bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term unsupervised recalibration of cursor BCIs
Authors: Wilson Guy H. , Willett Francis R. , Stein Elias A. , Kamdar Foram , Avansino Donald T. , Hochberg Leigh R. , Shenoy Krishna V. , Druckmann Shaul , Henderson Jaimie M. 
Published: February 2023

AbstractIntracortical brain-computer interfaces (iBCIs) require frequent recalibration to maintain robust performance due to changes in neural activity that accumulate over time. Compensating for this nonstationarity would enable consistently high performance without the need for supervised recalibration periods, where users cannot engage in free use of their device. Here we introduce a hidden Markov model (HMM) to infer what targets users are moving toward during iBCI use. We then retrain the system using these inferred targets, enabling unsupervised adaptation to changing neural activity. Our approach outperforms the state of the art in large-scale, closed-loop simulations over two months and in closed-loop with a human iBCI user over one month. Leveraging an offline dataset spanning five years of iBCI recordings, we further show how recently proposed data distribution-matching approaches to recalibration fail over long time scales; only target-inference methods appear capable of enabling long-term unsupervised recalibration. Our results demonstrate how task structure can be used to bootstrap a noisy decoder into a highly-performant one, thereby overcoming one of the major barriers to clinically translating BCIs.
Elevator Mechanism of Alternating Access in theEscherichia coliConcentrative Nucleoside Transporter NupC
Authors: Sun Lijie , Patching Simon G. 
Published: February 2023

AbstractMembers of the concentrative nucleoside transporter (CNT) family of proteins mediate uptake of nucleosides into cells driven by a cation gradient, which then enter salvage pathways for nucleic acid synthesis. In humans, they also transport hydrophilic anticancer and antiviral nucleoside analogue drugs into cells and tissues where they exert their pharmacological effects.Escherichia coliCNT NupC (400 residues) is pyrimidine-specific and driven by a proton gradient. We have used computational, biochemical, and biophysical methods to characterize evolutionary relationships, conservation of residues, structural domains, transmembrane helices, and residues involved in nucleoside binding and/or transport activity in NupC compared with those of sodium-drivenVibrio cholerae CNT (vcCNT) and human CNTs (hCNT1−3). As in the crystal structure of vcCNT, NupC appears to contain eight transmembrane-spanning α-helices. Wild-type NupC and single-cysteine-containing mutants were tested for transport activity in energizedE. coliwhole cells and for binding of nucleosides in non-energized native inner membranes using novel cross-polarization magic-angle spinning solid-state nuclear magnetic resonance methods. Wild-type NupC had an apparent affinity of initial rate transport (Kmapp) for [14C]uridine of 22.2 ± 3.7μM and an apparent binding affinity (Kdapp) for [1′-13C]uridine of 1.8−2.6 mM. Mutant S142C retained transport and binding affinities similar to those of the wild type. Mutants G146C and E149C had no transport activity but retained varying degrees of partial binding activity with affinities decreasing in the following order: wild type > S142C > G146C > E149C. Results were explained with respect to a homology model of NupC based on the structure of vcCNT and a hypothetical elevator-type mechanism of alternating access membrane transport in NupC.
Comparison of TRIBE and STAMP for identifying targets of RNA binding proteins in human andDrosophilacells
Authors: Abruzzi Katharine C. , Ratner Corrie , Rosbash Michael 
Published: February 2023

ABSTRACTRNA binding proteins (RBPs) perform a myriad of functions and are implicated in numerous neurological diseases. To identify the targets of RBPs in small numbers of cells, we developed TRIBE, in which the catalytic domain of the RNA editing enzyme ADAR (ADARcd) is fused to a RBP. When the RBP binds to a mRNA, ADAR catalyzes A to G modifications in the target mRNA that can be easily identified in standard RNA-sequencing. In STAMP, the concept is the same except the ADARcd is replaced by the RNA editing enzyme APOBEC. Here we compared the two enzymes fused to the RBP TDP-43 in human cells. Although they both identified TDP-43 target mRNAs, combining the two methods more successfully identified high confidence targets. We also assayed the two enzymes inDrosophilacells: RBP-APOBEC fusions generated only low numbers of editing sites, comparable to the level of control editing. This was true for two different RBPs, Hrp48 and Thor (DrosophilaEIF4E-BP), indicating that TRIBE performed better inDrosophila.
The self-renewal procedures of mesenchymal stem cells in the blood
Authors: Kong Wuyi , Wang Hong , Zhu XiaoPing , Han XiuJuan 
Published: February 2023

