bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Highly Selective Response to Food in Human Visual Cortex Revealed by Hypothesis-Free Voxel Decomposition
Authors: Khosla Meenakshi , Murty N Apurva Ratan , Kanwisher Nancy 
Published: June 2022

SummaryPrior work has identified cortical regions selectively responsive to specific categories of visual stimuli. However, this hypothesis-driven work cannot reveal how prominent these category selectivities are in the overall functional organization of visual cortex, or what others might exist that scientists have not thought to look for. Further, standard voxel-wise tests cannot detect distinct neural selectivities that coexist within voxels. To overcome these limitations, we used data-driven voxel decomposition methods to identify the main components underlying fMRI responses to thousands of complex photographic images (Allen et al 2021). Our hypothesis-neutral analysis rediscovered components selective for faces, places, bodies, and words, validating our method and showing that these selectivities are dominant features of the ventral visual pathway. The analysis also revealed an unexpected component with a distinct anatomical distribution that responded highly selectively to images of food. Alternative accounts based on low to mid-level visual features like color, shape or texture failed to account for the food selectivity of this component. High-throughput testing and control experiments with matched stimuli on a highly accurate computational model of this component confirm its selectivity for food. We registered our methods and hypotheses before replicating them on held-out participants and in a novel dataset. These findings demonstrate the power of data-driven methods, and show that the dominant neural responses of the ventral visual pathway include not only selectivities for faces, scenes, bodies, and words, but also the visually heterogeneous category of food, thus constraining accounts of when and why functional specialization arises in the cortex.
The effects of conscious movement processing on the neuromuscular control of posture
Authors: Jie Li-Juan , Kal Elmar , Ellmers Toby J. , Rosier Joëlle , Meijer Kenneth , Boonstra Tjeerd 
Published: June 2022

AbstractMaintaining balance is thought to primarily occur sub-consciously. Occasionally, however, individuals will direct conscious attention towards balance, e.g., in response to a threat to balance. Such conscious movement processing (CMP) increases the reliance on attentional resources and may disrupt balance performance. However, the underlying changes in neuromuscular control remain poorly understood. We investigated the effects of CMP (manipulated using verbal instructions) on neural control of posture in twenty-five adults (11 females, mean age = 23.9, range = 18–33). Participants performed 90-second, bipedal stance balance trials in high- and low-CMP conditions, during both stable (solid surface) and unstable (foam) task conditions. Postural sway amplitude, frequency and complexity were used to assess postural control. Surface EMG was recorded bilaterally from lower leg muscles (Soleus, Tibialis Anterior, Gastrocnemius Medialis, Peroneus Longus) and intermuscular coherence (IMC) was assessed for 12 muscle pairs across four frequency bands. We observed significantly increased sway amplitude, and decreased sway frequency and complexity in the high- compared to the low-CMP conditions. All sway variables increased in the unstable compared to the stable conditions. We observed reduced beta band IMC between several muscle pairs during high- compared to low-CMP, but these findings did not remain significant after controlling for multiple comparisons. Finally, IMC significantly increased in the unstable conditions for most muscle combinations and frequency bands. In all, results tentatively suggest that CMP-induced changes in sway outcomes may be facilitated by reduced beta-band IMC, but these findings need to be replicated before they can be interpreted more conclusively.
An α-π transition in S6 shapes the conformational cycle of the bacterial sodium channel NavAb
Authors: Choudhury Koushik , Howard Rebecca J , Delemotte Lucie 
Published: June 2022

