Podcasts about abstract while

Abstract: While, for understandable reasons, Protestant Christendom tends to downplay the question, the more ancient Christian churches have historically placed considerable weight on what is often termed “apostolic succession.” The Catholic church, for instance, strongly affirms the “primacy of Peter” and the status of the Bishop of Rome, the Pope, as ancient Peter's lineal successor. […] The post Who Holds the Keys? first appeared on The Interpreter Foundation.

Abstract: While, for understandable reasons, Protestant Christendom tends to downplay the question, the more ancient Christian churches have historically placed considerable weight on what is often termed “apostolic succession.” The Catholic church, for instance, strongly affirms the “primacy of Peter” and the status of the Bishop of Rome, the Pope, as ancient Peter's lineal successor. […] The post Who Holds the Keys? first appeared on The Interpreter Foundation.

Abstract: While, for understandable reasons, Protestant Christendom tends to downplay the question, the more ancient Christian churches have historically placed considerable weight on what is often termed “apostolic succession.” The Catholic church, for instance, strongly affirms the “primacy of Peter” and the status of the Bishop of Rome, the Pope, as ancient Peter's lineal successor. […] The post Who Holds the Keys? first appeared on The Interpreter Foundation.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Bias-Augmented Consistency Training Reduces Biased Reasoning in Chain-of-Thought, published by miles on March 11, 2024 on The AI Alignment Forum. [Twitter thread] I'm not going to add much additional commentary at the moment and will just let people check out the paper! But to give a bit more context: This paper is building off prior work we have done showing that chain-of-thought explanations can be misleading, which I wrote about on the alignment forum here. Broadly, this work fits into the process-based oversight agenda (e.g., here). Consistency training/evaluation also fits into scalable oversight: Evaluating consistency may be easier than evaluating a model's reasoning or final predictions directly (e.g., also explored here). Abstract: While chain-of-thought prompting (CoT) has the potential to improve the explainability of language model reasoning, it can systematically misrepresent the factors influencing models' behavior--for example, rationalizing answers in line with a user's opinion without mentioning this bias. To mitigate this biased reasoning problem, we introduce bias-augmented consistency training (BCT), an unsupervised fine-tuning scheme that trains models to give consistent reasoning across prompts with and without biasing features. We construct a suite testing nine forms of biased reasoning on seven question-answering tasks, and find that applying BCT to GPT-3.5-Turbo with one bias reduces the rate of biased reasoning by 86% on held-out tasks. Moreover, this model generalizes to other forms of bias, reducing biased reasoning on held-out biases by an average of 37%. As BCT generalizes to held-out biases and does not require gold labels, this method may hold promise for reducing biased reasoning from as-of-yet unknown biases and on tasks where supervision for ground truth reasoning is unavailable. Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org.

Abstract: While references to heaven in the Old Testament are sparse, non-explicit, and predominantly cosmological, the New Testament reveals a more complex concept of the afterlife that reflects a rapidly evolving understanding of Heaven. The Jewish apocalyptic literature of the late Second Temple period describes a heaven of multiple degrees that is populated with angels […] The post Degrees of Glory: A Brief History of Heaven and Graded Salvation first appeared on The Interpreter Foundation.

Abstract: While references to heaven in the Old Testament are sparse, non-explicit, and predominantly cosmological, the New Testament reveals a more complex concept of the afterlife that reflects a rapidly evolving understanding of Heaven. The Jewish apocalyptic literature of the late Second Temple period describes a heaven of multiple degrees that is populated with angels […] The post Degrees of Glory: A Brief History of Heaven and Graded Salvation first appeared on The Interpreter Foundation.

Abstract: While references to heaven in the Old Testament are sparse, non-explicit, and predominantly cosmological, the New Testament reveals a more complex concept of the afterlife that reflects a rapidly evolving understanding of Heaven. The Jewish apocalyptic literature of the late Second Temple period describes a heaven of multiple degrees that is populated with angels […] The post Degrees of Glory: A Brief History of Heaven and Graded Salvation first appeared on The Interpreter Foundation.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.31.551259v1?rss=1 Authors: Starck, L., Sarem, M., Heimrich, B., Sawarkar, R., Ritz, M.-F., Hutter, G., Shastri, V. P. Abstract: While the direct biological factors underlying the progression of GBM, an aggressive form of brain cancer, have been extensively studied, emerging evidence suggests that indirect biological triggers, such as traumatic brain injury (TBI), may also have a role. Since reactive astrocytes are associated with TBI, and astroglial cells are the source of proteoglycans which contribute to changes in biophysical characteristics (stochastic topography, stiffness) of the brain, we postulated a role for stochastic nanoroughness in the induction of glioma. Using a model system to emulate such physical cues, we demonstrate that human cortical astrocytes undergo spontaneous organization into spheroids in response to nanoroughness and retain the spheroid phenotype even upon withdrawal of the physical cues. Furthermore, spheroids serve as aggregation foci for naive astrocytes; express activated MMP2, and disseminate upon implantation in mouse brain. RNA-seq revealed a tumoral phenotype with a gene expression pattern involving p53, ADAMTS proteases and fibronectin. Moreover, nanoroughness mediates a cross-talk between cancer cells and astrocytes through induced senescence. These findings implicate a role for stochastic biophysical cues in driving a potential malignant transformation of astrocytes. 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/2023.07.25.550477v1?rss=1 Authors: Chang, L.-A., Engelmann, J. B. Abstract: While the effects of anxiety on various cognitive processes, including memory, attention, and learning, have been relatively well documented, the neurobiological effects of anxiety on social cognitive processes remain largely unknown. We address this gap using threat-of-shock to induce incidental anxiety while participants performed two false-belief tasks, a standard and an economic-games version. During belief formation and belief inferences, regions in a canonical social cognition network showed activation reflecting mentalizing, including the temporoparietal junction (TPJ), precuneus, and dorsomedial prefrontal cortex (dmPFC). At the same time, we found threat-related suppression of social cognition regions during belief inferences. A conjunction analysis confirmed that a network of regions was simultaneously engaged during mentalizing and suppressed by anxiety: bilateral TPJ, bilateral IFG, and putamen. We examined how threat impacted the connectivity between seed regions from the conjunction analyses and its targets. During belief formation, we found that anxiety suppressed the connectivity between the precuneus seed and two key mentalizing nodes, the dmPFC and right TPJ. Moreover, during belief inferences threat specificallty suppressed belief-based connectivity between putamen and its targets in IPS and dlPFC, and dispositional distress significantly modulated threat-related suppression of connectivity between the left TPJ seed and left IPS. Our results highlight important effects of incidental and dispositional anxiety on specific nodes of the social cognition network. Taken together, our study uncovers novel interactions between the reward, social cognition, and attentional systems, indicating that social cognitive processes rely on support from other large-scale networks, and that these network interactions are disrupted under incidental anxiety. 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/2023.07.19.549751v1?rss=1 Authors: Sorensen, D., Avcu, E., Lynch, S., Ahlfors, S., Gow, D. Abstract: While the neural bases of the earliest stages of speech categorization have been widely explored using neural decoding methods, there is still a lack of consensus on questions as basic as how wordforms are represented and in what way this word-level representation influences downstream processing in the brain. Isolating and localizing the neural representations of wordform is challenging because spoken words evoke activation of a variety of representations (e.g., segmental, semantic, articulatory) in addition to form-based representations. We addressed these challenges through a novel integrated neural decoding and effective connectivity design using region of interest (ROI)-based, source reconstructed magnetoencephalography/electroencephalography (MEG/EEG) data collected during a lexical decision task. To localize wordform representations, we trained classifiers on words and nonwords from different phonological neighborhoods and then tested the classifiers' ability to discriminate between untrained target words that overlapped phonologically with the trained items. Training with either word or nonword neighbors supported decoding in many brain regions during an early analysis window (100-400 ms) reflecting primarily incremental phonological processing. Training with word neighbors, but not nonword neighbors, supported decoding in a bilateral set of temporal lobe ROIs, in a later time window (400-600 ms) reflecting activation related to word recognition. These ROIs included bilateral posterior temporal regions implicated in wordform representation. Effective connectivity analyses among regions within this subset indicated that word-evoked activity influenced the decoding accuracy more than nonword-evoked activity did. Taken together, these results evidence functional representation of wordforms in bilateral temporal lobes isolated from phonemic or semantic representations. 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/2023.07.10.548401v1?rss=1 Authors: Chen, X., Sokirniy, I., Wang, X., Jiang, M., Mseis-Jackson, N., Williams, C., Mayes, K., Jiang, N., Puls, B., Du, Q., Shi, Y., Li, H. Abstract: While astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain elusive. MicroRNAs (miRNAs), as post-transcriptional regulators of gene expression, play crucial roles during development and under various pathological conditions. To understand the function of miRNAs during AtN reprogramming process, we performed RNA-seq of both mRNAs and miRNAs on human astrocyte (HA) cultures upon NeuroD1 overexpression. Bioinformatics analyses showed that NeuroD1 not only activates essential neuronal genes to initiate reprogramming process but also induces miRNA changes in HA. Among the upregulated miRNAs, we identified miR-375 and its targets, neuronal ELAVL genes (nELAVLs), which encode a family of RNA-binding proteins and are also upregulated by NeuroD1. We further showed that manipulating miR-375 level regulates nELAVLs expression during NeuroD1-mediated reprogramming. Interestingly, miR-375/nELAVLs are also induced by reprogramming factors Neurog2 and ASCL1 in HA suggesting a conserved function to neuronal reprogramming, and by NeuroD1 in the mouse astrocyte culture and spinal cord. Functionally, we showed that miR-375 overexpression improves NeuroD1-mediated reprogramming efficiency by promoting cell survival at early stages in HA even in cultures treated with the chemotherapy drug Cisplatin. Moreover, miR-375 overexpression does not appear to compromise maturation of the reprogrammed neurons in long term HA cultures. Lastly, overexpression of miR-375-refractory ELAVL4 induces apoptosis and reverses the cell survival-promoting effect of miR-375 during AtN reprogramming. Together, we demonstrate a neuro-protective role of miR-375 during NeuroD1-mediated AtN reprogramming and suggest a strategy of combinatory overexpression of NeuroD1 and miR-375 for improving neuronal reprogramming efficiency. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Abstract: While later Creedal Christians have come to view “the Ascension” recorded in the first chapter of Acts as a conclusive corporeal appearance of the Resurrected Lord, earliest Christians do not appear to have conceived of this appearance as “final” in any temporal or experiential sense. A careful investigation of canonical resurrection literature displays a […] The post “I Will Come to You”: An Investigation of Early Christian Beliefs about Post-Ascension Visitations of the Risen Jesus first appeared on The Interpreter Foundation.

