bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of cellular and synaptic mechanisms behind spontaneous cortical activity in vitro: Insights from optimization of spiking neuronal network models
Authors: Aćimović Jugoslava , Mäki-Marttunen Tuomo , Teppola Heidi , Linne Marja-Leena 
Published: November 2021

AbstractSpontaneous network bursts, the intervals of intense network-wide activity interleaved with longer periods of sparse activity, are a hallmark phenomenon observed in cortical networks at postnatal developmental stages. Generation, propagation and termination of network bursts depend on a combination of synaptic, cellular and network mechanisms; however, the interplay between these mechanisms is not fully understood. We study this interplay in silico, using a new data-driven framework for generating spiking neuronal networks fitted to the microelectrode array recordings. We recorded the network bursting activity from rat postnatal cortical networks under several pharmacological conditions. In each condition, the function of specific excitatory and inhibitory synaptic receptors was reduced in order to examine their impact on global network dynamics. The obtained data was used to develop two complementary model fitting protocols for automatic model generation. These protocols allowed us to disentangle systematically the modeled cellular and synaptic mechanisms that affect the observed network bursts. We confirmed that the change in excitatory and inhibitory synaptic transmission in silico, consistent with pharmacological conditions, can account for the changes in network bursts relative to the control data. Reproducing the exact recorded network bursts statistics required adapting both the synaptic transmission and the cellular excitability separately for each pharmacological condition. Our results bring new understanding of the complex interplay between cellular, synaptic and network mechanisms supporting the burst dynamics. While here we focused on analysis of in vitro data, our approach can be applied ex vivo and in vivo given that the appropriate experimental data is available.New & NoteworthyWe studied the role of synaptic mechanisms in shaping the neural population activity by proposing a new method to combine experimental data and data-driven computational modeling based on spiking neuronal networks. We analyze a dataset recorded from postnatal rat cortical cultures in vitro under the pharmacological influence of excitatory and inhibitory synaptic receptor antagonists. Our computational model identifies neurobiological mechanisms necessary to reproduce the changes in population activity seen across pharmacological conditions.
Blood pressure and the kidney cortex transcriptome response to high sodium diet challenge in female nonhuman primates
Authors: Riojas Angelica M. , Spradling-Reeves Kimberly D. , Shade Robert E. , Puppala Sobha R. , Christensen Clinton L. , Birnbaum Shifra , Glenn Jeremy P. , Li Cun , Shaltout Hossam , Hall-Ursone Shannan , Cox Laura A. 
Published: November 2021

AbstractBlood pressure (BP) is influenced by genetic variation and sodium intake. Ninety percent of Americans consume more than the AHA recommended amount of sodium. Studies on the impact of genetic variation and sodium intake on BP in nonhuman primates (NHP) to date have focused on males. We hypothesized that variation in renal transcriptional networks correlate with BP response to high dietary sodium in female baboons. Sodium-naïve female baboons (n=7) were fed a low-sodium (LS) diet for 6 weeks followed by a high sodium (HS) diet for 6 weeks. Sodium intake, serum 17 betaestradiol, and ultrasound-guided kidney biopsies for RNA-Seq BP were collected at the end of each diet. BP was continuously measured for 64-hour periods throughout the study by implantable telemetry devices. On the LS diet, Na+ intake and serum 17 beta-estradiol concentration correlated with BP.Kidney transcriptomes differed by diet; analysis by unbiased weighted gene co-expression network analysis revealed modules of genes correlated with BP on the HS diet. Cell type composition of renal biopsies was consistent among all animals for both diets. Network analysis of module genes showed causal networks linking hormone receptors, proliferation and differentiation, methylation, hypoxia, insulin and lipid regulation, and inflammation as regulators underlying variation in BP on the HS diet. Our results show variation in BP correlated with novel kidney gene networks with master regulators PPARG and MYC in female baboons on a HS diet. Identification of mechanisms underlying regulators that influence BP will inform better therapies towards greater precision medicine for women.
Comparative transcriptomics identifies the transcription factors BRANCHED1 and TCP4, as well as the microRNA miR166 as candidate genes involved in the evolutionary transition from dehiscent to indehiscent fruits in Lepidium (Brassicaceae)
Authors: Gramzow Lydia , Klupsch Katharina , Fernández Pozo Noé , Hölzer Martin , Marz Manja , Rensing Stefan A. , Theißen Günter 
Published: November 2021

