bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeat-induced point mutation and gene conversion coinciding with heterochromatin shape the genome of a plant pathogenic fungus
Authors: Komluski Jovan , Habig Michael , Stukenbrock Eva H. 
Published: December 2022

AbstractMeiosis is associated with genetic changes in the genome - via recombination, gene conversion, and mutations. The occurrence of gene conversion and mutations during meiosis may further be influenced by the chromatin conformation, in analogy to what is known for mutations during mitosis. To date, however, the exact distribution and type of meiosis-associated changes and the role of the chromatin conformation in this context is largely unexplored. Here, we determine recombination, gene conversion, andde novomutations using whole-genome sequencing of all meiotic products of 23 individual meioses inZymoseptoria tritici, an important pathogen of wheat. We could confirm a high genome-wide recombination rate of 65 cM/Mb and see higher recombination rates on the accessory compared to core chromosomes. A substantial fraction of 0.16% of all polymorphic markers was affected by gene conversions, showing a weak GC-bias, and occurring at higher frequency in regions of constitutive heterochromatin, indicated by the histone modification H3K9me3. Thede novomutation rate associated with meiosis was approx. three orders of magnitude higher than the corresponding mitotic mutation rate. Importantly, repeat-induced point mutation (RIP), a fungal defense mechanism against duplicated sequences, is active inZ. triticiand responsible for the majority of thesede novomeiotic mutations. Our results indicate that the genetic changes associated with meiosis are a major source of variability in the genome of an important plant pathogen and shape its evolutionary trajectory.ImportanceThe impact of meiosis on the genome composition via gene conversion and mutations is mostly poorly understood, in particular for non-model species. Here, we sequenced all four meiotic products for 23 individual meioses and determined the genetic changes caused by meiosis for the important fungal wheat pathogenZymoseptoria tritici. We found a high rate of gene conversions and an effect of the chromatin conformation on gene conversion rates. Higher conversion rates were found in regions enriched with the H3K9me3 – a mark for constitutive heterochromatin. Most importantly, meiosis was associated with a much higher frequency ofde novomutations than mitosis. 78% of the meiotic mutations were caused by repeat-induced point mutations – a fungal defense mechanism against duplicated sequences. In conclusion, the genetic changes associated with meiosis are therefore a major factor shaping the genome of this fungal pathogen.
Labour market participation after a sickness absence due to cancer: a dynamic cohort study in Catalonia (Spain)
Authors: Ayala-Garcia Amaya , Benavides Fernando G. , Serra Laura 
Published: December 2022

AbstractBackgroundConsequences of cancer on working life until retirement age remain unclear. This study aimed to compare labour market participation patterns in workers with a sickness absence (SA) due to cancer versus those with no SA and those with SA due to other diseases.MethodsRegistry-based cohort study of social security affiliates in Catalonia from 2012-2018. Cases consisted of workers with SA due to cancer between 2012-2015 (N=516) and were individually age- and sex-matched with an affiliate with SA due to other diagnoses and a worker without SA. All workers (N=1,548, 56% women) were followed-up until the end of 2018. Sequence analysis, optimal matching, and multinomial logistic regression were used to identify and assess the probability of future labour market participation patterns (LMPP). All analyses were stratified by sex.ResultsCompared with workers with SA due to cancer, male workers without SA and SA due to other causes showed lower probability of being in the LMPP of death (aRRR 0.02, 95% CI: 0.00−0.16; aRRR 0.17, 95% CI: 0.06−0.46, respectively), and in women lower probability of increasing permanent disability and death (aRRR 0.24, 95% CI: 0.10−0.57; aRRR 0.39, 95% CI: 0.19−0.83). Compared to workers with SA due to cancer, risk of future retirement was lower in workers with no SA (women aRRR 0.60, 95% CI: 0.22−1.65; men aRRR 0.64, 95%CI: 0.27−1.52).ConclusionsWorkplaces should be modified to the needs of cancer survivors in order to prevent more frequent early exit of labour market due to retirement and permanent disability when possible.Key MessagesWhat is already known on this topic. After the treatment stage and sickness absence (SA) period, some cancer survivors face adverse effects that affect their long-term work capacity and increase the likelihood of an early exit from labour market.What this study addsLabour market participation after cancer show that workers with an SA due to cancer manage to return to work and have stable employment. Anyhow, they show a higher likelihood of early retirement, receiving permanent disability benefits, and of dying than workers without a previous SA.How this study might affect research, practice or policyCancer survivors require their new health status to be considered when return to work. Actions should be taken in order to regulate programmes that help them remain working when possible and desired.
High-frequency longitudinal white matter diffusion- & myelin-based MRI database: reliability and variability
Authors: Edde Manon , Theaud Guillaume , Dumont Matthieu , Théberge Antoine , Valcourt-Caron Alex , Gilbert Guillaume , Houde Jean-Christophe , Maltais Loika , Rheault François , Spagnolo Federico , Barakovic Muhamed , Magon Stefano , Descoteaux Maxime 
Published: December 2022