Abstract: While later Creedal Christians have come to view “the Ascension” recorded in the first chapter of Acts as a conclusive corporeal appearance of the Resurrected Lord, earliest Christians do not appear to have conceived of this appearance as “final” in any temporal or experiential sense. A careful investigation of canonical resurrection literature displays a […] The post “I Will Come to You”: An Investigation of Early Christian Beliefs about Post-Ascension Visitations of the Risen Jesus first appeared on The Interpreter Foundation.

Abstract: While later Creedal Christians have come to view “the Ascension” recorded in the first chapter of Acts as a conclusive corporeal appearance of the Resurrected Lord, earliest Christians do not appear to have conceived of this appearance as “final” in any temporal or experiential sense. A careful investigation of canonical resurrection literature displays a […] The post “I Will Come to You”: An Investigation of Early Christian Beliefs about Post-Ascension Visitations of the Risen Jesus first appeared on The Interpreter Foundation.

Abstract: While some scholars have suggested that the doctrine of theosis — the transformation of human beings into divine beings — emerged only in Nauvoo, the essence of the doctrine was already present in the Book of Mormon, both in precept and example. The doctrine is especially well developed in 1 Nephi, Alma 19, and […] The post Theosis in the Book of Mormon: The Work and Glory of the Father, Mother and Son, and Holy Ghost first appeared on The Interpreter Foundation.

Abstract: While some scholars have suggested that the doctrine of theosis — the transformation of human beings into divine beings — emerged only in Nauvoo, the essence of the doctrine was already present in the Book of Mormon, both in precept and example. The doctrine is especially well developed in 1 Nephi, Alma 19, and […] The post Theosis in the Book of Mormon: The Work and Glory of the Father, Mother and Son, and Holy Ghost first appeared on The Interpreter Foundation.