AbstractVoltage gated sodium channels play an important role in electrical signaling in excitable cells. In response to changes in membrane potential, they cycle between nonconducting and conducting conformations. With recent advances in structural biology, structures of sodium channels have been captured in several distinct conformations, thought to represent different functional states. However, it has been difficult to capture the intrinsically transient open state. We recently showed that a proposed open state of the bacterial sodium channel NavMs was not conductive, and that a conformational change involving a transition to aπhelix in the pore-lining S6 helix converted this structure into a conducting state. However, the relevance of this structural feature in other sodium channels, and its implications for the broader gating cycle, remained unclear. Here, we propose a comparable open state of another class of bacterial channel fromAliarcobacter butzleri(NavAb), with characteristic pore hydration, ion permeation and drug binding properties. Furthermore, we show that aπ-helix transition can lead to pore opening, and that such a conformational change blocks fenestrations in the inner helix bundle. We also discover that a region in the C-terminal domain can undergo a disordering transition proposed to be important for pore opening. These results support a role for aπ-helix transition in the opening of NavAb, enabling new proposals for the structural annotation and drug modulation mechanisms in this important model sodium channel.
Predictive model of transcriptional elongation control identifies trans regulatory factors from chromatin signatures
Authors: Akcan Toray S. , Heinig Matthias 
Published: June 2022

ABSTRACTPromoter-proximal Polymerase II (Pol II) pausing is a key rate limiting step for gene expression. DNA and RNA-binding trans-acting factors regulating the extent of pausing have been identified. However, we lack a quantitative model of how interactions of these factors determine pausing, therefore the relative importance of implicated factors is unknown. Moreover, previously unknown regulators might exist. Here we address this gap with a machine learning model that accurately predicts the extent of promoter proximal Pol II pausing from large scale genome and transcriptome binding maps, as well as gene annotation and sequence composition features. We demonstrate high accuracy and generalizability of the model by validation on an independent cell line which reveals the model’s cell line agnostic character. Model interpretation in light of prior knowledge about molecular functions of regulatory factors confirms the interconnection of pausing with other RNA processing steps. Harnessing underlying feature contributions we assess the relative importance of each factor, quantify their predictive effects and systematically identify previously unknown regulators of pausing. We additionally identify 16 previously unknown 7SK ncRNA interacting RNA-binding proteins predictive of pausing. Our work provides a framework to further our understanding of the regulation of the critical early steps in transcriptional elongation.Key Points: Please provide 3 bullet points summarizing the manuscript’s contribution to the field-ML model that accurately predicts promoter proximal Pol II pausing from ChIP and eClip-seq data-Quantification of the interconnection of pausing and other steps of gene regulation-Identification of novel putative trans regulators of pausingGRAPHICAL ABSTRACT
Metabolic traits and the niche of bulk soil bacteria in a Mediterranean grassland
Authors: Zhalnina Kateryna , White Richard Allen , de Raad Markus , Deng Kai , Nicora Carrie D. , Karaoz Ulas , Pett-Ridge Jennifer , Firestone Mary K. , Lipton Mary S. , Northen Trent R. , Brodie Eoin L. 
Published: June 2022

ABSTRACTSoil microorganisms have adapted to compete and exploit different metabolic niches in their physically and chemically diverse environment via evolution and acquisition of distinct physiological and biochemical traits. As the interface for most carbon and nutrient exchange between plants and microorganisms, the rhizosphere has received substantial attention. By comparison, what is commonly termed bulk-soil (soil free of living roots) represents a far greater volume and surface area throughout the season, and substantially higher taxonomic and phylogenetic diversity; the traits and activity of its inhabitants may also have a significant impact on overall soil function. We used a combination of comparative genomics and exoproteomics to identify metabolic traits of bacteria adapted to life in bulk soil and compared these with traits of bacteria living in the rhizosphere of wild oat, Avena barbata. In bulk soil bacteria, we observed: (i) greater investment in extracellular polymer-degrading enzyme production; (ii) greater potential for secretion (presence of signal peptides) of polymer-degrading enzymes; (iii) production of accessory proteins (carbohydrate binding modules) fused with glycoside hydrolases that enhance substrate affinity, stabilize, and increase reaction rates of polymer degrading enzymes; and (iv) organization of polymer degradation machinery within gene clusters that facilitate co-transcription of enzymes, transcription factors and transporters for polymer depolymerization products. Together, these findings suggest that unlike rhizosphere-adapted bacteria—which specialize on small molecules released primarily as root exudates—bulk soil-adapted bacteria have evolved to exploit plant polymers. This biochemically costly strategy may be mitigated by protein-level adaptations that enhance the efficiency of extracellular enzyme-mediated substrate acquisition.IMPORTANCEPlant-soil-microbe interactions are dynamic and complex, with significant implications for ecosystem functioning. Microbial traits, such as nutrient acquisition and growth yield, combined with soil and climate parameters, impact major biogeochemical processes and can define the future fate of soil carbon. Diverse soil microorganisms occupy different physical habitats within soil and exploit distinct niches by expressing different metabolic traits. Identifying and quantifying traits that underlie their fitness and function is key for understanding and predicting how soil carbon transformation and stabilization will change in the future or can be managed through intervention.
Supercharged Protein Nanosheets for Cell Expansion on Bioemulsions
Authors: Chrysanthou Alexandra , Kanso Hassan , Zhong Wencheng , Shang Li , Gautrot Julien E. 
Published: June 2022

AbstractCell culture at liquid-liquid interfaces, for example at the surface of oil microdroplets, is an attractive strategy to scale up adherent cell manufacturing whilst replacing the use of microplastics. Such process requires the adhesion of cells at interfaces stabilized and reinforced by protein nanosheets displaying high elasticity, but also presenting cell adhesive ligands able to bind integrin receptors. In this report, supercharged albumins are found to form strong elastic protein nanosheets and mediate extracellular matrix (ECM) protein adsorption and cell adhesion. The interfacial mechanical properties and elasticity of supercharged nanosheets is characterized by interfacial rheology and behaviors are compared to those of native bovine serum albumin, human serum albumin and α-lactalbumin. ECM protein adsorption to resulting supercharged nanosheets is then quantified via surface plasmon resonance and fluorescence microscopy, demonstrating the dual role supercharged albumins are proposed to play, as scaffold proteins structuring liquid-liquid interfaces and substrates for the capture of ECM molecules. Finally, the adhesion and proliferation of primary human epidermal stem cells is investigated, at pinned droplets, as well as on bioemulsions stabilized by corresponding supercharged nanosheets. This study demonstrates the potential of supercharged proteins for the engineering of biointerfaces for stem cell manufacturing, and draws structure-property relationships that will guide further engineering of associated systems.
New, fast, and precise method of COVID-19 detection in nasopharyngeal and tracheal aspirate samples combining optical spectroscopy and machine learning
Authors: Ceccon Denny M. , Amaral Paulo Henrique R. , Lídia M. Andrade , da Silva Maria I. N. , Andrade Luis A. F. , Moraes Thais F.S. , Bagno Flavia F , Rocha Raissa P. , de Almeida Marques Daisymara Priscila , Ferreira Geovane Marques , Lourenço Alice Aparecida , Ribeiro Ágata Lopes , Coelho-dos-Reis Jordana G. A. , da Fonseca Flavio G. , Gonzalez J. C. 
Published: June 2022

AbstractFast, precise, and low-cost diagnostic testing to identify persons infected with SARS– CoV-2 virus is pivotal to control the global pandemic of COVID-19 that began in late 2019. The gold standard method of diagnostic recommended is the RT-qPCR test. However, this method is not universally available, and is time-consuming and requires specialized personnel, as well as sophisticated laboratories. Currently, machine learning is a useful predictive tool for biomedical applications, being able to classify data from diverse nature. Relying on the artificial intelligence learning process, spectroscopic data from nasopharyngeal swab and tracheal aspirate samples can be used to leverage characteristic patterns and nuances in healthy and infected body fluids, which allows to identify infection regardless of symptoms or any other clinical or laboratorial tests. Hence, when new measurements are performed on samples of unknown status and the corresponding data is submitted to such an algorithm, it will be possible to predict whether the source individual is infected or not. This work presents a new methodology for rapid and precise label-free diagnosing of SARS-CoV-2 infection in clinical samples, which combines spectroscopic data acquisition and analysis via artificial intelligence algorithms. Our results show an accuracy of 85% for detection of SARS-CoV-2 in nasopharyngeal swab samples collected from asymptomatic patients or with mild symptoms, as well as an accuracy of 97% in tracheal aspirate samples collected from critically ill COVID-19 patients under mechanical ventilation. Moreover, the acquisition and processing of the information is fast, simple, and cheaper than traditional approaches, suggesting this methodology as a promising tool for biomedical diagnosis vis-à-vis the emerging and re-emerging viral SARS-CoV-2 variant threats in the future.
What Do Child Abuse and Neglect Medical Evaluation Consultation Notes Tell Us?
Authors: Golonka Megan , Liu Yuerong , Rohrs Rosie , Copeland Jennie , Byrd Jessalyn , Stilwell Laura , Crew Carter , Kuehn Molly , Snyder-Fickler Elizabeth , Hurst Jillian , Evans Kelly , Terrell Lindsay , Gifford Elizabeth 
Published: June 2022

