Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV integration sites and implications for maintenance of the reservoir

Purpose of reviewTo provide an overview of recent research of how HIV integration relates to productive and latent infection and implications for cure strategies. Recent findingsHow and where HIV integrates provides new insights into how HIV persists on antiretroviral therapy (ART). Clonal expansion of infected cells with the same integration site demonstrates that T-cell proliferation is an important factor in HIV persistence, however, the driver of proliferation remains unclear. Clones with identical integration sites harbouring defective provirus can accumulate in HIV-infected individuals on ART and defective proviruses can express RNA and produce protein. HIV integration sites differ in clonally expanded and nonexpanded cells and in latently and productively infected cells and this influences basal and inducible transcription. There is a growing number of cellular proteins that can alter the pattern of integration to favour latency. Understanding these pathways may identify new interventions to eliminate latently infected cells. SummaryUsing advances in analysing HIV integration sites, T-cell proliferation of latently infected cells is thought to play a major role in HIV persistence. Clonal expansion has been demonstrated with both defective and intact viruses. Production of viral RNA and protein from defective viruses may play a role in driving chronic immune activation. The site of integration may determine the likelihood of proliferation and the degree of basal and induced transcription. Finally, host factors and gene expression at the time of infection may determine the integration site. Together these new insights may lead to novel approaches to elimination of latently infected cells.
Effect and interaction between external audit quality and ownership structure on earnings management for listed French companies

This study examines the effect of the interaction between audit quality variables and the ownership structure on earnings management based on a sample of 86 French companies listed on the stock exchange in the SBF 120 during 2010-2013. We conclude on one hand that the interaction between auditor reputation and the concentration of capital negatively affects earnings management and on the other hand, the interaction between auditor reputation and the size of float has a positive effect on earnings management. Also, the interaction between auditor seniority and the percentage of the voting rights held by the public reduces the practice of earnings management. For the effect of the interaction between auditor reputation and institutional investors, we find a negative and significant effect on the earnings management.
Television viewing and risk of type 2 diabetes, cardiovascular disease, and all-cause mortality: a meta-analysis.

CONTEXT Prolonged television (TV) viewing is the most prevalent and pervasive sedentary behavior in industrialized countries and has been associated with morbidity and mortality. However, a systematic and quantitative assessment of published studies is not available. OBJECTIVE To perform a meta-analysis of all prospective cohort studies to determine the association between TV viewing and risk of type 2 diabetes, fatal or nonfatal cardiovascular disease, and all-cause mortality. DATA SOURCES AND STUDY SELECTION Relevant studies were identified by searches of the MEDLINE database from 1970 to March 2011 and the EMBASE database from 1974 to March 2011 without restrictions and by reviewing reference lists from retrieved articles. Cohort studies that reported relative risk estimates with 95% confidence intervals (CIs) for the associations of interest were included. DATA EXTRACTION Data were extracted independently by each author and summary estimates of association were obtained using a random-effects model. DATA SYNTHESIS Of the 8 studies included, 4 reported results on type 2 diabetes (175,938 individuals; 6428 incident cases during 1.1 million person-years of follow-up), 4 reported on fatal or nonfatal cardiovascular disease (34,253 individuals; 1052 incident cases), and 3 reported on all-cause mortality (26,509 individuals; 1879 deaths during 202,353 person-years of follow-up). The pooled relative risks per 2 hours of TV viewing per day were 1.20 (95% CI, 1.14-1.27) for type 2 diabetes, 1.15 (95% CI, 1.06-1.23) for fatal or nonfatal cardiovascular disease, and 1.13 (95% CI, 1.07-1.18) for all-cause mortality. While the associations between time spent viewing TV and risk of type 2 diabetes and cardiovascular disease were linear, the risk of all-cause mortality appeared to increase with TV viewing duration of greater than 3 hours per day. The estimated absolute risk differences per every 2 hours of TV viewing per day were 176 cases of type 2 diabetes per 100,000 individuals per year, 38 cases of fatal cardiovascular disease per 100,000 individuals per year, and 104 deaths for all-cause mortality per 100,000 individuals per year. CONCLUSION Prolonged TV viewing was associated with increased risk of type 2 diabetes, cardiovascular disease, and all-cause mortality.
Habitat differentiation of Lauraceae species in a tropical lower montane forest in northern Thailand

Dependency on topographical habitat was examined for Lauraceae tree species in a lower montane forest using a large-scale research plot established at Doi Inthanon National Park, northern Thailand. Twenty species of 10 genera of Lauraceae were recorded in a 7.5-ha part of the plot; Lauraceae accounted for 18% of the total basal area. Lauraceae was the most species-rich and most abundant family in the plot. In a cluster analysis based on the matrix of spatial associations between species, two clusters were recognized. Members of one cluster seemed to associate with lower-elevation habitats, and members of the other associated with habitats on ridges. By subdividing the study plot into 20 m × 20 m squares, a discriminant analysis could be applied to the presence–absence data for the 17 species that had sufficient population density. The predictor variables used were the relative elevation, slope inclination, slope direction (transformed to deviation from SSW) and slope convexity for each of the squares. The discriminant models were tested statistically by applying the random shift technique. The models were significant for 11 of the species (65% of the species examined) and were associated with the topographical condition of the habitat. Stepwise selection of the predictor variables for these 11 species revealed that relative elevation and slope convexity were the most important factors for predicting the presence or absence of the Lauraceae species. Both these variables were considered to indicate the hydrological condition of the habitat.
Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading

Mouse aortic smooth muscle cells (SMCs) were loaded for 72 h with cholesterol by using cholesterol:methyl-β-cyclodextrin complexes, leading to ≈2-fold and ≈10-fold increases in the contents of total cholesterol and cholesteryl ester, respectively. Foam-cell formation was demonstrated by accumulation of intracellular, Oil Red O-stained lipid droplets. Immunostaining showed decreased protein levels of smooth muscle α-actin and α-tropomyosin and increased levels of macrophage markers CD68 and Mac-2 antigen. Quantitative real-time RT-PCR revealed that after cholesterol loading, the expression of SMC-related genes α-actin, α-tropomyosin, myosin heavy chain, and calponin H1 decreased (to 11.5 ± 0.5%, 29.3 ± 1.4%, 23.8 ± 1.4%, and 3.8 ± 0.5% of unloaded cells, respectively; P < 0.05 for all), whereas expression of macrophage-related genes CD68, Mac-2, and ABCA1 mRNA increased (to 709 ± 84%, 330 ± 11%, and 207 ± 13% of unloaded cells, respectively; P < 0.05 for all), thereby demonstrating that the protein changes were regulated at the mRNA level. Furthermore, these changes were accompanied by a gain in macrophage-like function as assessed by phagocytotic activity. Expression of vascular cell adhesion molecule 1 and monocyte chemoattractant protein 1, known responders to inflammation, were not changed. In conclusion, cholesterol loading of SMC causes phenotypic changes regulated at the mRNA level that result in a transdifferentiation to a macrophage-like state. This finding suggests that not all foam cells in lesions may have a macrophage origin, despite what is indicated by immunostaining for macrophage-related markers. Furthermore, inflammatory changes in foam cells observed in vivo may not be simple consequences of cholesterol accumulation.
No Independent Association Between HSP70 Gene Polymorphism and IDDM

A role for heat shock proteins (HSPs) in autoimmunity has recently been suggested by several authors. Autoantibodies against HSPs have been associated with such autoimmune diseases as systemic lupus erythematosus, polymyositis, and the NOD mouse model of diabetes. Moreover, genes for the major 70,000-Mr HSP (HSP70) are located within the MHC. To investigate a potential association of an HSP70–2 gene polymorphism with insulin-dependent diabetes mellitus (IDDM), we analyzed restriction-fragment–length polymorphism (RFLP) of this gene in 29 families with one or more member affected by IDDM. With the enzyme PstI, as reported previously, two HSP70–2 alleles of 8.5- and 9.0-kb were found. The 8.5-kb allele was found more frequently on diabetic haplotypes compared with control haplotypes (41 of 66 [62%] vs. 20 of 46 [43%], P = 0.03). This association was due to the conservation of alleles on extended haplotypes we previously reported to be associated with diabetes on initial analysis of families. Twenty-three of 26 diabetic DR3 haplotypes and 3 of 3 normal DR3 haplotypes and all instances of [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3] had the 8.5-kb allele, whereas 0 of 9 normal DR2 haplotypes and 0 of 2 diabetic DR2 haplotypes had the 8.5-kb allele (P = 8 × 10−7 DR3 vs. DR2 haplotypes). The alleles were equally distributed among DR4 haplotypes. Our studies indicate that the 8.5-kb allele is part of [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3] haplotypes, and the 9.0-kb allele is associated with DR2 but no independent association (greater than DR association) is found between HSP70–2 alleles and diabetes.
RAPID ALDOSTERONE‐INDUCED CELL VOLUME INCREASE OF ENDOTHELIAL CELLS MEASURED BY THE ATOMIC FORCE MICROSCOPE

