Mycobacterium protein tyrosine phosphatase B (mPTPB) is essential for the survival and persistence of Mycobacterium in the host. Thus small molecule inhibitors of mPTPB are potential anti-TB agents. We developed an efficient organocatalytic multicomponent reaction (MCR) between pyrrole, formaldehyde and aniline, affording a potent and selective mPTPB inhibitor with IC50 at 1.5 µM and >50-fold specificity. Our studies provide a successful example of using organocatalysis as a discovery tool for the acquisition of PTP inhibitors.
Rice stripe virus (RSV), a tenuivirus, is transmitted by small brown planthopper (SBPH) in a persistent-propagative manner. In this study, sequential infection of RSV in the internal organs of SBPH after ingestion of virus indicated that RSV initially infected the midgut epithelium, and then progressed to the visceral muscle tissues, through which RSV spread to the entire alimentary canal. Finally, RSV spread into the salivary glands and reproductive system. During viral infection, the nonstructural protein NS4 of RSV formed cytoplasmic inclusions in various tissues of viruliferous SBPH. We demonstrated that the ribonucleoprotein particles of RSV were closely associated with NS4-specific inclusions in the body of viruliferous SBPH through a direct interaction between NS4 and nucleoprotein of RSV. Moreover, the knockdown of NS4 expression due to RNA interference induced by dsRNA from NS4 gene significantly prevented the spread of RSV in the bodies of SBPHs without a significant effect on viral replication in continuous cell culture derived from SBPH. All these results suggest that the nonstructural protein NS4 of RSV plays a critical role in viral spread by the vector insects.
Despite advances in radiation therapy, chemotherapy, and newly developed molecular targeting therapies, long-term survival after resection for patients with NSCLC remains less than 50%. We investigated factors predicting postoperative locoregional recurrences and distant metastases in patients with clinical stage I non-small-cell lung cancer (NSCLC) after surgical resection.
All patients with clinical stage I NSCLC, who underwent surgical resection between January 2002 and June 2006, were reviewed retrospectively. Multiple logistic regression analyses were used to identify independent risk factors for patients with locoregional recurrences and distant metastases.
A total of 261 patients were eligible. Overall survival was significant related to locoregional recurrences (P = 0.03) and distant metastases (P <0.001). There were significant differences of locoregional recurrence in tumor differentiation (P = 0.032) and advanced pathological stage (P = 0.002). In the group of distant metastases, there were significant differences in tumor differentiation (P = 0.035), lymphovascular space invasion (P = 0.031). Among the relationship between pattern of distant metastasis and clinicopathologic variables in patients with clinical stage I NSCLC, SUVmax (P = 0.02) and tumor size (P = 0.001) had significant differences. According to multiple logistic regression analysis, tumor differentiation is the only risk factor of postoperative outcome for locoregional recurrence and serum CEA (>3.5 ng/mL) is the predictor of distant metastasis.
Tumor differentiation and serum CEA were predictors of postoperative relapse for clinical stage I NSCLC after surgical resection. Risk factors of postoperative recurrence in patients with clinical stage I NSCLC may enable us to optimize the patient selection for postoperative adjuvant therapies or neoadjuvant treatment before surgery.
Non-small cell lung cancer; Locoregional recurrence; Distant metastasis; Carcinoembryonic antigen
The importance of protein tyrosine phosphatases (PTPs) in the regulation of cellular signaling is well established. Malfunction of PTP activity is also known to be associated with cancer, metabolic syndromes, autoimmune disorders, neurodegenerative and infectious diseases. However, a detailed understanding of the roles played by the PTPs in normal physiology and in pathogenic conditions has been hampered by the absence of PTP-specific small molecule agents. In addition, the therapeutic benefits of modulating this target class are underexplored due to lack of suitable chemical probes. Potent and specific PTP inhibitors could significantly facilitate functional analysis of the PTPs in complex cellular signal transduction pathways and may constitute valuable therapeutics in the treatment of several human diseases. We will highlight the current challenges and opportunities in developing PTP-specific small molecule agents. We will also review available selective small molecule inhibitors developed for a number of PTPs, including PTP1B, TC-PTP, SHP2, Lyp, HePTP, CD45, PTPβ, PTPγ, PTPRO, VHR, MKP-1, MKP-3, Cdc25, YopH, mPTPA, and mPTPB.