AbstractAssessing the consistency of quantitative MRI measurements is critical for inclusion in longitudinal studies and clinical trials. Intraclass coefficient correlation and coefficient of variation were used to evaluate the different consistency aspects of diffusion- and myelinbased MRI measures. Multi-shell diffusion and inhomogeneous magnetization transfer datasets were collected from twenty healthy adults at a high-frequency of five MRI sessions. The consistency was evaluated across whole bundles and the track-profile along the bundles. The impact of the fiber populations on the consistency was also evaluated using the number of fiber orientations map. For whole and profile bundles, moderate to high reliability of diffusion and myelin measures were observed. We report higher reliability of measures for multiple fiber populations than single. The overall portrait of the most consistent measurements and bundles drawn from a wide range of MRI techniques presented here will be particularly useful for identifying reliable biomarkers capable of detecting, monitoring and predicting white matter changes in clinical applications and has the potential to inform patient-specific treatment strategies.Key pointsReliability and variability are excellent to good for DWI measurements, and good to moderate for MT measures for whole bundles and along the bundles.The number of fiber populations affects the reliability and variability of the MRI measurements.The reliability and variability of MRI measurements are also bundle dependent.
Bright and sensitive red voltage indicators for imaging action potentials in brain slices and pancreatic islets
Authors: Han Yi , Yang Junqi , Li Yuan , Chen Yu , Ren Huixia , Ding Ran , Qian Weiran , Ren Keyuan , Xie Beichen , Deng Mengying , Xiao Yinghan , Chu Jun , Zou Peng 
Published: December 2022

AbstractAs fast developing tools for observing cellular membrane potential, red-emitting genetically encoded voltage indicators (GEVIs) reduce auto-fluorescence background, allow multiplexed recordings, and enable all-optical electrophysiology, but have been limited by either insensitivity or dimness. Here, we report a pair of red GEVIs, Cepheid1b/s, with improved sensitivity, brightness, and photostability. Cepheid1 indicators faithfully report cellular excitability in pancreatic islets and neural activity in acute brain slices.
Distal regulatory sequences contribute to diversity in brain oxytocin receptor expression patterns and social behavior
Authors: Zhang Qi , Nagai Luis Augusto Eijy , Tsukamoto Mina , Kandasamy Lenin C. , Inoue Kiyoshi , Pires Maria F. , Shin Minsoo , Nagasawa Yutaro , Sambuu Tsetsegee , Ogawa Sonoko , Nakai Kenta , Itohara Shigeyoshi , Young Larry J 
Published: December 2022

SummaryThe oxytocin receptor (OXTR) modulates social behaviors in a species-specific manner. Remarkable inter- and intraspecies variation in brain OXTR distribution are associated with diversity in social behavior. To test the causal effect of developmental variation of OXTR expression on the diversity of social behaviors, and to investigate potential genetic mechanisms underlying the phylogenetic plasticity in brainOxtrexpression, we constructed BAC transgenic mice harboring the entire prairie voleOxtrlocus with the entire surrounding intergenic regulatory elements. Eight independent “volized”prairie vole-Oxtr(pvOxtr) mouse lines were obtained; remarkably, each line displayed a unique pattern of brain expression distinct from mice and prairie voles. FourpvOxtrlines were selected for further investigation. Despite robust differences in brain expression,Oxtrexpression in mammary tissue was conserved across lines. These results and topologically associating domain (TAD) structure analysis suggest thatOxtrexpression patterns in brain, but not other tissues, involve contributions of distal regulatory elements beyond our BAC construct. Moreover, “volized” mouse lines with different brainOxtrexpression patterns showed differences in partner preference and maternal behaviors. We speculate that transcriptional hypersensitivity to variable distal chromosomal sequences through long-distance interactions with proximal regulatory elements may contribute to “evolvability” of brainOxtrexpression. The “evolvability” of brainOxtrexpression constitutes a transcriptional mechanism to generate variability in brain OXTR which, through natural selection, can generate diversity in adaptive social behaviors while preserving critical peripheral expression. Transcriptional lability of brainOXTRexpression may also contribute to variability in social phenotype in humans, including psychiatric outcomes.
Actin contraction controls nuclear blebbing and rupture independent of actin confinement
Authors: Pho Mai , Berrada Yasmin , Gunda Aachal , Lavallee Anya , Chiu Katherine , Padam Arimita , Currey Marilena L. , Stephens Andrew D. 
Published: December 2022

