bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural genetic variation underlying the negative effect of elevated CO2on ionome composition inArabidopsis thaliana
Authors: Cassan Océane , Pimparé Léa-Lou , Mozzanino Timothy , Fizames Cécile , Devidal Sébastien , Roux Fabrice , Milcu Alexandru , Lèbre Sophie , Gojon Alain , Martin Antoine 
Published: June 2023

AbstractThe elevation of atmospheric CO2leads to a decline in the plant mineral content, which might pose a significant threat to food security in the coming decades. To date, very few genes have been identified as having a role in the negative effect of elevated CO2on plant mineral composition. Yet, several studies have shown a certain degree of diversity in the ionome’s response to elevated CO2, associated with genotypic variation. This suggests the existence of genetic factors controlling the effect of CO2on ionome composition. However, no large-scale studies have been carried out to date to explore the genetic diversity of the ionome responses to elevated CO2. Here, we used six hundredArabidopsis thalianaaccessions, representing geographical distributions ranging from worldwide to regional and local environments, to analyze the natural genetic variation underlying the negative effect of elevated CO2on the ionome composition in plants. We show that the growth under elevated CO2leads to a global and important decrease of the ionome content whatever the geographic distribution of the population. We also observed a high range of genetic diversity in the response of the ionome composition to elevated CO2, and we identified sub-populations, showing effects on their ionome ranging from the most pronounced to resilience or even to a benefit in response to elevated CO2. Using genome-wide association mapping on the response of each mineral element to elevated CO2or on integrative traits, we identified a large set of QTLs and genes associated with the ionome response to elevated CO2. Finally, we demonstrate that the function of one of these genes is associated to the negative effect of elevated CO2on the plant mineral composition. This resource will contribute to understand the genetic mechanisms underlying the negative effect of elevated CO2on plant mineral nutrition, and could help towards the development of crops adapted to a high-CO2world.
Convergent origin and accelerated evolution of vesicle-associated RhoGAP proteins in two unrelated parasitoid wasps
Authors: Colinet Dominique , Cavigliasso Fanny , Leobold Matthieu , Pichon Appoline , Urbach Serge , Cazes Dominique , Poullet Marine , Belghazi Maya , Volkoff Anne-Nathalie , Drezen Jean-Michel , Gatti Jean-Luc , Poirié Marylène 
Published: June 2023

AbstractAnimal venoms and other protein-based secretions that perform a variety of functions, from predation to defense, are highly complex cocktails of bioactive compounds. Gene duplication, accompanied by modification of the expression and/or function of one of the duplicates under the action of positive selection, followed by further duplication to produce multigene families of toxins is a well-documented process in venomous animals. This evolutionary model has been less described in parasitoid wasps, which use maternal fluids, including venom, to protect their eggs from encapsulation by the host immune system. Here, we evidence the convergent recruitment and accelerated evolution of two multigene families of RhoGAPs presumably involved in virulence in two unrelated parasitoid wasp species,Leptopilina boulardi(Figitidae) andVenturia canescens(Icheumonidae). In both species, these RhoGAPs are associated with vesicles that act as transport systems to deliver virulence factors, but are produced in different tissues: the venom gland inLeptopilinasp. and the ovarian calyx inV. canescens. We show that the gene encoding the cellular RacGAP1 is at the origin of the virulent RhoGAP families found inLeptopilinasp. andV. canescens. We also show that both RhoGAP families have undergone evolution under positive selection and that almost all of these RhoGAPs lost their GAP activity and GTPase binding ability due to substitutions in key amino acids. These results suggest an accelerated evolution and functional diversification of these vesicle-associated RhoGAPs in the two phylogenetically distant parasitoid species. The potential new function(s) and the exact mechanism of action of these proteins in host cells remain to be elucidated.
DiffSegR: An RNA-Seq data driven method for differential expression analysis using changepoint detection
Authors: Liehrmann Arnaud , Delannoy Etienne , Launay-Avon Alexandra , Gilbault Elodie , Loudet Olivier , Castandet Benoît , Rigaill Guillem 
Published: June 2023