Abstract: While some scholars have suggested that the doctrine of theosis — the transformation of human beings into divine beings — emerged only in Nauvoo, the essence of the doctrine was already present in the Book of Mormon, both in precept and example. The doctrine is especially well developed in 1 Nephi, Alma 19, and […] The post Theosis in the Book of Mormon: The Work and Glory of the Father, Mother and Son, and Holy Ghost first appeared on The Interpreter Foundation.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.12.536531v1?rss=1 Authors: Kwon, J., Kim, S., Kim, D.-K., Joo, J., Kim, S., Cha, M., Lee, C. J. Abstract: While huge strides have recently been made in language-based machine learning, the ability of artificial systems to comprehend the sequences that comprise animal behavior has been lagging behind. In contrast, humans instinctively recognize behaviors by finding similarities in behavioral sequences. Here, we develop an unsupervised behavior-mapping framework, SUBTLE (spectrogram-UMAP-based temporal-link embedding), to capture comparable behavioral repertoires from 3D action skeletons. To find the best embedding method, we devise a temporal proximity index as a metric to gauge temporal representation in the behavioral embedding space. The method achieves the best performance compared to current embedding strategies. Its spectrogram-based UMAP clustering not only identifies subtle inter-group differences but also matches human-annotated labels. SUBTLE framework automates the tasks of both identifying behavioral repertoires like walking, grooming, standing, and rearing, and profiling individual behavior signatures like subtle inter-group differences by age. SUBTLE highlights the importance of temporal representation in the behavioral embedding space for human-like behavioral categorization. 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/2023.04.03.535302v1?rss=1 Authors: Griffin, M., Talbott, H., Guardino, N., Guo, J., Spielman, A., Chen, K., Mascharak, S., Parker, J., Henn, D., Liang, N., King, M., Cotterell, A., Bauer-Rowe, K., Abbas, D., Deleon, N. M. D., Fahy, E., Sivaraj, D., Downer, M., Akras, D., Berry, C., Cook, J., Quarto, N., Klein, O. D., Lorenz, P., Gurtner, G., Januszyk, M., Wan, D. C., Longaker, M. T. Abstract: While past studies have suggested that plasticity exists between dermal fibroblasts and adipocytes, it remains unknown whether fat actively contributes to fibrosis in scarring. We show that adipocytes convert to scar-forming fibroblasts in response to Piezo-mediated mechanosensing to drive wound fibrosis. We establish that mechanics alone are sufficient to drive adipocyte-to-fibroblast conversion. By leveraging clonal-lineage-tracing in combination with scRNA-seq, Visium, and CODEX, we define a mechanically naive fibroblast-subpopulation that represents a transcriptionally intermediate state between adipocytes and scar-fibroblasts. Finally, we show that Piezo1 or Piezo2-inhibition yields regenerative healing by preventing adipocytes activation to fibroblasts, in both mouse-wounds and a novel human-xenograft-wound model. Importantly, Piezo1-inhibition induced wound regeneration even in pre-existing established scars, a finding that suggests a role for adipocyte-to-fibroblast transition in wound remodeling, the least-understood phase of wound healing. Adipocyte-to-fibroblast transition may thus represent a therapeutic target for minimizing fibrosis via Piezo-inhibition in organs where fat contributes to fibrosis. 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/2023.03.01.530653v1?rss=1 Authors: Chen, N., Zhang, Y., Rivera-Rodriguez, E., Yu, A., Hobin, M., Rosbash, M., Griffith, L. Abstract: While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (co-transmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling in Drosophila. We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins. Suppression of cholinergic signaling involves posttranscriptional regulation of cholinergic transcripts by the microRNA miR-190; chronic loss of miR-190 function allows expression of cholinergic machinery, reducing and fragmenting sleep. Using a translation-trap strategy we show that neurons in these populations have episodes of transient translation of cholinergic proteins, demonstrating that suppression of co-transmission is actively modulated. Posttranscriptional restriction of fast transmitter co-transmission provides a mechanism allowing reversible tuning of neuronal output. 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/2023.02.27.530205v1?rss=1 Authors: Copp, M. E., Shine, J., Brown, H. L., Nimmala, K. R., Chubinskaya, S., Collins, J. A., Loeser, R., Diekman, B. O. Abstract: While advanced age has long been recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). Using an acute irradiation model to bring the baseline level of all donors to the same starting point, this study demonstrates a decline in repair efficiency during aging when comparing chondrocytes from young (less than or equal to 45 years old), middle-aged (50-65 years old), or older ( greater than 70 years old) cadaveric donors with no known history of OA or macroscopic cartilage degradation at isolation. Activation of SIRT6 in middle-aged chondrocytes with MDL-800 (20 uM) improved the repair efficiency, while inhibition with EX-527 (10 uM) inhibited the rate of repair and the increased the percentage of cells that retained high levels of damage. Treating chondrocytes from older donors with MDL-800 for 48 hours significantly reduced the amount of DNA damage, despite this damage having accumulated over decades. Lastly, chondrocytes isolated from the proximal femurs of mice between 4 months and 22 months of age revealed both an increase in DNA damage with aging, and a decrease in DNA damage following MDL-800 treatment. 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/2023.02.26.529776v1?rss=1 Authors: Zhang, X., Li, J., Li, Z., HONG, B., Diao, T., Ma, X., Nolte, G., Engel, A. K., Zhang, D. Abstract: While our daily verbal communication is challenging with unavoidable environmental noise, the neural mechanisms underlying speech-in-noise comprehension remain to be elucidated. The present study investigated the neural tracking of acoustic and semantic speech information during noisy naturalistic speech comprehension. Participants listened to narrative audios mixed with spectrally matched stationary noise at three signal-to-ratio (SNR) levels and 60-channel electroencephalography signals were recorded. A temporal response function (TRF) method was employed to derive event-related-like responses to the continuous speech stream at both the acoustic and the semantic levels. Whereas the amplitude envelope of the naturalistic speech was taken as the acoustic feature, word entropy and word surprisal were extracted via the natural language processing method as two semantic features. Theta-band frontocentral TRF responses to the acoustic feature were observed at around 400 ms following speech fluctuation onset over all three SNR levels, and the response latency was more delayed with increasing SNR. Delta-band frontal TRF responses to the semantic feature of word entropy were observed at around 200 to 600 ms leading to speech fluctuation onset over all three SNR levels, and the response latency became more leading with increasing SNR. While the following responses to speech acoustics were consistent with previous studies, the leading responses to speech semantics suggest our brain could be taking an active approach to deal with noisy speech comprehension. 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/2023.02.15.528749v1?rss=1 Authors: Maxson, M. E., Huynh, K., Grinstein, S. Abstract: While it has been known for decades that luminal acidification is required for normal traffic along the endocytic pathway, the precise underlying mechanism(s) remain unknown. We found that dissipation of the endomembrane pH gradient resulted in acute formation of large Rab5- or Rab7-positive vacuoles. Vacuole formation was associated with and required hyperactivation of the Rabs, which was attributable to impaired GTPase activity, despite normal recruitment of cognate GAPs. Surprisingly, LRRK2 -a kinase linked to Parkinsons disease-was recruited to endomembranes and markedly activated upon dissipation of luminal acidification. LRRK2 phosphorylated Rab GTPases, rendering them insensitive to deactivation. Importantly, genetic deletion of LRRK2 prevented the {Delta}pH-induced vacuolation, implying that the kinase is required to modulate vesicular traffic. We propose that by dictating the state of activation of LRRK2 and in turn that of Rab GTPases, the development of a progressive luminal acidification serves as a timing device to control endocytic maturation. 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/2023.01.09.523031v1?rss=1 Authors: Zheng, H., Li, Q., Li, S., Li, Z., Brotto, M., Weiss, D., Prosdocimo, D., Xu, C., Reddy, A., Puchowicz, M., Zhao, X., Weitzmann, M. N., Jain, M. K., Qu, C.-K. Abstract: While mitochondria in different tissues have distinct preferences for energy sources, they are flexible in utilizing competing substrates for metabolism according to physiological and nutritional circumstances. However, the regulatory mechanisms and significance of metabolic flexibility are not completely understood. Here we report that the deletion of PTPMT1, a mitochondria-based phosphatase, critically alters mitochondrial fuel selection -- the utilization of pyruvate, a key mitochondrial substrate derived from glucose (the major simple carbohydrate), is inhibited, whereas the fatty acid utilization is enhanced. PTPMT1 knockout does not impact the development of the skeletal muscle or heart. However, the metabolic inflexibility ultimately leads to muscular atrophy, heart failure, and sudden death. Mechanistic analyses reveal that the prolonged substrate shift from carbohydrates to lipids causes oxidative stress and mitochondrial destruction, which in turn results in marked accumulation of lipids and profound damage in the knockout muscle cells and cardiomyocytes. Interestingly, PTPMT1 deletion from the liver or adipose tissue does not generate any local or systemic defects. These findings suggest that PTPMT1 plays an important role in maintaining mitochondrial flexibility and that their balanced utilization of carbohydrates and lipids is essential for maintaining both skeletal muscle and heart despite the two tissues having different preferred energy sources. 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/2023.01.05.522888v1?rss=1 Authors: Cazzagon, G., Roubinet, C., Baum, B. Abstract: While the Formin-nucleated actomyosin cortex has been shown to drive the changes in cell shape that accompany cell division in both symmetric and asymmetric cell divisions, it is not clear whether or not Arp2/3-nucleated branched actin filament networks also play a role. In order to look for mitotic roles of the Arp2/3 complex, here we use Drosophila neural stem cells as a model system. These cells are unusual in that they divide asymmetrically to produce a large and small daughter cell with different fates. Our analysis identifies a pool of Arp2/3-dependent actin-based membrane protrusions that form at the apical cortex of these cells as they enter mitosis. Strikingly, at metaphase, these protrusions co-localise with components of the SCAR complex. By perturbing Arp2/3 complex activity we show that this apical pool of actin likely functions to limit the accumulation of apical Myosin in metaphase. Following the onset of anaphase, the loss of these SCAR and Arp2/3 dependent structures then leads to a delay in the clearance of apical Myosin and to cortical instability at cytokinesis. These data point to a role for a polarised branched actin filament network in fine tuning the apical actomyosin cortex to enable the precise control of cell shape during asymmetric cell division. 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/2022.12.12.520171v1?rss=1 Authors: Yang, Y., Arnold, M. L., Choy, E. H., Lange, C. M., Poon, K., Broussalian, M., Sun, L.-H., Moreno, T. M., Singh, A., Driscoll, M., Kumsta, C., Hansen, M. Abstract: While autophagy is key to maintain cellular homeostasis, tissue-specific roles of individual autophagy genes are less understood. To study neuronal autophagy in vivo, we inhibited autophagy genes specifically in C. elegans neurons, and unexpectedly found that knockdown of early-acting autophagy genes, i.e., involved in formation of the autophagosome, except for atg-16.2, decreased PolyQ aggregates and increased lifespan, albeit independently of the degradation of autophagosomal cargo. Neuronal aggregates can be secreted from neurons via vesicles called exophers, and we found that neuronal inhibition of early-acting autophagy genes atg-7 and lgg-1/Atg8, but not atg-16.2 increased exopher formation. Moreover, atg-16.2 mutants were unable to form exophers, and atg-16.2 was required for the effects of early autophagy gene reduction on neuronal PolyQ aggregation, exopher formation, and lifespan. Notably, neuronal expression of full-length ATG-16.2 but not ATG-16.2 without a functional WD40 domain, important for non-canonical functions of ATG16L1 in mammalian cells, restored these phenotypes. Collectively, we discovered a specific role for C. elegans ATG-16.2 and its WD40 domain in exopher biogenesis, neuronal proteostasis, and lifespan determination, highlighting a possible role for non-canonical autophagy functions in both exopher formation and in aging. 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/2022.12.08.519285v1?rss=1 Authors: Lundquist, A., Lazar, E., Han, N. S., Emanuelsson, E., Reitzner, S. M., Chapman, M. A., Alkass, K., Druid, H., Petri, S., Sundberg, C. J., Bergmann, O. Abstract: While manual quantification is still considered the gold standard for skeletal muscle histological analysis, it is time-consuming and prone to investigator bias. We assembled an automated image analysis pipeline, FiNuTyper (Fiber and Nucleus Typer), from recently developed deep learning-based image segmentation methods, optimized for unbiased evaluation of fresh and postmortem human skeletal muscle. We validated and utilized SERCA1 and SERCA2 as type-specific myonucleus and myofiber markers. Parameters including myonuclei per fiber, myonuclear domain, central myonuclei per fiber, and grouped myofiber ratio were determined in a fiber type-specific manner, revealing a large degree of gender- and muscle-related heterogeneity. Our platform was also tested on pathological muscle tissue (ALS) and adapted for the detection of other resident cell types (leukocytes, satellite cells, capillary endothelium). In summary, we present an automated image analysis tool for the simultaneous quantification of myofiber and myonuclear types, to characterize the composition of healthy and diseased human skeletal muscle. 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/2022.11.25.517941v1?rss=1 Authors: Wybo, W. A. M., Tsai, M. C., Tran, V. A. K., Illing, B., Jordan, J., Morrison, A., Senn, W. Abstract: While sensory representations in the brain depend on context, it remains unclear how such modulations are implemented at the biophysical level, and how processing layers further in the hierarchy can extract useful features for each possible contextual state. Here, we first demonstrate that thin dendritic branches are well suited to implementing contextual modulation of feedforward processing. Such neuron-specific modulations exploit prior knowledge, encoded in stable feedforward weights, to achieve transfer learning across contexts. In a network of biophysically realistic neuron models with context-independent feedforward weights, we show that modulatory inputs to thin dendrites can solve linearly non-separable learning problems with a Hebbian, error-modulated learning rule. Finally, we demonstrate that local prediction of whether representations originate either from different inputs, or from different contextual modulations of the same input, results in representation learning of hierarchical feedforward weights across processing layers that accommodate a multitude of contexts. 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/2022.11.17.516923v1?rss=1 Authors: Wu, Y.-h., Podvalny, E., He, B. J. Abstract: While there is a wealth of knowledge about core object recognition--our ability to recognize clear, high-contrast object images, how the brain accomplishes object recognition tasks under increased uncertainty remains poorly understood. We investigated the spatiotemporal neural dynamics underlying object recognition under increased uncertainty by combining MEG and 7 Tesla fMRI in humans during a threshold-level object recognition task. We observed an early, parallel rise of recognition-related signals across ventral visual and frontoparietal regions that preceded the emergence of category-related information. Recognition-related signals in ventral visual regions were best explained by a two-state representational format whereby brain activity bifurcated for recognized and unrecognized images. By contrast, recognition-related signals in frontoparietal regions exhibited a reduced representational space for recognized images, yet with sharper category information. These results provide a spatiotemporally resolved view of neural activity supporting object recognition under uncertainty, revealing a pattern distinct from that underlying core object recognition. 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/2022.10.11.511819v1?rss=1 Authors: Kareva, I. Abstract: While the causes of autism spectrum disorder (ASD) remain unclear, some studies have shown that serotonin-mediated effects on enteric nervous system (ENT) correlate with ASD-like behavioral phenotype in mice. Introduced here is a mathematical model of interactions between gut serotonin and its impact on ENT. The model was used to identify three key factors that affect ENT size, namely, serotonin production, its clearance, and its ability to act as a growth factor on ENT. The model was used to reproduce experimentally reported results from a mouse model by Margolis et al. (2016), which connected serotonin-mediated ENT hypoplasia to an ASD phenotype. The proposed mathematical model was used to scale the quantified relationship from mice to humans to show how the combination of these three factors can translate to a quantifiable metric that could potentially be correlated to ASD spectrum. A detailed discussion of how ENT hypoplasia could mechanistically affect CNS activity concludes this paper. 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/2022.10.04.510883v1?rss=1 Authors: White, A. K., Drake, K. D., Porczak, A. E., Tirado-Mansilla, G., Lee, M. F., Hyatt, K. C., Chow, C., DeQuattro, T., Mickelsen, L. E., Sciolino, N. R., Jackson, A. C., Kanadia, R. N. Abstract: While gene regulatory networks underlying hypothalamic development are being characterized, minor intron splicing remains unexplored. Here, we used Nkx2.1-Cre to ablate Rnu11, encoding the minor spliceosome-specific U11 snRNA, in the progenitors of the ventral diencephalon (VD), to study minor intron splicing in hypothalamic development and control of energy balance in mice. Loss of U11 resulted in aberrant minor intron splicing, mitotic stalling, apoptosis, and altered neurogenesis. Mutant mice exhibited gross dysgenesis of hypothalamic architecture, while single-cell RNA sequencing (scRNAseq) revealed aberrant composition of neuronal subtypes implicated in feeding and energy balance. Mutant weanlings failed to thrive, followed by rapid weight gain, resulting in obesity. Assessment of energy imbalance and pair-feeding demonstrated that hyperphagia in adult mutants initiates weight gain, and is compounded by metabolic dysfunction, ultimately resulting in obesity. Our findings suggest a key role of minor intron splicing in the developmental patterning of hypothalamic neuronal subtypes underlying energy balance. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.03.509933v1?rss=1 Authors: Smiley, C. E., Pate, B. S., Bouknight, S. J., Francis, M. J., Nowicki, A. V., Harrington, E. N., Wood, S. K. Abstract: While over 95% of the population has reported experiencing extreme stress or trauma, females of reproductive age develop stress-induced neuropsychiatric disorders at twice the rate of males. This suggests that ovarian hormones may facilitate neural processes that increase stress susceptibility and underlie the heightened rates of these disorders, like depression and anxiety, that result from stress exposure in females. However, there is contradicting evidence in the literature regarding estrogen's role in stress-related behavioral outcomes. Estrogen signaling through estrogen receptor beta (ERb) has been traditionally thought of as anxiolytic, but recent studies suggest estrogen exhibits distinct effects in the context of stress. Furthermore, ERb is found abundantly in many stress-sensitive brain loci, including the central amygdala (CeA), in which transcription of the vital stress hormone, corticotropin releasing factor (CRF), can be regulated by an estrogen response element. Therefore, these experiments sought to identify the role of CeA ERb activity during stress on behavioral outcomes in naturally cycling, adult, female Sprague-Dawley rats. Rats were exposed to an ethological model of vicarious social stress, witness stress (WS), in which they experienced the sensory and psychological aspects of an aggressive social defeat encounter between two males. Following stress, rats exhibited stress-induced anxiety-like behaviors in the marble burying task, and, finally, brain analysis revealed increased ERb and CRF specifically within the CeA following exposure to stress cues. Subsequent experiments were designed to target this receptor in the CeA using microinjections of the ERb antagonist, PHTPP, prior to each stress session. Sucrose preference, acoustic startle, and marble burying tasks determined that blocking ERb in the CeA during WS prevented the development of depressive-,anxiety-like, and hypervigilant behaviors. Additionally, brain analysis revealed a long-term decrease of intra-CeA CRF expression in PHTPP-treated rats. These experiments indicate that ERb signaling in the CeA, through its effects on CRF, contributes to the development of negative valence behaviors that result from exposure to repeated social stress in female rats. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.03.510578v1?rss=1 Authors: Truong, C., Ruffino, C., Gaveau, J., Hilt, P., White, O., Papaxanthis, C. Abstract: While the time-of-day significantly impacts motor performance, its effect on motor learning has not yet been elucidated. Here, we investigated the influence of the time-of-day on skill acquisition (i.e., skill improvement immediately after a training-session) and consolidation (i.e., skill retention after a time interval). Three groups were trained at 10 a.m. (G10am), 3 p.m. (G3pm), or 8 p.m. (G8pm) on a finger-tapping task. We recorded the skill (i.e. the ratio between movement duration and accuracy), before and immediately after the training to evaluate skill acquisition, and after 24 hours, to measure skill consolidation. We did not observe any difference in acquisition according to the time of the day. However, we found an improvement in performance 24 hours after the evening training (G8pm) while the morning (G10am) and the afternoon (G3pm) groups deteriorated and stabilized their performance, respectively. Furthermore, two control experiments (G8wake and G8sleep) supported the idea that a night of sleep contributes to the skill consolidation of the evening group. These results show an influence of time-of-day on the consolidation process, with better consolidation when the training is carried out in the evening. This finding may have an important impact on the planning of training programs in sports, clinical, or experimental domains. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.26.509511v1?rss=1 Authors: Pan, Y., Frisson, S., Federmeier, K. D., Jensen, O. Abstract: While humans have a remarkable ability to read and comprehend text, the neuronal mechanisms supporting natural reading remain elusive. It is debated whether upcoming words in the parafovea are processed semantically. Here we show that the brain can indeed detect that a word is contextually implausible even before fixating on it. We demonstrated this by imperceivably flickering target words at 60 Hz that either were congruent or incongruent with the sentence context. While participants read these sentences, we used MEG to detect the flicker-response prior to saccades to the target words. We found a smaller tagging response for words that were incongruent with the sentence context; this reduction was related to the individual reading speed. We conclude that parafoveal semantic integration occurs during natural reading. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.25.509384v1?rss=1 Authors: Yu, Y., Gratton, C., Smith, D. M. Abstract: While correlations in the BOLD fMRI signal are widely used to capture functional connectivity (FC) and its changes across contexts, its interpretation is often ambiguous. The entanglement of multiple factors including local coupling of two neighbors and non-local inputs from the rest of the network (affecting one or both regions) limits the scope of the conclusions that can be drawn from correlation measures alone. Here we present a method of estimating the contribution of non-local network input to FC changes across different contexts. To disentangle the effect of task-induced coupling change from the network input change, we propose a new metric, "communication change", utilizing BOLD signal correlation and variance. With a combination of simulation and empirical analysis, we demonstrate that 1) input from the rest of the network accounts for a moderate but significant amount of task-induced FC change; 2) the proposed "communication change" is a promising candidate for tracking the local coupling in task context-induced change. Additionally, when compared to FC change across three different tasks, communication change can better discriminate specific task types. Taken together, this novel index of local coupling may have many applications in improving our understanding of local and widespread interactions across large-scale functional networks. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.16.508310v1?rss=1 Authors: Long, C., Lee, K., Yang, L., Dafalias, T., Wu, A. K., Masmanidis, S. C. Abstract: While the contribution of dopaminergic (DA) neurons to associative learning is firmly established, their importance for influencing imminent behavior on short (subsecond) timescales is less clear. Mechanistically, it is thought that DA neurons drive these behavioral changes because of their ability to rapidly alter striatal spiking activity. However, due to limitations of previous approaches, the straightforward prediction that striatal spiking is rapidly influenced by physiologically relevant DA signals has not been rigorously tested. Here, we monitored changes in spiking responses in the ventral striatum while transiently reducing or increasing DA levels. Contrary to the predicted effect, neither spontaneous nor reward-evoked striatal spiking activity was strongly influenced by optogenetic manipulations, except when DA exceeded reward-matched levels. These findings challenge the view that DA plays a major role in rapidly influencing striatal activity. Finally, they suggest a need to distinguish between the modulatory functions of DA under physiological and supra-physiological conditions. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