AbstractBackgroundFruits are the seed-bearing structures of flowering plants and are highly diverse in terms of morphology, texture and maturation. Dehiscent fruits split open upon maturation to discharge their seeds while indehiscent fruits are dispersed as a whole. Indehiscent fruits evolved from dehiscent fruits several times independently in the crucifer family (Brassicaceae). The fruits of Lepidium appelianum, for example, are indehiscent while the fruits of the closely related L. campestre are dehiscent. Here, we investigate the molecular and genetic mechanisms underlying the evolutionary transition from dehiscent to indehiscent fruits using these two Lepidium species as model system.ResultsWe have sequenced the transcriptomes and small RNAs of floral buds, flowers and fruits of L. appelianum and L. campestre and analyzed differentially expressed genes (DEGs) and differently differentially expressed genes (DDEGs). DEGs are genes that show significantly different transcript levels in the same structures (buds, flowers and fruits) in different species, or in different structures in the same species. DDEGs are genes for which the change in expression level between two structures is significantly different in one species than in the other. Comparing the two species, the highest number of DEGs was found in flowers, followed by fruits and floral buds while the highest number of DDEGs was found in fruits versus flowers followed by flowers versus floral buds. Several gene ontology terms related to cell wall synthesis and degradation were overrepresented in different sets of DEGs highlighting the importance of these processes for fruit opening. Furthermore, the fruit valve identity genes FRUITFUL and YABBY3 were among the DEGs identified. Finally, the microRNA miR166 as well as the TCP transcription factors BRANCHED1 (BRC1) and TCP FAMILY TRANSCRIPTION FACTOR 4 (TCP4) were found to be DDEGs.ConclusionsOur study reveals differences in gene expression between dehiscent and indehiscent fruits and uncovers miR166, BRC1 and TCP4 as possible causes for the evolutionary transition from dehiscent to indehiscent fruits in Lepidium.
Anisotropic Interaction and Motion States of Locusts in a Hopper Band
Authors: Weinburd Jasper , Landsberg Jacob , Kravtsova Anna , Lam Shanni , Sharma Tarush , Simpson Stephen J , Sword Gregory A , Buhl Jerome 
Published: November 2021

AbstractSwarming locusts present a quintessential example of animal collective motion. Juvenile locusts march and hop across the ground in coordinated groups called hopper bands. Composed of up to millions of insects, hopper bands exhibit aligned motion and various collective structures. These groups are well-documented in the field, but the individual insects themselves are typically studied in much smaller groups in laboratory experiments. We present the first trajectory data that detail the movement of individual locusts within a hopper band in a natural setting. Using automated video tracking, we derive our data from footage of four distinct hopper bands of the Australian plague locust,Chortoicetes terminifera. We reconstruct nearly twenty-thousand individual trajectories composed of over 3.3 million locust positions. We classify these data into three motion states: stationary, walking, and hopping. Distributions of relative neighbor positions reveal anisotropies that depend on motion state. Stationary locusts have high-density areas distributed around them apparently at random. Walking locusts have a low-density area in front of them. Hopping locusts have low-density areas in front and behind them. Our results suggest novel insect interactions, namely that locusts change their motion to avoid colliding with neighbors in front of them.
Worldwide analysis of reef surveys sorts coral taxa by associations with recent and past heat stress
Authors: Selmoni Oliver , Lecellier Gaël , Berteaux-Lecellier Véronique , Joost Stéphane 
Published: November 2021

