Assessing Computational Amino Acid β-Turn Propensities with a Phage-Displayed Combinatorial Library and Directed Evolution

SummaryStructure propensities of amino acids are important determinants in guiding proteins' local and global structure formation. We constructed a phage display library—a hexa-HIS tag upstream of a CXXC (X stands for any of the 20 natural amino acids) motif appending N-terminal to the minor capsid protein pIII of M13KE filamentous phage—and developed a novel directed-evolution procedure to select for amino acid sequences forming increasingly stable β-turns in the disulfide-bridged CXXC motif. The sequences that emerged from the directed-evolution cycles were in good agreement with type II β-turn propensities derived from surveys of known protein structures, in particular, Pro-Gly forming a type II β-turn. The agreement strongly supported the notion that β-turn formation plays an active role in initiating local structure folding in proteins

Genetic diversity and C2-like subgenogroup strains of enterovirus 71, Taiwan, 2008

<p>Abstract</p> <p>Background</p> <p>Human enterovirus 71 (EV-71) is known of having caused numerous outbreaks of hand-foot-mouth disease, and other clinical manifestations globally. In 2008, 989 EV-71 strains were isolated in Taiwan.</p> <p>Results</p> <p>In this study, the genetic and antigenic properties of these strains were analyzed and the genetic diversity of EV-71 subgenogroups surfacing in Taiwan was depicted, which includes 3 previously reported subgenogroups of C5, B5, and C4, and one C2-like subgenogroup. Based on the phylogenetic analyses using their complete genome nucleotide sequences and neutralization tests, the C2-like subgenogroup forms a genetically distinct cluster from other subgenogroups, and the antisera show a maximum of 128-fold decrease of neutralization titer against this subgenogroup. In addition, the subgenogroup C4 isolates of 2008 were found quite similar genetically to the Chinese strains that caused outbreaks in recent years and thus they should be carefully watched.</p> <p>Conclusions</p> <p>Other than to be the first report describing the existence of C2-like subgenogroup of EV-71 in Taiwan, this article also foresees a potential of subgenogroup C4 outbreaks in Taiwan in the near future.</p

Prescription characteristics of Xue-Fu-Zhu-Yu-Tang in pain management: a population-based study using the National Health Insurance Research Database in Taiwan

Objective: To explore the prevalence and distinctive features of Xue-Fu-Zhu-Yu-Tang (XFZYT) prescriptions by analyzing the National Health Insurance Research Database (NHIRD) to identify the specific medical problems for which XFZYT is prescribed.Methods: This nationwide, population-based, cross-sectional study included 109,073 XFZYT users and 532,848 XFZYT non-users among Chinese herbal product (CHP) users in NHIRD. Chi-squared tests were used to analyze disparities between the XFZYT user and XFZYT non-user cohorts, and the mean age was evaluated using the Wilcoxon rank-sum test. Logistic regression was used to compute the odds ratios (ORs) and 95% confidence intervals (95% CIs).Results: XFZYT was frequently used to treat pain. The top five conditions for which the Taiwanese traditional Chinese medicine (TCM) practitioners would prescribe XFZYT were chest pain; headache; myalgia and myositis; lumbago; and neuralgia, neuritis, and radiculitis.Conclusion: This study represents an inaugural comprehensive survey conducted on the utilization of XFZYT prescriptions among patients with diverse diseases. XFZYT is mostly used to treat pain conditions in Taiwan. Combined with the combination use of other CHPs, XFZYT is used to treat symptoms of the chest and respiratory system, soft tissue conditions, menstruation disorders, and joint and back discomfort. These results suggest that further clinical trials are warranted to verify the effects of XFZYT in pain management

Korean Red Ginseng Improves Blood Pressure Stability in Patients with Intradialytic Hypotension

Introduction. Intradialytic hypotension (IDH) is a common complication during hemodialysis which may increase mortality risks. Low dose of Korean red ginseng (KRG) has been reported to increase blood pressure. Whether KRG can improve hemodynamic stability during hemodialysis has not been examined. Methods. The 8-week study consisted of two phases: observation phase and active treatment phase. According to prehemodialysis blood pressure (BP), 38 patients with IDH were divided into group A (BP ≥ 140/90 mmHg, n = 18) and group B (BP < 140/90 mmHg, n = 20). Patients were instructed to chew 3.5 gm KRG slices at each hemodialysis session during the 4-week treatment phase. Blood pressure changes, number of sessions disturbed by symptomatic IDH, plasma levels of vasoconstrictors, blood biochemistry, and adverse effects were recorded. Results. KRG significantly reduced the degree of blood pressure drop during hemodialysis (P < 0.05) and the frequency of symptomatic IDH (P < 0.05). More activation of vasoconstrictors (endothelin-1 and angiotensin II) during hemodialysis was found. The postdialytic levels of endothelin-1 and angiotensin II increased significantly (P < 0.01). Conclusion. Chewing KRG renders IDH patients better resistance to acute BP reduction during hemodialysis via activation of vasoconstrictors. Our results suggest that KRG could be an adjuvant treatment for IDH

