Mktg

A new approach to learning the principles of marketing, MKTG is the Asia–Pacific edition of a proven, innovative solution to enhance the students' learning experience. Concise, yet complete, coverage supported by a suite of online learning aids equips students with the tools required to successfully undertake an introductory marketing course. Paving a new way to both teaching and learning, MKTG is designed to truly connect with today's busy tech-savy student. Students have access to online interactive quizzing, videos, podcasts, flashcards, marketing plans, games and more. An accessible, easy-to-read text along with tear out review cards complete a package which helps students to learn important concepts faster

Isotope labeling strategies for NMR studies of RNA

The known biological functions of RNA have expanded in recent years and now include gene regulation, maintenance of sub-cellular structure, and catalysis, in addition to propagation of genetic information. As for proteins, RNA function is tightly correlated with structure. Unlike proteins, structural information for larger, biologically functional RNAs is relatively limited. NMR signal degeneracy, relaxation problems, and a paucity of long-range 1H–1H dipolar contacts have limited the utility of traditional NMR approaches. Selective isotope labeling, including nucleotide-specific and segmental labeling strategies, may provide the best opportunities for obtaining structural information by NMR. Here we review methods that have been developed for preparing and purifying isotopically labeled RNAs, as well as NMR strategies that have been employed for signal assignment and structure determination

Recent Decisions

Comments on recent decisions by Cornelius F. Collins, Joseph P. Summers, Michael E. Phenner, Daniel J. Manelli, Ralph H. Witt, Richard C. Wilbur, and Raymond W. Brown

6th International Symposium on Retroviral Nucleocapsid

Retroviruses and LTR-retrotransposons are widespread in all living organisms and, in some instances such as for HIV, can be a serious threat to the human health. The retroviral nucleocapsid is the inner structure of the virus where several hundred nucleocapsid protein (NC) molecules coat the dimeric, genomic RNA. During the past twenty years, NC was found to play multiple roles in the viral life cycle (Fig. 1), notably during the copying of the genomic RNA into the proviral DNA by viral reverse transcriptase and integrase, and is therefore considered to be a prime target for anti-HIV therapy. The 6th NC symposium was held in the beautiful city of Amsterdam, the Netherlands, on the 20th and 21st of September 2007. All aspects of NC biology, from structure to function and to anti-HIV vaccination, were covered during this meeting

Targeting of MuLV Gag to the plasma membrane is mediated by PI(4,5)P2 and PhosphatidylSerine

Oral presentationInternational audienceMembrane targeting by the modern human immunodeficiency viruses is dependent on the plasma membrane-located phospholipid PI(4,5)P2. In order to determine if evolutionarily distant retroviruses are targeted by a similar mechanism, we generated mutant Gag constructs in the matrix (MA) domain of the Murine Leukemia Virus (MuLV) and examined their binding to membrane models and phenotypes in cell culture. Mutations in the MA polybasic region altered Gag localization, membrane binding and virion production. In addition, we show that MA binds with good affinity to all the phosphatidylinositol phosphates but displays a strong specificity for PI(4,5)P2 only if enhanced by phophatidylserine. Virus production was strongly impaired by PI(4,5)P2 depletion under 5ptaseIV overexpression. Our results suggest that the N-terminal polybasic region of MA is essential for Gag targeting to the plasma membrane and Gag cellular trafficking. The binding of the MA domain to PI(4,5)P2 appears to be a conserved feature among retroviruses, despite the fact that the MuLV-MA domain is structurally different from that of HIV-1 and -2 and lacks a readily identifiable PI(4,5)P2 binding cleft

Improving Underrepresented Minority Student Persistence in STEM.

Members of the Joint Working Group on Improving Underrepresented Minorities (URMs) Persistence in Science, Technology, Engineering, and Mathematics (STEM)-convened by the National Institute of General Medical Sciences and the Howard Hughes Medical Institute-review current data and propose deliberation about why the academic "pathways" leak more for URM than white or Asian STEM students. They suggest expanding to include a stronger focus on the institutional barriers that need to be removed and the types of interventions that "lift" students' interests, commitment, and ability to persist in STEM fields. Using Kurt Lewin's planned approach to change, the committee describes five recommendations to increase URM persistence in STEM at the undergraduate level. These recommendations capitalize on known successes, recognize the need for accountability, and are framed to facilitate greater progress in the future. The impact of these recommendations rests upon enacting the first recommendation: to track successes and failures at the institutional level and collect data that help explain the existing trends

Pulmonary retention of primed neutrophils: a novel protective host response, which is impaired in the acute respiratory distress syndrome.

RATIONALE: Acute respiratory distress syndrome (ARDS) affects over 200000 people annually in the USA. Despite causing severe, and often refractory, hypoxaemia, the high mortality and long-term morbidity of ARDS results mainly from extra-pulmonary organ failure; however the mechanism for this organ crosstalk has not been determined. METHODS: Using autologous radiolabelled neutrophils we investigated the pulmonary transit of primed and unprimed neutrophils in humans. Flow cytometry of whole blood samples was used to assess transpulmonary neutrophil priming gradients in patients with ARDS, sepsis and perioperative controls. MAIN RESULTS: Unprimed neutrophils passed through the lungs with a transit time of 14.2 s, only 2.3 s slower than erythrocytes, and with <5% first-pass retention. Over 97% of neutrophils primed ex vivo with granulocyte macrophage colony-stimulating factor were retained on first pass, with 48% still remaining in the lungs at 40 min. Neutrophils exposed to platelet-activating factor were initially retained but subsequently released such that only 14% remained in the lungs at 40 min. Significant transpulmonary gradients of neutrophil CD62L cell surface expression were observed in ARDS compared with perioperative controls and patients with sepsis. CONCLUSIONS: We demonstrated minimal delay and retention of unprimed neutrophils transiting the healthy human pulmonary vasculature, but marked retention of primed neutrophils; these latter cells then 'deprime' and are re-released into the systemic circulation. Further, we show that this physiological depriming mechanism may fail in patients with ARDS, resulting in increased numbers of primed neutrophils within the systemic circulation. This identifies a potential mechanism for the remote organ damage observed in patients with ARDS.This work was supported by the Wellcome Trust, MRC (UK), Papworth Hospital R&D, Intensive Care Society and NIHR Cambridge Biomedical Research Centre.This is the final published version, also available from http://thorax.bmj.com/content/early/2014/04/04/thoraxjnl-2013-204742.full

Ablation of AMP-Activated Protein Kinase α\alpha2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice

Objective: We determined whether muscle AMP-activated protein kinase (AMPK) has a role in the development of insulin resistance. Research Design and Methods: Muscle-specific transgenic mice expressing an inactive form of the AMPK $\alpha$2 catalytic subunit ($\alpha$2i TG) and their wild-type littermates were fed either a high-fat (60% kcal fat) or a control (10% kcal fat) diet for 30 weeks. Results: Compared with wild-type mice, glucose tolerance in $\alpha$2i TG mice was slightly impaired on the control diet and significantly impaired on the high-fat diet. To determine whether the whole-body glucose intolerance was associated with impaired insulin sensitivity in skeletal muscle, glucose transport in response to submaximal insulin (450 $\mu$U/ml) was measured in isolated soleus muscles. On the control diet, insulin-stimulated glucose transport was reduced by $\sim$50% in $\alpha$2i TG mice compared with wild-type mice. High-fat feeding partially decreased insulin-stimulated glucose transport in wild-type mice, while high-fat feeding resulted in a full blunting of insulin-stimulated glucose transport in the $\alpha$2i TG mice. High-fat feeding in $\alpha$2i TG mice was accompanied by decreased expression of insulin signaling proteins in gastrocnemius muscle. Conclusions: The lack of skeletal muscle AMPK $\alpha$2 activity exacerbates the development of glucose intolerance and insulin resistance caused by high-fat feeding and supports the thesis that AMPK $\alpha$2 is an important target for the prevention/amelioration of skeletal muscle insulin resistance through lifestyle (exercise) and pharmacologic (e.g., metformin) treatments

Combining Existing Monitoring Sites with a Probability Survey Design-Examples from U.S. EPA’s National Coastal Assessment

U.S. Environmental Protection Agency’s (EPA’s) National Coastal Assessment was envisioned as a research effort led by EPA’s Office of Research and Development to evaluate assessment methods for ecosystem condition monitoring. The program was conducted through strategic partnerships with the coastal states. These states conducted the survey in their waters with a common set of indicators. The resources targeted for initial monitoring were estuarine waters. A flexible probability survey design was used to incorporate, to the extent possible, existing state monitoring program sites. Three criteria were developed to evaluate existing monitoring program sites in the northeastern United States for possible incorporation into the national design: (1) the sites were selected to be representative, (2) the variables sampled at the sites were similar in distribution with variables from a probability design, and (3) the correlation structure of variables was equivalent to that for a probability design. Detailed examples were presented for Long Island Sound water quality sites, New Jersey coastal water quality sites, and Casco Bay, ME, sediment sites to illustrate the approach