Arabidopsis katanin binds microtubules using a multimeric microtubule-binding domain.

Katanin is a heterodimeric protein that mediates ATP-dependent destabilization of microtubules in animal cells. In plants, the catalytic subunit of Arabidopsis thaliana katanin (AtKSS, Arabidopsis thaliana Katanin Small Subunit) has been identified and its microtubule-severing activity has been demonstrated in vitro. In vivo, plant katanin plays a role in the organization of cortical microtubules, but the way it achieves this function is unknown. To go further in our understanding of the mechanisms by which katanin severs microtubules, we analyzed the functional domains of Arabidopsis katanin. We characterized the microtubule-binding domain of katanin both in vitro and in vivo. It corresponds to a poorly conserved sequence between plant and animal katanins that is located in the N-terminus of the protein. This domain interacts with cortical microtubules in vivo and has a low affinity for microtubules in vitro. We also observed that katanin microtubule-binding domain oligomerizes into trimers. These results show that, besides being involved in the interaction of katanin with microtubules, the microtubule-binding domain may also participate in the oligomerization of katanin. At the structural level, we observed that AtKSS forms ring-shaped oligomers

Gas emissions due to magma-sediment interactions during flood magmatism at the Siberian Traps: gas dispersion and environmental consequences.

International audienceWe estimate the fluxes of extremely reduced gas emissions produced during the emplacement of the Siberian Traps large igneous province, due to magma intrusion in the coaliferous sediments of the Tunguska Basin. Using the results of a companion paper (Iacono-Marziano et al. submitted to EPSL), and a recent work about low temperature interaction between magma and organic matter (Svensen et al., 2009), we calculate CO-CH4-dominated gas emission rates of 7×1015-2×1016 g/yr for a single magmatic/volcanic event. These fluxes are 7 to 20 times higher than those calculated for purely magmatic gas emissions, in the absence of interaction with organic matter-rich sediments. We investigate, by means of atmospheric modelling employing present geography of Siberia, the short and mid term dispersion of these gas emissions into the atmosphere. The lateral propagation of CO and CH4 leads to an important perturbation of the atmosphere chemistry, consisting in a strong reduction of the radical OH concentration. As a consequence, both CO and CH4 lifetimes in the lower atmosphere are enhanced by a factor of at least 3, at the continental scale, as a consequence of 30 days of magmatic activity. The short-term effect of the injection of carbon monoxide and methane into the atmosphere is therefore to increase the residence times of these two species and, in turn, their capacity of geographic expansion. The estimated CO and CH4 volume mixing ratios (i.e. the number of molecules of CO or CH4 per cm3, divided by the total number of molecules per cm3) in the low atmosphere are 2-5 ppmv at the continental scale and locally higher than 50 ppmv. The dimension of the area affected by these high volume mixing ratios decreases in the presence of a lava flow accompanying magma intrusion at depth. Complementary calculations for a 10-year duration of the magmatic activity suggest (i) an increase in the mean CH4 volume mixing ratio of the whole atmosphere up to values 3 to 15 times higher than the current one, and (ii) recovery times of 100 years to bring back the atmospheric volume mixing ratio of CH4 to the pre-magmatic value. Thermogenic methane emissions from the Siberian Traps has already been proposed to crucially contribute to end Permian-Early Triassic global warming and to the negative carbon isotopic shift observed globally in both marine and terrestrial sediments. Our results corroborate these hypotheses and suggest that concurrent high temperature CO emissions also played a key role by contributing to increase (i) the radiative forcing of methane and therefore in its global warming potential, and (ii) the input of isotopically light carbon into the atmosphere that generated the isotopic excursion. We also speculate a poisoning effect of high carbon monoxide concentrations on end-Permian fauna, at a local scale

Extremely reducing conditions reached during basaltic intrusion in organic matter-bearing sediments

