Abstract: Using the phase-space formulation of quantum mechanics, we derive a four-component Wigner equation for a system composed of spin-½ fermions (typically, electrons) including the Zeeman effect and the spin–orbit coupling. This Wigner equation is coupled to the appropriate Maxwell equations to form a self-consistent mean-field model. A set of semiclassical Vlasov equations with spin effects is obtained by expanding the full quantum model to first order in the Planck constant. The corresponding hydrodynamic equations are derived by taking velocity moments of the phase-space distribution function. A simple closure relation is proposed to obtain a closed set of hydrodynamic equations.

Supplementary material from "Phase-space methods for the spin dynamics in condensed matter systems";Jérôme Hurst;2017;Figshare


Abstract: Abstract Background Epigenetic modifications of DNA, such as 5-methylcytosine and 5-hydroxymethycytosine, play important roles in development and disease. Here, we present a cost-effective and versatile methodology for the analysis of DNA methylation in targeted genomic regions, which comprises multiplexed, PCR-based preparation of bisulfite DNA libraries followed by customized MiSeq sequencing. Results Using bisulfite and oxidative bisulfite conversion of DNA, we have performed multiplexed targeted sequencing to analyse several kilobases of genomic DNA in up to 478 samples, and achieved high coverage data of 5-methylcytosine and 5-hydroxymethycytosine at single-base resolution. Our results demonstrate the ability of this methodology to detect all levels of cytosine modifications at greater than 100× coverage in large sample sets at low cost compared to other targeted methods. Conclusions This approach can be applied to multiple settings, from candidate gene to clinical studies, and is especially useful for validation of differentially methylated or hydroxymethylated regions following whole-genome analyses.

Medium throughput bisulfite sequencing for accurate detection of 5-methylcytosine and 5-hydroxymethylcytosine;Gary Chen;2017;Figshare


Abstract: Microscopy techniques allowing observation of unlabeled samples have recently experienced a regain of interest. In particular, approaches based on recording of the optical field diffracted by the specimen, in amplitude and phase, have proven their capacities for biological investigations. When combined with variations of specimen illumination, tomographic acquisitions are possible. One limitation of previously developed approaches is the anisotropic resolution, characteristic of all transmission microscopes. In this context, an instrument, characterized by isotropic high-resolution 3D imaging capabilities, is still awaited. For the first time, to the best of our knowledge, we have developed tomographic diffractive microscopy combining specimen rotation and illumination rotation, which delivers images with (almost) isotropic resolution below 200 nm. The method is illustrated by observations of nanoscopic fiber tips, microcrystals and pollens, and should be helpful for characterizing freestanding natural (diatoms, spores, red or white blood cells, etc.) or artificial samples.

Tomographic diffractive microscopy with isotropic resolution;Bertrand Simon;2017;Figshare


Abstract: Over the past two decades, the development of methods for visualizing and analysing specimens digitally, in three and even four dimensions, has transformed the study of living and fossil organisms. However, the initial promise that the widespread application of such methods would facilitate access to the underlying digital data has not been fully achieved. The underlying datasets for many published studies are not readily or freely available, introducing a barrier to verification and reproducibility, and the reuse of data. There is no current agreement or policy on the amount and type of data that should be made available alongside studies that use, and in some cases are wholly reliant on, digital morphology. Here, we propose a set of recommendations for minimum standards and additional best practice for three-dimensional digital data publication, and review the issues around data storage, management and accessibility.

Supplementary material from "Open data and digital morphology";Thomas G. Davies;2017;Figshare

Earth and related environmental sciences


Abstract: Abstract Purpose Data for ANCA-associated vasculitis (AAV) patients requiring intensive care are scarce. Methods We included 97 consecutive patients with acute AAV manifestations (new onset or relapsing disease), admitted to 18 intensive care units (ICUs) over a 10-year period (2002–2012). A group of 95 consecutive AAV patients with new onset or relapsing disease, admitted to two nephrology departments with acute vasculitis manifestations, constituted the control group. Results In the ICU group, patients predominantly showed granulomatosis with polyangiitis and proteinase-3 ANCAs. Compared with the non-ICU group, the ICU group showed comparable Birmingham vasculitis activity score and a higher frequency of heart, central nervous system and lungs involvements. Respiratory assistance, renal replacement therapy and vasopressors were required in 68.0, 56.7 and 26.8% of ICU patients, respectively. All but one patient (99%) received glucocorticoids, 85.6% received cyclophosphamide, and 49.5% had plasma exchanges as remission induction regimens. Fifteen (15.5%) patients died during the ICU stay. The following were significantly associated with ICU mortality in the univariate analysis: the need for respiratory assistance, the use of vasopressors, the occurrence of at least one infection event in ICU, cyclophosphamide treatment, sequential organ failure assessment at admission and simplified acute physiology score II. After adjustment on sequential organ failure assessment or infection, cyclophosphamide was no longer a risk factor for mortality. Despite a higher initial mortality rate of ICU patients within the first hospital stay (p

Patients with ANCA-associated vasculitis admitted to the intensive care unit with acute vasculitis manifestations: a retrospective and comparative multicentric study;Julien Demiselle;2017;Figshare


Abstract: Social information use is common in a wide range of group-living animals, notably in humans. The role it plays in decision-making could be a key to understanding how social groups make collective decisions. The observation of road-crossing behaviours in the presence of other individuals is an ideal means to study the influence of social information on decision-making. This study investigated the influence of culture on social information used by pedestrians in a potentially dangerous scenario, namely road crossing. We scored the collective crossing of pedestrians at four locations in Nagoya (Japan) and three locations in Strasbourg (France). French pedestrians cross against the lights much more often (41.9%) than Japanese ones (2.1%). Individuals deciding to cross the road were strongly influenced by the behaviour and the presence of other pedestrians, especially in Japan, where a stronger conformism was noted. However, Japanese pedestrians were half as likely to be influenced by social information as their French counterparts when crossing at the red light, as they were more respectful of rules. Men show riskier behaviour than women (40.6% versus 25.7% of rule-breaking, respectively), deciding quickly and setting off earlier than women. Further related studies could help target specific preventive, culture-specific solutions for pedestrian safety.

Supplementary material from "Cultural influence of social information use in pedestrian road-crossing behaviours";Marie Pelé;2017;Figshare


Abstract: Abstract Background HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration. Recently a new class of IN inhibitors was described, the IN-LEDGF allosteric inhibitors (INLAIs). Designed to interfere with the IN-LEDGF interaction during integration, the major impact of these inhibitors was surprisingly found on virus maturation, causing a reverse transcription defect in target cells. Results Here we describe the MUT-A compound as a genuine INLAI with an original chemical structure based on a new type of scaffold, a thiophene ring. MUT-A has all characteristics of INLAI compounds such as inhibition of IN-LEDGF/p75 interaction, IN multimerization, dual antiretroviral (ARV) activities, normal packaging of genomic viral RNA and complete Gag protein maturation. MUT-A has more potent ARV activity compared to other INLAIs previously reported, but similar profile of resistance mutations and absence of ARV activity on SIV. HIV-1 virions produced in the presence of MUT-A were non-infectious with the formation of eccentric condensates outside of the core. In studying the immunoreactivity of these non-infectious virions, we found that inactivated HIV-1 particles were captured by anti-HIV-specific neutralizing and non-neutralizing antibodies (b12, 2G12, PGT121, 4D4, 10-1074, 10E8, VRC01) with efficiencies comparable to non-treated virus. Autologous CD4+ T lymphocyte proliferation and cytokine induction by monocyte-derived dendritic cells (MDDC) pulsed either with MUT-A-inactivated HIV or non-treated HIV were also comparable. Conclusions Although strongly defective in infectivity, HIV-1 virions produced in the presence of the MUT-A INLAI have a normal protein and genomic RNA content as well as B and T cell immunoreactivities comparable to non-treated HIV-1. These inactivated viruses might form an attractive new approach in vaccine research in an attempt to study if this new type of immunogen could elicit an immune response against HIV-1 in animal models.

The HIV-1 integrase-LEDGF allosteric inhibitor MUT-A: resistance profile, impairment of virus maturation and infectivity but without influence on RNA packaging or virus immunoreactivity;Céline Amadori;2017;Figshare


Abstract: The Plio–Pleistocene evolution of Equus and the subsequent domestication of horses and donkeys remains poorly understood, due to the lack of phenotypic markers capable of tracing this evolutionary process in the palaeontological/archaeological record. Using images from 345 specimens, encompassing 15 extant taxa of equids, we quantified the occlusal enamel folding pattern in four mandibular cheek teeth with a single geometric morphometric protocol. We initially investigated the protocol accuracy by assigning each tooth to its correct anatomical position and taxonomic group. We then contrasted the phylogenetic signal present in each tooth shape with an exome-wide phylogeny from 10 extant equine species. We estimated the strength of the phylogenetic signal using a Brownian motion model of evolution with multivariate K statistic, and mapped the dental shape along the molecular phylogeny using an approach based on squared-change parsimony. We found clear evidence for the relevance of dental phenotypes to accurately discriminate all modern members of the genus Equus and capture their phylogenetic relationships. These results are valuable for both palaeontologists and zooarchaeologists exploring the spatial and temporal dynamics of the evolutionary history of the horse family, up to the latest domestication trajectories of horses and donkeys.

Supplementary material from "Detecting taxonomic and phylogenetic signals in equid cheek teeth: towards new palaeontological and archaeological proxies";T. Cucchi;2017;Figshare


Abstract: Abstract Background With a constant increase in the number of new chemicals synthesized every year, it becomes important to employ the most reliable and fast in silico screening methods to predict their safety and activity profiles. In recent years, in silico prediction methods received great attention in an attempt to reduce animal experiments for the evaluation of various toxicological endpoints, complementing the theme of replace, reduce and refine. Various computational approaches have been proposed for the prediction of compound toxicity ranging from quantitative structure activity relationship modeling to molecular similarity-based methods and machine learning. Within the â  Toxicology in the 21st Centuryâ   screening initiative, a crowd-sourcing platform was established for the development and validation of computational models to predict the interference of chemical compounds with nuclear receptor and stress response pathways based on a training set containing more than 10,000 compounds tested in high-throughput screening assays. Results Here, we present the results of various molecular similarity-based and machine-learning based methods over an independent evaluation set containing 647 compounds as provided by the Tox21 Data Challenge 2014. It was observed that the Random Forest approach based on MACCS molecular fingerprints and a subset of 13 molecular descriptors selected based on statistical and literature analysis performed best in terms of the area under the receiver operating characteristic curve values. Further, we compared the individual and combined performance of different methods. In retrospect, we also discuss the reasons behind the superior performance of an ensemble approach, combining a similarity search method with the Random Forest algorithm, compared to individual methods while explaining the intrinsic limitations of the latter. Conclusions Our results suggest that, although prediction methods were optimized individually for each modelled target, an ensemble of similarity and machine-learning approaches provides promising performance indicating its broad applicability in toxicity prediction.

