Gendered aspects of perceived and internalized HIV-related stigma in China.

Although studies have demonstrated that females experience more HIV-related stigma than males do, questions remain regarding the different dimensions of the stigma (i.e., perceived versus internalized) in China. The present study investigated gender differences in perceived and internalized HIV-related stigma, taking into account the potential influence of education. The study was conducted between October 2011 and March 2013. A total of 522 people living with HIV (PLH) were recruited from Anhui Province, China. The PLH participated in a survey using the Computer Assisted Personal Interview (CAPI) method. The gender differences in perceived and internalized HIV-related stigma were calculated with and without stratifying by education level. Female participants had significantly less education than the male participants. No significant difference was observed between females and males with respect to perceived stigma. However, females reported significantly higher internalized stigma than males did (p < .001). When socio-demographic characteristics were controlled, the gender difference in internalized stigma remained significant among educated participants (p = .038). The findings suggested that gender differences in HIV-related stigma were primarily found for internalized stigma. Heightened intervention efforts are encouraged to reduce internalized HIV-related stigma, particularly among female PLH in China and other regions with similar gender dynamics

Gender Differences in Depressive Symptoms Among HIV-Positive Concordant and Discordant Heterosexual Couples in China.

HIV seropositive individuals and their heterosexual partners/spouses, either seropositive or seronegative, are facing several mental health challenges. The objective of this study was to examine gender differences in depressive symptoms among HIV-positive concordant and HIV-discordant couples. We identified heterosexual couples from participants of a randomized controlled trial conducted in Anhui province, China. A total of 265 couples, comprising 129 HIV+ male/HIV- female couples, 98 HIV- male/HIV+ female couples, and 38 HIV-positive concordant couples, were included in the analyses. We collected data using the computer-assisted personal interview method. We used a linear mixed-effects regression model to assess whether gender differences in depressive symptoms varied across couple types. HIV-positive women reported a significantly higher level of depressive symptoms than their partners/spouses. HIV-positive women with HIV-positive partners had higher depressive symptoms than those with HIV-negative partners, whereas HIV-positive men reported similar levels of depressive symptoms regardless of their partners' serostatus. Among the concordant couples, those with the highest annual family income showed the greatest gender differences in depressive symptoms. We suggest that family interventions should be gender- and couple-type specific and that mental health counseling is warranted not only for HIV-positive women but also for HIV-negative women in an HIV-affected relationship

Antiretroviral Therapy Initiation Following Policy Changes: Observations From China.

China's HIV/AIDS treatment policies have been evolving over the preceding decade. This study describes patterns of antiretroviral therapy (ART) initiation for a sample of people living with HIV/AIDS (PLHIV) in rural Anhui, China, where most PLHIV were infected via paid plasma donation during the 1990s. A total of 481 PLHIV who were receiving ART were included in our analyses. Times between HIV diagnosis and the initiation of ART were examined relative to the time points when major ART-related policies changed in China. More than half (53%) of PLHIV who had been diagnosed by 2003 received ART within 6 months, whereas 93% of PLHIV who had been diagnosed in 2010 or later received ART within 6 months. The study results provide additional support that the "Four Frees and One Care" policy in 2003 and the relaxation of ART eligibility in 2010 have facilitated the initiation of treatment for PLHIV in China

Atmospheric Deposition History of Trace Metals and Metalloids for the Last 200 Years Recorded by Three Peat Cores in Great Hinggan Mountain, Northeast China

A large number of studies on trace metals and metalloids (TMs) accumulations in peatlands have been reported in Europe and North America. Comparatively little information is available on peat chronological records of atmospheric TMs flux in China. Therefore, the objective of our study was to determine the concentrations and accumulation rates (ARs) of TMs in Motianling peatland from Great Hinggan Mountain, northeast China, and to assess these in relation to establish a historical profile of atmospheric metal emissions from anthropogenic sources. To meet these aims we analyzed 14 TMs (As, Ba, Cd, Co, Cr, Cu, Mo, Ni, Pb, Sr, Sb, Tl, and Zn) and Pb isotopes (206Pb, 207Pb, 208Pb) using ICP-AES and ICP-MS, respectively, in three peat sections dated by 210Pb and 137Cs techniques (approximately spanning the last 200 years). There is a general agreement in the elemental concentration profiles which suggests that all investigated elements were conserved in the Motianling bog. Three principal components were discriminated by principal componentanalysis (PCA) based on Eigen-values >1 and explaining 85% of the total variance of element concentrations: the first component representing Ba, Co, Cr, Mo, Ni, Sr and Tl reflected the lithogenic source; the second component covering As, Cu and Sb, and Cd is associated with an anthropogenic source from ore mining and processing; the third component (Pb isotope, Pb and Zn) is affected by anthropogenic Pb pollution from industrial manufacturing and fossil-fuel combustion. The pre-industrial background of typical pollution elements was estimated as the average concentrations of TMs in peat samples prior to 1830 AD and with a 207Pb/206Pb ratio close to 1.9. ARs and enrichment factors (EFs) of TMs suggested enhanced metal concentrations near the surface of the peatland (in peat layers dated from the 1980s) linked to an increasing trend since the 2000s. This pollution pattern is also fingerprinted by the Pb isotopic composition, even after the ban of leaded gasoline use in China. Emissions from coal and leaded gasoline combustions in northern China are regarded as one of the major sources of anthropogenic Pb input in this region; meanwhile, the long-distance transportation of Pb-bearing aerosols from Mongolia should be also taken into consideration. The reconstructed history of TMs’ pollution over the past ca. 200 years is in agreement with the industrial development in China and clearly illustrates the influence of human activities on local rural environments. This study shows the utility of taking multi-cores to show the heterogeneity in peat accumulation and applying PCA, EF and Pb isotope methods in multi-proxies analyses for establishing a high resolution geochemical metal record from peatland

