Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification

The genetic analysis of congenital skull malformations provides insight into normal mechanisms of calvarial osteogenesis. Enlarged parietal foramina (PFM) are oval defects of the parietal bones caused by deficient ossification around the parietal notch, which is normally obliterated during the fifth fetal month. PFM are usually asymptomatic, but may be associated with headache, scalp defects and structural or vascular malformations of the brain. Inheritance is frequently autosomal dominant, but no causative mutations have been identified in non-syndromic cases. We describe here heterozygous mutations of the homeobox gene MSX2 (located on 5q34-q35) in three unrelated families with PFM. One is a deletion of approximately 206 kb including the entire gene and the others are intragenic mutations of the DNA-binding homeodomain (RK159-160del and R172H) that predict disruption of critical intramolecular and DNA contacts. Mouse Msx2 protein with either of the homeodomain mutations exhibited more than 85% reduction in binding to an optimal Msx2 DNA-binding site. Our findings contrast with the only described MSX2 homeodomain mutation (P148H), associated with craniosynostosis, that binds with enhanced affinity to the same target. This demonstrates that MSX2 dosage is critical for human skull development and suggests that PFM and craniosynostosis result, respectively, from loss and gain of activity in an MSX2-mediated pathway of calvarial osteogenic differentiation.     

Mutations in a new member of the chromodomain gene family cause CHARGE syndrome

CHARGE syndrome is a common cause of congenital anomalies affecting several tissues in a nonrandom fashion. We report a 2.3-Mb de novo overlapping microdeletion on chromosome 8q12 identified by array comparative genomic hybridization in two individuals with CHARGE syndrome. Sequence analysis of genes located in this region detected mutations in the gene CHD7 in 10 of 17 individuals with CHARGE syndrome without microdeletions, accounting for the disease in most affected individuals.     

Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast

Under laboratory conditions 80% of yeast genes seem not to be essential for viability. This raises the question of what the mechanistic basis for dispensability is, and whether it is the result of selection for buffering or an incidental side product. Here we analyse these issues using an in silico flux model of the yeast metabolic network. The model correctly predicts the knockout fitness effects in 88% of the genes studied and in vivo fluxes. Dispensable genes might be important, but under conditions not yet examined in the laboratory. Our model indicates that this is the dominant explanation for apparent dispensability, accounting for 37-68% of dispensable genes, whereas 15-28% of them are compensated by a duplicate, and only 4-17% are buffered by metabolic network flux reorganization. For over one-half of those not important under nutrient-rich conditions, we can predict conditions when they will be important. As expected, such condition-specific genes have a more restricted phylogenetic distribution. Gene duplicates catalysing the same reaction are not more common for indispensable reactions, suggesting that the reason for their retention is not to provide compensation. Instead their presence is better explained by selection for high enzymatic flux.     

北京小龙门林场夏季小型鼠类群落结构及其年变化

北京小龙门林场夏季小型鼠类群落结构及其年变化房继明，赵欣如，宋杰，张正旺，郭冬生，倪喜军，张懿（北京师范大学生物学系，１００８７５，北京；第一作者３０岁，男，副教授）关键词群落结构；年变化；小型啮齿类分类号Ｑ９５８．８３７；Ｑ９５８．１５５ＹＥＡＲＬ...     

观察箱内成年雄性布氏田鼠间的行为和行为序

研究了不同大小观察箱内布氏田鼠（Ｍｉｃｒｏｔｕｓ ｂｒａｎｄｔｉ）陌生成年雄性个体间的行为和行为序。在大，小观察箱内，除了追逐行为，优势鼠，从属鼠的行为没有明显的差别。在观察期内，虽然一对鼠中优势鼠的非社会，社会探究，攻击行为都明显地高于从属鼠，但它们在遭遇后的第１个回合的交往中，２只鼠的社会行为没有显示的区别，社会探究，争斗行为之间相互独立，为负相关关系，而其各自内部均为正相关关系，其中社会探究     

布氏田鼠的嗅觉通讯II：2种不同方法下气味辨别实验的…

利用重复测量方差分析，研究２种不同的实验设计方法对布氏田鼠气味辨识别实验的影响，结果表明：给予单个气味刺激同时给予多个气味刺激的２种不同实验方法，所得到的数据结果没有显性差异，都能够反映出动物对气味的辨别能力。     

布氏四鼠的嗅觉通讯Ⅱ──2种不同方法下气味辨别实验的重复测量方差分析

利用重复测量方差分析，研究2种不同的实验设计方法对布氏四鼠气味辨别实验的影响．结果表明：给予单个气味刺激和同时给予多个气味刺激的2种不同实验方法，所得到的数据结果没有显著性差异，都能够反映出动物对气味的辨别能力．     

Polyphenolic phytochemicals – just antioxidants or much more?

Polyphenolic phytochemicals are ubiquitous in plants, in which they function in various protective roles. A ‘recommended’ human diet contains significant quantities of polyphenolics, as they have long been assumed to be ‘antioxidants’ that scavenge excessive, damaging, free radicals arising from normal metabolic processes. There is recent evidence that polyphenolics also have ‘indirect’ antioxidant effects through induction of endogenous protective enzymes. There is also increasing evidence for many potential benefits through polyphenolic-mediated regulation of cellular processes such as inflammation. Inductive or signalling effects may occur at concentrations much lower than required for effective radical scavenging. Over the last 2 – 3 years, there have been many exciting new developments in the elucidation of the in vivo mechanisms of the health benefits of polyphenolics. We summarise the current knowledge of the intake, bio-availability and metabolism of polyphenolics, their antioxidant effects, regulatory effects on signalling pathways, neuro-protective effects and regulatory effects on energy metabolism and gut health. Received 14 May 2007; received after revision 27 June 2007; accepted 24 July 2007