AbstractBackgroundAlthough mesenchymal stem cells (MSCs) are most commonly used in cell therapy and stem cell research, the mechanism and the locations of their self-renewal are still unknown.MethodMouse blood was collected, and examined under microscopy. The results were compared with the data of human umbilical cord blood (hUCB) collected 10 years ago.ResultsWe found that the procedure of self-renewal for the mesenchymal stem cells in mouse blood and hUCB needs at least 5 steps. First, tube-shaped stem cell niches release long segmented materials composed of sand-like particles and semitransparent granules. Second, the sand-like particles and semitransparent granules separate from the segmented materials. Third, each of the individual semitransparent granules releases groups of fusiform-shaped structures that do not stain to H&E. The sizes of the fusiform-shaped structures range from 1 to 100 μm in length in mouse blood, but can be 200 μm in hUCB. Fourth, the large-sized fusiform structures can directly transform into lineage-restricted cellular structures; the medium-sized fusiform structures fuse or engulf each other to form cellular structures. The cellular structures further acquire membranes from the adjacent nucleated cells. Fifth, the nucleolus appears in the new cellular structures before the nucleus. During all the procedures, the adjacent nucleated mesenchymal cells are must needed. Thus, these newly formed cellular structures will further differentiate into nucleated mesenchymal stem cells.ConclusionOur findings again provide new evidence that, in physiological conditions, mesenchymal stem cell self-renewal needs several steps to complete, which, however, does not occur by mitotic division. The tube-shaped structures are the niches of the stem cells.
Advancing Glycan Analysis: A New Platform Integrating SERS, Boronic Acids, and Machine Learning Algorithms
Authors: Hu Qiang , Kuai Dacheng , Park Hyundo , Clark Haley , Balbuena Perla B. , Kwon Joseph Sang-Il , Wu Hung-Jen 
Published: February 2023

AbstractGlycans are the most abundant and diverse fundamental biomolecules. Profiling glycans is essential to elucidate biomolecular mechanisms and to predict biological consequences; however, the analysis of glycans remains challenging due to their structural complexity. A novel glycan detection platform is established through the integration of surface-enhanced Raman spectroscopy (SERS), boronic acid receptors, and machine learning tools. SERS is able to distinguish isomeric structures and provide fingerprint information of molecules. Boronic acid receptors can selectively bind with glycans, and the reaction influences molecular vibrations, leading to unique Raman spectral patterns. For proof-of-concept, two boronic acids, 4-mercaptophenylboronic acid (4MBA) and 1-thianthrenylboronic acid (1TBA) were used for glycan detection. The spectra were analyzed by the machine learning algorithm. The sensing platform successfully recognized the stereoisomers (glucose, mannose, and galactose), the structural isomers with α-1,4 and α-1,6 glycosidic linkages, and the β-1,4 glycosidic linkage within lactose molecules. The collective spectra that combine the spectra from both boronic acid receptors could improve the performance of the support vector machine model due to the enrichment of the structural information of glycans. In addition to qualitative analysis, this new sensor could quantify the mole fraction of sialic acid in lactose background using the machine learning regression technique. The quantification accuracy reached a coefficient of determination (R2) value of 0.998 and a normalized mean square error (NMSE) of 0.00195. This low-cost, rapid, and highly accessible sensor will provide the scientific community with another option for frequent glycan screening in standard biological laboratories.
GardnerellaDiversity and Ecology in Pregnancy and Preterm Birth
Authors: Berman Hanna L. , Aliaga Goltsman Daniela S. , Anderson Megan , Relman David A. , Callahan Benjamin J. 
Published: February 2023

AbstractThe vaginal microbiome has been linked to numerous negative health outcomes including preterm birth. Specific taxa, includingGardnerellaspp., have been identified as risk factors for these conditions. Historically, microbiome analysis methods have treated allGardnerellaspp. as one species, but the broad diversity ofGardnerellahas recently become more apparent. In the present study, we explore the diversity ofGardnerellaclades and genomic species in the vaginal microbiome of pregnant women and their impacts on microbiome composition and associations with preterm birth.Shotgun metagenomic sequencing data collected longitudinally from three distinct cohorts of pregnant women were assessed. Relative abundance ofGardnerellaclades and genomic species and other taxa was quantified, and associations betweenGardnerellaclades and signatures of the vaginal microbiome were measured. We also assessed the diversity and abundance ofGardnerellavariants in 16S rRNA gene amplicon sequencing data from seven previously conducted studies in differing populations on the vaginal microbiome and preterm birth.Individual microbiomes often contained multipleGardnerellavariants, and the number of clades was associated with increased microbial load. The genusGardnerellawas also associated with increased microbial load, or the ratio of non-human reads to human reads. Taxon co-occurrence patterns matched previously described community structures, and were largely consistent acrossGardnerellaclades and among cohorts. Some variants previously described as rare were prevalent in other cohorts, highlighting the importance of surveying a diverse set of populations to fully capture the diversity ofGardnerella.The diversity ofGardnerellaboth across populations and within individual vaginal microbiomes has long been unappreciated, as has been the intra-species diversity of many other members of the vaginal microbiome.1The broad genomic diversity ofGardnerellahas led to its reclassification as multiple species; here we demonstrate the diversity ofGardnerellafound within and between vaginal microbiomes. Further studies should investigate the phenotypes ofGardnerellavariants that may underlie the mechanisms by whichGardnerellaspecies may differentially shape the vaginal microbiome.
OSCAR: an open-source controller for animal research
Authors: Dastin-van Rijn Evan M. , Sachse Elizabeth , Iacobucci Francesca , Mensinger Megan , Widge Alik S. 
Published: February 2023

AbstractOperant animal behavior training and monitoring is fundamental to scientific inquiry across fields necessitating evaluation via controlled laboratory tasks. However, current commercial and open-source systems enforce particular hardware and software, limiting reproducibility and technique and data sharing across sites. To address this issue, we developed OSCAR: an open-source controller for animal research that enables flexible control of a variety of industry standard hardware with platform-independent software. OSCAR offers millisecond latency with a flexible array of inputs and outputs at a fraction of the cost of commercial options. These features position OSCAR as a valuable option for improving consistency of behavioral experiments across studies.
Single-cell genomics reveals the divergent mitochondrial genomes of Retaria (Foraminifera and Radiolaria)
Authors: Macher Jan-Niklas , Coots Nicole L. , Poh Yu-Ping , Girard Elsa B. , Langerak Anouk , Muñoz-Gómez Sergio A. , Sinha Savar D. , Jirsová Dagmar , Vos Rutger , Wissels Richard , Gile Gillian H. , Renema Willem , Wideman Jeremy G. 
Published: February 2023

