Direct detection of more than 50% of the Duchenne muscular dystrophy mutations by field inversion gels

Duchenne muscular dystrophy (DMD) is an X-linked disorder affecting about 1 in 3,500 males. It is allelic with the milder Becker muscular dystrophy. The biochemical basis for both diseases is unknown and no effective treatment is available. Long-range physical mapping has shown that the DMD gene, localized in Xp21, is extremely large, exceeding 2 million base pairs. Until now, carrier detection and prenatal diagnosis has involved the use of linked restriction fragment length polymorphism markers which detect muscular dystrophy-associated deletions in about 10% of the cases. Field inversion gel electrophoresis (FIGE) allows the detection of structural rearrangements in 21 out of 39 of the DMD patients studied (54%), of which 14 (65%) were not detected by conventional methods. Large deletions seem to make up a much higher fraction of the DMD mutations than so far indicated by other methods. A region prone to deletion was located in the distal half of the gene. FIGE analysis could provide a valuable extension of information for carrier detection and prenatal diagnosis. The technique should be generally applicable to the study of diseases involving structural chromosomal rearrangements.     

Optimization of wear parameters of binary Al-25Zn and Al-3Cu alloys using design of experiments

Zinc-aluminum alloys have been used as bearing materials in the past. In recent years, binary Al-Zn alloys and Al-Zn-Cu alloys are being used as an alternative to the Zn-Al alloys for bearing applications. In this study, both binary Al-25Zn and Al-3Cu were prepared using stir casting process. Homogenization of the as-cast alloys was performed at 350℃ for 8 h and then, the alloys were furnace-cooled to 50℃. The homogenization led to the removal of the dendritic structure of the as-cast alloys. After homogenization, wear parameters optimization was carried out using Taguchi technique. For this purpose, L₉ orthogonal array was selected, and the control parameters selected are load, velocity, and sliding distance. The optimum parametric condition was obtained using signal-to-noise (S/N) ratio analysis, and specific wear rate (SWR) is the selected response. The "smaller-the-better" is the goal of the experiment for S/N ratio analysis. After the optimization, confirmation tests were carried out using analysis of variance (ANOVA) from the developed regression equation. Finally, wear mechanism studies were conducted using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) images.     

HIV preferentially infects HIV-specific CD4+ T cells

HIV infection is associated with the progressive loss of CD4(+) T cells through their destruction or decreased production. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4(+) T cells are preferentially affected. Here we show that HIV-specific memory CD4(+) T cells in infected individuals contain more HIV viral DNA than other memory CD4(+) T cells, at all stages of HIV disease. Additionally, following viral rebound during interruption of antiretroviral therapy, the frequency of HIV viral DNA in the HIV-specific pool of memory CD4(+) T cells increases to a greater extent than in memory CD4(+) T cells of other specificities. These findings show that HIV-specific CD4(+) T cells are preferentially infected by HIV in vivo. This provides a potential mechanism to explain the loss of HIV-specific CD4(+) T-cell responses, and consequently the loss of immunological control of HIV replication. Furthermore, the phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption.     

重载流多芯电缆周围的磁场 Ⅰ. 理论模型

多芯电力电缆在低压配电系统中常被用作配电干线，这种重载流电缆周围的极低频磁场可能干扰附近敏感电子设备的正常运行，甚至影响暴露于该场下的人体的健康，为分析这种磁场的分布特性，建立了多芯电缆周围磁场的载流平行螺旋线模型，并推导了周围磁场的简化计算公式，基于所提出的理想模型对电缆周围电磁的特性进行了分析，发现在电缆的半径方向上磁场随距离衰减的速度大于指数衰减速度，在平行于电缆轴线的直线上和在电缆抽轴圆周线上，磁场的幅值和相角都随观测点的位置周期变化，理论计算结果表明，常用规格的多芯电力电缆在载额定电流的情况下，距电缆2m外空间中的磁场已小于有关国际标准的限值。     

Towards sustainability in world fisheries

Fisheries have rarely been 'sustainable'. Rather, fishing has induced serial depletions, long masked by improved technology, geographic expansion and exploitation of previously spurned species lower in the food web. With global catches declining since the late 1980s, continuation of present trends will lead to supply shortfall, for which aquaculture cannot be expected to compensate, and may well exacerbate. Reducing fishing capacity to appropriate levels will require strong reductions of subsidies. Zoning the oceans into unfished marine reserves and areas with limited levels of fishing effort would allow sustainable fisheries, based on resources embedded in functional, diverse ecosystems.     

Aerosols implicated as a prime driver of twentieth-century North Atlantic climate variability

Systematic climate shifts have been linked to multidecadal variability in observed sea surface temperatures in the North Atlantic Ocean. These links are extensive, influencing a range of climate processes such as hurricane activity and African Sahel and Amazonian droughts. The variability is distinct from historical global-mean temperature changes and is commonly attributed to natural ocean oscillations. A number of studies have provided evidence that aerosols can influence long-term changes in sea surface temperatures, but climate models have so far failed to reproduce these interactions and the role of aerosols in decadal variability remains unclear. Here we use a state-of-the-art Earth system climate model to show that aerosol emissions and periods of volcanic activity explain 76 per cent of the simulated multidecadal variance in detrended 1860-2005 North Atlantic sea surface temperatures. After 1950, simulated variability is within observational estimates; our estimates for 1910-1940 capture twice the warming of previous generation models but do not explain the entire observed trend. Other processes, such as ocean circulation, may also have contributed to variability in the early twentieth century. Mechanistically, we find that inclusion of aerosol-cloud microphysical effects, which were included in few previous multimodel ensembles, dominates the magnitude (80 per cent) and the spatial pattern of the total surface aerosol forcing in the North Atlantic. Our findings suggest that anthropogenic aerosol emissions influenced a range of societally important historical climate events such as peaks in hurricane activity and Sahel drought. Decadal-scale model predictions of regional Atlantic climate will probably be improved by incorporating aerosol-cloud microphysical interactions and estimates of future concentrations of aerosols, emissions of which are directly addressable by policy actions.     

Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells

Embryonic stem (ES) cells, the totipotent outgrowths of blastocysts, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in M1 myeloid leukaemic cells and which we have recently purified, cloned and characterized. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice.     

Stem cells, cancer, and cancer stem cells.

Stem cell biology has come of age. Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine. Perhaps the most important and useful property of stem cells is that of self-renewal. Through this property, striking parallels can be found between stem cells and cancer cells: tumours may often originate from the transformation of normal stem cells, similar signalling pathways may regulate self-renewal in stem cells and cancer cells, and cancer cells may include 'cancer stem cells' - rare cells with indefinite potential for self-renewal that drive tumorigenesis.