bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theory of axo-axonic inhibition
Authors: Brette Romain 
Published: January 2025

AbstractThe axon initial segment of principal cells of the cortex and hippocampus is contacted by GABAergic interneurons called chandelier cells. The anatomy, as well as alterations in neurological diseases such as epilepsy, suggest that chandelier cells exert an important inhibitory control on action potential initiation. However, their functional role remains unclear, including whether their effect is indeed inhibitory or excitatory. One reason is that there is a relative gap in electrophysiological theory about the electrical effect of axo-axonic synapses. This contribution uses resistive coupling theory, a simplification of cable theory based on the observation that the small initial segment is resistively coupled to the large cell body acting as a current sink, to fill this gap. The main theoretical finding is that a synaptic input at the proximal axon shifts the action potential threshold by an amount equal to the product of synaptic conductance, driving force at threshold, and axial axonal resistance between the soma and either the synapse or of the middle of the initial segment, whichever is closer. The theory produces quantitative estimates useful to interpret experimental observations, and supports the idea that axo-axonic cells can potentially exert powerful inhibitory control on action potential initiation.Significance statementChandelier cells form GABAergic synapses on the initial segment of pyramidal cells of the cortex and hippocampus. Despite their striking morphology and alterations in neurological diseases such as epilepsy, their functional role remains unclear. This study develops a quantitative theory to precisely assess the electrical impact of a synaptic input at the proximal axon. It shows that axo-axonic inhibition acts by shifting the action potential threshold proportionally to the synaptic conductance. This work underlines the role of chandelier cells in controlling action potential initiation and provides a quantitative tool to interpret experimental observations.
PHACE: Phylogeny-Aware Co-Evolution
Authors: Kuru Nurdan , Adebali Ogun 
Published: January 2025

AbstractThe co-evolution trends of amino acids within or between genes offer valuable insights into protein structure and function. Existing tools for uncovering co-evolutionary signals primarily rely on multiple sequence alignments (MSAs), often neglecting considerations of phylogenetic relatedness and shared evolutionary history. Here, we present a novel approach based on the substitution mapping of amino acid changes onto the phylogenetic tree. We categorize amino acids into two groups: ‘tolerable’ and ‘intolerable,’ and assign them to each position based on the position dynamics concerning the observed amino acids. Amino acids deemed ‘tolerable’ are those observed phylogenetically independently and multiple times at a specific position, signifying the position’s tolerance to that alteration. Gaps are regarded as a third character type, and we only consider phylogenetically independent altered gap characters. Our algorithm is based on a tree traversal process through the nodes and computes the total amount of substitution per branch based on the probability differences of two groups of amino acids and gaps between neighboring nodes. We employ an MSA-masking approach to mitigate misleading artifacts from poorly aligned regions. When compared to tools utilizing phylogeny (CAPS and CoMap) and state-of-the-art MSA-based approaches (DCA, GaussDCA, PSICOV, and MIp), our method exhibits significantly superior accuracy in identifying co-evolving position pairs, as measured by statistical metrics including MCC, AUC, and F1 score. PHACE’s success arises from its ability to consider the frequently neglected phylogenetic dependency.
Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma
Authors: Shishikura Kyosuke , Li Jiasong , Chen Yiming , McKnight Nate R. , Bustin Katelyn A. , Barr Eric W. , Chilkamari Snehil R. , Ayub Mahaa , Kim Sun Woo , Lin Zongtao , Hu Ren-Ming , Hicks Kelly , Wang Xie , O’Rourke Donald M. , Bollinger J. Martin , Binder Zev A. , Parsons William H. , Martemyanov Kirill A. , Liu Aimin , Matthews Megan L. 
Published: January 2025

