Codon usage bias and its influencing factors for Y-linked genes in human

The non-uniform usage of synonymous codons during translation of a protein is the codon usage bias and is mainly influenced by natural selection and mutation pressure. We have used bioinformatic approaches to analyze codon usage bias of human Y-linked genes. Effective number of codon (ENC) suggested that the overall extent of codon usage bias of genes was low. The relative synonymous codon usage (RSCU) analysis revealed that AGA and CTG codons were over-represented in Y-linked genes. Compositional constraint under mutation pressure influenced the codon usage pattern as revealed by the correspondence analysis (COA). Parity plot suggests that both natural selection and mutation pressure might have influenced the codon usage bias of Y-linked genes.     

Considering Dependencies Amongst Genes Helps to Adjust the Significance Rank of DEGs

Lists of differentially expressed genes (DEGs) detected often show low reproducibility even in technique replicate experiments. The reproducibility is even lower for those real cancer data with large biological variations and limited number of samples. Since existing methods for identifying differentially expressed genes treat each gene separately, they cannot circumvent the problem of low reproducibility. Considering correlation structures of genes may help to mitigate the effect of errors on individual gene estimates and thus get more reliable lists of DEGs. We borrowed information from large amount of existing microarray data to define the expression dependencies amongst genes. We use this prior knowledge of dependencies amongst genes to adjust the significance rank of DEGs. We applied our method and four popular ranking algorithms including mean fold change (FC), SAM, t‐statistic and Wilcoxon rank sum‐test on two cancer microarray datasets. Our method achieved higher reproducibility than other methods across a range of sample sizes. Furthermore, our method obtained higher accuracy than other methods, especially when the sample size is small. The results demonstrate that considering the dependencies amongst genes helps to adjust the significance rank of genes and find those truly differentially expressed genes.     

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.     

Properties and engineering of a mutantSTA promoter ofSaccharomyces diastaticus

A new allelic variant of theSTA2 gene ofS. diastaticus, designated asSTA2 ^K, was cloned and characterized (1; accompanying paper). An application-oriented analysis of the promoter region ofSTA2 ^K is described, with an emphasis on its peculiar structural feature: A 1.1-kb natural deletion located 189 nucleotides upstream of the translation start codon. The strength of theSTA2 ^K promoter was found comparable to that of known strong constitutive yeast promoters(ADH1, GAPDH). Regulated glucoamylase expression was demonstrated by chimeric promoters, which were constructed by placing theSTA2 ^K promoter under the control of either thePH05 orCYC1 upstream regulatory sequences. On high-copy-number vectors, induction of the UASpho5-STA2^K chimeric promoter by phosphate depletion resulted in a destructive overexpression of the secreted glucoamylase, which completely halted cell growth, and promoted cell decay. In contrast, UAScyc1 was shown to mediate a fine-tuned regulation both by glucose concentration and, indirectly, by starch, the substrate for the glucoamylase to produce glucose.     

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.     

Regulatory Role of Nano-Curcumin against Tartrazine-Induced Oxidative Stress,Apoptosis-Related Genes Expression,and Genotoxicity in Rats

The present study evaluates the regulatory effect of Nano-Curcumin (Nano-CUR) against tartrazine (TZ)-induced injuries on apoptosis-related gene expression (i.e., p⁵³, CASP-3 and CASP-9), antioxidant status, and DNA damages in bone marrow in treated rats. Male rats were arbitrarily separated into five groups, and each group was comprised of 10 rats each. The 1st group served as control (G1). The 2nd group ingested 7.5 mg TZ/kg. b.w. (body weight). The 3rd group ingested Nano-CUR 1 g/kg b.w. The 4th and 5th groups were respectively administered with (1 g Nano-CUR + 7.5 mg TZ/kg. b.w.) and (2 g Nano-CUR + 7.5 mg TZ/kg. b.w.). At the end of the experiment, blood samples, livers, and kidneys were collected. Livers and kidneys were homogenized and used for the analysis of reduced glutathione, malonaldhyde, total antioxidant capacity, lipid peroxide antioxidant enzyme activities, apoptosis-related gene expression, and genotoxicity by comit test. The ingestion of TZ for 50 days resulted in significant decreases in body, and kidney weights in rats and a relative increase in the liver weight compared to control. In contrast, the ingestion of Nano-CUR with TZ remarkably upgraded the body weight and relative liver weight compared to the normal range in the control. Aditionally, TZ ingestion in rats increased the oxidative stress biomarkers lipid peroxide (LPO) and malonaldehyde (MDA) significantly, whereas it decreased the reduced glutathione (GSH) levels and total antioxidant capacity (TAC). Similarly, the levels of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) significantly deteriorated in response to TZ ingestion. Moreover, the results revealed a remarkable up-regulation in the level of expression for the three examined genes, including p⁵³, CASP-3, and CASP-9 in TZ-ingested rats compared to the control. On the other hand, the comet assay result indicates that the ingestion of TZ induced DNA damage in bone marrow. Notably, the administration of Nano-CUR protected the kidney and liver of TZ-ingested rats as evidenced by a significant elevation in all antioxidant activities of tested enzymes (i.e, SOD, GPx, and CAT), vital recovery in GSH and TAC levels, and a statistical decrease in LPO and MDA compared to TZ-ingested rats. Interestingly, the ingestion of rats with TZ modulates the observed up-regulation in the level of expression for the chosen genes, indicating the interfering role in the signaling transduction process of TZ-mediated poisoning. The results indicate that the administration of Nano-CUR may protect against TZ-induced DNA damage in bone marrow. According to the results, Nano-CUR exerted a potential protective effect against oxidative stress, DNA damage, and the up-regulation of apoptosis-related genes induced by TZ ingested to rats.     

质量-数量性状的遗传参数估计*Ⅱ.利用DH群体或RIL群体

采用混合分布理论与极大似然法，拓展了适用于双单倍体群体（ＤＨ）和重组近交系（ＲＩＬ）群体的质量－数量性状的遗传分析方法．据此方法可以鉴别主－微基因的存在、了解主基因的作用方式、估计主－微基因的遗传效应和方差等遗传参数．     

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.