bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rap1 promotes epithelial integrity and cell viability in a growing tissue
Authors: Messer C. Luke , McDonald Jocelyn A. 
Published: October 2022

AbstractHaving intact epithelial tissues is critical for embryonic development and adult homeostasis. How epithelia respond to damaging insults or tissue growth while still maintaining intercellular connections and barrier integrity during development is poorly understood. The conserved small GTPase Rap1 is critical for establishing cell polarity and regulating cadherin-catenin cell junctions. Here, we identified a new role for Rap1 in maintaining epithelial integrity and tissue shape duringDrosophilaoogenesis. Loss of Rap1 activity disrupted the follicle cell epithelium and the shape of egg chambers during a period of major growth. Rap1 was required for proper E-Cadherin localization in the anterior epithelium and for epithelial cell survival. Both Myo-II and the adherens junction-cytoskeletal linker protein α-Catenin were required for normal egg chamber shape but did not strongly affect cell viability. Blocking the apoptotic cascade failed to rescue the cell shape defects caused by Rap1 inhibition. One consequence of increased cell death caused by Rap1 inhibition was the preferential loss of the polar cells, which later in development led to fewer cells forming a properly migrating border cell cluster. Our results thus indicate dual roles for Rap1 in maintaining epithelia and cell survival in a growing tissue during development.
Predicting yield traits of individual field-grownBrassica napusplants from rosette-stage leaf gene expression
Authors: De Meyer Sam , Cruz Daniel Felipe , De Swaef Tom , Lootens Peter , De Block Jolien , Bird Kevin , Sprenger Heike , Van de Voorde Michael , Hawinkel Stijn , Van Hautegem Tom , Inzé Dirk , Nelissen Hilde , Roldán-Ruiz Isabel , Maere Steven 
Published: October 2022

ABSTRACTBackgroundIn the plant sciences, results of laboratory studies often do not translate well to the field because lab growth conditions are very different from field conditions. To help close this lab-field gap, we developed a new strategy for studying the wiring of plant traits directly in the field, based on molecular profiling and phenotyping of individual plants of the same genetic background grown in the same field. This single-plant omics strategy leverages uncontrolled micro-environmental variation across the field and stochastic variation among the individual plants as information sources, rather than controlled perturbations. Here, we use single-plant omics on winter-typeBrassica napus(rapeseed) plants to investigate to what extent rosette-stage gene expression profiles can be linked to the early and late phenotypes of individual field-grown plants.ResultsWe find that rosette leaf gene expression in autumn has substantial predictive power for both autumnal leaf phenotypes and final yield in spring. Many of the top predictor genes are linked to developmental processes known to occur in autumn in winter-typeB. napusaccessions, such as the juvenile-to-adult and vegetative-to-reproductive phase transitions, indicating that the yield potential of winter-typeB. napusis influenced by autumnal development.ConclusionsOur results show that profiling individual plants under uncontrolled field conditions is a valid strategy for identifying genes and processes influencing crop yield in the field.
Deep Reinforcement Learning for Stabilization of Large-scale Probabilistic Boolean Networks
Authors: Moschoyiannis Sotiris , Chatzaroulas Evangelos , Sliogeris Vytenis , Wu Yuhu 
Published: October 2022

AbstractThe ability to direct a Probabilistic Boolean Network (PBN) to a desired state is important to applications such as targeted therapeutics in cancer biology. Reinforcement Learning (RL) has been proposed as a framework that solves a discrete-time optimal control problem cast as a Markov Decision Process. We focus on an integrative framework powered by a model-free deep RL method that can address different flavours of the control problem (e.g., withorwithout control inputs; attractor stateora subset of the state space as the target domain). The method is agnostic to the distribution of probabilities for the next state, hence it does not use the probability transition matrix. The time complexity is onlylinearon the time steps, or interactions between the agent (deep RL) and the environment (PBN), during training. Indeed, we explore thescalabilityof the deep RL approach to (set) stabilization of large-scale PBNs and demonstrate successful control on large networks, including a metastatic melanoma PBN with200 nodes.
Bacterial aerobic methane cycling by the marine sponge-associated microbiome
Authors: Ramírez Gustavo A. , Bar-Shalom Rinat , Furlan Andrea , Romeo Roberto , Gavagnin Michelle , Calabrese Gianluca , Garber Arkadiy I. , Steindler Laura 
Published: October 2022