MiRNA-Directed Regulation of VEGF and Other Angiogenic Factors under Hypoxia

MicroRNAs (miRNAs) are a class of 20–24 nt non-coding RNAs that regulate gene expression primarily through post-transcriptional repression or mRNA degradation in a sequence-specific manner. The roles of miRNAs are just beginning to be understood, but the study of miRNA function has been limited by poor understanding of the general principles of gene regulation by miRNAs. Here we used CNE cells from a human nasopharyngeal carcinoma cell line as a cellular system to investigate miRNA-directed regulation of VEGF and other angiogenic factors under hypoxia, and to explore the principles of gene regulation by miRNAs. Through computational analysis, 96 miRNAs were predicted as putative regulators of VEGF. But when we analyzed the miRNA expression profile of CNE and four other VEGF-expressing cell lines, we found that only some of these miRNAs could be involved in VEGF regulation, and that VEGF may be regulated by different miRNAs that were differentially chosen from 96 putative regulatory miRNAs of VEGF in different cells. Some of these miRNAs also co-regulate other angiogenic factors (differential regulation and co-regulation principle). We also found that VEGF was regulated by multiple miRNAs using different combinations, including both coordinate and competitive interactions. The coordinate principle states that miRNAs with independent binding sites in a gene can produce coordinate action to increase the repressive effect of miRNAs on this gene. By contrast, the competitive principle states when multiple miRNAs compete with each other for a common binding site, or when a functional miRNA competes with a false positive miRNA for the same binding site, the repressive effects of miRNAs may be decreased. Through the competitive principle, false positive miRNAs, which cannot directly repress gene expression, can sometimes play a role in miRNA-mediated gene regulation. The competitive principle, differential regulation, multi-miRNA binding sites, and false positive miRNAs might be useful strategies in the avoidance of unwanted cross-action among genes targeted by miRNAs with multiple targets

Dynamic Interactions between TIP60 and p300 Regulate FOXP3 Function through a Structural Switch Defined by a Single Lysine on TIP60

SummaryThe human FOXP3 molecule is an oligomeric transcriptional factor able to mediate activities that characterize T regulatory cells, a class of lymphocytes central to the regulation of immune responses. The activity of FOXP3 is regulated at the posttranslational level, in part by two histone acetyltransferases (HATs): TIP60 and p300. TIP60 and p300 work cooperatively to regulate FOXP3 activity. Initially, p300 and TIP60 interactions lead to the activation of TIP60 and facilitate acetylation of K327 of TIP60, which functions as a molecular switch to allow TIP60 to change binding partners. Subsequently, p300 is released from this complex, and TIP60 interacts with and acetylates FOXP3. Maximal induction of FOXP3 activities is observed when both p300 and TIP60 are able to undergo cooperative interactions. Conditional knockout of TIP60 in Treg cells significantly decreases the Treg population in the peripheral immune organs, leading to a scurfy-like fatal autoimmune disease

Thrombospondin receptor α2δ-1 promotes synaptogenesis and spinogenesis via postsynaptic Rac1

Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit α2δ-1. α2δ-1 is a drug target for epilepsy and neuropathic pain; thus the TSP–α2δ-1 interaction is implicated in both synaptic development and disease pathogenesis. However, the mechanism by which this interaction promotes synaptogenesis and the requirement for α2δ-1 for connectivity of the developing mammalian brain are unknown. In this study, we show that global or cell-specific loss of α2δ-1 yields profound deficits in excitatory synapse numbers, ultrastructure, and activity and severely stunts spinogenesis in the mouse cortex. Postsynaptic but not presynaptic α2δ-1 is required and sufficient for TSP-induced synaptogenesis in vitro and spine formation in vivo, but an α2δ-1 mutant linked to autism cannot rescue these synaptogenesis defects. Finally, we reveal that TSP–α2δ-1 interactions control synaptogenesis postsynaptically via Rac1, suggesting potential molecular mechanisms that underlie both synaptic development and pathology

HIV-Infected Former Plasma Donors in Rural Central China: From Infection to Survival Outcomes, 1985–2008

BACKGROUND: The HIV epidemic among former plasma donors (FPDs) in rural Central China in the early-mid 1990s is likely the largest known HIV-infected cohort in the world related to commercial plasma donation but has never been fully described. The objectives of this study are to estimate the timing and geographic spread of HIV infection in this cohort and to demonstrate the impact of antiretroviral therapy on survival outcomes. METHODOLOGY/PRINCIPAL FINDINGS: HIV-infected FPDs were identified using the national HIV epidemiology and treatment databases. Locations of subjects were mapped. Dates of infection and survival were estimated using the midpoint date between initial-final plasma donation dates from 1985-2008 among those with plasma donation windows ≤2 years. Among 37,084 FPDs in the two databases, 36,110 were included. 95% were located in focal areas of Henan Province and adjacent areas of surrounding provinces. Midpoint year between initial-final plasma donation dates was 1994 among FPDs with known donation dates. Median survival from infection to AIDS was 11.8 years and, among those not treated, 1.6 years from AIDS to death. Among those on treatment, 71% were still alive after five years. Using Cox proportional hazard modeling, untreated AIDS patients were 4.9 times (95% confidence interval 4.6-5.2) more likely to die than those on treatment. CONCLUSIONS/SIGNIFICANCE: The epidemic of HIV-infected FPD in China was not widespread throughout China but rather was centered in Henan Province and the adjacent areas of surrounding provinces. Even in these areas, infections were concentrated in focal locations. Overall, HIV infections in this cohort peaked in 1994, with median survival of 13.4 years from infection to death among those not treated. Among AIDS patients on treatment, 71% were still alive after five years