bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relating local connectivity and global dynamics in recurrent excitatory-inhibitory networks
Authors: Shao Yuxiu , Ostojic Srdjan 
Published: August 2022

AbstractHow the connectivity of cortical networks determines the neural dynamics and the resulting computations is one of the key questions in neuroscience. Previous works have pursued two complementary strategies to quantify the structure in connectivity, by specifying either the local statistics of connectivity motifs between small groups of neurons, or by defining network-wide low-rank patterns of connectivity that determine the resulting low-dimensional dynamics. A direct relationship between these two approaches is however currently missing, and in particular it remains to be clarified how local connectivity statistics are related to the global connectivity structure and shape the low-dimensional activity. To bridge this gap, here we develop a method for mapping local connectivity statistics onto an approximate global low-rank structure. Our method rests on approximating the global connectivity matrix using dominant eigenvectors, which we compute using perturbation theory for random matrices. This approach demonstrates that multi-population networks defined from local connectivity properties can in general be approximated by low-rank connectivity with Gaussian-mixture statistics. We specifically apply this method to excitatory-inhibitory networks, and show that it leads to accurate predictions for both the low-dimensional dynamics, and for the activity of individual neurons. Altogether, our approach allows us to disentangle the effects of mean connectivity and reciprocal motifs on the global recurrent feedback, and provides an intuitive picture of how local connectivity shapes global network dynamics.Author summaryThe structure of connections between neurons is believed to determine how cortical networks control behaviour. Current experimental methods typically measure connections between small numbers of simultaneously recorded neurons, and thereby provide information on statistics of local connectivity motifs. Collective network dynamics are however determined by network-wide patterns of connections. How these global patterns are related to local connectivity statistics and shape the dynamics is an open question that we address in this study. Starting from networks defined in terms of local statistics, we develop a method for approximating the resulting connectivity by global low-rank patterns. We apply this method to classical excitatory-inhibitory networks and show that it allows us to predict both collective and single-neuron activity. More generally, our approach provides a link between local connectivity statistics and global network dynamics.
Systems-wide dissection of organic acid assimilation in Pseudomonas aeruginosa reveals a novel path to underground metabolism
Authors: Dolan Stephen K. , Wijaya Andre , Kohlstedt Michael , Gläser Lars , Brear Paul , Silva-Rocha Rafael , Wittmann Christoph , Welch Martin 
Published: August 2022

AbstractThe human pathogen Pseudomonas aeruginosa (Pa) is one of the most frequent and severe causes of nosocomial infection. This organism is also a major cause of airway infections in people with cystic fibrosis (CF). Pa is known to have a remarkable metabolic plasticity, allowing it to thrive in diverse environmental conditions and ecological niches, yet little is known about the central metabolic pathways which sustain its growth during infection, or precisely how these pathways operate. In this work, we used a combination of ‘omics approaches (transcriptomics, proteomics, metabolomics and 13C-fluxomics) and reverse genetics to provide a systems-level insight into how the infection-relevant organic acids, succinate and propionate, are metabolized by Pa. Moreover, through structural and kinetic analysis of the 2-methylcitrate synthase (PrpC) and its paralogue, citrate synthase (GltA), we show how these two crucial enzymatic steps are interconnected in Pa organic acid assimilation. We found that Pa can rapidly adapt to the loss of GltA function by acquiring mutations in a transcriptional repressor, which then de-represses prpC expression. Our findings provide a clear example of how ‘underground metabolism’, facilitated by enzyme substrate promiscuity, “rewires” Pa metabolism, allowing it to overcome the loss of a crucial enzyme. This pathogen-specific knowledge is critical for the advancement of a model-driven framework to target bacterial central metabolism.
SEC-seq: Association of molecular signatures with antibody secretion in thousands of single human plasma cells
Authors: Cheng Rene Yu-Hong , de Rutte Joseph , Ott Andee R. , Bosler Lucienne , Kuo Wei-Ying , Liang Jesse , Hall Brian E , Rawlings David J , Carlo Dino Di , James Richard G. 
Published: August 2022

