In the title compound, [Mn(C4H3N2O2)2(H2O)2], the MnII ion is located on a twofold rotation axis and displays a distorted octahedral coordination environment, defined by two N,O-bidentate 1H-imidazole-4-carboxylate ligands in the equatorial plane and two water molecules in axial positions. In the crystal, O—H⋯O and N—H⋯O hydrogen bonds link the molecules into a three-dimensional supramolecular network. π–π stacking interactions between the imidazole rings [centroid–centroid distances = 3.5188 (15) and 3.6687 (15) Å] further stabilize the structure.
Emerging evidence showed that common functional −31G>C polymorphism (rs9904341 G>C) in the promoter region of the survivin gene is involved in the regulation of survivin expression, thus increasing an individual’s susceptibility to gastrointestinal tract (GIT) cancer; but individually published results are inconclusive. The aim of this systematic review and meta-analysis was to derive a more precise estimation of the association between survivin −31G>C polymorphism and GIT cancer risk.
A literature search of PubMed, Embase, Web of Science and CBM databases was conducted from inception through July 1st, 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.
Nine case-control studies were included with a total of 2,231 GIT cancer cases and 2,287 healthy controls. The results indicated that survivin −31G>C polymorphism was associated with increased risk of GIT cancer. In the stratified analysis by cancer types, significant associations were observed between survivin −31G>C polymorphism and increased risk of colorectal and gastric cancers. However, the lack of association of survivin −31G>C polymorphism with esophageal cancer risk may be due to a lack of a sufficient number of eligible studies and the influence of different genetic and environmental factors.
Results from the current meta-analysis suggests that survivin −31G>C polymorphism might increase the risk of GIT cancer, especially among gastric and colorectal cancers.
This study aimed to examine the associations between reported exposure to anti-smoking warnings at the point-of-sale (POS) and smokers’ interest in quitting and their subsequent quit attempts by comparing reactions in Australia where warnings are prominent to smokers in other countries.
A prospective multi-country cohort design was employed.
Australia, Canada, the UK and the US.
21,613 adult smokers who completed at least one of the seven waves (2002-2008) of the International Tobacco Control Four Country Survey were included in the analysis.
Reported exposure to POS anti-smoking warnings and smokers’ interest in quitting at the same wave and quit attempts over the following year.
Compared to smokers in Canada, the UK and the US, Australian smokers reported higher levels of awareness of POS anti-smoking warnings, and this difference was consistent over the study period. Over waves in Australia (but not in the other three countries) there was a significantly positive association between reported exposure to POS anti-smoking warnings and interest in quitting (adjusted odds ratio = 1.139, 95% CI 1.039~1.249, p<0.01) and prospective quit attempts (adjusted odds ratio = 1.216, 95% CI 1.114~1.327, p<0.001) when controlling for demographics, smoking characteristics, overall salience of anti-smoking information, and awareness of anti-smoking material from channels other than POS.
Point-of-sale health warnings about tobacco are more prominent in Australia than US, UK or Canada and appear to act as a prompt to quitting.
Lentiviral vectors are beginning to emerge as a viable choice for human gene therapy. Here, we describe a method that combines the convenience of a suspension cell line with a scalable, nonchemically based, and GMP-compliant transfection technique known as flow electroporation (EP). Flow EP parameters for serum-free adapted HEK293FT cells were optimized to limit toxicity and maximize titers. Using a third generation, HIV-based, lentiviral vector system pseudotyped with the vesicular stomatitis glycoprotein envelope, both small- and large-volume transfections produced titers over 1×108 infectious units/mL. Therefore, an excellent option for implementing large-scale, clinical lentiviral productions is flow EP of suspension cell lines.
Witting and colleagues describe a flow electroporation (flow EP) transfection method for efficient, scalable, nonchemically based and GMP-compliant production of lentiviral vectors. Both small- and large-scale flow EP transfections of serum-free adapted HEK293FT cells using a third-generation HIV-based lentiviral vector system produce titers over 1 × 108 infectious units/ml.
