bluuebunny/crossref_metadata_2025_split huggingface dataset:
Piezo regulates epithelial topology and promotes precision in organ size control
Authors: Kumar Nilay , Mim Mayesha Sahir , Levis Megan , Unger Maria , Miranda Gabriel , Robinett Trent , Zartman Jeremiah 
Published: August 2023

AbstractMechanosensitive Piezo channels regulate cell division through calcium-mediated activation of ERK signaling or activate Rho signaling to mediate cell extrusion and cell death. However, systems-level functions of Piezo in regulating organogenesis remain poorly understood. Here, we demonstrate that Piezo controls epithelial cell topology to ensure precise organ growth through the integration of live imaging experiments with pharmacological and genetic perturbations and computational modeling. Notably, knockout or knockdown ofPiezoled to bilateral asymmetry in wing phenotypes. While pharmacological activation of Piezo stimulated an increase in the frequency of spikes in cytosolic Ca2+, we discovered thatPiezooverexpression counterintuitively reduces Ca2+signaling dynamics. Knockdown ofPiezoinhibited proliferation and decreased apoptosis, resulting in an overall increase in epithelial overcrowding. In contrast, either genetic overexpression or pharmacological activation of Piezo increased cell proliferation and cell removal through basal extrusion. Surprisingly,Piezooverexpression increased the hexagonality of cellular topology. To test whether Piezo regulates cell topology, we formulated computational simulations to investigate how expression levels of Piezo protein regulate cell proliferation and apoptosis through modulation of the cut-off tension required for Piezo channel activation. Quantitative analysis validated computational simulation predictions of how perturbations toPiezoimpacted epithelial topology. Overall, our findings demonstrate that Piezo promotes robustness in regulating epithelial topology and is necessary for precise organ size control.
Warming alters cascading effects of a dominant arthropod predator on microbial community composition in the Arctic
Authors: Koltz Amanda M. , Koyama Akihiro , Wallenstein Matthew 
Published: August 2023

ABSTRACTWarming is expected to increase abundances of wolf spider, the top predator in soil communities in the Arctic, but we have little understanding on how increased wolf spider density under warmer conditions affects soil microbial structure through trophic cascades. We tested the effects of wolf spider density and warming on bacterial and fungal community structure in litter through a fully factorial mesocosm experiment in Arctic tundra over two summers. Replicated litter bags were deployed at the soil surface and underground in the organic soil profile and collected at 2- and 14-month incubation. The litter samples were analyzed for community structure of bacteria and fungi and mass weight loss. After 2-month incubation, bacterial and fungal community compositions were already structured interactively by the spider density and warming treatments. Such interaction effect was also found in litter microbial community structure as well as litter mass loss rates after 14-month incubation. Our results show that wolf spiders have indirect, cascading effects on microbial community structure but that warming can alter these effects. The non-linear responses of microbial communities and litter decomposition to warming and increased spider density cast uncertainty in predicting structure and function of Arctic terrestrial ecosystem under warmer conditions in the future.IMPORTANCEThis is one of the first studies demonstrating that predator abundances and increased temperature interactively structure litter microbial communities in the Arctic. The Arctic is one of the fastest warming regions due to climate change and contains disproportionately large amounts of soil organic matter, including thick litter which accumulated over the long time because of slow decomposition. The accelerated soil organic matter decomposition due to the rapid warming can cause positive feedback where resulting greenhouse gas emission contribute to further global warming. Since microbial structure can affect decomposition rates of litter, the observed non-linear responses of soil microbial community compositions and litter decomposition rates indicate challenges in predicting Arctic ecosystem responses in the future.
A Spiking Neural Network with Continuous Local Learning for Robust Online Brain Machine Interface
Authors: Taeckens Elijah A. , Shah Sahil 
Published: August 2023

AbstractObjectiveSpiking neural networks (SNNs) are powerful tools that are well suited for brain machine interfaces (BMI) due to their similarity to biological neural systems and computational efficiency. They have shown comparable accuracy to state-of-the-art methods, but current training methods require large amounts of memory, and they cannot be trained on a continuous input stream without pausing periodically to perform backpropagation. An ideal BMI should be capable training continuously without interruption to minimize disruption to the user and adapt to changing neural environments.ApproachWe propose a continuous SNN weight update algorithm that can be trained to perform regression learning with no need for storing past spiking events in memory. As a result, the amount of memory needed for training is constant regardless of the input duration. We evaluate the accuracy of the network on recordings of neural data taken from the premotor cortex of a primate performing reaching tasks. Additionally, we evaluate the SNN in a simulated closed loop environment and observe its ability to adapt to sudden changes in the input neural structure.Main resultsThe continuous learning SNN achieves the same peak correlation (ρ= 0.7) as existing SNN training methods when trained offline on real neural data while reducing the total memory usage by 92%. Additionally, it matches state-of-the-art accuracy in a closed loop environment, demonstrates adaptability when subjected to multiple types of neural input disruptions, and is capable of being trained online without any prior offline training.SignificanceThis work presents a neural decoding algorithm that can be trained rapidly in a closed loop setting. The algorithm increases the speed of acclimating a new user to the system and also can adapt to sudden changes in neural behavior with minimal disruption to the user.
Temporal association activates projections from the perirhinal cortex and ventral CA1 to the prelimbic cortex and from the prelimbic cortex to the basolateral amygdala
Authors: Santos Thays Brenner dos , Kramer-Soares Juliana Carlota , Coelho Cesar Augusto de Oliveira , Oliveira Maria Gabriela Menezes 
Published: August 2023