ABSTRACTProtein secretion drives many functionsin vivo; however, methods to link secretions with surface markers and transcriptomes have been lacking. By accumulating secretions close to secreting cells held within cavity-containing hydrogel nanovials, we demonstrate workflows to analyze the amount of IgG secreted from single human antibody-secreting cells and link this information to surface marker expression and transcriptional profiles from the same cells. Measurements using flow cytometry and imaging flow cytometry corroborated an association between levels of IgG secretion and CD138 expression. Using oligonucleotide-labeled antibodies and droplet-based sequencing, we show that pathways encoding protein localization to the endoplasmic reticulum, NADH complex assembly, and mitochondrial respiration were most associated with high IgG secretion. Altogether, this method links secretion information to cell surface and single-cell sequencing information (SEC-seq) and enables exploration of links between genome and secretory function, laying the foundation for numerous discoveries in immunology, stem cell biology, and beyond.
PP4 inhibition sensitizes ovarian cancer to NK cell-mediated cytotoxicity via STAT1 activation and inflammatory signaling
Authors: Raja Remya , Wu Christopher , Rubino Thomas E , Utagawa Emma , Magtibay Paul , Butler Kristina A. , Curtis Marion 
Published: August 2022

ABSTRACTBackgroundIncreased infiltration of T cells into ovarian tumors has been repeatedly shown to be predictive of enhanced patient survival. However, despite the evidence of an active immune response in ovarian cancer (OC), the frequency of responses to immune checkpoint blockade (ICB) therapy in OC is much lower than other cancer types. Recent studies have highlighted that deficiencies in the DNA damage response (DDR) can drive increased genomic instability and tumor immunogenicity, which leads to enhanced responses to ICB. Protein phosphatase 4 (PP4) is a critical regulator of the DDR; however, its potential role in anti-tumor immunity is currently unknown.ResultsOur results show that the PP4 inhibitor, fostriecin, combined with carboplatin leads to increased carboplatin sensitivity, DNA damage, and micronuclei formation. Using multiple ovarian cancer cell lines, we show that PP4 inhibition or PPP4C knockdown combined with carboplatin triggers inflammatory signaling via NFκB and STAT1 activation. This resulted in increased expression of the pro-inflammatory cytokines and chemokines: CCL5, CXCL10, and IL6. In addition, IFNB1 expression was increased suggesting activation of the type I interferon response. Conditioned media from OC cells treated with the combination of PP4 inhibitor and carboplatin significantly increased migration of both CD8 T cell and NK cells over carboplatin treatment alone. Knockdown of STING in OC cells significantly abrogated the increase in CD8 T cell migration induced by PP4 inhibition. Co-culture of NK-92 cells and OC cells with PPP4C or PPP4R3B knockdown resulted in strong induction of NK cell activation as measured by IFN-γ levels. Further, we also observed increased degranulation and NK cell-mediated cytotoxicity against OC cells with PPP4C or PPP4R3B knockdown.ConclusionsOur work has identified a role for PP4 inhibition in promoting inflammatory signaling and enhanced immune cell effector function. These findings support the further investigation of PP4 inhibitors to enhance chemo-immunotherapy for ovarian cancer treatment.
Abiotic niche predictors of long-term trends in body mass and survival of Eastern Himalayan birds
Authors: Bharadwaj Akshay , Chanda Ritobroto , Biswakarma Aman , Tamang Bharath , Munda Binod , Pradhan Dambar K , Rai Mangal K , Rai Shambu , Srinivasan Umesh 
Published: August 2022

AbstractThe synergistic impacts of climate change and habitat degradation threaten tropical species worldwide. However, how species’ abiotic niches affect their demographic vital rates and phenotypic changes under anthropogenic change remains poorly understood. Using an 11-year mark-recapture dataset from primary and selectively logged forest in the Eastern Himalayas, we investigated how temperature-humidity niche characteristics predicted body mass and survival trends in understorey insectivorous birds over time in each habitat. Our results show that logged forest is hotter and drier than primary forest, and the arthropod community shows dramatic shifts in composition upon selective logging. In understorey insectivores, the degree of dissimilarity between species-specific primary and logged forest niches was strongly and negatively correlated with survival and body mass trends in logged forest. Here, we show that temperature-humidity niche shifts in response to anthropogenic habitat modification can impact demographic vital rates and body condition crucial for population persistence. This work has the potential to inform prompt, targeted conservation efforts toward species that are the most threatened in a warmer and more degraded world.
Generic Framework for Quantifying the Influence of the Mitral Valve on Ventricular Blood Flow
Authors: Thiel Jan-Niklas , Steinseifer Ulrich , Neidlin Michael 
Published: August 2022