Activation of the TRPM8 ion channel in sensory nerve endings produces a sensation of pleasant coolness. Here we show that inflammatory mediators such as bradykinin and histamine inhibit TRPM8 in intact sensory nerves, but do not do so via conventional signalling pathways. The G-protein subunit Gaq instead binds to TRPM8 and when activated by a Gq-coupled receptor directly inhibits ion channel activity. Deletion of Gaq largely abolished inhibition of TRPM8, and inhibition was rescued by a Gaq chimera whose ability to activate downstream signalling pathways was completely ablated. Activated Gaq protein, but not Gβγ, potently inhibits TRPM8 in excised patches. We conclude that Gaq pre-forms a complex with TRPM8 and inhibits activation of TRPM8, following activation of G-protein coupled receptors, by a direct action. This signalling mechanism may underlie the abnormal cold sensation caused by inflammation.
pain; TRPM8; G proteins; GPCR; inflammatory mediators; sensory transduction
Seed germination and flowering initiation are both transitions responding to similar seasonal cues. This study shows that ABSCISIC ACID-INSENSITIVE MUTANT 5 (ABI5), a bZIP transcription factor, which plays an important role in the abscisic acid (ABA)-arrested seed germination, is robustly associated with the floral transition in Arabidopsis. Under long-day conditions, overexpression of ABI5 could delay floral transition through upregulating FLOWERING LOCUS C (FLC) expression. In contrast, ectopically overexpressing FLC in an abi5 mutant reversed the earlier flowering phenotype. Further analysis indicated that transactivation of FLC could be promoted by ABI5 and/or other abscisic acid-responsive element (ABRE)-binding factors (ABFs). The expression of FLC that was promoted by ABI5 and/or other ABFs could be blocked in a triple SNF1-related protein kinase (SnRK) mutant, snrk2.2/2.3/2.6, despite the presence of ABA. In sharp contrast, when SnRK2.6 was coexpressed, the reduction of transactivity of FLC was reverted in mesophyll protoplasts of snrk2.2/2.3/2.6. Additional results from analysing transgenic plants carrying mutations of phosphoamino acids (ABI5
S42AS145AT201A), which are conserved in ABI5, suggested that SnRK2-mediated ABI5 and/or ABF phosphorylation may be crucial for promoting FLC expression. The transgenic plants ABI5
S42AS145AT201A were insensitive to ABA in seed germination, in addition to having an earlier flowering phenotype. Direct binding of ABI5 to the ABRE/G-box promoter elements existing in FLC was demonstrated by chromatin immunoprecipitation. Mutations at the ABRE/G-box regions in FLC promoter sequences abolished the ABI5-promoted transactivation of FLC. In summary, these results may decipher the inhibitory effect of ABA on floral transition in Arabidopsis.
ABA; ABFs; ABI5; chromatin immunoprecipitation; FLC; flowering time; SnRK2s.
Transcriptome variation plays an important role in affecting the phenotype of an organism. However, an understanding of the underlying mechanisms regulating transcriptome variation in segregating populations is still largely unknown. We sought to assess and map variation in transcript abundance in maize shoot apices in the intermated B73×Mo17 recombinant inbred line population. RNA–based sequencing (RNA–seq) allowed for the detection and quantification of the transcript abundance derived from 28,603 genes. For a majority of these genes, the population mean, coefficient of variation, and segregation patterns could be predicted by the parental expression levels. Expression quantitative trait loci (eQTL) mapping identified 30,774 eQTL including 96 trans-eQTL “hotspots,” each of which regulates the expression of a large number of genes. Interestingly, genes regulated by a trans-eQTL hotspot tend to be enriched for a specific function or act in the same genetic pathway. Also, genomic structural variation appeared to contribute to cis-regulation of gene expression. Besides genes showing Mendelian inheritance in the RIL population, we also found genes whose expression level and variation in the progeny could not be predicted based on parental difference, indicating that non-Mendelian factors also contribute to expression variation. Specifically, we found 145 genes that show patterns of expression reminiscent of paramutation such that all the progeny had expression levels similar to one of the two parents. Furthermore, we identified another 210 genes that exhibited unexpected patterns of transcript presence/absence. Many of these genes are likely to be gene fragments resulting from transposition, and the presence/absence of their transcripts could influence expression levels of their ancestral syntenic genes. Overall, our results contribute to the identification of novel expression patterns and broaden the understanding of transcriptional variation in plants.