This recording from September 5, 2022. Signum MA student Nadia Schafer will present her thesis “One Strange (s) Elf: Deep Ecology, Decolonization and the Radical Hope of Legolas Greenleaf ” and respond to questions from the audience in an interactive Thesis Theater. The discussion will be facilitated by Nadia's thesis supervisor, Dr. Sara Brown. Abstract: While living through a national reckoning, a global pandemic, and a worsening climate change crisis, what The Lord of the Rings can offer to those living on Turtle Island in the 2020s? This thesis argues that the text offers its reader radical hope through the ecocritical voice through the character Legolas Greenleaf. Strongly influenced by the writings of Joanna Macy, Donna Haraway, and Robin Wall Kimmerer, “One Strange (s)Elf” explores the narrative of Legolas' role in the process of decolonization and restoration in Middle-earth. Using a postcolonial analysis paired with Deep Ecology, this thesis establishes an Indigenous reading of the Silvan Elves. Building of this reading, it further demonstrates the power of making Oddkin as an act of decolonization, explores the elements of the Queer Gothic in the depiction of Fangorn's Huorns, and acknowledges the power of shared grief. Finally, this work demonstrates how Tolkien suggests to his audience an alternative to despair by offering the choice to stray. About the Presenter: Nadia Schafer (she/her) is a Social Services Worker, Certified Human Resources Professional, and speculative writer living on the Haldimand Tract in Southwestern Ontario. Her career as a jack-of-all-trades has included everything from non-profit consulting to teaching preschool. You can find her promoting her creative work as Nadia Steven Rysing on Twitter @atendency (https://twitter.com/atendency). About Signum Thesis Theaters: Each of our master's students writes a thesis at the end of their degree program, exploring a topic of their choice. The Thesis Theater is their opportunity to present their research to a general audience, and answer questions. All are welcome to attend! For more information about Signum University and our degree program, please visit: https://signumuniversity.org/ To view our upcoming courses: https://signumuniversity.org/degree-p... Learn about Signum University's mission, leadership and more: https://signumuniversity.org/about/

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.07.506894v1?rss=1 Authors: Yoshizawa, T., Ito, M., Doya, K. Abstract: While animal and human decision strategies are typically explained by model-free and model-based reinforcement learning, their choice sequences often follow simple procedures based on working memory of past actions and rewards. Here we address how working memory-based choice strategies, such as win-stay-lose-switch (WSLS), are represented in the prefrontal and motor cortico-basal ganglia loops by simultaneous recording of neuronal activities in the dorsomedial striatum (DMS), the dorsolateral striatum (DLS), the medial prefrontal cortex (mPFC), and the primary motor cortex (M1). In order to compare neuronal representations when rats employ working memory-based strategies, we developed a new task paradigm, a continuous/intermittent choice task, consisting of choice and no-choice trials. While the continuous condition (CC) consisted of only choice trials, in the intermittent condition (IC), a no-choice trial was inserted after each choice trial to disrupt working memory of the previous choice and reward. Behaviors in CC showed high proportions of win-stay and lose-switch choices, which could be regarded as "a noisy WSLS strategy." Poisson regression of neural spikes revealed encoding specifically in CC of the previous action and reward before action choice and prospective coding of WSLS action during action execution. A striking finding was that the DLS and M1 in the motor cortico-basal ganglia loop carry substantial WM information about previous choices, rewards, and their interactions, in addition to current action coding. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Cynthia Rudin (Duke University) gives a OxCSML Seminar on Friday 14th May 2021. Abstract: While the trend in machine learning has tended towards more complex hypothesis spaces, it is not clear that this extra complexity is always necessary or helpful for many domains. In particular, models and their predictions are often made easier to understand by adding interpretability constraints. These constraints shrink the hypothesis space; that is, they make the model simpler. Statistical learning theory suggests that generalization may be improved as a result as well. However, adding extra constraints can make optimization (exponentially) harder. For instance it is much easier in practice to create an accurate neural network than an accurate and sparse decision tree. We address the following question: Can we show that a simple-but-accurate machine learning model might exist for our problem, before actually finding it? If the answer is promising, it would then be worthwhile to solve the harder constrained optimization problem to find such a model. In this talk, I present an easy calculation to check for the possibility of a simpler model. This calculation indicates that simpler-but-accurate models do exist in practice more often than you might think. This talk is mainly based on the following paper Lesia Semenova, Cynthia Rudin, and Ron Parr. A Study in Rashomon Curves and Volumes: A New Perspective on Generalization and Model Simplicity in Machine Learning. In progress, 2020. https://arxiv.org/abs/1908.01755