Tyrosine phosphorylation; protein tyrosine phosphatases; small molecule inhibitors; chemical probes; potency and specificity; high throughput screening; structure-based design; virtual screening; fragment-based focus library
The acetylcholinesterase of Lepidoptera insects is encoded by two genes, ace1 and ace2. The expression of the ace1 gene is significantly higher than that of the ace2 gene, and mutations in ace1 are one of the major reasons for pesticide resistance in insects. In order to investigate the effects of the mutations in ace1’s characteristic sites on pesticide resistance, we generated mutations for three amino acids using site-directed mutagenesis, which were Ala(GCG)303Ser(TCG), Gly(GGA)329Ala(GCA) and Leu (TCT)554Ser(TTC). The Baculovirus expression system was used for the eukaryotic expression of the wild type ace1 (wace1) and the mutant ace1 (mace1). SDS-PAGE and Western blotting were used to detect the targeting proteins with expected sizeof about 76 kDa. The expression products were purified for the determination of AChE activity and the inhibitory effects of physostigmine and phoxim. We observed no significant differences in the overall activity of the wild type and mutant AChEs. However, with 10 min of physostigmine (10 μM) inhibition, the remaining activity of the wild type AChE was significantly lower than that of the mutant AChE. Ten min inhibition with 33.4 μM phoxim also resulted in significantly lower remaining activity of the wild type AChE than that of the mutant AChE. These results indicated that mutations for the three amino acids reduced the sensitivity of AChE to physostigmine and phoxim, which laid the foundation for future in vivo studies on AChE’s roles in pesticide resistance.
Bombyx mori; Acetylcholinesterase; Gene mutation
Recently, leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1), a negative regulator of EGFR, was discovered is a novel agent for suppressing bladder cancer. The aim of this study was to investigate the impact of LRIG1 on the biological features of aggressive bladder cancer cells and the possible mechanisms of enhanced apoptosis induced by upregulation of LRIG1.
In this study, we examined the mRNA and protein expression of LRIG1 and EGFR in bladder cancers and normal bladder. Meanwhile, we overexpressed LRIG1 with adenovirus vector in T24/5637 bladder cancer cell lines, and we used real time-PCR, western blot, and co-immunoprecipitation analysis in order to examine the effects of LRIG1 gene on EGFR. Furthermore, we evaluate the impact of LRIG1 gene on the function of human bladder cancer cells and EGFR signaling.
The expression of LRIG1 was decreased, while the expression of EGFR was increased in the majority of bladder cancer, and the ratio of EGFR/LRIG1 was increased in tumors versus normal tissue. We found that upregulation of LRIG1 induced cell apoptosis and cell growth inhibition, and further reversed invasion in bladder cancer cell lines in vitro by inhibiting phosphorylation of downstream MAPK and AKT signaling pathway.
Taken together, our findings provide us with an insight into LRIG1 function, and we conclude that LRIG1 evolved in bladder cancer as a rare feedback negative attenuator of EGFR, thus could offer a novel therapeutic target to treat patients with bladder cancer.
LRIG1; EGFR; Apoptosis; Invasion; Bladder cancer
RNAs fold into intricate structures that are determined by specific base pairing interactions encoded within their primary sequences. Recently, a number of transcriptome-wide studies have suggested that RNA secondary structure is a potent cis-acting regulator of numerous post-transcriptional processes in viruses and eukaryotes. However, the need for experimentally-based structure determination methods has not been well addressed. Here, we show that the regulatory significance of Arabidopsis RNA secondary structure is revealed specifically through high-throughput, sequencing-based, structure mapping data, not by computational prediction. Additionally, we find that transcripts with similar levels of secondary structure in their UTRs (5' or 3') or CDS tend to encode proteins with coherent functions. Finally, we reveal that portions of mRNAs encoding predicted protein domains are significantly more structured than those specifying inter-domain regions. In total, our findings show the utility of high-throughput, sequencing-based, structure-mapping approaches and suggest that mRNA folding regulates protein maturation and function.
