Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene

Studies of families with breast cancer have indicated that male carriers of BRCA2 mutations are at increased risk of prostate cancer, particularly at an early age. To evaluate the contribution of BRCA2 mutations to early-onset prostate cancer, we screened the complete coding sequence of BRCA2 for germline mutations, in 263 men with diagnoses of prostate cancer who were 相似文献   

Interaction of the antimicrobial peptide cyclo(RRWWRF) with membranes by molecular dynamics simulations

Antimicrobial peptides have gained a lot of interest in recent years due to their potential use as a new generation of antibiotics. It is believed that this type of relatively short, amphipathic, cationic peptide targets the bacterial membrane, and destroys the chemical gradients over the membrane via formation of stable or transient pores. Here we use the NMR structure of cyclo(RRWWRF) in a series of molecular dynamics simulations in membranes at various peptide/lipid ratios. We observe that the NMR structure of the peptide is still stable after 100 ns simulation. At a peptide/lipid ratio of 2:128, the membrane is only a little affected compared to a pure dipalmitoylphosphatidylcholine lipid membrane, but at a ratio of 12:128, the water-lipid interface becomes more fuzzy, the water molecules can reach deeper into the hydrophobic core, and the water penetration free-energy barrier changes. Moreover, we observe that the area per lipid decreases and the deuterium order parameters increase in the presence of the peptide. We suggest that the changes in the hydrophobic core, together with the changes in the headgroups, result in an imbalance of the membrane and that it is thus not an efficient hydrophobic barrier in the presence of the peptides, independent of pore formation.     

Crystallization and preliminary X-ray crystallographic analysis of Mirabilis antiviral protein.

Mirabilis antiviral protein is a single-chain ribosome-inactivating protein purified from the tuberous root of Mirabilis jalapa L. We obtained several forms of crystals of the protein by the hanging drop vapor diffusion method, but most of these crystals were not suitable for X-ray crystallography. After refining the growth conditions, crystals of crystallographic quality were grown in 20-microliters droplets of an equi-volume mixture of 1.5% (w/v) protein solution and a reservoir solution containing 49 to 50% (w/v) ammonium sulfate and 50 mM-ammonium citrate (pH 5.4) at room temperature. Addition of 2 mM-adenine sulfate reduced twinning and "crystal shower". The resulting trigonal crystals diffract beyond 2.5 A resolution using a rotating anode X-ray generator. The space group was determined to be P3(1)21 or P3(2)21 (a = b = 103.9.A, c = 134.6 A, alpha = beta = 90 degrees, gamma = 120 degrees) based on their precession photography of h0l and hk0 zones. There seems to be three monomers in an asymmetric unit for VM = 2.51 A3/Da.     

Chlamydia pneumoniae infection alters the junctional complex proteins of human brain microvascular endothelial cells

Chlamydia pneumoniae has been identified and associated with multiple sclerosis (MS) and Alzheimer's disease (AD) pathogenesis, although the relationship of this organism in these diseases remains controversial. We have hypothesized that one potential avenue of infection is through the junctional complexes between the blood-brain barrier (BBB) endothelia. C. pneumoniae is characteristically a respiratory pathogen, but has been implicated in atherosclerosis, coronary artery disease, and neuroinflammatory conditions. C. pneumoniae infection may lead to endothelial damage, junctional alterations, and BBB breakdown. Therefore, in this study, C. pneumoniae infection of human brain microvascular endothelial cells (HBMECs) resulted in increased expression of the zonula adherens proteins beta-catenin, N-cadherin, and VE-cadherin, and decreased expression of the tight junctional protein occludin, as determined by immunocytochemistry and Western blot analyses. These events may underlie a mechanism for the regulation of paracellular permeability while maintaining barrier integrity during C. pneumoniae infection associated with neuropathologies such as MS and AD.     

Fatigue after stroke: baseline predictors and influence on survival. Analysis of data from UK patients recruited in the International Stroke Trial

Background and Purpose

Little is known about the associations of post-stroke fatigue or its influence on survival. The vitality component of the Short Form 36 (SF-36) is a valid and reliable measure of post-stroke fatigue. We sought to identify associates of post-stroke fatigue and determine whether fatigue predicted survival.