Computational methods for prediction of in vitro effects of new chemical structures;Priyanka Banerjee;2016;Figshare


Abstract: Abstract Background The ciliopathies represent an umbrella group of >50 clinical entities that share both clinical features and molecular etiology underscored by structural and functional defects of the primary cilium. Despite the advances in gene discovery, this group of entities continues to pose a diagnostic challenge, in part due to significant genetic and phenotypic heterogeneity and variability. We consulted a pediatric case from asymptomatic, non-consanguineous parents who presented as a suspected ciliopathy due to a constellation of retinal, renal, and skeletal findings. Results Although clinical panel sequencing of genes implicated in nephrotic syndromes yielded no likely causal mutation, an oligo-SNP microarray identified a ~20-Mb region of homozygosity, with no altered gene dosage, on chromosome 16p13. Intersection of the probandâ  s phenotypes with known disease genes within the homozygous region yielded a single candidate, IFT140, encoding a retrograde intraflagellar transport protein implicated previously in several ciliopathies, including the phenotypically overlapping Mainzer-Saldino syndrome (MZSDS). Sanger sequencing yielded a maternally inherited homozygous c.634G>A; p.Gly212Arg mutation altering the exon 6 splice donor site. Functional studies in cells from the proband showed that the locus produced two transcripts: a majority message containing a mis-splicing event that caused a premature termination codon and a minority message homozygous for the p.Gly212Arg allele. Zebrafish in vivo complementation studies of the latter transcript demonstrated a loss of function effect. Finally, we conducted post-hoc trio-based whole exome sequencing studies to (a) test the possibility of other causal loci in the proband and (b) explain the Mendelian error of segregation for the IFT140 mutation. We show that the proband harbors a chromosome 16 maternal heterodisomy, with segmental isodisomy at 16p13, likely due to a meiosis I error in the maternal gamete. Conclusions Using clinical phenotyping combined with research-based genetic and functional studies, we have characterized a recurrent IFT140 mutation in the proband; together, these data are consistent with MZSDS. Additionally, we report a rare instance of a uniparental isodisomy unmasking a deleterious mutation to cause a ciliary disorder.

Partial uniparental isodisomy of chromosome 16 unmasks a deleterious biallelic mutation in IFT140 that causes Mainzer-Saldino syndrome;Benjamin Helm;2017;Figshare


Abstract: Abstract Background Microbial-associated molecular patterns activate several MAP kinases, which are major regulators of the innate immune response in Arabidopsis thaliana that induce large-scale changes in gene expression. Here, we determine whether microbial-associated molecular pattern-triggered gene expression involves modifications at the chromatin level. Results Histone acetylation and deacetylation are major regulators of microbial-associated molecular pattern-triggered gene expression and implicate the histone deacetylase HD2B in the reprogramming of defence gene expression and innate immunity. The MAP kinase MPK3 directly interacts with and phosphorylates HD2B, thereby regulating the intra-nuclear compartmentalization and function of the histone deacetylase. Conclusions By studying a number of gene loci that undergo microbial-associated molecular pattern-dependent activation or repression, our data reveal a mechanistic model for how protein kinase signaling directly impacts chromatin reprogramming in plant defense.

MAPK-triggered chromatin reprogramming by histone deacetylase in plant innate immunity;David Latrasse;2017;Figshare


Abstract: Abstract Background The structure of haplogroup H reveals significant differences between the western and eastern edges of the Mediterranean, as well as between the northern and southern regions. Human populations along the westernmost Mediterranean coasts, which were settled by individuals from two continents separated by a relatively narrow body of water, show the highest frequencies of mitochondrial haplogroup H. These characteristics permit the analysis of ancient migrations between both shores, which may have occurred via primitive sea crafts and early seafaring. We collected a sample of 750 autochthonous people from the southern Iberian Peninsula (Andalusians from Huelva and Granada provinces). We performed a high-resolution analysis of haplogroup H by control region sequencing and coding SNP screening of the 337 individuals harboring this maternal marker. Our results were compared with those of a wide panel of populations, including individuals from Iberia, the Maghreb, and other regions around the Mediterranean, collected from the literature. Results Both Andalusian subpopulations showed a typical western European profile for the internal composition of clade H, but eastern Andalusians from Granada also revealed interesting traces from the eastern Mediterranean. The basal nodes of the most frequent H sub-haplogroups, H1 and H3, harbored many individuals of Iberian and Maghrebian origins. Derived haplotypes were found in both regions; haplotypes were shared far more frequently between Andalusia and Morocco than between Andalusia and the rest of the Maghreb. These and previous results indicate intense, ancient and sustained contact among populations on both sides of the Mediterranean. Conclusions Our genetic data on mtDNA diversity, combined with corresponding archaeological similarities, provide support for arguments favoring prehistoric bonds with a genetic legacy traceable in extant populations. Furthermore, the results presented here indicate that the Strait of Gibraltar and the adjacent Alboran Sea, which have often been assumed to be an insurmountable geographic barrier in prehistory, served as a frequently traveled route between continents.

The distribution of mitochondrial DNA haplogroup H in southern Iberia indicates ancient human genetic exchanges along the western edge of the Mediterranean;Candela HernĂĄndez;2017;Figshare


Abstract: Abstract Background Human erythropoiesis is characterized by distinct gene expression profiles at various developmental stages. Previous studies suggest that fetal-to-adult hemoglobin switch is regulated by a complex mechanism, in which many key players still remain unknown. Here, we report our findings from whole transcriptome analysis of erythroid cells, isolated from erythroid tissues at various developmental stages in an effort to identify distinct molecular signatures of each erythroid tissue. Results From our in-depth data analysis, pathway analysis, and text mining, we opted to focus on the VEGFA gene, given its gene expression characteristics. Selected VEGFA genomic variants, identified through linkage disequilibrium analysis, were explored further for their association with elevated fetal hemoglobin levels in β-type hemoglobinopathy patients. Our downstream analysis of non-transfusion-dependent β-thalassemia patients, β-thalassemia major patients, compound heterozygous sickle cell disease/β-thalassemia patients receiving hydroxyurea as fetal hemoglobin augmentation treatment, and non-thalassemic individuals indicated that VEGFA genomic variants were associated with disease severity in β-thalassemia patients and hydroxyurea treatment efficacy in SCD/β-thalassemia compound heterozygous patients. Conclusions Our findings suggest that VEGFA may act as a modifier gene of human globin gene expression and, at the same time, serve as a genomic biomarker in β-type hemoglobinopathy disease severity and hydroxyurea treatment efficacy.

Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in β-type hemoglobinopathy patients;Vasiliki Chondrou;2017;Figshare


Abstract: With almost 50% of all surgeries in the U.S. being performed as minimally invasive procedures, there is a need to develop quantitative endoscopic imaging techniques to aid surgical guidance. Recent developments in widefield optical imaging make endoscopic implementations of real-time measurement possible. In this work, we introduce a proof-of-concept endoscopic implementation of a functional widefield imaging technique called 3D single snapshot of optical properties (3D-SSOP) that provides quantitative maps of absorption and reduced scattering optical properties as well as surface topography with simple instrumentation added to a commercial endoscope. The system’s precision and accuracy is validated using tissue-mimicking phantoms, showing a max error of 0.004 mm-1, 0.05 mm-1, and 1.1 mm for absorption, reduced scattering, and sample topography, respectively. This study further demonstrates video acquisition of a moving phantom and an in vivo sample with a framerate of approximately 11 frames per second.

Real-time endoscopic optical properties imaging;Joseph Angelo;2017;Figshare


Abstract: Abstract The Gram-negative beta-proteobacterium Zoogloea sp. LCSB751 (LMG 29444) was newly isolated from foaming activated sludge of a municipal wastewater treatment plant. Here, we describe its draft genome sequence and annotation together with a general physiological and genomic analysis, as the first sequenced representative of the Zoogloea genus. Moreover, Zoogloea sp. gene expression in its environment is described using metatranscriptomic data obtained from the same treatment plant. The presented genomic and transcriptomic information demonstrate a pronounced capacity of this genus to synthesize poly-Î˛-hydroxyalkanoate within wastewater.

First draft genome sequence of a strain belonging to the Zoogloea genus and its gene expression in situ;Emilie Muller;2017;Figshare


Abstract: Abstract Background Plasmodium falciparum M1 family aminopeptidase is currently considered as a promising target for anti-malarial chemotherapy. Several series of inhibitors developed by various research groups display IC50/Ki values down to nM range on native PfA-M1 or recombinant forms and block the parasite development in culture at µM to sub-µM concentrations. A handful of these inhibitors has been tested on murine models of malaria and has shown anti plasmodial in vivo activity. However, most of these inhibitors do also target the other neutral malarial aminopeptidase, PfA-M17, often with lower Ki values, which questions the relative involvement and importance of each enzyme in the parasite biology. Results An amino-benzosuberone derivative from a previously published collection of chemicals targeting specifically the M1-aminopeptidases has been identified; it is highly potent on PfA-M1 (Ki = 50 nM) and devoid of inhibitory activity on PfA-M17 (no inhibition up to 100 µM). This amino-benzosuberone derivative (T5) inhibits, in the µM range, the in vitro growth of two P. falciparum strains, 3D7 and FcB1, respectively chloroquino-sensitive and resistant. Evaluated in vivo, on the murine non-lethal model of malaria Plasmodium chabaudi chabaudi, this amino-benzosuberone derivative was able to reduce the parasite burden by 44 and 40% in a typical 4-day Peters assay at a daily dose of 12 and 24 mg/kg by intraperitoneal route of administration. Conclusions The evaluation of a highly selective inhibitor of PfA-M1, over PfA-M17, active on Plasmodium parasites in vitro and in vivo, highlights the relevance of PfA-M1 in the biological development of the parasite as well as in the list of promising anti-malarial targets to be considered in combination with current or future anti-malarial drugs.