Effects of Water Quality on Dissolution of Yerba Mate Extract Powders

Yerba mate tea is known as one of the most popular nonalcoholic beverages favoured by South Americans due to its nutrition facts and medicinal properties. The processing of yerba mate tea is found to affect the properties of its final forms. This study presents an investigation into the effects of water sources on the dissolution of yerba mate extract powders. Comparisons were conducted between yerba mate teas prepared by dissolving yerba mate extract powders into tap water and deionized water. Topics to be explored in this work are the major compositions and antioxidant activities, including total phenol content, reducing power, DPPH scavenging activity, and ABTS+• scavenging capacity. It is indicated that there is little difference for antioxidant activities and major constituents of yerba mate teas between both water sources. However, a deeper color is seen in the tap water case, resulting from the reaction between tannic acid and ions. This research finding can be treated as a way to benefit the yerba mate tea processing for applications

Discovery of selective inhibitors of Glutaminase-2, which inhibit mTORC1, activate autophagy and inhibit proliferation in cancer cells

Glutaminase, which converts glutamine to glutamate, is involved in Warburg effect in cancer cells. Two human glutaminase genes have been identified, GLS (GLS1) and GLS2. Two alternative transcripts arise from each glutaminase gene: first, the kidney isoform (KGA) and glutaminase C (GAC) for GLS; and, second, the liver isoform (LGA) and glutaminase B (GAB) for GLS2. While GLS1 is considered as a cancer therapeutic target, the potential role of GLS2 in cancer remains unclear. Here, we discovered a series of alkyl benzoquinones that preferentially inhibit glutaminase B isoform (GAB, GLS2) rather than the kidney isoform of glutaminase (KGA, GLS1). We identified amino acid residues in an allosteric binding pocket responsible for the selectivity. Treatment with the alkyl benzoquinones decreased intracellular glutaminase activity and glutamate levels. GLS2 inhibition by either alkyl benzoquinones or GLS2 siRNA reduced carcinoma cell proliferation and anchorage-independent colony formation, and induced autophagy via AMPK mediated mTORC1 inhibition. Our findings demonstrate amino acid sequences for selective inhibition of glutaminase isozymes and validate GLS2 as a potential anti-cancer target

Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells

The sensitivity of non-small cell lung cancer (NSCLC) patients to EGFR tyrosine kinase inhibitors (TKIs) is strongly associated with activating EGFR mutations. Although not as sensitive as patients harboring these mutations, some patients with wild-type EGFR (wtEGFR) remain responsive to EGFR TKIs, suggesting that the existence of unexplored mechanisms renders most of wtEGFR-expressing cancer cells insensitive.Here, we show that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI, gefitinib, is associated with elevated expression of breast cancer resistance protein (BCRP/ABCG2), which in turn leads to gefitinib efflux from cells. In addition, BCRP/ABCG2 expression correlates with poor response to gefitinib in both cancer cell lines and lung cancer patients with wtEGFR. Co-treatment with BCRP/ABCG2 inhibitors enhanced the anti-tumor activity of gefitinib.Thus, BCRP/ABCG2 expression may be a predictor for poor efficacy of gefitinib treatment, and targeting BCRP/ABCG2 may broaden the use of gefitinib in patients with wtEGFR

A neural network model for constructing endophenotypes of common complex diseases: an application to male young-onset hypertension microarray data

Motivation: Identification of disease-related genes using high-throughput microarray data is more difficult for complex diseases as compared with monogenic ones. We hypothesized that an endophenotype derived from transcriptional data is associated with a set of genes corresponding to a pathway cluster. We assumed that a complex disease is associated with multiple endophenotypes and can be induced by their up/downregulated gene expression patterns. Thus, a neural network model was adopted to simulate the gene–endophenotype–disease relationship in which endophenotypes were represented by hidden nodes

High-resolution spatial and genomic characterization of coral-associated microbial aggregates in the coral Stylophora pistillata

Bacteria commonly form aggregates in a range of coral species [termed coral-associated microbial aggregates (CAMAs)], although these structures remain poorly characterized despite extensive efforts studying the coral microbiome. Here, we comprehensively characterize CAMAs associated with Stylophora pistillata and quantify their cell abundance. Our analysis reveals that multiple Endozoicomonas phylotypes coexist inside a single CAMA. Nanoscale secondary ion mass spectrometry imaging revealed that the Endozoicomonas cells were enriched with phosphorus, with the elemental compositions of CAMAs different from coral tissues and endosymbiotic Symbiodiniaceae, highlighting a role in sequestering and cycling phosphate between coral holobiont partners. Consensus metagenome--assembled genomes of the two dominant Endozoicomonas phylotypes confirmed their metabolic potential for polyphosphate accumulation along with genomic signatures including type VI secretion systems allowing host association. Our findings provide unprecedented insights into Endozoicomonas-dominated CAMAs and the first direct physiological and genomic linked evidence of their biological role in the coral holobiont