Critical role for Gimap5 in the survival of mouse hematopoietic stem and progenitor cells

HSCs lacking the guanosine nucleotide-binding protein Gimap5, which stabilizes expression of the Mcl-1 Bcl2 family protein, exhibit impaired survival and long-term repopulation capacity

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Microbial community structure mediates response of soil C decomposition to litter addition and warming

Microbial activity has been highlighted as one of the main unknowns controlling the fate and turnover of soil organic matter (SOM) in response to climate change. How microbial community structure and function may (or may not) interact with increasing temperature to impact the fate and turnover of SOM, in particular when combined with changes in litter chemistry, is not well understood. The primary aim of this study was to determine if litter chemistry impacted the decomposition of soil and litter-derived carbon (C), and its interaction with temperature, and whether this response was controlled by microbial community structure and function. Fresh or pre-incubated eucalyptus leaf litter (13C enriched) was added to a woodland soil and incubated at 12, 22, or 32 �C. We tracked the movement of litter and soilderived C into CO2, water-extractable organic carbon (WEOC), and microbial phospholipids (PLFA). The litter additions produced significant changes in every parameter measured, while temperature, interacting with litter chemistry, predominately affected soil C respiration (priming and temperature sensitivity), microbial community structure, and the metabolic quotient (a proxy for microbial carbon use efficiency [CUE]). The direction of priming varied with the litter additions (negative with fresh litter, positive with pre-incubated litter) and was related to differences in the composition of microbial communities degrading soil-C, particularly gram-positive and gram-negative bacteria, resulting from litter addition. Soil-C decomposition in both litter treatments was more temperature sensitive (higher Q10) than in the soil-only control, and soil-C priming became increasingly positive with temperature. However, microbes utilizing soil-C in the litter treatments had higher CUE, suggesting the longer-term stability of soil-C may be increased at higher temperature with litter addition. Our results show that in the same soil, the growth of distinct microbial communities can alter the turnover and fate of SOM and, in the context of global change, its response to temperature

Technology Rich Biology Labs: Effects of Misconceptions

This paper describes a study conducted on the lab sections of the general biology course for non-science majors at the University of New England, and reports findings of student misconceptions about photosynthesis and the mass/carbon uptake during plant growth. The current study placed high technology analytic tools in the hands of introductory biology students allowing them to collect and analyze real carbon data, with the intent of increasing their conceptual understanding of photosynthesis concepts and decreasing the frequency of misconceptions. Two lab sections of the course were used as a study for the teaching of photosynthesis. The control section(A) used the more traditional qualitative chemical approach to presenting the material, and the treatment section (B) used sophisticated technology tostudy the process quantitatively. Using the plant Brassica rapa, students worked in groups to explore three different factors contributing to plant growth and photosynthesis, the treatment group. analytic technology. At the end of the laboratory activities about photosynthesis, the treatment students presented their work in the form of a symposium. Test scores, laboratory reports, and student semi-structured interview provided information about student understanding of photosynthesis. The paper reports detailed outlines of the class lab activities and technology use, and comments on the nature of student understanding of the mass/carbon uptake during photosynthesis. The study compared the understanding of students in both the treatment and control groups to assess the effectiveness of integrating technology into introductory biology lab activities on misconceptions about photosynthesis