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.
Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus Bunge, a medicinal herb used for cardiovascular diseases (CVD). In this work, we investigated the therapeutic mechanisms of AGS-IV at a network level by computer-assisted target identification with the in silico inverse docking program (INVDOCK). Targets included in the analysis covered all signaling pathways thought to be implicated in the therapeutic actions of all CVD drugs approved by US FDA. A total of 39 putative targets were identified. Three of these targets, calcineurin (CN), angiotensin-converting enzyme (ACE), and c-Jun N-terminal kinase (JNK), were experimentally validated at a molecular level. Protective effects of AGS-IV were also compared with the CN inhibitor cyclosporin A (CsA) in cultured cardiomyocytes exposed to adriamycin. Network analysis of protein-protein interactions (PPI) was carried out with reference to the therapeutic profiles of approved CVD drugs. The results suggested that the therapeutic effects of AGS-IV are based upon a combination of blocking calcium influx, vasodilation, anti-thrombosis, anti-oxidation, anti-inflammation and immune regulation.
HIV-1 integrase (IN) is a validated therapeutic target for antiviral agents. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands new structure and new mechanism IN inhibitors. Herein, we describe the design and discovery of novel IN inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75, which is essential for the HIV-1 integration as an IN cofactor. By merging the pharmacophores of salicylate and catechol, the 2,3-dihydroxybenzamide (5a) was identified as a new scaffold to inhibit the strand transfer reaction efficiently. Further structural modifications on the 2,3-dihydroxybenzamide scaffold revealed that the heteroaromatic functionality attached on the carboxamide portion and the piperidin-1-ylsulfonyl substituted at the phenyl ring are beneficial for the activity, resulting in a low micromolar IN inhibitor (5p, IC50 = 5 μM) with more than 40-fold selectivity for the strand transfer over the 3′-processing reaction. More significantly, this active scaffold remarkably inhibited the interaction between IN and LEDGF/p75 cofactor. The prototype example, N-(cyclohexylmethyl)-2,3-dihydroxy-5-(piperidin-1-ylsulfonyl) benzamide (5u) inhibited the IN-LEDGF/p75 interaction with an IC50 value of 8 μM. Based on the molecular modeling, the mechanism of action was hypothesized to involve the chelation of the divalent metal ions inside the IN active site. And the inhibitor of IN-LEDGF/p75 interaction was properly bound to the LEDGF/p75 binding site in IN protein. This work provided a new and efficient approach to evolve novel HIV-1 IN inhibitors from rational integration and optimization of previously reported inhibitors.
HIV-1 integrase inhibitors; 2,3-dihydroxybenzamide; strand transfer; 3′-process; LEDGF/p75; chelation
Asthma is an important health problem worldwide and the prevalence is increasing in most part of the world. The burden of this disease to governments, health-care systems, and patients and their families have been greater more than ever despite efforts advocated by Global Initiative for Asthma for total asthma controls. Using Taiwan National Health Insurance Research Database, in this review, the population-based prospective studies showed the costs and health care utilization of childhood asthma in Taiwan was 2 folds higher than non-asthmatic children, and the prescription patterns of anti-asthmatic medications among physician in different discipline were all far from satisfied. The appropriateness of combinational therapy of inhaled corticosteroids and long acting β-agonists for moderate to severe childhood asthma was only 62%. In a government-sponsored disease management program for asthmatic patients within national health insurance, though the total mean costs (26.5%) and outpatient costs (26.1%) increased, the mean emergency department visits and hospitalization rates were significantly reduced by 34.4% and 51.74%, respectively, compared to the previous year. Therefore, in the real-world situation, asthmatic patients as well as medical professions who take care of asthmatic children still have much space for their symptoms controls and knowledge improvement to reduce the burden of asthma. From the experience of care and management of childhood asthma in Taiwan may reveal same problems of childhood asthma care in the similar cultural and ecological environments of Asian pacific countries, and suggest government-sponsored program may also have significant impact aimed at improving the care of patients with asthma.
Childhood asthma; Health care utilization; Disease management; National health insurance
Lipid storage droplet protein 5 (LSDP5) is a lipid droplet-associated protein of the PAT (perilipin, adipophilin, and TIP47) family that is expressed in the liver in a peroxisome proliferator-activated receptor alpha (PPARα)-dependent manner; however, its exact function has not been elucidated. We noticed that LSDP5 was localized to the surface of lipid droplets in hepatocytes. Overexpression of LSDP5 enhanced lipid accumulation in the hepatic cell line AML12 and in primary hepatocytes. Knock-down of LSDP5 significantly decreased the triglyceride content of lipid droplets, stimulated lipolysis, and modestly increased the mitochondrial content and level of fatty-acid β-oxidation in the mitochondria. The expression of PPARα was increased in LSDP5-deficient cells and required for the increase in the level of fatty acid β-oxidation in LSDP5-deficient cells. Using serial deletions of LSDP5, we determined that the lipid droplet-targeting domain and the domain directing lipid droplet clustering overlapped and were localized to the 188 amino acid residues at the N-terminus of LSDP5. Our findings suggest that LSDP5, a novel lipid droplet protein, may contribute to triglyceride accumulation by negatively regulating lipolysis and fatty acid oxidation in hepatocytes.