Selective inhibition of PfA-M1, over PfA-M17, by an amino-benzosuberone derivative blocks malaria parasites development in vitro and in vivo;Lotfi Bounaadja;2017;Figshare


Abstract: Assisted reproductive technologies, including in vitro fertilization (IVF), are now frequently used, and increasing evidence indicates that IVF causes gene expression changes in children and adolescents that increase the risk of metabolic diseases. Although such gene expression changes are thought to be due to IVF-induced epigenetic changes, the mechanism remains elusive. We tested whether the transcription factor ATF7, – which mediates stress-induced changes in histone H3K9 tri- and di-methylation, typical marks of epigenetic silencing – is involved in the IVF-induced gene expression changes. IVF up- and down-regulated the expression of 688 and 204 genes, respectively, in the liver of 3-week-old wild-type (WT) mice, whereas 87% and 68% of these were not changed, respectively, by IVF in ATF7-deficient (Atf7—/—) mice. The genes, which are involved in metabolism, such as pyrimidine and purine metabolism, were up-regulated in WT mice but not in Atf7—/— mice. Of the genes whose expression was up-regulated by IVF in WT mice, 37% were also up-regulated by a loss of ATF7. These results indicate that ATF7 is a key factor in establishing the memory of IVF effects on metabolic pathways.

Dataset for: The transcription factor ATF7 mediates in vitro fertilization-induced gene expression changes in mouse liver;Yang Liu;2017;Figshare


Abstract: Abstract Background Insertion of retroviral genome DNA occurs in the chromatin of the host cell. This step is modulated by chromatin structure as nucleosomes compaction was shown to prevent HIV-1 integration and chromatin remodeling has been reported to affect integration efficiency. LEDGF/p75-mediated targeting of the integration complex toward RNA polymerase II (polII) transcribed regions ensures optimal access to dynamic regions that are suitable for integration. Consequently, we have investigated the involvement of polII-associated factors in the regulation of HIV-1 integration. Results Using a pull down approach coupled with mass spectrometry, we have selected the FACT (FAcilitates Chromatin Transcription) complex as a new potential cofactor of HIV-1 integration. FACT is a histone chaperone complex associated with the polII transcription machinery and recently shown to bind LEDGF/p75. We report here that a tripartite complex can be formed between HIV-1 integrase, LEDGF/p75 and FACT in vitro and in cells. Biochemical analyzes show that FACT-dependent nucleosome disassembly promotes HIV-1 integration into chromatinized templates, and generates highly favored nucleosomal structures in vitro. This effect was found to be amplified by LEDGF/p75. Promotion of this FACT-mediated chromatin remodeling in cells both increases chromatin accessibility and stimulates HIV-1 infectivity and integration. Conclusions Altogether, our data indicate that FACT regulates HIV-1 integration by inducing local nucleosomes dissociation that modulates the functional association between the incoming intasome and the targeted nucleosome.

Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration;Julien Matysiak;2017;Figshare


Abstract: Abstract Background To date, genome-scale analyses in the domestic horse have been limited by suboptimal single nucleotide polymorphism (SNP) density and uneven genomic coverage of the current SNP genotyping arrays. The recent availability of whole genome sequences has created the opportunity to develop a next generation, high-density equine SNP array. Results Using whole genome sequence from 153 individuals representing 24 distinct breeds collated by the equine genomics community, we cataloged over 23 million de novo discovered genetic variants. Leveraging genotype data from individuals with both whole genome sequence, and genotypes from lower-density, legacy SNP arrays, a subset of ~5 million high-quality, high-density array candidate SNPs were selected based on breed representation and uniform spacing across the genome. Considering probe design recommendations from a commercial vendor (Affymetrix, now Thermo Fisher Scientific) a set of ~2 million SNPs were selected for a next-generation high-density SNP chip (MNEc2M). Genotype data were generated using the MNEc2M array from a cohort of 332 horses from 20 breeds and a lower-density array, consisting of ~670 thousand SNPs (MNEc670k), was designed for genotype imputation. Conclusions Here, we document the steps taken to design both the MNEc2M and MNEc670k arrays, report genomic and technical properties of these genotyping platforms, and demonstrate the imputation capabilities of these tools for the domestic horse.

Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: Natural selection is expected to favour the integration of dispersal and phenotypic traits allowing individuals to reduce dispersal costs. Accordingly, associations have been found between dispersal and personality traits such as aggressiveness and exploration, which may facilitate settlement in a novel environment. However, the determinism of these associations has only rarely been explored. Here, we highlight the functional integration of individual personality in nest-defence behaviour and natal dispersal propensity in a long-lived colonial bird, the Alpine swift (<i>Apus melba</i>), providing insights into genetic constraints shaping the coevolution of these two traits. We report a negative association between natal dispersal and nest-defence (i.e. risk taking) behaviour at both the phenotypic and genetic level. This negative association may result from direct selection if risk-averseness benefits natal dispersers by reducing the costs of settlement in an unfamiliar environment, or from indirect selection if individuals with lower levels of nest defence also show lower levels of aggressiveness, reducing costs of settlement among unfamiliar neighbours in a colony. In both cases, these results highlight that risk taking is an important behavioural trait to consider in the study of dispersal evolution

Supplementary material from "Negative phenotypic and genetic correlation between natal dispersal propensity and nest-defence behaviour in a wild bird";Pierre Bize;2017;Figshare


Abstract: Abstract Background Nephropathic cystinosis is a rare inherited metabolic disorder leading to progressive renal failure and extra-renal comorbidity. The prognosis relies on early adherence to cysteamine treatment and symptomatic therapies. Developing nations [DiN] experience many challenges for management of cystinosis. The aim of this study was to assess the management characteristics in DiN compared with developed nations [DeN]. Methods A questionnaire was sent between April 2010 and May 2011 to 87 members of the International Pediatric Nephrology Association, in 50 countries. Results A total of 213 patients were included from 41 centres in 30 nations (109 from 17 DiN and 104 from 13 DeN). 7% of DiN patients died at a median age of 5 years whereas no death was observed in DeN. DiN patients were older at the time of diagnosis. In DiN, leukocyte cystine measurement was only available in selected cases for diagnosis but never for continuous monitoring. More patients had reached end-stage renal disease in DiN (53.2 vs. 37.9%, p = 0.03), within a shorter time of evolution (8 vs. 10 yrs., p = 0.0008). The earlier the cysteamine treatment, the better the renal outcome, since the median renal survival increased up to 16.1 [12.5−/] yrs. in patients from DeN treated before the age of 2.5 years of age (p = 0.0001). However, the renal survival was not statistically different between DeN and DiN when patients initiated cysteamine after 2.5 years of age. The number of transplantations and the time from onset of ESRD to transplantation were not different in DeN and DiN. More patients were kept under maintenance dialysis in DiN (26% vs.19%, p = 0.02); 79% of patients from DiN vs. 45% in DeN underwent peritoneal dialysis. Conclusions Major discrepancies between DiN and DeN in the management of nephropathic cystinosis remain a current concern for many patients living in countries with limited financial resources.

Worldwide view of nephropathic cystinosis: results from a survey from 30 countries;Aurélia Bertholet-Thomas;2017;Figshare


Abstract: Abstract Background Exponentially increasing numbers of NGS-based epigenomic datasets in public repositories like GEO constitute an enormous source of information that is invaluable for integrative and comparative studies of gene regulatory mechanisms. One of todayâ  s challenges for such studies is to identify functionally informative local and global patterns of chromatin states in order to describe the regulatory impact of the epigenome in normal cell physiology and in case of pathological aberrations. Critically, the most preferred Chromatin ImmunoPrecipitation-Sequencing (ChIP-Seq) is inherently prone to significant variability between assays, which poses significant challenge on comparative studies. One challenge concerns data normalization to adjust sequencing depth variation. Results Currently existing tools either apply linear scaling corrections and/or are restricted to specific genomic regions, which can be prone to biases. To overcome these restrictions without any external biases, we developed Epimetheus, a genome-wide quantile-based multi-profile normalization tool for histone modification data and related datasets. Conclusions Epimetheus has been successfully used to normalize epigenomics data in previous studies on X inactivation in breast cancer and in integrative studies of neuronal cell fate acquisition and tumorigenic transformation; Epimetheus is freely available to the scientific community.

Epimetheus - a multi-profile normalizer for epigenomic sequencing data;Mohamed-Ashick Saleem;2017;Figshare


Abstract: Additional file 3: Figure S3. In vitro interaction between HIV-1 IN, FACT and LEDGF/p75 variants. Immunoprecipitation or GST pull down were performed using recombinant cofactors, polyclonal anti-HIV-1 IN or anti-LEDGF antibodies. The interactions were monitored by direct gel staining using colloidal blue and quantified by Image J software.

MOESM3 of Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration;Julien Matysiak;2017;Figshare


Abstract: Additional file 4: Figure S4. FAIRE analysis and effect of UV-crosslinking on chromatin FACT and integration activities. FAIRE analyses were performed as indicated in materials and methods section and schematized in (A, adapted from [54]). Analysis of nucleosome remodeling activity of FACT on chromatinized substrates in vitro was performed by quantifying the free DNA recovered after FAIRE assay performed on naked p5S or chromatinized p5S loaded on 1% agarose gel after treatment or not with FACT complex and UV-treated or untreated (B). The recovered DNA was then quantified using ImageJ software and data are shown as the meanÂ ÂąÂ standard deviation (error bars) of at least three independent sets of experiments (C). A typical concerted integration performed with DNA substrate pre-treated with UV before FACT addition is reported in (D). Analysis of nucleosome remodeling activity of FACT on chromatinized substrates in vitro in the presence of absence of LEDGF/p75 is reported in (E).

MOESM4 of Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration;Julien Matysiak;2017;Figshare


Abstract: Abstract Background Stable insertion of the retroviral DNA genome into host chromatin requires the functional association between the intasome (integrase·viral DNA complex) and the nucleosome. The data from the literature suggest that direct protein–protein contacts between integrase and histones may be involved in anchoring the intasome to the nucleosome. Since histone tails are candidates for interactions with the incoming intasomes we have investigated whether they could participate in modulating the nucleosomal integration process. Results We show here that histone tails are required for an optimal association between HIV-1 integrase (IN) and the nucleosome for efficient integration. We also demonstrate direct interactions between IN and the amino-terminal tail of human histone H4 in vitro. Structure/function studies enabled us to identify amino acids in the carboxy-terminal domain of IN that are important for this interaction. Analysis of the nucleosome-binding properties of catalytically active mutated INs confirmed that their ability to engage the nucleosome for integration in vitro was affected. Pseudovirus particles bearing mutations that affect the IN/H4 association also showed impaired replication capacity due to altered integration and re-targeting of their insertion sites toward dynamic regions of the chromatin with lower nucleosome occupancy. Conclusions Collectively, our data support a functional association between HIV-1 IN and histone tails that promotes anchoring of the intasome to nucleosomes and optimal integration into chromatin.

Modulation of the functional association between the HIV-1 intasome and the nucleosome by histone amino-terminal tails;Mohamed Benleulmi;2017;Figshare


Abstract: Metatranscriptomic coverage for the predicted features of Zoogloea sp. LCSB751. Table S2. Metagenomic coverage for the assembly contigs of Zoogloea sp. LCSB751. Table S3. Zoogloea sp. LCSB751 CRISPR spacer complements (protospacer) as per reported by CRISPRTarget [32]. (XLSX 182Â kb)

Additional file 1: Table S1. of First draft genome sequence of a strain belonging to the Zoogloea genus and its gene expression in situ;Emilie Muller;2017;Figshare


Abstract: Sample breed and tagging breed groups. Samples (nÂ =Â 485) from either whole genome sequence (WGS) or from the 2M test array (SNP) were assigned to one of 15 tagging breed groups based on their reported breed. (XLSX 21 kb)

Additional file 5: Table S5. of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: Position of variants discovered from WGS data. File contains chromosome, bp position, distance from previous discovered SNP and alternate allele frequency for the 23 million SNP set. (TSV 828110 kb)

Additional file 6: of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: MNEc2M SNP information. Contains information for SNPs included on the MNEc2M array. Columns include MNEc identifiers, EquCab 2.0 coordinates, and fields indicating if the SNP was discovered in Draft and Pony groups (which were under-represented on the legacy arrays, See Additional file 2: Table S2). (CSV 82434 kb)

Additional file 7: of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: Breed specific tagging SNPs. File containing informative tagging SNPs broken down by breed. (CSV 172641 kb)

Additional file 8: of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: Figure S1. Alternate allele frequency for 23Â M and 10Â M SNP sets. Histograms show the alternative allele frequency for the ~23 million SNPs discovered by WGS and the ~10 million SNPs that were compatible with array design (see Table 1). A high number of SNPs were observed at 100% alternate allele frequency in a sample cohort that included deep sequencing (see Additional file 1: Table S1) of Twilight (the horse used for the reference genome) indicating likely Sanger sequence errors. (PNG 87 kb)

Additional file 9: of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: Additional file 7: Figure S7. Effect of FACT knock down on early steps of HIV-1 derived lentiviral vectors in HEK293T cells. The early steps of replication of lentiviral vectors in cells knockdown for SSRP1 (see Fig. 7) were evaluated by quantification of the viral DNA populations at 0–48 h post-transduction using quantitative PCR (data obtained after a 20 nM siRNA treatment are reported here). All values are shown as the mean ± standard deviation (error bars) of four independent sets of experiments done in duplicates.

MOESM7 of Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration;Julien Matysiak;2017;Figshare


Abstract: Figure S2. The effects of minor allele on imputation accuracy. SNPs were binned by minor allele count of the marker in the reference panel for each tagging breed group. SNPs were masked down to the 670k set then imputed up to ~2M. For SNPs in each minor allele count bin, a Pearson correlation was calculated between the imputed minor allele dosage and the true minor allele dosage. The x-axis in each panel are on a log scale to show the relationship for low minor allele count SNPs. (PNG 264 kb)

Additional file 10: of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: MNEc2M Inter-SNP distance and informativeness by breed. Distance between SNPs on the MNEc2M array were calculated by breed group (See Additional file 5: Table S5) at various minor allele frequency cutoffs (0, 0.01, 0.03, 0.05, 0.10). Breed groups with asterisk (*) indicate a combination of studbook breeds. (PNG 1152 kb)

Additional file 11: Figure S3. of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: Figure S4. MNEc670k Inter-SNP distance and informativeness by breed. Distance between SNPs on the MNEc670k array were calculated by breed group (Additional file 5: Table S5) at various minor allele frequency cutoffs (0, 0.01, 0.03, 0.05, and 0.10). Breed groups with asterisk (*) indicate a combination of studbook breeds. (PNG 1117 kb)

Additional file 12: of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: MNEc670k Breed Specific Alternate Allele Frequency. Alternate allele frequencies from variants present on the MNEc670k chip were split by breed group. Samples (WGSÂ +Â SNP) were split into 15 tagging breed groups (See Additional file 5: Table S5). Breed groups with asterisk (*) indicate a combination of studbook breeds. (PNG 814 kb)

Additional file 13: Figure S5. of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: Logistic regression of DNA Sample success. A logistic regression was fit, predicting the probability of a sample passing quality control using DNA concentration (Pico Green) and sample source as independent variables. (PNG 60 kb)

Additional file 14: Figure S6. of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: Whole genome sequencing (WGS) samples. Whole genome sequencing samples with horse identification and read depth. 153 Individuals representing 24 breeds (Twilight is included as 4 entries). Table includes horse identifier, breed, contributing laboratory and coverage statistics for each individual in both the nuclear and mitochondrial genomes. Variant calling groups indicate which individuals were grouped together during variant discovery. (XLSX 21 kb)

Additional file 1: Table S1. of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: SNP50 breed informativeness. Impact of breed on SNP50 informativeness. Table shows informativeness (MAF ≥ 0.05) of the legacy, SNP50 SNP set for light, draft, and pony breeds described by McCue et al. [1, 2]. Mean number of informative SNPs per breed was ~42,000 (~77%). 19,427 SNPs were informative in all 14 breeds. (XLSX 8 kb)

Additional file 2: Table S2. of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: SNP validation by discovery by variant calling group. SNPs discovered from whole genome sequence (See calling groups in Additional file 1: Table S1) were validated by assessing the minor allele frequency in individuals genotyped on the MNEc2M test array. (XLSX 8 kb)

Additional file 3: Table S3. of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: MNEc670k SNP information. Contains information on MNEc670k SNPs. Includes Affymetrix probe ID, genetic coordinates, MNEc Identifier, tissue origin indicating high quality genotyping in either hair root or blood, Affymetrix assigned genotyping cluster resolution, and inclusion criteria: Intra – SNP tags intra-breed haplotype, Inter – SNP tags inter-breed haplotype, MHC – SNP within Equine Major Histocompatibility Complex region, Diverse – SNP tags haplotype in 3 or more of diverse breeds that need many tagging SNPs (Quarter Horse, Pony, Morgan, Standardbred; See Additional file 4: Table S4), Density – SNP included to target at least 8 SNPs per 50 kb genomic window (targeting uniform genomic coverage). (XLSX 32510 kb)

Additional file 4: Table S4. of Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds;Robert Schaefer;2017;Figshare


Abstract: Additional file 1: Figure S1. Strategy for selection of cellular interactants of IN•viral DNA complex. Cellular extracts from HeLa P4 cells were first incubated with streptavidin beads coupled to the viral DNA fragments in order to avoid selecting proteins binding solely to the DNA. The elution was then incubated with streptavidin beads coupled to fractions enriched in active IN•viral DNA complexes (A). Formation of active IN•DNA complexes was checked in vitro concerted integration (B), the data obtained with increasing concentration of INs, 100, 200, 400 nM (lanes 1–3) are reported. The elution of the interacting proteins was loaded on 12% SDS-PAGE gel stained with silver nitrate and the bands were excised and electroeluted. A typical result from a selection performed with the IN•viral DNA and the control DNA alone is reported in (C).

MOESM1 of Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration;Julien Matysiak;2017;Figshare


Abstract: Additional file 2: Table S2. List of additionally selected proteins. Cellular extracts from HeLa P4 cells were incubated with streptavidin beads coupled to fraction enriched in active IN•viral DNA complexes as shown in Additional file 1: Figure S1. The elution of the interacting proteins was loaded on 12% SDS-PAGE gel stained with silver nitrate and the bands were excised from gel and submitted to electroelution. The selected proteins were identified by MS–MS. A list of proteins found only associated to IN•viral DNA complexes but not to control DNA alone and linked to chromatin or transcription is provided here in addition to the factors reported in Table 1.

MOESM2 of Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration;Julien Matysiak;2017;Figshare


Abstract: Additional file 5: Figure S5. Effect of FACT curaxin inhibitors on in vitro HIV-1 integration, cell viability and chromatin structure. The structure of CBL100 and CBL137 and their effect in typical concerted integration catalyzed by HIV-1 IN are shown in (A). The viability of the cells treated with curaxins was measured using a typical MTT assay and data are shown in (B). Effect of curaxin treatment on chromatin structure was analyzed by FAIR, as previously shown (C).

MOESM5 of Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration;Julien Matysiak;2017;Figshare


Abstract: Additional file 6: Figure S6. Effect of FACT-mediated chromatin remodeling chemical promotion on early steps of HIV-1 LAI virus and derived lentiviral vectors. HeLaP4 and HEK293T cells were treated with CBLC137 curaxin (0.1 µM) 6 h before cell infection with LAI wild type virus or transduction with lentiviral vectors. The effect on LAI virus (A) and viral vector (B) reverse transcription and integration was evaluated by quantitative PCR performed on the different viral DNA populations at 0–48 h post-transduction. All values are shown as the mean ± standard deviation (error bars) of at least three independent sets of experiments done in duplicates.