Atomic force microscopy (AFM) is a useful technique for imaging the surface of living cells in three dimensions. The authors applied AFM to obtain morphological information of individual cultured endothelial cells of bovine aorta under stationary and strain conditions and to simultaneously measure changes in cell volume in response to aldosterone. This mineralocorticoid hormone is known to have acute, non‐genomic effects on intracellular pH, intracellular electrolytes and inositol‐1,4,5‐triphosphate production. In this study whether endothelial cells under tension change their volume in response to aldosterone was tested. Such changes were already shown in human leukocytes measured by Coulter counter. In contrast to leukocytes that are more or less spherical and live in suspension, endothelial cells exhibit a complex morphology and adhere to a substrate. Thus, measurements of discrete cell volume changes in endothelial cells under physiological condition is only feasible with more sophisticated techniques. By using AFM we could precisely measure the absolute cell volume of individual living endothelial cells. Before the addition of aldosterone the cell volume of mechanically stressed endothelial cells mimicking arterial blood pressure was 1827±172fl. Cell volume was found to increase by 28% 5min after hormone exposure. Twenty‐five minutes later cell volume was back to normal despite the continuous presence of aldosterone in the medium. Amiloride, a blocker of the plasma membrane Na+/H+exchanger prevented the initial aldosterone‐induced volume increase. Taken together, AFM disclosed a transient swelling of endothelial cells induced by the activation of an aldosterone sensitive plasma membrane Na+/H+exchanger.
The Traf2- and Nck-interacting Kinase as a Putative Effector of Rap2 to Regulate Actin Cytoskeleton*

Rap2 belongs to the Ras family of small GTP-binding proteins, but its specific roles in cell signaling remain unknown. In the present study, we have affinity-purified from rat brain a Rap2-interacting protein of ∼155 kDa, p155. By liquid chromatography tandem mass spectrometry, we have identified p155 as Traf2- and Nck-interacting kinase (TNIK). TNIK possesses an N-terminal kinase domain homologous to STE20, the Saccharomyces cerevisiae mitogen-activated protein kinase kinase kinase kinase, and a C-terminal regulatory domain termed the citron homology (CNH) domain. TNIK induces disruption of F-actin structure, thereby inhibiting cell spreading. In addition, TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway. Among our observations, TNIK interacted with Rap2 through its CNH domain but did not interact with Rap1 or Ras. TNIK interaction with Rap2 was dependent on the intact effector region and GTP-bound configuration of Rap2. When co-expressed in cultured cells, TNIK colocalized with Rap2, while a mutant TNIK lacking the CNH domain did not. Rap2 potently enhanced the inhibitory function of TNIK against cell spreading, but this was not observed for the mutant TNIK lacking the CNH domain. Rap2 did not significantly enhance TNIK-induced JNK activation, but promoted autophosphorylation and translocation of TNIK to the detergent-insoluble cytoskeletal fraction. These results suggest that TNIK is a specific effector of Rap2 to regulate actin cytoskeleton.
Elevated incidence of lung cancer among HIV-infected individuals.

