A Locus for Autosomal Dominant Mitral Valve Prolapse on Chromosome 11p15.4

Mitral valve prolapse (MVP) is a common cardiovascular abnormality in the United States, occurring in approximately 2.4% of the general population. Clinically, patients with MVP exhibit fibromyxomatous changes in one or both of the mitral leaflets that result in superior displacement of the leaflets into the left atrium. Although often clinically benign, MVP can be associated with important accompanying sequelae, including mitral regurgitation, bacterial endocarditis, congestive heart failure, atrial fibrillation, and even sudden death. MVP is genetically heterogeneous and is inherited as an autosomal dominant trait that exhibits both sex- and age-dependent penetrance. In this report, we describe the results of a genome scan and show that a locus for MVP maps to chromosome 11p15.4. Multipoint parametric analysis performed by use of GENEHUNTER gave a maximum LOD score of 3.12 for the chromosomal region immediately surrounding the four-marker haplotype D11S4124-D11S2349-D11S1338-D11S1323, and multipoint nonparametric analysis (NPL) confirms this finding (NPL=38.59; P=.000397). Haplotype analysis across this region defines a 4.3-cM region between the markers D11S1923 and D11S1331 as the location of a new MVP locus, MMVP2, and confirms the genetic heterogeneity of this disorder. The discovery of genes involved in the pathogenesis of this common disease is crucial to understanding the marked variability in disease expression and mortality seen in MVP.     

ASK1 physically interacts with COI1 and is required for male fertility inArabidopsis

Jasmonates are a new class of plant hormones that play important roles in plant development and plant defense. TheCOI1 gene was previously shown to be required for jasmonate-regulated plant fertility and defense. We demonstrated for the first time that COI1 interacts with theArabidopsis SKP1-LIKE1 (ASK1) to form a complex that is required for jasmonate action inplanta. Functional analysis by antisense strategy showed thatASK1 is involved in male fertility.     

Expression of vascular endothelial growth factor receptors 1, 2, and 3 in quiescent endothelia.

The vascular endothelial growth factor (VEGF) family is involved in angiogenesis, and therefore VEGFs are considered as targets for anti-angiogenic therapeutic strategies against cancer. However, the physiological functions of VEGFs in quiescent tissues are unclear and may interfere with such systemic therapies. In pathological conditions, increased levels of expression of the VEGF receptors VEGFR-1, VEGFR-2, and VEGFR-3 accompany VEGF activity. In this study we investigated normal human and monkey tissues for expression patterns of these receptors. Immunohistochemical staining methods at the light and electron microscopic level were applied to normal human and monkey tissue samples, using monoclonal antibodies (MAbs) against the three VEGFRs and anti-endothelial MAbs PAL-E and anti-CD31 to identify blood and lymph vessels. In human and monkey, similar distribution patterns of the three VEGFRs were found. Co-expression of VEGFR-1, -2, and -3 was observed in microvessels adjacent to epithelia in the eye, gastrointestinal mucosa, liver, kidney, and hair follicles, which is in line with the reported preferential expression of VEGF-A in some of these epithelia. VEGFR-1, -2, and -3 expression was also observed in blood vessels and sinusoids of lymphoid tissues. Furthermore, VEGFR-1, but not VEGFR-2 and -3, was present in microvessels in brain and retina. Electron microscopy showed that VEGFR-1 expression was restricted to pericytes and VEGFR-2 to endothelial cells in normal vasculature of tonsils. These findings indicate that VEGFRs have specific distribution patterns in normal tissues, suggesting physiological functions of VEGFs that may be disturbed by systemic anti-VEGF therapy. One of these functions may be involvement of VEGF in paracrine relations between epithelia and adjacent capillaries.     

GABA对热应激仔鸡的影响

将一周龄的“882”肉仔鸡 ,随机分为 2组。让对照组仔鸡饮用蒸馏水 ,让试验组饮用 0 0 5 %的氨酪酸 (GABA)蒸馏水。 2组每天置于 32℃的箱中热处理 1 5h ,试验 4周。结果表明GABA对热应激肉仔鸡有一定的影响 :试验组仔鸡的呼吸频率极显著低于对照组 (P <0 0 1) ;红细胞数显著高于对照组 (P <0 0 5 ) ;料重比极显著低于对照组 (P <0 0 1) ,仔鸡增重是对照组鸡的 117 86 % (P <0 0 5 )。     

Light partitioning among species and species replacement in early successional grasslands

Abstract. We studied canopy structure, shoot architecture and light harvesting efficiencies of the species (photon flux captured per unit above‐ground plant mass) in a series of exclosures of different age (up to 4.5 yr) in originally heavily grazed grassland in N Japan.Vegetation height and Leaf Area Index (LAI) increased in the series and Zoysia japonica, the dominant in the beginning, was replaced by the much taller Miscanthus sinensis. We showed how this displacement in dominance can be explained by inherent constraints on the above‐ground architecture of these two species. In all stands light capture of plants increased with their above‐ground biomass but taller species were not necessarily more efficient in light harvesting. Some subordinate species grew disproportionally large leaf areas and persisted in the shady undergrowth. Some other species first grew taller and managed to stay in the better‐lit parts of the canopy, but ultimately failed to match the height growth of their neighbours in this early successional series. Their light harvesting efficiencies declined and this probably led to their exclusion. By contrast, species that maintained their position high in the canopy managed to persist in the vegetation despite their relatively low light harvesting efficiencies. In the tallest stands ‘later successional’ species had higher light harvesting efficiencies for the same plant height than ‘early successional’ species which was mostly the result of the greater area to mass ratio (specific leaf area, SLA) of their leaves. This shows how plant stature, plasticity in above‐ground biomass partitioning, and architectural constraints determine the ability of plants to efficiently capture light, which helps to explain species replacement in this early successional series.     

Patterning the optic neuroepithelium by FGF signaling and Ras activation.

During vertebrate embryogenesis, the neuroectoderm differentiates into neural tissues and also into non-neural tissues such as the choroid plexus in the brain and the retinal pigment epithelium in the eye. The molecular mechanisms that pattern neural and non-neural tissues within the neuroectoderm remain unknown. We report that FGF9 is normally expressed in the distal region of the optic vesicle that is destined to become the neural retina, suggesting a role in neural patterning in the optic neuroepithelium. Ectopic expression of FGF9 in the proximal region of the optic vesicle extends neural differentiation into the presumptive retinal pigment epithelium, resulting in a duplicate neural retina in transgenic mice. Ectopic expression of constitutively active Ras is also sufficient to convert the retinal pigment epithelium to neural retina, suggesting that Ras-mediated signaling may be involved in neural differentiation in the immature optic vesicle. The original and the duplicate neural retinae differentiate and laminate with mirror-image polarity in the absence of an RPE, suggesting that the program of neuronal differentiation in the retina is autonomously regulated. In mouse embryos lacking FGF9, the retinal pigment epithelium extends into the presumptive neural retina, indicating a role of FGF9 in defining the boundary of the neural retina.     

The role of strand 1 of the C β-sheet in the structure and function of α1-antitrypsin

Serpins inhibit cognate serine proteases involved in a number of important processes including blood coagulation and inflammation. Consequently, loss of serpin function or stability results in a number of disease states. Many of the naturally occurring mutations leading to disease are located within strand 1 of the C beta-sheet of the serpin. To ascertain the structural and functional importance of each residue in this strand, which constitutes the so-called distal hinge of the reactive center loop of the serpin, an alanine scanning study was carried out on recombinant alpha(1)-antitrypsin Pittsburgh mutant (P1 = Arg). Mutation of the P10' position had no effect on its inhibitory properties towards thrombin. Mutations to residues P7' and P9' caused these serpins to have an increased tendency to act as substrates rather than inhibitors, while mutations at P6' and P8' positions caused the serpin to behave almost entirely as a substrate. Mutations at the P6' and P8' residues of the C beta-sheet, which are buried in the hydrophobic core in the native structure, caused the serpin to become highly unstable and polymerize much more readily. Thus, P6' and P8' mutants of alpha(1)-antitrypsin had melting temperatures 14 degrees lower than wild-type alpha(1)-antitrypsin. These results indicate the importance of maintaining the anchoring of the distal hinge to both the inhibitory mechanism and stability of serpins, the inhibitory mechanism being particularly sensitive to any perturbations in this region. The results of this study allow more informed analysis of the effects of mutations found at these positions in disease-associated serpin variants.     

乙醛对人类神经tau磷酸化的影响

用乙醛对人类神经tau进行醛胺化,通过NCLK(neuronal cdc2-like protein kinase)和［γ-³²P］ATP对其磷酸化.磷酸化的产物经胃蛋白酶降解及HPLC(C-18)分析降解片段,发现醛胺化tau的降解物中有两个新的磷酸化肽段(A4和A6).     

分子疫苗防治老年性痴呆小鼠模型的研究进展

老年斑是老年性痴呆(Alzheimer's disease, AD)的特征性病理改变,β-淀粉样(β-amyloid,Aβ)是其主要成分.将Aβ作为疫苗对动物进行免疫,有明显抑制转基因小鼠脑内Aβ的沉积,清除原有斑块的作用,从而减少异常Aβ沉积对认知功能的损害.疫苗没有引起针对动物自身抗原的免疫反应,对中枢神经系统的正常功能也没有明显损害.