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The article focuses on the recent advances in biotechnology. It cites that the advances in the biotechnology have changed the key nature of biological researches. It relates that scientists in the past used paper notebooks or simple spreadsheets to document their experiments, but at present, scientists use various new tools such as gene chips or measuring gene expression or sequence variation that brought changes and has altered their works and reveals potential associations and interactions with a variety of genes and other biological entities. It also mentions that the advances in biotechnology brought a massive increase in the scientific knowledge of scientists. The establishment of the Text Retrieval Conference in the U.S. is also discussed.

The article presents a study that investigates the protein expression regulation of human cytomegalovirus (HCMV) in the U.S.

The article focuses on the DNA sequence variants that influence gene expression and disease risk in the U.S. It is pointed out that the effects of variations in DNA sequence are often subtle, such as altered levels of gene expression. Moreover, it is said that identifying those DNA sequences that determine levels of expression across individuals could have great medical potential. It also discusses one paper that illustrates the identification of DNA sequences which looks at the two major contractile proteins of the human heart.

The article reports on the study published by "Science Translational Medicine" which examines the significance of drug repositioning in the U.S. It highlights the discovery of new therapeutic uses for the anti-ulcer drug cimetidine and the anticonvulsant topiramate. It states that the authors utilized computational analysis of gene expression data to support the clinical significance of drug repositioning.

The article presents the activities that lead to development of the first gene expression array by scientists from Affymetrix Inc., David Lockhart and Mark Chee in the U.S. For over one year of experiments, the two designed a thousands of nucleotides as gene detectors which they synthesized into high-density array through the use of parallel combinatorial chemistry. The array was used for quantification of messenger RNA molecules in cells and RNA detection.

The article discusses on the study conducted by N. Tsankova and colleagues that determines the possible effects of antidepressant imipramine induce modifications of chromatin for the production of repressive states for gene expression. It emphasizes that antidepressant agents are the most common drugs prescribe in the U.S. for serious brain disorder. The researchers evaluates the effects of antidepressants by closely monitoring the expression of different splice variants of gene.

Lung adenocarcinoma is comprised of distinct mutational subtypes characterized by mutually exclusive oncogenic mutations in RTK/RAS pathway members KRAS, EGFR, BRAF and ERBB2, and translocations involving ALK, RET and ROS1. Identification of these oncogenic events has transformed the treatment of lung adenocarcinoma via application of therapies targeted toward specific genetic lesions in stratified patient populations. However, such mutations have been reported in only ∼55% of lung adenocarcinoma cases in the United States, suggesting other mechanisms of malignancy are involved in the remaining cases. Here we report somatic mutations in the small GTPase gene RIT1 in ∼2% of lung adenocarcinoma cases that cluster in a hotspot near the switch II domain of the protein. RIT1 switch II domain mutations are mutually exclusive with all other known lung adenocarcinoma driver mutations. Ectopic expression of mutated RIT1 induces cellular transformation in vitro and in vivo, which can be reversed by combined PI3K and MEK inhibition. These data identify RIT1 as a driver oncogene in a specific subset of lung adenocarcinomas and suggest PI3K and MEK inhibition as a potential therapeutic strategy in RIT1-mutated tumors. [ABSTRACT FROM AUTHOR]

Background:Squamous cell lung cancer (SqCC) is the second most common type of lung cancer in the United States. Previous studies have used gene-expression data to classify SqCC samples into four subtypes, including the primitive, classical, secretory and basal subtypes. These subtypes have different survival outcomes, although it is unknown whether these molecular subtypes predict response to therapy.Methods:Here, we analysed RNAseq data of 178 SqCC tumour samples and characterised the features of the different SqCC subtypes to define signature genes and pathway alterations specific to each subtype. Further, we compared the gene-expression features of each molecular subtype to specific time points in models of airway development. We also classified SqCC-derived cell lines and their reported therapeutic vulnerabilities.Results:We found that the primitive subtype may come from a later stage of differentiation, whereas the basal subtype may be from an early time. Most SqCC cell lines responded to one of five anticancer drugs (Panobinostat, 17-AAG, Irinotecan, Topotecan and Paclitaxel), whereas the basal-type cell line EBC-1 was sensitive to three other drugs (PF2341066, AZD6244 and PD-0325901).Conclusion:Compared with the other three subtypes of cell lines, the secretory-type cell lines were significantly less sensitive to the five most effective drugs, possibly because of their low proliferation activity. We provide a bioinformatics framework to explore drug repurposing for cancer subtypes based on the available genomic profiles of tumour samples, normal cell types, cancer cell lines and data of drug sensitivity in cell lines. [ABSTRACT FROM AUTHOR]

