A template-assembled model of the N-peptide helix bundle from HIV-1 Gp-41 with high affinity for C-peptide

The infection of target cells by HIV-1 is initiated by fusion of the viral and cell membranes, which is mediated by the viral glycoproteins, gp120 and gp41. After initial cell binding by gp120, the folding of gp41 to form a stable six-helix bundle structure is directly associated with membrane fusion. This helix bundle is composed of an alpha-helical trimer of gp41 N-peptide, with three copies of the alpha-helical gp41 C-peptide folded onto it in an antiparallel orientation. This report describes the synthesis and study of an N-peptide three-helix bundle structure, KTA-3N29b, that is assembled on a threefold symmetric template derived from Kemp's triacid. At neutral pH and in the presence of physiologic salt, KTA-3N29b, exists as a monomer with high helix content. Binding isotherms measured by circular dichroism spectropolarimetry indicate that KTA-3N29b binds three copies of the C-peptide native sequence, with a KD of about 260 nM. These features of KTA-3N29b demonstrate that this templated three-helix bundle serves as a functional model for the native N-peptide structure that will allow detailed studies of the folding and thermodynamic stability of the gp41 six-helix bundle, and may aid the future development of potent HIV-1 fusion inhibitors and immunogens.     

Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition

Multifactorial predisposition to melanoma includes genes involved in pigmentation, immunity and DNA repair. Nonetheless, missing heritability in melanoma is still important. We studied the role of 335 candidate SNPs in melanoma susceptibility by using a dedicated chip and investigating 110 genes involved in different pathways. A discovery set was comprised of 1069 melanoma patients and 925 controls from France. Data were replicated using validation phases II (1085 cases and 801 controls from Spain) and III (1808 cases and 1894 controls from Germany and a second set of Spanish samples). In addition, an exome sequencing study was performed in three high‐risk French melanoma families. Nineteen SNPs in 17 genes were initially associated with melanoma in the French population. Six SNPs were replicated in phase II, including two new SNPs in the WNT3 (rs199524) and VPS41 (rs11773094) genes. The role of VPS41 and WNT3 was confirmed in a meta‐analysis (3940 melanoma cases and 3620 controls) with two‐side p values of 0.002, (OR = 0.86) and 4.07 × 10^?10 (OR = 0.80), respectively. Exome sequencing revealed a non‐synonymous VPS41 variant in one family that was shown to be strongly associated with familial melanoma (OR = 4.46, p = 0.001) in an independent sample of 178 melanoma families. WNT3 belongs to WNT pathway known to play a crucial role in melanoma, whereas VPS41 regulates vesicular trafficking and is thought to play a role in pigmentation. Our work identified two new pathways involved in melanoma predisposition. These results may be useful in the future for identifying individuals highly predisposed to melanoma.     

Sensitivity of a rapid point of care assay for early HIV antibody detection is enhanced by its ability to detect HIV gp41 IgM antibodies

BackgroundAnti-HIV-1 IgM antibody is an important immunoassay target for early HIV antibody detection.ObjectivesThe objective of this study is to determine if the early HIV antibody sensitivity of the 60 s INSTI test is due to detection of anti-HIV-1 IgM in addition to IgG.Study DesignTo demonstrate HIV gp41 IgM antibody capture by the INSTI HIV-1 gp41 recombinant antigen, an HIV-IgM ELISA was conducted with commercial HIV-1 seroconversion samples. To demonstrate that the INSTI dye-labelled Protein A-based colour developer (CD) has affinity to human IgM, commercial preparations of purified human immunoglobulins (IgM, IgD, IgA, IgE, and IgG) were blotted onto nitrocellulose (NC) and probed with the CD to observe spot development. To determine that INSTI is able to detect anti-HIV-1 IgM antibody, early seroconversion samples, were tested for reduced INSTI test spot intensity following IgM removal.ResultsThe gp41-based HIV-IgM ELISA results for 6 early seroconversion samples that were INSTI positive determined that the assay signal was due to anti-HIV-1 IgM antibody capture by the immobilised gp41 antigen. The dye-labelled Protein-A used in the INSTI CD produced distinct spots for purified IgM, IgA, and IgG blotted on the NC membrane. Following IgM removal from 21HIV-1 positive seroconversion samples with known or undetermined anti-HIV-1 IgM levels that were western blot negative or indeterminate, all samples had significantly reduced INSTI test spot intensity.ConclusionsThe INSTI HIV-1/HIV-2 Antibody Test is shown to detect anti-HIV-1 IgM antibodies in early HIV infection which enhances its utility in early HIV diagnosis.     

Nordic Walking in Pulmonary Rehabilitation of Patients Referred for Lung Transplantation

Background

Although the effectiveness of pulmonary rehabilitation in patients with chronic obstructive lung disease, cystic fibrosis, and interstitial lung disease is well documented, little is known about pulmonary rehabilitation in patients who are referred for lung transplantation. Nordic walking is a low-cost and accessible form of physical exercise with proven benefits. The purpose of this prospective study was to examine the effects of Nordic walking on lung function, perception of dyspnea, and health-related quality of life in patients referred for lung transplantation.

抗HIV药物进展

文章讨论了现存各种抗AIDS药物及其作用与研究进展，文末附表作了概括，为抗HIV药物研究提供参考。     

球形芽孢杆菌C_（3－41）块剂和颗粒剂防制城市致乏库蚊动虫效果评价

本文报道球形芽孢杆菌Ｃ３－４１（下称Ｂ。ｓＣ３－４１）乳剂、颗粒剂和块剂控制致乏库蚊幼虫的效果及其评价。结果表明：乳剂和颗粒剂的即杀效果比块剂好，２００ＩＴＵ／μｌ的Ｂ．ｓＣ３－４１乳剂１、２、３ｍｌ／ｍ２和１４０ＩＴＵ／μｌ的颗粒剂４．８ｇ／ｍ２，４８ｈ平均幼虫下降率．分别为８２～９６％和８８￣１００％；而１６０ＩＴＵ／μｌ的块剂４．８ｇ／ｍ２，４８ｈ平均幼虫下降率只有３３～５６％。３种剂型的持效以块剂为佳，可达３个月以上。     

球形芽孢杆菌C3—41乳剂杀灭淡色库蚊幼虫试验观察

采用球形芽孢杆菌C3-41制剂处理淡色库蚊幼虫,实验室测试LC_(50)为0.0237ppm,回归方程式y=8.3337 2.0530x。现场试验结果表明,使用剂量为1ml/m~2时持效7天,3ml/m~2时持效2周以上。但该制剂对其卵和蛹无杀灭作用。