AbstractMitochondria originated from an ancient bacterial endosymbiont that underwent reductive evolution by gene loss and endosymbiont gene transfer to the nuclear genome. The diversity of mitochondrial genomes published to date has revealed that gene loss and transfer processes are ongoing in many lineages. Most well-studied eukaryotic lineages are represented in mitochondrial genome databases, except for the superphylum Retaria—the lineage comprising Foraminifera and Radiolaria. Using single-cell approaches, we present two complete mitochondrial genomes of Foraminifera and two near-complete mitochondrial genomes of radiolarians. We report the complete coding content of an additional 14 foram species. We show that foraminiferan and radiolarian mitochondrial genomes encode a nearly fully overlapping but reduced mitochondrial gene complement compared to other sequenced rhizarians. In contrast to animals and fungi, many protists encode a diverse set of proteins on their mitochondrial genomes, including several ribosomal genes; however, some aerobic eukaryotic lineages (euglenids, myzozoans, and chlamydomonas-like algae) have reduced mitochondrial gene content and lack all ribosomal genes. Similar to these reduced outliers, we show that retarian mitochondrial genomes lack ribosomal protein and tRNA genes, contain truncated and divergent small and large rRNA genes, and encode only 14-15 protein-coding genes, including nad1, 3, 4, 4L, 5, 7, cob, cox1, 2, 3, atp1, 6, and 9, with forams and radiolarians additionally encoding nad2 and nad6, respectively. In radiolarian mitogenomes, a non-canonical genetic code was identified in which all three stop codons encode amino acids. Collectively, these results add to our understanding of mitochondrial genome evolution and fill in one of the last major gaps in mitochondrial sequence databases.
Ligament injury in adult zebrafish triggers ECM remodeling and cell dedifferentiation for scar-free regeneration
Authors: Anderson Troy , Mo Julia , Gagarin Ernesto , Sherwood Desmarie , Blumenkrantz Maria , Mao Eric , Leon Gianna , Chen Hung-Jhen , Tseng Kuo-Chang , Fabian Peter , Crump J. Gage , Smeeton Joanna 
Published: February 2023

AbstractAfter traumatic injury, healing of mammalian ligaments is typically associated with fibrotic scarring as opposed to scar-free regeneration. In contrast, here we show that the ligament supporting the jaw joint of adult zebrafish is capable of rapid and complete scar-free healing. Following surgical transection of the jaw joint ligament, we observe breakdown of ligament tissue adjacent to the cut sites, expansion of mesenchymal tissue within the wound site, and then remodeling of extracellular matrix (ECM) to a normal ligament morphology. Lineage tracing of mature ligamentocytes following transection shows that they dedifferentiate, undergo cell cycle re-entry, and contribute to the regenerated ligament. Single-cell RNA sequencing of the regenerating ligament reveals dynamic expression of ECM genes in neural-crest-derived mesenchymal cells, as well as diverse immune cells expressing the endopeptidase-encoding genelegumain. Analysis oflegumainmutant zebrafish shows a requirement for early ECM remodeling and efficient ligament regeneration. Our study establishes a new model of adult scar-free ligament regeneration and highlights roles of immune-mesenchyme cross-talk in ECM remodeling that initiates regeneration.HighlightsRapid regeneration of the jaw joint ligament in adult zebrafishDedifferentiation of mature ligamentocytes contributes to regenerationscRNAseq reveals dynamic ECM remodeling and immune activation during regenerationRequirement of Legumain for ECM remodeling and ligament healing
Metabolomic Phenotypes Reflect Patient Sex and Injury Status: A Cross-Sectional Analysis of Human Synovial Fluid
Authors: Welhaven Hope D. , Welfley Avery H. , Pershad Prayag , Satalich James , O’Connell Robert , Bothner Brian , Vap Alexander R. , June Ronald K. 
Published: February 2023

