Light at night increases body mass by shifting the time of food intake

The global increase in the prevalence of obesity and metabolic disorders coincides with the increase of exposure to light at night (LAN) and shift work. Circadian regulation of energy homeostasis is controlled by an endogenous biological clock that is synchronized by light information. To promote optimal adaptive functioning, the circadian clock prepares individuals for predictable events such as food availability and sleep, and disruption of clock function causes circadian and metabolic disturbances. To determine whether a causal relationship exists between nighttime light exposure and obesity, we examined the effects of LAN on body mass in male mice. Mice housed in either bright (LL) or dim (DM) LAN have significantly increased body mass and reduced glucose tolerance compared with mice in a standard (LD) light/dark cycle, despite equivalent levels of caloric intake and total daily activity output. Furthermore, the timing of food consumption by DM and LL mice differs from that in LD mice. Nocturnal rodents typically eat substantially more food at night; however, DM mice consume 55.5% of their food during the light phase, as compared with 36.5% in LD mice. Restricting food consumption to the active phase in DM mice prevents body mass gain. These results suggest that low levels of light at night disrupt the timing of food intake and other metabolic signals, leading to excess weight gain. These data are relevant to the coincidence between increasing use of light at night and obesity in humans.     

RNA-mediated epigenetic regulation of DNA copy number

Increasing evidence suggests that parentally supplied RNA plays crucial roles during eukaryotic development. This epigenetic contribution may regulate gene expression from the earliest stages. Although present in a variety of eukaryotes, maternally inherited characters are especially prominent in ciliated protozoa, in which parental noncoding RNA molecules instruct whole-genome reorganization. This includes removal of nearly all noncoding DNA and sorting the remaining fragments, producing extremely gene-rich somatic genomes. Chromosome fragmentation and extensive replication produce variable DNA copy numbers in the somatic genome. Understanding the forces that drive and regulate copy number change is fundamental. We show that RNA molecules present in parental cells during sexual reproduction can regulate chromosome copy number in the developing nucleus of the ciliate Oxytricha. Experimentally induced changes in RNA abundance can both increase and decrease the levels of corresponding DNA molecules in progeny, demonstrating epigenetic inheritance of chromosome copy number. These results suggest that maternal RNA, in addition to controlling gene expression or DNA processing, can also program DNA amplification levels.     

Slipknotting upon native-like loop formation in a trefoil knot protein

Protein knots and slipknots, mostly regarded as intriguing oddities, are gradually being recognized as significant structural motifs. Recent experimental results show that knotting, starting from a fully extended polypeptide, has not yet been observed. Understanding the nucleation process of folding knots is thus a natural challenge for both experimental and theoretical investigation. In this study, we employ energy landscape theory and molecular dynamics to elucidate the entire folding mechanism. The full free energy landscape of a knotted protein is mapped using an all-atom structure-based protein model. Results show that, due to the topological constraint, the protein folds through a three-state mechanism that contains (i) a precise nucleation site that creates a correctly twisted native loop (first barrier) and (ii) a rate-limiting free energy barrier that is traversed by two parallel knot-forming routes. The main route corresponds to a slipknot conformation, a collapsed configuration where the C-terminal helix adopts a hairpin-like configuration while threading, and the minor route to an entropically limited plug motion, where the extended terminus is threaded as through a needle. Knot formation is a late transition state process and results show that random (nonspecific) knots are a very rare and unstable set of configurations both at and below folding temperature. Our study shows that a native-biased landscape is sufficient to fold complex topologies and presents a folding mechanism generalizable to all known knotted protein topologies: knotting via threading a native-like loop in a preordered intermediate.     

A Hospice-based Advanced Pharmacy Experience

Objective

To evaluate a hospice-based advanced pharmacy practice experience (APPE).

Design

Two years of data gathered from student evaluation forms and reflective journals were analyzed.

Assessment

Students completed reflective journals and expressed a high level of satisfaction with the hospice-based learning experience. They gained a better understanding of end-of-life care provided by a hospice and the pharmacist''s role in optimizing supportive care for patients receiving hospice care.

Conclusion

Hospice-based APPEs can provide a rich interdisciplinary learning environment for pharmacy students interested in developing knowledge, attitudes, and skills to effectively manage the pharmacotherapy of patients receiving end-of-life care.     

"Just like fever": a qualitative study on the impact of antiretroviral provision on the normalisation of HIV in rural Tanzania and its implications for prevention

Background  

Once effective therapy for a previously untreatable condition is made available, a normalisation of the disease often occurs. As part of a broader initiative to monitor the implementation of the national antiretroviral therapy (ART) programme, this qualitative study investigated the impact of ART availability on perceptions of HIV in a rural ward of North Tanzania and its implications for prevention.     

No association of three GRIN2B polymorphisms with lithium response in bipolar patients

We investigated three polymorphisms in the NMDAreceptor 2B subunit gene (GRIN2B) as a candidate gene for lithium response involved in glutamatergic neurotransmission. One hundred five bipolar patients treated with lithium for at least 5 years were analyzed. The lithium response was assessed as excellent – no affective episodes during lithium treatment; partial – 50% reduction in the episode index; or no response – less than 50% reduction, no change or worsening in the episode index. Genotypes for the -200G/T, 366C/G and rs890G/T GRIN2B polymorphisms were established using the PCR-RFLP method. Genotype distributions were in Hardy-Weinberg equilibrium for all three polymorphisms. No association was found between the three polymorphisms studied and the treatment response to lithium. The authors conclude that polymorphisms of the GRIN2B gene did not show an association with the treatment response to lithium in bipolar patients.     

Deborah Dunsire：万事皆有可能

继19位制药界的女精英被保健女企业家协会（HBA）推选为年度杰出女性后,千年制约CEO Deborah Dunsire近日被宣布当选为2009年HBA的年度女性。