AbstractChild abuse and neglect (CAN) medical experts provide specialized multidisciplinary care to children when there is concern for maltreatment. Their clinical notes contain valuable information on child- and family-level factors, clinical concerns, and service placements that may inform the needed supports for the family. We created and implemented a coding system for data abstraction from these notes. Participants were 1,397 children ages 0-17 years referred for a consultation with a CAN medical provider at an urban teaching and research hospital between March 2013 and December 2017. Coding themes were developed using an interdisciplinary team-based approach to qualitative analysis, and descriptive results are presented using a developmental-contextual framework. This study demonstrates the potential value of developing a coding system to assess characteristics and patterns from CAN medical provider notes, which could be helpful in improving quality of care and prevention and detection of child abuse.
Germline Transmission of a Circular Human Artificial Chromosome in the Mouse
Authors: Wudzinska Aleksandra , Mitchell Leslie A. , Brosh Ran , Bosco Nazario , Boccalatte Francesco , Aifantis Ioannis , Kim Sang Y. , Davoli Teresa , Boeke Jef D. 
Published: June 2022

AbstractAlthough the structure and function of the alphoid-tetO Human Artificial Chromosome (tetO-HAC) has been previously described in cell culture models and somatically in the mouse, in vivo persistence and stability throughout meiosis and across generations were not evaluated. Here we report germline transmission of a circular tetO-HAC across three mouse generations without observable health or reproductive deficiencies. Furthermore, we show that the tetO-HAC is maintained without selection as an episome and can be efficiently transmitted by both ova and sperm.
A database of accurate electrophoretic migration patterns for human proteins in cell lines
Authors: Mylonas Roman , Potts Alexandra , Waridel Patrice , Barblan Jachen , del Carmen Conde Rubio Maria , Widmann Christian , Quadroni Manfredo 
Published: June 2022

AbstractNative molecular weight (MW) is one of the defining features of proteins. Denaturing gel electrophoresis (SDS-PAGE) is a very popular technique for separating proteins and determining their MW. Coupled with antibody-based detection, SDS-PAGE is widely applied for protein identification and quantitation. Yet, electrophoresis is poorly reproducible and the MWs obtained are often inaccurate. This hampers antibody validation and negatively impacts the reliability of western blot data, resulting worldwide in a considerable waste of reagents and labour. To alleviate these problems there is a need to establish a database of reference MWs measured by SDS-PAGE. Using mass spectrometry as an orthogonal detection method, we acquired electrophoretic migration patterns for approximately 10’000 human proteins in five commonly used cell lines. We applied a robust internal calibration of migration to determine accurate and reproducible molecular weights. This in turn allows merging replicates to increase accuracy, but also enables comparing different cell lines. Mining of the data obtained highlights structural factors that affect migration of distinct classes of proteins. We also show that the information produced recapitulates known post-translational modifications and differential splicing and can be used to formulate hypotheses on new or poorly known processing events. The full information is freely accessible as a web resource through a user friendly graphical interface (https://pumba.dcsr.unil.ch/). We anticipate that this database will be useful to investigators worldwide for troubleshooting western blot experiments, but could also contribute to the characterization of human proteoforms.
Did circular DNA shape the evolution of mammalian genomes?
Authors: Holt Sylvester , Tané Gerard Arrey , Regenberg Birgitte 
Published: June 2022

