bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of concurrent and asynchronous running kinematics and kinetics from marker-based motion capture and markerless motion capture under two clothing conditions
Authors: Kanko Robert M. , Outerleys Jereme B. , Laende Elise K. , Selbie W. Scott , Deluzio Kevin J. 
Published: February 2023

AbstractAs markerless motion capture is increasingly used to measure three-dimensional human pose, it is important to understand how markerless results can be interpreted alongside historical marker-based data and how they are impacted by clothing. We compared concurrent running kinematics and kinetics between marker-based and markerless motion capture, and between two markerless clothing conditions. Thirty adults ran on an instrumented treadmill wearing motion capture clothing while concurrent marker-based and markerless data were recorded, and ran a second time wearing athletic clothing (shorts and t-shirt) while markerless data were recorded. Differences calculated between the concurrent signals from both systems, and also between each participant’s mean signals from both asynchronous clothing conditions were summarized across all participants using root-mean-square differences. Most kinematic and kinetic signals were visually consistent between systems and markerless clothing conditions. Between systems, joint center positions differed by 3 cm or less, sagittal plane joint angles differed by 5° or less, and frontal and transverse plane angles differed by 5°-10°. Joint moments differed by 0.3 Nm/kg or less between systems. Differences were sensitive to segment coordinate system definitions, highlighting the effects of these definitions when comparing against historical data or other motion capture modalities.
The AEGEAN-169 clade of bacterioplankton is synonymous with SAR11 subclade V (HIMB59) and metabolically distinct
Authors: Getz Eric W. , Lanclos V. Celeste , Kojima Conner Y. , Cheng Chuankai , Henson Michael W. , Schön Max Emil , Ettema Thijs J. G. , Faircloth Brant C. , Thrash J. Cameron 
Published: February 2023

ABSTRACTBacterioplankton of the SAR11 clade are the most abundant marine microorganisms and consist of numerous subclades spanning Order level divergence (Pelagibacterales). The assignment of the earliest diverging subclade V (a.k.a. HIMB59) to thePelagibacteralesis highly controversial, with multiple recent phylogenetic studies placing them completely separate from SAR11. Other than through phylogenomics, subclade V has not received detailed examination due to limited genomes from this group. Here, we assessed the ecogenomic characteristics of subclade V to better understand the role of this group in comparison to thePelagibacterales. We used a new isolate genome, recently released single amplified genomes (SAGs) and metagenome-assembled genomes (MAGs), and previously established SAR11 genomes to perform a comprehensive comparative genomics analysis. We paired this analysis with recruitment of metagenomes spanning open ocean, coastal, and brackish systems. Phylogenomics, average amino acid identity, and 16S rRNA gene phylogeny indicate that SAR11 subclade V is synonymous with the ubiquitous AEGEAN-169 clade, and support the contention that this group represents a taxonomic Family. AEGEAN-169 shared many bulk genome qualities with SAR11, such as streamlining and low GC content, but genomes were generally larger. AEGEAN-169 had overlapping distributions with SAR11 but was metabolically distinct from SAR11 in its potential to transport and utilize a broader range of sugars as well as in transport of trace metals and thiamin. Thus, regardless of the ultimate phylogenetic placement of AEGEAN-169, these organisms have distinct metabolic capacities that likely allow them to differentiate their niche from canonical SAR11 taxa.IMPORTANCEOne goal of marine microbiologists is to uncover the roles various microorganisms are playing in biogeochemical cycles. Success in this endeavor relies on differentiating groups of microbes and circumscribing their relationships. An early-diverging group (subclade V) of the most abundant bacterioplankton, SAR11, has recently been proposed as a separate lineage that does not share a most recent common ancestor. But beyond phylogenetics, little has been done to evaluate how these organisms compare with SAR11. Our work leverages dozens of new genomes to demonstrate the similarities and differences between subclade V and SAR11. In our analysis, we also establish that subclade V is synonymous with a group of bacteria established from 16S rRNA gene sequences, AEGEAN-169. Subclade V/AEGEAN-169 has clear metabolic distinctions from SAR11 and their shared traits point to remarkable convergent evolution if they do not share a most recent common ancestor.
Oxygen intrusions sustain aerobic nitrite-oxidizing bacteria in anoxic marine zones
Authors: Buchanan Pearse J. , Sun Xin , Weissman JL , McCoy Daniel , Bianchi Daniele , Zakem Emily 
Published: February 2023

