. Previous phase 3 studies have shown that the addition of an anti-CD38 antibody to triplet regimens improves outcomes in newly diagnosed patients. Based on early phase clinical trial data showing promising response rates with isatuximab, the IMROZ study was conducted to compare isatuximab VRd with VRd alone in patients who were either ineligible for transplant or had no immediate indication for transplant. IMROZ was a global study conducted in 21 countries that involved 446 patients randomly assigned 3:2 to induction therapy with Isa-VRd followed by continuous Isa-Rd or induction therapy with VRd followed by Rd alone. The rate of complete response or better was approximately 75% with Isa-VRd compared with 64% with VRd alone. Very good partial response or better was achieved in 89% of patients with Isa-VRd, compared with around 83% of those with VRd alone. With a median follow-up at 5 years, Isa-VRd followed by Isa-Rd had reduced the risk of progression or death by 40.4% compared with VRd alone. The 60-month progression-free survival rate was 63% for Isa-VRd compared with around 45% with VRd alone, and the progression-free survival benefit was maintained in most of the analyzed subgroups. Minimal residual disease negativity was also measured in this study in both the intent to treat population and those patients who achieved a complete response. For example, in the intent to treat population, the MRD negative rate was 58% with Isa-VRd compared with around 43% with VRd alone. There were also higher rates of sustained MRD negativity for 12 months or longer among patients assigned to Isa-VRd compared with VRd alone, reflecting deeper responses in the Isa-VRd arm. Although overall survival data is still immature, data from an interim analysis showed a favorable trend in the Isa-VRd arm with 22.4% risk reduction compared with VRd alone. There was little additional toxicity from the inclusion of isatuximab with the VRd regimen and the quality-of-life data were comparable and stable in both arms of the study. The investigators concluded that although overall survival data are immature, there is a trend in favor of Isa-VRd and this, combined with the favorable response, toxicity and progression-free survival data, establish isatuximab VRd as a potential new standard of care for newly diagnosed multiple myeloma patients not eligible for transplant. There was some discussion regarding the potential use of this regimen in patients over 80 years of age since the upper age limit was capped in IMROZ at 80 years. Although there are concerns for tolerance of the 4-drug regimen in the older patient group, it seems likely that this will be adopted, especially for those with good performance status and without major comorbidities.   Next up is LBA500. This abstract reports results of the A-BRAVE trial. This trial, presented by Dr. Pier Franco Conte from the University of Padova, Italy, was a phase 3 randomized trial to assess the efficacy of the immune checkpoint inhibitor avelumab in 2 groups of patients: those with early triple negative breast cancer, with residual disease after neoadjuvant chemotherapy; and those at high risk after primary surgery and adjuvant chemotherapy. As Dr. Conte explained in the introduction to this trial, there is a fairly compelling rationale for the use of checkpoint inhibitors in triple negative breast cancer. The disease has been shown to be more immunogenic than the other breast cancer types with immune biomarkers such as TILs and PDL-1 expression associated with better prognosis, added to which, data in metastatic breast cancer show a correlation between PDL-1 expression and checkpoint inhibitor response. In the A-BRAVE study, 477 high risk patients who had completed local, regional, and systemic treatment with curative intent were stratified according to adjuvant or post neoadjuvant status and randomized 1:1 to receive avelumab at 2-week intervals for 52 weeks or to observation only. Results of the study showed a non-statistically significant improvement in three-year disease-free survival in the overall intent to treat population at 5.1% and in the post neoadjuvant patients at 6.2%. Overall survival was a secondary endpoint in this trial. The results show a significant improvement in overall survival of 8.1% in the intent-to-treat population and a very similar improvement in the post-neoadjuvant patients. The authors reported good tolerance of avelumab, although in total almost 30% discontinued treatment at some point. In their conclusion, the investigators state that the 34% reduction in the risk of death suggests a potential role for avelumab in early triple negative breast cancer patients at high risk after primary surgery or with invasive disease after neoadjuvant chemotherapy. Correlative studies are planned on tumor plasma and feces in this study. These are interesting and somewhat tantalizing results, suggesting a real effect from avelumab. Although confounded somewhat by the sample size, it will be important to see how these results mature with further follow-up.   Today's third selected abstract is number 4508 reporting the final analysis of the JAVELIN Renal 101 phase 3 trial in patients with advanced renal cell carcinoma. This study compared the combination of axitinib plus avelumab with sunitinib in this patient group. The trial included 886 patients, of whom around 61% of those in the combination group and around 65% of those in the monotherapy group were PDL-1 positive. In the initial analysis from the JAVELIN Renal 101 study, after at least 6 months of follow-up, avelumab and axitinib significantly improved progression-free survival over sunitinib in patients with PDL-1 positive tumors and in the overall population with advanced renal cell carcinoma. In the fall cohort, the median progression-free survival with the combination was 13.8 months compared with only 8.4 months with sunitinib, and based on those results, the combination received FDA approval as a first-line treatment for patients with advanced renal cell carcinoma in May of 2019. The progression-free survival observed in the initial analysis was confirmed with a new long-term analysis in the overall population. Median progression-free survival with avelumab and axitinib was 13.9 months compared with only 8.5 months with sunitinib and the median duration of response with the combination was 19.4 months versus 14.5 months with sunitinib. However, no difference in overall survival was seen. At 60 months, the overall survival in the combination group was 38.8% and 36.2% with sunitinib. In patients who were PDL-1 positive at 60 months, overall survival with a combination was 37.1% compared with 33.4% with sunitinib.  Despite the sustained difference in progression-free survival seen with this combination, the discussant at this session pointed out that most oncologists are unlikely to recommend a combination which has not been shown to improve overall survival when published studies have reported on 4 combinations which do positively impact overall survival in this patient group. Despite the good tolerance of this regimen, it seems unlikely to be a preferred frontline regimen in advanced renal carcinoma moving forward.  That concludes today's report. Thanks for listening and we hope you have enjoyed listening to our top takeaways from ASCO24. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review and subscribe wherever you get your podcasts.   Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness

BUFFALO, NY- February 21, 2024 – A new research #perspective was #published in Oncotarget's Volume 15 on February 8, 2024, entitled, “Combining causal and correlative approaches to discover biomarkers of response to paclitaxel.” As discussed in this new paper, researchers Alberto Moscona-Nissan, Karl J. Habashy, Victor A. Arrieta, Adam M. Sonabend, and Crismita Dmello from Universidad Panamericana School of Medicine, Northwestern University and Universidad Nacional Autónoma de México recently discovered a putative paclitaxel response predictive biomarker for glioblastoma and breast cancer using the whole genome CRISPR knockout screen. The biomarker candidate was validated in two independent breast cancer patient cohorts that received taxane treatment. “To further evaluate the potential application of this biomarker in the clinic for patients with glioblastoma, a prospective validation in cohorts of patients with glioblastoma is essential and will be performed as part of our ongoing phase II clinical trial (NCT04528680).” The validation of novel biomarkers of susceptibility to therapy is critical to elucidate the efficacy signal of therapeutic agents. This is especially important in the context of glioblastoma, where therapeutic benefit is variable and unpredictable, leading to negative trials, yet the outcome of subset of patients has outperformed expectations. “Precision and personalized medicine can lead to a transition from a stochastic treatment response into predictable scenarios. Further identification of predictive biomarkers, validation, and study of combinations as predictive models is critical to generate a greater impact that can be translated to the bedside of patients.” DOI - https://doi.org/10.18632/oncotarget.28549 Correspondence to - Crismita Dmello - crismita.dmello@northwestern.edu, and Adam M. Sonabend - adam.sonabend@northwestern.edu Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28549 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, glioblastoma, predictive biomarker, CRISPR screen, paclitaxel About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551868v1?rss=1 Authors: Lin, Z., Zhang, X., Nandi, P., Lin, Y., Wang, L., Chu, Y., Paape, T., Yang, Y., Xiao, X., Liu, Q. Abstract: X-ray tomography and x-ray fluorescence imaging are two non-invasive imaging techniques to study cellular structures and chemical element distributions, respectively. However, correlative X-ray tomography and fluorescence imaging for the same cell has yet to be routinely realized due to challenges in sample preparation and X-ray radiation damage. Here we report an integrated experimental and computational workflow for achieving correlative multi-modality X-ray imaging of a single cell. The method consists of the preparation of radiation-resistant single-cell samples using live-cell imaging-assisted chemical fixation and freeze-drying procedures, targeting and labeling cells for correlative x-ray tomography and x-ray fluorescence measurement, and computational reconstruction of the correlative and multi-modality images. With X-ray tomography, cellular structures including the overall structure and intracellular organelles are visualized, while X-ray fluorescence imaging reveals the distribution of multiple chemical elements within the same cell. Our correlative method demonstrates the feasibility and broad applicability of using X-rays to understand cellular structures and the roles of multiple chemical elements and related proteins in signaling and other biological processes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

#correspondences #witchcraft #spellcasting What are the underlying philosophical principles behind using correspondences in magick, witchcraft, healing, divination, and astrology? Correlative thinking, macrocosm and microcosm and the related worldview. RECOMMENDED READINGS Dictionary of Gnosis and Western Esotericism https://amzn.to/3QTcVkX Plato's Timaeus https://amzn.to/3RSqGBB Plato's Ion https://amzn.to/3dl3jS4 Plato's https://amzn.to/3LmNN4C The Hermetic and Alchemical Writings of Paracelsus https://amzn.to/3BrwD1b The Signature of All Things by Boehme https://amzn.to/3LlHbUh REFERENCE Hanegraaff, W.J. and Brach, J.-P. (2006) ‘Correspondences', in W.J. Hanegraaff (ed.) Dictionary of Gnosis and Western Esotericism. Leiden, London: Brill, pp. 275–279. CONNECT & SUPPORT

In this episode, we delve into the latest data on bispecific antibodies in multiple myeloma with Dr. Ajai Chari. Here are the key studies discussed:1. Teclistamab (MajesTEC-1 trial): https://pubmed.ncbi.nlm.nih.gov/35661166/2. Correlative analysis from MajesTEC-1 trial: https://ashpublications.org/blood/article/140/Supplement%201/241/4876193.  Talquetamab (MonumenTAL-1 trial): https://pubmed.ncbi.nlm.nih.gov/36507686/4. Phase 1 trial of fixed-duration cevostamab: https://ashpublications.org/blood/article/140/Supplement%201/4415/4923395. Phase 1 trial of ABBV-383: https://pubmed.ncbi.nlm.nih.gov/36029527/6. Paper summarizing infections with different bispecific antibodies in myeloma: https://pubmed.ncbi.nlm.nih.gov/36716411/

