Early death of mice cloned from somatic cells

Here we report that the lifespan of mice cloned from somatic cells is significantly shorter than that of genotype- and sex-matched controls, most likely due to severe pneumonia and hepatic failure. This finding demonstrates the possibility of long-term deleterious effects of somatic-cell cloning, even after normal birth.     

TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer

The existence of tumor-suppressor genes was originally demonstrated by functional complementation through whole-cell and microcell fusion. Transfer of chromosome 11 into a human non-small-cell lung cancer (NSCLC) cell line, A549, suppresses tumorigenicity. Loss of heterozygosity (LOH) on the long arm of chromosome 11 has been reported in NSCLC and other cancers. Several independent studies indicate that multiple tumor-suppressor genes are found in this region, including the gene PPP2R1B at 11q23-24 (ref. 7). Linkage studies of NSCLC are precluded because no hereditary forms are known. We previously identified a region of 700 kb on 11q23.2 that completely suppresses tumorigenicity of A549 human NSCLC cells. Most of this tumor-suppressor activity localizes to a 100-kb segment by functional complementation. Here we report that this region contains a single confirmed gene, TSLC1, whose expression is reduced or absent in A549 and several other NSCLC, hepatocellular carcinoma (HCC) and pancreatic cancer (PaC) cell lines. TSLC1 expression or suppression is correlated with promoter methylation state in these cell lines. Restoration of TSLC1 expression to normal or higher levels suppresses tumor formation by A549 cells in nude mice. Only 2 inactivating mutations of TSLC1 were discovered in 161 tumors and tumor cell lines, both among the 20 primary tumors with LOH for 11q23.2. Promoter methylation was observed in 15 of the other 18 primary NSCLC, HCC and PaC tumors with LOH for 11q23.2. Thus, attenuation of TSLC1 expression occurred in 85% of primary tumors with LOH. Hypermethylation of the TSLC1 promoter would seem to represent the 'second hit' in NSCLC with LOH.     

预蠕变损伤对高温疲劳宏观裂纹扩展的影响

针对ＳＵＳ３０４不锈钢光滑试棒预先导入１０７３ Ｋ·ｃｐ－ｔｙｐｅ条件下的预蠕变疲劳损伤，然后开小切口进行时间依存性 ９２３ Ｋ·ｃｐ－ｔｙｐｅ，１０７３ Ｋ·ｃｐ－ｔｙｐｅ及循环数依存性９２３ Ｋ·ｐｐ－ｔｙｐｅ的宏观裂纹扩展试验，考察了试棒内部因预蠕变疲劳而产生的大量的粒界微小裂纹对高温疲劳宏观裂纹扩展的影响．结果如下： １．预损伤加速了９２３ Ｋ·ｃｐ－ｔｙｐｅ下的蠕变裂纹扩展，对于同一蠕变Ｊ积分范围△Ｊｃ，损伤值越大，裂纹扩展速度ｄｌ／ｄＮ也越大．这种加速起因于主裂纹与微小裂纹的合体． ２．１０７３ Ｋ·ｃｐ－ｔｙｐｅ下的预损伤材料和处女材料的ｄｌ／ｄＮ在同一△Ｊｃ。下相等．即，损伤材料的裂纹扩展速度的上限值由１０７３ Ｋ·ｃｐ－ｔｙｐｅ下的处女材料的ｄｌ／ｄＮ－△Ｊｃ关系给出． ３．在９２３ Ｋ·ｐｐ－ｔｙｐｅ条件下，对于同一疲劳Ｊ积分范围△Ｊｆ，预损伤材料的ｄｌ／ｄＮ要比处女材料快１０倍左右．一般ｐｐ－ｔｙｐｅ的破坏形式为粒内破坏．预损伤材料的场合，因为试棒内部分布有大量的微小粒界裂纹，主裂纹便沿这些破坏阻抗最小的微小裂纹边合体边扩展，主要在粒界上扩展．即微小粒界裂纹是裂纹扩展阻抗减小的主因．     

Crystal structure of the channelrhodopsin light-gated cation channel

Channelrhodopsins (ChRs) are light-gated cation channels derived from algae that have shown experimental utility in optogenetics; for example, neurons expressing ChRs can be optically controlled with high temporal precision within systems as complex as freely moving mammals. Although ChRs have been broadly applied to neuroscience research, little is known about the molecular mechanisms by which these unusual and powerful proteins operate. Here we present the crystal structure of a ChR (a C1C2 chimaera between ChR1 and ChR2 from Chlamydomonas reinhardtii) at 2.3?? resolution. The structure reveals the essential molecular architecture of ChRs, including the retinal-binding pocket and cation conduction pathway. This integration of structural and electrophysiological analyses provides insight into the molecular basis for the remarkable function of ChRs, and paves the way for the precise and principled design of ChR variants with novel properties.     

Variation of thickness of glomerular basement membrane in various experimental circumstances

Zusammenfassung Mehrere Faktoren wurden untersucht, die verantwortlich sind für die Dickenvariabilität der Glomerulisbasalmembran der Rattenniere unter verschiedenen, nicht pathologischen Bedingungen. Durchschnittsdicke und Frequenzverbreitungskurve der Basalmembran ändern sich in Abhängigkeit vom Nierenzustand.     

Sequence of simian immunodeficiency virus from African green monkey, a new member of the HIV/SIV group

Some wild African green monkeys are known to be naturally infected with a retrovirus related to human immunodeficiency virus (HIV) without having any apparent symptoms of an AIDS-like disease. This simian immunodeficiency virus, designated SIVAGM, may be helpful in clarifying the evolution and pathogenicity of HIV. Some virus strains that were previously reported to be isolated from African green monkeys were shown to be laboratory contaminations of SIVMAC (SIV from a rhesus macaque) Here we report the complete DNA sequence of authentic SIVAGM, which was isolated from a naturally infected African green monkey of Kenyan origin. Comparison of the genome of SIVAGM with those of known HIV/SIVs indicates that the virus is a new simian lentivirus that is approximately equally distantly related to HIV-1 and HIV-2 in contrast to SIVMAC, which is much closer to HIV-2 than to HIV-1 (refs 5, 9).     

Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans

Male embryonic mice with mutations in the X-linked aristaless-related homeobox gene (Arx) developed with small brains due to suppressed proliferation and regional deficiencies in the forebrain. These mice also showed aberrant migration and differentiation of interneurons containing gamma-aminobutyric acid (GABAergic interneurons) in the ganglionic eminence and neocortex as well as abnormal testicular differentiation. These characteristics recapitulate some of the clinical features of X-linked lissencephaly with abnormal genitalia (XLAG) in humans. We found multiple loss-of-function mutations in ARX in individuals affected with XLAG and in some female relatives, and conclude that mutation of ARX causes XLAG. The present report is, to our knowledge, the first to use phenotypic analysis of a knockout mouse to identify a gene associated with an X-linked human brain malformation.