bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eccentric exercise ≠ eccentric contraction
Authors: Tecchio Paolo , Raiteri Brent J. , Hahn Daniel 
Published: November 2023

AbstractWhether eccentric exercise involves active fascicle stretch is unclear due to muscle-tendon unit (MTU) series elasticity. Therefore, this study investigated the impact of changing the activation timing and level (i.e., pre-activation) on muscle fascicle kinematics and kinetics of the human tibialis anterior during dynamometer-controlled maximal voluntary MTU-stretch-hold contractions. B-mode ultrasound and surface electromyography were employed to assess muscle fascicle kinematics and muscle activity levels, respectively. While joint kinematics were similar for MTU-stretch-hold contractions, increasing pre-activation increased fascicle shortening and stretch amplitudes (9.9 - 23.2 mm,p≤ 0.015). This led to increasing positive and negative fascicle work with increasing pre-activation. Despite significantly different fascicle kinematics, similar peak fascicle forces during stretch occurred at similar fascicle lengths and joint angles regardless of pre-activation. Similarly, residual force enhancement (rFE) following MTU stretch was not significantly affected (6.5–7.6 %,p= 0.559) by pre-activation, but rFE was strongly correlated with peak fascicle force during stretch (rrm= 0.62,p= 0.003). These findings highlight that apparent eccentric exercise causes shortening-stretch contractions at the fascicle level rather than isolated eccentric contractions. The constant rFE despite different fascicle kinematics and kinetics suggests that a passive element was engaged at a common muscle length among conditions (e.g., optimal fascicle length). Although it remains unclear whether different fascicle mechanics trigger different adaptations to eccentric exercise, this study emphasizes the need to consider MTU series elasticity to better understand the mechanical drivers of adaptation to exercise.New & NoteworthyApparent eccentric exercises do not result in isolated eccentric contractions, but shortening-stretch contractions at the fascicle level. The amount of fascicle shortening and stretch depend on the pre-activation during the exercise andcannotbe estimated from the muscle-tendon unit or joint kinematics. As different fascicle mechanics might trigger different adaptations to eccentric exercise, muscle-tendon unit series elasticity and muscle pre-activation need to be considered when eccentric exercise protocols and designed and evaluated.
Personality and behavioral syndromes in two species of fruit bats (Chiroptera: Phyllostomidae)
Authors: Miguel Pedro Henrique , Batisteli Augusto F. , Cruz-Neto Ariovaldo P. 
Published: November 2023

ABSTRACTPersonality indicates consistency in individual behavioral responses across different contexts, and different personality traits may be correlated in behavioral syndromes. Studies on personality have important consequences for conservation ecology and, despite the ecological relevance of fruit bats, rare studies have tested the existence of personality and behavior syndromes in this group. In this context, this study aims to test whether the Neotropical fruit batsArtibeus lituratusandCarollia perspicillatapresent (1) individual repeatability (i.e. personality) related to the behaviors: activity, aggressiveness and boldness and (2) correlation between these personality axes, constituting behavioral syndromes. For each species, 27 adult males were captured and immediately placed in cloth bags individually, and we measured aggressiveness as the time they struggled in the bag within a 180-second interval. Bats were then kept in individual cages in a climate-controlled room for 48-h, after which we filmed them for 30 min in a flight tent as an activity test. In the boldness test, we quantified the latency to each animal to start feeding in front of an observer, assuming that bolder individuals had lower latency to feed. All tests were repeated after 48-h to analyze repeatability. We found high individual repeatability of aggressiveness, activity and boldness for both species, but different behavioral syndromes for each of them. ForC. perspicillata, the three behaviors were correlated to each other, with the most aggressive individuals being bolder and more active. ForA. lituratus, aggressiveness and boldness were also positively correlated, but activity did not correlate with the other two behaviors. Considering these different syndromes, our results suggest thatC. perspicillatahas less variation in behavioral profiles thanA. lituratusprobably as a result of species-specific selective pressures. The existence of behavioral syndromes in these frugivorous bats contributes to understanding the importance of individual variation on the ecological functions provided by seed dispersers.
Sex differences in intrinsic functional cortical organization reflect differences in network topology rather than cortical morphometry
Authors: Serio Bianca , Hettwer Meike D. , Wiersch Lisa , Bignardi Giacomo , Sacher Julia , Weis Susanne , Eickhoff Simon B. , Valk Sofie L. 
Published: November 2023