AbstractExtrachromosomal circular DNA of chromosomal origin (eccDNA) can rapidly shape the evolution and adaptation of mitotically dividing cells such as tumor cells. However, whether eccDNA has a permanent impact on genome evolution through the germline is largely unexplored. Here, we propose that a large fraction of the syntenic changes that are found between mammalian species are caused by germline transposition of eccDNA. We have previously shown the existence of eccDNA in mammalian meiotic cells. By reanalysis of available synteny maps, we now find that up to 6% of mammalian genomes might have rearranged via a circular DNA intermediate. Hence, eccDNA in the germline is expected to have large effects on evolution of gene order.HighlightsExtrachromosomal circular DNA (eccDNA) is present in mammalian germline cells showing that eccDNAs are not excluded, repressed or eliminated during meiosisLarge eccDNA reinsertions into the genome can change gene synteny in a recognizable pattern based on its circular junction and integration breakpoint.By reanalyzing synteny maps form 8 mammalian species, we show that 6% of genome of the ungulates cow and sheep can be explained by eccDNA insertions.We propose that reinsertion of large eccDNA that are fixed in germline cells may have contributed to speciation barriers and evolution of new species
The role of histone acetyltransferases Gcn5 and Esa1 in recruiting the RSC complex and maintaining nucleosome-depleted regions genome-wide in Saccharomyces cerevisiae
Authors: Biernat Emily , Verma Mansi , Werick Matthew , Khan Uzair , Joseph Sama , Govind Chhabi K. 
Published: June 2022

ABSTRACTChromatin remodelers are essential for the maintenance of chromatin structure and gene regulation. In this study, we examined the role of histone acetyltransferases (HATs) Gcn5 and Esa1 in regulating RSC and histone occupancies and their effects on transcription genome-wide. We identified contrasting roles of HATs in modulating RSC occupancies in promoters and ORFs. In HAT mutants, RSC accumulated in nucleosome depleted regions (NDRs) with “fragile nucleosomes (FNs)” more than those with stable -1 nucleosomes. Moreover, the accumulation was more significant in the Esa1 mutant than in the Gcn5 mutant. However, RSC NDR accumulation was not observed in cells lacking H3 or H4 tails. Furthermore, we observed marked increases in histone occupancies in NDRs in the HAT mutants genome-wide. Overall, these data suggest that FNs use hypoacetylated tails to recruit RSC to NDRs, and subsequent acetylation of the tails promote histone eviction. In contrast to the promoters, RSC occupancies were significantly reduced in transcribed ORFs in the HAT mutants. Additionally, the HAT mutants showed reduced TBP and Pol II binding at promoters. Thus, our data implicate HATs and RSC in maintaining NDRs, regulating chromatin structure, and promoting transcription.
Time-kill kinetics reveal heterogeneous tolerance to disinfectants
Authors: Nordholt Niclas , Lewerenz Dominique , Schreiber Frank 
Published: June 2022

AbstractDisinfection is an important strategy to limit the spread of infections. Failure of disinfection may facilitate evolution of resistance against disinfectants and antibiotics through the processes of cross-resistance and co-resistance. The best possible outcome of disinfection minimizes the number of surviving bacteria and the chance for resistance evolution. Resistance describes the ability to grow in previously inhibitory concentrations of an antimicrobial, whereas tolerance is associated with enhanced survival of lethal doses. Individual bacteria from the same population can display considerable heterogeneity in their ability to survive treatment (i.e. tolerance) with antimicrobials, which can result in unexpected treatment failure. Here, we investigated how phenotypic heterogeneity affects the ability of E. coli to survive treatment with six different substances commonly used as active substances in disinfectants, preservatives and antiseptics. A mathematical model which assumes that phenotypic heterogeneity underlies the observed disinfection kinetics was used to infer whether time-kill kinetics were caused by a tolerant subpopulation. The analysis identified bimodal kill kinetics for benzalkonium chloride (BAC), didecyldimethylammonium chloride (DDAC), and isopropanol (Iso). In contrast, kill kinetics by chlorhexidine (CHX), glutaraldehyde (GTA), and hydrogen peroxide (H2O2) were best explained by unimodal kill kinetics underpinned by a broad distribution of tolerance times for CHX as opposed to a narrow distribution of tolerance times for GTA and H2O2. These findings have implications for the risk of disinfection failure, with potential consequences for the evolution of antimicrobial resistance and tolerance.