Protection of Human Pancreatic Islets from Lipotoxicity by Modulation of the Translocon

Type 2 diabetes is characterized by peripheral insulin resistance and pancreatic beta cell dysfunction. Elevated free fatty acids (FFAs) may impair beta cell function and mass (lipotoxicity). Altered calcium homeostasis may be involved in defective insulin release. The endoplasmic reticulum (ER) is the major intracellular calcium store. Lipotoxicity induces ER stress and in parallel an ER calcium depletion through unknown ER calcium leak channels. The main purposes of this study is first to identify one of these channels and secondly, to check the opportunity to restore beta cells function (i.e., insulin secretion) after pharmacological inhibition of ER calcium store depletion. We investigated the functionality of translocon, an ER calcium leak channel and its involvement on FFAs-induced alterations in MIN6B1 cells and in human pancreatic islets. We evidenced that translocon acts as a functional ER calcium leak channel in human beta cells using anisomycin and puromycin (antibiotics), respectively blocker and opener of this channel. Puromycin induced a significant ER calcium release, inhibited by anisomycin pretreatment. Palmitate treatment was used as FFA model to induce a mild lipotoxic effect: ER calcium content was reduced, ER stress but not apoptosis were induced and glucose induced insulin secretion was decreased in our beta cells. Interestingly, translocon inhibition by chronic anisomycin treatment prevented dysfunctions induced by palmitate, avoiding reticular calcium depletion, ER stress and restoring insulin secretion. Our results provide for the first time compelling evidence that translocon actively participates to the palmitate-induced ER calcium leak and insulin secretion decrease in beta cells. Its inhibition reduces these lipotoxic effects. Taken together, our data indicate that TLC may be a new potential target for the treatment of type 2 diabetes.     

Concentrated starter productions in a two stage cell-recycle bioreactor plant

Summary Continuous production of concentratedLactobacillus acidophilus andBifidobacterium bifidum cells is described in two successive cell-recycle bioreactors. This process allows the study of the relationships between two microorganisms without mixed cultures.     

Fragmented and scrambled mitochondrial ribosomal RNA coding regions among green algae: a model for their origin and evolution

Mitochondrial ribosomal RNA coding regions in the only three green algal taxa investigated to date are fundamentally different in that they are continuous in Prototheca wickerhamii, but highly fragmented and scrambled in Chlamydomonas reinhardtii and Chlamydomonas eugametos. To gain more insight into the mode of evolution of fragmented and scrambled mitochondrial ribosomal RNA (rRNA) genes within the green algal group, this work (1) provides additional information on fragmentation patterns of mitochondrial small- and large-subunit (SSU and LSU) rRNAs that strongly supports the concept of a gradual increase in the extent of discontinuity of mitochondrial rRNAs among chlorophycean green algae and (2) reports the first example of fragmented and scrambled mitochondrial LSU rRNA coding regions in a green algal taxon outside the Chlamydomonas group. The present study (1) suggests that the scrambling of the mitochondrial rRNA coding regions may have occurred early in the evolution of fragmented and scrambled mitochondrial rRNA genes within the chlorophycean green algal group, most likely in parallel with the fragmentation events, (2) proposes recombination as a possible mechanism involved in the evolution of these mitochondrial rRNA genes, and (3) presents a hypothetical pathway for converting continuous mitochondrial rRNA genes into the highly fragmented and scrambled rRNA coding regions of Chlamydomonas through a series of recombinatorial events between short repeated sequences.      

Large-scale identification of polymorphic microsatellites using an <Emphasis Type="Italic">in silico</Emphasis> approach

Background  

Simple Sequence Repeat (SSR) or microsatellite markers are valuable for genetic research. Experimental methods to develop SSR markers are laborious, time consuming and expensive. In silico approaches have become a practicable and relatively inexpensive alternative during the last decade, although testing putative SSR markers still is time consuming and expensive. In many species only a relatively small percentage of SSR markers turn out to be polymorphic. This is particularly true for markers derived from expressed sequence tags (ESTs). In EST databases a large redundancy of sequences is present, which may contain information on length-polymorphisms in the SSR they contain, and whether they have been derived from heterozygotes or from different genotypes. Up to now, although a number of programs have been developed to identify SSRs in EST sequences, no software can detect putatively polymorphic SSRs.     

Phylogeography and historical demography of the Lusitanian snail <Emphasis Type="Italic">Elona quimperiana</Emphasis> reveal survival in unexpected separate glacial refugia

Background  

Present day distributions of Palearctic taxa in northern latitudes mainly result from populations having survived in local patches during the Late Pleistocene and/or from recolonizing populations from southern temperate refugia. If well-studied Mediterranean and eastern European refugia are widely accepted, some recent biogeographical assumptions still remain unclear, such as the occurrence of multiple glacial refugia in Iberia and cryptic refugia in northern Europe during the last glaciations. The Lusitanian snail Elona quimperiana has a remarkably disjunct distribution, limited to northwestern France (Brittany), northwestern Spain and the Basque Country. By describing the phylogeographical structure of this species across its entire range, the present study attempts to identify refugia and subsequent recolonization routes.     

Mental practice-based rehabilitation training to improve arm function and daily activity performance in stroke patients: a randomized clinical trial

Background  

Over 50% of patients with upper limb paresis resulting from stroke face long-term impaired arm function and ensuing disability in daily life. Unfortunately, the number of effective treatments aimed at improving arm function due to stroke is still low. This study aims to evaluate a new therapy for improving arm function in sub-acute stroke patients based on mental practice theories and functional task-oriented training, and to study the predictors for a positive treatment result. It is hypothesized that a six-week, mental practice-based training program (additional to regular therapy) targeting the specific upper extremity skills important to the individual patient will significantly improve both arm function and daily activity performance, as well as being cost effective.     

The genus Teliocrinus (Crinoidea,Echinodermata): a key taxon among pentacrinid stalked crinoids

The main characters of the stalked crinoids of the family Pentacrinitidae attributed to the genus Teliocrinus are re‐evaluated from a quantitative study of phenotype variation, new observations on arm and stalk articulations, and observation of ontogenetic trends. All of the specimens collected in the northern Indian Ocean belong to the same species, i.e. Teliocrinus springeri (Clark, 1909). However, two phenotypes living at different depths remain valid as subspecies: Teliocrinus springeri springeri (Clark, 1909) and Teliocrinus springeri liliaceus (Clark, 1909). Teliocrinus shares several ontogenetic trends with Endoxocrinus, especially in nonfunctional brachial articulations and stalk symplexies. Its assignment to the Diplocrininae is confirmed. A discussion of its affinities with pentacrinid fossil genera in which the crown is well preserved suggests that Diplocrininae could have first appeared during the Lower Cretaceous. A shortening of brachitaxes and a paedomorphic trend of stalk symplexies are the main other evolutionary traits. Nonfunctional articulations are frequently found at the paedomorphic pole of the heterochronic gradient, without clear derived characters. Classification of pentacrinids mainly based on such symplesiomorphy or paedomorphic characters must be definitively abandoned. However, in post‐Palaeozoic stalked crinoids the scarcity of well‐preserved fossils, the high frequency of paedomorphy, and convergent adaptive characters makes phylogenetic reconstruction only based on morphological characters very difficult and speculative. © 2009 The Linnean Society of London, Zoological Journal of the Linnean Society, 2009, 155 , 22–39.     

Comparison of linkage disequilibrium and haplotype diversity on macro- and microchromosomes in chicken

Background

Toll like receptors (TLR) play the central role in the recognition of pathogen associated molecular patterns (PAMPs). Mutations in the TLR1, TLR2 and TLR4 genes may change the ability to recognize PAMPs and cause altered responsiveness to the bacterial pathogens.

Results

The study presents association between TLR gene mutations and increased susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP) infection. Novel mutations in TLR genes (TLR1- Ser150Gly and Val220Met; TLR2 – Phe670Leu) were statistically correlated with the hindrance in recognition of MAP legends. This correlation was confirmed subsequently by measuring the expression levels of cytokines (IL-4, IL-8, IL-10, IL-12 and IFN-γ) in the mutant and wild type moDCs (mocyte derived dendritic cells) after challenge with MAP cell lysate or LPS. Further in silico analysis of the TLR1 and TLR4 ectodomains (ECD) revealed the polymorphic nature of the central ECD and irregularities in the central LRR (leucine rich repeat) motifs.

Conclusion

The most critical positions that may alter the pathogen recognition ability of TLR were: the 9^th amino acid position in LRR motif (TLR1–LRR10) and 4^th residue downstream to LRR domain (exta-LRR region of TLR4). The study describes novel mutations in the TLRs and presents their association with the MAP infection.