Cynthia Rudin (Duke University) gives a OxCSML Seminar on Friday 14th May 2021. Abstract: While the trend in machine learning has tended towards more complex hypothesis spaces, it is not clear that this extra complexity is always necessary or helpful for many domains. In particular, models and their predictions are often made easier to understand by adding interpretability constraints. These constraints shrink the hypothesis space; that is, they make the model simpler. Statistical learning theory suggests that generalization may be improved as a result as well. However, adding extra constraints can make optimization (exponentially) harder. For instance it is much easier in practice to create an accurate neural network than an accurate and sparse decision tree. We address the following question: Can we show that a simple-but-accurate machine learning model might exist for our problem, before actually finding it? If the answer is promising, it would then be worthwhile to solve the harder constrained optimization problem to find such a model. In this talk, I present an easy calculation to check for the possibility of a simpler model. This calculation indicates that simpler-but-accurate models do exist in practice more often than you might think. This talk is mainly based on the following paper Lesia Semenova, Cynthia Rudin, and Ron Parr. A Study in Rashomon Curves and Volumes: A New Perspective on Generalization and Model Simplicity in Machine Learning. In progress, 2020. https://arxiv.org/abs/1908.01755

Abstract: While many have written on ancient temples looking at the big picture, John Gee discusses one small detail on a single Egyptian temple from the New Kingdom. He focuses on depictions of Ramses III in and out of the temple of Medinet Habu. Outside the temple and when entering and leaving there are depictions […] The post “Put Off Thy Shoes from Off Thy Feet”: Sandals and Sacred Space first appeared on The Interpreter Foundation.