RNA genomics; mRNA secondary structure; protein domains; post-transcriptional regulation
The purpose of this study was to develop novel nanoscale biosensors using titania nanotubes (TNTs) made by anodization. Titania nanotubes were produced on pure titanium sheets by anodization at room temperature. In this research, the electrolyte composition ethylene glycol 250 mL/NH4F 1.5 g/DI water 20 mL was found to produce the best titania nanotubes array films for application in amperometric biosensors. The amperometric results exhibit an excellent linearity for uric acid (UA) concentrations in the range between 2 and 14 mg/dL, with 23.3 (μA·cm−2)·(mg/dL)−1 UA sensitivity, and a correlation coefficient of 0.993. The glucose biosensor presented a good linear relationship in the lower glucose concentration range between 50 and 125 mg/dL, and the corresponding sensitivity was approximately 249.6 (μA·cm−2)·(100 mg/dL)−1 glucose, with a correlation coefficient of 0.973.
titania nanotubes (TNTs); amperometry; glucose; uric acid (UA)
Persistent infection of the mouse central nervous system (CNS) with mouse hepatitis virus (MHV) induces a demyelinating disease pathologically similar to multiple sclerosis and is therefore used as a model system. There is little information regarding the host factors that correlate with and contribute to MHV-induced demyelination. Here, we detail the genes and pathways associated with MHV-induced demyelinating disease in the spinal cord. High-throughput sequencing of the host transcriptome revealed that demyelination is accompanied by numerous transcriptional changes indicative of immune infiltration as well as changes in the cytokine milieu and lipid metabolism. We found evidence that a Th1-biased cytokine/chemokine response and eicosanoid-derived inflammation accompany persistent MHV infection and that antigen presentation is ongoing. Interestingly, increased expression of genes involved in lipid transport, processing, and catabolism, including some with known roles in neurodegenerative diseases, coincided with demyelination. Lastly, expression of several genes involved in osteoclast or bone-resident macrophage function, most notably TREM2 and DAP12, was upregulated in persistently infected mouse spinal cord. This study highlights the complexity of the host antiviral response, which accompany MHV-induced demyelination, and further supports previous findings that MHV-induced demyelination is immune-mediated. Interestingly, these data suggest a parallel between bone reabsorption by osteoclasts and myelin debris clearance by microglia in the bone and the CNS, respectively. To our knowledge, this is the first report of using an RNA-seq approach to study the host CNS response to persistent viral infection.
Although electrocardiogram (ECG) fluctuates over time and physical activity, some of its intrinsic measurements serve well as biometric features. Considering its constant availability and difficulty in being faked, the ECG signal is becoming a promising factor for biometric authentication. The majority of the currently available algorithms only work well on healthy participants. A novel normalization and interpolation algorithm is proposed to convert an ECG signal into multiple template cycles, which are comparable between any two ECGs, no matter the sampling rates or health status. The overall accuracies reach 100% and 90.11% for healthy participants and cardiovascular disease (CVD) patients, respectively.
AIM: To apply a new, integrated technique for visualizing bacterial genomes to identify novel pathogenicity islands in Helicobacter pylori (H. pylori).
METHODS: A genomic barcode imaging method (converting frequency matrices to grey-scale levels) was designed to visually distinguish origin-specific genomic regions in H. pylori. The complete genome sequences of the six H. pylori strains published in the National Center for Biotechnological Information prokaryotic genome database were scanned, and compared to the genome barcodes of Escherichia coli (E. coli) O157:H7 strain EDL933 and a random nucleotide sequence. The following criteria were applied to identify potential pathogenicity islands (PAIs): (1) barcode distance distinct from that of the general background; (2) length greater than 10000 continuous base pairs; and (3) containing genes with known virulence-related functions (as determined by PfamScan and Blast2GO).
RESULTS: Comparison of the barcode images generated for the 26695, HPAG1, J99, Shi470, G27 and P12 H. pylori genomes with those for the E. coli and random sequence controls revealed that H. pylori genomes contained fewer anomalous regions. Among the H. pylori-specific continuous anomalous regions (longer than 20 kbp in each strain’s genome), two fit the criteria for identifying candidate PAIs. The bioinformatic-based functional analyses revealed that one of the two anomalous regions was the known pathogenicity island cag-PAI, this finding also served as proof-of-principle for the utility of the genomic barcoding approach for identifying PAIs, and characterized the other as a novel PAI, which was designated as tfs3-PAI. Furthermore, the cag-PAI and tfs3-PAI harbored genes encoding type IV secretion system proteins and were predicted to have potential for functional synergy.
CONCLUSION: Genomic barcode imaging represents an effective bioinformatic-based approach for scanning bacterial genomes, such as H. pylori, to identify candidate PAIs.
Helicobacter pylori; Genome analysis; Pathogenicity islands; Genomic bar coding
To investigate the prevalence of occult HBV infection (OBI) among children and to characterize virology of occult HBV, we conducted an epidemiological survey.
186 HB-vaccinated infants born to HBsAg-positive mothers were included in the study. Serological tests for HBV markers were performed using commercial ELISA kits. Real-time quantitative PCR and nested PCR were used to detect HBV DNA. PCR products of the C and pre-S/S regions were sequenced and analyzed.
1.61% (3/186) infants were HBsAg positive, and 4.92% (9/183) infants were considered as occult infection. The viral load of mothers was associated with occult infection (P = 0.020). Incomplete three-dose injections of HB vaccine was associated with HBV infection (P = 0.022). Six OBI infants were positive for anti-HBs, but their titers were not greater than 100 mIU/mL. Seven isolated HBV pre-S/S sequences were obtained from nine OBI infants. Three of the sequences were genotype C, and four of the sequences were genotype C/D. Escape mutation S143L was found in the four sequences of genotype C/D. All seven sequences lacked G145R and other escape mutation in S region.
Occult HBV infection was detected in anti-HBs positive infants born to HBsAg-positive mothers in China. Occult infection was associated with absent anti-HBs or with low anti-HBs level, high maternal viral loads and escape mutations in the S gene.
The discovery of microRNAs (miRNAs) provides a new and powerful tool for studying the mechanisms, diagnosis and treatments of cancer. In this study, we employed AFFX miRNA expression chips to search for miRNAs that may be aberrantly expressed in gastric cancer tissues and to investigate the potential roles that miRNAs may play in the development and progression of gastric cancer. 14 miRNAs were found to be down-regulated and 2 miRNAs up-regulated in gastric cancer tissues compared to the normal gastric tissues. Among the aberrantly expressed miRNAs, miR-574-3p was selected to further study its expression features and functional roles. Interestingly, the reduced expression of miR-574-3p occurred mainly in the early stages of gastric cancer or in cancers with high level of differentiation, suggesting that it can be used as a marker for a mild case of gastric cancer. Functional study revealed that cell proliferation, migration and invasion were significantly inhibited in miR-574-3p-transfected gastric cancer SGC7901 cells. Computational prediction and experimental validation suggest that Cullin2 may be one of the targets of miR-574-3p. Overall our study suggests that the aberrantly expressed miRNAs may play regulatory and functional roles in the development and progression of gastric cancer.
microRNA; gastric cancer; target gene; proliferation; invasion
Polyunsaturated fatty acids (PUFAs) have positive effect on the regulation of plasma lipids. But the mechanism for them to modulate lipid homeostasis in macrophage is still unclear. In this study, we employed PUFA to pretreat macrophages and evaluated the variations of lipid droplet (LD) content, lipid composition, and expressions of LD-associated genes in macrophage-derived foam cells.
THP-1-derived macrophages or human peripheral blood monocyte-derived macrophages were pre-treated with four non-esterified fatty acids (NEFAs) separately: saturated fatty acid (SFA)-palmitic acid (PA), monounsaturated fatty acids (MUFAs)-oleic acid (OA), PUFAs-linoleic acid (LA) and eicosapentaenoic acid (EPA). Intracellular lipid content and cholesterol efflux were analyzed in THP-1 macrophage-derived foam cells. Related gene expressions were detected by quantitative real-time PCR.
PUFA pre-treatment reduced cholesterol content in foam cells and increased cholesterol efflux to lipid-free apoAI in conditioned medium compared with PA or OA group. Cell death-inducing DFF45 like effector (CIDE) and Perilipin-Adipophilin-TIP47 (PAT) family members, as LD-associated proteins, showed specific gene expression profiles after PUFA pre-treatment. These results may help to explain the process of lipid metabolism within foam cells.
PUFA (LA or EPA) had a potential protective effect against cholesterol accumulation. The specific expressions of CIDE and PAT genes may provide clues to explore the protective mechanism of PUFA in foam cells.
Polyunsaturated fatty acid; CIDE; PAT; Lipid metabolism; Atherosclerosis
We report here the first novel HIV-1 second-generation intercirculating recombinant form 61_BC (inter-CRF61_BC), composed of two established CRFs (CRF07_BC and CRF08_BC), in China. CRF61_BC is the first CRF found among the heterosexual population in two different regions in China, suggesting the increasing significance of heterosexual transmission of HIV in China.
