Molecules from apoptotic pathways modulate HIV-1 replication in Jurkat cells

The replication of viruses involves control of some aspects of host cell homeostasis by modification of target cell metabolism and regulation of the apoptotic machinery. It is not well known whether molecules involved in apoptotic pathways affect human immunodeficiency virus type 1 (HIV-1) replication and regulate viral yields. Using the susceptible Jurkat cell line, we studied the relationship of apoptosis-associated molecules with HIV-1 virus production using a sensitive real-time RT-PCR assay. Here, we found that expression of proapoptotic proteins, including Fas ligand (FasL), FADD, or p53 significantly increased HIV-1 virus production. In contrast, the expression of antiapoptotic molecules, such as FLIP, Bcl-X_L, and XIAP, decreased HIV-1 virus production. Knockdown of Bax with siRNA and FADD with expression of its antisense mRNA also inhibited viral replication and the caspase-3 inhibitor, Z-DEVD, and decreased virus production. These data indicate that HIV-1 infection regulates the apoptosis process to facilitate viral replication and inhibition of apoptosis may inhibit HIV-1 replication and cytopathogenesis. We also discuss the effects of MAPK signaling pathways and apoptosis on HIV-1 replication.     

Time-of-day effect on cardiac responses to progressive exercise

This study was designed to examine time-of-day effects on markers of cardiac functional capacity during a standard progressive cycle exercise test. Fourteen healthy, untrained young males (mean?±?SD: 17.9?±?0.7 yrs of age) performed identical maximal cycle tests in the morning (08:00-11:00?h) and late afternoon (16:00-19:00?h) in random order. Cardiac variables were measured at rest, submaximal exercise, and maximal exercise by standard echocardiographic techniques. No differences in morning and afternoon testing values at rest or during exercise were observed for oxygen uptake, heart rate, cardiac output, or markers of systolic and diastolic myocardial function. Values at peak exercise for Vo(2) at morning and afternoon testing were 3.20?±?0.49 and 3.24?±?0.55?L min(-1), respectively, for heart rate 190?±?11 and 188?±?15?bpm, and for cardiac output 19.5?±?2.8 and 19.8?±?3.5?L min(-1). Coefficients of variation for morning and afternoon values for these variables were similar to those previously published for test-retest reproducibility. This study failed to demonstrate evidence for significant time-of-day variation in Vo(2)max or cardiac function during standard progressive exercise testing in adolescent males.     

Proteome reference map of the skin mucus of Atlantic cod (Gadus morhua) revealing immune competent molecules

The skin mucosal proteome of Atlantic cod (Gadus morhua) was mapped using a 2D PAGE, LC-MS/MS coupled approach. Mucosal proteins from naive fish were identified primarily by similarity searches across various cod EST databases. The identified proteins were clustered into 8 groups based on gene ontology classification for biological process. Most of the proteins identified from the gel are hitherto unreported for cod. Galectin-1, mannan binding lectin (MBL), serpins, cystatin B, cyclophilin A, FK-506 binding protein, proteasome subunits (alpha-3 and -7), ubiquitin, and g-type lysozyme are considered immune competent molecules. Five of the aforementioned proteins were cloned and their tissue distribution was analysed by RT-PCR.     

Absence of detectable XMRV and other MLV-related viruses in healthy blood donors in the United States

Background

Preliminary studies in chronic fatigue syndrome (CFS) patients and XMRV infected animals demonstrated plasma viremia and infection of blood cells with XMRV, indicating the potential risk for transfusion transmission. XMRV and MLV-related virus gene sequences have also been detected in 4–6% of healthy individuals including blood donors in the U.S. These results imply that millions of persons in the U.S. may be carrying the nucleic acid sequences of XMRV and/or MLV-related viruses, which is a serious public health and blood safety concern.

Methodology/Principal Findings

To gain evidence of XMRV or MLV-related virus infection in the U.S. blood donors, 110 plasma samples and 71 PBMC samples from blood donors at the NIH blood bank were screened for XMRV and MLV-related virus infection. We employed highly sensitive assays, including nested PCR and real-time PCR, as well as co-culture of plasma with highly sensitive indicator DERSE cells. Using these assays, none of the samples were positive for XMRV or MLV-related virus.

Conclusions/Significance

Our results are consistent with those from several other studies, and demonstrate the absence of XMRV or MLV-related viruses in the U.S. blood donors that we studied.     

Status of B-vitamins and homocysteine in diabetic retinopathy: association with vitamin-B12 deficiency and hyperhomocysteinemia

Diabetic retinopathy (DR) is a common cause of blindness. Although many studies have indicated an association between homocysteine and DR, the results so far have been equivocal. Amongst the many determinants of homocysteine, B-vitamin status was shown to be a major confounding factor, yet very little is known about its relationship to DR. In the present study, we, therefore, investigated the status of B-vitamins and homocysteine in DR. A cross-sectional case-control study was conducted with 100 normal control (CN) subjects and 300 subjects with type-2 diabetes (T2D). Of the 300 subjects with T2D, 200 had retinopathy (DR) and 100 did not (DNR). After a complete ophthalmic examination including fundus fluorescein angiography, the clinical profile and the blood levels of all B-vitamins and homocysteine were analyzed. While mean plasma homocysteine levels were found to be higher in T2D patients compared with CN subjects, homocysteine levels were particularly high in the DR group. There were no group differences in the blood levels of vitamins B1 and B2. Although the plasma vitamin-B6 and folic acid levels were significantly lower in the DNR and DR groups compared with the CN group, there were no significant differences between the diabetes groups. Interestingly, plasma vitamin-B12 levels were found to be significantly lower in the diabetes groups compared with the CN group; further, the levels were significantly lower in the DR group compared with the DNR group. Higher homocysteine levels were significantly associated with lower vitamin-B12 and folic acid but not with other B-vitamins. Additionally, hyperhomocysteinemia and vitamin-B12 deficiency did not seem to be related to subjects' age, body mass index, or duration of diabetes. These results thus suggest a possible association between vitamin-B12 deficiency and hyperhomocysteinemia in DR. Further, the data indicate that vitamin-B12 deficiency could be an independent risk factor for DR.     

Plasmodium chitinases: revisiting a target of transmission‐blockade against malaria

Malaria is a life‐threatening disease caused by one of the five species of Plasmodium, among which Plasmodium falciparum cause the deadliest form of the disease. Plasmodium species are dependent on a vertebrate host and a blood‐sucking insect vector to complete their life cycle. Plasmodium chitinases belonging to the GH18 family are secreted inside the mosquito midgut, during the ookinete stage of the parasite. Chitinases mediate the penetration of parasite through the peritrophic membrane, facilitating access to the gut epithelial layer. In this review, we describe Plasmodium chitinases with special emphasis on chitinases from P. falciparum and P. vivax, the representative examples of the short and long forms of this protein. In addition to the chitinase domain, chitinases belonging to the long form contain a pro‐domain and chitin‐binding domain. Amino acid sequence alignment of long and short form chitinase domains reveals multiple positions containing variant residues. A subset of these positions was found to be conserved or invariant within long or short forms, indicating the role of these positions in attributing form‐specific activity. The reported differences in affinities to allosamidin for P. vivax and P. falciparum were predicted to be due to different residues at two amino acid positions, resulting in altered interactions with the inhibitor. Understanding the role of these amino acids in Plasmodium chitinases will help us elucidate the mechanism of catalysis and the mode of inhibition, which will be the key for identification of potent inhibitors or antibodies demonstrating transmission‐blocking activity.     

Promoting life skills and preventing tobacco use among low-income Mumbai youth: effects of Salaam Bombay Foundation intervention

Background

In response to India''s growing tobacco epidemic, strategies are needed to decrease tobacco use among Indian youth, particularly among those who are economically disadvantaged. The objective of this study was to assess the effectiveness of a school-based life-skills tobacco control program for youth of low socio-economic status in Mumbai and the surrounding state of Maharashtra. We hypothesized that compared to youth in control schools, youth exposed to the program would have greater knowledge of effects of tobacco use; be more likely to take action to prevent others from using tobacco; demonstrate more positive life skills and attitudes; and be less likely to report tobacco use.

Methods/Findings

Using a quasi-experimental design, we assessed program effectiveness by comparing 8^th and 9^th grade students in intervention schools to 8^th grade students in comparable schools that did not receive the program. Across all schools, 1851 students completed a survey that assessed core program components in early 2010. The program consisted of activities focused on building awareness about the hazards of tobacco, developing life skills, and advocacy development. The primary outcome measure was self-reported tobacco use in the last 30 days.Findings indicate that 4.1% of 8^th grade intervention students (OR = 0.51) and 3.6% of 9^th grade intervention students (OR = 0.33) reported using tobacco at least once in the last 30 days, compared to 8.7% of students in the control schools. Intervention group students were also significantly more knowledgeable about tobacco and related legislation, reported more efforts to prevent tobacco use among others, and reported stronger life skills and self-efficacy than students in control schools. Limitations to the study include schools not being randomly assigned to condition and tobacco use being measured by self-report.

Conclusions

This program represents an effective model of school-based tobacco use prevention that low-income schools in India and other low- and middle-income countries can replicate.     

Socioeconomic status and health communication inequalities in Japan: a nationwide cross-sectional survey

Background

Considerable evidence suggests that communication inequality is one potential mechanism linking social determinants, particularly socioeconomic status, and health inequalities. This study aimed to examine how dimensions of health communication outcomes (health information seeking, self-efficacy, exposure, and trust) are patterned by socioeconomic status in Japan.

Methods

Data of a nationally representative cross-sectional survey of 2,455 people aged 15–75 years in Japan were used for secondary analysis. Measures included socio-demographic characteristics, subjective health, recent health information seeking, self-efficacy in seeking health information, and exposure to and trust in health information from different media.

Results

A total of 1,311 participants completed the questionnaire, giving a response rate of 53.6%. Multivariate logistic regression revealed that education and household income, but not employment, were significantly associated with health information seeking and self-efficacy. Socioeconomic status was not associated with exposure to and trust in health information from mass media, but was significantly associated with health information from healthcare providers and the Internet.

Conclusion

Health communication outcomes were patterned by socioeconomic status in Japan thus demonstrating the prevalence of health communication inequalities. Providing customized exposure to and enhancing the quality of health information by considering social determinants may contribute to addressing social disparities in health in Japan.