The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Competitive and Cooperative Interactions Mediate RNA Transfer from Herpesvirus Saimiri ORF57 to the Mammalian Export Adaptor ALYREF

The essential herpesvirus adaptor protein HVS ORF57, which has homologs in all other herpesviruses, promotes viral mRNA export by utilizing the cellular mRNA export machinery. ORF57 protein specifically recognizes viral mRNA transcripts, and binds to proteins of the cellular transcription-export (TREX) complex, in particular ALYREF. This interaction introduces viral mRNA to the NXF1 pathway, subsequently directing it to the nuclear pore for export to the cytoplasm. Here we have used a range of techniques to reveal the sites for direct contact between RNA and ORF57 in the absence and presence of ALYREF. A binding site within ORF57 was characterized which recognizes specific viral mRNA motifs. When ALYREF is present, part of this ORF57 RNA binding site, composed of an a-helix, binds preferentially to ALYREF. This competitively displaces viral RNA from the a-helix, but contact with RNA is still maintained by a flanking region. At the same time, the flexible N-terminal domain of ALYREF comes into contact with the viral RNA, which becomes engaged in an extensive network of synergistic interactions with both ALYREF and ORF57. Transfer of RNA to ALYREF in the ternary complex, and involvement of individual ORF57 residues in RNA recognition, were confirmed by UV cross-linking and mutagenesis. The atomic-resolution structure of the ORF57-ALYREF interface was determined, which noticeably differed from the homologous ICP27-ALYREF structure. Together, the data provides the first site-specific description of how viral mRNA is locked by a herpes viral adaptor protein in complex with cellular ALYREF, giving herpesvirus access to the cellular mRNA export machinery. The NMR strategy used may be more generally applicable to the study of fuzzy protein-protein-RNA complexes which involve flexible polypeptide regions

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

Meeting abstrac

Universality of Strength of Yukawa Couplings, Quark Singlets and Strength of CP Violation

We analyse the strength of CP violation in an extension of the standard model with an extra $Q=-1/3$ vector-like singlet quark, in the framework of the hypothesis of universality of strength of Yukawa couplings connecting standard quarks. We show that the correct pattern of quark masses and mixing can be obtained, including the observed strength of CP violation.Comment: 9 pages, no figure

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

The efficacy of four-slice helical CT in evaluating pancreatic trauma: a single institution experience

<p>Abstract</p> <p>Study objective</p> <p>To assess the efficacy of computed tomography (CT) in evaluating patients with pancreatic trauma.</p> <p>Methods</p> <p>We undertook a retrospective review of all blunt trauma patients admitted to the Chi-Mei Medical Center from January 2004 to June 2006. Every patients underwent abdominal CT scan in emergency department and the CT scans were obtained with a four-slice helical CT. Diagnosis of a pancreatic injury in these patients was by surgical observation or by CT findings. Radiographic pancreatic injuries were classified as deep or superficial lesions. Deep lesions were defined as the hematomas or lacerations >50% thickness of the pancreas. Superficial lesions were described as the hematomas or lacerations <50% thickness of the pancreas; pancreatic edema; and focal fluid accumulation around the pancreas</p> <p>Results</p> <p>Nineteen patients with pancreatic trauma, fourteen males and five females, average age 40.6 ± 21.4 years, were included. Most patients (73.7%) with pancreatic trauma had associated organ injuries. CT was performed in all patients and laparotomy in 14 patients. CT was 78.9% sensitive in detecting pancreatic trauma. All deep pancreatic lesions revealed on CT required surgical treatment, and complication was discovered in two patients undergoing delayed surgery. Superficial lesions were managed conservatively.</p> <p>Conclusion</p> <p>Four-slice helical CT can detect most pancreatic trauma and provide practical therapeutic guidance. Delayed operation might result in complications and is associated with prolonged hospital stays.</p

Body mass index and smoking-related lung cancer risk in the Singapore Chinese Health Study

10.1038/sj.bjc.6605496British Journal of Cancer1023610-61

Relevance of human metapneumovirus in exacerbations of COPD

BACKGROUND AND METHODS: Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR. RESULTS: We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 10(5 )viral copies/ml in nasal lavage and 1.88 × 10(5 )viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD. CONCLUSION: HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely