Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex

In mammalian cells, a conserved multiprotein complex of Mre11, Rad50 and NBS1 (also known as nibrin and p95) is important for double-strand break repair, meiotic recombination and telomere maintenance. This complex forms nuclear foci and may be a sensor of double-strand breaks. In the absence of the early region E4, the double-stranded DNA genome of adenovirus is joined into concatemers too large to be packaged. We have investigated the cellular proteins involved in this concatemer formation and how they are inactivated by E4 products during a wild-type infection. Here we show that concatemerization requires functional Mre11 and NBS1, and that these proteins are found at foci adjacent to viral replication centres. Infection with wild-type virus results in both reorganization and degradation of members of the Mre11-Rad50-NBS1 complex. These activities are mediated by three viral oncoproteins that prevent concatemerization. This targeting of cellular proteins involved in genomic stability suggests a mechanism for 'hit-and-run' transformation observed for these viral oncoproteins.     

Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4

Hearing depends on a high K(+) concentration bathing the apical membranes of sensory hair cells. K(+) that has entered hair cells through apical mechanosensitive channels is transported to the stria vascularis for re-secretion into the scala media(). K(+) probably exits outer hair cells by KCNQ4 K(+) channels(), and is then transported by means of a gap junction system connecting supporting Deiters' cells and fibrocytes() back to the stria vascularis. We show here that mice lacking the K(+)/Cl(-) (K-Cl) co-transporter Kcc4 (coded for by Slc12a7) are deaf because their hair cells degenerate rapidly after the beginning of hearing. In the mature organ of Corti, Kcc4 is restricted to supporting cells of outer and inner hair cells. Our data suggest that Kcc4 is important for K(+) recycling() by siphoning K(+) ions after their exit from outer hair cells into supporting Deiters' cells, where K(+) enters the gap junction pathway. Similar to some human genetic syndromes(), deafness in Kcc4-deficient mice is associated with renal tubular acidosis. It probably results from an impairment of Cl(-) recycling across the basolateral membrane of acid-secreting alpha-intercalated cells of the distal nephron.     

Comparative assessment of large-scale data sets of protein-protein interactions

Comprehensive protein protein interaction maps promise to reveal many aspects of the complex regulatory network underlying cellular function. Recently, large-scale approaches have predicted many new protein interactions in yeast. To measure their accuracy and potential as well as to identify biases, strengths and weaknesses, we compare the methods with each other and with a reference set of previously reported protein interactions.     

电动车尾门电动推杆用低音调齿轮的开发与验证

高速电动机目前被广泛用于汽车自主驾驶系统。由于高速电动机采用小质量设计，因此为了使转速和输出扭矩达到目标值，通常将渐开线齿轮组和它配套使用。然而，传统的渐开线齿轮在工作中噪声较大，因此一种新型的具有不规则轮齿设计的低音调（Low-Tone）齿轮被开发，以减少齿轮传动装置的噪声。通过优化算法，开发设计了一种Low-Tone齿轮，并应用于一个驱动电动车尾门启闭的电动推杆系统。之后在该系统运行期间，对使用Low-Tone齿轮和使用传统齿轮所产生的声压进行测量对比。结果表明，Low-Tone齿轮对于噪声有较好的抑制作用，其优势特别体现在音调特性方面。     

Prevention of graft-versus-host-disease with preserved graft-versus-leukemia-effect by ex vivo and in vivo modulation of CD4+ T-cells

This is the first report showing that an epitope-specific ex vivo modulation of an allogeneic hematopoietic stem cell graft by the anti-human CD4 antibody MAX.16H5 IgG₁ simultaneously facilitates the anti-tumor capacity of the graft (Graft-versus-leukemia effect, GvL) and the long-term suppression of the deleterious side effect Graft-versus-host-disease (GvHD). To distinguish and consolidate GvL from GvHD, the anti-human CD4 antibody MAX16.H5 IgG₁ was tested in murine GvHD and tumor models. The survival rate was significantly increased in recipients receiving a MAX.16H5 IgG₁ short-term (2 h) pre-incubated graft even when tumor cells were co-transplanted or when recipient mice were treated by MAX.16H5 IgG₁ before transplantation. After engraftment, regulatory T-cells are generated only supporting the GvL effect. It was also possible to transfer the immune tolerance from GvHD-free recipient chimeras into third party recipient mice without the need of reapplication of MAX.16H5 IgG₁ anti-human CD4 antibodies. These findings are also benefical for patients with leukemia when no matched related or unrelated donor is available and provides a safer allogeneic HSCT, which is more effective against leukemia. It also facilitates allogeneic (stem) cell transplantations for other indications (e.g., autoimmune-disorders).     

Expulsion and consumption of male ejaculates by promiscous female Euxesta eluta and Euxesta mazorca (Diptera: Ulidiidae)

While expulsion of male ejaculates by the females after copulation has been reported for various animal groups, expulsion followed by consumption of the expelled ejaculate is a rare behaviour outside spermatophylax-producing orthopterans. Among Diptera, this behaviour has been reported for a few species of Piophilidae, Empididae and Ulidiidae. Here we report on its occurrence among Euxesta eluta and Euxesta mazorca (Diptera: Ulidiidae). We also attempt to characterize the mating system of E. eluta in order to facilitate future hypothesis testing to understand the behavioural factors leading to the evolution of this peculiar behaviour. For this, courtship sequences, copulation duration, frequency of ejaculate expulsion and subsequent consumption, and latency to ejaculate expulsion for both E. eluta and E. mazorca were recorded. The time of sexual maturation, the time window of sexual receptivity during the day, and the mating frequency and variance in mating success for males and females (degree of polygamy) were determined for E. eluta. Both E. eluta and E. mazorca males engaged in elaborate courtship sequences involving visual and tactile displays before copulation. Females of both species almost invariably expelled and consumed ejaculates after copulation. Female E. eluta, required a 6- to 9-day period feeding on protein and sugar before becoming sexually receptive. Reproductive activity occurred continuously over the day with an early morning and late afternoon peak. Both males and females could mate multiply, with multiple partners over a 2-h observational period. Sexual network analysis revealed that some males and females had greater mating success than others. Ejaculate consumption appears to be widespread in the genus Euxesta. It is possible that females obtain nutrients from this behaviour while exerting some control over egg fertilization.     

底灰、粉煤灰及酸洗污泥协同制备泡沫微晶玻璃的相变及性能研究

底灰、粉煤灰和酸洗污泥给城市带来了严重的环境污染,以其为原料制备泡沫微晶玻璃是实现固体废物资源化利用,降低环境影响的有效途径。本文以碳酸钙为发泡剂协同处置以上三种固体废弃物,成功制备了泡沫微晶玻璃。不同底灰添加量对样品的孔形态、孔径分布、孔内外成分变化、物理性能、玻璃结构单元、物相及析晶的影响得到了分析。结果表明,随底灰添加量增加,玻璃相,Si–O–Si及Q3Si单元逐渐减少,玻璃转变温度降低,从而造成气泡融合及孔分布不均的现象。当底灰、粉煤灰、酸洗污泥添加量分别35wt%,45wt%和20wt%时,制备了具有均匀球形孔隙和优异物理性能的泡沫微晶玻璃。样品的体积密度为1.76 g/cm3,孔隙率达56.01%,抗压强度为16.23 MPa。这种低成本制备泡沫微晶玻璃的方法为协同处置固体废弃物提供了新思路。