MOESM6 of Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration;Julien Matysiak;2017;Figshare


Abstract: Mast cell purity analyzed by flow cytometry. Primary MCs generated by culturing mice bone marrow cells for 4 weeks with IL-3/SCF were processed for staining with PE-labeled rat anti-mouse CD 117 and APC-labeled american hamster anti-mouse FcεRI. A FACScalibur equipped with Flowjo software was used for flow cytometry analysis. (TIFF 8219 kb)

Additional file 1: Figure S1. of Interaction of primary mast cells with Borrelia burgdorferi (sensu stricto): role in transmission and dissemination in C57BL/6 mice;Quentin Bernard;2017;Figshare


Abstract: (PPTX 5057 kb)

Additional file 1: Figures S1–S12 and Table S1. of The Arabidopsis SWI/SNF protein BAF60 mediates seedling growth control by modulating DNA accessibility;Teddy Jégu;2017;Figshare


Abstract: Raw data, Data collected and analyzed in this study. (XLS 57 kb)

Additional file 1: of Does the unexpected death of the manikin in a simulation maintain the participantsâ   perceived self-efficacy? An observational prospective study with medical students;Anne Weiss;2017;Figshare


Abstract: List of HD2B target genes in mock and flg22 conditions. (XLSX 167Â kb)

Additional file 2: of MAPK-triggered chromatin reprogramming by histone deacetylase in plant innate immunity;David Latrasse;2017;Figshare


Abstract: List of H3K9 hyper- and hypo-acetylated genes after flg22 treatment. (XLSX 60Â kb)

Additional file 3: of MAPK-triggered chromatin reprogramming by histone deacetylase in plant innate immunity;David Latrasse;2017;Figshare


Abstract: List of deregulated genes in hd2b and mpk3 mutants. (XLSX 51Â kb)

Additional file 4: of MAPK-triggered chromatin reprogramming by histone deacetylase in plant innate immunity;David Latrasse;2017;Figshare


Abstract: List of deregulated genes after flg22 treatment in Wt. (XLSX 52Â kb)

Additional file 5: of MAPK-triggered chromatin reprogramming by histone deacetylase in plant innate immunity;David Latrasse;2017;Figshare


Abstract: List of primers used in this study. (XLSX 13Â kb)

Additional file 6: of MAPK-triggered chromatin reprogramming by histone deacetylase in plant innate immunity;David Latrasse;2017;Figshare


Abstract: TaqMan design for genotyping H and H1 lineages. (XLSX 10 kb)

Additional file 1: of The distribution of mitochondrial DNA haplogroup H in southern Iberia indicates ancient human genetic exchanges along the western edge of the Mediterranean;Candela Hernández;2017;Figshare


Abstract: Mitochondrial molecular characterization of 337 Andalusians belonging to haplogroup H. Control region information is showed jointly with coding SNPs. (XLSX 65 kb)

Additional file 3: of The distribution of mitochondrial DNA haplogroup H in southern Iberia indicates ancient human genetic exchanges along the western edge of the Mediterranean;Candela Hernández;2017;Figshare


Abstract: Amplification primers and probes for the three SNaPshot multiplex reactions. (XLSX 62 kb)

Additional file 2: of The distribution of mitochondrial DNA haplogroup H in southern Iberia indicates ancient human genetic exchanges along the western edge of the Mediterranean;Candela Hernández;2017;Figshare


Abstract: Literature compilation for haplogroup H comparative analyses. Geographic affiliations are as follows: WME (Western Mediterranean Europe), WEU (Western Europe), CEU (Central Europe), NEU (North Eastern Europe), EEU (Eastern Europe), CME (Central Mediterranean Europe), CAU (Caucasus), ANA (Anatolia), NES (Near East), ARA (Arabian Peninsula), NAF (North Africa), WAF (Western Africa). Those studies that reached a deep level of resolution inside clade H (towards the definition of specific sub-clades by coding SNP testing) are underlined. The table shows the total sample size (N) and the number of individuals classified as belonging to haplogroup H (NH) for each population. (XLSX 16 kb)

Additional file 4: of The distribution of mitochondrial DNA haplogroup H in southern Iberia indicates ancient human genetic exchanges along the western edge of the Mediterranean;Candela Hernández;2017;Figshare


Abstract: An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

CCDC 2384604: Experimental Crystal Structure Determination;Schutz, Dorian;2024;Cambridge Crystallographic Data Centre

Related Article: Dorian Schutz, Maxime Hourtoule, Laurence Miesch|2024|Org.Chem.Front.|12|185|doi:10.1039/D4QO01802H


CCDC 2384608: Experimental Crystal Structure Determination;Schutz, Dorian;2024;Cambridge Crystallographic Data Centre


CCDC 2384609: Experimental Crystal Structure Determination;Schutz, Dorian;2024;Cambridge Crystallographic Data Centre


Abstract: A growing body of studies is showing that offspring telomere length (TL) can be influenced by the age of their parents. Such a relationship might be explained by variation in TL at conception (gamete effect) and/or by alteration of early growth conditions in species providing parental care. In a long-lived bird with bi-parental care, the Alpine swift (<i>Apus melba</i>), we exchanged an uneven number of 2 to 4-day-old nestlings between pairs as part of a brood size manipulation. Nestling TL was measured at 50 days after hatching, which allowed investigation of the influence of the age of both their biological and foster parents on offspring TL, after controlling for the manipulation. Nestling TL was negatively related to the age of their biological father and foster mother. Nestling TL did not differ between enlarged and reduced broods. These findings suggest that offspring from older males were fertilized by gametes with shorter telomeres, presumably due to a greater cell division history or a longer accumulation of damage, and that older females may have provided poorer parental care to their offspring.

Supplementary material from "Offspring telomere length in the long lived Alpine swift is negatively related to the age of their biological father and foster mother";François Criscuolo;2017;Figshare


Abstract: Fluorescence imaging well suited to provide image guidance during resections in oncologic and vascular surgery. However, the distorting effects of tissue optical properties on the emitted fluorescence are poorly compensated for on even the most advanced fluorescence image guidance systems, leading to subjective and inaccurate estimates of tissue fluorophore concentrations. Here we present a novel fluorescence imaging technique that performs real-time (i.e., video rate) optical property corrected fluorescence imaging. We perform full field of view simultaneous imaging of tissue optical properties using Single Snapshot of Optical Properties (SSOP) and fluorescence detection. The estimated optical properties are used to correct the emitted fluorescence with a quantitative fluorescence model to provide quantitative fluorescence-Single Snapshot of Optical Properties (qF-SSOP) images with less than 5% error. The technique is rigorous, fast, and quantitative, enabling ease of integration into the surgical workflow with the potential to improve molecular guidance intraoperatively.

qF-SSOP: Real-time optical property corrected fluorescence imaging;Pablo Valdes;2017;Figshare


Apollo-University Of Cambridge Repository

Supplementary data for "Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements";SH Lewis;2017;Apollo - University of Cambridge Repository


Abstract: Cattle dominate archaeozoological assemblages from the north-central Europe between the sixth and fifth millennium BC and are frequently considered as exclusively used for their meat. Dairy products may have played a greater role than previously believed. Selective pressure on the lactase persistence mutation has been modelled to have begun between 6000 and 4000 years ago in central Europe. The discovery of milk lipids in late sixth millennium ceramic sieves in Poland may reflect an isolated regional peculiarity for cheese making or may signify more generalized milk exploitation in north-central Europe during the Early Neolithic. To investigate these issues, we analysed the mortality profiles based on age-at-death analysis of cattle tooth eruption, wear and replacement from 19 archaeological sites of the Linearbandkeramik (LBK) culture (sixth to fifth millennium BC). The results indicate that cattle husbandry was similar across time and space in the LBK culture with a degree of specialization for meat exploitation in some areas. Statistical comparison with reference age-at-death profiles indicate that mixed husbandry (milk and meat) was practised, with mature animals being kept. The analysis provides a unique insight into LBK cattle husbandry and how it evolved in later cultures in Central and Western Europe. It also opens a new perspective on how and why the Neolithic way of life developed through continental Europe and how dairy products became a part of the human diet.

Supplementary material from "The evolution of dual meat and milk cattle husbandry in Linearbandkeramik societies";Rosalind E. Gillis;2017;Figshare


Abstract: Abstract Background The death of a simulated patient is controversial. Some educators feel that having a manikin die is prejudicial to learning; others feel it is a way of better preparing students for these situations. Perceived self-efficacy (PSE) reflects a person’s perception of their ability to carry out a task. A high PSE is necessary to manage a task efficiently. In this study, we measured the impact of the death of a simulated patient on medical students’ perceived self-efficacy concerning their ability to cope with a situation of cardiac arrest. Methods We carried out a single-centre, observational, prospective study. In group 1 (n = 27), pre-graduate medical students were warned of the possible death of the manikin; group 2 students were not warned (n = 29). The students’ PSE was measured at the end of the simulated situation and after the debriefing. Results The PSE of the two groups was similar before the debriefing (p = 0.41). It had significantly progressed at the end of the debriefing (p

Does the unexpected death of the manikin in a simulation maintain the participants’ perceived self-efficacy? An observational prospective study with medical students;Anne Weiss;2017;Figshare


Abstract: Abstract Background Plant adaptive responses to changing environments involve complex molecular interplays between intrinsic and external signals. Whilst much is known on the signaling components mediating diurnal, light, and temperature controls on plant development, their influence on chromatin-based transcriptional controls remains poorly explored. Results In this study we show that a SWI/SNF chromatin remodeler subunit, BAF60, represses seedling growth by modulating DNA accessibility of hypocotyl cell size regulatory genes. BAF60 binds nucleosome-free regions of multiple G box-containing genes, opposing in cis the promoting effect of the photomorphogenic and thermomorphogenic regulator Phytochrome Interacting Factor 4 (PIF4) on hypocotyl elongation. Furthermore, BAF60 expression level is regulated in response to light and daily rhythms. Conclusions These results unveil a short path between a chromatin remodeler and a signaling component to fine-tune plant morphogenesis in response to environmental conditions.

