University of Montpellier

About: University of Montpellier is a education organization based out in Montpellier, Languedoc-Roussillon, France. It is known for research contribution in the topics: Population & Context (language use). The organization has 26816 authors who have published 53843 publications receiving 1646905 citations. The organization is also known as: Université de Montpellier.

Interpreting the genomic landscape of speciation: a road map for finding barriers to gene flow.

Abstract: Speciation, the evolution of reproductive isolation among populations, is continuous, complex, and involves multiple, interacting barriers. Until it is complete, the effects of this process vary along the genome and can lead to a heterogeneous genomic landscape with peaks and troughs of differentiation and divergence. When gene flow occurs during speciation, barriers restricting gene flow locally in the genome lead to patterns of heterogeneity. However, genomic heterogeneity can also be produced or modified by variation in factors such as background selection and selective sweeps, recombination and mutation rate variation, and heterogeneous gene density. Extracting the effects of gene flow, divergent selection and reproductive isolation from such modifying factors presents a major challenge to speciation genomics. We argue one of the principal aims of the field is to identify the barrier loci involved in limiting gene flow. We first summarize the expected signatures of selection at barrier loci, at the genomic regions linked to them and across the entire genome. We then discuss the modifying factors that complicate the interpretation of the observed genomic landscape. Finally, we end with a road map for future speciation research: a proposal for how to account for these modifying factors and to progress towards understanding the nature of barrier loci. Despite the difficulties of interpreting empirical data, we argue that the availability of promising technical and analytical methods will shed further light on the important roles that gene flow and divergent selection have in shaping the genomic landscape of speciation.

Multi-system neurological disease is common in patients with OPA1 mutations

Abstract: Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal 'dominant optic atrophy plus' variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44-6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08-4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment.

Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis

Abstract: Mesenchymal stem or stromal cells (MSCs) exert chondroprotective effects in preclinical models of osteoarthritis (OA). Most of their therapeutic effects are mediated via soluble mediators, which can be conveyed within extracellular vesicles (EVs). The objective of the study was to compare the respective role of exosomes (Exos) or microvesicles/microparticles (MPs) in OA. MPs and Exos were isolated from bone marrow murine BM-MSCs through differential centrifugation. Effect of MPs or Exos was evaluated on OA-like murine chondrocytes and chondroprotection was quantified by RT-qPCR. In OA-like chondrocytes, BM-MSC-derived MPs and Exos could reinduce the expression of chondrocyte markers (type II collagen, aggrecan) while inhibiting catabolic (MMP-13, ADAMTS5) and inflammatory (iNOS) markers. Exos and MPs were also shown to protect chondrocytes from apoptosis and to inhibit macrophage activation. In vivo, Exos or MPs were injected in the collagenase-induced OA (CIOA) model and histomorphometric analyses of joints were performed by µCT and confocal laser microscopy. BM-MSCs, MPs and Exos equally protected mice from joint damage. In conclusion, MPs and Exos exerted similar chondroprotective and anti-inflammatory function in vitro and protected mice from developing OA in vivo, suggesting that either Exos or MPs reproduced the main therapeutic effect of BM-MSCs.

International AIDS Society global scientific strategy: towards an HIV cure 2016

Abstract: Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.