Multi-parametric evaluation of sit-to-stand and stand-to-sit transitions in elderly people.

The aim of this study was to extract multi-parametric measures characterizing different features of sit-to-stand (Si-St) and stand-to-sit (St-Si) transitions in older persons, using a single inertial sensor attached to the chest. Investigated parameters were transition's duration, range of trunk tilt, smoothness of transition pattern assessed by its fractal dimension, and trunk movement's dynamic described by local wavelet energy. A measurement protocol with a Si-St followed by a St-Si postural transition was performed by two groups of participants: the first group (N=79) included Frail Elderly subjects admitted to a post-acute rehabilitation facility and the second group (N=27) were healthy community-dwelling elderly persons. Subjects were also evaluated with Tinetti's POMA scale. Compared to Healthy Elderly persons, frail group at baseline had significantly longer Si-St (3.85±1.04 vs. 2.60±0.32, p=0.001) and St-Si (4.08±1.21 vs. 2.81±0.36, p=0.001) transition's duration. Frail older persons also had significantly decreased smoothness of Si-St transition pattern (1.36±0.07 vs. 1.21±0.05, p=0.001) and dynamic of trunk movement. Measurements after three weeks of rehabilitation in frail older persons showed that smoothness of transition pattern had the highest improvement effect size (0.4) and discriminative performance. These results demonstrate the potential interest of such parameters to distinguish older subjects with different functional and health conditions.

Connexin36 contributes to INS-1E cells survival through modulation of cytokine-induced oxidative stress, ER stress and AMPK activity.

Cell-to-cell communication mediated by gap junctions made of Connexin36 (Cx36) contributes to pancreatic β-cell function. We have recently demonstrated that Cx36 also supports β-cell survival by a still unclear mechanism. Using specific Cx36 siRNAs or adenoviral vectors, we now show that Cx36 downregulation promotes apoptosis in INS-1E cells exposed to the pro-inflammatory cytokines (IL-1β, TNF-α and IFN-γ) involved at the onset of type 1 diabetes, whereas Cx36 overexpression protects against this effect. Cx36 overexpression also protects INS-1E cells against endoplasmic reticulum (ER) stress-mediated apoptosis, and alleviates the cytokine-induced production of reactive oxygen species, the depletion of the ER Ca(2+) stores, the CHOP overexpression and the degradation of the anti-apoptotic protein Bcl-2 and Mcl-1. We further show that cytokines activate the AMP-dependent protein kinase (AMPK) in a NO-dependent and ER-stress-dependent manner and that AMPK inhibits Cx36 expression. Altogether, the data suggest that Cx36 is involved in Ca(2+) homeostasis within the ER and that Cx36 expression is downregulated following ER stress and subsequent AMPK activation. As a result, cytokine-induced Cx36 downregulation elicits a positive feedback loop that amplifies ER stress and AMPK activation, leading to further Cx36 downregulation. The data reveal that Cx36 plays a central role in the oxidative stress and ER stress induced by cytokines and the subsequent regulation of AMPK activity, which in turn controls Cx36 expression and mitochondria-dependent apoptosis of insulin-producing cells.

Genetic Variations and Diseases in UniProtKB/Swiss-Prot: The Ins and Outs of Expert Manual Curation.

During the last few years, next-generation sequencing (NGS) technologies have accelerated the detection of genetic variants resulting in the rapid discovery of new disease-associated genes. However, the wealth of variation data made available by NGS alone is not sufficient to understand the mechanisms underlying disease pathogenesis and manifestation. Multidisciplinary approaches combining sequence and clinical data with prior biological knowledge are needed to unravel the role of genetic variants in human health and disease. In this context, it is crucial that these data are linked, organized, and made readily available through reliable online resources. The Swiss-Prot section of the Universal Protein Knowledgebase (UniProtKB/Swiss-Prot) provides the scientific community with a collection of information on protein functions, interactions, biological pathways, as well as human genetic diseases and variants, all manually reviewed by experts. In this article, we present an overview of the information content of UniProtKB/Swiss-Prot to show how this knowledgebase can support researchers in the elucidation of the mechanisms leading from a molecular defect to a disease phenotype.

Iris varix as a cause of late-onset inflammation after implantation of a phakic iris claw lens [Irisvarize als Ursache einer verzögerten Entzündung nach Implantation einer Iris-Clip-Linse ins phake Auge]

Implantation of a phakic iris claw intraocular lens is a common, effective and safe procedure to correct high myopia, hyperopia and astigmatism [2]. Due to the nature of its fixation on the iris using claws, chronic irritation and inflammation have remained a major concern with the Artisan® lens since its market introduction in 1998. Following iris claw implantation, monitoring of postoperative inflammation is mandatory [4][7]. Usually, signs of inflammation can be detected in the anterior chamber during the early postoperative period. We present here the first case of late-onset inflammation after implantation of an iris claw lens triggered by an iris varix. The iris varix is a rare benign iris vascular abnormality, with a low prevalence as a solitary primary lesion in the general population and little is known about its clinical characteristics [1][5][6]. This report shows that an iris varix could be a cause of a late onset and chronic inflammation after phakic Artisan® lens implantation.