The Arabidopsis SWI/SNF protein BAF60 mediates seedling growth control by modulating DNA accessibility;Teddy Jégu;2017;Figshare


Abstract: Abstract Background Nutrition guidelines recommendations differ on the use of parenteral nutrition (PN), and existing clinical trial data are inconclusive. Our recent observational data show that amounts of energy/protein received early in the intensive care unit (ICU) affect patient mortality, particularly for inadequate nutrition intake in patients with body mass indices (BMIs) of <25 or >35. Thus, we hypothesized increased nutrition delivery via supplemental PN (SPN) + enteral nutrition (EN) to underweight and obese ICU patients would improve 60-day survival and quality of life (QoL) versus usual care (EN alone). Methods In this multicenter, randomized, controlled pilot trial completed in 11 centers across four countries, adult ICU patients with acute respiratory failure expected to require mechanical ventilation for >72 hours and with a BMI of <25 or ≥35 were randomized to receive EN alone or SPN + EN to reach 100% of their prescribed nutrition goal for 7 days after randomization. The primary aim of this pilot trial was to achieve a 30% improvement in nutrition delivery. Results In total, 125 patients were enrolled. Over the first 7 post-randomization ICU days, patients in the SPN + EN arm had a 26% increase in delivered calories and protein, whereas patients in the EN-alone arm had a 22% increase (both p

A randomized trial of supplemental parenteral nutrition in underweight and overweight critically ill patients: the TOP-UP pilot trial;Paul E. Wischmeyer;2017;Figshare


Abstract: The genome of the spider mite Tetranychus urticae, a plant herbivore, is missing important elements of the canonical Drosophila immune pathways necessary to fight bacterial infections. However, it is not known whether spider mites can mount an immune response and survive bacterial infection. In other chelicerates, bacterial infection elicits a response mediated by immune effectors leading to the survival of infected organisms. In T. urticae, infection by either Escherichia coli or Bacillum megaterium did not elicit a response as assessed through genome-wide transcriptomic analysis. In line with this, spider mites died within days even upon injection with low doses of bacteria that are non-pathogenic to Drosophila. Moreover, bacterial populations grew exponentially inside the infected spider mites. By contrast, Sancassania berlesei, a litter-dwelling mite, controlled bacterial proliferation and resisted infections with both Gram-negative and Gram-positive bacteria lethal to T. urticae. This differential mortality between mite species was absent when mites were infected with heat-killed bacteria. Also, we found that spider mites harbour in their gut 1000-fold less bacteria than S. berlesei. We show that T. urticae has lost the capacity to mount an induced immune response against bacteria, in contrast to other mites and chelicerates but similarly to the phloem feeding aphid Acyrthosiphon pisum. Hence, our results reinforce the putative evolutionary link between ecological conditions regarding exposure to bacteria and the architecture of the immune response.

Supplementary material from "<i>Tetranychus urticae</i> mites do not mount an induced immune response against bacteria";Gonçalo Matos;2017;Figshare


Abstract: Telomeres, the non-coding ends of linear chromosomes, are thought to be an important mechanism of individual variability in performance. Research suggests that longer telomeres are indicative of better health and increased fitness; however, much of these data are correlational and whether these effects are casual are poorly understood. Experimental tests are emerging in medical and laboratory-based studies, but these types of experiments are rare in natural populations, which precludes conclusions at an evolutionary level. At the crossroads between telomere length and fitness is telomerase, an enzyme that can lengthen telomeres. Experimental modulation of telomerase activity is a powerful tool to manipulate telomere length, and to look at the covariation of telomerase, telomeres and individual life-history traits. Here, we review studies that manipulate telomerase activity in laboratory conditions and emphasize the associated physiological and fitness consequences. We then discuss how telomerase's impact on ageing may go beyond telomere maintenance. Based on this overview, we then propose several research avenues for future studies to explore how individual variability in health, reproduction and survival may have coevolved with different patterns of telomerase activity and expression. Such knowledge is of prime importance to fully understand the role that telomere dynamics play in the evolution of animal ageing.This article is part of the theme issue ‘Understanding diversity in telomere dynamics’.

Supplementary material from "Experimental manipulation of telomere length: does it reveal a corner-stone role for telomerase in the natural variability of individual fitness?";F. Criscuolo;2017;Figshare


Abstract: Abstract Background Borrelia burgdorferi (sensu lato), the causative agent of Lyme borreliosis is a bacterium transmitted by hard ticks, Ixodes spp. Bacteria are injected into the host skin during the tick blood meal with tick saliva. There, Borrelia and saliva interact together with skin cells such as keratinocytes, fibroblasts, mast cells and other specific immune cells before disseminating to target organs. Methods To study the role of mast cells in the transmission of Lyme borreliosis, we isolated mouse primary mast cells from bone marrow and incubated them in the presence of Borrelia burgdorferi (sensu stricto) and tick salivary gland extract. We further analyzed their potential role in vivo, in a mouse model of deficient in mast cells (Kit wsh−/− mice). Results To our knowledge, we report here for the first time the bacteria ability to induce the inflammatory response of mouse primary mast cells. We show that OspC, a major surface lipoprotein involved in the early transmission of Borrelia, induces the degranulation of primary mast cells but has a limited effect on the overall inflammatory response of these cells. In contrast, whole bacteria have an opposite effect. We also show that mast cell activation is significantly inhibited by tick salivary gland extract. Finally, we demonstrate that mast cells are likely not the only host cells involved in the early transmission and dissemination of Borrelia since the use of mast cell deficient Kit wsh−/− mice shows a limited impact on these two processes in the context of this mouse genetic background. Conclusions The absence of mast cells did not change the replication rate of Borrelia in the skin. However, in the absence of mast cells, Borrelia dissemination to the joints was faster. Mast cells do not control skin bacterial proliferation during primary infection and the establishment of the primary infection, as shown in the C57BL/6 mouse model studied. Nevertheless, the Borrelia induced cytotokine modulation on mast cells might be involved in long term and/or repeated infections and protect from Lyme borreliosis due to the development of a hypersensitivity to tick saliva.

Interaction of primary mast cells with Borrelia burgdorferi (sensu stricto): role in transmission and dissemination in C57BL/6 mice;Quentin Bernard;2017;Figshare


Abstract: Influence of age on mortality in patients with VZV pneumonia. (TIFF 675 kb)

Additional file 5: Figure S2. of Severe varicella-zoster virus pneumonia: a multicenter cohort study;Adrien Mirouse;2017;Figshare


Abstract: Seasonal distribution of VZV pneumonia from 1996 to 2015. (TIFF 731 kb)

Additional file 2: Figure S1. of Severe varicella-zoster virus pneumonia: a multicenter cohort study;Adrien Mirouse;2017;Figshare


Abstract: Abstract Background An important challenge of the longitudinal analysis of health-related quality of life (HRQOL) is the potential occurrence of a Response Shift (RS) effect. While the impact of RS effect on the longitudinal analysis of HRQOL has already been studied, few studies have been conducted on its impact on the determination of the Minimal Important Difference (MID). This study aims to investigate the impact of the RS effect on the determination of the MID over time for each scale of both EORTC QLQ-C30 and QLQ-BR23 questionnaires in breast cancer patients. Methods Patients with breast cancer completed the EORTC QLQ-C30 and the EORTC QLQ-BR23 questionnaires at baseline (time of diagnosis; T0), three months (T1) and six months after surgery (T2). Four hospitals and care centers participated in this study: cancer centers of Dijon and Nancy, the university hospitals of Reims and Strasbourg At T1 and T2, patients were asked to evaluate their HRQOL change during the last 3 months using the Jaeschke transition question. They were also asked to assess retrospectively their HRQOL level of three months ago. The occurrence of the RS effect was explored using the then-test method and its impact on the determination of the MID by using the Anchor-based method. Results Between February 2006 and February 2008, 381 patients were included of mean age 58 years old (SD = 11). For patients who reported a deterioration of their HRQOL level at each follow-up, an increase of RS effect has been detected between T1 and T2 in 13/15 dimensions of QLQ-C30 questionnaire, and 4/7 dimensions of QLQ-BR23 questionnaire. In contrast, a decrease of the RS effect was observed in 8/15 dimensions of QLQ-C30 questionnaire and in 5/7 dimensions of QLQ-BR23 questionnaire in case of improvement. At T2, the MID became ≥ 5 points when taking into account the RS effect in 10/15 dimensions of QLQ-C30 questionnaire and in 5/7 dimensions of QLQ-BR23 questionnaire. Conclusions This study highlights that the RS effect increases over time in case of deterioration and decreases in case of improvement. Moreover, taking the RS into account produces a reliable and significant MID.

Impact of the occurrence of a response shift on the determination of the minimal important difference in a health-related quality of life score over time;Ahmad Ousmen;2016;Figshare


Abstract: Abstract Background Cramps are involuntary painful muscle contractions that mainly affect older people. Cramps may cause severe pain and sleep disturbance. Little information exists on the prevalence and the main features of cramps in primary care settings. The objective of this study was to estimate the prevalence and the main features of cramps among primary care patients aged 60 years and older. Methods We prospectively enrolled 516 patients aged 60 years and older in a cross-sectional study at 25 general practices in Alsace – France between October 2011 and March 2012. Questionnaires were used to obtain information about demographics, cramp presence and main features, medical history, and treatment. Results The adjusted prevalence was 46 % (95 % CI: 38–53 %). Thirty-one per cent of the study sample reported being woken up by cramps, 15 % had cramps more than 3 times a month. Logistic regression revealed a slightly higher prevalence in the age group 65–69 years compared to 60–64 years. No significant association was observed between other age groups and prevalence, or between gender and prevalence. The main localization of cramps was in the calves (80 %). The duration since onset was 5 years or more for 58 %. Conclusions Cramps are common in primary care, and although only a minority of patients report suffering from cramps more than once a week, many patients report cramp-related sleep disturbance. Further studies are needed to assess risk factors and therapeutic options for patients suffering from cramps in primary care.

