Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human

Linkage analysis and haplotype mapping in interspecific mouse crosses (Mus musculus x Mus spretus) identified the gene encoding Aurora2 (Stk6 in mouse and STK15 in human) as a candidate skin tumor susceptibility gene. The Stk6 allele inherited from the susceptible M. musculus parent was overexpressed in normal cells and preferentially amplified in tumor cells from F(1) hybrid mice. We identified a common genetic variant in STK15 (resulting in the amino acid substitution F31I) that is preferentially amplified and associated with the degree of aneuploidy in human colon tumors. The Ile31 variant transforms rat1 cells more potently than the more common Phe31 variant. The E2 ubiquitin-conjugating enzyme UBE2N was a preferential binding partner of the 'weak' STK15 Phe31 variant form in yeast two-hybrid screens and in human cells. This interaction results in colocalization of UBE2N with STK15 at the centrosomes during mitosis. These results are consistent with an important role for the Ile31 variant of STK15 in human cancer susceptibility.     

气流阻力负荷对阻塞性睡眠呼吸暂停患者流速容量曲线的影响

探讨加用气流阻力负荷（ＦＲＬ） 状态下流速容量（ＦＶ） 曲线检查对初检ＯＳＡ 患者的意义对象为２４ 名健康成年男性及２１ 例男性阻塞性睡眠呼吸暂停（ＯＳＡ） 患者经整夜多导睡眠仪检查诊断或排除ＯＳＡ模拟实验结果发现只有同时加上可陷闭管及ＦＲＬ 时,才出现显著吸气气流受限无ＦＲＬ时,ＦＶ 曲线（ 以ＦＥＦ５０／ＦＩＦ５０ 比值大于１ 为指标） 检查发现ＯＳＡ的敏感性和特异性分别为３３ ．３ ％ 和９１ ．６ ％ ,阳性预测率为６３ ．６ ％ 加用ＦＲＬ 时敏感性为７６ ．２ ％ ,特异性为７５ ％ ,阳性预测率为７２ ．２ ％ 吸、呼气相峰值流速比值及中期峰值流速比值与ＯＳＡ 严重呈显著相关联合应用加ＦＲＬ及常规ＦＬ曲线检查可能对ＯＳＡ 患者初筛有较高价值     

PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos

The modification of DNA by 5-methylcytosine (5mC) has essential roles in cell differentiation and development through epigenetic gene regulation. 5mC can be converted to another modified base, 5-hydroxymethylcytosine (5hmC), by the tet methylcytosine dioxygenase (Tet) family of enzymes. Notably, the balance between 5hmC and 5mC in the genome is linked with cell-differentiation processes such as pluripotency and lineage commitment. We have previously reported that the maternal factor PGC7 (also known as Dppa3, Stella) is required for the maintenance of DNA methylation in early embryogenesis, and protects 5mC from conversion to 5hmC in the maternal genome. Here we show that PGC7 protects 5mC from Tet3-mediated conversion to 5hmC by binding to maternal chromatin containing dimethylated histone H3 lysine 9 (H3K9me2) in mice. In addition, imprinted loci that are marked with H3K9me2 in mature sperm are protected by PGC7 binding in early embryogenesis. This type of regulatory mechanism could be involved in DNA modifications in somatic cells as well as in early embryos.     

Cortical representations of olfactory input by trans-synaptic tracing

In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of 'starter' cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.     

阻塞性睡眠呼吸暂停患者的上气道狭窄与头姿变化

探讨阻塞性睡眠呼吸暂停（Ｏｂｓｔｒｕｃｔｉｖｅｓｌｅｅｐａｐｎｅａ，ＯＳＡ）患者上气道狭窄的程度、头姿改变情况，以及这些形态学指标与病理生理学参数之间的关系。研究对象为８６例男性ＯＳＡ患者及３７名健康男性。经整夜多导睡眠仪检查诊断或排除ＯＳＡ；采用数字化技术摄取受试者头颅侧位片，并用ＮＩＨＩｍａｇｅ软件测定上气道口径、面积及头姿指标共１５项。ＯＳＡ患者各水平上气道前后径均显著小于对照组；经年龄及身高体重指数校正后，上述结果不变。重症ＯＳＡ患者呈显著头颅前倾。头姿变化指标与呼吸暂停指数及多个水平的气道前后径呈显著相关。亚洲人种ＯＳＡ患者存在明显及广泛的上气道狭窄；随ＯＳＡ程度加重及上气道阻塞程度加重，患者可能出现代偿性头姿改变     

Inducement of blood vessel formation by ovarian extracts from mice injected with gonadotropins

Summary Ovarian extracts prepared from immature mice injected with human chorionic gonadotropin (hCG) and pregnant mare serum gonadotropin (PMSG) were assayed for angiogenic activity. The assay method consisted of implanting a film coated with ovarian extracts to the lateral wall of the m.rectus abdominus of a mouse for 20 days and examining the site for vascularization. The higher angiogenic activity obtained with PMSG-treated extract may be related to its follicle stimulating activity.Acknowledgment. Part of this work was supported by a grant from The Ministry of Education, Japan (No. 576165).