寿高九旬驾鹤西去 德范后人紫气东来——沉痛悼念焦瑞身先生

<正>焦瑞身(Jui-shen Chiao)1918-09-13,2009年12月22日卒于上海。1936年考取清华大学化学系,1941年毕业于西南联合大学并留校任化学系助教。1946年在北京大学农学院农化系任助教。     

SHP2及其在乳腺癌发生发展中的作用

SHP2是一种非受体型蛋白酪氨酸磷酸酶,其介导的信号转导异常与多种疾病包括肿瘤的发生和发展密切相关,对SHP2的深入研究有助于对其作用机制的阐明以及潜在药物学靶点的发现。本文简要介绍了SHP2的结构、功能及其介导的Ras/ERK信号通路,并着重阐述了SHP2与乳腺癌发展的关系。     

Sources and significance of variation in basal,summit and maximal metabolic rates in birds

The rates at which birds use energy may have profound effects on fitness, thereby influencing physiology, behavior, ecology and evolution. Comparisons of standardized metabolic rates (e.g., lower and upper limits of metabolic power output) present a method for elucidating the effects of ecological and evolutionary factors on the interface between physiology and life history in birds. In this paper we review variation in avian metabolic rates [basal metabolic rate (BMR; minimum normothermic metabolic rate), ...     

Geographic Distribution of Staphylococcus aureus Causing Invasive Infections in Europe: A Molecular-Epidemiological Analysis

Background

Staphylococcus aureus is one of the most important human pathogens and methicillin-resistant variants (MRSAs) are a major cause of hospital and community-acquired infection. We aimed to map the geographic distribution of the dominant clones that cause invasive infections in Europe.

Methods and Findings

In each country, staphylococcal reference laboratories secured the participation of a sufficient number of hospital laboratories to achieve national geo-demographic representation. Participating laboratories collected successive methicillin-susceptible (MSSA) and MRSA isolates from patients with invasive S. aureus infection using an agreed protocol. All isolates were sent to the respective national reference laboratories and characterised by quality-controlled sequence typing of the variable region of the staphylococcal spa gene (spa typing), and data were uploaded to a central database. Relevant genetic and phenotypic information was assembled for interactive interrogation by a purpose-built Web-based mapping application. Between September 2006 and February 2007, 357 laboratories serving 450 hospitals in 26 countries collected 2,890 MSSA and MRSA isolates from patients with invasive S. aureus infection. A wide geographical distribution of spa types was found with some prevalent in all European countries. MSSA were more diverse than MRSA. Genetic diversity of MRSA differed considerably between countries with dominant MRSA spa types forming distinctive geographical clusters. We provide evidence that a network approach consisting of decentralised typing and visualisation of aggregated data using an interactive mapping tool can provide important information on the dynamics of MRSA populations such as early signalling of emerging strains, cross border spread, and importation by travel.

Conclusions

In contrast to MSSA, MRSA spa types have a predominantly regional distribution in Europe. This finding is indicative of the selection and spread of a limited number of clones within health care networks, suggesting that control efforts aimed at interrupting the spread within and between health care institutions may not only be feasible but ultimately successful and should therefore be strongly encouraged. Please see later in the article for the Editors'' Summary     

HIV-1 Populations in Semen Arise through Multiple Mechanisms

HIV-1 is present in anatomical compartments and bodily fluids. Most transmissions occur through sexual acts, making virus in semen the proximal source in male donors. We find three distinct relationships in comparing viral RNA populations between blood and semen in men with chronic HIV-1 infection, and we propose that the viral populations in semen arise by multiple mechanisms including: direct import of virus, oligoclonal amplification within the seminal tract, or compartmentalization. In addition, we find significant enrichment of six out of nineteen cytokines and chemokines in semen of both HIV-infected and uninfected men, and another seven further enriched in infected individuals. The enrichment of cytokines involved in innate immunity in the seminal tract, complemented with chemokines in infected men, creates an environment conducive to T cell activation and viral replication. These studies define different relationships between virus in blood and semen that can significantly alter the composition of the viral population at the source that is most proximal to the transmitted virus.     