Prevalence of cramps in patients over the age of 60 in primary care : a cross sectional study;Hubert Maisonneuve;2016;Figshare


Abstract: Abstract Background Karyotypic integrity is essential for the successful germline transmission of alleles mutated in embryonic stem (ES) cells. Classical methods for the identification of aneuploidy involve cytological analyses that are both time consuming and require rare expertise to identify mouse chromosomes. Results As part of the International Mouse Phenotyping Consortium, we gathered data from over 1,500 ES cell clones and found that the germline transmission (GLT) efficiency of clones is compromised when over 50 % of cells harbour chromosome number abnormalities. In JM8 cells, chromosomes 1, 8, 11 or Y displayed copy number variation most frequently, whilst the remainder generally remain unchanged. We developed protocols employing droplet digital polymerase chain reaction (ddPCR) to accurately quantify the copy number of these four chromosomes, allowing efficient triage of ES clones prior to microinjection. We verified that assessments of aneuploidy, and thus decisions regarding the suitability of clones for microinjection, were concordant between classical cytological and ddPCR-based methods. Finally, we improved the method to include assay multiplexing so that two unstable chromosomes are counted simultaneously (and independently) in one reaction, to enhance throughput and further reduce the cost. Conclusion We validated a PCR-based method as an alternative to classical karyotype analysis. This technique enables laboratories that are non-specialist, or work with large numbers of clones, to precisely screen ES cells for the most common aneuploidies prior to microinjection to ensure the highest level of germline transmission potential. The application of this method allows early exclusion of aneuploid ES cell clones in the ES cell to mouse conversion process, thus improving the chances of obtaining germline transmission and reducing the number of animals used in failed microinjection attempts. This method can be applied to any other experiments that require accurate analysis of the genome for copy number variation (CNV).

Aneuploidy screening of embryonic stem cell clones by metaphase karyotyping and droplet digital polymerase chain reaction;Gemma Codner;2016;Figshare


Abstract: From 1735 to 1940, maize-based diets led to the death of hundreds of thousands of people from Pellagra, a complex disease caused by tryptophan and vitamin B3 deficiencies. The current cereal monoculture trend restricts farmland animals to similarly monotonous diets. However, few studies have distinguished the effects of crop nutritional properties on the reproduction of these species from those of other detrimental factors such as pesticide toxicity or agricultural ploughing. This study shows that maize-based diets cause high rates of maternal infanticides in the European hamster, a farmland species on the verge of extinction in Western Europe. Vitamin B3 supplementation is shown to effectively restore reproductive success in maize-fed females. This study pinpoints how nutritional deficiencies caused by maize monoculture could affect farmland animal reproduction and hence their fitness.

Supplementary material from "Diets derived from maize monoculture cause maternal infanticides in the endangered European hamster owing to a vitamin B3 deficiency";Mathilde L. Tissier;2016;Figshare


Abstract: Abstract Background Culicoides spp. biting midges transmit bluetongue virus (BTV), the aetiological agent of bluetongue (BT), an economically important disease of ruminants. In southern India, hyperendemic outbreaks of BT exert high cost to subsistence farmers in the region, impacting on sheep production. Effective Culicoides spp. monitoring methods coupled with accurate species identification can accelerate responses for minimising BT outbreaks. Here, we assessed the utility of sampling methods and DNA barcoding for detection and identification of Culicoides spp. in southern India, in order to provide an informed basis for future monitoring of their populations in the region. Methods Culicoides spp. collected from Tamil Nadu and Karnataka were used to construct a framework for future morphological identification in surveillance, based on sequence comparison of the DNA barcode region of the mitochondrial cytochrome c oxidase I (COI) gene and achieving quality standards defined by the Barcode of Life initiative. Pairwise catches of Culicoides spp. were compared in diversity and abundance between green (570Â nm) and ultraviolet (UV) (390Â nm) light emitting diode (LED) suction traps at a single site in Chennai, Tamil Nadu over 20 nights of sampling in November 2013. Results DNA barcode sequences of Culicoides spp. were mostly congruent both with existing DNA barcode data from other countries and with morphological identification of major vector species. However, sequence differences symptomatic of cryptic species diversity were present in some groups which require further investigation. While the diversity of species collected by the UV LED Center for Disease Control (CDC) trap did not significantly vary from that collected by the green LED CDC trap, the UV CDC significantly outperformed the green LED CDC trap with regard to the number of Culicoides individuals collected. Conclusions Morphological identification of the majority of potential vector species of Culicoides spp. samples within southern India appears relatively robust; however, potential cryptic species diversity was present in some groups requiring further investigation. The UV LED CDC trap is recommended for surveillance of Culicoides in southern India.

DNA barcoding and surveillance sampling strategies for Culicoides biting midges (Diptera: Ceratopogonidae) in southern India;Lara Harrup;2016;Figshare


Abstract: Abstract Background Blastocystis sp. is the most common intestinal parasite of humans. Despite its potential public health impact, epidemiological data regarding the prevalence and molecular subtype distribution of Blastocystis sp. in Europe are rarely reported. Therefore, the first multi-center epidemiological survey performed in Europe was conducted in France to diagnose and subtype Blastocystis sp. and to identify risk factors for infection. Methods Stool samples from 788 patients were collected either in summer or winter in 11 hospitals throughout France together with patient data. All stool samples were tested for the presence of Blastocystis sp. by quantitative PCR targeting the SSU rDNA gene. Positive samples were sequenced to determine the distribution of the subtypes in our cohort. Statistical analyses were performed to identify potential risk factors for infection. Results Using quantitative PCR, the overall prevalence of Blastocystis sp. was shown to reach 18.1 %. The prevalence was significantly higher in summer (23.2 %) than in winter (13.7 %). Travellers or subjects infected with other enteric parasites were significantly more infected by Blastocystis sp. than non-travellers or subjects free of other enteric parasites, respectively. Different age-related epidemiological patterns were also highlighted from our data. The prevalence of Blastocystis sp. was not significantly higher in patients with digestive symptoms or diagnosed with chronic bowel diseases. Among symptomatic patients, Blastocystis sp. infection was significantly associated with abdominal pain. Gender, socioeconomic status, and immune status were not identified as potential risk factors associated with infection. Among a total of 141 subtyped isolates, subtype 3 was predominant (43.3 %), followed by subtype 1 and subtype 4 (20 %), subtype 2 (12.8 %), subtype 6 and subtype 7 (2.1 %). No association between ST and clinical symptoms was statistically evidenced. Conclusions A high prevalence of Blastocystis sp. infection was found in our French patient population. Seasonal impact on the prevalence of Blastocystis sp. was highlighted and recent travels and age were identified as main risk factors for infection. Most cases were caused by subtypes 1 to 4, with a predominance of subtype 3. Large variations in both prevalence and ST distribution between hospitals were also observed, suggesting distinct reservoirs and transmission sources of the parasite.

Prevalence, risk factors for infection and subtype distribution of the intestinal parasite Blastocystis sp. from a large-scale multi-center study in France;Dima El Safadi;2016;Figshare


Abstract: Abstract Background The success of the CRISPR/Cas9 genome editing technique depends on the choice of the guide RNA sequence, which is facilitated by various websites. Despite the importance and popularity of these algorithms, it is unclear to which extent their predictions are in agreement with actual measurements. Results We conduct the first independent evaluation of CRISPR/Cas9 predictions. To this end, we collect data from eight SpCas9 off-target studies and compare them with the sites predicted by popular algorithms. We identify problems in one implementation but found that sequence-based off-target predictions are very reliable, identifying most off-targets with mutation rates superior to 0.1 %, while the number of false positives can be largely reduced with a cutoff on the off-target score. We also evaluate on-target efficiency prediction algorithms against available datasets. The correlation between the predictions and the guide activity varied considerably, especially for zebrafish. Together with novel data from our labs, we find that the optimal on-target efficiency prediction model strongly depends on whether the guide RNA is expressed from a U6 promoter or transcribed in vitro. We further demonstrate that the best predictions can significantly reduce the time spent on guide screening. Conclusions To make these guidelines easily accessible to anyone planning a CRISPR genome editing experiment, we built a new website ( http://crispor.org ) that predicts off-targets and helps select and clone efficient guide sequences for more than 120 genomes using different Cas9 proteins and the eight efficiency scoring systems evaluated here.

Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR;Maximilian Haeussler;2016;Figshare


Abstract: Abstract Background Dispersal is often associated with a suite of phenotypic traits that might reduce dispersal costs, but can be energetically costly themselves outside dispersal. Hence, dispersing and philopatric individuals might differ throughout their life cycle in their management of energy production. Because higher energy expenditure can lead to the production of highly reactive oxidative molecules that are deleterious to the organism if left uncontrolled, dispersing and philopatric individuals might differ in their management of oxidative balance. Here, we experimentally increased flight costs during reproduction via a wing load manipulation in female collared flycatchers (Ficedula albicollis) breeding in a patchy population. We measured the effects of the manipulation on plasmatic markers of oxidative balance and reproductive success in dispersing and philopatric females. Results The impact of the wing load manipulation on the oxidative balance differed according to dispersal status. The concentration of reactive oxygen metabolites (ROMs), a marker of pro-oxidant status, was higher in philopatric than dispersing females in the manipulated group only. Differences between dispersing and philopatric individuals also depended on habitat quality, as measured by local breeding density. In low quality habitats, ROMs as well as nestling body mass were higher in philopatric females compared to dispersing ones. Independently of the manipulation or of habitat quality, plasma antioxidant capacity differed according to dispersal status: philopatric females showed higher antioxidant capacity than dispersing ones. Nestlings raised by philopatric females also had a higher fledging success. Conclusions Our results suggest that dispersing individuals maintain a stable oxidative balance when facing challenging environmental conditions, at the cost of lower reproductive success. Conversely, philopatric individuals increase their effort, and thus oxidative costs, in challenging conditions thereby maintaining their reproductive success. Our study sheds light on energetics and oxidative balance as possible processes underlying phenotypic differences between dispersing and philopatric individuals.

