bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure to childhood maltreatment is associated with changes in sperm small non-coding RNA and DNA methylation profiles
Authors: Tuulari Jetro J. , Bourgery Matthieu , Ahonen Annukka , Ahmedani Ammar , Iversen Jo , Koefoed Thomas Gade , Kataja Eeva-Leena , Karlsson Linnea , Barrès Romain , Karlsson Hasse , Kotaja Noora 
Published: April 2023

ABSTRACTBackground:Childhood maltreatment exposure (CME) increases the risk of adverse long-term health consequences for the exposed individual. Animal studies suggest that CME may also influence the health and behaviour in the next generation offspring through CME-driven epigenetic changes in the paternal germ line. The contribution of paternal early life stress on the health of the next generation in humans is not fully elucidated.Methods:In this study, we measured paternal CME using the Trauma and Distress Scale (TADS) questionnaire and mapped sperm-borne sncRNAs expression by small RNA sequencing (small RNA-seq) and DNA methylation (DNAme) in spermatozoa by reduced-representation bisulfite sequencing (RRBS-seq) in males from the FinnBrain Birth Cohort Study. The study design was a (nested) case-control study, high-TADS (TADS ≥ 39, n = 25 for DNAme and n = 14 for small RNA-seq) and low-TADS (TADS ≤ 10, n = 30 for DNAme and n = 16 for small RNA-seq)). Groups were compared to identify specific epigenetic signatures associated with TADS levels in the spermatozoa of participants.Results:Compared to the control group, high CME was associated with altered sperm sncRNA expression and DNAme profiles. Particularly, we identified several tRNA-derived small RNAs (tsRNAs) and miRNAs with markedly changed levels in males with high CME. DNA methylation analysis identified several genomic regions with differentially methylated CpGs between groups. Notably, we identified two epigenetic marks related to brain development with distinct profiles between CME and controls, the miRNA hsa-mir-34c-5p and differential methylation of the region in proximity of FSCN1.Conclusions:This study provides further evidence that early life stress influences the paternal germ line epigenome and supports a possible contribution in the development of the central nervous system of the next generation.
Interplay between fecundity, sexual and growth selection on the spring phenology of European beech (Fagus sylvaticaL.)
Authors: Oddou-Muratorio Sylvie , Bontemps Aurore , Gauzere Julie , Klein Etienne 
Published: April 2023

ABSTRACTBackgroundPlant phenological traits such as the timing of budburst or flowering can evolve on ecological timescales through response to fecundity and viability selection. However, interference with sexual selection may arise from assortative mating. This study aims to investigate how these three components of selection on spring phenology may combine in European beech populations in contrasting environments (high versus low altitude).Methodswe monitored the timing of budburst (TBB) in 339 adult beech trees and estimated their fecundity using spatially explicit mating models. Fecundity selection was infered by regressing fecundities on TBB, while sexual selection was inferred by regressing fecundities on mating opportunities (i.e., TBB mismatch). The correlation between mates for flowering time (i.e., assortative mating) was estimated based on paternity analyses. Morever, TBB and growth were surveyed in 3261 seedlings from 40 families grown planted in a common garden, and viability selection was inferred by regressing growth on TBB.ResultsOverall, directional fecundity selection on female fitness favored trees with earlier TBB. Sexual selection acted only on male fitness through assortative mating favoring trees with mean TBB value (stabilizing selection). In the common garden, early budburst was associated with higher seedling growth. The respective intensities of directional and stabilizing selection varied with the environment: at low altitude, directional selection for earlier phenology was modulated by strong assortative mating and by an interaction effect between TBB an size on female fecundity, whereas at high altitude, directional selection for earlier phenology was reinforced by selection through male fecundity.DiscussionThis study showed that selection through female fecundity and seedlings growth predominantly selected for earlier TBB, while sexual selection on male fitness through assortative mating modulated this trend. This interplay between fecundity and sexual selection calls for an integrative approach to predict the evolution of spring phenology under a changing climate.
RareSH2B3coding variants identified in lupus patients impair B cell tolerance and predispose to autoimmunity
Authors: Zhang Yaoyuan , Morris Rhiannon , Lorenzo Ayla May D. , Meng Xiangpeng , Kershaw Nadia J. , Kiridena Pamudika , Brown Grant J. , Burgio Gaétan , Cappello Jean Y. , Shen Qian , Wang Hao , Turnbull Cynthia M. , Lea-Henry Tom , Stanley Maurice , Yu Zhijia , Ballard Fiona , Chuah Aaron , Lee James C. , Hatch Ann-Maree , Headley Alexander P. , Trnka Peter , Mallon Dominic , Fletcher Jeffery T. , Walters Giles D. , Šestan Mario , Jelušić Marija , Cook Matthew C. , Athanasopoulos Vicki , Fulcher David A. , Babon Jeffrey J. , Vinuesa Carola G. , Ellyard Julia I. 
Published: April 2023

AbstractSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, with a clear genetic component. While most SLE patients carry rare gene variants in lupus risk genes, little is known about their contribution to disease pathogenesis. Amongst them,SH2B3- a negative regulator of cytokine and growth factor receptor signaling – harbors rare coding variants in over 5% of SLE patients. Here we show that unlike the variant found exclusively in healthy controls, mostSH2B3rare variants found in lupus patients are predominantly hypomorphic alleles. Generation of two mouse lines carrying variants orthologous to those found in patients revealed SH2B3 is important to limit the numbers of immature and transitional B cells. Furthermore, hypomorphic SH2B3 was shown to impair negative selection of immature/transitional self-reactive B cells and accelerate autoimmunity in sensitized mice, at least in part due to increased IL-4R signaling and BAFF-R expression. This work identifies a previously unappreciated role forSH2B3in human B cell tolerance and lupus risk.SummaryZhanget al. reveal a role for hypomorphic SH2B3 in lupus risk. The study shows rare and damaging variants identified in lupus patients enable breach of B cell immune tolerance checkpoints and suggests involvement for dysregulated IL-4R signaling and BAFF-R expression.
A Mechanistic Reinterpretation of Fast Inactivation in Voltage-Gated Na+Channels
Authors: Liu Yichen , Bassetto Carlos AZ , Pinto Bernardo I , Bezanilla Francisco 
Published: April 2023

AbstractFast Inactivation in voltage-gated Na+channels plays essential roles in numerous physiological functions. The canonical hinged-lid model has long predicted that a hydrophobic motif in the DIII-DIV linker (IFM) acts as the gating particle that occludes the permeation pathway during fast inactivation. However, the fact that the IFM motif is located far from the pore in recent high-resolution structures of Nav+channels contradicts thisstatus quomodel. The precise molecular determinants of fast inactivation gate once again, become an open question. Here, we provide a mechanistic reinterpretation of fast inactivation based on ionic and gating current data. In Nav1.4 the actualinactivation gateis comprised of two hydrophobic rings at the bottom of S6. These functionin seriesand closing once the IFM motif binds. Reducing the volume of the sidechain in both rings led to a partially conductive inactivated state. Our experiments also point to a previously overlooked coupling pathway between the bottom of S6 and the selectivity filter.
Inconsistent shifts in warming and temperature variability negatively impact avian fitness
Authors: Taff Conor C. , Shipley J. Ryan 
Published: April 2023

ABSTRACTClimate change can create challenging conditions for reproduction by creating mismatches between breeding activity, resource availability, and favorable weather. Phenological advancement may mitigate some of these effects, but it can also result in exposing developing offspring to greater temperature variability during reproduction. We combined >300,000 community science breeding records with data on historical temperature to understand how exposure to extreme climatic events (ECEs) has changed for 24 North American songbirds during breeding. More specifically, we wanted to understand if changes in average spring temperature were associated with when the latest cold-snap or earliest heat-wave occurred across the breeding range and the relationship to individual fitness. While average spring temperature increased universally across North America since 1950, the change in timing of ECEs was inconsistent in both direction and magnitude. Moreover, increase in average temperature did not predict the amount of change in average cold-snap and heat-wave timing. Thus, the current relationships between temperature and temperature variability differ from those experienced historically during breeding. After accounting for covariates, we found that 16 of 24 species had reduced reproductive success when a cold-snap occurred during the breeding attempt and 11 of 24 had reduced success when a heat-wave occurred. Four of the five aerial insectivores included showed marked sensitivity to ECEs, as did all the sallying insectivores. For three widespread species, we found evidence for latitudinal differences in susceptibility to temperature extremes. However, the pattern of sensitivity differed for each species, suggesting that life history details might play an important role in species responses to ECEs. Large-scale patterns and consequences of climate change on breeding birds ultimately result from the accumulated effects of individual susceptibility. Our results add to evidence demonstrating that understanding individual and species level sensitivity and linking them to population level processes is critical for predicting vulnerability to changing climates.
Novel Anammox Bacteria Discovered in the Untapped Subsurface Aquifers
Authors: Wu Jiapeng , Yang Yuchun , Gu Ji-Dong , Hong Yiguo 
Published: April 2023