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.24.538041v1?rss=1 Authors: Franzkoch, R., Anand, A., Breitsprecher, L., Psathaki, O. E., Barisch, C. Abstract: The infection course of Mycobacterium tuberculosis is highly dynamic and comprises sequential stages that require damaging and crossing of several membranes to enable the translocation of the bacteria into the cytosol or their escape from the host. Many important breakthroughs such as the restriction of vacuolar and cytosolic mycobacteria by the autophagy pathway and the recruitment of sophisticated host repair machineries to the Mycobacterium-containing vacuole have been gained in the Dictyostelium discoideum/M. marinum system. Despite the availability of well-established light and advanced electron microscopy techniques in this system, a correlative approach that integrates both methodologies with almost native ultrastructural preservation is still lacking at the moment. This is most likely due to the low ability of D. discoideum to adhere to surfaces, which results in cell loss even after fixation. To address this problem, we improved the adhesion of cells and developed a straightforward and convenient workflow for 3D-correlative light and electron microscopy. This approach includes high-pressure freezing, which is an excellent technique for preserving membranes. Thus, our method allows to monitor the ultrastructural aspects of vacuole escape which is of central importance for the survival and dissemination of bacterial pathogens. 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/2023.01.27.525698v1?rss=1 Authors: Mocaer, K., Mizzon, G., Gunkel, M., Halavatyi, A., Steyer, A. M., Oorschot, V., Schorb, M., Le Kieffre, C., Yee, D. P., Chevalier, F., Gallet, B., Decelle, J., Schwab, Y., Ronchi, P. Abstract: Photosynthetic microalgae are responsible for an important fraction of CO2 fixation and O2 production on Earth. Three-dimensional ultrastructural characterization of these organisms in their natural environment can contribute to a deeper understanding of their cell biology. However, the low throughput of volume electron microscopy (vEM) methods, along with the complexity and heterogeneity of environmental samples, pose great technical challenges. In the present study, we used a workflow based on a specific EM sample preparation, compatible with both light and vEM imaging in order to target one cell among a complex natural community. This method revealed the 3D subcellular landscape of a photosynthetic dinoflagellate with quantitative characterization of multiple organelles. We could show that this cell contains a single convoluted chloroplast and the arrangement of the flagellar apparatus with its associated photosensitive elements. Moreover, we observed chromatin features that could shed light on how transcriptional activity takes place in organisms where chromosomes are permanently condensed. Together with providing insights in dinoflagellates biology, this proof-of-principle study illustrates an efficient tool for the targeted ultrastructural analysis of environmental microorganisms in heterogeneous mixes. 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/2023.01.10.523473v1?rss=1 Authors: Bosch, C., Lindenau, J., Pacureanu, A., Peddie, C. J., Majkut, M., Douglas, A. C., Carzaniga, R., Rack, A., Collinson, L., Schaefer, A., Stegmann, H. Abstract: Correlative multimodal imaging is a useful approach to investigate complex structural relations in life sciences across multiple scales. For these experiments, sample preparation workflows that are compatible with multiple imaging techniques must be established. In one such implementation, a fluorescently-labelled region of interest in a biological soft tissue sample can be imaged with light microscopy before staining the specimen with heavy metals, enabling follow-up higher resolution structural imaging at the targeted location, bringing context where it is required. Alternatively, or in addition to fluorescence imaging, other microscopy methods such as synchrotron X-ray computed tomography with propagation-based phase contrast (SXRT) or serial blockface scanning electron microscopy (SBF-SEM) might also be applied. When combining imaging techniques across scales, it is common that a volumetric region of interest (ROI) needs to be carved from the total sample volume before high resolution imaging with a subsequent technique can be performed. In these situations, the overall success of the correlative workflow depends on the precise targeting of the ROI and the trimming of the sample down to a suitable dimension and geometry for downstream imaging. Here we showcase the utility of a novel femtosecond laser device to prepare microscopic samples (1) of an optimised geometry for synchrotron X-ray microscopy as well as (2) for subsequent volume electron microscopy applications, embedded in a wider correlative multimodal imaging workflow (Fig. 1). 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/2022.12.20.520730v1?rss=1 Authors: Austin, T. T., Thomas, C., Clifton, L., Blockley, A., Warren, B. Abstract: Aging is due to a complex decline of multiple biological processes. Some of the causes include oxidative damage, mitochondrial and proteostatic dysfunction and DNA damage. This results in deterioration as biological systems age. This age-related decline is well quantified, and experienced, for human hearing and is presumed to be due to a decrease in the ears metabolism; specifically a decrease in ability to maintain an electrochemical gradient, the endocochlear potential. However, direct measurements of metabolism across a lifespan in an auditory system are lacking. Even if metabolism does decrease with age is it a cause of age-related auditory decline or simply correlative? All auditory systems across the animal kingdom share functional principles including ion pumping cells, auditory receptors, spiking auditory nerves and multiple supporting cells. Therefore, we used an insect, the desert locust, Schistocerca gregaria, as a physiologically versatile model to understand how cellular metabolism correlates with age and impacts on age-related auditory decline. We found that although metabolism correlates with age-related auditory decline it is not causative. 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/2022.11.22.516823v1?rss=1 Authors: Redpath, G. M. I., Rae, J. A., Yao, Y., Ruan, J., Cagigas, M. L., Whan, R., Hardeman, E. C., Gunning, P. W., Ananthanarayanan, V., Parton, R. G., Ariotti, N. Abstract: Unambiguous targeting of cellular structures for in situ cryo-electron microscopy in the heterogeneous, dense, and compacted environment of the cytoplasm remains challenging. Here we have developed a novel cryogenic correlative light and electron microscopy (cryo-CLEM) workflow which combines thin cells grown on a mechanically defined substratum to rapidly analyse organelles and macromolecular complexes in the cell by cryo-electron tomography (cryo-ET). We coupled these advancements with optogenetics to redistribute perinuclear-localised organelles to the cell periphery for cryo-ET. This reliable and robust workflow allows for fast in situ analyses without the requirement for cryo-focused ion beam milling. We have developed a protocol where cells can be frozen, imaged by cryo-fluorescence microscopy and ready for batch cryo-ET within a day. 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/2022.11.19.517200v1?rss=1 Authors: Kirchweger, P., Mullick, D., Sawin, P. P., Wolf, S. G., Elbaum, M. Abstract: Cryo-electron tomography (cryo-ET) is the prime method for cell biological studies in three dimensions (3D) at high resolution. We have introduced cryo-scanning transmission electron tomography (CSTET), which can access larger 3D volumes, on the scale of 1 micron, making it ideal to study organelles and their interactions in situ. Here we introduce two relevant advances: a) we demonstrate the utility of multi-color super-resolution radial fluctuation light microscopy under cryogenic conditions (cryo-SRRF), and b) we extend the use of deconvolution processing for dual-axis CSTET data. We show that cryo-SRRF nanoscopy is able to reach resolutions in the range of 100 nm, using commonly available fluorophores and a conventional widefield microscope for cryo-correlative light-electron microscopy (cryo-CLEM). Such resolution aids in precisely identifying regions of interest before tomographic acquisition and enhances precision in localizing features of interest within the 3D reconstruction. Dual-axis CSTET tilt series data and application of entropy regularized deconvolution during post-processing results in close-to isotropic resolution in the reconstruction without averaging. We show individual protein densities in a mitochondrion-ER contact in a cell region 850 nm thick. The integration of cryo-SRRF with deconvolved dual-axis CSTET provides a versatile workflow for studying unique objects in a cell. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Nomadology: The War Machine by Deleuze and Guattari; Axiom 3, Proposition 9, the final part