ABSTRACTBrain size robustly differs between sexes. However, the consequences of this anatomical dimorphism on sex differences in intrinsic brain function remain unclear. We investigated the extent to which sex differences in intrinsic cortical functional organization may be explained by differences in cortical morphometry, namely brain size, microstructure, and the geodesic distances of connectivity profiles. For this, we computed a low dimensional representation of functional cortical organization, the sensory-association axis, and identified widespread sex differences. Contrary to our expectations, observed sex differences in functional organization were not fundamentally associated with differences in brain size, microstructural organization, or geodesic distances, despite these morphometric properties beingper seassociated with functional organization and differing between sexes. Instead, functional sex differences in the sensory-association axis were associated with differences in functional connectivity profiles and network topology. Collectively, our findings suggest that sex differences in functional cortical organization extend beyond sex differences in cortical morphometry.TeaserInvestigating sex differences in functional cortical organization and their association to differences in cortical morphometry.
Kinexinfers causal kinases from phosphoproteomics data
Authors: Valeanu Alexandra , Golz Verena , Avila David W. , Tzouros Manuel , Siebourg-Polster Juliane , Badi Laura , Zhang Jitao David 
Published: November 2023

AbstractMotivationPhosphoproteomics data are essential for characterising signalling pathways, identifying drug targets, and evaluating efficacy and safety profiles of drug candidates. Emerging resources, including a substrate-specificity atlas and drug-induced phosphoproteomics profiles, may transform the inference of causal kinases. However, there is currently no open-source software that leverages insights derived from these resources.ResultsWe introduceKinex,a workflow implemented in the same-name Python package, which infers causal serine/threonine kinases from phosphoproteomics data. Kinex allows users to score kinase-substrate interactions, perform enrichment analysis, visualise candidates of causal regulators, and query similar profiles in a database of drug-induced kinase activities. Analysing seven published studies and one newly generated dataset, we demonstrate that analysis with Kinex recovers causal effects of perturbations and reveals novel biological insights. We foresee that Kinex will become an indispensable tool for basic and translational research including drug discovery.AvailabilityKinex is released with the GNU General Public License and available athttps://github.com/bedapub/kinex.
IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections
Authors: Creusat Florent , Jouan Youenn , Gonzalez Loïc , Barsac Emilie , Ilango Guy , Lemoine Roxane , Soulard Daphnée , Boisseau Chloé , Guillon Antoine , Lin Qiaochu , de Amat Herbozo Carolina , Sencio Valentin , Winter Nathalie , Trottein François , Si-Tahar Mustapha , Briard Benoit , Mallevaey Thierry , Faveeuw Christelle , Baranek Thomas , Paget Christophe 
Published: November 2023

AbstractNeutrophil subsets endowed with regulatory/suppressive properties are widely regarded as deleterious immune cells that can jeopardize antitumoral response and/or antimicrobial resistance. Here, we describe a sizeable fraction of neutrophils characterized by the expression of Programmed death-ligand 1 (PD-L1) in biological fluids of humans and mice with severe viral respiratory infections (VRI). Biological and transcriptomic approaches indicated that VRI-driven PD-L1+neutrophils are endowed with potent regulatory functions and reduced classical antimicrobial properties, as compared to their PD-L1-counterpart. VRI-induced regulatory PD-L1+neutrophils were generated in the bone marrow in an IFN-γ-dependent manner and were quickly mobilized into the inflamed lungs where they fulfilled their maturation. Neutrophil depletion and PD-L1 blockade during experimental VRI resulted in higher mortality, increased local inflammation and reduced expression of resolving factors. These findings suggest that PD-L1+neutrophils are important players in disease tolerance by mitigating local inflammation during severe VRI and that they may constitute relevant targets for future immune interventions.
Generation of site-specifically labelled fluorescent human XPA to investigate DNA binding dynamics during nucleotide excision repair
Authors: Kuppa Sahiti , Corless Elliot , Caldwell Colleen , Spies Maria , Antony Edwin 
Published: November 2023

AbstractNucleotide excision repair (NER) promotes genomic integrity by correcting bulky DNA adducts damage caused by external factors such as ultraviolet light. Defects in NER enzymes are associated with pathological conditions such as Xeroderma Pigmentosum, trichothiodystrophy, and Cockayne syndrome. A critical step in NER is the binding of the Xeroderma Pigmentosum group A protein (XPA) to the DNA adduct. To better capture the dynamics of XPA interactions with DNA during NER we have utilized the fluorescence enhancement through non-canonical amino acids (FEncAA) approach. 4-azido-L-phenylalanine (4AZP) was incorporated at Arg-153 in human XPA and conjugated to Cy3 using strain-promoted azide-alkyne cycloaddition. The resulting fluorescent human XPA protein (hXPACy3) shows no loss in DNA binding activity and generates a robust change in fluorescence upon binding to DNA. Here we describe methods to generate hXPACy3and detail experimental conditions required to stably maintain the protein during biochemical and biophysical studies.
Heritability of complex traits in sub-populations experiencing bottlenecks and growth
Authors: Taylor Cameron S. , Lawson Daniel J. 
Published: November 2023

1AbstractPopulations that have experienced a bottleneck are regularly used in Genome Wide Association Studies (GWAS) to investigate variants associated with complex traits. It is generally understood that these isolated sub-populations may experience high frequency of otherwise rare variants with large effect size, and therefore provide a unique opportunity to study said trait. However, the demographic history of the population under investigation affects all SNPs that determine the complex trait genome-wide, changing its heritability and genetic architecture. We use a simulation-based approach to identify the impact of the demographic processes of drift, expansion, and migration on the heritability of complex trait. We show that demography has considerable impact on complex traits. We then investigate the power to resolve heritability of complex traits in GWAS studies subjected to demographic effects. We find that demography is an important component for interpreting inference of complex traits and has a nuanced impact on the power of GWAS. We conclude that demographic histories need to be explicitly modelled in order to properly quantify the history of selection on a complex trait.
Experience-dependent place-cell referencing in hippocampal area CA1
Authors: Qian Fish Kunxun , Li Yiding , Magee Jeffrey C. 
Published: November 2023

AbstractCA1 hippocampal place cells (PCs) are known for using both self-centric (egocentric) and world-centric (allocentric) reference frames to support a cognitive map1,2. The mechanism of PC referencing and the role of experience in this process, however, remain poorly understood3–5. Here we longitudinally recorded the activity of CA1 PCs while mice performed a spatial learning task. In a familiar environment, the CA1 representation consisted of PCs that were referenced to either spatial locations (allocentric PCs) or mouse running (egocentric PCs) in approximately equal proportions. In a novel environment, however, the CA1 representation became predominately egocentrically referenced. Notably, individual allocentric PCs in a familiar environment adaptively switched reference frames to become egocentric in a novel environment. In addition, intracellular membrane potential recordings revealed that individual CA1 neurons simultaneously received both ego- and allo-centric synaptic inputs, and the ratio of these two input streams correlated with the level of individual PC referencing. Furthermore, behavioral timescale synaptic plasticity6,7(BTSP) was an active participant in shaping PC referencing through the rapid adjustment of synaptic weights on many PCs. Together, these results suggest that experience-dependent adjustment of synaptic input shapes ego and allocentric PC referencing to support a flexible cognitive map in CA1.
Genome-wide Quantification of Polycistronic Transcription inLeishmania major
Authors: Grünebast Janne , Lorenzen Stephan , Clos Joachim 
Published: November 2023

AbstractLeishmania majoris a human-pathogenic, obligate parasite and the etiological agent of the most prevalent, cutaneous form of leishmaniasis, which is an important neglected, tropical disease with ∼1.2 Mio new infections per year.Leishmania, and the whole order Trypanosomatida, are early eukaryotes with highly diverged gene expression and regulation pathways, setting them apart from their mammalian hosts and from most other eukaryotes. Using precision run-on sequence analysis, we performed a genome-wide mapping and density analysis of RNA polymerases in isolated nuclei of the protozoan parasiteLeishmania major. We map transcription initiation sites within the chromosomes and correlate them with known sites of chromatin modifications. We confirm continuous, polycistronic RNA synthesis in all RNA polymerase II-dependent gene arrays but find varying RNA polymerase activities in polycistronic transcription units (PTUs), excluding gene-specific transcription regulation, but not PTU-specific variations as possible targets of modulatory pathways. Lastly, we find evidence for transcriptional pausing of all three RNA polymerase classes, hinting at a possible mechanism of transcriptional regulation.Significance StatementLeishmaniaspp. are pathogens of humans and animals and cause one of the most important neglected tropical diseases. Regulation of gene expression inLeishmaniabut also in the relatedTrypanosomais radically different from all eukaryotic model organisms, dispensing with regulated, gene-specific transcription, and relying instead on highly regulated translation. Our work sheds light on the initiation, elongation and termination of transcription, maps unidirectional, polycistronic transcription units, provides evidence for transcriptional pausing at or near starting points of RNA synthesis, and quantifies the varying transcription rates of the polycistronic transcription units. Our results will further the understanding of these important pathogens and should provide a valuable ressource for researchers in the field of eukaryotic microbiology.
Kisspeptin modulates sex-like phenotypes in the neonatal period
Authors: Neves João R. , Castelo-Branco Miguel , Gonçalves Joana 
Published: November 2023

ABSTRACTIn recent years, our understanding of the physiological role of kisspeptin (Kiss1) has evolved significantly, revealing its pivotal role in shaping sexual differentiation within the brain. Predominantly expressed in the hypothalamus, Kiss1 plays a crucial role in regulating release of the gonadotrophin-releasing hormone (GnRH). Kisspeptin 1 receptor (Kiss1R) exhibits sex-dependent expression in various brain regions, including the medial amygdala and preoptic area (POA) of the hypothalamus, regions underlying sexual development. Importantly, in the critical period for the sexual development in mammals occurs a synchronized surge of Kiss1 and testosterone, highlighting its importance in sexual dimorphism. It has been suggested that the neonatal Kiss1 surge is associated with the buildup of gender-linked social development. We investigated this hypothesis by testing the effect of neonatal blockage of Kiss1 signaling on the sex-like phenotype in rats. We postulate that Kiss1 actions are both time and region-dependent, particularly during the neonatal period, having lasting impact on social interactions.For that we injected intracerebroventricular (ICV) a Kiss1R antagonist, Kp234, in the first 24h of life. Our data showed, that neonatal Kiss1 is determinant in modulating physiological responses, such as weight and testis development in males (N: males Veh = 10; males Kp234 = 10). Also, we document, for the first time, that Kiss1 modulates the testosterone surge in males and inhibits it in females (N: males Vehicle = 3; males Kp234 = 4; females Vehicle = 3; females Kp234 = 4). Furthermore, neonatal Kiss1 blockade modulated the sexual drive in, while the sexual performance in both sexes is maintained males (N: males Vehicle = 8; males Kp234 = 9; females Vehicle = 7; females Kp234 = 8).In conclusion, this study underscores the significance of Kiss1 during the neonatal period, a critical phase for sexual differentiation and neuroplasticity. Neonatal Kiss1 emerges as a key player in the development of a sex-like phenotype in rats. Additionally, our findings show dimorphic patterns in Kiss1 influence. This work raises the intriguing possibility that the early influence of Kiss1 in brain circuitry is pivotal in the modulation of gender and plays a role in the social construction of the bimodality of gender identity.
Successful spread ofmcr-1-bearing IncX4 plasmids is associated with variant in replication protein of IncX4 plasmids
Authors: Yi Lingxian , Yu Kaiyang , Gao Guolong , Zhang Rongmin , Lv Luchao , Yu Daojin , Yang Jun , Liu Jian-Hua 
Published: November 2023

AbstractIncX4 plasmids are one of the most epidemiologically successful vehicles formcr-1spread. Here we found that the IncX4 plasmids carried two different replication proteins encoded by genespir-1andpir-2, respectively, butmcr-1was only carried by IncX4 plasmid encodingpir-1. The copy number ofpir-2encoding plasmids (3.15±0.9 copies) are higher than that ofpir-1encoding plasmids (0.85±0.5 copies). Whenmcr-1was cloned into IncX4 plasmid encodingpir-2, the higher copy number of these plasmids resulted in increased expression ofmcr-1and a greater fitness burden on their host cells. However, these plasmids exhibited a lower rate of invasion into the bacterial population compared tomcr-1positive plasmids encoding thepir-1gene. These findings collectively explain the absence ofmcr-1in all IncX4 plasmids encodingpir-2. Our results further confirmed that low-copy numbers are important for the spread ofmcr-1plasmid from the perspective of natural evolution.
Rationale and Design of the BECA Project: Smartwatch-based Activation of the Chain of Survival for Out-of-Hospital Cardiac Arrest
Authors: Hup Roelof G. , Linssen Emma C. , Eversdijk Marijn , Verbruggen Bente , Bak Marieke A.R. , Habibovic Mirela , Kop Willem J. , Willems Dick L. , Dekker Lukas R.C. , Haakma Reinder , Vernooij Carlijn A. , Kooy Tom A. , Tan Hanno L. , Vullings Rik 
Published: November 2023

ABSTRACTIntroductionOut-of-hospital cardiac arrest (OHCA) is a major health problem, and the overall survival rate is low (4.6%-16.4%). The initiation of the current chain of survival depends on the presence of a witness of the OHCA, which is not present in 29.7%-63.4% of the cases. Furthermore, a delay in starting this chain is common in witnessed OHCA. This project aims to reduce morbidity and mortality due to OHCA by developing a smartwatch-based solution to expedite the chain of survival in the case of (un)witnessed OHCA.Methods and analysisWithin the BECA (BEating Cardiac Arrest) project, we aim to develop a demonstrator product that can detect OHCA using photoplethysmography and accelerometer analysis, and autonomously alert emergency medical services. A target group study will be performed to determine who benefits the most from this product. Furthermore, several clinical studies will be conducted to capture or simulate data on OHCA cases, as to develop detection algorithms and validate their diagnostic performance. Volunteers will be asked to simulate OHCA by interrupting radial arterial and venous blood flow by blood pressure cuff inflation while lying still. Data will also be captured during cardiac electrophysiologic and implantable cardioverter defibrillator (ICD) testing procedures. In addition, patients at risk for OHCA are recruited to acquire measurements over a longer period. Moreover, studies on psychosocial and ethical acceptability will be conducted, consisting of surveys, focus groups, and interviews. These studies will focus on end-user preferences and needs, to ensure that important individual and societal values are respected in the design process.Ethics and disseminationEthical approval or waivers will be sought from the research ethics committees of the different institutions. Written informed consent will be obtained from the participants of all studies. Study findings will be submitted to international peer-reviewed journals and will be presented at international scientific conferences.STRENGTHS AND LIMITATIONSStrengths-This research project aims to develop unobtrusive technology that could save lives by autonomously alerting emergency medical services in case of out-of-hospital cardiac arrest.-The project includes a broad range of aspects to maximize the technology’s chance of adoption: clinical, technical, psychological, and ethical.-The project aims for the inclusion of a wide and diverse research sample and the involvement of different stakeholder groups to minimize bias and ensure accessibility for everyone in society.Limitations-Smartwatch-obtained data of OHCA cases is scarce and hard to acquire: the more realistic the data is, the more difficult its acquisition is.