Endoplasmic reticulum stress signalling – from basic mechanisms to clinical applications

The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one‐third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling‐centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes

Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota

Background Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Methodology/Principal findings Secondary abiotic mice were generated by broad- spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra- intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. Conclusion/Significance With respect to the intestinal microbiota composition “humanized” mice display acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation

Search for supersymmetry with photons in pp collisions at √s=8TeV

Two searches for physics beyond the standard model in events containing photons are presented. The data sample used corresponds to an integrated luminosity of 19.7  fb−1 of proton-proton collisions at √s=8  TeV, collected with the CMS experiment at the CERN LHC. The analyses pursue different inclusive search strategies. One analysis requires at least one photon, at least two jets, and a large amount of transverse momentum imbalance, while the other selects events with at least two photons and at least one jet, and uses the razor variables to search for signal events. The background expected from standard model processes is evaluated mainly from data. The results are interpreted in the context of general gauge-mediated supersymmetry, with the next-to-lightest supersymmetric particle either a bino- or wino-like neutralino, and within simplified model scenarios. Upper limits at the 95% confidence level are obtained for cross sections as functions of the masses of the intermediate supersymmetric particles

The complete mitochondrial and plastid genomes of Corallina chilensis (Corallinaceae, Rhodophyta) from Tomales Bay, California, USA

Genomic analysis of the marine alga Corallina chilensis from Tomales Bay, California, USA, resulted in the assembly of its complete mitogenome (GenBank accession number MK598844) and plastid genome (GenBank MK598845). The mitogenome is 25,895 bp in length and contains 50 genes. The plastid genome is 178,350 bp and contains 233 genes. The organellar genomes share a high-level of gene synteny to other Corallinales. Comparison of rbcL and cox1 gene sequences of C. chilensis from Tomales Bay reveals it is identical to three specimens from British Columbia, Canada and very similar to a specimen of C. chilensis from southern California. These genetic data confirm that C. chilensis is distributed in Pacific North America