Phenotypes are determined by the expression of genes, the environment, and the interaction of gene expression and the environment. However, a complete understanding of the inheritance of and genome-wide regulation of gene expression is lacking. One approach, called expression quantitative trait locus (eQTL) mapping provides the opportunity to examine the genome-wide inheritance and regulation of gene expression. In this paper, we conducted high-throughput sequencing of gene transcripts to examine gene expression in the shoot apex of a maize biparental mapping population. We quantified expression levels from 28,603 genes in the population and showed that the vast majority of genes exhibited the expected pattern of Mendelian inheritance. We genetically mapped the expression patterns and identified genomic regions associated with gene expression. Notably, we detected gene expression patterns that exhibited non-Mendelian inheritance. These included 145 genes that exhibited expression patterns in the progeny that were similar to only one of the parents and 210 genes with unexpected presence/absence expression patterns. The findings of non-Mendelian inheritance underscore the complexity of gene expression and provide a framework for understanding these complexities.
To describe some of the variability across the world in levels of quit smoking attempts and use of various forms of cessation support.
Use of the International Tobacco Control Policy Evaluation Project surveys of smokers, using the 2007 survey wave (or later, where necessary).
Australia, Canada, China, France, Germany, Ireland, Malaysia, Mexico, Netherlands, New Zealand, South Korea, Thailand, UK, Uruguay and USA.
Self-report on use of cessation aids and on visits to health professionals and provision of cessation advice during the visits.
Prevalence of quit attempts in the last year varied from under 20% to over 50% across countries. Similarly, smokers varied greatly in reporting of visiting health professionals in the last year (< 20% to over 70%), and among those who did, provision of advice to quit also varied greatly. There was also marked variability in the levels and types of help reported. Use of medication was generally more common than use of behavioural support, except where medications are not readily available.
There is wide variation across countries in rates of attempts to stop smoking and use of assistance with higher overall use of medication than behavioural support. There is also wide variation in the provision of brief advice to stop by health professionals.
The glutamate excitotoxicity, mediated through N-methyl-d-aspartate receptors (NMDARs), plays an important role in cerebral ischemia injury. Transient receptor potential vanilloid 4 (TRPV4) can be activated by multiple stimuli that may happen during stroke. The present study evaluated the effect of TRPV4 activation on NMDA-activated current (INMDA) and that of blocking TRPV4 on brain injury after focal cerebral ischemia in mice. We herein report that activation of TRPV4 by 4α-PDD and hypotonic stimulation increased INMDA in hippocampal CA1 pyramidal neurons, which was sensitive to TRPV4 antagonist HC-067047 and NMDAR antagonist AP-5, indicating that TRPV4 activation potentiates NMDAR response. In addition, the increase in INMDA by hypotonicity was sensitive to the antagonist of NMDAR NR2B subunit, but not of NR2A subunit. Furthermore, antagonists of calcium/calmodulin-dependent protein kinase II (CaMKII) significantly attenuated hypotonicity-induced increase in INMDA, while antagonists of protein kinase C or casein kinase II had no such effect, indicating that phosphorylation of NR2B subunit by CaMKII is responsible for TRPV4-potentiated NMDAR response. Finally, we found that intracerebroventricular injection of HC-067047 after 60 min middle cerebral artery occlusion reduced the cerebral infarction with at least a 12 h efficacious time-window. These findings indicate that activation of TRPV4 increases NMDAR function, which may facilitate glutamate excitotoxicity. Closing TRPV4 may exert potent neuroprotection against cerebral ischemia injury through many mechanisms at least including the prevention of NMDAR-mediated glutamate excitotoxicity.
