Converging on the function of intrinsically disordered nucleoporins in the nuclear pore complex

Several biological mechanisms involve proteins or proteinaceous components that are intrinsically disordered. A case in point pertains to the nuclear pore complex (NPC), which regulates molecular transport between the nucleus and the cytoplasm. NPC functionality is dependent on unfolded domains rich in Phe-Gly (FG) repeats (i.e., FG-domains) that collectively act to promote or hinder cargo translocation. To a large extent, our understanding of FG-domain behavior is limited to in vitro investigations given the difficulty to resolve them directly in the NPC. Nevertheless, recent findings indicate a collective convergence towards rationalizing FG-domain function. This review aims to glean further insight into this fascinating problem by taking an objective look at the boundary conditions and contextual details underpinning FG-domain behavior in the NPC. Here, we treat the FG-domains as being commensurate with polymeric chains to address ambiguities such as for instance, how FG-domains tethered to the central channel of the NPC would behave differently as compared with their free-floating counterparts in solution. By bringing such fundamental questions to the fore, this review seeks to illuminate the importance of how such parameters can hold influence over the structure-function relation of intrinsically disordered proteins in the NPC and beyon

Managing peer relationships online - Investigating the use of Facebook by juvenile delinquents and youths-at-risk

10.1016/j.chb.2012.04.025Computers in Human Behavior2918-15CHBE

Sulphonylurea Usage in Melioidosis Is Associated with Severe Disease and Suppressed Immune Response

10.1371/journal.pntd.0002795PLoS Neglected Tropical Diseases84

The Role of Translation Initiation Regulation in Haematopoiesis

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control

Respiratory Infections during SARS Outbreak, Hong Kong, 2003

The effect of community hygienic measures during the outbreak of severe acute respiratory syndrome in Hong Kong was studied by comparing the proportion of positive specimens of various respiratory viruses in 2003 with those from 1998 to 2002. Community hygienic measures significantly reduced the incidence of various respiratory viral infections

Stroke Prevention in Atrial Fibrillation:A Scientific Statement of JACC: Asia (Part 2)

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with substantial increases in the risk for stroke and systemic thromboembolism. With the successful introduction of the first non-vitamin K antagonistdirect oral anticoagulant agent (NOAC) in 2009, the role of vitamin K antagonists has been replaced in most clinical settings except in a few conditions for which NOACs are contraindicated. Data for the use of NOACs in different clinical scenarios have been accumulating in the past decade, and a more sophisticated strategy for patients with AF is now warranted. JACC: Asia recently appointed a working group to summarize the most updated information regarding stroke prevention in AF. The aim of this statement is to provide possible treatment options in daily practice. Local availability, cost, and patient comorbidities should also be considered. Final decisions may still need to be individualized and based on clinicians’ discretion. This is part 2 of the statement

Stroke Prevention in Atrial Fibrillation:A Scientific Statement of JACC: Asia (Part 1)

Atrial fibrillation is the most common sustained cardiac arrhythmia and is associated with substantial increases in the risk of stroke and systemic thromboembolism. With the successful introduction of the first non-vitamin K antagonist direct oral anticoagulant (NOAC) in 2009, the role of vitamin K antagonists has been replaced in most clinical settings except in a few conditions when NOACs are contraindicated. Data for the use of NOACs in different clinical scenarios have been accumulating in the recent decade, and a more sophisticated strategy for atrial fibrillation patients is now warranted. JACC: Asia recently appointed a working group to summarize the most updated information regarding stroke prevention in AF. This statement aimed to provide possible treatment option in daily practice. Local availability, cost, and patient comorbidities should also be considered. Final decisions may still need to be individualized and based on clinicians’ discretion. This is the part 1 of the whole statement

Pyrimidin‐6‐yl trifluoroborate salts as versatile templates for heterocycle synthesis

We report a novel and general method to access a highly under‐studied privileged scaffold – pyrimidines bearing a trifluoroborate at C4, and highlight the broad utility of these intermediates in a rich array of downstream functionalization reactions. This chemistry is underpinned by the unique features of the trifluoroborate group; its robustness provides an opportunity to carry out chemoselective reactions at other positions on the pyrimidine while providing a pathway for elaboration at the C‐B bond when suitably activated