AbstractAnaerobic ammonium-oxidation (anammox) reaction is a crucial microbial nitrogen (N) transformation process contributing to the global N cycling. The currently known anammox bacteria are affiliated with two families, the marineCa. Scalinduaceae and the freshwaterCa. Brocadiaceae, in thePlanctomycetes. Here we report a discovery of new groups of anammox bacteria consisting of two new orders, two new families, and six new genera within the classCandidatusBrocadiia, all from geochemically distinct aquifer systems. Up to 25 high-quality metagenome-assembled genomes (MAGs) equipped with the core anammox metabolisms were recovered from 13 metagenomic datasets of aquifers and dominated the anammox bacterial communities in distinct aquifers unexpectedly. The comparatively smaller genome size (< 2.6 Mb) and higher coding density (> 85%) likely confer the survival advantage of them by reducing the energy consumption in cell replication and maintenance to increase the nutrient acquisition efficiency in the typically oligotrophic aquifers. Overall, the highly diversity of novel anammox bacterial lineages in aquifer systems largely expands our knowledge of the taxonomic diversity of anammox bacteria and highlights their global importance in aquifer N cycling.
Assembly of Synaptic Protein-DNA Complexes: Critical Role of Non-Specific Interactions
Authors: Vemulapalli Sridhar , Hashemi Mohtadin , Kolomeisky Anatoly B. , Lyubchenko Yuri L. 
Published: April 2023

AbstractThe synaptic protein-DNA complexes, formed by specialized proteins that bridge two or more distant sites on DNA, are critically involved in various genetic processes. However, the molecular mechanism by which the protein searches for these sites and how it brings them together is not well understood. Our previous studies directly visualized search pathways used by SfiI, and we identified two pathways, DNA threading and site-bound transfer pathways, specific to the site search process for synaptic DNA-protein systems. To investigate the molecular mechanism behind these site search pathways, we assembled complexes of SfiI with various DNA substrates corresponding to different transient states and measured their stability using a single-molecule fluorescence approach. These assemblies corresponded to specific-specific (synaptic), non-specific-non-specific (non-specific), and specific-non-specific (pre-synaptic) SfiI-DNA states. Unexpectedly, there was an elevated stability in pre-synaptic complexes assembled with specific and non-specific DNA substrates has been found. To explain these surprising observations, a theoretical approach that describes the assembly of these complexes and compares the predictions with the experiment is developed. The theory explains this effect by utilizing entropic arguments, according to which, after the partial dissociation, the non-specific DNA template has multiple possibilities of rebinding, effectively increasing the stability. Such difference in the stabilities of SfiI complexes with specific and non-specific DNA explains the utilization of threading and site-bound transfer pathways in the search process of synaptic protein-DNA complexes discovered in the time-lapse AFM experiments.
Targeted spectroscopy in the eye fundus
Authors: Lapointe Nicolas , Akitegetse Cléophace , Poirier Jasmine , Picard Maxime , Sauvageau Patrick , Sauvageau Dominic 
Published: April 2023

