The role of key residues in structure, function, and stability of cytochrome-c

Cytochrome-c (cyt-c), a multi-functional protein, plays a significant role in the electron transport chain, and thus is indispensable in the energy-production process. Besides being an important component in apoptosis, it detoxifies reactive oxygen species. Two hundred and eighty-five complete amino acid sequences of cyt-c from different species are known. Sequence analysis suggests that the number of amino acid residues in most mitochondrial cyts-c is in the range 104?±?10, and amino acid residues at only few positions are highly conserved throughout evolution. These highly conserved residues are Cys14, Cys17, His18, Gly29, Pro30, Gly41, Asn52, Trp59, Tyr67, Leu68, Pro71, Pro76, Thr78, Met80, and Phe82. These are also known as “key residues”, which contribute significantly to the structure, function, folding, and stability of cyt-c. The three-dimensional structure of cyt-c from ten eukaryotic species have been determined using X-ray diffraction studies. Structure analysis suggests that the tertiary structure of cyt-c is almost preserved along the evolutionary scale. Furthermore, residues of N/C-terminal helices Gly6, Phe10, Leu94, and Tyr97 interact with each other in a specific manner, forming an evolutionary conserved interface. To understand the role of evolutionary conserved residues on structure, stability, and function, numerous studies have been performed in which these residues were substituted with different amino acids. In these studies, structure deals with the effect of mutation on secondary and tertiary structure measured by spectroscopic techniques; stability deals with the effect of mutation on T _m (midpoint of heat denaturation), ?G _D (Gibbs free energy change on denaturation) and folding; and function deals with the effect of mutation on electron transport, apoptosis, cell growth, and protein expression. In this review, we have compiled all these studies at one place. This compilation will be useful to biochemists and biophysicists interested in understanding the importance of conservation of certain residues throughout the evolution in preserving the structure, function, and stability in proteins.     

Interferon-γ links ultraviolet radiation to melanomagenesis in mice

Cutaneous malignant melanoma is a highly aggressive and frequently chemoresistant cancer, the incidence of which continues to rise. Epidemiological studies show that the major aetiological melanoma risk factor is ultraviolet (UV) solar radiation, with the highest risk associated with intermittent burning doses, especially during childhood. We have experimentally validated these epidemiological findings using the hepatocyte growth factor/scatter factor transgenic mouse model, which develops lesions in stages highly reminiscent of human melanoma with respect to biological, genetic and aetiological criteria, but only when irradiated as neonatal pups with UVB, not UVA. However, the mechanisms underlying UVB-initiated, neonatal-specific melanomagenesis remain largely unknown. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-γ (IFN-γ), but not type-I interferons. IFN-γ was produced by macrophages recruited to neonatal skin by UVB-induced ligands to the chemokine receptor Ccr2. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-γ blockade abolished macrophage-enhanced melanoma growth and survival. IFN-γ-producing macrophages were also identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-γ in promoting melanocytic cell survival/immunoevasion, identifying a novel candidate therapeutic target for a subset of melanoma patients.     

Lipids of guinea-pig alveolar macrophages

Zusammenfassung Lipidanalyse von Meerschweinchen-Makrophagen.

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Authors are grateful to Dr.O. Isler of F. Hoffmann La Roche Co. Ltd., Basle, for generous gifts of synthetic ubiquinone samples.     

薄吸积盘及其发射线的研究

在轴对称、几何薄、光学厚吸积盘模型的基础上,应用新的粘滞定律（磁粘滞为主）以避免标准吸积盘内区的热不稳定及粘滞不稳定定。考虑了自引力的作用,计算出了稳定的磁粘滞自引力薄吸积盘外区的结构,综合盘外区的结构,讨论了吸积盘外区的辐射性质以及发射线的有关问题．     

低碳锰钢中周期性带状组织

用扫描电镜和电子探针研究了低碳锰钢中的周期性带状组织，结果表明，在全部研究用钢中，钢锭经热轧后均出现这种组织，其严重程度随钢的成分而异，并随坯带加工顺序而增加，带状组织与锰的显微偏析等因素有关，适当的调整碳锰以及形成模跨铁素体带的转变产物可降低带状组织的严重程度。     

Scientific Governance in Britain 1914–79

John Harrison (1693–1776) is regarded as the father of chronometry. During his lifetime, he relentlessly pursued one of humankind's greatest and oldest challenges—that of finding the longitude at sea. In succeeding (according to the rules dictated by an Act of Parliament), he bequeathed to humankind the most accurate portable timekeeper the world had ever seen. It is a remarkable fact that his timekeeper, known today as H4, remains more accurate than the majority of expensive mechanical wristwatches manufactured today. Such accuracy required novel approaches to address the various difficulties that befall all mechanical watches, and Harrison overcame many of these with his own innovations. The reduction or elimination of friction is one such problem with clocks and watches, and from an early age Harrison demonstrated his mastery in this subject. This is typified by his choice of woods in his early clocks, and in later clocks by his ‘grasshopper’ escapement. In the 1750s, Harrison's attention switched from clocks to watches, necessitating a hardwearing, low friction material to be found for the pallets in the escapement of his timekeepers. He found these properties in diamond, and in utilizing this to great effect in H4's escapement, he became one of the first people to use diamond as a high-tech material. This paper describes a scientific investigation into the diamond pallets of H4 using Raman microscopy, X-ray diffraction and optical microscopy, to elucidate why diamond was used rather than a more conventional jewel such as ruby, and to gain some insight into how Harrison might have achieved their unconventional morphology. From the evidence presented here, together with evidence collected from primary sources, it is shown that his use of diamond as a hard, low friction material was nothing other than extraordinary, and should be regarded in the same high esteem as his other technological gifts to the world.     

A Buffer Management Scheme for Packet Queues in MANET

We introduce a new scheme of buffer management to handle packet queues in Mobile Ad hoc Networks （MANETs） for fixed and mobile nodes. In this scheme, we try to achieve efficient queuing in the buffer of a centrally communicating MANET node through an active queue management strategy by assigning dynamic buffer space to all neighboring nodes in proportion to the number of packets received from neighbors and hence controlling packet drop probabilities. Our simulation study reveals that the proposed scheme is a way to improve the buffer management for packet queues in MANET nodes in terms of packet loss ratio, transmission efficiency, and some other important system parameters.