Adeno-associated virus (AAV) is a common vector utilized in gene therapy. The NIH/3T3 cell line, which is a potential induced pluripotent stem (iPS) cell type, was identified to be a less-permissive cell type to AAV due to its defective endosomal processing. Ultrasound-targeted microbubble destruction (UTMD) enhanced the gene transduction of AAV in permissive cells. However, there are no data concerning UTMD enhancement in less-permissive cells, and the exact mechanism of UTMD enhancement in cellular uptake is unclear. Greater knowledge concerning the rate-limiting steps in NIH/3T3 cells would aid in the elucidation of the mechanism of UTMD enhancement in the gene transduction of AAV. In the present study, UTMD enhanced the gene transduction of AAV in NIH/3T3 cells, suggesting that UTMD-enhanced AAV-mediated gene transduction may be beneficial for gene therapy in iPS cells. The dose dependence of UTMD enhancement indicated that mechanisms other than sonoporation were involved in the cellular uptake of AAV. However, UTMD did not greatly increase the gene transduction of AAV in NIH/3T3 cells. Additionally, the similar degree of enhancement in the two cell types resulted in no correlation between UTMD and endosomal processing. Future studies on UTMD-mediated AAV transduction in other non- or less-permissive cell types may aid in elucidating the exact mechanism of UTMD enhancement in cellular uptake.
ultrasonics; microbubbles; adeno-associated virus; induced pluripotent stem cells; sonoporation
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis). The annotation of functional genome and signaling network in M. tuberculosis are still not systematic. Essential gene modules are a collection of functionally related essential genes in the same signaling or metabolic pathway. The determination of essential genes and essential gene modules at genomic level may be important for better understanding of the physiology and pathology of M. tuberculosis, and also helpful for the development of drugs against this pathogen. The establishment of genomic operon database (DOOR) and the annotation of gene pathways have felicitated the genomic analysis of the essential gene modules of M. tuberculosis.
Bibliometric approach has been used to perform a High-throughput screen for essential genes of M. tuberculosis strain H37Rv. Ant colony algorithm were used to identify the essential genes in other M. tuberculosis reference strains. Essential gene modules were analyzed by operon database DOOR. The pathways of essential genes were assessed by Biocarta, KEGG, NCI-PID, HumanCyc and Reactome. The function prediction of essential genes was analyzed by Pfam.
A total approximately 700 essential genes were identified in M. tuberculosis genome. 40% of operons are consisted of two or more essential genes. The essential genes were distributed in 92 pathways in M. tuberculosis. In function prediction, 61.79% of essential genes were categorized into virulence, intermediary metabolism/respiration,cell wall related and lipid metabolism, which are fundamental functions that exist in most bacteria species.
We have identified the essential genes of M. tuberculosis using bibliometric approach at genomic level. The essential gene modules were further identified and analyzed.
Mycobacterium tuberculosis; Essential gene modules; Operon; Pathway
The generally accepted mechanism for ultrasound targeted microbubble destruction (UTMD) to enhance drug and gene delivery is through sonoporation. However, passive uptake of adeno-associated virus (AAV) into cells following sonoporation does not adequately explain observations of enhanced transduction by UTMD. This study investigated alternative mechanisms of UTMD enhancement in AAV delivery. UTMD significantly enhanced transduction efficiency of AAV in a dose-dependent manner. UTMD stimulated a persistent uptake of AAV into the cytoplasm and nucleus. This phenomenon occurred over several hours, suggesting that some viral particles are endocytosed by cells rather than exclusively passing through pores created by sonoporation. Additionally, UTMD enhanced clathrin expression and accumulation at the plasma membrane suggesting greater clathrin-mediated endocytosis following UTMD. Transmission electron microscopy (TEM) revealed that UTMD stimulated formation of clathrin-coated pits (CPs) and uncoated pits (nCPs). Furthermore, inhibition of clathrin-mediated endocytosis partially blocked the enhancement of AAV uptake following UTMD. The results of this study implicate endocytosis as a mechanism that contributes to UTMD-enhanced AAV delivery.
ultrasound; microbubbles; endocytosis; adeno-associated virus; sonoporation
Gastric cancer is one of the most common malignant tumors in the world. Finding effective diagnostic biomarkers in urine or serum would represent the most ideal solution to detecting gastric cancer during annual physical examination. This study was to evaluate the potential of endothelial lipase (EL) as a urinary biomarker for diagnosis of gastric cancer.