AbstractSignificanceThe assessment of biomarkers in the eye is rapidly gaining traction for the screening, diagnosis and monitoring of ocular and neurological diseases. Targeted ocular spectroscopy is a new technology that enables the user to concurrently image the eye fundus and acquire high quality spectra from a targeted region –1.5 degrees– within the imaged area. The combination of imaging and high-sensitivity spectroscopy provides structural, compositional, and functional information of selected regions of the eye fundus. This opens the door to new, non-invasive approaches to the detection of biomarkers in the eye.AimThe aim of this study was to demonstrate the multi-modal functionality and validation of the targeted ocular spectroscopy developed. This was done in vitro, using a reference target and a model eye, and in vivo.ApproachImages and spectra from different regions of a reference target and a model eye were acquired and analyzed to validate the system. The same eye model was used to obtain fluorescence images and spectra, highlighting the capability of the system to also perform targeted ocular fluorescence spectroscopy. Subsequently, in vivo imaging and diffuse reflectance spectra were acquired to assess blood oxygen saturation in the optic nerve head and the parafovea of healthy subjects.ResultsTests conducted with the reference target showed that spectral analysis could be accurately performed within specific areas of the imaging space. Moving to the model eye, distinct spectral signatures were observed for the targeted spectral analysis done in the optic disc, the retina and the macula, consistent with the variations in tissue composition and functions between these regions mimicked by the model eye. Further, it was shown that the targeted spectral analysis could also be performed in a fluorescence mode to distinguish various fluorophores present within the imaging space. Finally, in vivo ocular oximetry experiments performed in the optic nerve head and parafovea of healthy patients showed significant differences in blood oxygen saturation between these regions (p = 0.004).ConclusionsEnabling non-invasive, sensitive diffuse reflectance and fluorescence spectroscopy in specific regions of the eye fundus opens the door to a whole new range of monitoring and diagnostic capabilities, from assessment of oxygenation in glaucoma and diabetic retinopathy to photo-oxidation and photo-degradation in age-related macular degeneration.
The Impact of Severe Ventricular Remodeling on Quality-of-Life Outcomes after Transcatheter Aortic Valve Replacement
Authors: Reddy Pavan , Merdler Ilan , Zhang Cheng , Cellamare Matteo , Ben-Dor Itsik , Satler Lowell F. , Rogers Toby , Weintraub William S. , Waksman Ron 
Published: April 2023

AbstractBackgroundAmong patients with aortic stenosis, severe ventricular remodeling can limit the augmentation of flow with exertion, even after valve intervention. While long-term mortality risk has been shown be elevated in this patient population, the effect on quality of life (QoL) improvement has not been studied. Our objective was to determine the effect of severe ventricular remodeling on QoL outcomes after transcatheter aortic valve replacement (TAVR).MethodsAll patients undergoing TAVR from 2011-2021 at our institution were included. Groups were divided according to guideline-recommended cutoffs for left ventricular (LV) wall thickness. Normal or mild wall thickness was designated as non-remodeled (NR) and moderate/severe wall thickness defined the remodeled group (REM). The Kansas City Cardiomyopathy Questionnaire (KCCQ) was utilized to assess QoL and the primary outcome was KCCQ change <5 from baseline to 30 days and 1 year.ResultsWe analyzed 679 patients (NR: N=389, REM: N=290). Baseline KCCQ overall score [OS] trended higher in the NR group (60.1 vs. 56.6, p=0.053). Echocardiographic baseline differed between NR and REM by septal thickness (1.12 cm vs. 1.44 cm, p<0.001), posterior wall thickness (1.08 cm vs. 1.33 cm, p<0.001), and LV internal diastolic diameter (4.34 cm vs. 4.19 cm, p=0.006). The primary outcome was similar between NR and REM at 30 days (31.6% vs. 28.6%, p=0.449) and at 1 year (27.7% vs. 21.5%, p=0.217). NR and REM experienced similar proportions of worsening or no change, small, moderate, and large improvements in KCCQ score (<5, 5-10, 10-19, ≥20, respectively). Both groups experienced similar domain score changes and NYHA improvement. At one year, NR demonstrated greater reduction in 5MWT time compared to REM (−1.98 s vs. -0.2 s, p=0.028). A subgroup analysis of REM patients did not reveal interaction with cavity size, stroke volume, mitral regurgitation, E/A ratio, valvulo-arterial impedance, or hyperdynamic ejection fraction.ConclusionsPatients with severe ventricular remodeling and aortic stenosis have similar QoL changes after intervention compared to patients without significant remodeling. Findings from this study support aortic valve intervention irrespective of ventricular remodeling.What is Known; What the Study AddsWhat is Known?Ventricular remodeling occurs due to aortic stenosis, limiting cardiac output even after valve replacement.The effect of ventricular remodeling on quality of life after TAVR is unknown.What the Study AddsQuality of life improvement occurred in the majority of patients undergoing TAVR, with and without severe ventricular remodeling, and to a similar degree regardless of remodeling.From a quality-of-life perspective, TAVR should remain a viable consideration for patients with severe ventricular remodeling
APOL1Risk Variants Associate with the Prevalence of Stroke in African American Current and Past Smokers
Authors: Mustra Rakic Jelena , Pullinger Clive R. , Van Blarigan Erin L. , Movsesyan Irina , Oestreicher Stock Eveline , Malloy Mary J. , Kane John P. 
Published: April 2023

