Updating the CTD Story: From Tail to Epic

Eukaryotic RNA polymerase II (RNAPII) not only synthesizes mRNA but also coordinates transcription-related processes via its unique C-terminal repeat domain (CTD). The CTD is an RNAPII-specific protein segment consisting of repeating heptads with the consensus sequence Y1S2P3T4S5P6S7 that has been shown to be extensively post-transcriptionally modified in a coordinated, but complicated, manner. Recent discoveries of new modifications, kinases, and binding proteins have challenged previously established paradigms. In this paper, we examine results and implications of recent studies related to modifications of the CTD and the respective enzymes; we also survey characterizations of new CTD-binding proteins and their associated processes and new information regarding known CTD-binding proteins. Finally, we bring into focus new results that identify two additional CTD-associated processes: nucleocytoplasmic transport of mRNA and DNA damage and repair

Suicide in Eastern Europe, the Commonwealth of Independent States, and the Baltic Countries: Social and Public Health Determinants

While suicide is a major public health problem worldwide, the countries of the former Soviet Union, including the Baltic States and the Commonwealth of Independent States (CIS), have some of the highest rates in the world. High suicide rates across Eastern Europe have been correlated with the post-Soviet transitional period and the societal changes associated with that transition. Many scholars have speculated that the sudden collapse of the paternalistic Soviet system and the introduction of a market economy - and the psychosocial distress that ensued.contributed to the suicide mortality crisis that most of the former Soviet republics experienced in the 1990s. It is unclear whether the transitional period has ended or is still ongoing. While suicide mortality rates in many countries have declined since then, they remain alarmingly high. In some countries, such as Belarus, the rates have increased. From September 14 to 15, 2010, suicidologists and other scholars and professionals with expertise in suicide and suicide prevention gathered in Tallinn, Estonia, to discuss the evidence base for social and public health determinants of suicide in the Baltic States, the CIS, and Eastern Europe. The participants identified research and data gaps that, if filled, would strengthen the foundation for developing effective suicide prevention policies and programs. This report summarizes the presentations and discussions that took place during the conference

RECQ5 helicase associates with the C-terminal repeat domain of RNA polymerase II during productive elongation phase of transcription

It is known that transcription can induce DNA recombination, thus compromising genomic stability. RECQ5 DNA helicase promotes genomic stability by regulating homologous recombination. Recent studies have shown that RECQ5 forms a stable complex with RNA polymerase II (RNAPII) in human cells, but the cellular role of this association is not understood. Here, we provide evidence that RECQ5 specifically binds to the Ser2,5-phosphorylated C-terminal repeat domain (CTD) of the largest subunit of RNAPII, RPB1, by means of a Set2-Rpb1-interacting (SRI) motif located at the C-terminus of RECQ5. We also show that RECQ5 associates with RNAPII-transcribed genes in a manner dependent on the SRI motif. Notably, RECQ5 density on transcribed genes correlates with the density of Ser2-CTD phosphorylation, which is associated with the productive elongation phase of transcription. Furthermore, we show that RECQ5 negatively affects cell viability upon inhibition of spliceosome assembly, which can lead to the formation of mutagenic R-loop structures. These data indicate that RECQ5 binds to the elongating RNAPII complex and support the idea that RECQ5 plays a role in the maintenance of genomic stability during transcriptio

RECQ5 helicase associates with the C-terminal repeat domain of RNA polymerase II during productive elongation phase of transcription