AbstractAnaerobic metabolisms are thought to dominate nitrogen cycling in anoxic marine zones (AMZs). However, thriving populations of aerobic nitrite-oxidizing bacteria (NOB) in AMZs challenge this assumption and remain unexplained. Using theory and modelling, we show how periodic oxygen intrusions sustain aerobic NOB in AMZs alongside more competitive aerobic heterotrophs. Ecological theory, supported by genomics and numerical simulations, frames NOB as opportunists exploiting a fleeting supply of oxygen. Consistent within situobservations, we show that simulated NOB contribute substantially (>40%) to oxygen consumption at AMZ boundaries, which implies that NOB may provide a unique stabilizing feedback to AMZs. Fine-scale ocean currents increase the metabolic diversity in AMZs, which could stabilize AMZ volume under climate change.One-Sentence SummaryFleeting whiffs of oxygen to the ocean ‘s anoxic zones increase microbial diversity and alter biogeochemical cycling.
Quantitative Time-Course Analysis of Osmotic and Salt Stress inArabidopsis thalianausing Short Gradient Multi-CV FAIMSpro BoxCar DIA
Authors: Gallo M.C. Rodriguez , Li Q. , Talasila M. , Uhrig RG 
Published: February 2023

AbstractA major limitation when undertaking quantitative proteomic time-course experimentation is the tradeoff between depth-of-analysis and speed-of-analysis. In high complexity and high dynamic range sample types, such as plant extracts, balance between resolution and time is especially apparent. To address this, we evaluate multiple composition voltage (CV) HighFieldAsymetric WaveformIonMobilitySpectrometry (FAIMSpro) settings using the latest label-free single-shot Orbitrap-based DIA acquisition workflows for their ability to deeply-quantify theArabidopsis thalianaseedling proteome. Using a BoxCarDIA acquisition workflow with a −30 −50 −70 CV FAIMSpro setting we are able to consistently quantify >5000Arabidopsisseedling proteins over a 21-minute gradient, facilitating the analysis of ~42 samples per day. Utilizing this acquisition approach, we then quantified proteome-level changes occurring inArabidopsisseedling shoots and roots over 24 h of salt and osmotic stress, to identify early and late stress response proteins and reveal stress response overlaps. Here, we successfully quantify >6400 shoot and >8500 root protein groups, respectively, quantifying nearly ~9700 unique protein groups in total across the study. Collectively, we pioneer a short gradient, multi-CV FAIMSpro BoxCarDIA acquisition workflow that represents an exciting new analysis approach for undertaking quantitative proteomic time-course experimentation in plants.
Joint testing of rare variant burden scores using non-negative least squares
Authors: Ziyatdinov Andrey , Mbatchou Joelle , Marcketta Anthony , Backman Joshua , Gaynor Sheila , Zou Yuxin , Joseph Tyler , Geraghty Benjamin , Herman Joseph , Watanabe Kyoko , Ghosh Arkopravo , Kosmicki Jack , Locke Adam ,   Regeneron Genetics Center, Thornton Timothy , Kang Hyun Min , Ferreira Manuel , Baras Aris , Abecasis Goncalo , Marchini Jonathan 
Published: February 2023

AbstractGene-based burden tests are a popular and powerful approach for analysis of exome-wide association studies. These approaches combine sets of variants within a gene into a single burden score that is then tested for association. Typically, a range of burden scores are calculated and tested across a range of annotation classes and frequency bins. Correlation between these tests can complicate the multiple testing correction and hamper interpretation of the results. We introduce a new method called the Sparse Burden Association Test (SBAT) that tests the joint set of burden scores under the assumption that causal burden scores act in the same effect direction. The method simultaneously assesses the significance of the model fit and selects the set of burden scores that best explain the association at the same time. Using simulated data, we show that the method is well calibrated and highlight some scenarios where the test outperforms existing gene-based tests. We apply the method to 73 quantitative traits from the UK Biobank which further illustrates the power of the method. This test is implemented in the REGENIE software.
The most probable ancestral sequence reconstruction yields proteins without systematic bias in thermal stability or activity
Authors: Sennett Michael A. , Beckett Brian C. , Theobald Douglas L. 
Published: February 2023

