Les grès inférieurs du Trias cévennol : systèmes sédimentaires fluviatiles et laguno-marins.

Mémoire HS n° 13 - Géologie Alpine : Le détritisme dans le Sud-Est de la France - Colloque Association des Géologues du Sud-est - Grenoble 11-12 décembre 1986La série des Grès inférieurs du Trias cévenol s'organise en deux mégaséquences positives. La première débute par l'installation générale d 'un système fluviatile en tresse. La dynamique fluviatile s'affaiblit ensuite nettement (systèmes en tresse distaux ou rivière à forte sinuosité) tandis que vers l'aval et latéralement, des domaines lagunaires et laguno-marins, à tranche d'eau faible et permanente, s'installent progressivement et de façon plus prononcée au NE et au SW. La présence d'organismes marins (Echinodermes, ForaIninifères) est la preuve d 'une communication avec le milieu marin. La seconde mégaséquence débute également par un épisode fluviatile plus localisé géographiquement ou par l'installation d'une plaine alluviale très distale, passant progressivement à des milieux lagunaires. Avec la Barre Carbonatée Médiane (Carnien basal), on assiste à un retour des milieux marins peu profonds. Leur arrivée brutale reflète sans doute un évenement structural majeur sur la bordure. Les apports fluviatiles principaux ont été guidés par des couloirs orientés NW-SE tandis qu'une structuration NE-SW, parallèle à la bordure , a régi la distribution géographique des domaines de sédimentation évaporitique importants

Reliability of a Field-Based Test for Hamstrings and Quadriceps Strength Assessment in Football Players

Background: Field-based tests using portable devices are extremely helpful to assist physicians and coaches in the assessment of athletes’ muscle strength and for injury risk screening. The aim of this study was to investigate the reliability of a field-based test to assess unilateral hamstring and quadriceps isometric muscle strength in a nearly extended position (30 knee flexion) in football players. Methods: Nineteen male football players completed the field-based test on two separate occasions, one week apart, to produce a test–retest design. To complete the test, participants performed maximal isometric efforts on a custom-built bench with 30 of knee flexion and 90 of hip flexion while the force applied was measured with a portable load cell at 80 Hz. On each occasion, participants performed two 2 s maximal isometric repetitions intending to flex and extend the knee to assess hamstring and quadriceps strength, respectively. In each repetition, the force developed during the maximum voluntary isometric contraction (MVIC) and rate of force development (RFD) metrics for hamstring (H) and quadriceps (Q) were collected, and the H:Q ratio was calculated afterwards. Results: MVIC showed the highest reliability for the measurement of both hamstring and quadriceps strength (ICC > 0.80, [95% CI: 0.55, 0.96]; CV 0.75, [95% CI: 0.48, 0.95]; CV < 15%, [95% CI: 8.9, 22.4]). RFD0–150 and RFD0–250 yielded moderate reliability values for hamstring strength (ICC = 0.78–0.86, [95% CI: 0.52, 0.94]; CV = 20–27%, [95% CI: 15, 39.7]). RFD0–50 presented the largest variability (ICC 25%, [95% CI: 19.2, 45.3]). Conclusions: The field-based test presented here provided reliable results for the measurement of maximal isometric hamstring and quadriceps strength and for the calculation of the H:Q ratio. However, the measurement of RFD with this test is less reliable. This test allows reliable field-based assessments of hamstring and quadriceps maximal isometric strength which can be helpful to identify muscle strength deficits and imbalances during injury prevention and management processes in football players.Ministry of Universities of Spain (grant number: FPU21/04536

Anthropometric profiles in table tennis players: Analysis of sex, age, and ranking

Table tennis has recently evolved towards a more spectacular sport increasing match-play demands and the intensity and speed of actions by regulations and equipment modification. Since these changes can alter the body composition and performance, this study aimed to analyze the differences in anthropometric attributes of 495 table tennis players (288 men, 207 women) according to sex, age, and ranking. Players were classified according to sex, age categories (Senior, Under-18, Under-15, Under 13, and Under 11), and ranking position. Anthropometry measurements included eight skinfolds’ thicknesses (biceps brachii, triceps, subscapular, iliac crest, supraspinal, abdominal, thigh, and medial calf), four girths (biceps brachii relaxed and contracted, thigh, and calf), and three breadths (biepicondylar femur, biepicondylar humerus, and bistiloyd wrist) to determine fat mass, lean mass, bone, cross sectional area (CSA) for arm, leg, and thigh, and somatotype. Results revealed that table tennis players presented differences in body mass composition, anthropometry, and somatotype according to sex and age category and ranking. It seems confirmed that regular table tennis practice during the childhood is associated with a healthy body composition status, that appears to be maintained across older ages if keeping the practice. Senior table tennis players showed a fat mass <20% and lean mass ~45% in men and ~37% in women. A new contribution is that higher lean mass in the upper limbs was associated with higher ranking position (i.e., better performance), endomorphic somatotypes were negative related to performance, and ectomorphic profiles seems more effective, which suggest the potential influence of morphologic changes in table tennis competition performance

