Cathelicidin preserves intestinal barrier function in polymicrobial sepsis.

ObjectivesThe intestinal epithelium compartmentalizes the sterile bloodstream and the commensal bacteria in the gut. Accumulating evidence suggests that this barrier is impaired in sepsis, aggravating systemic inflammation. Previous studies reported that cathelicidin is differentially expressed in various tissues in sepsis. However, its role in sepsis-induced intestinal barrier dysfunction has not been investigated.DesignTo examine the role of cathelicidin in polymicrobial sepsis, cathelicidin wild-(Cnlp+/+) and knockout (Cnlp-/-) mice underwent cecal-ligation and puncture (CLP) followed by the assessment of septic mortality and morbidity as well as histological, biochemical, immunological, and transcriptomic analyses in the ileal tissues. We also evaluated the prophylactic and therapeutic efficacies of vitamin D3 (an inducer of endogenous cathelicidin) in the CLP-induced murine polymicrobial sepsis model.ResultsThe ileal expression of cathelicidin was increased by three-fold after CLP, peaking at 4 h. Knockout of Cnlp significantly increased 7-day mortality and was associated with a higher murine sepsis score. Alcian-blue staining revealed a reduced number of mucin-positive goblet cells, accompanied by reduced mucin expression. Increased number of apoptotic cells and cleavage of caspase-3 were observed. Cnlp deletion increased intestinal permeability to 4kD fluorescein-labeled dextran and reduced the expression of tight junction proteins claudin-1 and occludin. Notably, circulating bacterial DNA load increased more than two-fold. Transcriptome analysis revealed upregulation of cytokine/inflammatory pathway. Depletion of Cnlp induced more M1 macrophages and neutrophils compared with the wild-type mice after CLP. Mice pre-treated with cholecalciferol (an inactive form of vitamin D3) or treated with 1alpha, 25-dihydroxyvitamin D3 (an active form of VD3) had decreased 7-day mortality and significantly less severe symptoms. Intriguingly, the administration of cholecalciferol after CLP led to worsened 7-day mortality and the associated symptoms.ConclusionsEndogenous cathelicidin promotes intestinal barrier integrity accompanied by modulating the infiltration of neutrophils and macrophages in polymicrobial sepsis. Our data suggested that 1alpha, 25-dihydroxyvitamin D3 but not cholecalciferol is a potential therapeutic agent for treating sepsis

Spatio-Temporal Characteristics of Global Warming in the Tibetan Plateau during the Last 50 Years Based on a Generalised Temperature Zone - Elevation Model

Temperature is one of the primary factors influencing the climate and ecosystem, and examining its change and fluctuation could elucidate the formation of novel climate patterns and trends. In this study, we constructed a generalised temperature zone elevation model (GTEM) to assess the trends of climate change and temporal-spatial differences in the Tibetan Plateau (TP) using the annual and monthly mean temperatures from 1961-2010 at 144 meteorological stations in and near the TP. The results showed the following: (1) The TP has undergone robust warming over the study period, and the warming rate was 0.318°C/decade. The warming has accelerated during recent decades, especially in the last 20 years, and the warming has been most significant in the winter months, followed by the spring, autumn and summer seasons. (2) Spatially, the zones that became significantly smaller were the temperature zones of -6°C and -4°C, and these have decreased 499.44 and 454.26 thousand sq km from 1961 to 2010 at average rates of 25.1% and 11.7%, respectively, over every 5-year interval. These quickly shrinking zones were located in the northwestern and central TP. (3) The elevation dependency of climate warming existed in the TP during 1961-2010, but this tendency has gradually been weakening due to more rapid warming at lower elevations than in the middle and upper elevations of the TP during 1991-2010. The higher regions and some low altitude valleys of the TP were the most significantly warming regions under the same categorizing criteria. Experimental evidence shows that the GTEM is an effective method to analyse climate changes in high altitude mountainous regions

Climate variability of southern Chile since the Last Glacial Maximum : a continuous sedimentological record from Lago Puyehue (40°S)

Author Posting. © Springer, 2007. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Paleolimnology 39 (2008): 179-195, doi:10.1007/s10933-007-9117-y.This paper presents a multi-proxy climate record of an 11 m long core collected in Lago Puyehue (southern Chile, 40°S) and extending back to 18,000 cal yr BP. The multi-proxy analyses include sedimentology, mineralogy, grain size, geochemistry, loss-on-ignition, magnetic susceptibility and radiocarbon datings. Results demonstrate that sediment grain size is positively correlated with the biogenic sediment content and can be used as a proxy for lake paleoproductivity. On the other hand, the magnetic susceptibility signal is correlated with the aluminium and titanium concentrations and can be used as a proxy for the terrigenous supply. Temporal variations of sediment composition evidence that, since the last glacial maximum, the Chilean Lake District was characterized by 3 abrupt climate changes superimposed on a long-term climate evolution. These rapid climate changes are: (1) an abrupt warming at the end of the last glacial maximum at 17,300 cal yr BP; (2) a 13,100-12,300 cal yr BP cold event, ending rapidly and interpreted as the local counter part of the Younger Dryas cold period, and (3) a 3400-2900 cal yr BP climatic instability synchronous with a period of low solar activity. The timing of the 13,100-12,300 cold event is compared with similar records in both hemispheres and demonstrates that this southern hemisphere climate change lags behind the northern hemisphere Younger Dryas cold period by 500 to 1000 years.This research is supported by the Belgian OSTC project EV/12/10B "A continuous Holocene record of ENSO variability in southern Chile"

Constraints on southern hemisphere tropical climate change during the Little Ice Age and Younger Dryas based on glacier modeling of the Quelccaya Ice Cap, Peru

© 2015 The Authors. Improving the late Quaternary paleoclimate record through climate interpretations of low-latitude glacier length changes advances our understanding of past climate change events and the mechanisms for past, present, and future climate change. Paleotemperature reconstructions at low-latitude glaciers are uniquely fruitful because they can provide both site-specific information and enhanced understanding of regional-scale variations due to the structure of the tropical atmosphere. We produce Little Ice Age (LIA) and Younger Dryas (YD) paleoclimate reconstructions for the Huancané outlet glacier of the Quelccaya Ice Cap (QIC) and low-latitude southern hemisphere regional sea surface temperatures (SSTs) using a coupled ice-flow and energy balance model. We also model the effects of long-term changes in the summit temperature and precipitiation rate and the effects of interannual climate variability on the Huancané glacier length. We find temperature to be the dominant climate driver of glacier length change. Also, we find that interannual climate variability cannot adequately explain glacier advances inferred from the geomorphic record, necessitating that these features were formed during past colder climates. To constrain our LIA reconstruction, we incorporate the QIC ice core record, finding a LIA air temperature cooling at the ice cap of between ~0.7 °C and ~1.1 °C and ~0.4 °C and regional SSTs cooling of ~0.6 °C. For the YD paleoclimate reconstructions, we propose two limits on the precipitation rate, since the ice core record does not extend into the Pleistocene: 1) the precipitation rate scales with the Clausius-Clapeyron relationship (upper limit on cooling) and 2) the precipitation rate increases by 40% (lower limit on cooling), which is an increase about twice as great as the regional increases realized in GCM simulations for the period. The first limit requires ~1.6 °C cooling in ice cap air temperatures and ~0.9 °C cooling in SSTs, and the second limit requires ~1.0 °C cooling in ice cap air temperatures and ~0.5 °C cooling in SSTs. Our temperature reconstructions are in good agreement with the magnitude and trend of GCM simulations that incorporate the forcing mechanisms hypothesized to have caused these climate change events

Palaeoenvironment reconstruction, volcanic evolution and geochronology of the Cerro Blanco subcomplex, Nevados de Chillan volcanic complex, Central Chile

Nevados de Chillán Volcanic Complex, central Chile, has been active for at least 640 ka—a period spanning a number of glacial and interglacial periods. Geologic mapping, radiometric dating and geochemical analysis have identified six new volcanic units and produced four new 40Ar/39Ar ages for Cerro Blanco, the northern subcomplex of Nevados de Chillán volcano. Compositions range from dacite to basaltic-andesite and a new geologic map is presented. Examination of lava fracture structures on both newly mapped lavas and those mapped during previous studies has enabled interpretations of former eruptive environments. Palaeoenvironment reconstructions, combined with 40Ar/39Ar ages and comparison with the marine oxygen isotope record, show that at least three phases of volcanic activity have occurred during the evolution of Cerro Blanco: (1) a constructive, pre-caldera collapse period; (2) a period of caldera formation and collapse; and (3) a constructive period of dome growth forming the modern day volcanic centre. This style of volcanic evolution, whereby large-scale caldera collapse is followed by growth of a new stratocone is common at Andean volcanoes