Differences in the oxidative balance of dispersing and non-dispersing individuals: an experimental approach in a passerine bird;Charlotte Récapet;2016;Figshare


Abstract: Abstract Background Theory of mind (ToM) refers to the ability to attribute mental states, thoughts (cognitive component) or feelings (affective component) to others. This function has been studied in many neurodegenerative diseases; however, to our knowledge, no studies investigating ToM in dementia with Lewy bodies (DLB) have been published. The aim of our study was to assess ToM in patients with DLB and to search for neural correlates of potential deficits. Methods Thirty-three patients with DLB (DLB group) and 15 patients with Alzheimer’s disease (AD group), all in the early stage of the disease, as well as 16 healthy elderly control subjects (HC group), were included in the study. After a global cognitive assessment, we used the Faux Pas Recognition (FPR) test, the Reading the Mind in the Eyes (RME) test and Ekman’s Facial Emotion Recognition test to assess cognitive and affective components of ToM. Patients underwent cerebral 3-T magnetic resonance imaging, and atrophy of grey matter was analysed using voxel-based morphometry. We performed a one-sample t test to investigate the correlation between each ToM score and grey matter volume and a two-sample t test to compare patients with DLB impaired with those non-impaired for each test. Results The DLB group performed significantly worse than the HC group on the FPR test (P = 0.033) and the RME test (P = 0.015). There was no significant difference between the AD group and the HC group or between the DLB group and the AD group. Some brain regions were associated with ToM impairments. The prefrontal cortex, with the inferior frontal cortex and the orbitofrontal cortex, was the main region, but we also found correlations with the temporoparietal junction, the precuneus, the fusiform gyrus and the insula. Conclusions This study is the first one to show early impairments of ToM in DLB. The two cognitive and affective components both appear to be affected in this disease. Among patients with ToM difficulties, we found atrophy in brain regions classically involved in ToM, which reinforces the neuronal network of ToM. Further studies are now needed to better understand the neural basis of such impairment.

Cognitive and affective theory of mind in dementia with Lewy bodies and Alzheimer’s disease;Camille Heitz;2016;Figshare


Abstract: Abstract Background Plasmodium vivax is considered to be absent from western Africa, where the prevalence of Duffy-negative red blood cell phenotype proves to be high. Several studies have, however, detected P. vivax infection cases in this part of Africa, raising the question of what is the actual prevalence of P. vivax in local populations. Methods The presence of P. vivax was investigated in a large population of healthy blood donors in Benin using microscopy, serology and molecular detection. The seroprevalence was measured with species-specific ELISA using two recombinant P. vivax proteins, namely rPvMSP1 and rPvCSP1. Specific molecular diagnosis of P. vivax infection was carried out using nested-PCR. The performances and cut-off values of both rPvCSP1 and rPvMSP1 ELISA were first assessed using sera from P. vivax-infected patients and from non-exposed subjects. Results Among 1234 Beninese blood donors, no parasites were detected when using microscopy, whereas 28.7% (354/1234) of patients exhibited had antibodies against rPvMSP1, 21.6% (266/1234) against rPvCSP1, and 15.2% (187/1234) against both. Eighty-four samples were selected for nested-PCR analyses, of which 13 were positive for P. vivax nested-PCR and all Duffy negative. Conclusion The results of the present study highlight an unexpectedly high exposure of Beninese subjects to P. vivax, resulting in sub-microscopic infections. This suggests a probably underestimated and insidious parasite presence in western Africa. While the vaccination campaigns and therapeutic efforts are all focused on Plasmodium falciparum, it is also essential to consider the epidemiological impact of P. vivax.

The hide and seek of Plasmodium vivax in West Africa: report from a large-scale study in Beninese asymptomatic subjects;Philippe Poirier;2016;Figshare


Abstract: Abstract Conventional techniques for single-base resolution mapping of epigenetic modifications of DNA such as 5-hydroxymethylcytosine (5hmC) rely on the sequencing of bisulfite-modified DNA. Here we present an alternative approach called SCL-exo which combines selective chemical labeling (SCL) of 5hmC in genomic DNA with exonuclease (exo) digestion of the bead-trapped modified DNA molecules. Associated with a straightforward bioinformatic analysis, this new procedure provides an unbiased and fast method for mapping this epigenetic mark at high resolution. Implemented on mouse genomic DNA from in vitro-differentiated neural precursor cells, SCL-exo sheds light on an intrinsic lack of conservation of hydroxymethylated CpGs across vertebrates.

Single-CpG resolution mapping of 5-hydroxymethylcytosine by chemical labeling and exonuclease digestion identifies evolutionarily unconserved CpGs as TET targets;Aurélien Sérandour;2016;Figshare


Abstract: Riboswitches are non-coding elements upstream or downstream of mRNAs that, upon binding of a specific ligand, regulate transcription and/or translation initiation in bacteria, or alternative splicing in plants and fungi. We have studied thiamine pyrophosphate (TPP) riboswitches regulating translation of thiM operon and transcription and translation of thiC operon in E. coli, and that of THIC in the plant A. thaliana. For all, we ascertained an induced-fit mechanism involving initial binding of the TPP followed by a conformational change leading to a higher-affinity complex. The experimental values obtained for all kinetic and thermodynamic parameters of TPP binding imply that the regulation by A. thaliana riboswitch is governed by mass-action law, whereas it is of kinetic nature for the two bacterial riboswitches. Kinetic regulation requires that the RNA polymerase pauses after synthesis of each riboswitch aptamer to leave time for TPP binding, but only when its concentration is sufficient. A quantitative model of regulation highlighted how the pausing time has to be linked to the kinetic rates of initial TPP binding to obtain an ON/OFF switch in the correct concentration range of TPP. We verified the existence of these pauses and the model prediction on their duration. Our analysis also led to quantitative estimates of the respective efficiency of kinetic and thermodynamic regulations, which shows that kinetically regulated riboswitches react more sharply to concentration variation of their ligand than thermodynamically regulated riboswitches. This rationalizes the interest of kinetic regulation and confirms empirical observations that were obtained by numerical simulations.

Quantitative and predictive model of kinetic regulation by <i>E. coli</i> TPP riboswitches;Sondés Guedich;2016;Figshare


Supplementary material from "Scratch that itch%3A revisiting links between self-directed behaviour and parasitological, social and environmental factors in a free-ranging primate";Julie Duboscq;2016;Figshare


Abstract: Abstract Background Pertuzumab, trastuzumab, and docetaxel is standard of care for first-line treatment of HER2-positive metastatic breast cancer (MBC). However, alternative chemotherapy partners are required to align with patient/physician preferences and to increase treatment flexibility. We report VELVET Cohort 1 results in which the efficacy and safety of pertuzumab and trastuzumab, administered sequentially in separate infusions, followed by vinorelbine, were evaluated. Cohort 2, where pertuzumab and trastuzumab were administered in a single infusion, followed by vinorelbine, recruited after Cohort 1 was fully enrolled, will be reported later. Methods In this multicenter, two-cohort, open-label, phase II study, patients with HER2-positive locally advanced or MBC who had not received chemotherapy or biological therapy for their advanced disease received 3-weekly pertuzumab (840 mg loading, 420 mg maintenance doses) and trastuzumab (8 mg/kg loading, 6 mg/kg maintenance doses), followed by vinorelbine (25 mg/m2 initial dose, 30–35 mg/m2 maintenance doses) on days 1 and 8 or 2 and 9 of each 3-weekly cycle. Study treatment was given until investigator-assessed disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate (ORR) in patients with measurable disease at baseline per RECIST v1.1. Secondary endpoints included progression-free survival (PFS) and safety. Results Cohort 1 enrolled 106 patients. Investigator-assessed ORR was 74.2% (95% CI 63.8–82.9) in intent-to-treat patients with measurable disease (89/106 [84.0%]). Median PFS was 14.3 months (95% CI 11.2–17.5) in the intent-to-treat population. Treatment was reasonably well tolerated, with no unexpected toxicities. Diarrhea (61/106 patients [57.5%]) and neutropenia (54/106 [50.9%]) were the most common adverse events (AEs); neutropenia (33/106 [31.1%]) and leukopenia (14/106 [13.2%]) were the most common grade ≥3 AEs. Serious AEs were reported in 32/106 (30.2%) patients. AEs led to study drug discontinuation in 36/106 patients (34.0%). Eighteen of 106 patients (17.0%) had AEs suggestive of congestive heart failure; however, there were no confirmed cases. Conclusions The vinorelbine, pertuzumab, and trastuzumab combination is active and reasonably well tolerated. This regimen offers an alternative for patients who cannot receive docetaxel for first-line treatment of HER2-positive locally advanced or MBC. Trial registration ClinicalTrials.gov: NCT01565083 , registered on 26 March 2012.

Safety and efficacy of vinorelbine in combination with pertuzumab and trastuzumab for first-line treatment of patients with HER2-positive locally advanced or metastatic breast cancer: VELVET Cohort 1 final results;Edith Perez;2016;Figshare


Abstract: Abstract Background Modulation of protein activity by phosphorylation through kinases and subsequent de-phosphorylation by phosphatases is one of the most prominent cellular control mechanisms. Thus, identification of kinase substrates is pivotal for the understanding of many â   if not all â   molecular biological processes. Equally, the possibility to deliberately tune kinase activity is of great value to analyze the biological process controlled by a particular kinase. Results Here we have applied a chemical genetic approach and generated an analog-sensitive version of CDKA;1, the central cell-cycle regulator in Arabidopsis and homolog of the yeast Cdc2/CDC28 kinases. This variant could largely rescue a cdka;1 mutant and is biochemically active, albeit less than the wild type. Applying bulky kinase inhibitors allowed the reduction of kinase activity in an organismic context in vivo and the modulation of plant growth. To isolate CDK substrates, we have adopted a two-dimensional differential gel electrophoresis strategy, and searched for proteins that showed mobility changes in fluorescently labeled extracts from plants expressing the analog-sensitive version of CDKA;1 with and without adding a bulky ATP variant. A pilot set of five proteins involved in a range of different processes could be confirmed in independent kinase assays to be phosphorylated by CDKA;1 approving the applicability of the here-developed method to identify substrates. Conclusion The here presented generation of an analog-sensitive CDKA;1 version is functional and represent a novel tool to modulate kinase activity in vivo and identify kinase substrates. Our here performed pilot screen led to the identification of CDK targets that link cell proliferation control to sugar metabolism, proline proteolysis, and glucosinolate production providing a hint how cell proliferation and growth are integrated with plant development and physiology.

Modulation of plant growth in vivo and identification of kinase substrates using an analog-sensitive variant of CYCLIN-DEPENDENT KINASE A;1;Hirofumi Harashima;2016;Figshare