AbstractThe vasodilator hydralazine (HYZ) has been used clinically for ∼ 70 years and remains on the World Health Organization’s List of Essential Medicines as a therapy for preeclampsia. Despite its longstanding use and the concomitant progress toward a general understanding of vasodilation, the target and mechanism of HYZ have remained unknown. We show that HYZ selectively targets 2-aminoethanethiol dioxygenase (ADO) by chelating its metal cofactor and alkylating one of its ligands. This covalent inactivation slows entry of proteins into the Cys/N-degron pathway that ADO initiates. HYZ’s capacity to stabilize regulators of G-protein signaling (RGS4/5) normally marked for degradation by ADO explains its effect on blood vessel tension and comports with prior associations of insufficient RGS levels with human preeclampsia and analogous symptoms in mice. The established importance of ADO in glioblastoma led us to test HYZ in these cell types. Indeed, a single treatment induced senescence, suggesting a potential new HYZ-based therapy for this deadly brain cancer.
Phosphorylation of α-synuclein fibrils at S129 changes DNAJB1 binding as probed by solid-state NMR
Authors: Pacheco Sayuri , Reselammal Dhanya S. , Zhang Qingya , Siemer Ansgar B. 
Published: January 2025

AbstractAmyloid fibrils composed of the protein α-synuclein (aSyn) are implicated in the pathogenesis of synucleinopathies. These pathological fibrils, characterized by their rigid amyloid cores, also feature flexible intrinsically disordered regions (IDRs) that interact with various cellular components. Due to their solvent exposure and flexibility, the N- and C-termini, IDRs of aSyn fibrils, have been used as targets for immunotherapies and serve as binding sites for many chaperones. Chaperones are known to play a vital role in preventing and reversing amyloid formation in neurodegenerative diseases, but how they recognize misfolded proteins is often poorly understood. DNAJB1 is a co-chaperone that is part of a larger complex formed with Hsp70 and Apg2, which collectively disaggregate amyloid fibrils such as those formed by aSyn, tau, or huntingtin. Although the entire chaperone and co-chaperone complex are required for aggregate disassembly, DNAJB1 directly recognizes these amyloid fibrils. More specifically, DNAJB1 preferentially binds to the C-terminus of wild-type aSyn. However, over 90% of aSyn fibrils in Lewy bodies are phosphorylated at S129. Here, we determine the effect of S129 phosphorylation on DNAJB1-aSyn fibril binding using biochemical assays and solid-state NMR. We show that DNAJB1 preferentially binds aSyn pS129 fibrils and that the aSyn binding site of pS129 and wild-type fibrils is different. These results suggest that pS129 might influence chaperone-mediated degradation efficiency.
Learning a Pairwise Epigenomic and Transcription Factor Binding Association Score Across the Human Genome
Authors: Kwon Soo Bin , Ernst Jason 
Published: January 2025

AbstractIdentifying pairwise associations between genomic loci is an important challenge for which large and diverse collections of epigenomic and transcription factor (TF) binding data can potentially be informative. We therefore developed Learning Evidence of Pairwise Association from Epigenomic and TF binding data (LEPAE). LEPAE uses neural networks to quantify evidence of association for pairs of genomic windows from large-scale epigenomic and TF binding data along with distance information. We applied LEPAE using thousands of human datasets. We present evidence using additional data that LEPAE captures biologically meaningful pairwise relationships between genomic loci and expect LEPAE scores to be a resource.
NIRDuino: A modular, Bluetooth-enabled, Android®-configurable fNIRS system with dual-intensity mode built on Arduino®
Authors: Kumar Anupam , Crawford Seth , Le Tiffany-Chau , Jounghani Ali Rahimpour , Carbonell Laura Moreno , Capps Alexandra Sargent , Walter Alec B. , Liu Daniel , Sullivan Reed , Jansen E. Duco , Hosseini SM Hadi , Bowden Audrey K. 
Published: January 2025

AbstractSignificanceWe present NIRDuino: an Open-source Android®-configurable, modular, and Bluetooth-enabled fNIRS system that allows researchers to perform neuroimaging studies with up to eight emitters and 16 detectors. The complete system (including Android tablet) can be assembled for less than $1000, and the emitters and detectors can be arranged in any configuration to achieve the desired short and long channels required for their study.AimThe system has been designed with non-engineers in mind, and the researcher only needs to design the wearable interfaces to attach the emitters and detectors to the body appropriate for their intended application.ApproachThe system consists of a battery-powered, wireless controller built on the Arduino® Nano ESP32 platform, a dongle with sockets for each of the eight emitters and detectors that can be connected, and individual wired probes for emitters and detectors. In accompaniment, Arduino®-based firmware and an Android®application have also been developed and provided. The selected emitters and detectors can be arranged in any desired configuration, and the emitters can be configured to output light with both regular intensities and low intensities to collect data for “long channels” with sufficient signal quality and “short channels” without saturation. This paper details the system’s design and characterization on phantom and two physiological experiences on a human.ResultsThe easy-to-configure hardware/software system demonstrated stability in fNIRS measurements using a single emitter-detector pair placed on a phantom, and reproduced previously published outcomes for arterial cuff measurements on the forearm and a arithmetic experiment on the forehead.ConclusionThe NIRDuino circuitry and software demonstrated modularity and usability for NIRS experiments, and this low-cost platform will provide researchers globally with an affordable fNIRS system to easily adopt and adapt for their unique experimental needs.
Does Precision Grip Research Extend to Unconstrained, Multidigit Grasping?
Authors: Lepori Fabrizio , Hartmann Frieder , Dehn Kira , Chessa Manuela , Fleming Roland W , Maiello Guido 
Published: January 2025