AbstractBackgroundMethanotrophy by the sponge-hosted microbiome has been mainly reported in the ecological context of deep-sea hydrocarbon seep niches where methane is either produced geothermically or via anaerobic methanogenic archaea inhabiting the sulfate-depleted sediments. However, methane oxidizing bacteria from the candidate phylum Binatota have recently been described and shown to be present in oxic shallow-water marine sponges, where sources of methane remain undescribed.ResultsHere, using an integrative -omicsapproach, we provide evidence for sponge-hosted bacterial methanogenesis occurring in fully oxygenated shallow water habitats. Specifically, we suggest methanogenesis occursviaat least two independent pathways involving methylamine and methylphosphonate transformations that, concomitantly to aerobic methane production, generate bioavailable nitrogen and phosphate, respectively. Methylphosphonate may be sourced from seawater continuously filtered by the sponge host. Methylamines may also be externally sourced or, alternatively, generated by a multi-step metabolic process where carnitine, derived from sponge cell debris, is transformed to methylamine by different sponge-hosted microbial lineages. Finally, methanotrophs specialized in pigment production, affiliated to the phylum Binatota, may provide a photoprotective function, closing a previously undescribed C1-metabolic loop that involves both the sponge host and specific members of the associated microbial community.ConclusionGiven the global distribution of this ancient animal lineage and their remarkable water filtration activity, sponge hosted methane cycling may affect methane supersaturation in oxic coastal environments. Depending on the net balance between methanogenesis and methanotrophy, sponges may serve as marine sources or sinks of this potent greenhouse gas.
Potential role of immediate early genesEgr-1, Hr-38andKakuseiin the foraging behavior and learning of in honeybees
Authors: Singh Asem Surindro , Chanu Machathoibi Takhellambam 
Published: October 2022

AbstractThe foraging behavior of honeybees is one of the most systematically composed behaviors among social insects which are admirable to watch. The main purpose of honeybee foraging is to collect food for their colony and since ancient days honeybee products have been used for various medicinal purposes (Singh and Takhellambam 2021). During foraging, honeybees gather information and transmit to their colony members regarding the location, distance, and profitability of forage sites with the help of unique movements called waggle dance. The capacities of honeybees time memory enable the foragers to return to a good food source in anticipation of the time of day. This highly intellectual, dynamic, and well-coordinated behavior of honeybees makes them to be one of the best choices of behavioral model to study various aspects of dynamic behaviors. As a result, vast knowledge in honeybee behavior has been accumulated and several recent studies immerge towards finding the underpinning regulatory biology of honeybee foraging behaviors. Immediate early genes (IE) genes are well documented neural markers and their promising roles in honeybee foraging have been demonstrated. Two of our recent studies showed three IE genesEgr-1, Hr38andKakuseiinvolvement during the daily foraging of honeybees. This finding has provided an avenue to further explore and identify the regulatory genes/proteins and neurons that underlie a specific behavior such as learning, memory, communication, and interaction etc. In this study we further analyze our previous published data to examine interaction of the three genes during the daily foraging of honeybees.
The role of thioredoxin proteins inMycobacterium tuberculosisprobed by proteome-wide target profiling
Authors: Sugandhi Sapna , Taunk Khushman , Jadhav Sushama , Nema Vijay , Rapole Srikanth , Mande Shekhar C. 
Published: October 2022