TRPV4; NMDA receptor; NR2B subunit; phosphorylation; excitotoxicity; cerebral ischemia
Irritable bowel syndrome (IBS) is characterized by chronic visceral hyperalgesia (CVH) that manifested with persistent or recurrent abdominal pain and altered bowel movement. However, the pathogenesis of the CVH remains unknown. The aim of this study was to investigate roles of endogenous hydrogen sulfide (H2S) producing enzyme cystathionine beta-synthetase (CBS) and p65 nuclear factor-kappa B subunits in CVH.
CVH was induced by neonatal maternal deprivation (NMD) in male rats on postnatal days 2–15 and behavioral experiments were conducted at the age of 7–15 weeks. NMD significantly increased expression of CBS in colon-innervating DRGs from the 7th to 12th week. This change in CBS express is well correlated with the time course of enhanced visceromoter responses to colorectal distention (CRD), an indicator of visceral pain. Administration of AOAA, an inhibitor of CBS, produced a dose-dependent antinociceptive effect on NMD rats while it had no effect on age-matched healthy control rats. AOAA also reversed the enhanced neuronal excitability seen in colon-innervating DRGs. Application of NaHS, a donor of H2S, increased excitability of colon-innervating DRG neurons acutely dissociated from healthy control rats. Intrathecal injection of NaHS produced an acute visceral hyperalgesia. In addition, the content of p65 in nucleus was remarkably higher in NMD rats than that in age-matched controls. Intrathecal administration of PDTC, an inhibitor of p65, markedly reduced expression of CBS and attenuated nociceptive responses to CRD.
The present results suggested that upregulation of CBS expression, which is mediated by activation of p65, contributes to NMD-induced CVH. This pathway might be a potential target for relieving CVH in patients with IBS.
Dorsal root ganglion; Neonatal maternal deprivation; Chronic visceral pain; Hydrogen sulfide; Nuclear factor kappa B
Supplement use among cancer patients is high, and folic acid intake in particular may adversely affect the progression of colorectal cancer. Few studies have evaluated the use of folic acid-containing supplements (FAS) and its predictors in colorectal cancer patients.
To assess the use of FAS, change in use, and its predictors after colorectal cancer diagnosis.
We used logistic regression models to investigate predictors of FAS use and its initiation after colorectal cancer diagnosis in 1,092 patients recruited through the Colon Cancer Family Registry (C-CFR).
The prevalence of FAS use was 35.4% before and 55.1% after colorectal cancer diagnosis (p=0.004). Women were more likely than men to use FAS after diagnosis (OR 1.47, 95% CI 1.14-1.89), as were those consuming more fruit (ptrend<0.0001) or vegetables (ptrend=0.001), and US residents (p<0.0001). Less likely to use FAS after diagnosis were non-white patients (OR 0.66, 95% CI 0.45-0.97), current smokers (OR 0.67, 95% CI 0.46-0.96), and those with higher meat intake (ptrend=0.03). Predictors of FAS initiation after diagnosis were generally similar to those of FAS use after diagnosis, though associations with race and vegetable intake were weaker and those with exercise stronger.
Our analysis showed substantial increases in the use of folic acid-containing supplements after diagnosis with colorectal cancer, with use or initiation more likely among women, Caucasians, U.S. residents, and those with a health-promoting lifestyle.
Studies of cancer prognosis that rely on pre-diagnostic exposure information may result in substantial misclassification.
Neutrophils, in response to a chemoattractant gradient, undergo dynamic F actin remodeling, a process important for their directional migration or chemotaxis. However, signaling mechanisms for chemoattractants to regulate the process are incompletely understood. Here, we characterized chemoattractant-activated signaling mechanisms that regulate cofilin dephosphorylation and actin cytoskeleton reorganization and are critical for neutrophil polarization and chemotaxis. In neutrophils, chemoattractants induced phosphorylation and inhibition of GSK3 via both PLCβ-PKC and PI3Kγ-AKT pathways, leading to the attenuation of GSK3-mediated phosphorylation and inhibition of the cofilin phosphatase slingshot2 and an increase in dephosphorylated, active cofilin. The relative contribution of this GSK3-mediated pathway to neutrophil chemotaxis regulation depended on neutrophil polarity preset by integrin-induced polarization of PIP5K1C. Therefore, our study characterizes a signaling mechanism for chemoattractant-induced actin cytoskeleton remodeling and elucidates its context-dependent role in regulating neutrophil polarization and chemotaxis.