It is known that transcription can induce DNA recombination, thus compromising genomic stability. RECQ5 DNA helicase promotes genomic stability by regulating homologous recombination. Recent studies have shown that RECQ5 forms a stable complex with RNA polymerase II (RNAPII) in human cells, but the cellular role of this association is not understood. Here, we provide evidence that RECQ5 specifically binds to the Ser2,5-phosphorylated C-terminal repeat domain (CTD) of the largest subunit of RNAPII, RPB1, by means of a Set2–Rpb1-interacting (SRI) motif located at the C-terminus of RECQ5. We also show that RECQ5 associates with RNAPII-transcribed genes in a manner dependent on the SRI motif. Notably, RECQ5 density on transcribed genes correlates with the density of Ser2-CTD phosphorylation, which is associated with the productive elongation phase of transcription. Furthermore, we show that RECQ5 negatively affects cell viability upon inhibition of spliceosome assembly, which can lead to the formation of mutagenic R-loop structures. These data indicate that RECQ5 binds to the elongating RNAPII complex and support the idea that RECQ5 plays a role in the maintenance of genomic stability during transcription

Enrollment in HIV Care Two Years after HIV Diagnosis in the Kingdom of Swaziland: An Evaluation of a National Program of New Linkage Procedures

To improve early enrollment in HIV care, the Swaziland Ministry of Health implemented new linkage procedures for persons HIV diagnosed during the Soka Uncobe male circumcision campaign (SOKA, 2011–2012) and the Swaziland HIV Incidence Measurement Survey (SHIMS, 2011). Abstraction of clinical records and telephone interviews of a retrospective cohort of HIV-diagnosed SOKA and SHIMS clients were conducted in 2013–2014 to evaluate compliance with new linkage procedures and enrollment in HIV care at 92 facilities throughout Swaziland. Of 1,105 clients evaluated, within 3, 12, and 24 months of diagnosis, an estimated 14.0%, 24.3%, and 37.0% enrolled in HIV care, respectively, after adjusting for lost to follow-up and non-response. Kaplan-Meier functions indicated lower enrollment probability among clients 14–24 (P = 0.0001) and 25–29 (P = 0.001) years of age compared with clients > 35 years of age. At 69 facilities to which clients were referred for HIV care, compliance with new linkage procedures was low: referral forms were located for less than half (46.8%) of the clients, and few (9.6%) were recorded in the appointment register or called either before (0.3%) or after (4.9%) their appointment. Of over one thousand clients newly HIV diagnosed in Swaziland in 2011 and 2012, few received linkage services in accordance with national procedures and most had not enrolled in HIV care two years after their diagnosis. Our findings are a call to action to improve linkage services and early enrollment in HIV care in Swaziland

Investigation of False Positive Results with an Oral Fluid Rapid HIV-1/2 Antibody Test

BACKGROUND: In March 2004, the OraQuick® rapid HIV antibody test became the first rapid HIV test approved by the US Food and Drug Administration for use on oral fluid specimens. Test results are available in 20 minutes, and the oral fluid test is non-invasive. From August 2004–June 2005, we investigated a sudden increase in false-positive results occurring in a performance study of OraQuick® oral-fluid rapid HIV tests in Minnesota. METHODOLOGY/PRINCIPAL FINDINGS: In a field investigation, we reviewed performance study data on oral-fluid and whole-blood OraQuick® rapid HIV test device lots and expiration dates and assessed test performance and interpretation with oral-fluid and whole-blood specimens by operators who reported false-positive results. We used multivariate logistic regression to evaluate client demographic and risk characteristics associated with false-positive results. Next, we conducted an incidence study of false-positive OraQuick rapid HIV tests in nine US cities and tested both oral-fluid and finger-stick whole-blood specimens from clients; reactive tests were confirmed with Western blot. Sixteen (4.1%) false-positive oral-fluid results occurred in the performance study from April 15, 2004 through August 31, 2004 with unexpired devices from six test lots among 388 HIV-uninfected clients (specificity, 95.9%; 95% CI: 93.4–97.6). Three test operators who had reported false-positive results performed and interpreted the test according to package-insert instructions. In multivariate analysis, only older age was significantly associated with false-positive results (adjusted odds ratio = 4.5, 95% CI: 1.2–25.7). In the incidence study, all valid oral-fluid and whole-blood results from 2,268 clients were concordant and no false-positive results occurred (100% specificity). CONCLUSIONS/SIGNIFICANCE: The field investigation did not identify a cause for the increase in false-positive oral-fluid results, and the incidence study detected no false-positive results. The findings suggest this was an isolated cluster; the test's overall performance was as specified by the manufacturer