AbstractThe nucleus is a mechanically stable compartment of the cell that contains the genome and performs many essential functions. Nuclear mechanical components chromatin and lamins maintain nuclear shape, compartmentalization, and function by resisting antagonistic actin contraction and confinement. However, studies have yet to compare chromatin and lamins perturbations side-by-side as well as modulated actin contraction while holding confinement constant. To accomplish this, we used NLS-GFP to measure nuclear shape and rupture in live cells with chromatin decompaction (VPA), loss of lamin B1 (LMNB1-/-), and loss of lamin A/C (LMNA-/-). We then modulated actin contraction while maintaining actin confinement measured by nuclear height. Wild type, chromatin decompaction, and lamin B1 null present bleb-based nuclear deformations and ruptures dependent on actin contraction and independent of actin confinement. Inhibition of actin contraction by Y27632 decreased nuclear blebbing and ruptures to near 0% of cells while activation of actin contraction by CN03 increased the frequency of ruptures by nearly two-fold. However, lamin A/C null results in overall abnormal shape, but similar blebs and ruptures as wild type which were unaffected by actin contraction modulation. Actin contraction control of nuclear shape and ruptures showed that DNA damage levels were more correlated with perturbed nuclear shape than they were with changes in nuclear ruptures. We reveal that lamin B1 is a chromatin decompaction phenotype because using GSK126, which mimics the loss of facultative heterochromatin in lamin B1 null, is sufficient to phenocopy increased nuclear blebbing and ruptures. Furthermore, even though blebs and ruptures in lamin A/C null cells are insensitive to actin contraction, they do have the capacity to form increased levels of nuclear blebs and bleb-based ruptures, shown by treating with VPA. Thus, nuclear bleb formation and bleb-based nuclear ruptures are driven by actin contraction and independent of changes in actin confinement.
Crosstalk of platelets with macrophages and fibroblasts aggravates inflammation, aortic wall stiffening and osteopontin release in abdominal aortic aneurysm
Authors: Wagenhäuser MU , Mulorz J , Krott KJ , Bosbach A , Feige T , Rhee YH , Chatterjee M , Petzold N , Böddeker C , Ibing W , Krüger I , Popovic AM , Roseman A , Spin JM , Tsao PS , Schelzig H , Elvers M 
Published: December 2022

AbstractAbdominal aortic aneurysm (AAA) is a highly lethal disease with progressive dilatation of the abdominal aorta accompanied by degradation and remodelling of the vessel wall due to chronic inflammation. Platelets play an important role in cardiovascular diseases but their role in AAA is poorly understood. The present study revealed that platelets play a crucial role in promoting AAA through modulation of inflammation and degradation of the ECM. They are responsible for the up-regulation ofSPP1(osteopontin, OPN)gene expression in macrophages and aortic tissue, which triggers inflammation and remodeling but also platelet adhesion and migration into the abdominal aortic wall and the intraluminal thrombus (ILT). Further, enhanced platelet activation and pro-coagulant activity results in elevated gene expression of various cytokines,Mmp9andCol1a1in macrophages andIl-6andMmp9in fibroblasts. Enhanced platelet activation and pro-coagulant activity was also detected in AAA patients. Further, we detected platelets and OPN in the vessel wall and in the ILT of patients who underwent open repair of AAA. Platelet depletion in experimental murine AAA reduced inflammation and ECM remodeling, with reduced elastin fragmentation and aortic diameter expansion. Of note, OPN co-localized with platelets, suggesting a potential role of OPN for the recruitment of platelets into the ILT and the aortic wall. In conclusion, our data strongly supports the potential relevance of anti-platelet therapy to reduce AAA progression and rupture in AAA patients.Translational perspectiveAbdominal aortic aneurysm (AAA) is a severe cardiovascular disease (CVD) with high mortality. Since the role of platelets is unclear, we explored platelet-mediated processes in the pathogenesis of AAA. Results from platelet depleted mice and patients with AAA revealed that platelets modulate inflammatory and stiffness-related gene expression of macrophages and fibroblasts. Further, platelets induce the release of osteopontin important for the recruitment of platelets to the aortic wall and to the intraluminal thrombus (ILT). Consequently, platelet depletion significantly reduced aneurysm growth. Thus, therapeutic targeting of platelet activation might be crucial for the treatment of patients to reduce AAA formation and progression.
Investigating population continuity and ghost admixture among ancient genomes
Authors: McKenna James , Bernhardsson Carolina , Waxman David , Jakobsson Mattias , Sjödin Per 
Published: December 2022

