The transition from transcription initiation to elongation involves phosphorylation of the large subunit (Rpb1) of RNA polymerase II on the repetitive carboxyl-terminal domain. The elongating hyperphosphorylated Rpb1 is subject to ubiquitination, particularly in response to UV radiation and DNA-damaging agents. By using computer modeling, we identified regions of Rpb1 and the adjacent subunit 6 of RNA polymerase II (Rpb6) that share sequence and structural similarity with the domain of hypoxia-inducible transcription factor 1␣ (HIF-1␣) that binds von Hippel-Lindau tumor suppressor protein (pVHL). pVHL confers substrate specificity to the E3 ligase complex, which ubiquitinates HIF-␣ and targets it for proteasomal degradation. In agreement with the computational model, we show biochemical evidence that pVHL specifically binds the hyperphosphorylated Rpb1 in a proline-hydroxylationdependent manner, targeting it for ubiquitination. This interaction is regulated by UV radiation.
Latex of dandelion roots contains a serine proteinase that hydrolyzes a chromogenic peptide substrate Glp-Ala-AlaLeu-pNA optimally at pH 8.0. Maximal activity of the proteinase in the roots is attained in April, at the beginning of plant development after the winter period. The protease was isolated by ammonium sulfate precipitation of the root extract followed by affinity chromatography on a Sepharose-Ala-AlaLeu-mrp and gel filtration on Superose 6R performed in FPLC regime. Pure serine proteinase named taraxalisin was inactivated by specific inhibitors of serine proteinases, diisopropylfluorophosphate (DFP) and phenylmethylsulfonylfluoride (PMSF). Its molecular mass is 67 kDa and pI 4.5. pH stability range is 6^9 in the presence of 2 mM Ca P+ , temperature optimum is at 40³C; K m =0.37 þ 0.06 mM. The substrate specificity of taraxalisin towards synthetic peptides and insulin B-chain is comparable with that of two other subtilisin-like serine proteinases, cucumisin and macluralisin. The taraxalisin N-terminal sequence traced for 15 residues revealed 40% coinciding residues when aligned with that of subtilisin Carlsberg.z 1998 Federation of European Biochemical Societies.
Objective To test a novel social network HIV risk reduction intervention for MSM in Russia and Hungary, where same-sex behavior is stigmatized and men may best be reached through their social network connections. Design A 2-arm trial with 18 sociocentric networks of MSM randomized to the social network intervention or standard HIV/STD testing/counseling. Setting St. Petersburg, Russia and Budapest, Hungary. Participants 18 “seeds” from community venues invited the participation of their MSM friends who, in turn, invited their own MSM friends into the study, a process that continued outward until eighteen 3-ring sociocentric networks (mean size=35 members, n=626) were recruited. Intervention Empirically-identified network leaders were trained and guided to convey HIV prevention advice to other network members. Main Outcome and Measures Changes in sexual behavior from baseline to 3- and 12-month followup, with composite HIV/STD incidence measured at 12-months to corroborate behavior changes. Results There were significant reductions between baseline, first followup, and second followup in the intervention versus comparison arm for proportion of men engaging in any unprotected anal intercourse (P=.04); UAI with a nonmain partner (P=.04); and UAI with multiple partners (P=.002). The mean percentage of unprotected AI acts significantly declined (P=.001), as well as the mean number of UAI acts among men who initially had multiple partners (P=.05). Biological HIV/STD incidence was 15% in comparison condition networks and 9% in intervention condition networks. Conclusions Even where same-sex behavior is stigmatized, it is possible to reach MSM and deliver HIV prevention through their social networks.
Background Although the dire life circumstances of labor migrants working in Russia are well-known, their HIV risk vulnerability and prevention needs are understudied. Low socioeconomic status, lack of access to services, separation from family, and limited risk awareness all contribute to migrants’ HIV vulnerability. Methods Male labor migrants in St. Petersburg (n=499) were administered assessments of their sexual behavior practices, substance use, and psychosocial characteristics related to risk and well-being. Results Thirty percent of migrants reported multiple female partners in the past 3 months. Condom use was low, ranging from 35% with permanent to 52% with casual partners. Central Asian migrants had very low AIDS knowledge, low levels of substance use, moderate sexual risk, high depression, and poor social supports. Eastern European migrants had higher AIDS knowledge, alcohol and drug use, and sexual risk. Discussion Improved HIV prevention efforts are needed to reduce the risk vulnerability of migrants who relocate to high disease prevalence areas.