The article reports on the research on microRNAs in the U.S. The research revealed that microRNAs are needed to safeguard the function of regulatory T cells, and are required to maintain T cells activity, which befit their suggested role in buffering gene expression in conditions of environmental stress. It is concluded that this study highlights an essential role for microRNA-dependent regulation of gene expression in the maintenance of T cells homeostasis and suppressive function.

Background: Regulatory T cells (Tregs) have an essential role in tolerance and immune regulation. However, few and controversial data have been published to date on the role and number of these cells in food allergic children. The forkhead/winged-helix transcription factor box protein 3 (FOXP3) is considered the most reliable marker for Tregs. Objective: This study aims to investigate the FOXP3, interleukin (IL)-10, and transforming growth factor (TGF-β) genes expression in children with IgE-dependent food allergy. Material and Methods: The study group consisted of 54 children with IgE-dependent food allergy (FA) and a control group of 26 non-atopic healthy children. The diagnosis of FA was established using questionnaires, clinical criteria, skin prick tests, serum sIgE antibodies (UniCAP 100 Pharmacia Upjohn), and a double-blind placebo control food challenge. In order to assess gene expression, the isolation of nucleated cells was performed using Histopaque-1077 (Sigma-Aldrich, Germany). The concentration of RNA obtained was measured using a super-sensitive NanoDrop ND1000 spectrophotometer (Thermo Scientific, USA). A reverse transcription reaction was performed using a commercially available set of High Capacity cDNA Archive Kit (Applied Biosystems, USA). Analysis have been carried out in the genetic analyzer 7900HT Real-Time PCR (Applied Biosystems, USA). Results: The average level of the FOXP3 gene expression in the studied group was 2.19 ± 1.16 and in the control group 2.88 ± 1.66 ( p = 0.03). The average level of IL10 mRNA expression in the study group was 13.6 ± 1.07 and was significantly lower than corresponding values in the control group 14.3 ± 1.1 ( p = 0.01). There were no significant differences in the average level of the TGF-β mRNA expression in the study group (3.4 ± 0.4) and controls (3.5 ± 0.3; p > 0.05). The FOXP3 gene expression was the highest in children who acquired tolerance to food (3.54 ± 0.75), lower in heated allergen-tolerant children (2.43 ± 0.81), and the lowest in heated allergen-reactive children (1.18 ± 0.5; p = 0.001 control vs heated allergen reactive; p = 0.005 heated allergen tolerant vs heated allergen reactive; p = 0.001 outgrown vs heated allergen reactive). The significant tendency toward lower total IgE levels with a higher FOXP3 mRNA expression was detected ( n = 54; Pearson r = −0.4393; p = 0.001). Conclusions: Children with FA showed statistically significant lower level of the FOXP3 and IL10 gene expression than healthy children. Children acquiring tolerance to the food show significantly higher levels of the FOXP3 gene expression than children with active FA. The correlation between the level of FOXP3 and total IgE was detected. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and ∼2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10−8). The most significant SNP (rs3814113; P = 2.5 × 10−17) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79–0.86, Ptrend = 5.1 × 10−19). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73–0.81, Ptrend = 4.1 × 10−21). [ABSTRACT FROM AUTHOR]