Methods

We used SF-36 vitality scores obtained by postal questionnaires from 1080 UK patients randomised in the International Stroke Trial, at a mean of 64 weeks after stroke onset. We used logistic regression to explore factors at randomisation which predicted SF-36 vitality at follow-up, and the relationship between SF-36 vitality and both SF-36 mental health and SF-36 emotional role function at follow-up. We used Cox proportional hazards to explore the influence of SF-36 vitality at follow-up on subsequent survival, using four different statistical models for handling missing data.

Results

Female sex, increasing age, lower mental health and lower emotional role function scores were associated with greater degrees of fatigue after stroke (i.e. lower vitality scores) but these factors explained <30% of the variance (R²) in fatigue. In two models, fatigue at follow-up was associated with shorter subsequent survival.

Conclusion

Increasing age, female sex, emotional role function and mental health were associated with increased fatigue at a mean of 64 weeks after stroke onset, but explained less than 30% of the variance. Fatigue was associated with reduced subsequent long-term survival in 2/4 models. Further work is needed to identify the biological substrate of fatigue and to clarify its influence on survival.     

Viruses in a 14th-Century Coprolite

Coprolites are fossilized fecal material that can reveal information about ancient intestinal and environmental microbiota. Viral metagenomics has allowed systematic characterization of viral diversity in environmental and human-associated specimens, but little is known about the viral diversity in fossil remains. Here, we analyzed the viral community of a 14th-century coprolite from a closed barrel in a Middle Ages site in Belgium using electron microscopy and metagenomics. Viruses that infect eukaryotes, bacteria, and archaea were detected, and we confirmed the presence of some of them by ad hoc suicide PCR. The coprolite DNA viral metagenome was dominated by sequences showing homologies to phages commonly found in modern stools and soil. Although their phylogenetic compositions differed, the metabolic functions of the viral communities have remained conserved across centuries. Antibiotic resistance was one of the reconstructed metabolic functions detected.     

The Concept of Electroosmotically Driven Flow and Its Application to Biomimetics

1　IntroductionOneaimofthephysicsscienceresearchistodevel opfundamentalandportableconceptswhichhelpunitedifferentresearchfrontiers.Inthisrespect ,Helmholtz’selectricdoublelayer (DEL)theory ,whichwasdevel opedin 1879andrelatedtheelectricandflowparame tersforelectrokinetictransport ,isaseminal,havingprovidedaframeworkforinterpretingawiderangeofelectrokineticphenomena .DespitethesimplicityoftheEDLtheory ,whichwewilldescribeindetail,ithasprovidedachallengeformathematicianstounderstanditsimplic…     

Geometric design of crab-like climbing and walking robots

1 Introduction Many CLAWAR (CLimbing And WAlking Robots)researchers have concentrated on navigation, gait gen-eration and control, rather than mechanical design. Whenprototypes have been developed, it has often been as-sumed that the mechanical design principles are knownand the problem is one of applying them. In practise, thisis far from the truth, as the performance of existing pro-totypes testifies. The most common design approach is tocopy the geometry of insects and mammals wit…     

Palatal fistulas: rare with the two-flap palatoplasty repair

The purpose of this study was to examine the palatal fistula rate after repair with the two-flap palatoplasty technique. This is a retrospective review of 119 consecutive cleft-palate repairs performed over a 5-year interval by a single surgeon. The two-flap palatoplasty technique was used to provide tension-free, multilayer repairs. The age of these children at the time of repair ranged from 7 to 84 months (mode, 9 months). The initial follow-up visit occurred 2 to 12 weeks after the repair operation (mean, 4 weeks). The postoperative follow-up duration ranged from 7 to 48 months. This review of 119 cleft-palate repairs revealed a fistula rate of 3.4 percent (four fistulas in 119 repairs). This experience demonstrates the lowest reported palatal fistula complication rate with use of the two-flap palatoplasty technique.