SummaryBlood flow within the left ventricle provides important information regarding cardiac function in health and disease. The mitral valve strongly influences the formation of flow structures and there exist various approaches for the representation of the valve in numerical models of left ventricular blood flow. However, a systematic comparison of the various mitral valve models is missing, making a priori decisions considering the overall model’s context of use impossible. Within this study, a benchmark setup to compare the influence of mitral valve modeling strategies on intraventricular flow features was developed. Then, five mitral valve models of increasing complexity: no modeling, static wall, 2D and 3D porous medium with time-dependent porosity, and one-way Fluid-Structure-Interaction (FSI) were compared with each other. The flow features velocity, kinetic energy, transmitral pressure drop, vortex formation, flow asymmetry as well as computational cost and ease-of-implementation were evaluated. The one-way FSI approach provides the highest level of flow detail, which is accompanied by the highest numerical costs and challenges with the implementation. As an alternative, the porous medium approach with our new expansion including time-dependent porosity provides good results with up to 10% deviations in the flow features (except the transmitral pressure drop) in comparison to the FSI model and only a fraction (11%) of numerical costs. Taken together, our benchmark setup allows a quantitative comparison of various mitral valve modeling approaches and is provided to the scientific community for further testing and expansion..
Task matters: individual MEG signatures from naturalistic and neurophysiological brain states
Authors: Colenbier Nigel , Sareen Ekansh , del-Águila Puntas Tamara , Griffa Alessandra , Pellegrino Giovanni , Mantini Dante , Marinazzo Daniele , Arcara Giorgio , Amico Enrico 
Published: August 2022

AbstractThe discovery that human brain connectivity data can be used as a “fingerprint” to identify a given individual from a population, has become a burgeoning research area in the neuroscience field. Recent studies have identified the possibility to extract these brain signatures from the temporal rich dynamics of resting-state magnetoencephalography (MEG) recordings. However, to what extent MEG signatures constitute a marker of human identifiability when engaged in task-related behavior remains an open question. Here, using MEG data from naturalistic and neurophysiological tasks, we show that identification improves in tasks relative to resting-state, providing compelling evidence for a task dependent axis of MEG signatures. Notably, improvements in identifiability were more prominent in strictly controlled tasks. Lastly, the brain regions contributing most towards individual identification were also modified when engaged in task activities. We hope that this investigation advances our understanding of the driving factors behind brain identification from MEG signals.
Non-cyanobacterial diazotrophs from the Rhizobiales order support marine microalgae in nitrogen-depleted environments
Authors: Chandola Udita , Gaudin Marinna , Trottier Camille , Lavier Aydat Louis Josselin , Manirakiza Eric , Menicot Samuel , Fischer Erik Jörg , Louvet Isabelle , Lacour Thomas , Chaumier Timothée , Tanaka Atsuko , Pohnert Georg , Chaffron Samuel , Tirichine Leïla 
Published: August 2022

AbstractBackgroundNon-cyanobacteria diazotrophs (NCDs) were shown to dominate in surface waters shifting the long-held paradigm of cyanobacteria dominance and raising fundamental questions on how these putative heterotrophic bacteria thrive in sunlit oceans. The absence of laboratory cultures of these bacteria significantly limits our ability to understand their behavior in natural environments and, consequently, their contribution to the marine nitrogen cycle.ResultsHere, we used a multidisciplinary approach and report an unprecedented finding in the diatomPhaeodactylum tricornutum(Pt) of NCDs in the phycosphere or the pelagic community sustaining its survival in the absence of bioavailable nitrogen. We sequenced the bacterial metacommunity associated with Pt and assembled several bacterial genomes, identifying multiple NCDs from the Rhizobiales order, includingBradyrhizobium,Mesorhizobium,GeorhizobiumandMethylobacterium. We demonstrated the nitrogen-fixing ability of PtNCDs through in silico identification of nitrogen fixation genes, or by using PCR, acetylene reduction, or 15N incorporation. We showed the wide occurrence of this type of interactions with the isolation of NCDs from other microalgae, their identification in the environment, and their predicted associations with photosynthetic microalgae.ConclusionsOur study underscores the importance of microalgae interactions with NCDs to permit and support nitrogen fixation. This work provides a unique model Pt-NCDs to study the ecology of this interaction advancing our understanding of the key drivers of global marine nitrogen fixation.
Revealing the molecular mechanisms underlying neural transmission of female pheromone signals in the male antennae of Antheraea pernyi by integrative proteomics and metabolomics analysis
Authors: Wang Guobao , Ji Xiang , Nie Lei 
Published: August 2022

AbstractDetection of sex pheromones of insects relies on the antennae. The female pheromone signal transmission in the male antennae ultimately initiates the courtship and mating behaviors of males. To investigate the proteins and metabolites involved in this neural transduction, the study adopted integrative proteomics and metabolomics analysis including tandem mass tag (TMT) proteomic quantification and liquid chromatography tandem mass spectrometry (LC/MS)-based metabolomics for comparing proteomic and metabolic changes between the antennae of male moths following stimulation by females and the non-stimulated males of A. pernyi. A total of 92 differentially expressed proteins (DEPs) containing 52 up-regulated and 40 down-regulated proteins and 545 differentially expressed metabolites (DEMs) including 218 up- and 327 down-regulated metabolites were identified from the antennae of female-stimulated male moths based on the proteome and metabolome data, respectively. GO enrichment analysis showed that 45 DEPs could be enriched into different GO terms on different levels. COG analysis indicated that 61 DEPs were assigned to 20 functional categories. The 160 DEMs respectively fell into 11 and 44 classes at SuperClass and Class levels based on HMDB annotation. KEGG pathway enrichment analysis indicated that totally 43 DEMs were enriched into 6, 27, and 87 pathways on level 1, 2, and 3, respectively. A number of DEPs and DEMs related to neural transmission of female pheromone signals in the male antennae of A. pernyi were screened, including tyrosine hydroxylase, cryptochrome-1, tachykinin, arylalkylamine N-acetyltransferase, cadherin-23, glutathione S-transferase delta 3, tyramine, tryptamine, n-oleoyl dopamine, n-stearoyl dopamine, and n-stearoyl tyrosine. We concluded that the altered expression levels of those proteins or metabolites were involved in regulating the neuron activity for enhanced transmission of neural impulses and continuous perception, reception, and transduction of female pheromone signals. Our findings yielded novel insights into the potential molecular mechanisms in the antennae of male A. pernyi responding to female attraction.
Deep learning-driven insights into super protein complexes for outer membrane protein biogenesis in bacteria
Authors: Gao Mu , An Davi Nakajima , Skolnick Jeffrey 
Published: August 2022

AbstractTo reach their final destinations, outer membrane proteins (OMPs) of gram-negative bacteria undertake an eventful journey beginning in the cytosol. Multiple molecular machines, chaperones, proteases, and other enzymes facilitate the translocation and assembly of OMPs. These helpers usually associate, often transiently, forming large protein assemblies. They are not well-understood due to experimental challenges in capturing and characterizing protein-protein interactions (PPIs), especially transient ones. Using AF2Complex, we introduce a high-throughput, deep learning pipeline to identify PPIs within the E. coli cell envelope and apply it to several proteins from an OMP biogenesis pathway. Among the top confident hits obtained from screening ~1,500 envelope proteins, we find not only expected interactions but also unexpected ones with profound implications. Subsequently, we predict atomic structures for these protein complexes. These structures, typically of high confidence, explain experimental observations, and lead to mechanistic hypotheses for how a chaperone assists a nascent, precursor OMP emerging from a translocon, how another chaperone prevents it from aggregating and docks to an β-barrel assembly port, and how a protease performs quality control. This work presents a general strategy for investigating biological pathways by using structural insights gained from deep learning-based predictions.
Single-cell RNA-seq reveals stepwise fate conversion of supporting cells to hair cells in the chick auditory epithelium
Authors: Matsunaga Mami , Yamamoto Ryosuke , Kita Tomoko , Ohnishi Hiroe , Yamamoto Norio , Okano Takayuki , Omori Koichi , Nakagawa Takayuki 
Published: August 2022