AbstractCoral reefs around the world are under threat from anomalous heat waves that are causing the widespread decline of hard corals. Different coral taxa are known to have different sensitivities to heat, although variation in susceptibilities have also been observed within the same species living in different environments. Characterizing such taxa-specific variations is key to enforcing efficient reef conservation strategies.Here, we combine worldwide-reef-survey data with remote sensed environmental variables to evaluate how local differences in taxa-specific coral cover are associated with past trends of thermal anomalies, as well as of non-heat related conditions. While the association with non-heat related environmental variation was seldom significant, we found that heat stress trends matched local differences in coral cover. Coral taxa were sorted based on the different patterns of associations with heat stress.For branching, tabular and corymbose Acroporidae, reefs exposed to recent heat stress (measured the year before the survey) had lower coral cover than locally expected; and among these reefs, those previously exposed to frequent past heat stress (measured since 1985) displayed relatively higher coral cover, compared to those less frequently exposed. For massive and encrusting Poritidae, and for meandroid Favidae and Mussidae, we observed a negative association of coral cover with recent heat stress; however, unlike with Acroporidae, these associations were weaker and did not vary with past heat exposure. For Pocilloporidae, we found a positive association between coral cover and recent heat stress for reefs frequently exposed to past heat, while we found a negative association at reefs less frequently exposed to past heat. A similar pattern was observed for the branching Poritidae, although the associations were weaker and not statistically significant.Overall, these results show taxa-specific heat association patterns that might correspond to taxa-specific responses to past heat exposure, such as shifts in the assembly of coral communities, evolutionary adaptation or physiological acclimation.
Comprehensive analysis of behavioral dynamics in the protochordateCiona intestinalis
Authors: Athira Athira , Dondorp Daniel , Rudolf Jerneja , Peytral Olivia , Chatzigeorgiou Marios 
Published: November 2021

AbstractVertebrate nervous systems can generate a remarkable diversity of behaviors. However, our understanding of how behaviors may have evolved in the chordate lineage is limited by the lack of neuroethological studies leveraging our closest invertebrate relatives.Here we combine high-throughput video acquisition with pharmacological perturbations of bioamine signaling to systematically reveal the global structure of the motor behavioral repertoire in theCiona intestinalislarvae. Most ofCiona’spostural variance can be captured by six basic shapes, which we term “Eigencionas”. Motif analysis of postural time series further demonstrated that bioamines influence numerous stereotyped behavioral maneuvers including “startle-like” and “beat-and-glide”. Employing computational modeling of swimming dynamics and spatio-temporal embedding of postural features revealed that subtle behavioural differences are generated at the levels of motor modules and the transitions between, both modulated by bioamines. Finally, we show that flexible motor module usage gives rise to diverse behaviors in response to different light stimuli.
mTOR-neuropeptide Y signaling sensitizes nociceptors to drive neuropathic pain
Authors: Chen Lunhao , Hu Yaling , Wang Siyuan , Cao Kelei , Mai Weihao , Sha Weilin , Ma Huan , Gao Yong-Jing , Duan Shumin , Wang Yue , Gao Zhihua 
Published: November 2021

AbstractNeuropathic pain is a refractory condition that involves de novo protein synthesis in the nociceptive pathway. The mechanistic target of rapamycin (mTOR) is a master regulator of protein translation; however, mechanisms underlying its role in neuropathic pain remain elusive. Using spared nerve injury-induced neuropathic pain model, we found that mTOR is preferentially activated in large-diameter dorsal root ganglion (DRG) neurons and spinal microglia. However, selective ablation of mTOR in DRG neurons, rather than microglia, alleviated neuropathic pain. We show that injury- induced mTOR activation promoted transcriptional induction of NPY likely via signal transducer and activator of transcription 3 (STAT3) phosphorylation. NPY further acted primarily on Y2 receptors (Y2R) to enhance nociceptor excitability. Peripheral replenishment of NPY reversed pain alleviation upon mTOR removal, whereas Y2R antagonists prevented pain restoration. Our findings reveal an unexpected link between mTOR and NPY in promoting nociceptor sensitization and neuropathic pain, through NPY/Y2R signaling-mediated intra-ganglionic transmission.
IMPACT OF ADOLESCENT INTERMITTENT ETHANOL EXPOSURE IN MALE AND FEMALE RATS ON SOCIAL DRINKING AND NEUROPEPTIDE GENE EXPRESSION
Authors: Towner Trevor T. , Papastrat Kimberly M. , Spear Linda P. , Varlinskaya Elena I. , Werner David F. 
Published: November 2021

AbstractBackgroundAlcohol use during adolescence can alter maturational changes that occur in brain regions associated with social and emotional responding. Our previous studies have shown that adult male, but not female rats demonstrate social anxiety-like alterations and enhanced sensitivity to ethanol-induced social facilitation following adolescent intermittent ethanol (AIE) exposure. These consequences of AIE may influence adult social drinking in a sex-specific manner.MethodsTo test effects of AIE on social drinking, male and female Sprague-Dawley rats exposed to water or ethanol [0 or 4 g/kg, intragastrically, every other day, between postnatal day (P) 25 and 45] were tested as adults (P72-83) in a social drinking paradigm (30-minute access to a 10% ethanol solution in supersac or supersac alone in groups of three same-sex littermates across two 4-day cycles separated by 4 days off). Social behavior was assessed during the last drinking session, with further assessment of oxytocin (OXT), oxytocin receptor (OXTR), vasopressin (AVP) and vasopressin receptors 1a and 1b (AVPR1a, AVPR1b) in the hypothalamus and lateral septum.ResultsMales exposed to AIE consumed more ethanol than water-exposed controls during the second drinking cycle, whereas AIE did not affect supersac intake in males. AIE-exposed females consumed less ethanol and more supersac than water-exposed controls. Water-exposed females drinking ethanol showed more social investigation as well as significantly higher hypothalamic OXTR, AVP, and AVPR1b gene expression than their counterparts ingesting supersac and AIE females drinking ethanol. In males, hypothalamic AVPR1b gene expression was affected by drinking solution, with significantly higher expression evident in males drinking ethanol than those consuming supersac.ConclusionsCollectively, these findings provide new evidence regarding sex-specific effects of AIE on social drinking and suggest that the hypothalamic OXT and AVP systems are implicated in the effects of ingested ethanol on social behavior in a sex- and adolescent exposure-dependent manner.
Analyzing and Reconciling Colocalization and Transcriptome-wide Association Studies from the Perspective of Inferential Reproducibility
Authors: Hukku Abhay , Sampson Matthew G. , Luca Francesca , Pique-Regi Roger , Wen Xiaoquan 
Published: November 2021

AbstractTranscriptome-wide association studies and colocalization analysis are popular computational approaches for integrating genetic association data from molecular and complex traits. They show the unique ability to go beyond variant-level genetic association evidence and implicate critical functional units, e.g., genes, in disease etiology. However, in practice, when the two approaches are applied to the same molecular and complex trait data, the inference results can be markedly different. This paper systematically investigates the inferential reproducibility between the two approaches through theoretical derivation, numerical experiments, and analyses of 4 complex trait GWAS and GTEx eQTL data. We identify two classes of inconsistent inference results. We find that the first class of inconsistent results may suggest an interesting biological phenomenon, i.e., horizontal pleiotropy; thus, the two approaches are truly complementary. The inconsistency in the second class can be understood and effectively reconciled. To this end, we propose a novel approach for locus-level colocalization analysis. We demonstrate that the joint TWAS and locus-level colocalization analysis improves specificity and sensitivity for implicating biological-relevant genes.
Identification and tracking of alloreactive T cell clones in Rhesus Macaques through the RM-scTCR-Seq platform
Authors: Gerdemann Ulrike , Fleming Ryan A. , Kaminski James , McGuckin Connor , Rui Xianliang , Lane Jennifer F. , Keskula Paula , Cagnin Lorenzo , Shalek Alex K. , Tkachev Victor , Kean Leslie S. 
Published: November 2021