AbstractIn temporal associations, the prelimbic cortex (PL) has persistent activity during the interval between the conditioned stimulus (CS) and the unconditioned stimulus (US), which maintains a CS representation. Regions cooperating for this function or encoding the CS before the interval could neuroanatomically connect to the PL, supporting learning. The basolateral amygdala (BLA) has CS- and US-responsive neurons, convergently activated. The PL could directly project to the BLA to associate the transient CS memory with the US. We investigated the neural circuit supporting temporal associations using the CFC-5s task, in which a 5-second interval separates the contextual CS from the US. Injecting retrobeads, we quantified c-Fos in PL- or BLA-projecting neurons from 9 regions after CFC-5s or contextual fear conditioning (CFC), in which CS/US overlap. The CFC-5s activated ventral CA1 (vCA1) and perirhinal cortex (PER) neurons projecting to the PL, and PL neurons projecting to BLA. Both CFC-5s and CFC activated vCA1 and lateral entorhinal (LEC) neurons projecting to BLA, and BLA neurons projecting to PL. Both conditioning activated the PER, LEC, cingulate and infralimbic cortices, nucleus reuniens, and ventral subiculum. Results added new relevance to the PER→PL projection and showed that the PL/BLA are reciprocally functionally connected in CFC-5s.
Broadening the scope: Multiple functional connectivity networks underlying threat and safety signaling
Authors: Cushing Cody A. , Peng Yujia , Anderson Zachary , Young Katherine S. , Bookheimer Susan Y. , Zinbarg Richard E. , Nusslock Robin , Craske Michelle G. 
Published: August 2023

AbstractIntroductionThreat learning and extinction processes are thought to be foundational to anxiety and fear-related disorders. However, the study of these processes in the human brain has largely focused on a priori regions of interest, owing partly to the ease of translating between these regions in human and non-human animals. Moving beyond analyzing focal regions of interest to whole-brain dynamics during threat learning is essential for understanding the neuropathology of fear-related disorders in humans.Methods223 participants completed a 2-day Pavlovian threat conditioning paradigm while undergoing fMRI. Participants completed threat acquisition and extinction. Extinction recall was assessed 48 hours later. Using a data-driven group independent component analysis (ICA), we examined large-scale functional connectivity networks during each phase of threat conditioning. Connectivity networks were tested to see how they responded to conditional stimuli during early and late phases of threat acquisition and extinction and during early trials of extinction recall.ResultsA network overlapping with the default mode network involving hippocampus, vmPFC, and posterior cingulate was implicated in threat acquisition and extinction. Another network overlapping with the salience network involving dACC, mPFC, and inferior frontal gyrus was implicated in threat acquisition and extinction recall. Other networks overlapping with parts of the salience, somatomotor, visual, and fronto-parietal networks were involved in the acquisition or extinction of learned threat responses.ConclusionsThese findings help confirm previous investigations of specific brain regions in a model-free fashion and introduce new findings of spatially independent networks during threat and safety learning. Rather than being a single process in a core network of regions, threat learning involves multiple brain networks operating in parallel coordinating different functions at different timescales. Understanding the nature and interplay of these dynamics will be critical for comprehensive understanding of the multiple processes that may be at play in the neuropathology of anxiety and fear-related disorders.
Protein Structure Refinement via DeepTracer and AlphaFold2
Authors: Chen Jason , Zia Ayisha , Wang Fengbin , Hou Jie , Cao Renzhi , Si Dong 
Published: August 2023