AbstractAncestral sequence resurrection (ASR) is the inference of extinct biological sequences from extant sequences, the most popular of which are based on probabilistic models of evolution. ASR is becoming a popular method for studying the evolution of enzyme characteristics. The properties of ancestral enzymes are biochemically and biophysically characterized to gain some knowledge regarding the origin of some enzyme property. Current methodology relies on resurrection of the single most probable (SMP) sequence and is systematically biased. Previous theoretical work suggests this will result in a thermostability bias in resurrected SMP sequences, and even the activity, calling into question inferences derived from ancestral protein properties. We experimentally test the potential stability bias hypothesis by resurrecting 40 malate and lactate dehydrogenases. Despite the methodological bias in resurrecting an SMP protein, the measured biophysical and biochemical properties of the SMP protein are not biased in comparison to other, less probable, resurrections. In addition, the SMP protein property seems to be representative of the ancestral probability distribution. Therefore, the conclusions and inferences drawn from the SMP protein are likely not a source of bias.SignificanceAncestral sequence resurrection (ASR) is a powerful tool for: determining how new protein functions evolve; inferring the properties of an environment in which species existed; and protein engineering applications. We demonstrate, using lactate and malate dehydrogenases (L/MDHs), that resurrecting the single most probable sequence (SMP) from a maximum likelihood phylogeny does not result in biased activity and stability relative to sequences sampled from the posterior probability distribution. Previous studies using experimentally measured phenotypes of SMP sequences to make inferences about the environmental conditions and the path of evolution are likely not biased in their conclusions. Serendipitously, we discover ASR is also a valid tool for protein engineering because sampled reconstructions are both highly active and stable.
O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations
Authors: Huynh Duc T. , Hu Jimin , Schneider Jordan R. , Tsolova Kalina N. , Soderblom Erik J. , Watson Abigail J. , Chi Jen-Tsan , Evans Chantell S. , Boyce Michael 
Published: February 2023

AbstractThe neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. In particular, the neurofilament-light (NF-L) subunit is required for NF assemblyin vivoand is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. NFs are highly dynamic, and the regulation of NF assembly state is incompletely understood. Here, we demonstrate that human NF-L is modified in a nutrient-sensitive manner by O-linked-β-N-acetylglucosamine (O-GlcNAc), a ubiquitous form of intracellular glycosylation. We identify five NF-L O-GlcNAc sites and show that they regulate NF assembly state. Interestingly, NF-L engages in O-GlcNAc-mediated protein-protein interactions with itself and with the NF component α-internexin, implying that O-GlcNAc is a general regulator of NF architecture. We further show that NF-L O-GlcNAcylation is required for normal organelle trafficking in primary neurons, underlining its functional significance. Finally, several CMT-causative NF-L mutants exhibit perturbed O-GlcNAc levels and resist the effects of O-GlcNAcylation on NF assembly state, indicating a potential link between dysregulated O-GlcNAcylation and pathological NF aggregation. Our results demonstrate that site-specific glycosylation regulates NF-L assembly and function, and aberrant NF O-GlcNAcylation may contribute to CMT and other neurodegenerative disorders.
Dynamic walking behavior during odor trail-following in locusts
Authors: Traner Mike , Raman Barani 
Published: February 2023