A poem about being not poet-cool. Hey, thanks for listening to Carrie Does Poems. These podcasts and more writing tips are at Carrie's website, carriejonesbooks.blog. There's also a donation button there. Even a dollar inspires a happy dance in Carrie, so thank you for your support. The music you hear is made available through the creative commons and it's a bit of a shortened track from the fantastic Eric Van der Westen and the track is called “A Feather” and off the album The Crown Lobster Trilogy. While Carrie only posts poems weekly here, she has them (in written form) almost every other weekday over on Medium. You should check it out! https://freemusicarchive.org/music/eric-van-der-westen/the-crown-lobster-trilogy-selection --- Send in a voice message: https://anchor.fm/carriejonesbooks/message Support this podcast: https://anchor.fm/carriejonesbooks/support

Ahhh, this one was SO GOOD! It couldn't be denied! Three months ago, I had an amazing coaching session with one of my lovely students who has since passed the test. In this podcast, I breakdown exactly HOW she correlates her ideas and if it doesn't, question it. Put yourself into the shoes of the examiner and those that grade your essay and ask yourself "how " would you question both ideas back to back. Stay tuned!TOEFL iBT Reading Course: https://arsenioseslpodcast.podia.com/toefl-ibt-reading-courseTOEFL iBT Writing Course: https://arsenioseslpodcast.podia.com/toefl-ibt-pre-writing-courseTOEFL iTP Course (Reading): https://arsenioseslpodcast.podia.com/toefl-itp-reading/buyTOEFL iTP Course (Structure): https://arsenioseslpodcast.podia.com/toefl-itp-structure/buyTOEFL iTP Course (Written Expression): https://arsenioseslpodcast.podia.com/toefl-itp-written-expressionTOEFL iTP Course (Listening): https://arsenioseslpodcast.podia.com/toefl-itp-listeningInstagram ESL Podcast: https://www.instagram.com/arsenioseslpodcast/Podcast on Spotify: https://open.spotify.com/show/7hdzplWx6xB8mhwDJYiP6fFacebook: https://www.facebook.com/Arseniobuck/?ref=bookmarksYoutube: https://www.youtube.com/channel/UCIzp4EdbJVMhhSnq_0u4ntABuzz sprout: https://www.buzzsprout.com/165390