AbstractT cell receptor clonotype tracking is a powerful tool for interrogating T cell mediated immune processes. New methods to pair a single cell’s transcriptional program with its T cell receptor (TCR) identity allow monitoring of T cell clonotype-specific transcriptional dynamics. While these technologies have been available for human and mouse T cells studies, they have not been developed for Rhesus Macaques, a critical translational organism for autoimmune diseases, vaccine development and transplantation. We describe a new pipeline, ‘RM-scTCR-Seq’, which, for the first time, enables RM specific single cell TCR amplification, reconstitution and pairing of RM TCR’s with their transcriptional profiles. We apply this method to a RM model of GVHD, and identify and track in vitro detected alloreactive clonotypes in GVHD target organs and explore their GVHD driven cytotoxic T cell signature. This novel, state-of-the-art platform fundamentally advances the utility of RM to study protective and pathogenic T cell responses.
Evolutionary history limits species’ ability to match color sensitivity to available habitat light
Authors: Murphy Matthew J. , Westerman Erica L. 
Published: November 2021

AbstractThe spectrum of light that an animal sees – from ultraviolet to far red light – is governed by the number and wavelength sensitivity of a family of retinal proteins called opsins. It has been hypothesized that the spectrum of light available in an environment influences the range of colors that a species has evolved to see. However, invertebrates and vertebrates use phylogenetically distinct opsins in their retinae, and it remains unclear whether these distinct opsins influence what animals see, or how they adapt to their light environments. Systematically utilizing published visual sensitivity data from across animal phyla, we found that terrestrial animals are more sensitive to shorter and longer wavelengths of light than aquatic animals, and that invertebrates are more sensitive to shorter wavelengths of light than vertebrates. Controlling for phylogeny removes the effects of habitat and lineage on visual sensitivity. Closed and open habitat terrestrial species have similar spectral sensitivities when comparing across the Metazoa, and deep water animals are more sensitive to shorter wavelengths of light than shallow water animals. Our results suggest that animals do adapt to their light environment, however the invertebrate-vertebrate evolutionary divergence has limited the degree to which animals can perform visual tuning.
Solvation dynamics-powered structure and function of multi-molecular cellular systems exemplified by non-equilibrium cereblon-degrader-CK1α ternary complex formation
Authors: Wan Hongbin , Aravamuthan Vibhas , Williams Sarah , Wartchow Charles , Duca José S. , Pearlstein Robert A. 
Published: November 2021

AbstractCellular functions are executed via a form of analog computing that is based on the switchable covalent and non-covalent states of multi-molecular fluxes (i.e., time-dependent species/state concentrations) operating in the non-linear dynamics regime. We and others have proposed that the non-covalent states and state transitions of aqueous fluxes are powered principally by the storage and release of potential energy to/from the anisotropic H-bond network of solvating water (which we refer to as the “solvation field”), which is a key tenet of a first principles theory on cellular structure and function (called Biodynamics) that we outlined previously. This energy is reflected in water occupancy as a function of solute surface position, which can be probed computationally using WATMD software. In our previous work, we used this approach to deduce the structural dynamics of the COVID main protease, including substrate binding-induced enzyme activation and dimerization, and product release-induced dimer dissociation. Here, we examine:1)The general relationships between surface composition/topology and solvation field properties for both high and low molecular weight (HMW and LMW) solutes.2)The general means by which structural dynamics are powered by solvation free energy, which we exemplify via binding between the E3 ligase CUL4A/RBX1/DDB1/CRBN, LMW degraders, and substrates. We propose that degraders organize the substrate binding surface of cereblon toward complementarity with native and neo substrates, thereby speeding the association rate constant and incrementally slowing the dissociation rate constant.3)Structure-activity relationships (SAR) based on complementarity between the solvation fields of cognate protein-ligand partners exemplified via LMW degraders.