Maintenance treatment with esomeprazole following initial relief of non-steroidal anti-inflammatory drug-associated upper gastrointestinal symptoms: the NASA2 and SPACE2 studies

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 (COX-2) inhibitors, cause upper gastrointestinal (GI) symptoms that are relieved by treatment with esomeprazole. We assessed esomeprazole for maintaining long-term relief of such symptoms. Six hundred and ten patients with a chronic condition requiring anti-inflammatory therapy who achieved relief of NSAID-associated symptoms of pain, discomfort, or burning in the upper abdomen during two previous studies were enrolled and randomly assigned into two identical, multicentre, parallel-group, placebo-controlled studies of esomeprazole 20 mg or 40 mg treatment (NASA2 [Nexium Anti-inflammatory Symptom Amelioration] and SPACE2 [Symptom Prevention by Acid Control with Esomeprazole] studies; ClinicalTrials.gov identifiers NCT00241514 and NCT00241553, respectively) performed at various rheumatology, gastroenterology, and primary care clinics. Four hundred and twenty-six patients completed the 6-month treatment period. The primary measure was the proportion of patients with relapse of upper GI symptoms, recorded in daily diary cards, after 6 months. Relapse was defined as moderate-to-severe upper GI symptoms (a score of more than or equal to 3 on a 7-grade scale) for 3 days or more in any 7-day period. Esomeprazole was significantly more effective than placebo in maintaining relief of upper GI symptoms throughout 6 months of treatment. Life-table estimates (95% confidence intervals) of the proportion of patients with relapse at 6 months (pooled population) were placebo, 39.1% (32.2% to 46.0%); esomeprazole 20 mg, 29.3% (22.3% to 36.2%) (p = 0.006 versus placebo); and esomeprazole 40 mg, 26.1% (19.4% to 32.9%) (p = 0.001 versus placebo). Patients on either non-selective NSAIDs or selective COX-2 inhibitors appeared to benefit. The frequency of adverse events was similar in the three groups. Esomeprazole maintains relief of NSAID-associated upper GI symptoms in patients taking continuous NSAIDs, including selective COX-2 inhibitors.     

Merino and Merino-derived sheep breeds: a genome-wide intercontinental study

Background

Merino and Merino-derived sheep breeds have been widely distributed across the world, both as purebred and admixed populations. They represent an economically and historically important genetic resource which over time has been used as the basis for the development of new breeds. In order to examine the genetic influence of Merino in the context of a global collection of domestic sheep breeds, we analyzed genotype data that were obtained with the OvineSNP50 BeadChip (Illumina) for 671 individuals from 37 populations, including a subset of breeds from the Sheep HapMap dataset.

Results

Based on a multi-dimensional scaling analysis, we highlighted four main clusters in this dataset, which corresponded to wild sheep, mouflon, primitive North European breeds and modern sheep (including Merino), respectively. The neighbor-network analysis further differentiated North-European and Mediterranean domestic breeds, with subclusters of Merino and Merino-derived breeds, other Spanish breeds and other Italian breeds. Model-based clustering, migration analysis and haplotype sharing indicated that genetic exchange occurred between archaic populations and also that a more recent Merino-mediated gene flow to several Merino-derived populations around the world took place. The close relationship between Spanish Merino and other Spanish breeds was consistent with an Iberian origin for the Merino breed, with possible earlier contributions from other Mediterranean stocks. The Merino populations from Australia, New Zealand and China were clearly separated from their European ancestors. We observed a genetic substructuring in the Spanish Merino population, which reflects recent herd management practices.

Conclusions

Our data suggest that intensive gene flow, founder effects and geographic isolation are the main factors that determined the genetic makeup of current Merino and Merino-derived breeds. To explain how the current Merino and Merino-derived breeds were obtained, we propose a scenario that includes several consecutive migrations of sheep populations that may serve as working hypotheses for subsequent studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-015-0139-z) contains supplementary material, which is available to authorized users.     