ABSTRACTMost daily tasks require using our hands. Whether taking a sip from a glass or throwing a ball, we effortlessly select appropriate grasps. Yet, despite many possible hand configurations, most grasping research has focused on the finger-and-thumb ‘precision grip’. We thus questioned whether findings on precision grip hold under unconstrained grasping conditions. To test this, we compared how participants grasped 3D objects made of brass and wood, with both precision grip and unconstrained grasps. When unconstrained, participants rarely selected precision grips, favoring multi-digit grasps. Nevertheless, in both conditions, participants shifted grasps towards the objects’ center of mass and, when grasp factors conflicted, the variability in their selections increased, indicating greater uncertainty about the optimal strategy. Further, despite favoring multidigit grasps, participants consistently placed the thumb and index finger on the same positions on the objects, suggesting that in multidigit grasps, the additional fingers primarily provided support. Our findings thus reveal that object material affects unconstrained grasping similarly to precision grip and imply that previous precision grip research may extend to unconstrained, multidigit conditions.NEW & NOTEWORTHYMost grasping research focuses on two-digit ‘precision grips’, yet humans have more than two fingers. Here, we test whether previous precision grip findings apply to unconstrained grasping. We find that participants often use more than two digits when free to choose but consistently place thumb and index finger similarly on objects regardless of the number of fingers used. Our results thus highlight how the large body of precision grip literature can extend to multidigit grasping.
The yeast CST and Polα/primase complexes act in concert to ensure proper telomere maintenance and protection
Authors: Calugaru Kimberly , Yu Eun Young , González-Rodríguez Nayim , Coloma Javier , Lue Neal F. 
Published: January 2025

AbstractPolα/primase, the polymerase that initiates DNA synthesis at replication origins, also completes the task of genome duplication by synthesizing the telomere C-strand under the control of the CST complex. Using cryo-EM structures of the human CST-Polα/primase-DNA complex as guides in conjunction with AlphaFold modeling, we identified structural elements in yeast CST and Polα/primase that promote complex formation. Mutating these structures inCandida glabrataStn1, Ten1, Pri1 and Pri2 abrogated the stimulatory activity of CST on Polα/primasein vitro,supporting the functional relevance of the physical contacts in cryo-EM structures as well as the conservation of mechanisms between yeast and humans. Introducing these mutations intoC. glabratayielded two distinct groups of mutants. One group exhibited progressive, telomerase-dependent telomere elongation without evidence of DNA damage. The other manifested slow growth, telomere length heterogeneity, ssDNA accumulation and elevated C-circles, which are indicative of telomere deprotection. These telomere deprotection phenotypes are altered or suppressed by mutations in multiple DDR and DNA repair factors. We conclude that in yeast, the telomerase inhibition and telomere protection function previously ascribed to the CST complex are mediated jointly by both CST and Polα/primase, highlighting the critical importance of a replicative DNA polymerase in telomere regulation.
Integrating predator energetic balance, risk-taking behavior and microhabitat in functional response: Untangling indirect interactions in a multispecies vertebrate community
Authors: Beardsell Andréanne , Dulude-De-Broin Frédéric , Gauthier Gilles , Gravel Dominique , Legagneux Pierre , DeLong John P. , Berteaux Dominique , Bêty Joël 
Published: January 2025

