Iodine adsorption characteristics of newly-formed rat liver glycogen

Zusammenfassung Es wird für die Bestimmung des Leberglykogens eine Jod-Adsorptionsmethode mit der üblichen Hydrolyse zu Glukose verglichen. Für normale und unbehandelte diabetische Ratten zeigen die Glykogenwerte mit beiden Methoden gute Übereinstimmung. Dagegen ist die Farbintensität je Gewichtseinheit des Jod-Glykogen-Komplexes bei insulinbehandelten diabetischen Ratten ebenso wie bei fastenden glukosegefütterten Ratten wesentlich grösser als bei normalen Tieren. Daraus lässt sich schliessen, dass frisch gebildetes Glykogen eine erhöhte Jod-Adsorptionsfähigkeit besitzt. Qualitativ erfährt die Farbe des Jod-Glykogen-Komplexes unter den verschiedenen Bedingungen keine Veränderung.     

高速弧齿锥齿轮弹流润滑特性分析

以某航空发动机高速弧齿锥齿轮为研究对象,在弧齿锥齿轮加载接触分析基础上,建立起适合弹流润滑分析的动态坐标系。用点弹流润滑理论对高速弧齿锥齿轮在啮合过程中的最大油膜压力和最小油膜厚度变化情况进行描述,寻找出载荷、速度和润滑油粘度等因素对轮齿弹流润滑特性的影响规律。     

基于主曲率匹配的五坐标刀位轨迹优化

为了克服传统五轴加工采用固定走刀方向和后跟角的加工方法的不足,提出了一种基于刀具扫描面与曲面主曲率匹配、以行距最大为目标的走刀方向和后跟角的优化算法,实践证明,这种方法能够优化刀位轨迹,提高加工效率。     

Femtosecond X-ray protein nanocrystallography

X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (～200?nm to 2?μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.     

Initial genome sequencing and analysis of multiple myeloma

Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.     

Ocular dominance shift in kitten visual cortex caused by imbalance in retinal electrical activity

Monocular lid suture during the sensitive period early in the life of a kitten disrupts normal development of inputs from the two eyes to the visual cortex, causing a decrease in the fraction of cortical cells responding to the deprived eye. Such an ocular dominance shift has been assumed to depend on patterned visual experience, because no change in cortical physiology is produced by inequalities between the two eyes in retinal illumination or temporally modulated diffuse light stimulation. A higher-level process, involving gating signals from areas outside striate cortex, has been proposed to ensure that sustained changes in synaptic efficacy occur only in response to behaviourally significant visual inputs. To test whether such a process is necessary for ocular dominance plasticity, we treated 4-week-old kittens with visual deprivation and monocular tetrodotoxin (TTX) injections to create an imbalance in the electrical activities of the two retinas in the absence of patterned vision. After 1 week of treatment we determined the ocular dominance distribution of single units in primary visual cortex. In all kittens studied, a significant ocular dominance shift was found. In addition to this physiological change, there was an anatomical change in the lateral geniculate nucleus, where cells were larger in laminae receiving input from the more active eye. Our results indicate that patterned vision is not necessary for visual cortical plasticity, and that an imbalance in spontaneous retinal activity alone can produce a significant ocular dominance shift.     

复杂曲面的无干涉刀位轨迹生成

提出了基于X－map思路的干涉处理方法，将干涉处理由空间三角片之间的距离判断简化为一维坐标轴上两点之间的位置比较，并构造了包括干涉检查、干涉消除及欠切区域处理等的完整干涉处理方法，此法可以提高干涉处理的效率及稳定性，简化欠切区域的单独处理，对三坐标加工的干涉处理具有很好的实用价值。     

Substrate-targeting gamma-secretase modulators

Selective lowering of Abeta42 levels (the 42-residue isoform of the amyloid-beta peptide) with small-molecule gamma-secretase modulators (GSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer's disease. To identify the target of these agents we developed biotinylated photoactivatable GSMs. GSM photoprobes did not label the core proteins of the gamma-secretase complex, but instead labelled the beta-amyloid precursor protein (APP), APP carboxy-terminal fragments and amyloid-beta peptide in human neuroglioma H4 cells. Substrate labelling was competed by other GSMs, and labelling of an APP gamma-secretase substrate was more efficient than a Notch substrate. GSM interaction was localized to residues 28-36 of amyloid-beta, a region critical for aggregation. We also demonstrate that compounds known to interact with this region of amyloid-beta act as GSMs, and some GSMs alter the production of cell-derived amyloid-beta oligomers. Furthermore, mutation of the GSM binding site in the APP alters the sensitivity of the substrate to GSMs. These findings indicate that substrate targeting by GSMs mechanistically links two therapeutic actions: alteration in Abeta42 production and inhibition of amyloid-beta aggregation, which may synergistically reduce amyloid-beta deposition in Alzheimer's disease. These data also demonstrate the existence and feasibility of 'substrate targeting' by small-molecule effectors of proteolytic enzymes, which if generally applicable may significantly broaden the current notion of 'druggable' targets.     

The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor

Mammalian Toll-like receptors (TLRs) 3, 7, 8 and 9 initiate immune responses to infection by recognizing microbial nucleic acids; however, these responses come at the cost of potential autoimmunity owing to inappropriate recognition of self nucleic acids. The localization of TLR9 and TLR7 to intracellular compartments seems to have a role in facilitating responses to viral nucleic acids while maintaining tolerance to self nucleic acids, yet the cell biology regulating the transport and localization of these receptors remains poorly understood. Here we define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel to endolysosomes in mouse macrophages and dendritic cells. The ectodomains of TLR9 and TLR7 are cleaved in the endolysosome, such that no full-length protein is detectable in the compartment where ligand is recognized. Notably, although both the full-length and cleaved forms of TLR9 are capable of binding ligand, only the processed form recruits MyD88 on activation, indicating that this truncated receptor, rather than the full-length form, is functional. Furthermore, conditions that prevent receptor proteolysis, including forced TLR9 surface localization, render the receptor non-functional. We propose that ectodomain cleavage represents a strategy to restrict receptor activation to endolysosomal compartments and prevent TLRs from responding to self nucleic acids.