The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition

The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.260

A CADM3 variant causes Charcot-Marie-Tooth disease with marked upper limb involvement

The CADM family of proteins consists of four neuronal specific adhesion molecules (CADM1, CADM2, CADM3 and CADM4) that mediate the direct contact and interaction between axons and glia. In the peripheral nerve, axon-Schwann cell interaction is essential for the structural organization of myelinated fibres and is primarily mediated by the binding of CADM3, expressed in axons, to CADM4, expressed by myelinating Schwann cells. We have identified—by whole exome sequencing—three unrelated families, including one de novo patient, with axonal Charcot-Marie-Tooth disease (CMT2) sharing the same private variant in CADM3, Tyr172Cys. This variant is absent in 230 000 control chromosomes from gnomAD and predicted to be pathogenic. Most CADM3 patients share a similar phenotype consisting of autosomal dominant CMT2 with marked upper limb involvement. High resolution mass spectrometry analysis detected a newly created disulphide bond in the mutant CADM3 potentially modifying the native protein conformation. Our data support a retention of the mutant protein in the endoplasmic reticulum and reduced cell surface expression in vitro. Stochastic optical reconstruction microscopy imaging revealed decreased co-localization of the mutant with CADM4 at intercellular contact sites. Mice carrying the corresponding human mutation (Cadm3Y170C) showed reduced expression of the mutant protein in axons. Cadm3Y170C mice showed normal nerve conduction and myelin morphology, but exhibited abnormal axonal organization, including abnormal distribution of Kv1.2 channels and Caspr along myelinated axons. Our findings indicate the involvement of abnormal axon-glia interaction as a disease-causing mechanism in CMT patients with CADM3 mutations. A correction has been published: Brain, Volume 144, Issue 7, July 2021, Page e64, https://doi.org/10.1093/brain/awab18

Cell Surface Sialylation and Fucosylation Are Regulated by L1 via Phospholipase Cγ and Cooperate to Modulate Neurite Outgrowth, Cell Survival and Migration

BACKGROUND: Cell surface glycosylation patterns are markers of cell type and status. However, the mechanisms regulating surface glycosylation patterns remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using a panel of carbohydrate surface markers, we have shown that cell surface sialylation and fucosylation were downregulated in L1(-/y) neurons versus L1(+/y) neurons. Consistently, mRNA levels of sialyltransferase ST6Gal1, and fucosyltransferase FUT9 were significantly reduced in L1(-/y) neurons. Moreover, treatment of L1(+/y) neurons with L1 antibodies, triggering signal transduction downstream of L1, led to an increase in cell surface sialylation and fucosylation compared to rat IgG-treated cells. ShRNAs for both ST6Gal1 and FUT9 blocked L1 antibody-mediated enhancement of neurite outgrowth, cell survival and migration. A phospholipase Cgamma (PLCgamma) inhibitor and shRNA, as well as an Erk inhibitor, reduced ST6Gal1 and FUT9 mRNA levels and inhibited effects of L1 on neurite outgrowth and cell survival. CONCLUSIONS: Neuronal surface sialylation and fucosylation are regulated via PLCgamma by L1, modulating neurite outgrowth, cell survival and migration

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes

Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes

Assessing non-Mendelian inheritance in inherited axonopathies

PURPOSE: Inherited axonopathies (IA) are rare, clinically and genetically heterogeneous diseases that lead to length-dependent degeneration of the long axons in central (hereditary spastic paraplegia [HSP]) and peripheral (Charcot–Marie–Tooth type 2 [CMT2]) nervous systems. Mendelian high-penetrance alleles in over 100 different genes have been shown to cause IA; however, about 50% of IA cases do not receive a genetic diagnosis. A more comprehensive spectrum of causative genes and alleles is warranted, including causative and risk alleles, as well as oligogenic multilocus inheritance. METHODS: Through international collaboration, IA exome studies are beginning to be sufficiently powered to perform a pilot rare variant burden analysis. After extensive quality control, our cohort contained 343 CMT cases, 515 HSP cases, and 935 non-neurological controls. We assessed the cumulative mutational burden across disease genes, explored the evidence for multilocus inheritance, and performed an exome-wide rare variant burden analysis. RESULTS: We replicated the previously described mutational burden in a much larger cohort of CMT cases, and observed the same effect in HSP cases. We identified a preliminary risk allele for CMT in the EXOC4 gene (p value= 6.9 × 10-6, odds ratio [OR] = 2.1) and explored the possibility of multilocus inheritance in IA. CONCLUSION: Our results support the continuing emergence of complex inheritance mechanisms in historically Mendelian disorders