Mutational signatures of de-differentiation in functional non-coding regions of melanoma genomes

Much emphasis has been placed on the identification, functional characterization, and therapeutic potential of somatic variants in tumor genomes. However, the majority of somatic variants lie outside coding regions and their role in cancer progression remains to be determined. In order to establish a system to test the functional importance of non-coding somatic variants in cancer, we created a low-passage cell culture of a metastatic melanoma tumor sample. As a foundation for interpreting functional assays, we performed whole-genome sequencing and analysis of this cell culture, the metastatic tumor from which it was derived, and the patient-matched normal genomes. When comparing somatic mutations identified in the cell culture and tissue genomes, we observe concordance at the majority of single nucleotide variants, whereas copy number changes are more variable. To understand the functional impact of non-coding somatic variation, we leveraged functional data generated by the ENCODE Project Consortium. We analyzed regulatory regions derived from multiple different cell types and found that melanocyte-specific regions are among the most depleted for somatic mutation accumulation. Significant depletion in other cell types suggests the metastatic melanoma cells de-differentiated to a more basal regulatory state. Experimental identification of genome-wide regulatory sites in two different melanoma samples supports this observation. Together, these results show that mutation accumulation in metastatic melanoma is nonrandom across the genome and that a de-differentiated regulatory architecture is common among different samples. Our findings enable identification of the underlying genetic components of melanoma and define the differences between a tissue-derived tumor sample and the cell culture created from it. Such information helps establish a broader mechanistic understanding of the linkage between non-coding genomic variations and the cellular evolution of cancer.     

关联维数法在皮肤激光散斑测量中的应用

本文采用关联维数方法研究了皮肤厚度对皮肤激光散斑测量的影响。计算了６种模拟皮肤厚度情况下的生物散斑关联维数。结果表明,维数随皮肤厚度的增加而减小,而且重复性很好。这说明,关联维数方法可以应用在皮肤激光散斑的研究中     

SPERM WHALE DIVES TRACKED BY RADIO TAG TELEMETRY

Dives of a 12-m sperm whale ( Physeter catodon Linnaeus, 1758) were tracked in the southeast Caribbean by long range, 30 MHz radio tag with dive-profile telemetry over 4.6 d, 26 April-1 May 1995. Over the 295-km track, average speed was 0.7 m/sec (2.6 km/h). Of 158 dives (defined as submergences longer than 3 min), 65 were shallow (<200 m). The 93 deep dives averaged 990 m (range 420–1,330 m) in depth, and 44.4 min in duration (range 18.2–65.3 min). Water depth was at least 200 m deeper than the whale dive depth. The whale was engaged in activities at or near the surface, shallow dives, and deep dives during 22.6%, 23.4%, and 54% of the time, respectively. Depth and duration of dives were correlated, but there was little relationship between the length or depth of dives with the duration of surfacings either before or after dives. Deep dives occurred day and night. In 44.4% of the deep dives, the vertical movement of descents and ascents was interrupted at intermediate depths, lengthening these dives by an average of 10.8 min. During dives without stops at intermediate depths, descents averaged 11 min at 1.52 m/sec, and ascents averaged 11.8 min at 1.4 m/sec.     

中国洞穴蜘蛛多样性及其对洞穴环境的适应

对中国洞穴蜘蛛的多样性、地理分布信息进行了详细的闸述.初步探讨了洞穴蜘蛛对洞穴环境的适应性特征及其进化机制.我国洞穴蜘蛛目前已知16科27属80种,其巾暗蛛科、弱蛛科、泰莱蛛科和巨蟹蛛科物种最多;在属级阶元上,以弱蛛属Leptoneta14种、泰莱蛛属Telema lO种、龙角蛛属Draamar如和巾遁蛛属Sinopoda各9种,宽隙蛛属Platocoelotes 8种居多.我国洞穴蜘蛛主要集中分布在贵卅、海南、云南、北京、浙江、广西等喀斯特洞穴较为密集地区,在河北、河南、湖北和湖南也有部分报道.在不同地区分布的洞穴蜘蛛类群或优势类群及区系成分等都存在较大差异.洞穴蜘蛛中约有20%～30%的种类凶为长期生活在黑暗无光、食物匮乏以及缺乏温度和光周期的季节调节等特殊环境,出现了一些地表生境蜘蛛类群中所没有的刘洞穴环境的适应性特征,如缺乏体色素、眼退化共至无眼、附肢延长、全身牛有很多具较敏锐触觉和嗅觉功能的感觉毛、繁殖无季节性、耗氧量降低而新陈代谢缓慢、代谢率降低、产牛的后代少、单个卵粒包含更多的营养等.     