AbstractMycobacterium tuberculosisencounters diverse microenvironments as it attempts to establish itself within its human host. The bacterium survives oxidative assault (ROS and RNS) when it is inside the host macrophages. Redox sensory and regulation processes therefore assume significant importance, as these are essential processes forM. tuberculosisto survive under these hostile conditions. The thioredoxin system that maintains balance between the thiol/dithiol couple plays a key role in maintaining redox homeostasis inM. tuberculosis. The most explored function of the thioredoxin system is elimination of toxic molecules such as free radicals, while very little is known about its role in other metabolic processes. In the present study, we aimed to reduce the knowledge gap about the thioredoxin system inM. tuberculosis. We attempted to capture targets of all the thioredoxins (viz., TrxB and TrxC) and a thioredoxin-like protein, NrdH inM. tuberculosisunder aerobic and hypoxic conditions by performing thioredoxin trapping chromatography followed by mass spectrometry. Targets were classified using the PANTHER classification system and most enriched processes were figured out using Gene Ontology analysis. We found that TrxC captured the maximum number of targets in both the physiological conditions. Also, we suggest that the thioredoxin system might play an important role in hypoxic conditions by targeting proteins responsible to sense and maintain hypoxic conditions. Furthermore, our studies establish a link between TrxB and iron-sulfur cluster biogenesis inM. tuberculosis. Ultimately, these findings open a novel avenue to target the thioredoxin system for screening new anti-mycobacterial drug targets.ImportanceTuberculosis (TB), an infectious disease caused by bacteriaM. tuberculosis, is the leading cause of death in the list of infectious diseases. Worldwide 1.7 billion people are estimated to be infected with TB, containing active and latent cases. An alarming situation is thatM. tuberculosishas developed resistance against one or many of the first line drugs leading to emergence of drug resistant or multidrug resistant TB. Novel drugs targeting the drug resistant bacteria is an urgent need to cure the disease. Our study provides the framework to identify new drug targets. The significance of our study is to understand the thioredoxin system in more details by identifying their target proteins, which might facilitate development of new anti-tubercular drugs.
Electrophysiological correlates of associative recognition memory for identity, spatial, and temporal relations
Authors: Hugeri Ofer , Vakil Eli , Levy Daniel A. 
Published: October 2022

AbstractThe formation of associative representations and their retrieval from episodic memory are vital cognitive functions. However, it is unclear to what extent retrieval of the basic component relations of episodic memory – identity, time, and space – requires different or shared brain mechanisms. In the current study, we employed EEG to track the time courses of electrophysiological correlates of retrieval processes of memory for identity relations, temporal order, and spatial configuration. Participants engaged in pair-associate learning of serially presented and spatially configured object picture pairs, followed by discrimination of identity, spatially, or temporally intact and rearranged pairs. Event-related brain potentials (ERPs) revealed distinct patterns of activity during successful retrieval of identity, spatial, and temporal relations that differed by the status of association, across the three retrieval time windows examined (300-500, 500-800, and 800-1000 ms). The identity relations condition was distinguished by a widespread greater negative-going deflection for rearranged relative to intact pairs in all three time windows. For the temporal relations condition, we observed a widespread more negative-going deflection for rearranged than intact pairs, significant in the second time window only. For the spatial relations condition, there was a widespread positive-going deflection greater for rearranged than for intact pairs, significant in the early and in middle time windows. These patterns of activity suggest that retrieval of associative memory traces for identity, spatial, and temporal relationships involve dynamically different processes, which may partially rely on different sets of basic associative mechanisms.
Systematic loss of function screens identify pathway specific functional circular RNAs
Authors: Liu Ling , Neve Matthew , Perlaza-Jimenez Laura , Hawdon Azelle , Conn Simon J. , Zenker Jennifer , Tamayo Pablo , Goodall Gregory J. , Rosenbluh Joseph 
Published: October 2022