1AbstractPredator-prey interactions are universal, governing the flow of energy between trophic levels and shaping ecological communities. Despite >70 years of research, our knowledge of the mechanisms modulating the strength of these interactions is limited.To untangle proximate mechanisms governing species interactions and improve our ability to quantify interaction strength, we developed a mechanistic model that integrates predator risk-taking behavior, predator energetic balance and anti-predator refuges in a natural vertebrate community.Our model, based on species traits and behavior, was inspired by the Arctic tundra, where the main predator (the arctic fox) feeds primarily on cyclic small rodents (lemmings) and eggs of various tundra-nesting bird species such as sandpipers eggs(non-risky prey) and gulls eggs (risky prey). We confront the model predictions with 20 years of data on species density and reproductive success.According to the energetic model, lemmings are the most important contributor to the energetic balance of foxes, with a threshold density of 89 lemmings per km2required to switch to a positive energetic balance. When the fox energetic balance goes from positive (high lemming density) to negative (low lemming density), the acquisition rate of gull eggs increases 1.7 times on shores and 9.5 times on islands, a partial refuge and riskier habitat for the predator. Variation in gull hatching success generated by the mechanistic model aligned with empirical observations for both habitat.Our results show that changes in predator energetic balance, translating into a change in attack and capture probabilities, can be a major mechanism underlying predator-mediated effect of lemmings on gulls hatching success.This study is a critical step towards the integration of energetic and landscape characteristics into predator-multiprey models and presents one of the rare mechanistic models parameterized in a natural vertebrate community. Such a model can strongly improve our ability to quantify interaction strengths in multi-species communities.
HAPP: High-Accuracy Pipeline for Processing deep metabarcoding data
Authors: Sundh John , Granqvist Emma , Iwaszkiewicz-Eggebrecht Ela , Manoharan Lokeshwaran , van Dijk Laura J. A. , Goodsell Robert , Godeiro Nerivania N. , Bellini Bruno C. , Łukasik Piotr , Miraldo Andreia , Roslin Tomas , Tack Ayco J. M. , Andersson Anders F. , Ronquist Fredrik 
Published: January 2025

AbstractWe introduce HAPP, a high-accuracy pipeline for processing deep metabarcoding data, leveraging data richness to enhance the signal-to-noise-ratio. Starting with denoised amplicon sequence variants, the pipeline consists of four steps: (1) additional chimera removal, using UCHIME and a strict sample-based approach; (2) taxonomic annotation, combiningk-mer matching (SINTAX) to a reference library with phylogenetic placement (EPA-NG) on a reference tree; (3) OTU clustering using SWARM, an open-source algorithm with precision and recall comparable to RESL used in circumscribing BOLD BINs; and (4) noise filtering (NUMTs and sequencing errors), using a new algorithm introduced here, NEEAT, which combines “echo” signals across samples with detection of unusual evolutionary signatures among clusters with similar DNA sequences. HAPP computations are parallelized across taxa, making analyses tractable on very large datasets. The performance of HAPP was validated through extensive benchmarks, involving CO1 data from BOLD and Malaise trap data, demonstrating significant improvements over the state of the art.
Two neuropeptide signalings regulate post-mating refusal behavior and reproductive system in male crickets
Authors: Zhu Zhen , Nagata Shinji 
Published: January 2025

AbstractAfter mating, insects always perform mating refusal behavior, termed post-mating refractoriness, due to physiological restrictions. Male crickets,Gryllus bimaculatus, characteristically exhibit 1-hour post-mating refractory stage, controlled by terminal abdominal ganglion. The molecular mechanisms underlying the male-specific precisely timed refractory stage remain elucidated. Here we show that among 28 neuropeptide precursors expressed in the terminal abdominal ganglion,DH31,myosuppressin,allatotropin, andsNPFexhibited male-specific expression based on RT-qPCR andin situhybridization. However, RNA interference experiments showed that only knockdown ofallatotropinandsNPFchanged the duration of the refractoriness. Furthermore,allatotropinandsNPFknockdown influenced functions of male reproductive system by inhibiting seminal fluid secretion from male accessory gland and decreasing sperm storage in seminal vesicles, respectively. Knockdown of their receptors caused similar phenotypes. In conclusion, this study demonstrated the regulation of post-mating refusal behavior and reproductive system by Allatotropin and sNPF signalings in male crickets.
Kinesin-1 is highly flexible and adopts an open conformation in the absence of cargo
Authors: Smith Evelyn R. , Turner Emma D. , Abdelhamid Mahmoud A. S. , Craggs Timothy D. , Twelvetrees Alison E. 
Published: January 2025

ABSTRACTKinesin-1 is an essential anterograde microtubule motor protein. The core kinesin motor is a homodimer of two heavy chains; N-terminal motor domains hydrolyse ATP and walk along microtubules, whilst a long elongated coiled-coil stalk and an intrinsically disordered C-terminal tail region bind cargos. Kinesin autoinhibition is key to preventing futile ATP consumption and occurs, at least in part, through direct interactions between N-terminal motor domains and C-terminal inhibitory motifs. Despite significant advances in our understanding of kinesin walking, little is known about the kinesin-1 conformational landscape of the stalk and tail domains. Here we apply solution based biophysical analysis tools to study conformational changes in kinesin-1, with full rotational freedom, and in response to changes in ionic strength, mutations, and the presence of microtubules. This has allowed us to uncover the inherent flexibility in kinesin-1 which gives insights into autoinhibition and the regulation of intracellular transport.
Contrasted effect of climate and anthropogenic change on future invasion risk of a solitary beeAmegilla pulchra
Authors: Dubos Nicolas , Geslin Benoit , Jourdan Hervé , Renault David , Zakardjian Marie 
Published: January 2025

AbstractAmegilla pulchrais a solitary bee from Australia that has recently been spread throughout many islands of the Pacific. The non-regulated human-driven spread of the species may affect the local pollinator communities and their interactions with host plants. We used an ecological niche modelling approach, accounting for non-equilibrium and anthropogenic spread with the most recently recommended approach, and predicted the potential spread of the species under current and future conditions. We expected climate change and increase in human density to offer new suitable environments for the spread of the species. Invasion risks will increase in the future overall, but more in the non-native regions compared to the native region. In the native region, the projected effect of future environmental change was highly contrasted, with increasing invasion risk in human-dense areas but decreasing elsewhere. We found high risks of invasion in eastern Asia and provided a world ranking of entry points for surveillance priority which accounts for maritime traffic. This study highlights potential contrasted effects between climate and anthropogenic change, with differing projections between the native and the non-native regions. Public awareness and prevention will be the key to prevent further spread and mitigate potential adverse effects of the species on island systems. In regions that are already invaded, we propose that habitat restoration is a promising strategy for both the mitigation of the spread and the conservation of local communities.
Molecular architecture of human dermal sleeping nociceptors
Authors: Körner Jannis , Howard Derek , Solinski Hans Jürgen , Moreno Marisol Mancilla , Haag Natja , Fiebig Andrea , Bhuiyan Shamsuddin A. , Toklucu Idil , Bott Raya , Sankaranarayanan Ishwarya , Tavares-Ferreira Diana , Shiers Stephanie , Inturi Nikhil N. , Maxion Anna , Ernst Lisa , Bonaguro Lorenzo , Schulte-Schrepping Jonas , Beyer Marc D. , Stiehl Thomas , Renthal William , Kurth Ingo , Price Theodore , Schmelz Martin , Namer Barbara , Tripathy Shreejoy , Lampert Angelika 
Published: January 2025

AbstractHuman dermal sleeping nociceptors display ongoing activity in neuropathic pain, affecting 10% of the population. Despite advances in rodents, a molecular marker for these mechano-insensitive C-fibers (CMis) in human skin remains elusive, preventing targeted therapy. In this translational Patch-seq study, we combine single-cell transcriptomics following electrophysiological characterization with single-nucleus and spatial transcriptomics from pigs and humans. We functionally identified CMis in pig sensory neurons with patch-clamp using adapted protocols from human microneurography. We identified oncostatin-M-receptor (OSMR) and somatostatin (SST) as marker genes for CMis. Following dermal injection in healthy human volunteers, oncostatin-M, the ligand of OSMR, exclusively modulates CMis. We identified the entire molecular architecture of human dermal sleeping nociceptors, providing new therapeutic targets and the basis for a mechanistic understanding of neuropathic pain.One Sentence SummaryWe identify the molecular architecture and specifically OSMR and SST as molecular markers for human dermal sleeping nociceptors, key players in the generation of neuropathic pain.Short versionIn this Patch-seq study, we identify OSMR and SST as molecular markers for human dermal sleeping nociceptors, key players in the generation of neuropathic pain.