The expression levels of EL was measured using Western blotting and immunohistochemical staining experiments on (tissue, serum, and urine) samples of gastric cancer patients versus healthy people. We also checked the EL levels in the urine samples of other cancer types (lung, colon and rectum cancers) and benign lesions (gastritis and gastric leiomyoma) to check if EL was specific to gastric cancer.
We observed a clear separation between the EL expression levels in the urine samples of 90 gastric cancer patients and of 57 healthy volunteers. It was approximately 9.9 fold average decrease of the EL expression levels in the urine samples of gastric cancer compared to the healthy controls (P <0.0001), achieving a 0.967 AUC value for the ROC (receiver operating characteristic) curve, demonstrating it’s highly accurate as a diagnostic marker for gastric cancer. Interestingly, the expression levels of EL in tissue and serum samples were not nearly as discriminative as in urine samples (P = 0.90 and P = 0.79). In immunohistochemical experiments, positive expression of the EL protein was found in 67% (8/12) of gastric adjacent noncancerous and in 58% (7/12) of gastric cancer samples. There was no significant statistical in the expression levels of this protein between the gastric cancer and the matching noncancerous tissues (P =0.67).
The urinary EL as a highly accurate gastric cancer biomarker that is potentially applicable to the general screening with high sensitivity and specificity.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4527331618757552
Endothelial lipase; Biomarker; Gastric cancer; Diagnosis
Protein tyrosine phosphatases (PTPs) constitute a large and structurally diverse family of signaling enzymes that control the cellular levels of protein tyrosine phosphorylation. Malfunction of PTP activity has significant implications in many human diseases, and the PTP protein family provides an exciting array of validated diabetes/obesity (PTP1B), oncology (SHP2), autoimmunity (Lyp), and infectious disease (mPTPB) targets. However, despite the fact that PTPs have been garnering attention as novel therapeutic targets, they remain largely an untapped resource. The main challenges facing drug developers by the PTPs are inhibitor specificity and bioavailability. Work over the last ten years has demonstrated that it is feasible to develop potent and selective inhibitors for individual members of the PTP family by tethering together small ligands that can simultaneously occupy both the active site and unique nearby peripheral binding sites. Recent results with the bicyclic salicylic acid pharmacophores indicate that the new chemistry platform may provide a potential solution to overcome the bioavailability issue that has plagued the PTP drug discovery field for many years. Structural analysis of PTP-inhibitor complexes reveals molecular determinants important for the development of more potent and selective PTP inhibitors, thus offering hope in the medicinal chemistry of a largely unexploited protein class with a wealth of attractive drug targets.
protein tyrosine phosphatases; therapeutic target; salicylic acid; inhibitor specificity and bioavailability; combinatorial chemistry
Information about the prevalence of serious mental illness (SMI) among adults or serious emotional disturbance (SED) among youth in small domains such as counties, states, or schools is valuable for mental health policy planning purposes, but prohibitively expensive to collect with semi-structured surveys. Commonly used synthetic estimation methods yield imprecise estimates. An improved method is described here that combines information about socio-demographic covariates with screening scale scores obtained from a sample of individuals, using a prediction equation derived from a Bayesian multilevel regression model with bivariate outcomes fitted to a larger population survey. This method is illustrated using K6 screening scale scores to predict school-level prevalence of SED in the sample of 282 schools that participated in the National Comorbidity Survey Replication Adolescent Supplement. Respondents completed a diagnostic interview that was used to define DSM-IV SED. SED prevalence varied significantly across schools and was strongly correlated with aggregate K6 scores (ρ = .70). Calculations suggest that near-maximum precision of school-level SED prevalence estimates could be attained with K6 samples of 200 students per school. This modeling approach holds great promise for generating accurate estimates of SMI/SED in small-area planning units based on K6 scores collected in ongoing health tracking surveys.
K6 screening scale; small-area estimation; psychiatric epidemiology; serious emotional disturbance (SED)
To explore the feasibility of using Internet outreach to encourage men who have sex with men (MSM) to get tested for HIV at voluntary counseling and testing (VCT) clinics in Beijing and Urumqi, China.
From June to August 2007, two volunteers contacted MSM using instant messaging, online chat rooms, mobile phone, and e-mail (active recruitment). Banners with study information were put at the front pages of three major Chinese gay websites (passive recruitment). Those contacted were offered a modest financial incentive to seek HIV testing at existing VCT clinics. Those who subsequently sought HIV testing services at VCT clinics and provided informed consent completed a questionnaire and a blood draw to test for HIV and syphilis.