Russia has a large HIV epidemic, but medical care engagement is low. Eighty HIV-positive persons in St. Petersburg completed in-depth interviews to identify barriers and facilitators of medical HIV care engagement. The most commonly-reported barriers involved difficulties accessing care providers, dissatisfaction with the quality of services, and negative attitudes of provider staff. Other barriers included not having illness symptoms, life stresses, low value placed on health, internalized stigma and wanting to hide one’s HIV status, fears of learning about one’s true health status, and substance abuse. Care facilitators were feeling responsible for one’s health and one’s family, care-related support from other HIV-positive persons, and the onset of health decline and fear of death. Substance use remission facilitated care engagement, as did good communication from providers and trust in one’s doctor. Interventions are needed in Russia to address HIV care infrastructural barriers and integrate HIV, substance abuse, care, and psychosocial services.
Russia has seen one of the world’s fastest-growing HIV epidemics. Transmission risk behavior, HAART-taking, and psychosocial distress of the growing population of Russian people living with HIV (PLH) in the HAART era are understudied. Participants of a systematically-recruited cross-sectional sample of 492 PLH in St. Petersburg completed measures of sexual and drug injection practices, adherence, perceived discrimination, and psychosocial distress. Since learning of their status, 59% of participants had partners of HIV-negative or unknown serostatus (mean=5.9). 52% reported unprotected intercourse with such partners, with 29% of acts unprotected. Greater perceived discrimination predicted lower condom use. 23% of IDU PLH still shared needles, predicted by having no primary partner, lower education, and more frequently-encountered discrimination. 25% of PLH had been refused general health care, 11% refused employment, 6% fired, and 6% forced from family homes. 39% of participants had probable clinical depression, 37% had anxiety levels comparable to psychiatric inpatients, and social support was low. 54% of PLH were on HAART, 16% of PLH refused HAART regimens, and 5% took less than 90% of their doses. Comprehensive community services for Russian PLH are needed to reduce AIDS-related psychosocial distress and continued HIV transmission risk behaviors. Social programs should reduce stigma and discrimination, and promote social integration of affected persons and their families.
We have selected a set of urinary variables that could be considered as a perspective combination of indicators (syndromes) of outcome of pre-operation BCG therapy of patients with superficial bladder cancer. A larger patient database will provide testing and evaluation of the biological and clinical significance of selected features. The computational syndrome-disease approach should be applicable for the solution of decision-making problems for management of cancer.
This study recruited four sociocentric networks (n = 156) of men who have sex with men in Budapest, Hungary, and St. Petersburg, Russia. The sampling approach was based on identifying an initial "seed" in the community for each network, and then recruiting three successive friendship group waves out from the seed. HIV prevalence in the networks was 9%, and the composite rate of other sexually transmitted diseases was 6%. 57% of participants reported both main and casual male partners, and two thirds reported unprotected anal intercourse in the past 3 months. Fifty-five percent of men's most recent anal intercourse acts were with nonexclusive partners, and 56% of most recent anal intercourse acts were unprotected. Sexual risk predictors were generally consistent with behavioral science theory. In addition, risk was associated with more often talking with friends about AIDS, higher ecstasy use, and less often drinking. Sociocentric social network sampling approaches are feasible and constitute a modality for reaching hidden high-risk populations inaccessible through conventional methods.Almost unknown during the socialist era, the HIV epidemic in parts of central and eastern Europe quickly accelerated beginning in the mid-1990s. Although HTV primarily first affected injection drug users (IDUs) in post-Soviet countries, transmission has shifted to a predominantly sexual pattern (UNAIDS, 2008). In spite of the rapid emergence of HIV in the region, there has been comparatively little published research on risk behavior as well as HIV/ STD prevalence in postsocialist countries. Men who have sex with men (MSM) remain among the world's most vulnerable populations, and research is needed to identify HIV risk behavior patterns and their determinants among MSM in eastern Europe. In addition, innovative NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript approaches need to be tested that can access those MSM community segments likely to be missed using conventional sampling methods.The appearance of the HIV epidemic in eastern Europe coincided with massive political, economic, and cultural transitions across the region. These included the breakup of the former Soviet Union and the appearance of new and sometimes fragile democracies in other former socialist countries. These transformations also resulted in fewer authoritarian controls, more personal freedoms including greater travel opportunities, liberalized sexual behaviors and norms, and increased drug use. In the context of these changes and given a weak public health infrastructure, intertwined HIV and sexually transmitted disease (STD) epidemics quickly emerged in many of the region's countries (Borisenko, Tichonova, & Renton, 1999), Russia and Ukraine are among the countries hardest hit by the HIV epidemic, with a more gradual rise in central Europe. UNAIDS estimates that 940,000 in Russia and 3,000 in Hungary, a much smaller country (UNAIDS, 2008).During the socialist era, homosexuality was officially proscribed, and there were few pub...
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