In this podcast, Andy will teach you how to use ‘the correlative comparative'. You don't need to know the name. Think of it as ‘the more, the more'. This is a common sentence structure that helps us connect ideas in a fun way using comparative adjectives; it will help you give advice, talk about your feelings and goals, and you'll be able to do it easily and enjoyably! Remember... if you need extra practice with your English grammar – you can do this by going to www.e2english.com

The gang discusses two papers that explore the functional morphology of ancient groups. The first paper looks at soft tissue in ammonites which can be used to infer locomotion, and the second paper looks at how functional morphology changed as tetrapods transitioned from marine to terrestrial environments. Meanwhile, James explores the evolution of baked goods, Curt develops a new business plan, and Amanda dreams of Tiktaalik.   Up-Goer Five (Curt Edition): Our friends talk about two papers that look into how we can learn how very old animals moved and how that moving changes over time by looking at the parts we can find in the ground. The first paper looks at animals with a lot of arms who live in a big hard round hard part. Today, while we have a lot of these animals with lots of arms, only one of those animals today lives in a big round thing. In the past, there was a big group of animals that lived in a round thing, but they did it in a different way than the one we have around today. However, because it is hard to find pieces that are not hard, we have used the animal that is around today as our best guess for how these old animals may have moved. This paper finds some soft pieces which give us a better idea of how the soft parts that allow animals to move were put together. And these old animals probably moved in a very different way from the other animal from today who lives in a round thing. In fact, the old animals that live in round parts may have moved in a way that is sort of like how the animals with many arms who do not live in round things today move (but not exactly the same). The second paper looks at how the hard parts of animals with four legs changed when they animals moved onto land. This paper looks at these changes and also looks at how these changes make it so these animals move in different ways. They find that the animals with four legs in the water all have legs that look like we would expect for moving in water. The animals that are on land also have legs that fit the moving we would see for things that need to hold themselves up and move on land. The fun thing is that the animals who come from the animals who are not quite on land and not quite in water yet (the ones in the middle of this change) do not fit into any space where we would expect the animal to be able to move well. This could mean that these animals (which did well enough) were living in a time when it was alright to suck at moving. Also, it may be that some groups of animals that moved onto land from this group that sucks at moving might have had some of the animals in that group that came back to this sucking at moving space.   References: Dickson, Blake V., et al. "Functional adaptive landscapes predict terrestrial capacity at the origin of limbs." Nature 589.7841 (2021): 242-245. Cherns, Lesley, et al. "Correlative  tomography of an exceptionally preserved Jurassic ammonite implies  hyponome-propelled swimming." Geology (2021).

Suppliers, manufacturers and end users demand ever-increasing quality standards, so an advanced technical cleanliness program is fundamental to eradicating critical particulate contamination along the entire production process. ZEISS Technical Cleanliness Solutions identify the root cause of contamination, allowing you to make the right decision faster.

Oncotarget published "The acylfulvene alkylating agent, LP-184, retains nanomolar potency in non-small cell lung cancer carrying otherwise therapy-refractory mutations" which reported that KEAP1 mutant NSCLCs further activate NRF2 and upregulate its client PTGR1. LP-184, a novel alkylating agent belonging to the acylfulvene class is a prodrug dependent upon PTGR1. The authors hypothesized that NSCLC with KEAP1 mutations would continue to remain sensitive to LP-184. LP-184 demonstrated highly potent anticancer activity both in primary NSCLC cell lines and in those originating from brain metastases of primary lung cancers. LP-184 activity correlated with PTGR1 transcript levels but was independent of mutations in key oncogenes and tumor suppressors. Correlative analyses of sensitivity with cell line gene expression patterns indicated that alterations in NRF2, MET, EGFR and BRAF consistently modulated LP-184 sensitivity. These correlations were then extended to TCGA analysis of 517 lung adenocarcinoma patients, out of which 35% showed elevated PTGR1, and 40% of those further displayed statistically significant co-occurrence of KEAP1 mutations. The gene correlates of LP-184 sensitivity allow additional personalization of therapeutic options for future treatment of NSCLC. Dr. Aditya Kulkarni from The Lantern Pharma, Inc. said, "KEAP1, KRAS, TP53 and STK11/LKB1 are among the commonly altered genes with considerable clinical prevalence in non-small cell lung cancers (NSCLC)." The authors profiled primary and metastatic in vitro models of NSCLC for their sensitivity to LP-184 as well as standard of care agents, evaluated gene correlates of LP-184 response, and obtained evidence on in vivo anti-tumor effect of LP-184. Mutated KEAP1 and concomitant decreased KEAP1 activity in cancer cells induces greater nuclear accumulation of NRF2, causing enhanced transcriptional induction of antioxidants, xenobiotic metabolism enzymes, and drug efflux pumps, thereby rendering KEAP1 mutations predictive of chemotherapy resistance in NSCLC patients. The identification of a trend toward detrimental overall survival among a subset of platinum-treated NSCLC patients harboring co-occurring KRAS and STK11 mutations could label a more aggressive molecular subtype of NSCLC. They therefore investigated LP-184 sensitivity in NSCLC cell lines harboring individual or concomitant mutations in KEAP1, KRAS, TP53 and STK11. They sought to assess LP-184 activity in a panel of selected NSCLC adenocarcinoma cell lines, determine associations between genomic and transcriptomic profiles and responses of cell lines tested, and compare in vitro potency of LP-184 with that of approved chemotherapy agents. The Kulkarni Research Team concluded in their Oncotarget Research Output, "Our key findings demonstrate that the alkylating agent LP-184 has nanomolar potency in several NSCLC cell lines and is more potent than selected approved alkylating chemotherapeutics. Additionally, LP-184 has the potential to target tumors with elevated PTGR1 regardless of presence of other co-occurring mutations but is especially found to be effective in the background of clinically significant KEAP1 mutations. We propose further evaluation of LP-184 in multiple PTGR1 high NSCLC settings that may not necessarily be mutually exclusive, including in highly prevalent KEAP1 and KRAS mutant tumors (Figure 6), and in patients with lack of actionable targets or resistance-related genes with no effective therapy options available." DOI - https://doi.org/10.18632/oncotarget.27943 Full text - https://www.oncotarget.com/article/27943/text/ Correspondence to - Aditya Kulkarni - aditya@lanternpharma.com Keywords - non-small cell lung cancer, acylfulvene, alkylating agent, PTGR1, LP-184 About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