ABSTRACTTo fully understand gene regulation, it is necessary to have a thorough understanding of both the transcriptome and the enzymatic and RNA-binding activities that shape it. While many RNA-Seq-based tools have been developed to analyze the transcriptome, most only consider the abundance of sequencing reads along annotated patterns (such as genes). These annotations are typically incomplete, leading to errors in the differential expression analysis. To address this issue, we present DiffSegR - an R package that enables the discovery of transcriptome-wide expression differences between two biological conditions using RNA-Seq data. DiffSegR does not require prior annotation and uses a multiple changepoints detection algorithm to identify the boundaries of differentially expressed regions in the per-base log2 fold change. In a few minutes of computation, DiffSegR could rightfully predict the role of chloroplast ribonuclease Mini-III in rRNA maturation and chloroplast ribonuclease PNPase in (3’/5’)-degradation of rRNA, mRNA, and tRNA precursors as well as intron accumulation. We believe DiffSegR will benefit biologists working on transcriptomics as it allows access to information from a layer of the transcriptome overlooked by the classical differential expression analysis pipelines widely used today. DiffSegR is available athttps://aliehrmann.github.io/DiffSegR/index.html.
The first complete genome of the extinct European wild ass (Equus hemionus hydruntinus)
Authors: Özkan Mustafa , Gürün Kanat , Yüncü Eren , Vural Kıvılcım Başak , Atağ Gözde , Akbaba Ali , Fidan Fatma Rabia , Sağlıcan Ekin , Altınışık N. Ezgi , Koptekin Dilek , Pawłowska Kamilla , Hodder Ian , Adcock Sarah E. , Arbuckle Benjamin S. , Steadman Sharon R. , McMahon Gregory , Erdal Yılmaz Selim , Bilgin C. Can , Geigl Eva-Maria , Götherstrom Anders , Grange Thierry , Togan İnci , Özer Füsun , Somel Mehmet 
Published: June 2023

AbstractWe present paleogenomes of three morphologically-unidentified Anatolian equids dating to the 1stmillennium BCE, sequenced to coverages of 0.6-6.4X. Mitochondrial DNA haplotypes of the Anatolian individuals clustered with those ofEquus hydruntinus(orEquus hemionus hydruntinus), the extinct European wild ass. The Anatolian wild ass whole genome profiles fall outside the genomic diversity of other extant and past Asiatic wild ass (E.hemionus) lineages. These observations strongly suggest that the three Anatolian wild asses representE.hydruntinus, making them the latest recorded survivors of this lineage, about a millennium later than the latest observations in the zooarchaeological record. Comparative genomic analyses suggest thatE.hydruntinuswas a sister clade to all ancient and present-dayE.hemionuslineages, representing an early split. We also find indication of gene flow between hydruntines and Middle Eastern wild asses. Analyses of genome-wide heterozygosity and runs of homozygosity reveal that the Anatolian wild ass population had severely lost genetic diversity by the mid-1stmillennium BCE, a likely omen of its eventual demise.
Multidimensional analysis of a social behavior identifies regression and phenotypic heterogeneity in a female mouse model for Rett syndrome
Authors: Mykins Michael , Bridges Benjamin , Jo Angela , Krishnan Keerthi 
Published: June 2023

AbstractRegression is a key feature of neurodevelopmental disorders such as Autism Spectrum Disorder, Fragile X Syndrome and Rett syndrome (RTT). RTT is caused by mutations in the X-linked gene Methyl CpG-Binding Protein 2 (MECP2). It is characterized by an early period of typical development with subsequent regression of previously acquired motor and speech skills in girls. The syndromic phenotypes are individualistic and dynamic over time. Thus far, it has been difficult to capture these dynamics and syndromic heterogeneity in the preclinicalMecp2-heterozygous female mouse model (Het). The emergence of computational neuroethology tools allow for robust analysis of complex and dynamic behaviors to model endophenotypes in pre-clinical models. Towards this first step, we utilized DeepLabCut, a marker-less pose estimation software to quantify trajectory kinematics, and multidimensional analysis to characterize behavioral heterogeneity in Het over trials in the previously benchmarked, ethologically relevant social cognition task of pup retrieval. We report the identification of two distinct phenotypes of adult Het: Het that display a delay in efficiency in early days and then improve over days like wild-type mice, and Het that regress and perform worse in later days. Furthermore, regression is dependent on age, behavioral context, and is identifiable in early days of retrieval. Together, the novel identification of two populations of Het suggest differential effects on neural circuitry and opens new directions of exploration to investigate the underlying molecular and cellular mechanisms, and better design experimental therapeutics.
Phylogeogrphy reveals expansion of yellow fever virus genotypes in West and Central Africa
Authors: Motayo Babatunde Olanrewaju , Opayele Adewale , Akinduti Paul Akiniyi , Faneye Adedayo Omotayo , Omoregie Isibor Patrick , Oranusi Solomon Uche 
Published: June 2023