A total of 3,332 MSM were contacted and 429 attended VCT clinics. One out of every 4 men that were recruited through instant messaging actually went for HIV testing, while the recruitment yields for online gay chat rooms, mobile phone contact, and email were 1∶6, 1∶10, and 1∶140, respectively. The majority of participants (80%, 317/399) reported being motivated to seek HIV testing out of concern for their health, and only 3% (11/399) reported being motivated by the financial incentive. Active recruitment tend to recruit MSM who are younger (X2 = 11.400, P = 0.001), never tested for HIV (X2 = 4.281, P = 0.039), tested less often (X2 = 5.638, P = 0.018).
Internet outreach is a promising way to encourage MSM to seek HIV testing at existing VCT clinics. Active recruitment can target MSM who are younger, never tested for HIV and tested less often.
Mast cells require KIT receptor tyrosine kinase signaling for development and survival. Here, we report that SH2 domain-containing phosphatase 2 (SHP2) signaling downstream of KIT is essential for mast cell survival and homeostasis in mice. Using a novel mouse model with shp2 deletion within mature mast cells (MC-shp2 knockout [KO]), we find that SHP2 is required for the homeostasis of connective tissue mast cells. Consistently with the loss of skin mast cells, MC-shp2 KO mice fail to mount a passive late-phase cutaneous anaphylaxis response. To better define the phenotype of shp2-deficient mast cells, we used an inducible shp2 knockout approach in bone marrow-derived mast cells (BMMCs) or cultured peritoneal mast cells and found that SHP2 promotes mast cell survival. We show that SHP2 promotes KIT signaling to extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase and downregulation of the proapoptotic protein Bim in BMMCs. Also, SHP2-deficient BMMCs failed to repopulate mast cells in mast cell-deficient mice. Silencing of Bim partially rescued survival defects in shp2-deficient BMMCs, consistent with the importance of a KIT → SHP2 → Ras/ERK pathway in suppressing Bim and promoting mast cell survival. Thus, SHP2 is a key node in a mast cell survival pathway and a new potential therapeutic target in diseases involving mast cells.
Consumption of functional foods for lowering serum cholesterol has globally gained acceptance by the general public. Turtle jelly (TJ), also called gui-ling-gao, is a popular traditional functional food in southern China. The hypocholesterolemic effect of consuming TJ was investigated in rats fed with normal diet, high-cholesterol diet or high-cholesterol diet supplemented with simvastatin (3 mg/kg bw per day, p.o.) or TJ (3.3 or 10 mL/kg bw per day, p.o.) for 30 days. TJ markedly reversed the increased serum total cholesterol, increased high-density lipoprotein, and decreased high-density lipoprotein induced by hypercholesterolemic diet with a dose-dependent improvement on the atherogenic index. It also demonstrated good hepatoprotective function by reducing fat depositions and overall lipid contents in the liver and increasing the activities of hepatic antioxidative enzymes. The blunted nitric oxide/endothelium-mediated aortic relaxation in rats fed with hypercholesterolemic diet was partially restored after TJ consumption. It is postulated that the hypocholesterolemic effect is the primary beneficial effect given by TJ; it then leads to secondary beneficial effects such as vasoprotective and hepatoprotective functions. The results revealed that TJ could block the downregulation of LDLR and PEPCK and upregulation of PPARα mRNA and protein expressions in the livers of rats fed with hypercholesterolemic diet.
Measles remains a severe global health threat, and nearly 30 million new cases are reported annually. Although many studies have analyzed measles viruses (MV) at the epidemiologic and phylogenetic levels, no study has yet to integrate these two types of data. To this end, we isolated 16 wild-type MV strains China's Jilin province. The MV genotype H1 was the most prevalent strain. After sequencing the nucleoprotein (N) genes of these strains, a maximum clade credibility tree was constructed by the Bayesian Markov Chain Monte Carlo method using 450 MV strains from GenBank with epidemiological information. The MV N gene evolution rate was 1.127E-3. Analysis of the time of the most recent common ancestor (TMRCA) for genotypes A/B/C/G/H revealed that genotypes D and B had the largest and smallest TMRCA (45.86 and 26.63, respectively). The highest level of genetic diversity for the MV N gene occurred around the year 2000. Here in this study, we uncovered the MV genotypes circulating in China's Jilin Province and estimated the epidemiologic and phylogenetic relationship for the six different genotypes of MV.