Have fun with this special podcast episode with your favorite ESL teacher Billgreen54! --- Send in a voice message: https://anchor.fm/english-grammar-review/message Support this podcast: https://anchor.fm/english-grammar-review/support

How do we use correlative conjunctions? Visit Larisa Web Content Creators! --- Send in a voice message: https://anchor.fm/english-grammar-review/message Support this podcast: https://anchor.fm/english-grammar-review/support

Correlative conjunctions are one of the least taught subjects to ESL students. Learn more with Billgreen54! Visit Larisa Web Content Creators! --- Support this podcast: https://anchor.fm/bill-green/support

Conjunctions connect words, phrases and more! Let Billgreen54 explain American English in simple terms! Visit Larisa Web Content Creators! --- Support this podcast: https://anchor.fm/bill-green/support

Correlative Conjunctions can be confusing. Bill explains American English grammar is simple terms! Visit Larisa Web Content Creators! --- Support this podcast: https://anchor.fm/bill-green/support

What are correlative conjunctions? They are just one of the many parts of English! Learn more with Billgreen54! Visit Larisa Web Content Creators! --- Support this podcast: https://anchor.fm/bill-green/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.09.374157v1?rss=1 Authors: Navikas, V., Leitao, S. M., Grussmayer, K. S., Descloux, A., Drake, B., Yserentant, K., Werther, P., Herten, D.-P., Wombacher, R., Radenovic, A., Fantner, G. E. Abstract: High-resolution live-cell imaging is necessary to study complex biological phenomena. Modern fluorescence microscopy methods are increasingly combined with complementary, label-free techniques to put the fluorescence information into the cellular context. The most common high-resolution imaging approaches used in combination with fluorescence imaging are electron microscopy and atomic-force microscopy (AFM), originally developed for solid-state material characterization. AFM routinely resolves atomic steps, however on soft biological samples, the forces between the tip and the sample deform the fragile membrane, thereby distorting the otherwise high axial resolution of the technique. Here we present scanning ion-conductance microscopy (SICM) as an alternative approach for topographical imaging of soft biological samples, preserving high axial resolution on cells. SICM is complemented with live-cell compatible super-resolution optical fluctuation imaging (SOFI). To demonstrate the capabilities of our method we show correlative 3D cellular maps with SOFI implementation in both 2D and 3D with self-blinking dyes for two-color high-order SOFI imaging. Finally, we employ correlative SICM/SOFI microscopy for visualizing actin dynamics in live COS-7 cells with subdiffractional resolution. Copy rights belong to original authors. Visit the link for more info

Do you remember correlative conjunctions? Visit Larisa Web Content Creators! --- Send in a voice message: https://anchor.fm/english-grammar-review/message Support this podcast: https://anchor.fm/english-grammar-review/support

Do you know your correlative conjunctions? Visit Larisa Web Content Creators! --- Send in a voice message: https://anchor.fm/english-grammar-review/message Support this podcast: https://anchor.fm/english-grammar-review/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.07.327734v1?rss=1 Authors: Fulton, K. A., Briggman, K. L. Abstract: A dense reconstruction of neuronal synaptic connectivity typically requires high-resolution 3D electron microscopy (EM) data, but EM data alone lacks functional information about neurons and synapses. One approach to augment structural EM datasets is with the fluorescent immunohistochemical (IHC) localization of functionally relevant proteins. We describe a protocol that obviates the requirement of tissue permeabilization in thick tissue sections, a major impediment for correlative pre-embedding IHC and EM. We demonstrate the permeabilization free labeling of neuronal cell types, intracellular enzymes, and synaptic proteins in tissue sections hundreds of microns thick in multiple brain regions while simultaneously retaining the ultrastructural integrity of the tissue. Finally, we explore the utility of this protocol by performing proof-of-principle correlative experiments combining two-photon imaging of protein distributions and 3D electron microscopy. Copy rights belong to original authors. Visit the link for more info

