Vowel production: a potential speech biomarker for early detection of dysarthria in Parkinson’s disease

ObjectivesOur aim is to detect early, subclinical speech biomarkers of dysarthria in Parkinson’s disease (PD), i.e., systematic atypicalities in speech that remain subtle, are not easily detectible by the clinician, so that the patient is labeled “non-dysarthric.” Based on promising exploratory work, we examine here whether vowel articulation, as assessed by three acoustic metrics, can be used as early indicator of speech difficulties associated with Parkinson’s disease.Study designThis is a prospective case–control study.MethodsSixty-three individuals with PD and 35 without PD (healthy controls-HC) participated in this study. Out of 63 PD patients, 43 had been diagnosed with dysarthria (DPD) and 20 had not (NDPD). Sustained vowels were recorded for each speaker and formant frequencies were measured. The analyses focus on three acoustic metrics: individual vowel triangle areas (tVSA), vowel articulation index (VAI) and the Phi index.ResultstVSA were found to be significantly smaller for DPD speakers than for HC. The VAI showed significant differences between these two groups, indicating greater centralization and lower vowel contrasts in the DPD speakers with dysarhtria. In addition, DPD and NDPD speakers had lower Phi values, indicating a lower organization of their vowel system compared to the HC. Results also showed that the VAI index was the most efficient to distinguish between DPD and NDPD whereas the Phi index was the best acoustic metric to discriminate NDPD and HC.ConclusionThis acoustic study identified potential subclinical vowel-related speech biomarkers of dysarthria in speakers with Parkinson’s disease who have not been diagnosed with dysarthria

Результаты российского проспективного обсервационного исследования СПЕКТР

ПРОСПЕКТИВНЫЕ ИССЛЕДОВАНИЯНАСЕЛЕНИЯ ГРУПП ИЗУЧЕНИЕВЕНОЗНАЯ НЕДОСТАТОЧНОСТЬКРОВЕНОСНЫХ СОСУДОВ БОЛЕЗН

HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32).

International audienceThe t(5;14)(q35;q32) chromosomal translocation is specifically observed in up to 20% of childhood T-cell acute lymphoblastic leukemia (T-ALL). It affects the BCL11B/CTIP2 locus on chromosome 14 and the RANBP17-TLX3/HOX11L2 region on chromosome 5. It leads to ectopic activation of TLX3/HOX11L2. To investigate the reasons of the association between t(5;14) and T-ALL, we isolated the translocation breakpoints in 8 t(5;14) patients. Sequence analyses did not involve recombinase activity in the genesis of the translocation. We used DNAse1 hypersensitive experiments to locate transcriptional regulatory elements downstream of BCL11B. By transient transfection experiments, 2 of the 6 regions demonstrated cis-activation properties in T cells and were also effective on the TLX3 promoter. Our data indicate that the basis of the specific association between t(5;14) and T-ALL lies on the juxtaposition of TLX3 to long-range cis-activating regions active during T-cell differentiation

The cis-regulatory architecture of a gene desert controlling pleiotropic Shox2 expression and cardiac pacemaker development

Trabajo presentado en Weinstein Meeting, celebrado en Marsella (Francia) del 12 al 14 de mayo de 2022