1.AbstractBackgroundPost-traumatic osteoarthritis (PTOA) is caused by knee injuries like anterior cruciate ligament (ACL) injuries. Often, ACL injuries are accompanied by damage to other tissues and structures within the knee including the meniscus. Both are known to cause PTOA but underlying cellular mechanisms driving disease remain unknown. Aside from injury, patient sex is a prevalent risk factor associated with PTOA.HypothesisMetabolic phenotypes of synovial fluid that differ by knee injury pathology and participant sex will be distinct from each other.Study DesignA cross-sectional study.MethodsSynovial fluid from n=33 knee arthroscopy patients between 18 and 70 years with no prior knee injuries was obtained pre-procedure and injury pathology assigned post-procedure. Synovial fluid was extracted and analyzed via liquid chromatography mass spectrometry metabolomic profiling to examine differences in metabolism between injury pathologies and participant sex. Additionally, samples were pooled and underwent fragmentation to identify metabolites.ResultsMetabolite profiles revealed that injury pathology phenotypes were distinct from each other where differences in endogenous repair pathways that are triggered post-injury were detected. Specifically, acute differences in metabolism mapped to amino acid metabolism, lipid-related oxidative metabolism, and inflammatory-associated pathways. Lastly, sexual dimorphic metabolic phenotypes were examined between male and female participants, and within injury pathology. Specifically, Cervonyl Carnitine and other identified metabolites differed in concentration between sexes.ConclusionsThe results of this study suggest that different injuries (e.g., ligament vs. meniscus), as well as sex are associated with distinct metabolic phenotypes. Considering these phenotypic associations, a greater understanding of metabolic mechanisms associated with specific injuries and PTOA development may yield data regarding how endogenous repair pathways differ between injury types. Furthermore, ongoing metabolomic analysis of synovial fluid in injured male and female patients can be performed to monitor PTOA development and progression.Clinical RelevanceExtension of this work may potentially lead to the identification of biomarkers as well as drug targets that slow, stop, or reverse PTOA progression based on injury type and patient sex.
A novel enhancer-AAV approach selectively targeting dentate granule cells
Authors: Banks Emmie , Gutekunst Claire-Anne , Vargish Geoffrey A. , Eaton Anna , Pelkey Kenneth A. , McBain Chris J. , Zheng James Q. , Oláh Viktor Janos , Rowan Matthew JM 
Published: February 2023

SummaryThe mammalian brain contains the most diverse array of cell types of any organ, including dozens of neuronal subtypes with distinct anatomical and functional characteristics. The brain leverages these neuron-type-specializations to perform diverse circuit operations and thus execute different behaviors properly. Through the use of Cre lines, access to specific neuron types has steadily improved over past decades. Despite their extraordinary utility, development and cross-breeding of Cre lines is time-consuming and expensive, presenting a significant barrier to entry for many investigators. Furthermore, cell-based therapeutics developed in Cre mice are not clinically translatable. Recently, several AAV vectors utilizing neuron-type-specific regulatory transcriptional sequences (enhancer-AAVs) were developed which overcome these limitations. Using a publicly available RNAseq dataset, we evaluated the potential of several candidate enhancers for neuron-type-specific targeting in the hippocampus. Here we identified a promising enhancer-AAV for targeting dentate granule cells and validated its selectivity in wild-type adult mice.
Data-driven identification of major axes of functional variation in bacteria
Authors: Lajoie Geneviève , Kembel Steven W. 
Published: February 2023

AbstractThe discovery of major axes of correlated functional variation among species and habitats has revealed the fundamental trade-offs structuring both functional and taxonomic diversity in eukaryotes such as plants. Whether such functional axes exist in the bacterial realm and whether they could explain bacterial taxonomic turnover among ecosystems remains unknown. Here we use a data-driven approach to leverage global genomic and metagenomic datasets to reveal the existence of major axes of functional variation explaining both evolutionary differentiation within Bacteria and their ecological sorting across diverse habitats. We show that metagenomic variation among bacterial communities from various ecosystems is structured along a few axes of correlated functional pathways. Similar clusters of traits explained phylogenetic trait variation among >16,000 bacterial genomes, suggesting that functional turnover among bacterial communities from distinct habitats does not only result from the differential filtering of similar functions among communities, but also from phylogenetic correlations among these functions. Concordantly, functional pathways associated with trait clusters that were most important for defining functional turnover among bacterial communities were also those that had the highest phylogenetic signal in the bacterial genomic phylogeny. This study overall underlines the important role of evolutionary history in shaping contemporary distributions of bacteria across ecosystems.Originality-Significance StatementIn this article, we use a trait screening approach based on genomic and metagenomic data to identify the key functional strategies of bacteria across ecosystems but also across the bacterial tree of life. This novel approach allows us to quantify the role of evolutionary processes in structuring microbial ecological differences among ecosystems. By reducing the high-dimensionality of trait variation observed among microorganisms around a small number of fundamental axes of trait covariation, we make a significant step towards generalization of the drivers of biological diversity in microbes but also across study systems. This research provide a major advance in our understanding of the origin and maintenance of bacterial biological diversity, expanding on related findings for plants and animals.