AbstractCircular RNAs (circRNAs) are covalently closed single stranded RNAs that are produced by RNA back-splicing. A small number of circRNAs have been implicated as functional, however, we still lack systematic understanding of cellular processes and signalling pathways that are regulated by circRNAs. A major gap in understanding circRNA function is the ability to define pathways that are regulated by circRNAs. Here, we generated a pooled shRNA library targeting the back-splice junction of 3,354 human circRNAs that are expressed at low to high levels in humans. We used this library for loss of function proliferation screens in a panel of 18 cancer cell lines from four tissue types that harbour mutations leading to constitutive activity of defined pathways. Using this dataset, we identify context specific and non-specific circRNAs. We validated these observations with a secondary screen and uncovered a role forcircRERE, a cell essential circRNA that regulates ferroptosis. Furthermore, we characterised the functional roles of pathway-specific circRNA,circSMAD2, a novel regulator of the WNT pathway andcircMTO1, a regulator of MAPK signalling in aPTENdependent manner. Our work sheds light on molecular pathways regulated by circRNAs and provides a catalogue of circRNAs with a measurable function in human cells.
Toehold-Mediated Strand Displacement in Random Sequence Pools
Authors: Mayer Thomas , Oesinghaus Lukas , Simmel Friedrich C. 
Published: October 2022

ABSTRACTToehold-mediated strand displacement (TMSD) has been used extensively for molecular sensing and computing in DNA-based molecular circuits. As these circuits grow in complexity, sequence similarity between components can lead to cross-talk causing leak, altered kinetics, or even circuit failure. For small non-biological circuits, such unwanted interactions can be designed against. In environments containing a huge number of sequences, taking all possible interactions into account becomes infeasible. Therefore, a general understanding of the impact of sequence backgrounds on TMSD reactions is of great interest. Here, we investigate the impact of random DNA sequences on TMSD circuits. We begin by studying individual interfering strands and use the obtained data to build machine learning models that estimate kinetics. We then investigate the influence of pools of random strands and find that the kinetics are determined by only a small subpopulation of strongly interacting strands. Consequently, their behavior can be mimicked by a small collection of such strands. The equilibration of the circuit with the background sequences strongly influences this behavior, leading to up to one order of magnitude difference in reaction speed. Finally, we compare two established and a novel technique that speed up TMSD reactions in random sequence pools: a threeletter alphabet, protection of toeholds by intramolecular secondary structure, or by an additional blocking strand. While all of these techniques were useful, only the latter can be used without sequence constraints. We expect that our insights will be useful for the construction of TMSD circuits that are robust to molecular noise.
Glucagon-like peptide-1 receptor in the human hypothalamus is associated with body mass index and colocalizes with the anorexigenic neuropeptide nucleobindin-2/nesfatin-1
Authors: Psilopanagioti Aristea , Nikou Sofia , Logotheti Souzana , Arbi Marina , Chartoumpekis Dionysios V. , Papadaki Helen 
Published: October 2022

AbstractIntroductionGlucagon-like peptide-1 (GLP-1) anorexigenic and anti-obesogenic effects are centrally mediated. Data on animals emphasize the importance of neuronal GLP-1 receptor (GLP-1R) for feeding suppression, although it is unclear whether astrocytes participate in the transduction of anorectic GLP-1R-dependent signals. In humans, the brain circuitry underlying these effects remains insufficiently investigated. GLP-1R neuroanatomic localization in human hypothalamus, a brain region with a pivotal role in energy homeostasis regulation, is essential in order to improve our understanding of GLP-1 signaling pathways and central metabolic functions. The present study aimed to explore GLP-1R protein expression in human hypothalamus and its correlation with body mass index (BMI).MethodsSections of hypothalamus from 28 autopsy cases, 11 with normal weight (BMI < 25 Kg/m2) and 17 with non-normal weight (BMI ≥ 25 Kg/m2), were examined using immunohistochemistry and double immunofluorescence labeling.ResultsProminent GLP-1R immunoexpression was detected in neurons of several hypothalamic nuclei, including paraventricular, supraoptic, and infundibular nuclei, lateral hypothalamic area (LH), and basal forebrain nuclei. Interestingly, in LH, GLP-1R protein expression was significantly decreased in individuals with BMI ≥ 25 Kg/m2, compared with normal weight counterparts (p=0.03). Furthermore, GLP-1R was moderately and negatively correlated (τb=-0.347, p=0.024) with BMI levels only in the LH. GLP-1R extensively colocalized with the anorexigenic and anti-obesogenic neuropeptide nucleobindin-2/nesfatin-1, but not with the astrocytic marker glial fibrillary acidic protein (GFAP).ConclusionThese data suggest a potential role for GLP-1R in the regulation of energy balance in human hypothalamus, possibly through interactions with nesfatin-1. In LH, an appetite- and reward-related brain region, reduced GLP-1R immunoexpression may contribute to dysregulation of homeostatic and/or hedonic feeding behavior. GLP-1R colocalization with nesfatin-1 in the basal forebrain, a cognition-related brain area, might give impetus towards elucidating additional central actions of GLP-1R.
Influence of MUC1 on trafficking of TRPV5 and TRPV6 andin vivoCa2+homeostasis
Authors: Al-bataineh Mohammad M. , Kinlough Carol L. , Marciszyn Allison , Lam Tracey , Ye Lorena , Kidd Kendrah , Maggiore Joseph C. , Poland Paul A. , Bleyer Anthony , Bain Daniel J. , Kleyman Thomas R. , Hughey Rebecca P. , Ray Evan C. 
Published: October 2022