Evaluation of global fire simulations in CMIP6 Earth system models

Fire is the primary form of terrestrial ecosystem disturbance on a global scale and an important Earth system process. Most Earth system models (ESMs) have incorporated fire modeling, with 19 out of them submitting model outputs of fire-related variables to the Coupled Model Intercomparison Project Phase 6 (CMIP6). This study provides the first comprehensive evaluation of CMIP6 historical fire simulations by comparing them with multiple satellite-based products and charcoal-based historical reconstructions. Our results show that most CMIP6 models simulate the present-day global burned area and fire carbon emissions within the range of satellite-based products. They also capture the major features of observed spatial patterns and seasonal cycles, the relationship of fires with precipitation and population density, and the influence of El Niño-Southern Oscillation (ENSO) on the interannual variability of tropical fires. Regional fire carbon emissions simulated by the CMIP6 models from 1850 to 2010 generally align with the charcoal-based reconstructions, although there are regional mismatches, such as in southern South America and eastern temperate North America prior to the 1910s and in temperate North America, eastern boreal North America, Europe, and boreal Asia since the 1980s. The CMIP6 simulations have addressed three critical issues identified in the CMIP5: (1) the simulated global burned area less than half of the observations, (2) the failure to reproduce the high burned area fraction observed in Africa, and (3) the weak fire seasonal variability. Furthermore, the CMIP6 models exhibit improved accuracy in capturing the observed relationship between fires and both climatic and socioeconomic drivers, and better align with the historical long-term trends indicated by charcoal-based reconstructions in most regions worldwide. However, the CMIP6 models still fail to reproduce the decline in global burned area and fire carbon emissions observed over the past two decades, mainly attributed to an underestimation of anthropogenic fire suppression, and the spring peak in fires in the Northern Hemisphere mid-latitudes, mainly due to an underestimation of crop fires. In addition, the model underestimates the fire sensitivity to wet-dry conditions, indicating the need to improve fuel wetness estimation. Based on these findings, we present specific guidance for fire scheme development and suggest the post-processing methodology for using CMIP6 multi-model outputs to generate reliable fire projection products

Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: Association with subtype, body-mass index, severity and age of onset.

Anorexia nervosa (AN) affects 0.3% of young girls with a mortality of 6%/decade and is strongly familial with genetic factors. Ghrelin is an upstream regulator of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to leptin's effects on NPY/AgRP-expressing neurons, resulting in an increase in feeding and body weight. Obestatin which counteracts ghrelin action on feeding is derived from the same propeptide than ghrelin. BDNF has been involved in body weight regulation and its Val66Met polymorphism associated with AN. We therefore re-investigated the association between AN and the Leu72Met and Gln90Leu polymorphisms of the prepro-ghrelin/obestatin gene, the Ala67Thr polymorphism of AgRP and the Val66Met polymorphism of BDNF taking into account clinical subtypes (restrictive-ANR-and bingeing/purging-ANB-subtypes). Family trios study of these 4 single nucleotide polymorphisms were performed in 114 probands with AN and both their parents recruited in two specialized French centres. A transmission disequilibrium was observed for the Leu72Met SNP of the preproghrelin gene and for the Ala67Thr SNP of the AgRP gene. When stratified by clinical subtype, these two polymorphisms were preferentially transmitted for the trios with a bingeing/purging proband. An excess of transmission of the Gln90Leu72 preproghrelin/obestatin haplotype in patients with AN was observed. These results do not provide evidence for a preferential transmission of the 66Met allele of BDNF but support the hypothesis that ghrelin and AGRP polymorphisms confers susceptibility to AN. Further simultaneous analysis of genetic variants of the biological determinants of energy metabolism and feeding behaviour in very large populations should contribute to the understanding of the high degree of heritability of eating disorders and to the description of pathophysiological patterns leading to life-threatening conditions in a highly redundant system

BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination

In meiotic homologous recombination (HR), BRCA2 facilitates loading of the recombinases RAD51 and DMC1 at the sites of double-strand breaks (DSBs). The HSF2BP-BRME1 complex interacts with BRCA2. Its absence causes a severe reduction in recombinase loading at meiotic DSB. We previously showed that, in somatic cancer cells ectopically producing HSF2BP, DNA damage can trigger HSF2BP-dependent degradation of BRCA2, which prevents HR. Here, we report that, upon binding to BRCA2, HSF2BP forms octameric rings that are able to interlock into a large ring-shaped 24-nucleotide oligomer. Addition of BRME1 leads to dissociation of both of these ring structures and cancels the disruptive effect of HSF2BP on cancer cell resistance to DNA damage. It also prevents BRCA2 degradation during interstrand DNA crosslink repair in Xenopus egg extracts. We propose that, during meiosis, the control of HSF2BP-BRCA2 oligomerization by BRME1 ensures timely assembly of the ring complex that concentrates BRCA2 and controls its turnover, thus promoting HR.</p