Independent external validation of nomograms for predicting risk of low-trauma fracture and hip fracture

Background

A set of nomograms based on the Dubbo Osteoporosis Epidemiology Study predicts the five- and ten-year absolute risk of fracture using age, bone mineral density and history of falls and low-trauma fracture. We assessed the discrimination and calibration of these nomograms among participants in the Canadian Multicentre Osteoporosis Study.

Methods

We included participants aged 55–95 years for whom bone mineral density measurement data and at least one year of follow-up data were available. Self-reported incident fractures were identified by yearly postal questionnaire or interview (years 3, 5 and 10). We included low-trauma fractures before year 10, except those of the skull, face, hands, ankles and feet. We used a Cox proportional hazards model.

Results

Among 4152 women, there were 583 fractures, with a mean follow-up time of 8.6 years. Among 1606 men, there were 116 fractures, with a mean follow-up time of 8.3 years. Increasing age, lower bone mineral density, prior fracture and prior falls were associated with increased risk of fracture. For low-trauma fractures, the concordance between predicted risk and fracture events (Harrell C) was 0.69 among women and 0.70 among men. For hip fractures, the concordance was 0.80 among women and 0.85 among men. The observed fracture risk was similar to the predicted risk in all quintiles of risk except the highest quintile of women, where it was lower. The net reclassification index (19.2%, 95% confidence interval [CI] 6.3% to 32.2%), favours the Dubbo nomogram over the current Canadian guidelines for men.

Interpretation

The published nomograms provide good fracture-risk discrimination in a representative sample of the Canadian population.Current recommendations for the treatment of osteoporosis are in transition. The T-score-based definition of osteoporosis and osteopenia by the expert committee of the World Health Organization on bone mineral density has been used in many guidelines to set intervention thresholds for treatment. However, studies have consistently reported that the highest number of fractures in a given population occurs in those with osteopenic or normal bone mineral density.^1,2 In fact, the National Osteoporosis Foundation has singled out people with osteopenic bone mineral density as a population in which assessment for fracture risk is merited.³Nevertheless, appropriate prevention and treatment strategies for such people are uncertain.⁴ Recent developments include the assessment of absolute fracture risk based on bone mineral density and other risk factors. Current Canadian methodology determines categorical risk based on age, sex, T-score, fracture history and glucocorticoid use.⁵ These criteria were derived from Swedish data, but have been assessed and validated in a cohort of Manitoba women.⁶ Newer nomograms based on the Australian cohort of the Dubbo Osteoporosis Epidemiology Study⁷ are now available for the calculation of low-trauma hip fracture⁸ and any fracture.⁹ These nomograms provide continuous estimates for five- and 10-year absolute fracture risk in both men and women (available at http://fractureriskcalculator.com). The use of factors in addition to bone mineral density may provide a better assessment of fracture risk for people who are near the T-score thresholds and facilitate decisions regarding therapeutic intervention.A key step in the development of any prediction model is the assessment of its validity.¹⁰ The aim of our study was to assess the performance of the Australian-derived nomogram among community-dwelling Canadians aged 55–95 years old. The first part of this assessment was a comparison of the nomogram model using the same variables, but using data from a Canadian population — participants in the Canadian Multicentre Osteoporosis Study (www.camos.org). The second part involved computing the calibration and discrimination of the nomogram in a Canadian cohort. The final part was comparison of the new assessments with the existing Canadian risk classification system.     

广西蕨类植物孢子形态的研究Ⅲ.凤尾蕨科

利用光学显微镜和扫描电子显微镜对广西产凤尾蕨科及其近缘科蕨科、姬蕨科和碗蕨科5属9种植物的孢子形态进行了观察研究,详细描述了9种植物孢子的形态及表面纹饰特征.井栏边草、刺齿凤尾蕨、隆林凤尾蕨、剑叶凤尾蕨、林下凤尾蕨、蕨和碗蕨植物的孢子为三裂缝,辐射对称;极面观为钝三角形,赤道面观为半圆形或超半圆形;栗蕨和姬蕨植物孢子为...