Neutrophil; Chemotaxis; polarization; Chemoattractant signaling; Slingshot; PLC; GSK3
With the progress of nanotechnology, one frequently has to model biological macromolecules simultaneously with nano-objects. However, the atomic structures of the nano objects are typically not available or they are solid state entities. Because of that, the researchers have to investigate such nano systems by generating models of the nano objects in a manner that the existing software be able to carry the simulations. In addition, it should allow generating composite objects with complex shape by combining basic geometrical figures and embedding biological macromolecules within the system.
Here we report the Protein Nano-Object Integrator (ProNOI) which allows for generating atomic-style geometrical objects with user desired shape and dimensions. Unlimited number of objects can be created and combined with biological macromolecules in Protein Data Bank (PDB) format file. Once the objects are generated, the users can use sliders to manipulate their shape, dimension and absolute position. In addition, the software offers the option to charge the objects with either specified surface or volumetric charge density and to model them with user-desired dielectric constants. According to the user preference, the biological macromolecule atoms can be assigned charges and radii according to four different force fields: Amber, Charmm, OPLS and PARSE. The biological macromolecules and the atomic-style objects are exported as a position, charge and radius (PQR) file, or if a default dielectric constant distribution is not selected, it is exported as a position, charge, radius and epsilon (PQRE) file. As illustration of the capabilities of the ProNOI, we created a composite object in a shape of a robot, aptly named the Clemson Robot, whose parts are charged with various volumetric charge densities and holds the barnase-barstar protein complex in its hand.
The Protein Nano-Object Integrator (ProNOI) is a convenient tool for generating atomic-style nano shapes in conjunction with biological macromolecule(s). Charges and radii on the macromolecule atoms and the atoms in the shapes are assigned according to the user’s preferences allowing various scenarios of modeling. The default output file is in PQR (PQRE) format which is readable by almost any software available in biophysical field. It can be downloaded from: http://compbio.clemson.edu/downloadDir/ProNO_integrator.tar.gz
Biological macromolecules; Electrostatic calculations; Molecular modeling; Nano technology; DelPhi; Poisson-Boltzmann equation
A Genome-wide association study (GWAS) identified significant association between variants in MEIS1, BTBD9, and MAP2K5/SKOR1 and restless legs syndrome (RLS). However, many independent replication studies are needed to unequivocally establish a valid genotype-phenotype association across various populations. To further validate the GWAS findings, we investigated three variants, rs2300478 in MEIS1, rs9357271 in BTBD9 and rs1026732 in MAP2K5/SKOR1 in 38 RLS families and 189 RLS patients/560 controls from the U.S. for their association with RLS.
Both family-based and population-based case-control association studies were carried out.
The family-based study showed that SNP rs1026732 in MAP2K5/SKOR1 was significantly associated with RLS (P=0.01). Case-control association studies showed significant association between all three variants and RLS (P=0.0001/OR=1.65, P=0.0021/OR=1.59 and P=0.0011/OR=1.55 for rs2300478, rs9357271 and rs1026732, respectively).
Variants in MEIS1, BTBD9 and MAP2K5/SKOR1 confer a significant risk of RLS in a U.S. population.
restless legs syndrome (RLS); Genome-wide association studies (GWAS); single nucleotide polymorphisms (SNP); MEIS1; BTBD; MAP2K5/SKOR1
Our objective is to assess the incidence of cardiac and intraspinal abnormities in Chinese congenital scoliosis (CS) patients and to study the relationship between the associated abnormities and the different CS types. Five-hundred and thirty-nine consecutive Chinese patients with CS were retrospectively studied, and the records of echocardiography, plain radiograph of the entire spine, magnetic resonance imaging of the entire spine and/or myelogram were reviewed. The results indicated that the incidence of cardiac and intraspinal abnormities in CS patients was 14.1 and 24.5%, respectively. There was no difference in the incidence of associated cardiac and intraspinal abnormities in different CS types (P > 0.05). The most common cardiac abnormities in CS patients was mitral valve prolapse, which was followed by congenital heart diseases, including atrial septal defect, ventricular septal defect, bicuspid aortic valve and patent ductus ateriosus. The cardiac abnormities were not likely to be concurrent with intraspinal abnormities in CS patients (P = 0.04). The intraspinal abnormities were more common in female and older patients (all P < 0.05). One or more abnormities mentioned above could be found in 36.8% CS patients and were more likely to be found in female patients (P < 0.01). We concluded that CS is not a simple abnormity, due to the high incidence of associated deformities of other organs, comprehensive assessment was strongly recommended before the surgical correction for CS patients.