Salmonella control in poultry flocks and its public health impact

An increase in confirmed human salmonellosis cases in the EU after 2014 triggered investigation of contributory factors and control options in poultry production. Reconsideration of the five current target serovars for breeding hens showed that there is justification for retaining Salmonella Enteritidis, Salmonella Typhimurium (including monophasic variants) and Salmonella Infantis, while Salmonella Virchow and Salmonella Hadar could be replaced by Salmonella Kentucky and either Salmonella Heidelberg, Salmonella Thompson or a variable serovar in national prevalence targets. However, a target that incorporates all serovars is expected to be more effective as the most relevant serovars in breeding flocks vary between Member State (MS) and over time. Achievement of a 1% target for the current target serovars in laying hen flocks is estimated to be reduced by 254,400 CrI95[98,540; 602,700] compared to the situation in 2016. This translates to a reduction of 53.4% CrI95[39.1; 65.7] considering the layer-associated human salmonellosis true cases and 6.2% considering the overall human salmonellosis true cases in the 23 MSs included in attribution modelling. A review of risk factors for Salmonella in laying hens revealed that overall evidence points to a lower occurrence in non-cage compared to cage systems. A conclusion on the effect of outdoor access or impact of the shift from conventional to enriched cages could not be reached. A similar review for broiler chickens concluded that the evidence that outdoor access affects the occurrence of Salmonella is inconclusive. There is conclusive evidence that an increased stocking density, larger farms and stress result in increased occurrence, persistence and spread of Salmonella in laying hen flocks. Based on scientific evidence, an impact of Salmonella control programmes, apart from general hygiene procedures, on the prevalence of Campylobacter in broiler flocks at the holding and on broiler meat at the end of the slaughter process is not expected

Human papillomavirus genotype distribution and socio-behavioural characteristics in women with cervical pre-cancer and cancer at the start of a human papillomavirus vaccination programme: the CIN3+ plus study.

The Swiss Federal Office of Public Health has recommended vaccination against human papillomavirus (HPV) to prevent cervical cancer since 2008. To establish monitoring of the future public health impact of vaccination, baseline population-based data are required. The objectives of this study were to examine the distribution of oncogenic HPV genotypes in biopsies with cervical intraepithelial neoplasia stage 3 or more severe lesions (CIN3+) at the beginning of HPV vaccination programmes and to compare sociodemographic and behavioural factors of women with CIN3+ with women in the Swiss general population. We conducted a retrospective and prospective cross-sectional study with women diagnosed with CIN3+ in Switzerland. Ten pathology institutes from six cantons and three language regions participated. We conducted HPV typing on formaldehyde fixed-paraffin embedded specimens from 2014 and 2015. Women enrolled in 2015 were asked to complete a questionnaire. We described frequencies of HPV types. We also compared demographic characteristics and socioeconomic status in the CIN3 + plus group with the Swiss National Cohort in 2014 and compared risk factors for HPV infection with the Swiss Health Survey in 2012. We included 768 biopsies from 767 women. Four hundred and seventy-five (61.8%) biopsies were positive for HPV 16 and/or 18, 687 (89.5%) were positive for oncogenic HPV genotypes 16, 18, 31, 33, 45, 52, and/or 58 and five (0.7%) were HPV negative. Twenty-eight (10.3%) of the 273 women who completed the patient questionnaire reported having received at least one dose of an HPV vaccine. When compared with Swiss women in the six study cantons, fewer women in the CIN3+ plus study group were of Swiss nationality, more were born abroad and more were single. The study group also had a higher proportion of women with ≥2 partners in the last year, current smokers and was younger at age of first sexual intercourse. Introduction of the nonavalent vaccine could cover approximately 90% of CIN3+ lesions in Swiss women compared with around 60% with the quadrivalent vaccine. Surveillance of HPV genotype distribution in CIN3+, together with information about vaccination and CIN3+ incidence will allow monitoring of the public health impact of vaccination programmes. ClinicalTrials.gov, NCT02323997 . Registered 24 December 2014