PURPOSE People with HIV infection in the United States frequently smoke tobacco. We sought to characterize lung cancer incidence among HIV-infected individuals, examine whether cancer risk was related to HIV-induced immunosuppression, and assess whether the high prevalence of smoking explained elevated risk. METHODS We conducted a retrospective cohort study at an HIV specialty clinic in Baltimore, MD (1989-2003). Incident lung cancers were identified using hospital records. We used negative binomial regression to compare incidence across subgroups defined by demographics, use of highly active antiretroviral therapy (HAART), and HIV markers. Standardized incidence ratios (SIRs) compared incidence with an urban reference population (Detroit, MI). We adjusted SIRs for the effect of smoking, using smoking prevalences estimated from part of the cohort and the general population. 95% CIs and P values were two sided. RESULTS Thirty-three lung cancers were observed among 5,238 HIV-infected patients (incidence: 170 per 100,000 person-years). Incidence increased with age (P < .0001), but did not differ by sex, race, or CD4 count. Incidence tended to increase with calendar year (P = .09) and HAART use (P = .10), and was inversely related to HIV viral load (P = .03), but these associations were attenuated with age adjustment. The SIR was 4.7 (95% CI, 3.2 to 6.5) versus the general population. Twenty-eight lung cancer patients (85%) and 69% of the cohort were smokers. After smoking adjustment, risk remained elevated (SIR, 2.5; 95% CI, 1.6 to 3.5). CONCLUSION Lung cancer risk was substantially elevated in HIV-infected individuals. Incidence was unrelated to HIV-induced immunosuppression. Notably, incidence remained high after adjustment for smoking, suggesting the involvement of additional factors.
Eating disorders and maladaptive dietary/insulin management among youths with childhood-onset insulin-dependent diabetes mellitus.

OBJECTIVE To determine the prevalence of DSM-III eating disorder and the conjoint symptoms of maladaptive dietary/insulin management (irrespective of eating disorder) and their psychiatric and biomedical correlates among youths with childhood-onset insulin-dependent diabetes mellitus (IDDM). METHOD Forty-four girls and 35 boys, 8 to 13 years old at IDDM onset, were repeatedly interviewed during an interval of up to 14 years (mean = 9 years) to ascertain psychiatric disorders and behaviors related to diabetes care. Metabolic control and IDDM-related hospitalizations also were monitored. RESULTS By the mean age of approximately 21 years, 3.8% of the sample had DSM-III eating disorders and 11.4% had "eating problems," defined as the conjoint symptoms of severe dietary indiscretion and repeated insulin omission (irrespective of eating disorders). Youths with "eating problems" were nine times more likely to have had a psychiatric disorder than the rest of the patients, and they had a significantly higher rate of pervasive noncompliance with medical treatment. No between-group differences were found in metabolic control and rates of multiple hospitalizations. CONCLUSIONS The diabetes-specific symptom-pair of serious dietary indiscretion and repeated insulin omission appears to identify youths who have had other problems as well. The association of eating problems with psychiatric disorders (other than eating disorders) suggests that a subgroup of diabetic youths have various difficulties in coping with the medical illness and require close monitoring and psychosocial intervention.
Remineralization of Caries Lesions Extending into Dentin

Remineralization is one aspect of the overall process of tooth decay. However, it is primarily studied in shallow lesions. The aim of this study was to explore whether caries lesions in enamel and extending into the dentin can be remineralized. A single-section model was developed for the longitudinal and non-destructive monitoring of changes in enamel and dentin. Lesions at least 200 μm into dentin were formed in undersaturated acetate buffers. Next, the lesions were divided into groups (three treatment and one control) and remineralized. The treatments were: weekly immersion in 1000 ppm fluoride, single treatment with methanehydroxybisphosphonate, and a constant level of 1 ppm fluoride. De- and remineralization was assessed by transverse microradiography. Remineralization was observed in enamel, but also in dentin, indicating that, deep into dentin, the pores become supersaturated to apatite formation. Treatments affected remineralization only in the outer part of enamel. Both findings are explained by a relatively fast diffusion of mineral ions, with precipitation being rate-limiting. The results suggest that dentin remineralization, underneath enamel, can be achieved and could possibly be used in clinical treatment strategies.
Variants of chemokine receptor 2 and interleukin 4 receptor, but not interleukin 10 or Fas ligand, increase risk of cervical cancer