International audienceRedox conditions in magma are widely interpreted as internally buffered and closely related to that of their mantle source regions. We use thermodynamic calculations to show that high-temperature interaction between magma and organic matter can lead to a dramatic reduction of the magma redox state, and significant departure from that of the original source. Field studies provide direct evidence of the process that we describe, with reported occurrences of graphite and native iron in igneous mafic rocks, implying very reducing conditions that are almost unknown in average terrestrial magmas. We calculate that the addition of 0.6 wt% organic matter (in the form of CH or CH2) to a standard basalt triggers graphite and native iron crystallisation at depths of few hundred meters. Interaction with organic matter also profoundly affects the abundance and the redox state of the gases in equilibrium with the magma, which are CO-dominated with H2 as the second most abundant species on a molar basis, H2O and CO2 being minor constituents. The assimilation of only 0.1 wt% organic matter by a basalt causes a decrease in its oxygen fugacity of 2-orders of magnitude. The assimilation of 0.6 wt% organic matter at depths < 500 m implies minimum CO content in the magma of 1 wt%, other gas components being less than 0.1 wt%. In the light of our calculations, we suggest that the production of native iron-bearing lava flows and associated intrusions was most likely accompanied by degassing of CO-rich gases, whose fluxes depended on the magma production rates

Segregation between SMCHD1 mutation, D4Z4 hypomethylation and Facio-Scapulo-Humeral Dystrophy: a case report

International audienceBackground: The main form of Facio-Scapulo-Humeral muscular Dystrophy is linked to copy number reduction of the 4q D4Z4 macrosatellite (FSHD1). In 5 % of cases, FSHD phenotype appears in the absence of D4Z4 reduction (FSHD2). In 70-80 % of these patients, variants of the SMCHD1 gene segregate with 4qA haplotypes and D4Z4 hypomethylation.Case presentation: We report a family presenting with neuromuscular symptoms reminiscent of FSHD but without D4Z4 copy reduction. We characterized the 4q35 region using molecular combing, searched for mutation in the SMCHD1 gene and determined D4Z4 methylation level by sodium bisulfite sequencing. We further investigated the impact of the SMCHD1 mutation at the protein level and on the NMD-dependent degradation of transcript. In muscle, we observe moderate but significant reduction in D4Z4 methylation, not correlated with DUX4-fl expression. Exome sequencing revealed a heterozygous insertion of 7 bp in exon 37 of the SMCHD1 gene producing a loss of frame with premature stop codon 4 amino acids after the insertion (c.4614-4615insTATAATA). Both wild-type and mutated transcripts are detected.Conclusion: The truncated protein is absent and the full-length protein level is similar in patients and controls indicating that in this family, FSHD is not associated with SMCHD1 haploinsufficiency

Environmental risk factors in puppies and kittens for developing chronic disorders in adulthood: A call for research on developmental programming

Many dogs and cats are affected by chronic diseases that significantly impact their health and welfare and relationships with humans. Some of these diseases can be challenging to treat, and a better understanding of early-life risk factors for diseases occurring in adulthood is key to improving preventive veterinary care and husbandry practices. This article reviews early-life risk factors for obesity and chronic enteropathy, and for chronic behavioral problems, which can also be intractable with life-changing consequences. Aspects of early life in puppies and kittens that can impact the risk of adult disorders include maternal nutrition, establishment of the gut microbiome, maternal behavior, weaning, nutrition during growth, growth rate, socialization with conspecifics and humans, rehoming and neutering. Despite evidence in some species that the disorders reviewed here reflect the developmental origins of health and disease (DOHaD), developmental programming has rarely been studied in dogs and cats. Priorities and strategies to increase knowledge of early-life risk factors and DOHaD in dogs and cats are discussed. Critical windows of development are proposed: preconception, gestation, the suckling period, early growth pre-neutering or pre-puberty, and growth post-neutering or post-puberty to adult size, the durations of which depend upon species and breed. Challenges to DOHaD research in these species include a large number of breeds with wide genetic and phenotypic variability, and the existence of many mixed-breed individuals. Moreover, difficulties in conducting prospective lifelong cohort studies are exacerbated by discontinuity in pet husbandry between breeders and subsequent owners, and by the dispersed nature of pet ownership

Highlighting of the interactions of MYD88 and NFKB1 SNPs in rats resistant to decompression sickness: toward an autoimmune response

