Microbiota depletion promotes browning of white adipose tissue and reduces obesity.

Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the inguinal subcutaneous adipose tissue (ingSAT) and perigonadal visceral adipose tissue (pgVAT) is promoted by the depletion of microbiota either by means of antibiotic treatment or in germ-free mice. This leads to improved glucose tolerance and insulin sensitivity and decreased white fat and adipocyte size in lean mice, obese leptin-deficient (ob/ob) mice and high-fat diet (HFD)-fed mice. Such metabolic improvements are mediated by eosinophil infiltration, enhanced type 2 cytokine signaling and M2 macrophage polarization in the subcutaneous white fat depots of microbiota-depleted animals. The metabolic phenotype and the browning of the subcutaneous fat are impaired by the suppression of type 2 cytokine signaling, and they are reversed by recolonization of the antibiotic-treated or germ-free mice with microbes. These results provide insight into the microbiota-fat signaling axis and beige-fat development in health and metabolic disease.

Mice overexpressing BAFF develop a commensal flora-dependent, IgA-associated nephropathy

B cell activation factor of the TNF family (BAFF) is a potent B cell survival factor. BAFF overexpressing transgenic mice (BAFF-Tg mice) exhibit features of autoimmune disease, including B cell hyperplasia and hypergammaglobulinemia, and develop fatal nephritis with age. However, basal serum IgA levels are also elevated, suggesting that the pathology in these mice may be more complex than initially appreciated. Consistent with this, we demonstrate here that BAFF-Tg mice have mesangial deposits of IgA along with high circulating levels of polymeric IgA that is aberrantly glycosylated. Renal disease in BAFF-Tg mice was associated with IgA, because serum IgA was highly elevated in nephritic mice and BAFF-Tg mice with genetic deletion of IgA exhibited less renal pathology. The presence of commensal flora was essential for the elevated serum IgA phenotype, and, unexpectedly, commensal bacteria-reactive IgA antibodies were found in the blood. These data illustrate how excess B cell survival signaling perturbs the normal balance with the microbiota, leading to a breach in the normal mucosal-peripheral compartmentalization. Such breaches may predispose the nonmucosal system to certain immune diseases. Indeed, we found that a subset of patients with IgA nephropathy had elevated serum levels of a proliferation inducing ligand (APRIL), a cytokine related to BAFF. These parallels between BAFF-Tg mice and human IgA nephropathy may provide a new framework to explore connections between mucosal environments and renal pathology.

Rapid assessment of cerebral autoregulation by near-infrared spectroscopy and a single dose of phenylephrine

Rapid bedside determination of cerebral blood pressure autoregulation (AR) may improve clinical utility. We tested the hypothesis that cerebral Hb oxygenation (HbDiff) and cerebral Hb volume (HbTotal) measured by near-infrared spectroscopy (NIRS) would correlate with cerebral blood flow (CBF) after single dose phenylephrine (PE). Critically ill patients requiring artificial ventilation and arterial lines were eligible. During rapid blood pressure rise induced by i.v. PE bolus, ΔHbDiff and ΔHbTotal were calculated by subtracting values at baseline (normotension) from values at peak blood pressure elevation (hypertension). With the aid of NIRS and bolus injection of indocyanine green, relative measures of CBF, called blood flow index (BFI), were determined during normotension and during hypertension. BFI during hypertension was expressed as percentage from BFI during normotension (BFI%). Autoregulation indices (ARIs) were calculated by dividing BFI%, ΔHbDiff, and ΔHbTotal by the concomitant change in blood pressure. In 24 patients (11 newborns and 13 children), significant correlations between BFI% and ΔHbDiff (or ΔHbTotal) were found. In addition, the associations between Hb-based ARI and BFI%-based ARI were significant with correlation coefficients of 0.73 (or 0.72). Rapid determination of dynamic AR with the aid of cerebral Hb signals and PE bolus seems to be reliable.

Lymphotoxin β receptor signaling promotes development of autoimmune pancreatitis

Little is known about the pathogenic mechanisms of autoimmune pancreatitis (AIP), an increasingly recognized, immune-mediated form of chronic pancreatitis. Current treatment options are limited and disease relapse is frequent. We investigated factors that contribute to the development of AIP and new therapeutic strategies.

Changing climates, moving people: framing migration, displacement and planned relocation

Different policies are required for different types of human mobility related to climatic changes. Hence, it is necessary to distinguish between migration, displacement and planned relocation in climate policy and operations. The purpose of this Policy Brief is to help distinguish between human migration, displacement and planned relocation and present state-of-the-art thinking about some of the key issues related to addressing these in the context of climate policy.

Recent trends in Inner Asian forest dynamics to temperature and precipitation indicate high sensitivity to climate change

Semi-arid ecosystems play an important role in regulating global climate with the fate of these ecosystems in the Anthropocene depending upon interactions among temperature, precipitation, and CO2. However, in cool-arid environments, precipitation is not the only limitation to forest productivity. Interactions between changes in precipitation and air temperature may enhance soil moisture stress while simultaneously extending growing season length, with unclear consequences for net carbon uptake. This study evaluates recent trends in productivity and phenology of Inner Asian forests (in Mongolia and Northern China) using satellite remote sensing, dendrochronology, and dynamic global vegetation model (DGVM) simulations to quantify the sensitivity of forest dynamics to decadal climate variability and trends. Trends in photosynthetically active radiation fraction (FPAR) between 1982 and 2010 show a greening of about 7% of the region in spring (March, April, May), and 3% of the area ‘browning’ during summertime (June, July, August). These satellite observations of FPAR are corroborated by trends in NPP simulated by the LPJ DGVM. Spring greening trends in FPAR are mainly explained by long-term trends in precipitation whereas summer browning trends are correlated with decreasing precipitation. Tree ring data from 25 sites confirm annual growth increments are mainly limited by summer precipitation (June, July, August) in Mongolia, and spring precipitation in northern China (March, April, May), with relatively weak prior-year lag effects. An ensemble of climate projections from the IPCC CMIP3 models indicates that warming temperatures (spring, summer) are expected to be associated with higher summer precipitation, which combined with CO2 causes large increases in NPP and possibly even greater forest cover in the Mongolian steppe. In the absence of a strong direct CO2 fertilization effect on plant growth (e.g., due to nutrient limitation), water stress or decreased carbon gain from higher autotrophic respiration results in decreased productivity and loss of forest cover. The fate of these semi-arid ecosystems thus appears to hinge upon the magnitude and subtleties of CO2 fertilization effects, for which experimental observations in arid systems are needed to test and refine vegetation models.