AbstractOne of the important subsets of odor sources used in olfactory navigation is surface-bound sources, which can broadly take the form of point sources or trails. Odor trails, in particular, have been observed to be highly relevant components of olfactory-based navigation for species as broadly distributed as dogs and ants. Here, we present an automated treadmill setup capable of dynamically printing odor trails of arbitrary lengths and configurations, and with closed-loop control of speed based on the subject’s movement. We used this setup to characterize trail-following behavior in locusts (Schistocerca americana). The free-moving behavior of the locusts is more naturalistic and is richer in plumbable data than many traditional assays. We reveal broad classes of behavioral walking motifs and their dynamic transitions as locusts pursue or avoid an odor trail. Furthermore, we show how these motifs vary across individuals, with the identity of the odorant and with respect to the sex of the organism. Our dataset and analyses provide a first demonstration that this model organism is capable of robust odor trail following, and provides a comprehensive analysis of the dynamic motifs that underlie this behavioral capability.
Isoform-specific targeting properties of the protocadherin CDHR5 control its apical delivery to promote brush border assembly
Authors: Matoo Samaneh , Graves Maura J. , Choi Myoung Soo , El Sheikh Idris Rawnag A. , Acharya Prashun , Thapa Garima , Nguyen Tram , Atallah Sarah Y. , Tipirneni Ashna K. , Stevenson Phillip J. , Crawley Scott W. 
Published: February 2023

ABSTRACTTransporting epithelial cells of the gut and kidney interact with their luminal environment through a densely-packed collection of apical microvilli known as the brush border. Proper brush border assembly depends on the intermicrovillar adhesion complex (IMAC), a protocadherin-based adhesion complex found at the distal tips of microvilli that mediates adhesion between neighboring protrusions to promote their organized packing. Loss of the IMAC adhesion molecule Cadherin-related family member 5 (CDHR5) correlates with poor prognosis of colon cancer patients, though the functional properties of this protocadherin have not been thoroughly explored in relevant cell systems. Here, we show that the two dominant CDHR5 splice isoforms expressed in enterocytes interact to form an apparentcis-oligomer that is competent to target to the apical domain to drive microvillar elongation. The two isoforms exhibited distinct sequence-dependent apical targeting properties, with one isoform requiring its cytoplasmic tail. Library screening identified the Ezrin-associated scaffolds EBP50 and E3KARP as cytoplasmic binding partners for CDHR5. Consistent with this, loss of EBP50 disrupted proper brush border assembly with cells exhibiting markedly reduced apical IMAC levels. Together, our results shed light on the apical targeting determinants of CDHR5 and further define the interactome of the IMAC involved in brush border assembly.
DR-BERT: A Protein Language Model to Annotate Disordered Regions
Authors: Nambiar Ananthan , Forsyth John Malcolm , Liu Simon , Maslov Sergei 
Published: February 2023

AbstractDespite their lack of a rigid structure, intrinsically disordered regions in proteins play important roles in cellular functions, including mediating protein-protein interactions. Therefore, it is important to computationally annotate disordered regions of proteins with high accuracy. Most popular tools use evolutionary or biophysical features to make predictions of disordered regions. In this study, we present DR-BERT, a compact protein language model that is first pretrained on a large number of unannotated proteins before being trained to predict disordered regions. Although it does not use any explicit evolutionary or biophysical information, DR-BERT shows a statistically significant improvement when compared to several existing methods on a gold standard dataset. We show that this performance is due to the information learned during pretraining and DR-BERT’s ability to use contextual information. A web application for using DR-BERT is available athttps://huggingface.co/spaces/nambiar4/DR-BERTand the code to run the model can be found athttps://github.com/maslov-group/DR-BERT.
A cell state specific metabolic vulnerability to GPX4-dependent ferroptosis in glioblastoma
Authors: Banu Matei A. , Dovas Athanassios , Argenziano Michael G. , Zhao Wenting , Grajal Henar Cuervo , Higgins Dominique M.O. , Sperring Colin P. , Pereira Brianna , Ye Ling F. , Mahajan Aayushi , Humala Nelson , Furnari Julia L. , Upadhyayula Pavan S. , Zandkarimi Fereshteh , Nguyen Trang T. T. , Wu Peter B. , Hai Li , Karan Charles , Razavilar Aida , Siegelin Markus D. , Kitajewski Jan , Bruce Jeffrey N. , Stockwell Brent R. , Sims Peter A. , Canoll Peter D. 
Published: February 2023

SUMMARYGlioma cells hijack developmental transcriptional programs to control cell state. During neural development, lineage trajectories rely on specialized metabolic pathways. However, the link between tumor cell state and metabolic programs is poorly understood in glioma. Here we uncover a glioma cell state-specific metabolic liability that can be leveraged therapeutically. To model cell state diversity, we generated genetically engineered murine gliomas, induced by deletion of p53 alone (p53) or with constitutively active Notch signaling (N1IC), a pathway critical in controlling cellular fate. N1IC tumors harbored quiescent astrocyte-like transformed cell states while p53 tumors were predominantly comprised of proliferating progenitor-like cell states. N1IC cells exhibit distinct metabolic alterations, with mitochondrial uncoupling and increased ROS production rendering them more sensitive to inhibition of the lipid hydroperoxidase GPX4 and induction of ferroptosis. Importantly, treating patient-derived organotypic slices with a GPX4 inhibitor induced selective depletion of quiescent astrocyte-like glioma cell populations with similar metabolic profiles.
Modulation of quantitative trait loci forArabidopsis thalianaseed performance by the maternal and germination environment
Authors: Snoek Basten L. , Serin Elise A. R. , Nijveen Harm , Willems Leo A. J. , Rienstra Juriaan A. , van Zanten Martijn , Hilhorst Henk W. M. , Ligterink Wilco 
Published: February 2023

AbstractThe quality of seeds contributes to plant performance, especially during germination and in the young seedling stage, and hence affects the economic value of seed crops. A seed’s innate quality is determined during seed development and the following seed maturation phase. It is tightly controlled by the genetic make-up of the mother plant and further shaped by the environmental conditions of the mother plant. The interaction between genotype and environment can result in substantial quantitative variation in seed traits like dormancy and viability.Making use of naturally occurring variation within theArabidopsis thalianagermplasm, we studied the interaction between seed production environments and the genetic architecture of mother plants on diverse seed quality traits. An Arabidopsis Bayreuth-0 x Shahdara recombinant inbred line (RIL) population was grown in four different seed production environments: high temperature, high light, low phosphate, and control conditions. The seeds harvested from the mother plants that were exposed to these environments from flowering until seed harvest were subsequently subjected to germination assays under standard and mild stress conditions (cold, heat, osmotic stress and added phytohormone ABA). Quantitative trait locus (QTL) analysis identified many environmental-sensitive QTLs (QTL x E) as well as several interactions between the maternal and germination environments. Variation in the number and position of the QTLs was largely determined by the germination conditions, however effects of the maternal environment were clearly present regarding the genomic location as well as significance of the individual QTLs.Together, our findings uncover the extensive environmental modulation of the genetic influence on seed performance and how this is shaped by the genetic make-up of the mother plant. Our data provides a systems-view of the complex genetic basis of genotype-by-environment interactions determining seed quality.
Foxp3 Orchestrates Reorganization of Chromatin Architecture to Establish Regulatory T Cell Identity
Authors: Liu Zhi , Lee Dong-Sung , Liang Yuqiong , Zheng Ye , Dixon Jesse R 
Published: February 2023

SUMMARYChromatin conformation reorganization is emerging as an important layer of regulation for gene expression and lineage specification. Yet, how lineage-specific transcription factors contribute to the establishment of cell type-specific 3D chromatin architecture in the immune cells remains unclear, especially for the late stages of T cell subset differentiation and maturation. Regulatory T cells (Treg) are mainly generated in the thymus as a subpopulation of T cells specializing in suppressing excessive immune responses. Here, by comprehensively mapping 3D chromatin organization during Treg cell differentiation, we show that Treg-specific chromatin structures were progressively established during its lineage specification, and highly associated with Treg signature gene expression. Additionally, the binding sites of Foxp3, a Treg lineage specifying transcription factor, were highly enriched at Treg-specific chromatin loop anchors. Further comparison of the chromatin interactions between wide-type Tregs versus Treg cells from Foxp3 knock-in/knockout or newly-generated Foxp3 domain-swap mutant mouse revealed that Foxp3 was essential for the establishment of Treg-specific 3D chromatin architecture, although it was not dependent on the formation of the Foxp3 domain-swapped dimer. These results highlighted an underappreciated role of Foxp3 in modulating Treg-specific 3D chromatin structure formation.