The Role of Single-Nucleotide Variants of NOS1, NOS2, and NOS3 Genes in the Comorbidity of Arterial Hypertension and Tension-Type Headache

Patients with tension-type headache (TTH) have an increased risk of developing arterial hypertension (AH), while hypertensive subjects do seem to have an increased risk of TTH. We searched for full-text English publications in databases using keywords and combined word searches over the past 15 years. In addition, earlier publications of historical interest were included in the review. In our review, we summed up the single nucleotide variants (SNVs) of Nitric Oxide Synthases (NOSs) genes involved in the development of essential AH and TTH. The results of studies we discussed in this review are contradictory. This might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical characteristics. However, the contribution of genetic and environmental factors remains understudied. This makes the issue interesting for researchers, as understanding these mechanisms can contribute to a search for new approaches to pathogenetic and disease-modifying treatment of the AH and TTH phenotype. New drugs against AH and TTH can be based on inhibition of nitric oxide (NO) production, blockade of steps in the NO-cGMP pathway, or NO scavenging. Indeed, selective neuronal NOS (n-NOS) and inducible NOS (i-NOS) inhibitors are already in early clinical development.     

第五讲 生物医学信息处理——DNA微阵列数据在医学中的应用

飞速发展的生物信息技术为现代医学提供了更为有效的工具.特别是随着人类基因组计划的基本完成和逐步细化,人们已经试图从基因水平上来认识生命现象,特别是一些重要疾病的机理.由于生物特性一般都涉及到多个基因的共同表达,这便出现了同时衡量成千上万个基因的表现水平的所谓DNA微阵列技术与数据.DNA微阵列数据也被称为大规模基因表达谱.根据这些微阵列数据,人们不仅能够对一些疾病进行分析,并且还能够发现一些新的生物特性与规律.另外,利用微阵列数据能够选取出疾病的相关基因并进行疾病的分类与诊断.这项研究无疑将推动医学的发展.最近,人们还进一步通过基因表达水平值来发现基因之间的调控方式,这将为疾病病理的研究与治疗提供更科学的依据.     

Time series interpolation via global optimization of moments fitting

Most time series forecasting methods assume the series has no missing values. When missing values exist, interpolation methods, while filling in the blanks, may substantially modify the statistical pattern of the data, since critical features such as moments and autocorrelations are not necessarily preserved.     

A Genetically Encoded β‐Lactamase Reporter for Ultrasensitive 129Xe NMR in Mammalian Cells

Molecular imaging holds considerable promise for elucidating biological processes in normal physiology as well as disease states, but requires noninvasive methods for identifying analytes at sub‐micromolar concentrations. Particularly useful are genetically encoded, single‐protein reporters that harness the power of molecular biology to visualize specific molecular processes, but such reporters have been conspicuously lacking for in vivo magnetic resonance imaging (MRI). Herein, we report TEM‐1 β‐lactamase (bla) as a single‐protein reporter for hyperpolarized (HP) ¹²⁹Xe NMR, with significant saturation contrast at 0.1 μm . Xenon chemical exchange saturation transfer (CEST) interactions with the primary allosteric site in bla give rise to a unique saturation peak at 255 ppm, well removed (≈60 ppm downfield) from the ¹²⁹Xe‐H₂O peak. Useful saturation contrast was also observed for bla expressed in bacterial cells and mammalian cells.     

Nonrandom features of the human immunoglobulin variable region gene repertoire expressed in response to HIV-1

Characterization of the immune response toward HIV is important for understanding the basic mechanisms of the disease and may give essential information for development of an anti-HIV vaccine. Paradoxically, although HIV infection is associated with a strong antibody response to structural and nonstructural HIV proteins, this immune response does not seem to halt disease progression. Both quantitative and qualitative B-cell abnormalities are associated with disease progression. The immunological abnormalities in HIV-1 infection include abnormal cytokine production and expansion of HIV-1-specific B-cell precursors that may reach 40%. There is also evidence that gpl20 exerts a B-cell superantigen-like activity on human B-cells through binding to gene products of the third heavy-chain variable region family (VH3). This property of gpl20 may induce abnormal mechanisms of selection of the antibody repertoire. It may also account for the apparent paucity of anti-gpl20 antibodies expressing VH3 genes and for the polyclonal activation seen in the early stages of HIV infection. This expansion would reflect specific stimulation of VH3 B-cells, but not all B-cells. It would then be followed by a significant deletion of this B-cell subset. Finally, autoimmune phenomena have been described in HIV infection, and several hypotheses have been put forward to account for such associations. On the basis of the superantigen concept discussed above, one may suggest that gpl20 may trigger B-cell subsets bearing receptors with specificities for self-components. This would explain the multiplicity of autoantibody specificities seen in this disease.     

Loss- and Gain-of-Function Mutations in Cancer: Mass-action, Spatial and Hierarchical Models

We study the stochastic dynamics of the two most common patterns in cancer initiation and progression: loss-of-function and gain-of-function mutations. We consider three stochastic models of cell populations with a constant size: a mass-action model, a spatial model and a hierarchical model. For gain-of-function mutations, we calculate the probability of mutant fixation starting from one mutant cell. For loss-of-function mutations, we calculate the rate of production of double-hit mutants. It turns out that the results are different in all models. This suggests that simple mass-action models are often misleading when studying cancer dynamics. Moreover, our results also allow us to think about various types of tissue architecture and its protective role against cancer. In particular, we show that hierarchical tissue organization lowers the risk of cancerous transformations. Also, cellular motility and long-range signaling can decrease the risk of cancer in solid tissues.     

利用基因芯片技术筛选差异表达基因的方法研究

为了探讨高维基因芯片基因表达谱数据筛选差异表达基因的方法,分析比较t检验法、秩和检验法、BON法、SIDAK法及ALSU法5种算法的差异表达基因筛选效率;采用模拟实验对t检验法、ALSU法等5种算法进行比较,并使用第一类、第二类错误率、总体错误率、筛选差异表达基因数及其均方根误差等5种指标进行评价;t检验法、秩和检验法计算结果过于灵敏,筛选差异表达基因个数较多,会促使筛选差异表达基因中假阴性事件的发生,BON法、SIDAK法筛选结果过于保守,筛选的差异表达基因个数较少,假阳性事件发生率较为显著,ALSU法能较稳定的抑制第一、二类错误率的发生,同时ALSU法筛选结果受系统扰动误差影响较笺LSU方法能够稳定的、高效的筛选差异表达基因,在使用高纬基因表达谱数据筛选差异表达基因时应首选ALSU法.     

Cross-validated wavelet shrinkage

Cross-validation has been successfully used in various areas of statistics. However, it has not been used much in wavelet shrinkage estimation because fast wavelet methods cannot be applied to deleted data. In this paper, we show this problem can be avoided by using a fast imputation of data. This allows level-dependent cross- validation which is attractive to data with different sparseness. The proposed methods can be easily extended to higher dimensional problem such as image. Results from simulation and examples demonstrate the promising empirical properties of the procedure. In particular, the methods proposed in this work provide outstanding results for non-Gaussian noises because cross-validation is not based on normality assumptions.