Project description:Biogenic methane formation, methanogenesis, a key process in the global carbon cycle is the only energy metabolism known to sustain growth of the microorganisms employing it, the methanogenic archaea. All known methanogenic pathways converge at the methane-liberating step where also the terminal electron acceptor of methanogenic respiration, the heterodisulfide of coenzyme M and coenzyme B is formed. Carbon monoxide (CO) utilization of Methanosarcina acetivorans is unique in that the organism can shift from methanogenesis towards acetogenesis. Here, we show that M. acetivorans can dispense of methanogenesis for energy conservation completely. By disrupting the methanogenic pathway through targeted mutagenesis, followed by adaptive evolution, a strain capable of sustained growth by CO-dependent acetogenesis was created. Still, a minute flux through the methane-liberating reaction remained essential, which was attributed to the involvement of the heterodisulfide in at least one essential anabolic reaction. Genomic and proteomic analysis showed that substantial metabolic rewiring had occurred in the strain. Most notably, heterodisulfide reductase, the terminal respiratory oxidoreductase was eliminated to funnel the heterodisulfide towards anabolism. These results suggest that the metabolic flexibility of “methanogenic” archaea is much greater than anticipated and open avenues for probing the mechanism of energetic coupling and the crosstalk between catabolism and anabolism.
Project description:Nutrition-related health issues have emerged as a major threat to public health since the rebirth of the economy in China starting in the 1980s. To meet this challenge, the Chinese Academy of Sciences established the Institute for Nutritional Sciences (INS) at Shanghai, China ≈ 8 y ago. The mission of the INS is to apply modern technologies and concepts in nutritional research to understand the molecular mechanism and provide means of intervention in the combat against nutrition-related diseases, including type 2 diabetes, metabolic syndrome, obesity, cardiovascular diseases, and many types of cancers. Through diligent and orchestrated efforts by INS scientists, graduate students, and research staff in the past few years, the INS has become the leading institution in China in the areas of basic nutritional research and metabolic regulation. Scientists at the INS have made important progress in many areas, including the characterization of genetic and nutritional properties of the Chinese population, metabolic control associated with nutrient sensing, molecular mechanisms underlying glucose and lipid metabolism, regulation of metabolism by adipokines and inflammatory pathways, disease intervention using functional foods or extracts of Chinese herbs, and many biological studies related to carcinogenesis. The INS will continue its efforts in understanding the optimal nutritional needs for Chinese people and the molecular causes associated with metabolic diseases, thus paving the way for effective and individualized intervention in the future. This review highlights the major research endeavors undertaken by INS scientists in recent years.
Project description:BACKGROUND: An excessive immune-mediated inflammation is associated with cardiac dysfunction and poor clinical outcomes after myocardial infarction (MI). However, the precise regulatory mechanism to control the inflammatory response and subsequent tissue repair following MI is unclear. METHODS AND RESULTS: Bone-marrow (BM) cells from CD11c-diphtheria toxin receptor/GFP transgenic mice were transplanted into lethally irradiated wild-type (WT) recipient mice. After reconstitution of BM-derived cells, the recipient mice were treated with either diphtheria toxin (DC ablation) or vehicle (control), and MI was created by left coronary ligation. CD11c+ GFP+ DCs expressing CD11b and MHC class II were recruited into the heart, peaking on day 7 after MI in control group. Mice with DC ablation for 7 days showed deteriorated left ventricular (LV) function and remodeling. The DC-ablated group demonstrated enhanced and sustained expression of inflammatory cytokines, prolonged extracellular matrix degradation associated with a high level of matrix metalloproteinase-9 activity, and diminished expression level of interleukin (IL)-10 and endothelial cell proliferation post-MI compared with control group. In vivo and in vitro analyses revealed that DC-ablated infarcts had an enhanced capacity of monocyte/macrophage recruitment. Among these cells, augmented infiltration of proinflammatory Ly6Chigh monocytes and F4/80+ CD206 M1 macrophages and, conversely, impaired recruitment of anti-inflammatory Ly6Clow monocytes and F4/80+ CD206+ M2 macrophages in the infarcted myocardium were identified in DC-ablated group than in control group. Flow cytometric analysis for inflammatory cells extracted from infarcted tissue revealed that CD11c+ DC is one of the major sources of IL-10. Adoptive transfer of BM-derived DCs from WT, but not IL-10-deficient mice, abrogated the adverse effects of DC depletion on inflammatory response and LV remodeling after MI. CONCLUSION: DC could be a potent immunoprotective regulator during the postinfarction healing process, via controlling monocyte/macrophage homeostasis through IL-10 secretion.
Project description:New locality records for Madecorphnusniger Frolov, 2010, Madecorphnusfalcatus Paulian, 1992, Madecorphnussimplex Frolov, 2010, and Triodontusitremoi Paulian, 1977, are given. Endophallus armature of Madecorphnusniger Frolov, 2010, is described and illustrated.
Project description:The National Academy of Sciences-National Research Council Twin Registry (NAS-NRC Twin Registry) is a comprehensive registry of White male twin pairs born in the USA between 1917 and 1927, both of the twins having served in the military. The purpose was medical research and ultimately improved clinical care. The cohort was assembled in the early 1960s with identification of approximately 16,000 twin pairs, review of service records, a brief mailed questionnaire assessing zygosity, and a health survey largely comparable to questionnaires used at that time with Scandinavian twin registries. Subsequent large-scale data collection occurred in 1974, 1985 and 1998, repeating the health survey and including information on education, employment history and earnings. Self-reported data have been supplemented with mortality, disability and medical data through record linkage. Potential collaborators should access the study website [http://www.iom.edu/Activities/Veterans/TwinsStudy.aspx] or e-mail the Medical Follow-up Agency at [Twins@nas.edu]. Questionnaire data are being prepared for future archiving with the National Archive of Computerized Data on Aging (NACDA) at the Inter-University Consortium for Political and Social Research (ICPSR), University of Michigan, MI.