Congenital scoliosis; Associated abnormities; Chinese population
Due to shared transmission routes, hepatitis C virus (HCV) infection is highly prevalent among people infected with human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is associated with hepatotoxicity, leading to the negative effects on patients with HIV/HCV co-infection. In order to provide valuable information for HCV management in this particular population, we investigated the HCV genotypes in HIV-infected individuals from Henan and Guangxi, the two provinces with the most HIV-infected cases in China.
Individuals, who acquired HIV infection through various risk routes, were recruited from Henan and Guangxi. Test of antibodies against HCV (anti-HCV) was conducted, and detection of HCV RNA was performed by PCR amplification. HCV subtypes were determined by direct sequencing of amplicons, followed by phylogenetic analysis.
We recruited a total of 1,112 HIV-infected people in this present study. Anti-HCV was detected from 218 (50.1%) patients from Henan and 81 (12.0%) patients from Guangxi, respectively. The highest prevalence of HIV/HCV co-infection was observed from FBDs (former blood donors) (87.2%) in Henan and IDUs (intravenous drug users) (81.8%) in Guangxi, respectively. The seroprevalence rate of HCV among people with sexual contact was significantly higher in Henan than in Guangxi (18.7% vs. 3.5%, P<0.05). The positive rate of HCV RNA in Henan and Guangxi was 30.6% (133/435) and 11.2% (76/677), respectively. Moreover, we found that 20 anti-HCV negative samples were HCV positive by PCR amplification. HCV subtype 1b (52.7%) was predominant in Henan, followed by subtype 2a (41.9%). The most frequently detected subtypes in Guangxi were 6a (35.6%) and 3b (32.9%).
The HCV genotype distributions were different in HIV-infected people from Henan and Guangxi. HIV/HCV co-infection was not only linked to the transmission routes, but also associated with the geographic position.
In acupuncture brain imaging trials, there are many non-acupuncture factors confounding the neuronal mapping. The modality of the placebo, subjects’ psychological attitude to acupuncture and their physical state are the three most confounding factors.
To obtain more precise and accurate cerebral fMRI mapping of acupuncture.
Design and Setting
A 2×2 randomized, controlled, participant-blinded cross-over factorial acupuncture trial was conducted at Xuanwu Hospital in Beijing, China.
Forty-one college students with myopia were recruited to participate in our study and were allocated randomly to four groups, Group A, Group B, Group C and Group D.
Group A received real acupuncture (RA) and treatment instruction (TI); Group B received RA and non-treatment instruction (NI); Group C received sham acupuncture (SA) and TI; Group D received SA and NI.
Stimulation at LR3 activated some areas of the visual cortex, and the cerebral response to non-acupuncture factors was complex and occurred in multiple areas.
The results provide more evidence regarding the credibility of acupuncture therapy and suggest that more precise experimental designs are needed to eliminate sources of bias in acupuncture controlled trials and to obtain sound results.
Mutations associated with HIV drug resistance have been extensively characterized at the HIV-1 polymerase domain, but more studies have verified that mutations outside of the polymerase domain also results in resistance to antiviral drugs. In this study, mutations were identified in 354 patients experiencing antiretroviral therapy (ART) failure and in 97 naïve-therapy patients. Mutations whose impact on antiviral drugs was unknown were verified by phenotypic testing.
Pol sequences of HIV subtype B′ obtained from patients experiencing ART failure and from naïve-therapy patients were analyzed for mutations distinct between two groups. Mutations that occurred at a significantly higher frequency in the ART failure than the naïve-therapy group were submitted to the Stanford HIV Drug Resistance Database (SHDB) to analyze the correlation between HIV mutations and drug resistance. For mutations whose impact on the antiviral drug response is unknown, the site-directed mutagenesis approach was applied to construct plasmids containing the screened mutations. 50% inhibitory concentration (IC50) to AZT, EFV and NVP was measured to determine the response of the genetically constructed viruses to antiviral drugs.
7 mutations at 6 positions of the RT region, D123E, V292I, K366R, T369A, T369V, A371V and I375V, occurred more frequently in the ART failure group than the naïve-therapy group. Phenotypic characterization of these HIV mutants revealed that constructed viruses with mutations A371V and T369V exhibited dual resistance to AZT and EFV respectively, whereas the other 5 mutations showed weak resistance. Although the impact of the other six mutations on response to NVP was minimal, mutation T369V could enhance resistance to NVP.
This study demonstrated that mutations at the RT C-terminal in subtype B′ could result in resistance to RT inhibitors if the mutations occurred alone, but that some mutations could promote susceptibility to antiviral drugs.
Resting pulse rate has been observed to be associated with cardiovascular diseases. However, its association with lipid metabolic dysfunctions remains unclear, especially resting pulse rate as an indicator for identifying the risk of lipid metabolic dysfunctions. The purpose of this study was to examine the association between resting pulse rate and lipid metabolic dysfunctions, and then evaluate the feasibility of resting pulse rate as an indicator for screening the risk of lipid metabolic dysfunctions.
A cross-sectional survey was performed, and 16,926 subjects were included in this study from rural community residents aged 35–78 years. Resting pulse rate and relevant covariates were collected from a standard questionnaire. The fasting blood samples were collected and measured for lipid profile. Predictive performance was analyzed by receiver operating characteristic (ROC) curve.
A significant correlation was observed between resting pulse rate and TC (r = 0.102, P = 0.001), TG (r = 0.182, P = 0.001), and dyslipidemia (r = 0.037, P = 0.008). In the multivariate models, the adjusted odds ratios for hypercholesterolemia (from 1.07 to 1.15), hypertriglyceridemia (1.11 to 1.16), low HDL hypercholesterolemia (1.03 to 1.06), high LDL hypercholesterolemia (0.92 to 1.14), and dyslipidemia (1.04 to 1.07) were positively increased across quartiles of resting pulse rate (P for trend <0.05). The ROC curve indicated that resting pulse rate had low sensitivity (78.95%, 74.18%, 51.54%, 44.39%, and 54.22%), specificity (55.88%, 59.46%, 57.27%, 65.02%, and 60.56%), and the area under ROC curve (0.70, 0.69, 0.54, 0.56, and 0.58) for identifying the risk of hypercholesterolemia, hypertriglyceridemia, low HDL hypercholesterolemia, high LDL hypercholesterolemia, and dyslipidemia, respectively.
Fast resting pulse rate was associated with a moderate increased risk of lipid metabolic dysfunctions in rural adults. However, resting pulse rate as an indicator has limited potential for screening the risk of lipid metabolic dysfunctions.
As a major concern in public health, methicillin-resistant staphylococci (MRS) still remains one of the most prevalent pathogens that cause nosocomial infections throughout the world and has been recently labeled as a “super bug” in antibiotic resistance. Thus, surveillance and investigation on antibiotic resistance mechanisms involved in clinical MRS strains may raise urgent necessity and utmost significance. As a novel antibiotic resistance mechanism, class 1 integron has been identified as a primary source of antimicrobial resistance genes in Gram-negative organisms. However, most available studies on integrons had been limited within Gram-negative microbes, little is known for clinical Gram-positive bacteria. Based on series studies of systematic integrons investigation in hundreds of staphylococci strains during 2001–2006, this review concentrated on the latest development of class 1 integron in MRS isolates, including summary of prevalence and occurrence of class 1 integron, analysis of correlation between integron and antibiotic resistance, further demonstration of the role integrons play as antibiotic determinants, as well as origin and evolution of integron-associated gene cassettes during this study period.