ABSTRACTYellow Fever virus remains the most medically significant Arbovirus in Africa, with the occurrence of large outbreaks with human fatalities in recent years in Africa. Molecular epidemiology has shown the presence of 4 genotypes circulating across Africa; however, paucity of data still exists regarding directional spread and phylogeography of the African Yellow fever genotypes. The need to fill this gap with information from spatiotemporal data from continuous occurrence of YF outbreaks in Africa conceptualized this study; which aims to investigate the most recent transmission events and directional spread of YF virus using updated genomic sequence data. Archived Yellow Fever sequence data was utilized along with epidemiologic data from outbreaks in Africa, to analyze the case/fatality distribution. Phylogeograhic analysis was also utilized to demonstrate the ancestral introduction and geographic clustering of YF genotypes in Africa. Directional spread and geographic transmission of YF was also investigated. African YF genotypes were found to be geographical distinct, circulating within distinct geographical boundaries. Spatiotemporal spread however revealed an eastward spread of the West African genotypes over time, and recent northward movement of the East African genotype. We conclude by recommending expanded human/ vectoral surveillance of YF and other Arboviruses of public health importance, and upscaling sequencing capabilities of new and existing public health labs in Africa to help in the defense against public health threats.
The Neonatal Gyrencephalic Cortex Maintains Regionally Distinct Streams of Neuroblasts
Authors: Kim JaeYeon , Sandoval Kadellyn , Poddar Aunoy , Chu Julia , Horton Emma , Cui Di , Nakamura Keira , Bartels Theresa , Wood Christian , Rowitch David H. , Kim Hosung , Sherwood Chet C. , Kramer Boris W , Roberts Angela C. , Ross Pablo J. , Xu Duan , Robertson Nicola J. , Ji Peng , Maga Elizabeth A. , Paredes Mercedes F. 
Published: June 2023

AbstractNeurodevelopmental mechanisms have evolved to support the formation of diverse brain structures, such as in humans, during the perinatal period. Here, we demonstrate that neonatal gyrencephalic brains harbor an expanded subventricular zone, termed the Arc, defined by tiered arrangement of doublecortin (DCX)-expressing neuroblasts and vascular enrichment at the ventricular wall. The Arc is the origin of dorsal and ventral populations of migratory neuroblasts that target multiple regions involved in higher cognitive functions. Arc-derived migratory streams, primarily from the caudal ganglionic eminence, are composed of diverse neuronal subtypes with distinct spatial and migratory-receptor profiles. Our findings indicate the Arc is a structure present in phylogenetically divergent species that supports the expansion of postnatal neuronal migration, contributing to a protracted formation of cortical circuits in gyrencephalic brains.One-Sentence SummaryThe ventricular cytoarchitecture of gyrencephalic brains supports an ongoing supply of migratory neurons to the neonatal cortex.
AutoMacq: an automatic pipeline to analyse macaque structural MRI data
Authors: Kindred Nathan , Carella Susanna , van den Heuvel Martijn P , Balezeau Fabien , Wang Yujiang , Poirier Colline 
Published: June 2023

AbstractMRI scanning of rhesus macaques is a growing field due to their evolutionary proximity and similar neuroanatomy to humans. As such, there is a need for automatic macaque MRI processing pipelines. AutoMacq is a pipeline capable of processing rhesus macaque MRI data to produce both voxel-based and surface-based metrics. It involves minimal manual intervention and can be carried out without expert knowledge of macaque neuroanatomy. To test the quality of the pipeline, scans from 74 subjects across 8 different sites were processed. Results indicate that over 87% of tissue segmentations and surfaces were of satisfactory quality to not require additional manual correction. Hemispheric comparisons and analyses of scan-rescan data showed strong reliability of the volumetric and surface-based outputs. Finally, to illustrate potential applications of AutoMacq, the change in grey matter volume with ageing was investigated cross-sectionally using subjects aged 3-15 years (corresponding to adolescence until mid-adulthood). The analysis revealed a linear decrease in grey matter volume with age similar to what has been found in humans, reinforcing the value of rhesus macaques as a model of healthy human ageing.
Visual activity enhances neuronal excitability in thalamic relay neurons
Authors: Duménieu Maël , Fronzaroli-Molinieres Laure , Iborra-Bonnaure Cécile , Wakade Anushka , Zanin Emilie , Aziz Aurore , Ankri Norbert , Incontro Salvatore , Denis Danièle , Brette Romain , Marquèze-Pouey Béatrice , Debanne Dominique , Russier Michael 
Published: June 2023

AbstractThe dorsal lateral geniculate nucleus (dLGN) has long been held to act as a basic relay for visual information travelling from the retina to cortical areas, but recent findings suggest a largely underestimated functional plasticity of dLGN neurons. However, the cellular mechanisms supporting this functional plasticity have not been yet explored. In particular, it remains to elucidate whether intrinsic neuronal excitability change upon visual stimuli. We show here that monocular deprivation for 10 days reduces the intrinsic excitability of dorsal LGN relay cells. Furthermore, dLGN neurons exhibit long-term potentiation of their intrinsic excitability (LTP-IE) when suprathreshold afferent retinal inputs are stimulated at 40 Hz or when spikes are induced with direct somatic current injection to reproduce patterns of retinal activity. LTP-IE is observed after eye opening and requires calcium influx mediated by L-type calcium channels. It involves activation of PKA and is expressed through the down-regulation of Kv1 potassium channels. In conclusion, our study provides the first evidence for intrinsic plasticity in dLGN relay cells, thus further pointing the role of thalamic neurons in activity-dependent visual plasticity and amblyopia.
Autism- and epilepsy-associatedEEF1A2mutations lead to translational dysfunction and altered actin bundling
Authors: Mohamed Muhaned S. , Klann Eric 
Published: June 2023

AbstractProtein synthesis is a fundamental cellular process in neurons that is essential for synaptic plasticity and memory consolidation. Here, we describe our investigations of a neuron- and muscle-specific translation factor,eukaryoticElongationFactor1a2(eEF1A2), which when mutated in patients results in autism, epilepsy, and intellectual disability. We characterize three most commonEEF1A2patient mutations, G70S, E122K, and D252H, and demonstrate that all three mutations decreasede novoprotein synthesis and elongation rates in HEK293 cells. In mouse cortical neurons, theEEF1A2mutations not only decreasede novoprotein synthesis, but also alter neuronal morphology, regardless of endogenous levels of eEF1A2, indicating that the mutations act via a toxic gain of function. We also show that eEF1A2 mutant proteins display increased tRNA binding and decreased actin bundling activity, suggesting that these mutations disrupt neuronal function by decreasing tRNA availability and altering the actin cytoskeleton. More broadly, our findings are consistent with the idea that eEF1A2 acts as a bridge between translation and the actin skeleton, which is essential for proper neuron development and function.Significance StatementEukaryoticElongationFactor 1A2 (eEF1A2) is a muscle- and neuron-specific translation factor responsible for bringing charge tRNAs to the elongating ribosome. Why neurons express this unique translation factor is unclear; however, it is known that mutations inEEF1A2cause severe drug-resistant epilepsy, autism and neurodevelopmental delay. Here, we characterize the impact of three common disease-causing mutations inEEF1A2and demonstrate that they cause decreased protein synthesis via reduced translation elongation, increased tRNA binding, decreased actin bundling activity, as well as altered neuronal morphology. We posit that eEF1A2 serves as a bridge between translation and the actin cytoskeleton, linking these two processes that are essential for neuronal function and plasticity.
Mechanisms of dual modulatory effects of spermine on the mitochondrial calcium uniporter complex
Authors: Tu Yung-Chi , Chao Fan-Yi , Tsai Ming-Feng 
Published: June 2023

AbstractThe mitochondrial Ca2+uniporter mediates the crucial cellular process of mitochondrial Ca2+uptake, which regulates cell bioenergetics, intracellular Ca2+signaling, and cell death initiation. The uniporter contains the pore-forming MCU subunit, an EMRE protein that binds to MCU, and the regulatory MICU1 subunit, which can dimerize with MICU1 or MICU2 and under resting cellular [Ca2+] occludes the MCU pore. It has been known for decades that spermine, which is ubiquitously present in animal cells, can enhance mitochondrial Ca2+uptake, but the underlying mechanisms remain unclear. Here, we show that spermine exerts dual modulatory effects on the uniporter. In physiological concentrations of spermine, it enhances uniporter activity by breaking the physical interactions between MCU and the MICU1-containing dimers to allow the uniporter to constitutively take up Ca2+even in low [Ca2+] conditions. This potentiation effect does not require MICU2 or the EF-hand motifs in MICU1. When [spermine] rises to millimolar levels, it inhibits the uniporter by targeting the pore region in a MICU-independent manner. The MICU1-dependent spermine potentiation mechanism proposed here, along with our previous finding that cardiac mitochondria have very low MICU1, can explain the puzzling observation in the literature that mitochondria in the heart show no response to spermine.
Recognition of centromere-specific histone Cse4 by the inner kinetochore Okp1-Ame1 complex
Authors: Deng Sunbin , Cai Jiaxi , Harrison Stephen C. , Zhou Huilin , Hinshaw Stephen M. 
Published: June 2023

AbstractSuccessful mitosis depends on the timely establishment of correct chromosomal attachments to microtubules. The kinetochore, a modular multiprotein complex, mediates this connection by recognizing specialized chromatin containing a histone H3 variant called Cse4 in budding yeast and CENP-A in vertebrates. Structural features of the kinetochore that enable discrimination between Cse4/CENP-A and H3 have been identified in several species. How and when these contribute to centromere recognition and how they relate to the overall structure of the inner kinetochore are unsettled questions. We have determined the crystal structure of a Cse4 peptide bound to the essential inner kinetochore Okp1-Ame1 heterodimer from budding yeast. The structure and related experiments show in detail an essential point of Cse4 contact and provide information about the arrangement of the inner kinetochore.
The white-footed deermouse, an infection-tolerant reservoir for several zoonotic agents, tempers interferon responses to endotoxin in comparison to the mouse and rat
Authors: Milovic Ana , Duong Jonathan V. , Barbour Alan G. 
Published: June 2023

AbstractThe white-footed deermousePeromyscus leucopus, a long-lived rodent, is a key reservoir for agents of several zoonoses, including Lyme disease. While persistently infected, this deermouse is without apparent disability or diminished fitness. For a model for inflammation elicited by various pathogens, the endotoxin lipopolysaccharide (LPS) was used to compare genome-wide transcription in blood byP. leucopus,Mus musculusandRattus norvegicusand adjusted for white cell concentrations. Deermice were distinguished from the mice and rats by LPS response profiles consistent with non-classical monocytes and alternatively-activated macrophages. LPS-treatedP. leucopus, in contrast to mice and rats, also displayed little transcription of interferon-gamma and lower magnitude fold-changes in type 1 interferon-stimulated genes. This was associated with comparatively reduced transcription of endogenous retrovirus sequences and cytoplasmic pattern recognition receptors in the deermice. The results reveal a mechanism for infection tolerance in this species and perhaps other animal reservoirs for agents of human disease.
The double-edged role of FASII regulator FabT inStreptococcus pyogenesinfection
Authors: Lambert Clara , Gaillard Marine , Wongdontree Paprapach , Bachmann Caroline , Hautcoeur Antoine , Gloux Karine , Guilbert Thomas , Méhats Celine , Prost Bastien , Solgadi Audrey , Abreu Sonia , Andrieu Muriel , Poyart Claire , Gruss Alexandra , Fouet Agnes 
Published: June 2023

AbstractInStreptococcus pyogenes, the type II fatty acid (FA) synthesis pathway FASII is feedback- controlled by the FabT repressor bound to an acyl-Acyl carrier protein. Despite FabT defects being linked to reduced virulence in animal models, spontaneousfabTmutants arisein vivo. To resolve this paradox, we characterized the conditions and mechanisms that require FabT activity, and those that promotefabTmutant emergence. The primaryfabTmutant defect is energy dissipation: specific nutrients are consumed, but the mutant fails to grow on human tissue, cells, or cell filtrates where nutrients are limited. These features explain the FabT requirement during infection. Conversely,fabTmutants exhibited a marked growth advantage over the wild-type in biotopes rich in saturated FAs.fabTmutants emerge in this context, where continued FASII activity prevented environmental FA incorporation. Anex vivomuscle model demonstrated that wild-typeS. pyogeneswas inhibited, whilefabTmutant growth was stimulated, but conditional to FASII activity. Our findings elucidate the rationale for emergingfabTmutants that improve survival in lipid-rich biotopes, but lead to a genetic impasse for infection.