AbstractAncient DNA (aDNA) can prove a valuable resource when investigating the evolutionary relationships between ancient and modern populations. Performing demographic inference using datasets that include aDNA samples however, requires statistical methods that explicitly account for the differences in drift expected among a temporally distributed sample. Such drift due to temporal structure can be challenging to discriminate from admixture from an unsampled, or “ghost”, population, which can give rise to very similar summary statistics and confound methods commonly used in population genetics. Sequence data from ancient individuals also have unique characteristics, including short fragments, increased sequencing-error rates, and often limited genome-coverage that poses further challenges. Here we present a novel and conceptually simple approach for assessing questions of population continuity among a temporally distributed sample. We note that conditional on heterozygote sites in an individual genome at a particular point in time, the mean proportion of derived variants at those sites in other individuals has different expectations forwards in time and backwards in time. The difference in these processes enables us to construct a statistic that can detect population continuity in a temporal sample of genomes. We show that the statistic is sensitive to historical admixture events from unsampled populations. Simulations are used to evaluate the power of this approach. We investigate a set of ancient genomes from Early Neolithic Scandinavia to assess levels of population continuity to an earlier Mesolithic individual.
Behavioral discrimination and olfactory bulb encoding of odor plume intermittency
Authors: Gumaste Ankita , Baker Keeley L. , Izydorczak Michelle , True Aaron C. , Vasan Ganesh , Crimaldi John P. , Verhagen Justus V. 
Published: December 2022

AbstractIn order to survive, animals often need to navigate a complex odor landscape where odors can exist in airborne plumes. Several odor plume properties change with distance from the odor source, providing potential navigational cues to searching animals. Here we focus on odor intermittency, a temporal odor plume property that measures the fraction of time odor is present at a given point within the plume and decreases with increasing distance from the odor source. We sought to determine if mice are capable of using changes in intermittency to locate an odor source. To do so, we trained mice on an intermittency discrimination task. We establish that mice can discriminate odor plume samples of low and high intermittency and that the neural responses in the olfactory bulb can account for task performance and support intermittency encoding. Modulation of sniffing, a behavioral parameter that is highly dynamic during odor-guided navigation, affects both behavioral outcome on the intermittency discrimination task as well as neural representation of intermittency. Together, this work demonstrates that intermittency is an odor plume property that can inform olfactory search and more broadly supports the notion that mammalian odor-based navigation can be guided by temporal odor plume properties.
AUTS2 gene dosage affects synaptic AMPA receptors via a local dendritic spine AUTS2-TTC3-AKT-mTORC1 signaling dysfunction
Authors: Lepagnol-Bestel Aude-Marie , Duchon Arnaud , Viard Julia , Kvajo Mirna , Daudin Rachel , Khelfaoui Malik , Haziza Simon , Loe-Mie Yann , Aime Mattia , Suizu Futoshi , Birling Marie-Christine , Bensaid Mounia , Jacquot Sylvie , Koebel Pascale , Reverdy Céline , Rain Jean-Christophe , Noguchi Masayuki , Marquez Xavier , Triller Antoine , Humeau Yann , Hérault Yann , Karayiorgou Maria , Gogos Joseph A. , Simonneau Michel 
Published: December 2022