Abstract: While many have written on ancient temples looking at the big picture, John Gee discusses one small detail on a single Egyptian temple from the New Kingdom. He focuses on depictions of Ramses III in and out of the temple of Medinet Habu. Outside the temple and when entering and leaving there are depictions […] The post “Put Off Thy Shoes from Off Thy Feet”: Sandals and Sacred Space first appeared on The Interpreter Foundation.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.18.388819v1?rss=1 Authors: De Melo, G. D., Lazarini, F., Levallois, S., Hautefort, C., Michel, V., Larrous, F., Verillaud, B., Aparicio, C., Wagner, S., Gheusi, G., Kergoat, L., Kornobis, E., Cokelaer, T., Hervochon, R., Madec, Y., Roze, E., Salmon, D., Bourhy, H., Lecuit, M., Lledo, P.-M. Abstract: While recent investigations have revealed viral, inflammatory and vascular factors involved in SARS-CoV-2 lung pathogenesis, the pathophysiology of neurological disorders in COVID-19 remains poorly understood. Yet, olfactory and taste dysfunction are rather common in COVID-19, especially in pauci-symptomatic patients which constitutes the most frequent clinical manifestation of the infection. We conducted a virologic, molecular, and cellular study of the olfactory system from COVID-19 patients presenting acute loss of smell, and report evidence that the olfactory epithelium represents a highly significant infection site where multiple cell types, including olfactory sensory neurons, support cells and immune cells, are infected. Viral replication in the olfactory epithelium is associated with local inflammation. Furthermore, we show that SARS-CoV-2 induces acute anosmia and ageusia in golden Syrian hamsters, both lasting as long as the virus remains in the olfactory epithelium and the olfactory bulb. Finally, olfactory mucosa sampling in COVID-19 patients presenting with persistent loss of smell reveals the presence of virus transcripts and of SARS-CoV-2-infected cells, together with protracted inflammation. Viral persistence in the olfactory epithelium therefore provides a potential mechanism for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management and future therapeutic strategies. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.11.377655v1?rss=1 Authors: Seijdel, N., Loke, J., van de Klundert, R., van der Meer, M., Quispel, E., van Gaal, S., de Haan, E. H., Scholte, H. S. Abstract: While feed-forward activity may suffice for recognizing objects in isolation, additional visual operations that aid object recognition might be needed for real-world scenes. One such additional operation is figure-ground segmentation; extracting the relevant features and locations of the target object while ignoring irrelevant features. In this study of 60 participants, we show objects on backgrounds of increasing complexity to investigate whether recurrent computations are increasingly important for segmenting objects from more complex backgrounds. Three lines of evidence show that recurrent processing is critical for recognition of objects embedded in complex scenes. First, behavioral results indicated a greater reduction in performance after masking objects presented on more complex backgrounds; with the degree of impairment increasing with increasing background complexity. Second, electroencephalography (EEG) measurements showed clear differences in the evoked response potentials (ERPs) between conditions around 200ms - a time point beyond feed-forward activity and object decoding based on the EEG signal indicated later decoding onsets for objects embedded in more complex backgrounds. Third, Deep Convolutional Neural Network performance confirmed this interpretation; feed-forward and less deep networks showed a higher degree of impairment in recognition for objects in complex backgrounds compared to recurrent and deeper networks. Together, these results support the notion that recurrent computations drive figure-ground segmentation of objects in complex scenes. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.08.373126v1?rss=1 Authors: Yao, S., Zhou, M., Zhang, Y., Zhang, Q., Zhao, Z., Jiang, X., Xu, X., Becker, B., Kendrick, K. M. Abstract: While a number of functional and structural changes occur in large-scale brain networks in autism spectrum disorder (ASD), reduced interhemispheric resting state functional connectivity (rsFC) between homotopic regions may be of particular importance as a biomarker. ASD is an early-onset developmental disorder and neural changes are often age-dependent, reflecting dysregulated developmental trajectories, although no studies have investigated whether homotopic interhemispheric rsFC alterations occur in ASD children. The present study conducted a voxel-based homotopic interhemispheric rsFC analysis in 152 ASD and 185 typically developing children under age 10 and examined associations with symptom severity in the Autism Brain Imaging Data Exchange datasets. Given the role of corpus callosum (CC) in interhemispheric connectivity and reported CC volume changes in ASD we additionally examined whether there were parallel volume changes in ASD children. Results demonstrated decreased homotopic rsFC in ASD children in the medial prefrontal cortex, precuneus and posterior cingulate cortex of the default mode network (DMN), the dorsal anterior cingulate cortex of the salience network, the precentral gyrus and inferior parietal lobule of the mirror neuron system, the lingual, fusiform and inferior occipital gyri of the visual processing network and thalamus. Symptom severity was associated with homotopic rsFC in regions in the DMN and visual processing network. There were no significant CC volume changes in ASD children. The present study shows that reduced homotopic interhemispheric rsFC in brain networks in ASD adults/adolescents is already present in children of 5-10 years old and further supports their potential use as a general ASD biomarker. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.07.372805v1?rss=1 Authors: Voorhies, W. I., Miller, J. A., Yao, J., Bunge, S. A., Weiner, K. S. Abstract: While the disproportionate expansion of lateral prefrontal cortex (LPFC) throughout evolution is commonly accepted, the relationship between evolutionarily new LPFC brain structures and uniquely human cognitive skills is largely unknown. Here, we tested the relationship between variability in evolutionarily new LPFC tertiary sulci and reasoning skills in a pediatric cohort. A novel data-driven approach in independent discovery and replication samples revealed that the depth of specific LPFC tertiary sulci predicts individual differences in reasoning skills beyond age. These findings support a classic, yet untested, theory linking the protracted development of tertiary sulci to late-developing cognitive processes. We conclude by proposing a mechanistic hypothesis relating the depth of LPFC tertiary sulci to anatomical connections. We suggest that deeper LPFC tertiary sulci reflect reduced short-range connections in white matter, which in turn, improve the efficiency of local neural signals underlying cognitive skills such as reasoning that are central to human cognitive development. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.07.372839v1?rss=1 Authors: Szabo, A., Akkouh, I. A., Vandenberghe, M., Osete, J. R., Hughes, T., Heine, V., Smeland, O. B., Glover, J. C., Andreassen, O., Djurovic, S. Abstract: While neurodevelopmental abnormalities have been associated with schizophrenia (SCZ), the role of astroglia in disease pathophysiology remains poorly understood. In this study we used a human induced pluripotent stem cell (iPSC)-derived astrocyte model to investigate the temporal patterns of astroglia differentiation during developmental stages critical for SCZ using RNA-sequencing. The model generated astrocyte-specific patterns of gene expression during differentiation, and demonstrated that these patterns correspond well to astroglia-specific expression signatures of in vivo cortical fetal development. Applying this model, we were able to identify SCZ-specific expression dynamics in human astrocytes, and found that SCZ-associated differentially expressed genes were significantly enriched in the medial prefrontal cortex, striatum, and temporal lobe, targeting VWA5A and ADAMTS19. In addition, SCZ astrocytes displayed alterations in calcium signaling, and significantly decreased glutamate uptake and metalloproteinase activity relative to controls. These results provide strong support for the validity of our astrocyte model, and implicate novel transcriptional dynamics in astrocyte differentiation in SCZ together with functional changes that are potentially important biological components of SCZ pathology. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.03.366385v1?rss=1 Authors: Braha, M., Porciatti, V., Chou, T.-H. Abstract: While albino mice are widely used in research which includes the use of visually guided behavioral tests, information on their visual capability is scarce. We compared the spatial resolution (acuity) of albino mice (BALB/c) with that of pigmented mice (C57BL/6J). We used a high-throughput pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) method for objective assessment of retinal and cortical acuity, as well as optomotor head-tracking response/ reflex (OMR). We found that PERG, PVEP, and OMR acuities of C57BL/6J mice were all in the range of 0.5-0.6 cycles/degree (cyc/deg). BALB/c mice had PERG and PVEP acuities in the range of 0.1-0.2 cyc/deg but were unresponsive to OMR stimulus. Results indicate that retinal and cortical acuity can be reliably determined with electrophysiological methods in BALB/c mice, although PERG/PVEP acuities are lower than those of C57BL/6J mice. The reduced acuity of BALB/c mice appears to be primarily determined at retinal level. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.23.353094v1?rss=1 Authors: McCormick, E. M., Peters, S., Crone, E. A., Telzer, E. H. Abstract: While it is well understood that the brain experiences changes across short-term experience/learning and long-term development, it is unclear how these two mechanisms interact to produce developmental outcomes. Here we test an interactive model of learning and development where certain learning-related changes are constrained by developmental changes in the brain against an alternative development-as-practice model where outcomes are determined primarily by the accumulation of experience regardless of age. Participants (8-29 years) participated in a three-wave, accelerated longitudinal study during which they completed a feedback learning task during an fMRI scan. Adopting a novel longitudinal modeling approach, we probed the unique and moderated effects of learning, experience, and development simultaneously on behavioral performance and network modularity during the task. We found nonlinear patterns of development for both behavior and brain, and that greater experience supported increased learning and network modularity relative to naive subjects. We also found changing brain-behavior relationships across adolescent development, where heightened network modularity predicted improved learning, but only following the transition from adolescence to young adulthood. These results present compelling support for an interactive view of experience and development, where changes in the brain impact behavior in context-specific fashion based on developmental goals. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.05.326314v1?rss=1 Authors: Pan, Y., Frisson, S., Jensen, O. Abstract: While reading is an essential human skill, many of the neuronal mechanisms supporting reading are not well understood. In spite of the reduced visual acuity, parafoveal information plays a critical role in natural reading; however, it is strongly debated whether words are previewed parafoveally at the lexical level. This is a key dispute for competing models on reading and of great significance since lexical retrieval is important for guiding eye movements. We found evidence for parafoveal previewing at the lexical level by combining a novel rapid invisible frequency tagging (RIFT)10,11 approach with magnetoencephalography (MEG) and eye-tracking. In a silent reading task, target words of either low or high lexical frequency were tagged (flickered) subliminally at 60 Hz. The tagging response measured when fixating on the pre-target word reflected parafoveal previewing of the target word. We observed a stronger tagging response as early as 100 ms following fixations on pre-target words that were followed by target words of low compared with high lexical frequency. Moreover, the difference in tagging response with respect to target lexicality predicted individual reading speed. Our findings demonstrate that reading unfolds in the fovea and parafovea simultaneously to support fluent reading. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.04.325639v1?rss=1 Authors: Blake, A. J., Couture, S., Go, M. C., Gries, G. Abstract: While it is well documented that insects exploit polarized sky light for navigation, their use of reflected polarized light for object detection has been less well studied. Recently, we have shown that the small white butterfly, Pieris rapae, distinguishes between host and non-host plants based on the degree of linear polarization (DoLP) of light reflected from their leaves. To determine how polarized light cues affect host plant foraging by female P. rapae across their entire visual range including the ultraviolet (300-650 nm), we applied photo polarimetry demonstrating large differences in the DoLP of leaf-reflected light among plant species generally and between host and non-host plants specifically. As polarized light cues are directionally dependent, we also tested, and modelled, the effect of approach trajectory on the polarization of plant-reflected light and the resulting attractiveness to P. rapae. Using photo polarimetry measurements of plants under a range of light source and observer positions, we reveal several distinct effects when polarized reflections are examined on a whole-plant basis rather than at the scale of pixels or of entire plant canopies. Most notably from our modeling, certain approach trajectories are optimal for foraging butterflies, or insects generally, to discriminate between plant species on the basis of the DoLP of leaf-reflected light. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.29.318931v1?rss=1 Authors: Nadeau, R., Shahryari Fard, S., Scheer, A., Hashimoto-Roth, E., Nygard, D., Abramchuk, I., Chung, Y.-E., Bennett, S. A. L., Lavallee-Adam, M. Abstract: While the COVID-19 pandemic is causing important loss of life, knowledge of the effects of the causative SARS-CoV-2 virus on human cells is currently limited. Investigating protein-protein interactions (PPIs) between viral and host proteins can provide a better understanding of the mechanisms exploited by the virus and enable the identification of potential drug targets. We therefore performed an in-depth computational analysis of the interactome of SARS-CoV-2 and human proteins in infected HEK293 cells published by Gordon et al. to reveal processes that are potentially affected by the virus and putative protein binding sites. Specifically, we performed a set of network-based functional and sequence motif enrichment analyses on SARS-CoV-2-interacting human proteins and on a PPI network generated by supplementing viral-host PPIs with known interactions. Using a novel implementation of our GoNet algorithm, we identified 329 Gene Ontology terms for which the SARS-CoV-2-interacting human proteins are significantly clustered in the network. Furthermore, we present a novel protein sequence motif discovery approach, LESMoN-Pro, that identified 9 amino acid motifs for which the associated proteins are clustered in the network. Together, these results provide insights into the processes and sequence motifs that are putatively implicated in SARS-CoV-2 infection and could lead to potential therapeutic targets. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.24.311779v1?rss=1 Authors: Jin, Y., Kotler, J. L. M., Wang, S., Huang, B., Halpin, J. C., Street, T. O. Abstract: While cytosolic Hsp70 and Hsp90 chaperones have been extensively studied, less is known about how the ER Hsp70 and Hsp90 paralogs (BiP and Grp94) recognize clients and influence their folding. Here, we examine how BiP and Grp94 influence the folding of insulin-like growth factor 2 (IGF2). Full-length proIGF2 is composed of an insulin-like hormone and an E-peptide that has sequence characteristics of an intrinsically disordered region. We find that the E-peptide region allows proIGF2 to form oligomers. BiP and Grp94 influence both the folding and the oligomerization of proIGF2. BiP and Grp94 exert a similar holdase function on proIGF2 folding by preferentially binding the proIGF2 unfolded state, rather than stabilizing specific folding intermediates and changing the proIGF2 folding process. In contrast, BiP and Grp94 exert counteracting effects on proIGF2 oligomerization. BiP suppresses proIGF2 oligomerization under both ADP and ATP conditions. Interestingly, Grp94 can enhance proIGF2 oligomerization when Grp94 adopts an open conformation (ADP conditions), but not when Grp94 is in the closed conformation (ATP conditions). We propose that BiP and Grp94 regulate the assembly of proIGF2 oligomers, and that regulated oligomerization may enable proIGF2 to be effectively packaged for export from the ER to the Golgi. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.16.298653v1?rss=1 Authors: Kurtev-Rittstieg, R., Achatz, S., Nourinia, A., Mittermeyer, S. Abstract: While directional deep brain stimulation (DBS) shows promising clinical effects by providing a new degree of freedom in programming, precise knowledge of the lead position and orientation is necessary to mitigate the resulting increased complexity. Two methods for orientation assessment based on postoperative CT imaging have become available, but neither of them is currently able to resolve the respective 180{degrees} artifact symmetry. Both rely on information about the intended orientation and assume that a deviation of more than {+/-} 90{degrees} is very unlikely. Our aim was to develop an enhanced algorithm capable of detecting asymmetries in the CT data and to thus eliminate the need for user interaction. Two different approaches are presented: one based on the lead marker's center of mass (COM) and one based on asymmetric sampling of the marker's intensity profile (ASM). Both were tested on a total of 98 scans of 2 lead phantoms, resulting in 165 measurements with a large variety of lead implantation and orientation angles. The 180{degrees} ambiguity was correctly resolved in 99.4% of cases by COM and in 96.4% of cases by ASM. These results demonstrate the substantial and currently unused asymmetry in CT and the potential for a truly automated workflow. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.04.282434v1?rss=1 Authors: Basrur, N. S., De Obaldia, M. E., Morita, T., Herre, M., von Heynitz, R. K., Tsitohay, Y. N., Vosshall, L. B. Abstract: While sexual dimorphism in courtship and copulation behavior is common in the animal kingdom, sexual dimorphism in feeding behavior is rare. The Aedes aegypti mosquito provides an example of extreme sexual dimorphism in feeding, because only the females show strong attraction to humans, and bite them to obtain a blood-meal necessary to stimulate egg production. The genetic basis of this complex, modular, and sexually dimorphic feeding behavior is unknown. The fruitless gene is sex-specifically spliced in the brain of multiple insect species including mosquitoes and encodes a BTB zinc-finger transcription factor that has been proposed to be a master regulator of male courtship and mating behavior across insects. Here we use CRISPR-Cas9 to mutate the fruitless gene in male mosquitoes. fruitless mutant males fail to mate, confirming the ancestral function of this gene in male sexual behavior. Remarkably, fruitless mutant males also gain strong attraction to a live human host, a behavior that wild-type males never display. Humans produce multiple sensory cues that attract mosquitoes and we show that fruitless specifically controls host-seeking in response to human odor. These results suggest that male mosquitoes possess the neural circuits required to host-seek and that removing fruitless reveals this latent behavior in males. Our results highlight an unexpected repurposing of a master regulator of male-specific sexual behavior to control one module of female-specific blood-feeding behavior in a deadly vector of infectious diseases. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.23.234237v1?rss=1 Authors: Csaba, G., Berchtold, E., Hadziahmetovic, A., Gruber, M., Ammar, C., Zimmer, R. Abstract: While absolute quantification is challenging in high-throughput measurements, changes of features between conditions can often be determined with high precision. Therefore, analysis of fold changes is the standard method, but often, a doubly differential analysis of "changes of changes" is required. Differential alternative splicing is an example of a doubly differential analysis, i.e. fold changes between conditions for different isoforms of a gene. EmpiRe is a quantitative approach for various kinds of omics data based on fold changes for appropriate features of biological objects. Empirical error distributions for these fold changes are estimated from Replicate measurements and used to quantify feature fold changes and their directions. We assess the performance of EmpiRe to detect differentially expressed genes applied to RNA-Seq using simulated data. It achieved higher precision than established tools at nearly the same recall level. Furthermore, we assess the detection of alternatively Spliced genes via changes of isoform fold changes (EmpiReS) on distribution-free simulations and experimentally validated splicing events. EmpiReS achieves the best precision-recall values for simulations based on different biological datasets. We propose EmpiRe(S) as a general, quantitative and fast approach with high reliability and an excellent trade-off between sensitivity and precision in (doubly) differential analyses. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.17.254631v1?rss=1 Authors: Heath-Heckman, E., Yoo, S., Winchell, C., Pellegrino, M., Angstadt, J., Lammardo, V., Bautista, D. M., de Miguel, F. F., Weisblat, D. A. Abstract: While leeches in the genus Hirudo have long been models for neurobiology, the molecular underpinnings of nervous system structure and function in this group remain largely unknown. To begin to bridge this gap, we performed RNASeq on pools of identified neurons of the central nervous system (CNS): sensory T (touch), P (pressure) and N (nociception) neurons; neurosecretory Retzius cells; and ganglia from which these four cell types had been removed. Bioinformatic analyses identified 2,812 putative genes whose expression differed significantly among the samples. These genes clustered into 7 groups which could be associated with one or more of the identified cell types. We verified predicted expression patterns through in situ hybridization on whole CNS ganglia, and found that orthologous genes were for the most part similarly expressed in a divergent leech genus, suggesting evolutionarily conserved roles for these genes. Transcriptional profiling allowed us to identify candidate phenotype-defining genes from expanded gene families. Thus, we identified one of eight hyperpolarization-activated cyclic-nucleotide gated (HCN) channels as a candidate for mediating the prominent sag current in P neurons, and found that one of five inositol triphosphate receptors (IP3Rs), representing a sub-family of IP3Rs absent from vertebrate genomes, is expressed with high specificity in T cells. We also identified one of two piezo genes, two of ~65 deg/enac genes, and one of at least 16 transient receptor potential (trp) genes as prime candidates for involvement in sensory transduction in the three distinct classes of leech mechanosensory neurons. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.12.246405v1?rss=1 Authors: Sela, Y., Hoekstra, M. M. B., Franken, P. Abstract: While brain temperature is of neurobiological and clinical importance, it is still unclear which factors contribute to its daily dynamics and to what degree. We recorded cortical temperature in mice alongside sleep-wake state during 4 days including a 6h sleep deprivation, and developed a mathematical tool to simulate temperature based on the sleep-wake sequence. The model estimated temperature with remarkable precision accounting for 91% of its variance based on three main factors with the sleep-wake sequence accounting for most of the variance (74%) and time-of-day (circadian) the least (9%). As third factor, prior wake prevalence, was discovered to up-regulate temperature, explaining 43% of the variance. With similar accuracy the model predicted cortical temperature in a second, independent cohort using the parameters optimized for the first. Our model corroborates the profound influence of sleep-wake state on brain temperature, and can help differentiate thermoregulatory from sleep-wake driven effects in experiments affecting both. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.07.242347v1?rss=1 Authors: Eguchi, R. R., Anand, N., Choe, C. A., Huang, P.-S. Abstract: While deep learning models have seen increasing applications in protein science, few have been implemented for protein backbone generation -- an important task in structure-based problems such as active site and interface design. We present a new approach to building class-specific backbones, using a variational auto-encoder to directly generate the 3D coordinates of immunoglobulins. Our model is torsion- and distance-aware, learns a high-resolution embedding of the dataset, and generates novel, high-quality structures compatible with existing design tools. We show that the Ig-VAE can be used to create a computational model of a SARS-CoV2-RBD binder via latent space sampling. We further demonstrate that the model's generative prior is a powerful tool for guiding computational protein design, motivating a new paradigm under which backbone design is solved as constrained optimization problem in the latent space of a generative model. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.02.233197v1?rss=1 Authors: Diao, J. A., Chui, W. F., Wang, J. K., Mitchell, R. N., Rao, S. K., Resnick, M. B., Lahiri, A., Maheshwari, C., Glass, B., Mountain, V., Kerner, J. K., Montalto, M. C., Khosla, A., Wapinski, I. N., Beck, A. H., Taylor-Weiner, A., Elliott, H. Abstract: While computational methods have made substantial progress in improving the accuracy and throughput of pathology workflows for diagnostic, prognostic, and genomic prediction, lack of interpretability remains a significant barrier to clinical integration. In this study, we present a novel approach for predicting clinically-relevant molecular phenotypes from histopathology whole-slide images (WSIs) using human-interpretable image features (HIFs). Our method leverages >1.6 million annotations from board-certified pathologists across >5,700 WSIs to train deep learning models for high-resolution tissue classification and cell detection across entire WSIs in five cancer types. Combining cell- and tissue-type models enables computation of 607 HIFs that comprehensively capture specific and biologically-relevant characteristics of multiple tumors. We demonstrate that these HIFs correlate with well-known markers of the tumor microenvironment (TME) and can predict diverse molecular signatures, including immune checkpoint protein expression and homologous recombination deficiency (HRD). Our HIF-based approach provides a novel, quantitative, and interpretable window into the composition and spatial architecture of the TME. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.28.226118v1?rss=1 Authors: Benady, A., Zadik, S., Ben-Gal, O., Cano Porras, D., Wenkert, A., Gilaie-Dotan, S., Plotnik, M. Abstract: While walking, our locomotion is affected by and adapts to the environment based on vision-based and body-based (vestibular and proprioception) cues, all contributing to an "Internal Model of Gravity". During surface inclination transitions, we modulate gait to counteract gravitational forces by braking during downhill walking to avoid uncontrolled acceleration or by exerting effort to avoid deceleration while walking uphill. In this study, we investigated the role of vision in gait modulation during surface inclination transitions by using an immersive large-scale Virtual Reality (VR) system equipped with a self-paced treadmill and projected visual scenes that allowed us to modulate physical-visual inclinations congruence parametrically. Gait speed and leg muscle electromyography (EMG) were measured in 12 healthy young adults. In addition, the magnitude of subjective visual misperception of verticality was measured by the rod and frame test. During virtual (non-veridical) inclination transitions, vision modulated gait speed after transitions by (i) slowing down to counteract the excepted gravitational 'boost' in virtual downhill inclinations and by (ii) speeding up to counteract the expected gravity resistance in virtual uphill inclinations. These gait speed modulations were reflected in muscle activation intensity changes and associated with subjective visual verticality misperception. However, temporal patterns of muscle activation, which are significantly affected by real gravitational inclination transitions, were not affected by virtual (visual) inclination transitions. Our results delineate the contribution of vision to functional locomotion on uneven surfaces and may lead to enhanced rehabilitation strategies for neurological disorders affecting movement. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.28.225730v1?rss=1 Authors: Marderstein, A. R., Davenport, E., Kulm, S., Van Hout, C. V., Elemento, O., Clark, A. G. Abstract: While thousands of loci have been associated with human phenotypes, the role of gene-environment (GxE) interactions in determining individual risk of human diseases remains unclear. This is partly due to the severe erosion of statistical power resulting from the massive number of statistical tests required to detect such interactions. Here, we focus on improving the power of GxE tests by developing a statistical framework for assessing quantitative trait loci (QTLs) associated with the trait means and/or trait variances. When applying this framework to body mass index (BMI), we find that GxE discovery and replication rates are significantly higher when prioritizing genetic variants associated with the variance of the phenotype (vQTLs) compared to assessing all genetic variants. Moreover, we find that vQTLs are enriched for associations with other non-BMI phenotypes having strong environmental influences, such as diabetes or ulcerative colitis. We show that GxE effects first identified in quantitative traits such as BMI can be used for GxE discovery in disease phenotypes such as diabetes. A clear conclusion is that strong GxE interactions mediate the genetic contribution to body weight and diabetes risk. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.23.218859v1?rss=1 Authors: Al-Tahan, H., Mohsenzadeh, Y. Abstract: While vision evokes a dense network of feedforward and feedback neural processes in the brain, visual processes are primarily modeled with feedforward hierarchical neural networks, leaving the computational role of feedback processes poorly understood. Here, we developed a generative autoencoder neural network model and adversarially trained it on a categorically diverse data set of images. We hypothesized that the feedback processes in the ventral visual pathway can be represented by reconstruction of the visual information performed by the generative model. We compared representational similarity of the activity patterns in the proposed model with temporal (magnetoencephalography) and spatial (functional magnetic resonance imaging) visual brain responses. The proposed generative model identified two segregated neural dynamics in the visual brain. A temporal hierarchy of processes transforming low level visual information into high level semantics in the feedforward sweep, and a temporally later dynamics of inverse processes reconstructing low level visual information from a high level latent representation in the feedback sweep. Our results append to previous studies on neural feedback processes by presenting a new insight into the algorithmic function and the information carried by the feedback processes in the ventral visual pathway. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.29.178236v1?rss=1 Authors: Marti-Prats, L., Belin-Rauscent, A., Fouyssac, M., Puaud, M., Cocker, P. J., Everitt, B. J., Belin, D. Abstract: While most individuals with access to alcohol drink it recreationally, about 5% lose control over their intake and progressively develop an alcohol use disorder (AUD), characterised by compulsive alcohol drinking accompanied by decreased interest in alternative sources of reinforcement. The neural and molecular mechanisms underlying the vulnerability to switch from controlled to compulsive alcohol intake have not been fully characterized, so limiting the development of new treatments for AUD. It has recently been shown that rats having reduced levels of expression of the gamma-aminobutyric acid (GABA) transporter, GAT-3, in the amygdala tend to persist in seeking and drinking alcohol even when adulterated with quinine, suggesting that pharmacological interventions aimed at restoring GABA homeostasis in these individuals may provide a targeted treatment to limit compulsive alcohol drinking. Here, we tested the hypothesis that the GABAB receptor agonist baclofen, which decreases GABA release, specifically decreases compulsive alcohol drinking in vulnerable individuals. In a large cohort of Sprague-Dawley rats allowed to drink alcohol under an intermittent two-bottle choice procedure, a cluster of individuals was identified that persisted in drinking alcohol despite adulteration or the availability of an alternative ingestive reinforcer, saccharin. In these rats, that were characterised by decreased GAT-3 mRNA levels in the central amygdala, acute baclofen administration (1.5 mg/kg, intraperitoneal) resulted in a decrease in compulsive drinking. These results indicate that low GAT-3 mRNA levels in the central amygdala represent an endophenotype of AUD and that the associated compulsive alcohol drinking characteristic is sensitive to baclofen. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.12.143834v1?rss=1 Authors: Fjell, A., Grydeland, H., Wang, Y., Amlien, I. K., Bartres-Faz, D., Brandmaier, A., Duzel, S., Elman, J., Franz, C., Haberg, A., Kietzmann, T. C., Kievit, R. A., Kremen, W., Krogsrud, S. K., Kuhn, S. A., Lindenberger, U., Macia, D., Mowinckel, A. M., Nyberg, L., Panizzon, M., Sole-Padulles, C., Sorensen, O., Westerhausen, R., Walhovd, K. B. Abstract: While development and aging of the cerebral cortex show a similar topographic organization and are mainly governed by the same genes, it is unclear whether the same is true for subcortical structures, which follow fundamentally different ontogenetic and phylogenetic principles than the cerebral cortex. To test the hypothesis that genetically governed neurodevelopmental processes can be traced in subcortical structures throughout life, we analyzed a longitudinal magnetic resonance imaging dataset (n = 974, age 4-89 years), identifying five clusters of longitudinal change in development. With some exceptions, these clusters followed placement along the cranial axis in embryonic brain development, suggesting continuity in the pattern of change from prenatal stages. Developmental change patterns were conserved through the lifespan and predicted general cognitive function in an age-invariant manner. The results were replicated in longitudinal data from the Lifebrain consortium (n = 756, age 19-83 years). Genetic contributions to longitudinal brain changes were calculated from the Vietnam Era Twin Study of Aging (n = 331 male twins, age 51-60 years), revealing that distinct sets of genes tended to govern change for each developmental cluster. This finding was confirmed with single nucleotide polymorphisms and cross-sectional MRI data from the UK Biobank (n = 20,588, age 40-69), demonstrating significantly higher co-heritability among structures belonging to the same developmental clusters. Together, these results suggest that coordination of subcortical change adheres to fundamental principles of lifespan continuity, genetic organization and age-invariant relationships to cognitive function. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.05.136531v1?rss=1 Authors: Gann, M. A., King, B. R., Dolfen, N., Veldman, M. P., Chan, K. L., Puts, N. A. J., Edden, R. A. E., Davare, M., Swinnen, S. P., Mantini, D., Robertson, E. M., Albouy, G. Abstract: While it is widely accepted that motor sequence learning (MSL) is supported by a prefrontal-mediated interaction between hippocampal and striatal networks, it remains unknown whether the functional responses of these networks can be modulated in humans with targeted experimental interventions. The present proof-of-concept study employed a comprehensive multimodal neuroimaging approach, including functional magnetic resonance (MR) imaging and MR spectroscopy, to investigate whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex can modulate responses in the hippocampus and striatum during motor learning. Our results indicate that stimulation influenced task-related connectivity patterns within hippocampo-frontal and striatal networks. Stimulation also altered the relationship between the levels of gamma-aminobutyric acid (GABA) in the stimulated prefrontal cortex and learning-related changes in both activity and connectivity in fronto-striato-hippocampal networks. This study provides the first experimental evidence that brain stimulation can alter motor learning-related functional responses in the striatum and hippocampus. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.01.128140v1?rss=1 Authors: Ryu, J., Torres, E. B. Abstract: While attempting to bridge motor control and cognitive science, the nascent field of embodied cognition has primarily addressed intended, goal-oriented actions. Less explored however, have been unintended motions. Such movements tend to occur largely beneath awareness, while contributing to the spontaneous control of redundant degrees of freedom across the body in motion. We posit that the consequences of such unintended actions implicitly contribute to our autonomous sense of action ownership and agency. We question whether biorhythmic activities from these motions are separable from those which intentionally occur. Here we find that fluctuations in the biorhythmic activities of the nervous systems can unambiguously differentiate across levels of intent. More important yet, this differentiation is remarkable when we examine the fluctuations in biorhythmic activity from the autonomic nervous systems. We find that when the action is intended, the heart signal leads the body kinematics signals; but when the action segment spontaneously occurs without instructions, the heart signal lags the bodily kinematics signals. We posit that such differentiation within the nervous system, may be necessary to acquire the sense of action ownership, which in turn, contributes to the sense of agency. We discuss our results while considering their potential translational value. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.29.120220v1?rss=1 Authors: Holden, S. S., Aboubakr, O., Higashikubo, B., Cho, F. S., Chang, A. H., Morningstar, A., Mathur, V., Kuhn, L. J., Suri, P., Sankaranarayanan, S., Andrews-Zwilling, Y., Aronica, E., Yednock, T., Paz, J. T. Abstract: While traumatic brain injury (TBI) acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of cortical injury that does not directly damage subcortical structures, we found a chronic increase in C1q expression specifically in the corticothalamic circuit. Increased C1q expression co-localized with neuron loss and chronic inflammation, and correlated with altered cortical rhythms. Blocking C1q counteracted most of these outcomes, suggesting that C1q is a disease modifier in TBI. Since the corticothalamic circuit is important for sensory processing, attention, cognition, and sleep, all of which can be impaired by TBI, this circuit could be a new target for treating TBI-related disabilities. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.26.116152v1?rss=1 Authors: Bodin, C., Pron, A., Le Mao, M., Regis, J., Belin, P., Coulon, O. Abstract: While there is a profusion of functional investigations involving the superior temporal sulcus (STS), our knowledge of the anatomy of this sulcus is still limited by a large variability across individuals. Several "plis de passage" (PPs), annectant gyri buried inside the fold, can separate the STS into distinct segments and could explain part of the observed variability. However, an accurate characterization is lacking to properly extract and fully understand the nature of PPs. The aim of the present study is twofold: i. to characterize the STS PPs by directly identifying them within individual STS, using the geometry of the surrounding surface and considering both deep and superficial PPs. ii. to test the hypothesis that PPs constitute local increases of the short-range structural connectivity. Performed on 90 subjects from the Human Connectome Project database, our study revealed that PPs constitute surface landmarks that can be identified from the geometry of the STS walls and that they constitute critical pathways of the U-shaped white-matter connecting the two banks of the STS. Specifically, a larger amount of fibers was extracted at the location of PPs compared to other locations in the STS. This quantity was also larger for superficial PPs than for deep buried ones. These findings raise new hypotheses regarding the relation between the cortical surface geometry and structural connectivity, as well as the possible role of PPs in the functional organization of the STS. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.20.105759v1?rss=1 Authors: Xia, Z., Wang, C., Hancock, R., Vandermosten, M., Hoeft, F. Abstract: While advanced paternal age (APA) has repeatedly been associated with a higher risk for neuropsychiatric disorders, its effects on cognitive processes such as reading have received minimal attention. Therefore, we examined the relationship between APA, offspring's reading abilities, and brain measures in a longitudinal neuroimaging study following 51 children from kindergarten through third grade. APA significantly predicted reduced reading performance, independent of parental reading history, socioeconomic status, home literacy environment, and birth order. This effect was mediated by gray matter volume change in the left posterior thalamus, predominantly the pulvinar nuclei. Complementary analyses using diffusion imaging data, Neurosynth, and 1000 Functional Connectome data indicated the APA-related cluster links to the dorsal attention network. These findings provide novel insights into the neurocognitive mechanisms underlying APA effect on reading during its earliest phase of reading acquisition and suggest future avenues of research on APA-related factors, such as de novo mutation, in reading. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.18.102913v1?rss=1 Authors: Murphy, C. A., Banks, M. I. Abstract: While their behavioral effects are well-characterized, the mechanisms by which anesthetics induce loss of consciousness are largely unknown. Anesthetics may disrupt integration and propagation of information in corticothalamic networks. Recent studies have shown that isoflurane diminishes synaptic responses of thalamocortical (TC) and corticocortical (CC) afferents in a pathway-specific manner. However, whether the synaptic effects of isoflurane observed in extracellular recordings persist at the cellular level has yet to be explored. Here, we activate TC and CC layer 1 inputs in non-primary mouse neocortex in ex vivo brain slices and explore the degree to which isoflurane modulates synaptic responses in pyramidal cells and in two inhibitory cell populations, somatostatin-positive (SOM+) and parvalbumin-positive (PV+) interneurons. We show that the effects of isoflurane on synaptic responses and intrinsic properties of these cells varies among cell type and by cortical layer. Layer 1 inputs to L4 pyramidal cells were suppressed by isoflurane at both TC and CC synapses, while those to L2/3 pyramidal cells and PV+ interneurons were not. TC inputs to SOM+ cells were rarely observed at all, while CC inputs to SOM+ interneurons were robustly suppressed by isoflurane. These results suggest a mechanism by which isoflurane disrupts integration and propagation of incoming cortical signals. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.13.094672v1?rss=1 Authors: Imam, N., Finlay, B. Abstract: While the mechanisms generating the topographic organization of primary sensory areas in the neocortex are well-studied, what generates secondary cortical areas is virtually unknown. Using physical parameters representing primary and secondary visual areas as they vary from monkey to mouse, we derived a growth model to explore if characteristic features of secondary areas could be produced from correlated activity patterns arising from V1 alone. We found that V1 seeded variable numbers of secondary areas based on activity-driven wiring and wiring density limits within the cortical surface. These secondary areas exhibited the typical mirror-reversal of map topography on cortical area boundaries and progressive reduction of the area and spatial resolution of each new map on the caudorostral axis. Activity-based map formation may be the basic mechanism that establishes the matrix of topographically-organized cortical areas available for later computational specialization. Copy rights belong to original authors. Visit the link for more info