Evidence of linkage of familial hypoalphalipoproteinemia to a novel locus on chromosome 11q23

Coronary heart disease (CHD) accounts for half of the 1 million deaths annually ascribed to cardiovascular disease and for almost all of the 1.5 million acute myocardial infarctions. Within families affected by early and apparently heritable CHD, dyslipidemias have a much higher prevalence than in the general population; 20%-30% of early familial CHD has been ascribed to primary hypoalphalipoproteinemia (low HDL-C). This study assesses the evidence for linkage of low HDL-C to chromosomal region 11q23 in 105 large Utah pedigrees ascertained with closely related clusters of early CHD and expanded on the basis of dyslipidemia. Linkage analysis was performed by use of 22 STRP markers in a 55-cM region of chromosome 11. Two-point analysis based on a general, dominant-phenotype model yielded LODs of 2.9 for full pedigrees and 3.5 for 167 four-generation split pedigrees. To define a localization region, model optimization was performed using the heterogeneity, multipoint LOD score (mpHLOD). This linkage defines a region on 11q23.3 that is approximately 10 cM distal to-and apparently distinct from-the ApoAI/CIII/AIV gene cluster and thus represents a putative novel localization for the low HDL-C phenotype.     

A role for caleosin in degradation of oil-body storage lipid during seed germination

Caleosin is a Ca(2+)-binding oil-body surface protein. To assess its role in the degradation of oil-bodies, two independent insertion mutants lacking caleosin were studied. Both mutants demonstrated significant delay of breakdown of the 20:1 storage lipid at 48 and 60 h of germination. Additionally, although germination rates for seeds were not affected by the mutations, mutant seedlings grew more slowly than wild type when measured at 48 h of germination, a defect that was corrected with continued growth for 72 and 96 h in the light. After 48 h of germination, wild-type central vacuoles had smooth contours and demonstrated internalization of oil bodies and of membrane containing alpha- and delta-tonoplast intrinsic proteins (TIPs), markers for protein storage vacuoles. In contrast, mutant central vacuoles had distorted limiting membranes displaying domains with clumps of the two TIPs, and they contained fewer oil bodies. Thus, during germination caleosin plays a role in the degradation of storage lipid in oil bodies. Its role involves both the normal modification of storage vacuole membrane and the interaction of oil bodies with vacuoles. The results indicate that interaction of oil bodies with vacuoles is one mechanism that contributes to the degradation of storage lipid.     

犬MC1R基因R306ter与毛色性状相关性研究

目的　分析犬MC1R基因中R30 6ter位点多态性与犬毛色表型的相关性 ,为遗传育种 ,培育出更加优良的实验用犬奠定基础。方法　采用PCR SSCP技术 ,对MC1R基因R30 6ter位点进行基因多态性检测 ,分析位点多态性与毛色性状之间的相关性 ,并对该位点进行克隆测序。结果　PCR SSCP分析结果表明 ,R30 6ter位点序列具有多态性 ,表现为C、D二个等位基因和CC、CD及DD三种基因型。对R30 6ter多态性片段克隆测序发现 ,MC1R基因在编码第 30 6位氨基酸的密码子处存在一个由CGA到TGA的终止突变。结论　经统计分析结果表明在杂种犬中MC1R基因多态性与毛色性状不存在显著的相关性 ,这可能是由于外科手术学教学用犬是杂种犬 ,其遗传背景不同所致。由于MC1R基因的R30 6ter位点内存在碱基变异 ,因此在杂种犬中表现出明显的PCR SSCP多态性     

鞑靼滨藜挥发性化学成分分析

对鞑靼滨藜全草的挥发性化学成分进行分析。采用水蒸气蒸馏法及索氏提取法提取鞑靼滨藜全草中的挥发性化学成分,用GC-MS联用技术分析其化学组成,计算其相对百分含量,并对两种提取方法进行比较研究。结果表明:水蒸气蒸馏法提取物的成分比索氏提取法较多。从水蒸气蒸馏法分离出的53个色谱峰中鉴定了51种成分,含量最高的是茴香脑(45.84%),其次为正二十七烷(9.28%),羟基吲哚(6.81%),α-羟基-2-甲基丙基苯乙酸酯(4.03%)。从索氏提取法分离出的26个色谱峰中鉴定了22种成分,含量最高的是正二十九烷(22.63%),其次为硬酯酸(16.69%),十六醛(6.89%),棕榈酸(5.43%)。