SUMMARYPolymorphism of the gene encoding mucin 1 (MUC1) is associated with skeletal and dental phenotypes in human genomic studies. Animals lacking MUC1 exhibit mild reduction in bone density. These phenotypes could be a consequence of modulation of bodily Ca homeostasis by MUC1, as suggested by the previous observation that MUC1 enhances cell surface expression of the Ca2+-selective channel, TRPV5 in cultured unpolarized cells. Using biotinylation of cell-surface proteins, we asked whether MUC1 influences endocytosis of TRPV5 and another Ca2+-selective TRP channel, TRPV6, in cultured polarized epithelial cells. Results indicate that MUC1 reduces endocytosis of both channels, enhancing cell surface expression. Further, mice lacking MUC1 lose apical localization of TRPV5 and TRPV6 in the renal tubular and duodenal epithelium. Females, but not males, lacking MUC1 exhibit reduced blood Ca2+. However, mice lacking MUC1 exhibited no differences in basal urinary Ca excretion or Ca retention in response to PTH receptor signaling, suggesting compensation by transport mechanisms independent of TRPV5 and TRPV6. Finally, humans with autosomal dominant tubulointerstitial kidney disease due to frame-shift mutation of MUC1 (ADTKD-MUC1) exhibit reduced plasma Ca concentrations compared to control individuals with mutations in the gene encoding uromodulin (ADTKD-UMOD), consistent with MUC1 haploinsufficiency causing reduced bodily Ca2+.
Fast yet force-effective mode of supracellular collective cell migration on aligned fibers due to extracellular force transmission
Authors: Bagchi Amrit , Sarker Bapi , Zhang Jialiang , Foston Marcus , Pathak Amit 
Published: October 2022

AbstractCell collectives, like other motile entities, generate and use forces to move forward. Here, we ask whether environmental configurations alter this proportional force-speed relationship, since aligned extracellular matrix fibers are known to cause directed migration. We show that aligned fibers serve as active conduits for spatial propagation of cellular mechanotransduction through matrix exoskeleton, leading to efficient directed collective cell migration. Epithelial (MCF10A) cell clusters adhered tosoftsubstrates with aligned collagen fibers (AF) migrate faster with much lesser traction forces, compared to random fibers (RF). Fiber alignment causes higher motility waves and transmission of normal stresses deeper into cell monolayer while minimizing shear stresses and increased cell-division based fluidization. By contrast, fiber randomization induces cellular jamming due to breakage in motility waves, disrupted transmission of normal stresses, and heightened shear driven flow. Using a novel motor-clutch model, we explain that such ‘force-effective’ fast migration phenotype occurs due to rapid stabilization of contractile forces at the migrating front, enabled by higher frictional forces arising from simultaneous compressive loading of parallel fiber-substrate connections. We also model’haptotaxis’ to show that increasing ligand connectivity (but not continuity) increases migration efficiency. According to our model, increased rate of front stabilization via higher resistance to substrate deformation is sufficient to capture ‘durotaxis’. Thus, our findings reveal a new paradigm wherein the rate of leading-edge stabilization determines the efficiency of supracellular collective cell migration.