"More money for health - more health for the money": a human resources for health perspective

<p>Abstract</p> <p>Background</p> <p>At the MDG Summit in September 2010, the UN Secretary-General launched the Global Strategy for Women's and Children's Health. Central within the Global Strategy are the ambitions of "more money for health" and "more health for the money". These aim to leverage more resources for health financing whilst simultaneously generating more results from existing resources - core tenets of public expenditure management and governance. This paper considers these ambitions from a human resources for health (HRH) perspective.</p> <p>Methods</p> <p>Using data from the UK Department for International Development (DFID) we set out to quantify and qualify the British government's contributions on HRH in developing countries and to establish a baseline.. To determine whether activities and financing could be included in the categorisation of 'HRH strengthening' we adopted the Agenda for Global Action on HRH and a WHO approach to the 'working lifespan' of health workers as our guiding frameworks. To establish a baseline we reviewed available data on Official Development Assistance (ODA) and country reports, undertook a new survey of HRH programming and sought information from multilateral partners.</p> <p>Results</p> <p>In financial year 2008/9 DFID spent £901 million on direct 'aid to health'. Due to the nature of the Creditor Reporting System (CRS) of the Organisation for Economic Co-operation and Development (OECD) it is not feasible to directly report on HRH spending. We therefore employed a process of imputed percentages supported by detailed assessment in twelve countries. This followed the model adopted by the G8 to estimate ODA on maternal, newborn and child health. Using the G8's model, and cognisant of its limitations, we concluded that UK 'aid to health' on HRH strengthening is approximately 25%.</p> <p>Conclusions</p> <p>In quantifying DFID's disbursements on HRH we encountered the constraints of the current CRS framework. This limits standardised measurement of ODA on HRH. This is a governance issue that will benefit from further analysis within more comprehensive programmes of workforce science, surveillance and strategic intelligence. The Commission on Information and Accountability for Women's and Children's Health may present an opportunity to partially address the limitations in reporting on ODA for HRH and present solutions to establish a global baseline.</p

Analysing interactions in a teacher network forum: a sociometric approach

This article presents the sociometric analysis of the interactions in a forum of a social network created for the professional development of Portuguese-speaking teachers. The main goal of the forum, which was titled Stricto Sensu, was to discuss the educational value of programmes that joined the distance learning model in Brazil. The empirical study focused on the sociometrie analysis of the social interactions that take place in asynchronous online environments. This approach, according to literature, allows for new means to observe, analyse, and interpret the reality of a new social paradigm. This type of analysis tries to understand the relationship established between the different actors, seeking to verify if the roles they play in both the access to information and the construction of shared knowledge. The data collected allow the researchers to deduce that the indicators used in the analysis are important for understanding and intervening in the dynamics and functioning of the network to propose improvements in its structure and organisation. In the specific case of the aforementioned discussion forum, the results of the sociometrie analysis of the perceived interactions were not surprising, considering that the nature of the topic did not demand deep reflection to contribute to the debate.This work is funded by Portuguese Foundation for Science and Technology under the doctoral grant SFRH/BD/60677/2009

Implementing Routine HIV Testing: The Role of State Law

In September 2006, the Centers for Disease Control and Prevention (CDC) recommended routine HIV testing for all Americans aged 13–64, which would eliminate requirements for written consent and pretest counseling as previously required. However, this approach may conflict with state requirements concerning pretest counseling and informed consent for HIV testing. Our survey of state HIV testing laws demonstrates that the majority of states have HIV testing requirements that are inconsistent with the CDC's recommendations. Moreover, states that have recently amended their laws have not eased the requirements for pretest counseling and informed consent. The reasons for the persistence of these legal requirements must be understood to effect policy changes to increase HIV testing