RNA secondary structure is required for the proper regulation of the cellular transcriptome. This is because the functionality, processing, localization and stability of RNAs are all dependent on the folding of these molecules into intricate structures through specific base pairing interactions encoded in their primary nucleotide sequences. Thus, as the number of RNA sequencing (RNA-seq) data sets and the variety of protocols for this technology grow rapidly, it is becoming increasingly pertinent to develop tools that can analyze and visualize this sequence data in the context of RNA secondary structure. Here, we present Sequencing Annotation and Visualization of RNA structures (SAVoR), a web server, which seamlessly links RNA structure predictions with sequencing data and genomic annotations to produce highly informative and annotated models of RNA secondary structure. SAVoR accepts read alignment data from RNA-seq experiments and computes a series of per-base values such as read abundance and sequence variant frequency. These values can then be visualized on a customizable secondary structure model. SAVoR is freely available at http://tesla.pcbi.upenn.edu/savor.
Ten (2.7%) Shiga toxin–producing Escherichia coli (STEC) were isolated from 370 samples of raw minced beef, mutton, pork, and chicken from the Jilin region of China; and additional 10 E. coli O157:H7 isolates were previously isolated from different Jilin regions. Seventeen of the isolates were multiresistant, exhibiting resistance to ampicillin, ciprofloxacin, tetracycline, sulfamethoxazole-trimethoprim, gentamycin, and streptomycin. Class 1 integrons were detected in nine (45.0%) of the STEC isolates and consisted of serogroups O157, O62, O113, O149, and O70. Integrons containing amplicons of a 0.5–1.5 or 1.0 kb gene cassette were found in seven (77.8%) of the integron-containing isolates. Sequencing analysis revealed that these gene cassettes encode genes conferring resistance to trimethoprim (dfrA1) and streptomycin (aadA1). The 0.5 kb cassette described here was found to encode a putative transporter peptide in the STEC. Seventeen isolates contained plasmids with different bands, and transfer by conjugation between strains of E. coli demonstrated that class 1 integrons located on mobile plasmids could contribute to the emergence and dissemination of antimicrobial resistance to ampicillin, gentamycin, streptomycin, and sulfamethoxazole-trimethoprim amongst STEC. These data revealed the high prevalence of antimicrobial-resistant STEC isolates in Jilin's surrounding regions, providing important and useful surveillance information reflecting antimicrobial selection pressure.
To investigate the overall prevalence of cardiovascular disease (CVD) in subjects hospitalized for chronic obstructive pulmonary disease (COPD), and explore the prevalence of the major CVD complications and trends in patients with COPD over a 10-year period.
Medical records in the PLA General Hospital, Beijing Union Medical College Hospital, and Beijing Hospital from 2000/01/01 to 2010/03/03 were retrospectively reviewed. A total of 4960 patients with COPD were reviewed in the study (3570 males, mean age, 72.2 ± 10.5 years; 1390 females, mean age, 72.0 ± 10.4 years).
The prevalence of CVD in COPD patients was 51.7%. The three most prevalent CVDs were ischemic heart disease (28.9%), heart failure (19.6%), and arrhythmia (12.6%). During the 10-year study period, the prevalence of various CVDs in COPD patients showed a gradual increasing trend with increasing age. There was higher morbidity due to ischemic heart disease (P < 0.01) in male COPD patients than in the female counterparts. However, heart failure (P < 0.01) and hypertension (P < 0.01) occurred less frequently in male COPD patients than in female COPD patients. Furthermore, the prevalence of ischemic heart disease decreased year by year. In addition to heart failure, various types of CVD complications in COPD patients tended to occur in younger subjects. The prevalence of all major types of CVD in women tended to increase year by year.
The prevalence of CVD in patients hospitalized for COPD in Beijing was high. Age, sex and CVD trends, as well as life style changes, should be considered when prevention and control strategies are formulated.
Prevalence; Cross-sectional investigation; Chronic obstructive pulmonary disease; Cardiovascular disease
Although the regulatory role of cognitive reappraisal in negative emotional responses is widely recognized, this reappraisal's effect on acute saliva secretory immunoglobulin A (SIgA), as well as the relationships among affective, immunological, and event-related potential (ERP) changes, remains unclear. In this study, we selected only people with low positive coping scores (PCSs) as measured by the Trait Coping Style Questionnaire to avoid confounding by intrinsic coping styles. First, we found that the acute stress of viewing unpleasant pictures consistently decreased SIgA concentration and secretion rate, increased perceptions of unpleasantness and amplitude of late positive potentials (LPPs) between 200–300 ms and 400–1000 ms. After participants used cognitive reappraisal, their SIgA concentration and secretion rate significantly increased and their unpleasantness and LPP amplitudes significantly decreased compared with a control condition. Second, we found a significantly positive correlation between the increases in SIgA and the decreases in unpleasantness and a significantly negative correlation between the increases in SIgA and the increases in LPP across the two groups. This study is the first to demonstrate that cognitive reappraisal reverses the decrease of SIgA. In addition, it revealed strong correlations among affective, SIgA and electrophysiological changes with convergent multilevel evidence.