ABSTRACTIntroductionAmong African Americans, tobacco smokers have 2.5 times higher risk for stroke compared to non-smokers; the tobacco-related stroke risk being higher than in other races/ethnicities. About one half of African Americans carry at least one of two genetic variants (G1 and G2; rare in other races) of apolipoprotein L1 (apoL1), a component of high-density lipoproteins. Several studies showedAPOL1G1/G2 risk variants associate with stroke. However, the role ofAPOL1variants in tobacco-related stroke is unknown.MethodsIn a cross-sectional study, we examined whetherAPOL1risk variants modify the relationship between smoking and stroke in 513 African American adults (median age 58 years, 52% female) recruited through the University of California, San Francisco Lipid Clinic. Using DNA, plasma, and questionnaires we determinedAPOL1variants, smoking status, and history of stroke. Using unstratified and stratified multivariable logistic regression models we examined the association between smoking history (eversmokers vs.neversmokers) and odds of stroke overall, and among carriers of risk variants and non-carriers, separately.ResultsAmong participants, 41% wereever(currentandpast) smokers, 54% were carriers of theAPOL1risk variant, and 41 have had stroke. In all stroke cases, where full medical records were available, stroke types were determined to be an ischemic, and not hemorrhagic, stroke. The association of smoking history and stroke differed byAPOL1genotype status in the unstratified model (Pinteraction term=0.016). Among carriers of risk variants,eversmokers had odds ratio (OR) =2.88 for stroke compared toneversmokers (P=0. 0.038). The OR for stroke comparingevervs.neversmokers showed a dose-response trend among carriers of one risk allele of 2.35 and two risk alleles of 4.96. Among non-carriers, smoking history was not associated with a stroke.ConclusionIn conclusion, current and past smokers who carryAPOL1G1 and/or G2 risk variants may be more susceptible to stroke, in particular ischemic stroke, among African Americans.
Expression pattern of nicotinic acetylcholine receptor subunit transcripts in neurons and astrocytes in the ventral tegmental area and locus coeruleus
Authors: Gao Runbo , Schneider Amelia M. , Mulloy Sarah M. , Lee Anna M. 
Published: April 2023

AbstractAcetylcholine is the endogenous agonist for the neuronal nicotinic acetylcholine receptor (nAChR) system, which is involved in attention, memory, affective behaviors, and substance use disorders. Brain nAChRs are highly diverse with 11 different subunits that can form multiple receptor subtypes, each with distinct receptor and pharmacological properties. Different neuronal cell types can also express different nAChR subtypes, resulting in highly complex cholinergic signaling. Identifying which nAChR subunit transcripts are expressed in cell types can provide an indication of which nAChR combinations are possible and which receptor subtypes may be most pharmacologically relevant to target. In addition to differences in expression across cell types, nAChRs also undergo changes in expression levels from adolescence to adulthood. In this study, we used fluorescentin situhybridization to identify and quantify the expression of α4, α5, α6, β2 and β3 nAChR subunit transcripts in dopaminergic, GABAergic, glutamatergic, and noradrenergic neurons and astrocytes in the ventral tegmental area (VTA) and locus coeruleus (LC) in adult and adolescent, male and female C57BL/6J mice. There were distinct differences in the pattern of nAChR subunit transcript expression between the two brain regions. LC noradrenergic neurons had high prevalence of α6, β2 and β3 expression, with very low expression of α4, suggesting the α6(non-α4)β2β3 receptor as a main subtype in these neurons. VTA astrocytes from adult mice showed greater prevalence of α5, α6, β2 and β3 transcript compared with adolescent mice. These data highlight the complex nAChR expression patterns across brain region and cell type.