AbstractUnderstanding the structures of proteins has numerous applications, such as vaccine development. It is a slow and labor-intensive task to manually build protein structures from experimental electron density maps, therefore, machine learning approaches have been proposed to automate this process. However, most of the experimental maps are not atomic resolution, so they are insufficient for computer vision-based machine learning methods to precisely determine the protein structure. On the other hand, methods that utilize evolutionary information from protein sequences to predict structures, like AlphaFold2, have recently achieved groundbreaking accuracy but often require manual effort to refine the results. We propose DeepTracer-Refine, an automated method to refine AlphaFold structures by aligning them to DeepTracer’s predicted structure. We tested our method on 39 multi-domain proteins and we improved the average residue coverage from 78.2% to 90.0% and average lDDT score from 0.67 to 0.71. We also compared DeepTracer-Refine against another method, Phenix’s AlphaFold refinement, to demonstrate that our method not only performs better when the initial AlphaFold model is less precise but also exceeds Phenix in run-time performance.
Continuous quasi-attractors dissolve with too much – or too little – variability
Authors: Schönsberg Francesca , Monasson Rémi , Treves Alessandro 
Published: August 2023

AbstractHippocampal place cells in bats flying in a 200m tunnel have been shown to be active at multiple locations, with considerable variability in place field size and peak rate. We ask whether such disorderly representation of one’s own position in a large environment could be stored in memory through Hebbian plasticity, and be later retrieved from a partial cue. Simulating an autoassociative network in which similarly variable place fields are encoded with a covariance rule, we find that it may serve spatial memory only within a certain variability range, in particular of field width. The working range is flanked by two dysfunctional regions, accessed through apparent phase transitions. For a large network, phase boundaries can be estimated analytically to depend only on the number of fields per cell in one case, and to be a pure number in the other, implying a maximal size of the environment that can be stored in memory.
Triaging of ⍺-helical proteins to the mitochondrial outer membrane by distinct chaperone machinery based on substrate topology
Authors: Muthukumar Gayathri , Stevens Taylor A. , Inglis Alison J. , Esantsi Theodore K. , Saunders Reuben A. , Schulte Fabian , Voorhees Rebecca M. , Guna Alina , Weissman Jonathan S. 
Published: August 2023

SUMMARYMitochondrial outer membrane ⍺-helical proteins play critical roles in mitochondrial-cytoplasmic communication, but the rules governing the targeting and insertion of these biophysically diverse substrates remain unknown. Here, we first defined the complement of required mammalian biogenesis machinery through genome-wide CRISPRi screens using topologically distinct membrane proteins. Systematic analysis of nine identified factors across 21 diverse ⍺-helical substrates reveals that these components are organized into distinct targeting pathways which act on substrates based on their topology. NAC is required for efficient targeting of polytopic proteins whereas signal-anchored proteins require TTC1, a novel cytosolic chaperone which physically engages substrates. Biochemical and mutational studies reveal that TTC1 employs a conserved TPR domain and a hydrophobic groove in its C-terminal domain to support substrate solubilization and insertion into mitochondria. Thus, targeting of diverse mitochondrial membrane proteins is achieved through topological triaging in the cytosol using principles with similarities to ER membrane protein biogenesis systems.
The D-mannose/L-galactose pathway plays a predominant role in ascorbate biosynthesis in the liverwortMarchantia polymorphabut is not regulated by light and oxidative stress
Authors: Ishida Tetsuya , Tanaka Yasuhiro , Maruta Takanori , Ishikawa Takahiro 
Published: August 2023

SUMMARYAscorbate plays an indispensable role in plants, functioning as both an antioxidant and a cellular redox buffer. It is widely acknowledged that the ascorbate biosynthesis in the photosynthetic tissues of land plants is governed by light-mediated regulation of the D-mannose/L-galactose (D-Man/L-Gal) pathway. At the core of this light-dependent regulation lies theVTC2gene, encoding the rate-limiting enzyme GDP-L-Gal phosphorylase. TheVTC2expression is regulated by signalsviathe photosynthetic electron transport system. In this study, we directed our attention to the liverwortMarchantia polymorpha, representing one of the basal land plants, enabling us to conduct an in-depth analysis of its ascorbate biosynthesis. TheM. polymorphagenome harbors a solitary gene for each enzyme involved in the D-Man/L-Gal pathway, includingVTC2, along with three lactonase orthologs, which may be involved in the alternative ascorbate biosynthesis pathway. Through supplementation experiments with potential precursors, we observed that only L-Gal exhibited effectiveness in ascorbate biosynthesis. Furthermore, the generation ofVTC2-deficient mutants through genome editing unveiled the inability of thallus regeneration in the absence of L-Gal supplementation, thereby revealing the importance of the D-Man/L-Gal pathway in ascorbate biosynthesis withinM. polymorpha. Interestingly, gene expression analyses unveiled a distinct characteristic ofM. polymorpha, where none of the genes associated with the D-Man/L-Gal pathway, includingVTC2, showed upregulation in response to light, unlike other known land plants. This study sheds light on the exceptional nature ofM. polymorphaas a land plant that has evolved distinctive mechanisms concerning ascorbate biosynthesis and its regulation.
Mosaic of local adaptation between white clover and rhizobia along an urbanization gradient
Authors: Murray-Stoker David , Johnson Marc T. J. 
Published: August 2023