Cigarette smoking is the leading preventable cause of death in the United States. Although smoking behavior has a significant genetic determination, the specific genes and associated mechanisms underlying the smoking behavior are largely unknown. Here, we carried out a genome-wide association study on smoking behavior in 840 Caucasians, including 417 males and 423 females, in which we examined ∼380 000 single nucleotide polymorphisms (SNPs). We found that a cluster of nine SNPs upstream from the IL15 gene were associated with smoking status in males, with the most significant SNP, rs4956302, achieving a P-value (8.80 × 10−8) of genome-wide significance. Another SNP, rs17354547 that is highly conserved across multiple species achieved a P-value of 5.65 × 10−5. These two SNPs, together with two additional SNPs (rs1402812 and rs4956396) were selected from the above nine SNPs for replication in an African-American sample containing 1251 subjects, including 412 males and 839 females. The SNP rs17354547 was replicated successfully in the male subgroup of the replication sample; it was associated with smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerstrom Test for Nicotine Dependence (FTND), with P-values of 0.031, 0.0046 and 0.019, respectively. In addition, a haplotype formed by rs17354547, rs1402812 and rs4956396 was also associated with SQ, HSI and FTND, achieving P-values of 0.039, 0.0093 and 0.0093, respectively. To further confirm our findings, we carried out an in silico replication study of the nine SNPs in a Framingham Heart Study sample containing 7623 Caucasians from 1731 families, among which, 3491 subjects were males and 4132 were females. Again, the male-specific association with smoking status was observed, for which seven of the nine SNPs achieved significant P-values (P<0.05) and two achieved marginally significant P-values (P<0.10) in males. Several of the nine SNPs, including the highly conserved one across species, rs17354547, are located at potential transcription factor binding sites, suggesting transcription regulation as a possible function for these SNPs. Through this function, the SNPs may modulate the gene expression of IL15, a key cytokine regulating immune function. As the immune system has long been recognized to influence drug addiction behavior, our association findings suggest a novel mechanism for smoking addiction involving immune modulation through the IL15 pathway.Molecular Psychiatry (2009) 14, 668–680; doi:10.1038/mp.2009.3; published online 3 February 2009 [ABSTRACT FROM AUTHOR]

Cholesterol gallstone disease affects 40 million Americans, and evidence indicates that there is a genetic component to human gallstone disease. In a mouse model of gallstone formation, where mice are fed a lithogenic diet, QTL analysis has been employed to identify the Lith 1 locus on Chromosome (Chr) 2. In order to identify genes in which the difference in expression is independent of factors other than strain-specific genotype, we employed microarray analysis of hepatic gene expression in gallstone-susceptible (C57L/J) and gallstone-resistant (AKR/J) mice. We observed 57 genes with consistent differential expression between C57L/J and AKR/J mice, including many cytochrome, antioxidant, and lipid peroxidation genes. Analysis of differentially expressed genes identified numerous genes involved in fatty acid metabolism. Northern analysis of selected lipid metabolic genes further confirmed the strain-specific differential expression. Literature searches of common regulatory elements within antioxidant systems identified the nuclear transcription factor Nrf2, which maps to the Lith 1 loci. Hepatic Nrf2 gene and protein expression is also increased in strain AKR/J, compared with C57L/J mice, identifying Nrf2 as a putative Lith 1 gallstone gene. These data indicate that microarray analysis may complement QTL analysis to identify systems of regulation and genotypic differences responsible for polygenic diseases. [ABSTRACT FROM AUTHOR]

The article presents a medical study conducted by Tyler Jacks and his colleagues at the Massachusetts Institute of Technology pertaining to the gene that protects against cancer in the U.S. It states that the team studied mouse models of cancer in which one of both copies of Dicer1, a gene that encodes a protein that is vital for processing fragments of RNA called microRNA is deleted. From the research, the team found out that deleting a single copy of Dicer1 led to more tumors, lower levels of microRNA and reduced survival and a full loss of Dicer1 blocked the formation of tumor because some level of its protein is required for cell growth or viability.

The article reports on the development concerning the methodological solutions for handling membrane protein structures in the Protein Data Bank in the U.S. It is revealed that methods are addressing the challenges in membrane protein expression, solubilization and crystallization bottlenecks. The use of solid-state nuclear magnetic resonance are rapidly advancing, but still needs sensitivity and resolution enhancements to make a robust technology.