MIB Agents OsteoBites S1 Ep20: Correlative Science Leading to Active and Emerging Clinical Trials for #Osteosarcoma ... Guest Information: *Richard Gorlick, MD Division Head, Dept Chair and Professor Pediatrics Director of the Pediatric Sarcoma Research Lab The University of Texas, MD Anderson Cancer Center *J. Andrew Livingston, MD Assistant Professor, Department of Sarcoma Medical Oncology Department of Pediatrics Co-leader for the MDACC Adolescent and Young Adult Program University of Texas MD Anderson Cancer Center *Sajad Khazal, MB. ChB. Assistant Professor, Department of Pediatrics Patient Care Division of Pediatrics The University of Texas MD Anderson Cancer Center Panelists: *Charlotte Murdoff OsteoWarrior & MIB Fund Holder *Ryan Kennington OsteoWarrior & MIB Agents Junior Board Member *Amanda Levine OsteoWarrior & Patient Advocate Hosted By Ann Graham, MIB Agents President ... Register for next week when we will be speaking with: Kurt Weiss, MD Fellow for Innovative Cancer Research Associate Professor, University of Pittsburgh School of Medicine Department of Orthopaedic Surgery/Musculoskeletal Oncology Vice Chair of Translational Research and Director of the Musculoskeletal Oncology Laboratory Baylor College of Medicine ... MIB Agents is a leading pediatric #osteosarcoma nonprofit dedicated to Making It Better for our community of patients, caregivers, doctors, and researchers with the goal of less toxic, more effective treatments and a cure for this aggressive bone cancer. More information at www.mibagents.org ... --- Support this podcast: https://anchor.fm/mibagents/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.12.247643v1?rss=1 Authors: Shashkova, S., Nyström, T., Leake, M. C., Wollman, A. J. Abstract: Most cells adapt to their environment by switching combinations of genes on and off through a complex interplay of transcription factor proteins (TFs). The mechanisms by which TFs respond to signals, move into the nucleus and find specific binding sites in target genes is still largely unknown. Single-molecule fluorescence microscopes, which can image single TFs in live cells, have begun to elucidate the problem. Here, we show that different environmental signals, in this case carbon sources, yield a unique single-molecule fluorescence pattern of foci of a key metabolic regulating transcription factor, Mig1, in the nucleus of the budding yeast, Saccharomyces cerevisiae. This pattern serves as a 'barcode' of the gene regulatory state of the cells which can be correlated with cell growth characteristics and other biological function. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.06.240481v1?rss=1 Authors: Yang, J. E., Larson, M. R., Sibert, B. S., Shrum, S., Wright, E. R. Abstract: Cryo-correlative light and electron microscopy (CLEM) is a technique that uses the spatiotemporal cues from fluorescence light microscopy (FLM) to investigate the high-resolution ultrastructure of biological samples by cryo-electron microscopy (cryo-EM). Cryo-CLEM provides advantages for identifying and distinguishing fluorescently labeled proteins, macromolecular complexes, and organelles from the cellular environment. Challenges remain on how correlation workflows and software tools are implemented on different microscope platforms to support microscopy-driven structural studies. Here, we present an open-source desktop application tool, CorRelator, to bridge between cryo-FLM and cryo-EM/ET data collection instruments. CorRelator was designed to be flexible for both on-the-fly and post-acquisition correlation schemes. The CorRelator workflow is easily adapted to any fluorescence and transmission electron microscope (TEM) system configuration. CorRelator was benchmarked under cryogenic and ambient temperature conditions using several FLM and TEM instruments, demonstrating that CorRelator is a rapid and efficient application for image and position registration in CLEM studies. CorRelator is a cross-platform software featuring an intuitive Graphical User Interface (GUI) that guides the user through the correlation process. CorRelator source code is available at: https://github.com/wright-cemrc-projects/corr. Copy rights belong to original authors. Visit the link for more info

Join Tom as he further discusses After Life.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.16.206284v1?rss=1 Authors: Rogenmoser, L., Arnicane, A., Jancke, L., Elmer, S. Abstract: Background: Absolute pitch (AP) refers to the ability of effortlessly identifying given pitches without the reliance on any reference pitch. Correlative evidence suggests that the left posterior dorsolateral prefrontal cortex (DLPFC) is responsible for the process underlying pitch labeling in AP. Objective: Here, we aimed at investigating the causal relationship between the DLPFC and the pitch-labeling process underlying AP. Methods: To address this, we measured sight-reading performance of right-handed AP possessors and matched control musicians (N=18 per sample) under cathodal and sham transcranial direct current stimulation of the left DLPFC. The participants were instructed to report visually presenting notations as accurately and fast as possible by playing with their right hand on a piano. The notations were simultaneously presented with distracting auditory stimuli that either matched or mismatched them in different semitone degrees. Results: Unlike the control participants, the AP possessors revealed an interference effect in that they responded slower in mismatching conditions than in the matching one. Under cathodal stimulation, half of the time discrepancies between matching and mismatching conditions vanished; specifically, the ones with small up to moderate deviations. Conclusions: These findings confirm that the pitch-labeling process underlying AP occurs automatically and is largely non-suppressible when triggered by tone exposure. The improvement of the AP possessors' sight-reading performance in response to the suppression of the left DLPFC using cathodal stimulation confirms a causal relationship between this brain structure and pitch labeling. Copy rights belong to original authors. Visit the link for more info