ABSTRACTThe Human 1.2-MbAUTS2locus on chromosome 7q11.22 encodes a 1259-aa full-length protein, and a 711-aa C-terminal isoform. Functions of these AUTS2 proteins are only partly known. The major traits found in patients displayingAUTS2locus mutations are Intellectual Disabilities, microcephaly attention deficit hyperactivity disorder (ADHD) (54%), and autistic traits. Furthermore,AUTS2common variants were recently found associated to alcohol consumption and dyslexia using GWAS approaches. Auts2 localizes mainly in cell nuclei. We evidenced by super-resolution that Auts2 is present in dendritic spines. Auts2 interacts with Ttc3, the Akt2 E3 ligase, and negatively regulates Akt2 ubiquitination. Auts2 haploinsufficiency affects Akt/mTorc1 pathway with a decrease in AMPA and NMDA receptor subunits and in synaptic currents. Akt2 injection in postsynaptic neurons is sufficient to reverse changes in synaptic currents generated by Auts2 haploinsufficiency. Using chromosome engineering based on targeted meiotic recombination, we generated two mouse models withAuts2locus deletion and duplication. DeletedAuts2locus mice display stereotypies (rearing), perseveration and abnormal recognition memory. DuplicatedAuts2locus mice display similar perseveration and abnormal recognition memory but also a decrease in cued and contextual fear memory. Gene dosage induce changes in brain sub-region neuronal networks. In the thalamo-lateral amygdala pathway linked to cued fear memory, we found synaptic impairments linked to AMPA receptors, with a specific decrease in pAKT/total AKT ratio in duplicated Auts2 mice. Altogether, our study thereby provides a novel mechanistic and potentially therapeutic understanding of synaptic AKT/mTORC1 deregulated signaling and its related behavioral and cognitive phenotypes.
Erp and Rev adhesins of the Lyme disease spirochete’s ubiquitous cp32 prophages assist the bacterium during vertebrate infection
Authors: Stevenson Brian , Brissette Catherine A. 
Published: December 2022

AbstractAlmost all spirochetes in the genusBorrelia(sensu lato) naturally contain multiple variants of closely related prophages. In the Lyme disease borreliae, these prophages are maintained as circular episomes that are called cp32s (circularplasmid32kb). The cp32s of Lyme agents are particularly unique in that they encode two distinct families of lipoproteins, Erp and Rev, that are expressed on the bacteria’s outer surface during infection of vertebrate hosts. All identified functions of those outer surface proteins involve interactions between the spirochetes and host molecules: Erp proteins bind plasmin(ogen), laminin, glycosaminoglycans, and/or components of complement, and Rev proteins bind fibronectin. Thus, cp32 prophages provide their bacterial hosts with surface proteins that can enhance infection processes, thereby facilitating their own survival. Horizontal transfer via bacteriophage particles increases spread of beneficial alleles and creates diversity among Erp and Rev proteins.
Phylogeny and biogeography of the algal DMS-releasing enzyme
Authors: Shemi Adva , Ben-Dor Shifra , Rotkopf Ron , Dym Orly , Vardi Assaf 
Published: December 2022

AbstractPhytoplankton produce the volatile dimethyl sulfide (DMS), an important infochemical, which is emitted to the atmosphere and affecting the global climate. Albeit the enzymatic source for DMS in eukaryotes was elucidated, namely a DMSP lyase (DL) called Alma1, we still lack basic knowledge regarding its taxonomy and biogeographic distribution. We defined unique sequence motifs which enable the identification of DL homologs (DLHs) in model systems and environmental populations. We used these motifs to predict DLHs in diverse algae by analyzing hundreds of genomic and transcriptomic sequences from model systems under stress conditions and from environmental samples. Our findings show that the DL enzyme is more taxonomically widespread than previously thought, as it is encoded by known algal taxa as haptophytes and dinoflagellates, but also by chlorophytes, pelagophytes and diatoms, which were conventionally considered to lack the DL enzyme. By exploring theTaraOceans database, we showed that DLHs are widespread across the oceans and are predominantly expressed by dinoflagellates. Certain dinoflagellate DLHs were differentially expressed between the euphotic and mesopelagic zones, suggesting a functional specialization and an involvement in the metabolic plasticity of mixotrophic dinoflagellates. In specific regions as the Southern Ocean, DLH expression by haptophytes and diatoms was correlated with environmental drivers such as nutrient availability. The expanded repertoire of putative DL enzymes from diverse microbial origins and geographic niches suggests new potential players in the marine sulfur cycle and provides a foundation to study the cellular function in marine microbes.