Decompression sickness (DCS) with neurological disorders includes an inappropriate inflammatory response which degenerates slowly, even after the disappearance of the bubbles. There is high inter-individual variability in terms of the occurrence of DCS that could have been mastered by the selection and then the breeding of DCS-resistant rats. We hypothesized the selection of single-nucleotide polymorphisms (SNPs) linked to autoimmunity operated upon a generation of a DCS-resistant strain of rats. We used the candidate gene approach and targeted SNPs linked to the signaling cascade that directly regulates inflammation of innate immunity transiting by the Toll-like receptors. Twenty candidate SNPs were investigated in 36 standard rats and 33 DCS-resistant rats. For the first time, we identify a diplotype (i.e., with matched haplotypes)—when coinherited—that strengthens protection against DCS, which is not strictly homozygous and suggests that a certain tolerance may be considered. We deduced an ideal haplotype of six variants from it (MyD88_50-T, _49-A, _97-C coupled to NFKB_85-T, _69-T, _45-T) linked to the resistant phenotype. Four among the six identified variants are located in pre- and/or post-transcriptional areas regulating MyD88 or NFKB1 expression. Because of missense mutations, the other two variants induce a structural change in the NFKB1 protein complex including one damage alteration according to the Missense3D algorithm. In addition to the MyD88/NFKB1 haplotype providing rats with a strong resistance to DCS, this also highlights the importance that the immune response, here linked to the genetic heritage, can have in the development of DCS and offer a new perspective for therapeutic strategies

A high-density linkage map of the RN region in pigs

The porcine RN locus affects muscle glycogen content and meat quality. We previously mapped the RN locus to chromosome 15. This study describes the identification of polymorphisms for four class I and four class II markers located in the RN region. Resource families were genotyped with F-SSCP markers (fluorescent single strand conformation polymorphism) and microsatellite markers. Subsequent multipoint linkage analysis revealed the order FN1-IGFBP5-S1000-S1001-IL8RB-VIL1-RN-Sw936-Sw906. The gene order is identical to the previously reported porcine RH map of the same region. The described map will facilitate positional cloning of the RN gene

Admission criteria and management of critical care patients in a pandemic context: position of the Ethics Commission of the French Intensive Care Society, update of April 2021.

Intensive care unit professionals have experience in critical care and its proportionality, collegial decision-making, withholding or withdrawal of treatment deemed futile, and communication with patients' relatives. These elements rely on ethical values from which we must not deviate in a pandemic situation. The recommendations made by the Ethics Commission of the French Intensive Care Society reflect an approach of responsibility and solidarity towards our citizens regarding the potential impact of a pandemic on critical care resources in France, with the fundamental requirement of respect for human dignity and equal access to health care for all

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Réflectométrie en lumière polarisée faiblement cohérente

The complex amplitude of the reflection coefficient of a component can be derived from Optical Low Coherence Reflectometry measurements. When the samples are birefringent, beat lobes can be observed in reflection coefficient amplitude as well as oscillations in phase curve which make their data processing difficult. In order to characterize these components, it is then necessary to take the polarization into consideration in the analysis considering not only the sample but also the different elements of the apparatus. In this thesis, we have integrated polarization in the reflectometer theory to characterize polarization maintaining fibres or photonic crystal fibres which are arrangements of micrometric longitudinal air channels. We have developed a method which requires only a few measurements and leads to the characteristic parameters of single axis components : the phase birefringence, the group birefringence and the chromatic dispersion along the component’s eigenaxis. A numerical analysis and the measurements performed on these fibres show the validity of our method.La réflectométrie en lumière faiblement cohérente est une méthode parfaitement éprouvée permettant de mesurer le coefficient de réflexion en amplitude d’un composant. Cependant, pour des composants biréfringents, des battements apparaissent dans le spectre du coefficient de réflexion ainsi que des oscillations dans la courbe de phase ce qui rend difficile leur exploitation. Il est donc impératif, pour caractériser de tels composants, d’intégrer la polarisation dans l’analyse en tenant compte de l’échantillon sous test mais également des différents éléments constituant l’appareil de mesures. Dans cette thèse, nous avons intégré la polarisation dans la théorie du réflectomètre pour caractériser des fibres à maintien de polarisation ou des fibres microstructurées qui sont des fibres spéciales constituées d’un arrangement de canaux d’air longitudinaux de section micronique. Nous avons mis au point une méthode permettant en quelques mesures seulement d’accéder aux paramètres caractéristiques d’un composant uniaxe tels la biréfringence de phase, la biréfringence de groupe et la dispersion chromatique suivant les deux axes propres du composant. Une étude numérique et des mesures effectuées sur ces fibres ont démontré la validité de notre méthode