Do you know what correlative conjunctions are? --- Send in a voice message: https://anchor.fm/english-grammar-review/message Support this podcast: https://anchor.fm/english-grammar-review/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.09.142885v1?rss=1 Authors: Zhang, H., Karisetty, B. C., Bhatnagar, A., Armour, E. M., Beaver, M., Roach, T. V., Mortazavi, S., Mandloi, S., Elefant, F. Abstract: Alzheimer's disease is an age-related neurodegenerative disorder hallmarked by amyloid-{beta} (A{beta}) plaque accumulation, neuronal cell death, and cognitive deficits that worsen during disease progression. Histone acetylation dysregulation, caused by an imbalance between the histone acetyltransferases (HAT) Tip60 and histone deacetylase 2 (HDAC2), can directly contribute to AD pathology. Nevertheless, early and late-stage regulatory epigenetic alterations remain to be characterized. Here we profile Tip60 HAT/HDAC2 dynamics and transcriptional changes across early and late stage AD pathology in the Drosophila brain produced solely by human amyloid-{beta}42. We show that early A{beta}42 induction leads to disruption of Tip60 HAT/HDAC2 balance during early neurodegenerative stages preceding A{beta} plaque accumulation that persists into late AD stages. Correlative transcriptome studies reveal alterations in biological processes we classified as transient (early-stage only), late-onset (late-stage only), and constant (both). Increasing Tip60 HAT levels in the A{beta}42 fly brain protects against AD functional pathologies that include A{beta} plaque accumulation, neural cell death, cognitive deficits, and shorter life-span. Strikingly, Tip60 also protects against A{beta}42 induced transcriptomic alterations via distinct mechanisms during early and late stages of neurodegeneration. Our findings provide new insights into distinct modes of epigenetic gene alterations and Tip60 neuroprotection during early versus late stages in AD progression. Copy rights belong to original authors. Visit the link for more info

Correlative conjunctions are one of the least taught subjects to ESL students. Learn more with Billgreen54!

Conjunctions connect words, phrases and more! Let Billgreen54 explain American English in simple terms!

Correlative Conjunctions can be confusing. Bill explains American English grammar is simple terms!

What are correlative conjunctions? They are just one of the many parts of English! Learn more with Billgreen54!

Did you know that there are 4 different types of conjunctions? Take a minute and learn what correlative conjunctions are! ---- Follow Us Online Here: Website: Facebook: Twitter: Instagram: YouTube: Medium: Spotify: --- Send in a voice message: https://anchor.fm/homework-help-global/message

Correlative conjunctions are words used in combination with each other. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/english-grammar-review/message Support this podcast: https://anchor.fm/english-grammar-review/support

Correlative conjunctions are used in pairs! --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/english-grammar-review/message Support this podcast: https://anchor.fm/english-grammar-review/support

Correlative conjunctions are all about more than one! --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/english-grammar-review/message Support this podcast: https://anchor.fm/english-grammar-review/support

Correlative Conjunctions are always an interesting subject! --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/english-grammar-review/message Support this podcast: https://anchor.fm/english-grammar-review/support

This podcast is part of the 2017 NSH Symposium/Convention Poster Podcast Series.  The lead author of this poster is Debbie Guerrero. For more information on the author and to view the abstract, visit The Block.

In this webinar, you will learn about the power of 3D imaging of larger samples. In particular, you will: - Gain insight in to how to use x-ray microscopy to analyze biological samples - Learn the basics about sample preparation for x-ray microscopy - Understand the benefits and drawbacks to different imaging conditions X-Ray Microscopy (XRM) is a relatively new technique that combines the geometric magnification of traditional micro-CT with the optical magnification of light microscopy. Using XRM you can image the internal structure of objects with fine resolution without destroying the sample. For example, the Zeiss Versa XRM system allows an unprecedented view inside samples varying in size from the mesoscale (cm) to the microscale (µm) at consistently sub-micron image resolutions. This webinar will focus on biological applications of X-Ray microscopy. We will cover imaging calcified structures, such as bone, to soft tissues, like the intervertebral disc. You will also learn about visualizing blood vessels using vascular tracing agents. In addition, we will cover the basics of sample preparation along with the pros and cons of different imaging conditions. Finally, we will give you a sneak view into using XRM to spatially target, in three-dimensions, tissue specific structures in a whole organism for 3D ultrastructural imaging using Focused Ion Beam – Scanning Electron Microscopy (FIB-SEM) using the ATLAS 5 Correlative Workspace.

In a live Studio class, advanced writers discuss the short story, Chicxulub, by TC Boyle. They are particularly interested in the literary device known as the objective correlative, the infusion of description and the movement of the scenes it's used in this story.

When working with time series data, there are a number of important diagnostics one should consider to help understand more about the data. The auto-correlative function, plotted as a correlogram, helps explain how a given observations relates to recent preceding observations. A very random process (like lottery numbers) would show very low values, while temperature (our topic in this episode) does correlate highly with recent days.   See the show notes with details about Chapel Hill, NC weather data by visiting:   https://dataskeptic.com/blog/episodes/2016/acf-correlograms