Cervical cancer is caused by persistent infection of oncogenic human papillomavirus (HPV). Most infected women clear the virus without developing cervical lesions and it is likely that immunological host factors affect susceptibility to cervical cancer. The impact of the human leukocyte antigen (HLA) locus on the risk of cervical cancer is established and several other genes involved in immunological pathways have been suggested as biologically plausible candidates. The aim of this study was to examine the potential role of polymorphisms in 4 candidate genes by analysis of 1,306 familial cervical cancer cases and 288 controls. The following genes and polymorphisms were studied: Chemokine receptor 2 (CCR‐2) V64I; Interleukin 4 receptor α (IL‐4R) I75V, S503P and Q576R; Interleukin 10 (IL‐10) −592; and Fas ligand (FasL) −844. The CCR‐2 64I variant was associated with decreased risk of cervical cancer; homozygote carriers of the 64I variant had an odds ratio of 0.31 (0.12–0.77). This association was detected in both carriers and noncarriers of the HLA DQB1*0602 cervical cancer risk allele. The IL‐4R 75V variant was associated with increased risk of cervical tumors, cases homozygote for 75V had an odds ratio of 1.91 (1.27–2.86) with a tendency that the association was stronger in noncarriers of the DQB1*0602 allele. We did not find any association for IL‐10 −592, or FasL −844, previously reported to be associated with cervical cancer in the Dutch and Chinese populations, respectively. © 2007 Wiley‐Liss, Inc.
T-cell-independent resistance to infection and generation of immunity to Francisella tularensis

The intraperitoneal 50% lethal dose (LD50) for Francisella tularensis LVS in both normal control heterozygote BALB/c nu/+ mice and BALB/c nu/nu mice was 2 x 10(0). Both nu/+ and nu/nu mice given 10(7) LVS bacteria or more intradermally (i.d.) died, with a mean time to death of about 7 to 8 days. On the other hand, nu/+ mice given 10(6) LVS bacteria or less survived for more than 60 days and cleared systemic bacteria, while nu/nu mice given 10(6) LVS bacteria or less survived for more than 10 days but died between days 25 and 30. Thus, the short-term (i.e., < 10-day) i.d. LD50 of both nu/nu and nu/+ mice was 3 x 10(6), but the long-term (i.e., > 10-day) i.d. LD50 of nu/nu mice was less than 7 x 10(0). The short-term survival of i.d. infection was dependent on tumor necrosis factor and gamma interferon: treatment of nu/nu mice with anti-tumor necrosis factor or anti-gamma interferon at the time of i.d. infection resulted in death from infection 7 to 8 days later, whereas control infected nu/nu mice survived for 26 days. nu/nu mice infected with LVS i.d. generated LVS-specific serum antibodies, which were predominantly immunoglobulin M: titers peaked 7 days after i.d. infection but declined sharply by day 21, after which mice died. Surprisingly, nu/nu mice given 10(3) LVS bacteria i.d. became resistant to a lethal challenge (5,000 LD50s) of LVS intraperitoneally within 2 days after i.d. infection; nu/nu mice similarly infected with LVS i.d. and challenged with Salmonella typhimurium (10 LD50s) were not protected. nu/nu mice given nu/+ spleen cells intravenously as a source of mature T cells survived i.d. infection for more than 60 days and cleared bacteria. Taken together, these studies demonstrate that i.d. infection of nu/nu mice with LVS rapidly generates T-cell-independent, short-term, specific protective immunity against lethal challenge, but T lymphocytes are essential for long-term survival.
“I Feel Like More of a Man”: A Mixed Methods Study of Masculinity, Sexual Performance, and Circumcision for HIV Prevention

Ethnographic studies from numerous societies have documented the central role of male circumcision in conferring masculinity and preparing boys for adult male sexuality. Despite this link between masculinity, sexuality, and circumcision, there has been little research on these dynamics among men who have been circumcised for HIV prevention. We employed a mixed methods approach with data collected from recently circumcised men in the Dominican Republic (DR) to explore this link. We analyzed survey data collected six to 12 months post-circumcision (N = 293) as well as in-depth interviews conducted with a subsample of those men (n = 30). We found that 42% of men felt more masculine post-circumcision. In multivariate analysis, feeling more masculine was associated with greater concern about being perceived as masculine (OR = 1.70, 95% CI: 1.25–2.32), feeling more potent erections post-circumcision (OR = 2.25, 95% CI: 1.26–4.03), and reporting increased ability to satisfy their partners post-circumcision (OR = 2.30, 95% CI: 1.11–4.77). In qualitative interviews, these factors were all related to masculine norms of sexually satisfying one’s partner, and men’s experiences of circumcision were shaped by social norms of masculinity. This study highlights that circumcision is not simply a biomedical intervention and that circumcision programs need to incorporate considerations of masculine norms and male sexuality into their programming.