AbstractUrbanization frequently alters the biotic and abiotic environmental context. Variation in both the biotic and abiotic environment can result in selection mosaics that lead to locally adapted phenotypes. Ecological changes to urban environments have been found to result in evolutionary responses across a diverse array of plants and animals, but the effects of urbanization on local adaptation and coevolution between species remains largely unstudied.Using a common garden experiment of 30 populations and 1080 plants, we tested for local adaptation in the mutualism between white clover (Trifolium repens) and rhizobia (Rhizobium leguminosarumsymbiovartrifolii) along an urbanization gradient. We asked: (Q1) are white clover and rhizobia locally adapted? (Q2) Does nitrogen (N) addition mediate the strength of local adaptation? (Q3) Is the strength of local adaptation in host plants related to the strength of local adaptation in rhizobia, as expected if white clover and rhizobia are co-adapting? And (Q4) How does the degree of local adaptation vary with urbanization?We found evidence for local adaptation for both white clover and rhizobia, with stronger signatures of local adaptation for rhizobia than white clover (Q1). While N addition positively affected plant biomass and negatively affected nodule density, N addition did not consistently mediate patterns of local adaptation (Q2). The strength of local adaptation was positively related between white clover and rhizobia under N addition, suggesting that soil N mediates co-adaptation between white clover and rhizobia (Q3). We did not find a consistent relationship between measures of urbanization and local adaptation (Q4). Additionally, fitness responses for white clover and rhizobia were unrelated toRhizobiumabundance and local adaptation was unrelated to the broader bacterial microbiome in the soil inoculants or root endosphere.Synthesis. Our results show a spatial mosaic in local adaptation, with stronger local adaptation for rhizobia than white clover. While urbanization does influence the ecology of plant-microbe interactions, our study suggests urbanization does not disrupt local adaptation and coevolution among mutualists.
Real-time assessment of the impacts of polystyrene and silver nanoparticles on hatching process and early-stage development ofArtemiausing a microfluidic platform
Authors: Dey Preyojon , Bradley Terence M. , Boymelgreen Alicia 
Published: August 2023

AbstractThe development of real-time in-situ monitoring techniques is key to advancing a mechanistic understanding of the impacts of marine pollution, which is challenging to acquire through traditional end-point toxicity testing. We investigated the impacts of different nanopollutants on the hatching process and early-stage development of marine organisms, a vulnerable life stage, by observing oxygen consumption in real-time and morphological changes at regular intervals using a microfluidic platform. Here, two common and distinct nanoparticle (NP) types - polystyrene (PS) nanoplastic and silver (Ag) nanometal, were examined to assess and compare impacts on the hatching process and nauplius stage (first larval stage) ofArtemia, a widely used zooplankton model in ecotoxicological studies. The study was conducted over a wide range of doses that are relevant to different environmental conditions, ranging from 0-1 mg/L, over a period of 24 hours. The hatching process ofArtemiais comprised of four distinct stages which can be differentiated by metabolism and morphology: hydration, differentiation, emergence, and hatching. During hatching, NP exposure altered the time needed for the resumption of dormantArtemiacysts (hydration duration) at the lowest dose, dramatically prolonged the differentiation stage, and slowed embryo emergence from the cysts. The remaining time for the hatching stage during the experimental timeframe was also shortened. Overall, the presence of NPs led to increased oxygen consumption in multiple stages of the hatching process. Hatchability increased significantly with NP concentration although mortality showed an inverse pattern. This may be attributed to the increased aggregation of NPs in saltwater with increasing concentration which limits bioavailability during hatching but may be more readily consumed post-hatch. Ag NPs had a greater effect on hatching and mortality in comparison to PS NPs. A significant impact of NPs on swimming speed was observed, with a decrease observed in the presence of PS NPs and an increase observed in the presence of Ag NPs.Graphical abstractHighlightsUtilization of oxygen sensor integrated microfluidic chip and microscopy for ecotoxicological study.Bioaccumulation of NPs affected hatching stages and respiration leading to inhibition of hatchability, with greater toxicity of silver NPs.NPs caused significant mortality and alteration in swimming performance.
Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques
Authors: Huang Lulu , Zhao Tongyi , Zhao Weijun , Shao Andong , Zhao Huajun , Ma Wenxuan , Gong Yingfei , Zeng Xianhuan , Weng Changzhen , Bu Lingling , Di Zhenhua , Sun Shiyu , Dai Qinsheng , Sun Minhui , Wang Limei , Liu Zhenguang , Shi Leilei , Hu Jiesen , Fang Shentong , Zhang Cheng , Zhang Jian , Wang Guan , Loré Karin , Yang Yong , Lin Ang 
Published: August 2023

AbstractHerpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has a remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signaling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. The mRNA platform therefore holds prospects for further investigations in next-generation VZV vaccine development.