Class 1 integron; Methicillin-resistance staphylococci (MRS); Antibiotic resistance; Mobile genetic element; SCCmec
Several studies identified HIV-1 recombination in some distinct areas in Yunnan, China. However, no comprehensive studies had been fulfilled in the whole province up to now. To illustrate the epidemiology and recombination form of Unique Recombinant Forms (URFs) circulating in Yunnan, 788 HIV-1 positive individuals residing in 15 prefectures of Yunnan were randomly enrolled into the study. Full-length gag and pol genes were amplified and sequenced. Maximum likelihood tree was constructed for phylogenetic analysis. Recombinant breakpoints and genomic schematics were identified with online software jpHMM. 63 (10.2%) unique recombinant strains were identified from 617 strains with subtypes. The URFs distributed significantly differently among prefectures (Pearson chi-square test, P<0.05). IDUs contained more URFs than sexual transmitted population (Pearson chi-square test, P<0.05). Two main recombinant forms were identified by considering the presence of CRF01_AE segments in full length gag-pol genes, which were B′/C and B′/C/CRF01-AE recombinants. Three clusters were identified in the ML tree which contained more than three sequences and supported by high bootstrap values. One CRF was identified. Many of URFs contained identical breakpoints. The results will contribute to our understanding on HIV recombination and provide clues to the identification of potential CRFs in China.
The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.
The title compound, C16H16N2O2, was synthesized using a novel tandem annulation reaction between 1-(1H-benzo[d]imidazol-2-yl)ethanone and ethyl (E)-4-bromobut-2-enoate under mild conditions. The dihedral angles formed by the mean plane of the five-membered imidazole ring with the dihydropyridin and benzene rings are 1.54 (9) and 1.85 (9)°, respectively.
Idiopathic membranous nephropathy (IMN) is the most common pathological type for nephrotic syndrome in adults in western countries and China. The benefits and harms of immunosuppressive treatment in IMN remain controversial.
To assess the efficacy and safety of different immunosuppressive agents in the treatment of nephrotic syndrome caused by IMN.
PubMed, EMBASE, Cochrane Library and wanfang, weipu, qinghuatongfang, were searched for relevant studies published before December 2011. Reference lists of nephrology textbooks, review articles were checked. A meta-analysis of randomized controlled trials (RCTs) meeting the criteria was performed using Review Manager.
17 studies were included, involving 696 patients. Calcineurin inhibitors had a better effect when compared to alkylating agents, on complete remission (RR 1.61, 95% CI 1.13, to 2.30 P = 0.008), partial or complete remission (effective) (CR/PR, RR 1.29, 95% CI 1.09 to 1.52 P = 0.003), and fewer side effects. Among calcineurin inhibitors, tacrolimus (TAC) was shown statistical significance in inducing more remissions. When compared to cyclophosphamide (CTX), leflunomide (LET) showed no beneficial effect, mycophenolate mofetil (MMF) showed significant beneficial on effectiveness (CR/PR, RR: 1.41, 95% CI 1.16 to 1.72 P = 0.0006) but not significant on complete remission (CR, RR: 1.38, 95% CI 0.89 to 2.13 P = 0.15).
This analysis based on Chinese adults and short duration RCTs suggested calcineurin inhibitors, especially TAC, were more effective in proteinuria reduction in IMN with acceptable side effects. Long duration RCTs were needed to confirm the long-term effects of those agents in nephrotic IMN.
A small-molecule mimetic of Smac/Diablo that specifically counters the apoptosis-inhibiting activity of IAP proteins has been shown to enhance apoptosis induced by cell surface death receptors as well as chemotherapeutic drugs. Survey of a panel of 50 human non-small-cell lung cancer cell lines has revealed, surprisingly, that roughly one-quarter of these lines are sensitive to the treatment of Smac mimetic alone, suggesting that an apoptotic signal has been turned on in these cells and is held in check by IAP proteins. This signal has now been identified as the autocrine-secreted cytokine tumor necrosis factor alpha (TNFα). In response to autocrine TNFα signaling, the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis.