The triggering receptor expressed on myeloid cells (TREM) in inflammatory bowel disease pathogenesis

The Triggering Receptors Expressed on Myeloid cells (TREM) are a family of cell-surface molecules that control inflammation, bone homeostasis, neurological development and blood coagulation. TREM-1 and TREM-2, the best-characterized receptors so far, play divergent roles in several infectious diseases. In the intestine, TREM-1 is highly expressed by macrophages, contributing to inflammatory bowel disease (IBD) pathogenesis. Contrary to current understanding, TREM-2 also promotes inflammation in IBD by fueling dendritic cell functions. This review will focus specifically on recent insights into the role of TREM proteins in IBD development, and discuss opportunities for novel treatment approaches

X-Box Binding Protein 1 Is Essential for the Anti-Oxidant Defense and Cell Survival in the Retinal Pigment Epithelium

Damage to the retinal pigment epithelium (RPE) is an early event in the pathogenesis of age-related macular degeneration (AMD). X-box binding protein 1 (XBP1) is a key transcription factor that regulates endoplasmic reticulum (ER) homeostasis and cell survival. This study aimed to delineate the role of endogenous XBP1 in the RPE. Our results show that in a rat model of light-induced retinal degeneration, XBP1 activation was suppressed in the RPE/choroid complex, accompanied by decreased anti-oxidant genes and increased oxidative stress. Knockdown of XBP1 by siRNA resulted in reduced expression of SOD1, SOD2, catalase, and glutathione synthase and sensitized RPE cells to oxidative damage. Using Cre/LoxP system, we generated a mouse line that lacks XBP1 only in RPE cells. Compared to wildtype littermates, RPE-XBP1 KO mice expressed less SOD1, SOD2, and catalase in the RPE, and had increased oxidative stress. At age 3 months and older, these mice exhibited apoptosis of RPE cells, decreased number of cone photoreceptors, shortened photoreceptor outer segment, reduced ONL thickness, and deficit in retinal function. Electron microscopy showed abnormal ultrastructure, Bruch's membrane thickening, and disrupted basal membrane infolding in XBP1-deficient RPE. These results indicate that XBP1 is an important gene involved in regulation of the anti-oxidant defense in the RPE, and that impaired activation of XBP1 may contribute to RPE dysfunction and cell death during retinal degeneration and AMD

Pathogen-Induced Proapoptotic Phenotype and High CD95 (Fas) Expression Accompany a Suboptimal CD8+ T-Cell Response: Reversal by Adenoviral Vaccine

MHC class Ia-restricted CD8+ T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8+ T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8+ T cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8+ T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8+ T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8+ cells expanded during infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8+ T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination

Beryllium-sensitive nuclear protein kinases

Much effort has been spent over the last decade in producing so called "Machine Vision" systems for use in robotics, automated inspection, assembly and numerous other fields. Because of the large amount of data involved in an image (typically ¼ MByte) and the complexity of many algorithms used, the processing times required have been far in excess of real time on a VAX-class serial processor. We review a number of image understanding algorithms that compute a globally defined "state", and show that they may be computed using simple local operations that are suited to parallel implementation. In recent years, many massively parallel machines have been designed to apply local operations rapidly across an image. We review several vision machines. We develop an algebraic analysis of the performance of a vision machine and show that, contrary to the commonly-held belief, the time taken to relay images between serial streams can exceed by far the time spent processing. We proceed to investigate the roles that a variety of pipelining techniques might play. We then present three pipelined designs for vision, one of which has been built. This is a parallel pipelined bit slice convolution processor, capable of operating at video rates. This design is examined in detail, and its performance analysed in relation to the theoretical framework of the preceeding chapters. The construction and debugging of the device, which is now operational in its hardware is detailed

Changing climate and glacio-hydrology in Indian Himalayan Region : a review

This study presents a comprehensive review of the published literature on the evidences of a changing climate in the Indian Himalayan Region (IHR) and its impacts on the glacio-hydrology of the region. The IHR serves as an important source of fresh water for the densely populated areas downstream. It is evident from the available studies that temperature is significantly increasing in all parts of the IHR, whereas precipitation is not indicative of any particular spatiotemporal trend. Glacio-hydrological proxies for changing climate, such as, terminus and areal changes of the glaciers, glacier mass balance, and streamflow in downstream areas, highlight changes more evidently in recent decades. On an average, studies have predicted an increase in temperature and precipitation in the region, along with increase in streamflow of major rivers. Such trends are already apparent in some sub-basins of the western IHR. The region is particularly vulnerable to changing climate as it is highly dependent on snow and glacier melt run-off to meet its freshwater demands. We present a systematic review of key papers dealing with changing temperature, precipitation, glaciers, and streamflow in the IHR. We discuss these interdisciplinary themes in relation to each other, in order to establish the present and future impacts of climatic, glaciological, and hydrological changes in the region.Validerad; 2016; Nivå 2; 20160316 (andbra)</p

Slight mass gain of Karakorum glaciers in the early 21st century

International audienceThere is a severe lack of observations to assess the state of health of Hindu Kush-Karakoram-Himalaya glaciers and constrain their contribution to regional hydrology and global sea-level rise1. In the context of a negative globally-average mass balance of glaciers and ice caps1,2,3, an anomalous behaviour of Karakoram glaciers has been suggested2,4,5,6, but not confirmed by recent mass balance measurements. Furthermore, the presence of numerous glacier surges in the region7,8,9,10,11 complicates the interpretation of the few observations available (e.g., length and velocity changes). Here, we observe the regional mass balance of glaciers in the central Karakoram between 1999 and 2008 by differencing two digital elevation models. The spatial pattern of glacier elevation changes is highly heterogeneous, confirms that glacier surges are widespread and shows that high ice thinning and ablation rates can occur on debris-covered glacier tongues. The regional mass balance is slightly positive (+0.11 ± 0.22 m a-1 water equivalent) and in agreement with a decreasing runoff from rivers originating in this area12. We thereby confirm the so-called "Karakoram anomaly" and show that the sea-level rise contribution of glaciers in this mountain range was -0.01 mm a-1 during 1999-2008, a reduction by 0.05 mm a-1 compared to a recent estimate1