AbstractIn contrast to mammals, the avian cochlea, specifically the basilar papilla, can regenerate sensory hair cells, which involves fate conversion of supporting cells to hair cells. To determine the mechanisms for converting supporting cells to hair cells, we used single-cell RNA sequencing during hair cell regeneration in explant cultures of chick basilar papillae. We identified dynamic changes in the gene expression of supporting cells, and the pseudotime trajectory analysis demonstrated the stepwise fate conversion from supporting cells to hair cells. Initially, supporting cell identity was erased and transition to the precursor state occurred. A subsequent gain in hair cell identity progressed together with downregulation of precursor-state genes. Transforming growth factor beta receptor 1-mediated signaling was involved in induction of the initial step, and its inhibition resulted in suppression of hair cell regeneration. Our data provide new insights for understanding fate conversion from supporting cells to hair cells in avian basilar papillae.
Genome-wide peptidoglycan profiling of Vibrio cholerae
Authors: Hernandez Sara B. , Alvarez Laura , Ritzl-Rinkenberger Barbara , Schiffthaler Bastian , Serrano Alonso R. , Cava Felipe 
Published: August 2022

SUMMARYMost bacteria cells are protected by a peptidoglycan cell wall. Defining the chemical structure of the peptidoglycan has been instrumental to characterize cell wall associated proteins and to illuminate the mode of action of cell wall-acting antibiotics. However, a major roadblock for a comprehensive understanding of peptidoglycan homeostasis has been the lack of methods to conduct large-scale, systematic studies. Here we have developed and applied an innovative high throughput peptidoglycan analytical pipeline to analyze the entire non-essential, arrayed mutant library of Vibrio cholerae. The unprecedented breadth of these analyses revealed that peptidoglycan homeostasis is preserved by a large percentage of the genome organized in complex networks that functionally link peptidoglycan features with genetic determinants. As an example, we discovered a novel bifunctional penicillin-binding protein in V. cholerae. Collectively, genome-wide peptidoglycan profiling provides a fast, easy, and unbiased method for systematic identification of the genetic determinants of peptidoglycan synthesis and remodeling.
Inhibition of S6K lowers age-related inflammation and immunosenescence and increases lifespan through the endolysosomal system
Authors: Zhang Pingze , Catterson James H. , Grönke Sebastian , Partridge Linda 
Published: August 2022

AbstractThe nutrient-sensing Target of Rapamycin complex 1 (TORC1) is an evolutionarily conserved regulator of longevity and healthspan. S6 kinase (S6K) is an essential downstream mediator for the effect of TORC1 on longevity. However, mechanistic insights on how TORC1-S6K signalling promotes lifespan and healthspan are still limited. Here we show that activity of S6K in theDrosophilafat body is essential for rapamycin-mediated longevity. Fat-body-specific activation of S6K blocked lifespan extension upon rapamycin feeding and induced accumulation of multilamellar lysosomal enlargements. By proteomics analysis we identified Syntaxin 13 (Syx13) as an important downstream mediator of TORC1-S6K signalling involved in regulating lysosomal morphology. Inhibition of TORC1-S6K signalling decreased age-associated hyperactivation of the NF-κB-like IMD pathway in the fat body and promoted bacterial clearance, mediated by Syx13, suggesting that lysosomal and immune function are connected during ageing. Middle-age-onset repression of IMD pathway in the fat body by Relish RNAi promoted bacteria clearance and extended fly lifespan. In mice, chronic rapamycin treatment elevated Syntaxin 12/13 (Stx12) level in liver. We identified alleviated immune processes in the aged liver as a common signature of S6K1-deficient and rapamycin-treated mice. Thus, our results indicate that suppression of the TORC1-S6K-Syx13 axis ameliorates both inflammageing and immunosenescence in hepatic tissues via the endolysosomal system and thereby extends longevity, providing a mechanistic explanation for the effects of rapamycin and suppression of S6K on immune function and lifespan in model organisms and, potentially, humans.