A biological consequence of variation in the site of D-JH gene rearrangement

One mechanism which generates diversity in immunoglobulin variable (V) regions is flexibility in the site of recombination among the constituent genetic elements. Within a specific antibody family (that is, a particular VH-VL combination), variability in V-D-J rearrangement not only leads to sequence diversity at the boundary of the juxtaposed genes, but also enables the total length of the third complementarity-determining region (CDR-3) of the heavy chain to be conserved. We demonstrate here that the junctional diversity inherent in rearranged immunoglobulin genes can have consequences for the biology of the immune system. Sequence analysis of the expressed immunoglobulin genes of idiotypically variant as opposed to conventional B lymphocytes of a dominant antibody family showed that the variant B cells undergo a novel D-JH joining event such that an extra amino acid is inserted into the heavy chain CDR-3. The unique D-region conformation possessed by the variant B cells accounts for previous observations which showed that variant and conventional B cells could be differentially regulated in vivo by an autologous set of idiotope-specific B lymphocytes. Our findings indicate that D-region structure can determine the expression of regulatory idiotopes and suggest that the conservation of heavy-chain CDR-3 length within an antibody family may reflect regulatory as well as functional constraints.     

上海市百岁老人的谱系及其分析

本文调查了上海市百岁老人的性别、职业和谱系,并绘制了57个完整的寿命谱系图,其中男性10名(占总数的17.5%),女性47名(占82.5%).男性中脑力劳动者4名(占男性总数的40%),体力劳动者6名(占60%);女性中脑力劳动者1人(占女性总数的2.1%),体力劳动者3人(占6.4%),操持家务者43人(占91.5%).有长寿家族史者40人(占寿命家族史清楚者的70.2%),无长寿家族史者17人(占29.8%).百岁老人配偶寿长≥70岁者,其已故子女的平均寿命高于配偶<70岁的.作者认为长寿是遗传的,并着重从遗传和环境两方面分析了女寿星数明显多于男寿星数的原因.     

协方差矩阵的MINQUE和简单估计的比较

在二次损失函数下,作者研究了多元线性模型协方差矩阵的MINQUE估计和简单估计的比较问题,其中多元线性模型的设计矩阵和离散矩阵可以不满秩,得到了一个充分和必要条件。     

Alteration of the serine protease PRSS56 causes angle-closure glaucoma in mice and posterior microphthalmia in humans and mice

Angle-closure glaucoma (ACG) is a subset of glaucoma affecting 16 million people. Although 4 million people are bilaterally blind from ACG, the causative molecular mechanisms of ACG remain to be defined. High intraocular pressure induces glaucoma in ACG. High intraocular pressure traditionally was suggested to result from the iris blocking or closing the angle of the eye, thereby limiting aqueous humor drainage. Eyes from individuals with ACG often have a modestly decreased axial length, shallow anterior chamber and relatively large lens, features that predispose to angle closure. Here we show that genetic alteration of a previously unidentified serine protease (PRSS56) alters axial length and causes a mouse phenotype resembling ACG. Mutations affecting this protease also cause a severe decrease of axial length in individuals with posterior microphthalmia. Together, these data suggest that alterations of this serine protease may contribute to a spectrum of human ocular conditions including reduced ocular size and ACG.     

Meta-Action Research on a Leadership Development Program: A Process Model for Life-long Learning

Our purpose in this paper is to contribute to the field of systemic practice by sharing a process of professional learning based on meta-action research. The process emerged as we engaged with evaluation data from a leadership development program (LDP). The aim of this LDP had been to help leaders design their team projects on poverty reduction through action research methods in six African countries. As facilitators of the program we discuss our experiential learning based on critical reflection. We explain how meta-action research can transform understandings of ways to improve professional practice in future applications. We present three process models: (1) a model of reflection on action, (2) a meta-action research model, and (3) a model for lifelong learning through meta-action research. These models may be of benefit and interest to readers who facilitate systemic practice and action research in education, higher education, communities, industry and government.     

Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy

Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.     

心肌宁冲剂对抗垂体后叶素所致大鼠急性心肌缺血实验研究

心肌宁冲剂按1.75g/kg,0.875g/kg剂量,每天早晚分两次灌胃给药,连续7天,均能明显对抗垂体后叶素所诱发的大鼠急性心肌缺血的心电图改变。