bluuebunny/crossref_metadata_2025_split huggingface dataset:
DESpace: spatially variable gene detection via differential expression testing of spatial clusters
Authors: Cai Peiying , Robinson Mark D , Tiberi Simone 
Published: April 2023

AbstractMotivationSpatially resolved transcriptomics (SRT) enables scientists to investigate spatial context of mRNA abundance, including identifying spatially variable genes (SVGs), i.e., genes whose expression varies across the tissue. Although several methods have been proposed for this task, native SVG tools cannot jointly model biological replicates, or identify the key areas of the tissue affected by spatial variability.ResultsHere, we introduceDESpace, a framework, based on an original application of existing methods, to discover SVGs. In particular, our approach inputs all types of SRT data, summarizes spatial information via spatial clusters, and identifies spatially variable genes by performing differential gene expression testing between clusters. Furthermore, our framework can identify (and test) the main cluster of the tissue affected by spatial variability; this allows scientists to investigate spatial expression changes in specific areas of interest. Additionally,DESpaceenables joint modelling of multiple samples (i.e., biological replicates); compared to inference based on individual samples, this approach increases statistical power, and targets SVGs with consistent spatial patterns across replicates. Overall, in our benchmarks,DESpacedisplays good true positive rates, controls for false positive and false discovery rates, and is computationally efficient.Availability and implementationDESpaceis freely distributed as a Bioconductor R package.
Loss of ASD-Related Molecule Cntnap2 Affects Colonic Motility in Mice
Authors: Robinson Beatriz G. , Oster Beau A. , Robertson Keiramarie , Kaltschmidt Julia A. 
Published: April 2023

AbstractGastrointestinal (GI) symptoms are highly prevalent among individuals with autism spectrum disorder (ASD), but the molecular link between ASD and GI dysfunction remains poorly understood. The enteric nervous system (ENS) is critical for normal GI motility and has been shown to be altered in mouse models of ASD and other neurological disorders. Contactin-associated protein-like 2 (Cntnap2) is an ASD-related synaptic cell-adhesion molecule important for sensory processing. In this study, we examine the role of Cntnap2 in GI motility by characterizing Cntnap2’s expression in the ENS and assessing GI function inCntnap2mutant mice. We find Cntnap2 expression predominately in enteric sensory neurons. We further assessin-vivoandex-vivoGI motility inCntnap2mutants and show altered transit time and colonic motility patterns. The overall organization of the ENS appears undisturbed. Our results suggest that Cntnap2 plays a role in GI function and may provide a molecular link between ASD and GI dysfunction.
Comparing data-driven physiological denoising approaches for resting-state fMRI: Implications for the study of aging
Authors: Golestani Ali M , Chen J. Jean 
Published: April 2023

AbstractPhysiological nuisance contributions by cardiac and respiratory signals has a significant impact on resting-state fMRI data quality. As these physiological signals are often not recorded, data-driven denoising methods are commonly used to estimate and remove physiological noise from fMRI data. To investigate the efficacy of these denoising methods, one of the first steps is to accurately capture the cardiac and respiratory signals, which requires acquiring fMRI data with high temporal resolution. In this study, we used such high-temporal resolution fMRI data to evaluate the effectiveness of several data-driven denoising methods, including global-signal regression (GSR), white matter and cerebrospinal fluid regression (WM-CSF), anatomical (aCompCor) and temporal CompCor (tCompCor), ICA-AROMA. Our analysis focused on each method’s ability to remove cardiac and respiratory signal power, as well as its ability to preserve low-frequency signals and age-related functional connectivity (fcMRI) differences. Our findings revealed that ICA-AROMA and GSR consistently remove more heart-beat and respiratory frequencies, but also the most low-frequency signals. Our results confirm that the ICA-AROMA and GSR removed the most physiological noise at the expense of meaningful age-related fcMRI differences. On the other hand, aCompCor and tCompCor seem to provide a good balance between removing physiological signals and preserving fcMRI information. Lastly, methods differ in performance on young- and older-adult data sets. While this study cautions direct comparisons of fcMRI results based on different denoising methods in the study of aging, it also informs the choice of denoising method for broader fcMRI applications.
The hagfish genome and the evolution of vertebrates
Authors: Marlétaz Ferdinand , Timoshevskaya Nataliya , Timoshevskiy Vladimir , Simakov Oleg , Parey Elise , Gavriouchkina Daria , Suzuki Masakazu , Kubokawa Kaoru , Brenner Sydney , Smith Jeramiah , Rokhsar Daniel S. 
Published: April 2023

AbstractAs the only surviving lineages of jawless fishes, hagfishes and lampreys provide a critical window into early vertebrate evolution. Here, we investigate the complex history, timing, and functional role of genome-wide duplications in vertebrates in the light of a chromosome-scale genome of the brown hagfishEptatretus atami. Using robust chromosome-scale (paralogon-based) phylogenetic methods, we confirm the monophyly of cyclostomes, document an auto-tetraploidization (1RV) that predated the origin of crown group vertebrates ∼517 Mya, and establish the timing of subsequent independent duplications in the gnathostome and cyclostome lineages. Some 1RVgene duplications can be linked to key vertebrate innovations, suggesting that this early genomewide event contributed to the emergence of pan-vertebrate features such as neural crest. The hagfish karyotype is derived by numerous fusions relative to the ancestral cyclostome arrangement preserved by lampreys. These genomic changes were accompanied by the loss of genes essential for organ systems (eyes, osteoclast) that are absent in hagfish, accounting in part for the simplification of the hagfish body plan; other gene family expansions account for hagfishes’ capacity to produce slime. Finally, we characterise programmed DNA elimination in somatic cells of hagfish, identifying protein-coding and repetitive elements that are deleted during development. As in lampreys, the elimination of these genes provides a mechanism for resolving genetic conflict between soma and germline by repressing germline/pluripotency functions. Reconstruction of the early genomic history of vertebrates provides a framework for further exploration of vertebrate novelties.
ATP-induced crosslinking of a biomolecular condensate
Authors: Coupe Sebastian , Fakhri Nikta 
Published: April 2023

AbstractDEAD-box helicases are important regulators of biomolecular condensates. However, the mechanisms through which these enzymes affect the dynamics of biomolecular condensates have not been systematically explored. Here, we demonstrate the mechanism by which mutation of a DEAD-box helicase’s catalytic core alters ribonucleoprotein condensate dynamics in the presence of ATP. Through altering RNA length within the system, we are able to attribute the altered biomolecular dynamics and material properties to physical crosslinking of RNA facilitated by the mutant helicase. These results suggest the mutant condensates approach a gel transition when RNA length is increased to lengths comparable to eukaryotic mRNA. Lastly, we show that this crosslinking effect is tunable with ATP concentration, uncovering a system whose RNA mobility and material properties vary with enzyme activity. More generally, these findings point to a fundamental mechanism for modulating condensate dynamics and emergent material properties through nonequilibrium, molecular-scale interactions.SignificanceBiomolecular condensates are membraneless organelles which organize cellular biochemistry. These structures have a diversity of material properties and dynamics which are crucial to their function. How condensate properties are determined by biomolecular interactions and enzyme activity remain open questions. DEAD-box helicases have been identified as central regulators of many protein-RNA condensates, though their specific mechanistic roles are ill-defined. In this work, we demonstrate that a DEAD-box helicase mutation crosslinks condensate RNA in an ATP-dependent fashion via protein-RNA clamping. Protein and RNA diffusion can be tuned with ATP concentration, corresponding to an order of magnitude change in condensate viscosity. These findings expand our understanding of control points for cellular biomolecular condensates that have implications for medicine and bioengineering.
Nuclear NFκB Activity Balances Purine Metabolism in Cellular Senescence
Authors: Tabata Sho , Matsuda Keita , Nagai Kenshiro , Izumi Yoshihiro , Takahashi Masatomo , Motomura Yasutaka , Nagasato Ayaka Ichikawa , Shimma Shuichi , Moro Kazuyo , Bamba Takeshi , Okada Mariko 
Published: April 2023

SUMMARYUpregulation of nuclear factor κB (NFκB) signaling is a hallmark of aging and major cause of age-related chronic inflammation; however, its physiological functions and mechanisms remain unclear. By combining mathematical modeling and experiments, we show that dysfunction of negative feedback regulators of NFκB, IκBα and A20, alters the NFκB nuclear dynamics from oscillatory to sustained, promoting cellular senescence by remodeling epigenetic regulation and metabolic landscape. Sustained NFκB activity by IκBα downregulation enhanced inflammation- and senescence-associated gene expression through increased NFκB-DNA binding and slowed the cell cycle by upregulating purine catabolism via mTORC2/AKT pathways. Notably, IκBα knockdown combined with A20 overexpression resulted in lower NFκB amplitude, cytokine expression, and SA-β-gal activity than IκBα knockdown alone. IκBα downregulation is correlated with hypoxanthine phosphoribosyltransferase 1 (HPRT1) expression in the purine salvage pathway in aged mouse hearts. Our study suggests that nuclear NFκB homeostasis is critical for balancing purine metabolism associated with chronic inflammation and tissue aging.
Growth consequences of the inhomogeneous organization of the bacterial cytoplasm
Authors: van Heerden Johan H. , Berkvens Alicia , de Groot Daan H. , Bruggeman Frank J. 
Published: April 2023

AbstractIn many bacteria, translating ribosomes are excluded from the nucleoid, while amino-acid and energy-supplying metabolic enzymes spread evenly throughout the cytoplasm. Here we show with time-lapse fluorescence microscopy that this inhomogeneous organisation of the cytoplasm can cause singleEscherichia colicells to experience an imbalance between biosynthesis and metabolism when they divide, resulting in cell size-dependent growth rate perturbations. After division, specific growth rate and ribosome concentration correlates negatively with birthsize, and positively with each other. These deviations are compensated during the cell-cycle, but smaller-than-average cells do so with qualitatively different dynamics than larger-thanaverage cells. A mathematical model of cell growth, division and regulation of biosynthetic and metabolic resource allocation reproduces our experimental findings, suggesting a simple mechanism through which long-term growth rate homeostasis is maintained while heterogeneity is continuously generated. This work shows that the life of single bacterial cells is intrinsically out-of-steady-state, dynamic and reliant on cytoplasmic organization.Popular summaryClassical, population-level studies of the metabolism and growth of bacteria indicate that the average cell in a growing population operates at steady state and can be viewed as an homogeneous ‘bag of enzymes’. Here we show that this view does not capture the lives of single cells. At birth, they are perturbed from the steady state of their mother cell after which they need their entire cell cycle to return to this state by active regulation. Then they divide and their daughters are perturbed again; a never ending cycle that is inescapable and akin to a Sisyphean task. This behaviouremerges from the delicate interplay of the intrinsic randomness of (uneven) cell division, the inhomogeneous localisation of metabolic and ribosomal proteins in the cell, unbalanced metabolism, and compensatory steering of gene expression.
A palmitoyl transferase chemical genetic system to map ZDHHC-specificS-acylation
Authors: Ocasio Cory A. , Baggelaar Marc P. , Sipthorp James , de la Lastra Ana Losada , Volarić Jana , Soudy Christelle , Storck Elisabeth M. , Palma-Duran Susana A. , MacRae James I. , Tomic Goran , Carr Lotte , Downward Julian , Eggert Ulrike S. , Tate Edward W. 
Published: April 2023

AbstractThe 23 human ZDHHCS-acyltransferases catalyze long-chainS-acylation at cysteine residues across an extensive network of hundreds of proteins important for normal physiology or dysregulated in disease. Here we present a technology platform to directly map the protein substrates of a specific ZDHHC for the first time at the whole proteome level, in intact cells. Structure-guided engineering of paired ZDHHC ‘hole’ mutants and ‘bumped’ chemically tagged fatty acid probes enabled probe transfer to specific protein substrates with excellent selectivity over wild type ZDHHCs. Chemical genetic systems were exemplified for five ZDHHCs (3, 7, 11, 15 and 20), and applied to generate the firstde novoZDHHC substrate profiles, identifying >300 unique and shared substrates across multiple cell lines andS-acylation sites for novel functionally diverse substrates. We expect that this powerful and versatile platform will open a new window onS-acylation biology for a wide range of models and organisms.
Fine Tuning Rigid Body Docking Results Using the Dreiding Force Field: A Computational Study of 36 Known Nanobody-Protein Complexes
Authors: Hacisuleyman Aysima , Erman Burak 
Published: April 2023

AbstractThis paper aims to understand the binding strategies of a nanobody-protein pair by studying known complexes. Rigid body protein-ligand docking programs produce several complexes, called decoys, which are good candidates with high scores of shape complementarity, electrostatic interactions, desolvation, buried surface area, and Lennard-Jones potentials. It is not known which decoy represents the true structure. We studied thirty-seven nanobody-protein complexes from the Single Domain Antibody Database, sd-Ab DB,http://www.sdab-db.ca/. For each structure, a large number of decoys are generated using the Fast Fourier Transform algorithm of the software ZDOCK. The decoys were ranked according to their target protein-nanobody interaction energies, calculated by using the Dreiding Force Field, with rank 1 having the lowest interaction energy. Out of thirty-six PDB structures, twenty-five true structures were predicted as rank 1. Eleven of the remaining structures required Ångstrom size rigid body translations of the nanobody relative to the protein to match the given PDB structure. After the translation the Dreiding interaction (DI) energies of all complexes decreased and became rank 1. In one case, rigid body rotations as well as translations of the nanobody were required for matching the crystal structure. We used a Monte Carlo algorithm that randomly translates and rotates the nanobody of a decoy and calculates the DI energy. Results show that rigid body translations and the DI energy are sufficient for determining the correct binding location and pose of ZDOCK created decoys. A survey of the sd-Ab DB showed that each nanobody makes at least one salt bridge with its partner protein, indicating that salt bridge formation is an essential strategy in nanobody-protein recognition. Based on the analysis of the thirty-six crystal structures and evidence from existing literature, we propose a set of principles that could be used in the design of nanobodies.
The transition from vision to language: distinct patterns of functional connectivity for sub-regions of the visual word form area
Authors: Yablonski Maya , Karipidis Iliana I. , Kubota Emily , Yeatman Jason D. 
Published: April 2023

AbstractReading entails transforming visual symbols to sound and meaning. This process depends on specialized circuitry in the visual cortex, the Visual Word Form Area (VWFA). Recent findings suggest that this word-selective cortex comprises at least two distinct subregions: the more posterior VWFA-1 is sensitive to visual features, while the more anterior VWFA-2 processes higher level language information. Here, we explore whether these two subregions exhibit different patterns of functional connectivity, and whether these patterns have relevance for reading development. We address these questions using two complementary datasets: Using the Natural Scenes Datasets (NSD; Allen et al, 2022) we identify word-selective responses in high-quality 7T individual adult data (N=8; 6 females), and investigate functional connectivity patterns of VWFA-1 and VWFA-2 at the individual level. We then turn to the Healthy Brain Network (HBN; Alexander et al., 2017) database to assess whether these patterns a) replicate in a large developmental sample (N=224; 98 females, age 5-21y), and b) are related to reading development. In both datasets, we find that VWFA-1 is more strongly correlated with bilateral visual regions including ventral occipitotemporal cortex and posterior parietal cortex. In contrast, VWFA-2 is more strongly correlated with language regions in the frontal and lateral parietal lobes, particularly bilateral inferior frontal gyrus (IFG). Critically, these patterns do not generalize to adjacent face-selective regions, suggesting a unique relationship between VWFA-2 and the frontal language network. While connectivity patterns increased with age, no correlations were observed between functional connectivity and reading ability. Together, our findings support the distinction between subregions of the VWFA, and portray the functional connectivity patterns of the reading circuitry as an intrinsic stable property of the brain.
Proton-transfer salts of diphenylphosphinic acid with substituted 2-aminopyridine: crystal structure, spectroscopic and DFT studies
Authors: Yuan Haokun , Zhang Ran , Hu Kai , Fang Ruiqin 
Published: April 2023

Three proton-transfer salts of diphenylphosphinic acid (DPPA) with 2-amino-5-(X)-pyridine (AMPY, X = Cl, CN or CH3), namely, 2-amino-5-chloropyridinium diphenylphosphinate, C5H6ClN2
+·C12H10O2P− (1, X = Cl), 2-amino-5-cyanopyridinium diphenylphosphinate, C6H6N3
+·C12H10O2P− (2, X = CN), and 2-amino-5-methylpyridinium diphenylphosphinate, C6H9N2
+·C12H10O2P− (3, X = CH3), have been synthesized and characterized by FT–IR and 1H NMR spectroscopy, and X-ray crystallography. The crystal structures of compounds 1–3 were determined in the space group P-1 for 1 and 2, and C2/c for 3. All three compounds contain N—H...O hydrogen-bonding interactions due to proton transfer from the O=P—OH group of DPPA as donor to the pyridine N atom of AMPY as acceptor. The proton transfer of compounds 1–3 was also verified by 1H NMR and FT–IR spectroscopy. The stoichiometry of all three proton-transfer salts was determined to be 1:1 and the Benesi–Hildebrand equation was applied to determine the formation constant (K
CT) and the molar extinction coefficient (ɛCT) in each case. Theoretical density functional theory (DFT) calculations were performed to investigate the optimized geometries, the molecular electrostatic potentials (MEP) and the highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) of all three proton-transfer salts. The results showed good agreement between the experimental data and the DFT computational analysis.
Environmental awareness and shareholder proposals: the case of the Deepwater Horizon oil spill disaster
Authors: D'Augusta Carlo , Grossetti Francesco , Imperatore Claudia 
Published: April 2023

Purpose
The authors study the effect of increasing environmental awareness on shareholders' activism. Specificallly, this study aims to examine whether growing environmental awareness is reflected in more aggressive environmental shareholder proposals.

Design/methodology/approach
This study uses the 2010 Deepwater Horizon oil spill disaster as an exogenous event that increased shareholders' environmental awareness. This study analyzes the spill’s effect on the tone of proposals about environmental issues and nonenvironmental topics.

Findings
After the disaster, the tone of environmental proposals (i.e. the treatment group) is significantly more negative. In contrast, the tone of nonenvironmental proposals (i.e. the control group) is unaffected. This study interprets this finding as direct evidence that the oil spill led to increased shareholder environmental activism through proposals that targeted the environmental risks surrounding the business more aggressively. By contrast, this study finds no effect of the oil spill on the tone of managers' responses to the proposals, consistent with managers refraining from emphasizing environmental threats.

Originality/value
Anecdotal evidence and recent studies suggest a link between environmental disasters and shareholder pressure for corporate change. However, no prior research has investigated the channel through which shareholders could have exerted such pressure or has looked for direct evidence of it in the negotiations between shareholders and managers. By finding such evidence in shareholder proposals, this study fills in this gap.