The bacteriohopanepolyol inventory of novel aerobic methane oxidising bacteria reveals new biomarker signatures of aerobic methanotrophy in marine systems

Aerobic methane oxidation (AMO) is one of the primary biologic pathways regulating the amount of methane (CH4) released into the environment. AMO acts as a sink of CH4, converting it into carbon dioxide before it reaches the atmosphere. It is of interest for (paleo)climate and carbon cycling studies to identify lipid biomarkers that can be used to trace AMO events, especially at times when the role of methane in the carbon cycle was more pronounced than today. AMO bacteria are known to synthesise bacteriohopanepolyol (BHP) lipids. Preliminary evidence pointed towards 35-aminobacteriohopane-30,31,32,33,34-pentol (aminopentol) being a characteristic biomarker for Type I methanotrophs. Here, the BHP compositions were examined for species of the recently described novel Type I methanotroph bacterial genera Methylomarinum and Methylomarinovum, as well as for a novel species of a Type I Methylomicrobium. Aminopentol was the most abundant BHP only in Methylomarinovum caldicuralii, while Methylomicrobium did not produce aminopentol at all. In addition to the expected regular aminotriol and aminotetrol BHPs, novel structures tentatively identified as methylcarbamate lipids related to C-35 amino-BHPs (MCBHPs) were found to be synthesised in significant amounts by some AMO cultures. Subsequently, sediments and authigenic carbonates from methane-influenced marine environments were analysed. Most samples also did not contain significant amounts of aminopentol, indicating that aminopentol is not a useful biomarker for marine aerobic methanotophic bacteria. However, the BHP composition of the marine samples do point toward the novel MC-BHPs components being potential new biomarkers for AMO

The basidiomycetous yeast Trichosporon may cause severe lung exacerbation in cystic fibrosis patients - clinical analysis of Trichosporon positive patients in a Munich cohort

Background: The relevance of Trichosporon species for cystic fibrosis (CF) patients has not yet been extensively investigated. Methods: The clinical course of CF patients with Trichosporon spp. in their respiratory secretions was analysed between 2003 and 2010 in the Munich CF center. All respiratory samples of 360 CF patients (0 - 52.4 years; mean FEV1 2010 81.4% pred) were investigated. Results: In 8 patients (2.2%, 3 male, mean age 21.8 years) Trichosporon was detected at least once. One patient carried T. asahii. One patient carried T. mycotoxinivorans and one patient T. inkin as determined by DNA sequencing. As potential risk factors for Trichosporon colonization steroid treatment, allergic bronchopulmonary aspergillosis (ABPA) and CF associated diabetes were identified in 6, 5, and 2 patients respectively. For one patient, the observation period was not long enough to determine the clinical course. One patient had only a single positive specimen and exhibited a stable clinical course determined by change in forced expiratory volume in one second (FEV1), body-mass-index (BMI), C-reactive protein (CRP) and immunoglobulin G (IgG). Of 6 patients with repeatedly positive specimen (mean detection period 4.5 years), 4 patients had a greater decline in FEV1 than expected, 2 of these a decline in BMI and 1 an increase in IgG above the reference range. 2 patients received antimycotic treatment: one patient with a tormenting dry cough subjectively improved under Amphotericin B inhalation; one patient with a severe exacerbation due to T. inkin was treated with i.v. Amphotericin B, oral Voriconazole and Posaconazole which stabilized the clinical condition. Conclusions: This study demonstrates the potential association of Trichosporon spp. with severe exacerbations in CF patients

Variation in MSRA Modifies Risk of Neonatal Intestinal Obstruction in Cystic Fibrosis

Meconium ileus (MI), a life-threatening intestinal obstruction due to meconium with abnormal protein content, occurs in approximately 15 percent of neonates with cystic fibrosis (CF). Analysis of twins with CF demonstrates that MI is a highly heritable trait, indicating that genetic modifiers are largely responsible for this complication. Here, we performed regional family-based association analysis of a locus that had previously been linked to MI and found that SNP haplotypes 5′ to and within the MSRA gene were associated with MI (P = 1.99×10−5 to 1.08×10−6; Bonferroni P = 0.057 to 3.1×10−3). The haplotype with the lowest P value showed association with MI in an independent sample of 1,335 unrelated CF patients (OR = 0.72, 95% CI [0.53–0.98], P = 0.04). Intestinal obstruction at the time of weaning was decreased in CF mice with Msra null alleles compared to those with wild-type Msra resulting in significant improvement in survival (P = 1.2×10−4). Similar levels of goblet cell hyperplasia were observed in the ilea of the Cftr−/− and Cftr−/−Msra−/− mice. Modulation of MSRA, an antioxidant shown to preserve the activity of enzymes, may influence proteolysis in the developing intestine of the CF fetus, thereby altering the incidence of obstruction in the newborn period. Identification of MSRA as a modifier of MI provides new insight into the biologic mechanism of neonatal intestinal obstruction caused by loss of CFTR function

Central CD4+ T cell tolerance: deletion versus regulatory T cell differentiation

The diversion of MHC class II-restricted thymocytes into the regulatory T (Treg) cell lineage, similarly to clonal deletion, is driven by intrathymic encounter of agonist self-antigens. Somewhat paradoxically, it thus seems that the expression of an autoreactive T cell receptor is a shared characteristic of T cells that are subject to clonal deletion and those that are diverted into the Treg cell lineage. Here, we discuss how thymocyte-intrinsic and -extrinsic determinants may specify the choice between these two fundamentally different T cell fates

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Projecting the Medium-Term: Outcomes and Errors for GDP Growth

The focus of this paper is the evaluation of a very popular method for potential output estimation and medium-term forecasting - the production function approach - in terms of predictive performance. For this purpose, a forecast evaluation for the three to five years ahead predictions of GDP growth for the individual G7 countries is conducted. To carry out the forecast performance check a particular testing framework is derived that allows the computation of robust test statistics given the specific nature of the generated out-of sample forecasts. In addition, medium-term GDP projections from national and international institutions are examined and it is assessed whether these projections convey a reliable view about future economic developments and whether there is scope for improving their predictive content