G-Quadruplex Dynamics Contribute To Regulation Of Mitochondrial Gene Expression

Single-stranded DNA or RNA sequences rich in guanine (G) can adopt non-canonical structures known as G-quadruplexes (G4). Mitochondrial DNA (mtDNA) sequences that are predicted to form G4 are enriched on the heavy-strand and have been associated with formation of deletion breakpoints. Increasing evidence supports the ability of mtDNA to form G4 in cancer cells; however, the functional roles of G4 structures in regulating mitochondrial nucleic acid homeostasis in non-cancerous cells remain unclear. Here, we demonstrate by live cell imaging that the G4-ligand RHPS4 localizes primarily to mitochondria at low doses. We find that low doses of RHPS4 do not induce a nuclear DNA damage response but do cause an acute inhibition of mitochondrial transcript elongation, leading to respiratory complex depletion. We also observe that RHPS4 interferes with mtDNA levels or synthesis both in cells and isolated mitochondria. Importantly, a mtDNA variant that increases G4 stability and anti-parallel G4-forming character shows a stronger respiratory defect in response to RHPS4, supporting the conclusion that mitochondrial sensitivity to RHPS4 is G4-mediated. Taken together, our results indicate a direct role for G4 perturbation in mitochondrial genome replication, transcription processivity, and respiratory function in normal cells

Placing the Common Era in a Holocene context: millennial to centennial patterns and trends in the hydroclimate of North America over the past 2000 years

A synthesis of 93 hydrologic records from across North and Central America, and adjacent tropical and Arctic islands, reveals centennial to millennial trends in the regional hydroclimates of the Common Era (CE; past 2000 years). The hydrological records derive from materials stored in lakes, bogs, caves, and ice from extant glaciers, which have the continuity through time to preserve low-frequency ( \u3e 100 year) climate signals that may extend deeper into the Holocene. The most common pattern, represented in 46 (49 %) of the records, indicates that the centuries before 1000 CE were drier than the centuries since that time. Principal component analysis indicates that millennial-scale trends represent the dominant pattern of variance in the southwestern US, northeastern US, mid-continent, Pacific Northwest, Arctic, and tropics, although not all records within a region show the same direction of change. The Pacific Northwest and the southernmost tier of the tropical sites tended to dry toward present, as many other areas became wetter than before. In 22 records (24 %), the Medieval Climate Anomaly period (800–1300 CE) was drier than the Little Ice Age (1400–1900 CE), but in many cases the difference was part of the longer millennial-scale trend, and, in 25 records (27 %), the Medieval Climate Anomaly period represented a pluvial (wet) phase. Where quantitative records permitted a comparison, we found that centennial-scale fluctuations over the Common Era represented changes of 3–7% in the modern interannual range of variability in precipitation, but the accumulation of these long-term trends over the entirety of the Holocene caused recent centuries to be significantly wetter, on average, than most of the past 11 000 years

"My Children and I Will no Longer Suffer from Malaria": A Qualitative Study of the Acceptance and Rejection of Indoor Residual Spraying to Prevent Malaria in Tanzania.

The objective of this study was to identify attitudes and misconceptions related to acceptance or refusal of indoor residual spraying (IRS) in Tanzania for both the general population and among certain groups (e.g., farmers, fishermen, community leaders, and women). This study was a series of qualitative, semi-structured, in-depth interviews and focus group discussions conducted from October 2010 to March 2011 on Mainland Tanzania and Zanzibar. Three groups of participants were targeted: acceptors of IRS (those who have already had their homes sprayed), refusers (those whose communities have been sprayed, but refused to have their individual home sprayed), and those whose houses were about to be sprayed as part of IRS scale-up. Interviews were also conducted with farmers, fishermen, women, community leaders and members of non-government organizations responsible for community mobilization around IRS. Results showed refusers are a very small percentage of the population. They tend to be more knowledgeable people such as teachers, drivers, extension workers, and other civil servants who do not simply follow the orders of the local government or the sprayers, but are skeptical about the process until they see true results. Refusal took three forms: 1) refusing partially until thorough explanation is provided; 2) accepting spray to be done in a few rooms only; and 3) refusing outright. In most of the refusal interviews, refusers justified why their houses were not sprayed, often without admitting that they had refused. Reasons for refusal included initial ignorance about the reasons for IRS, uncertainty about its effectiveness, increased prevalence of other insects, potential physical side effects, odour, rumours about the chemical affecting fertility, embarrassment about moving poor quality possessions out of the house, and belief that the spray was politically motivated. To increase IRS acceptance, participants recommended more emphasis on providing thorough public education, ensuring the sprayers themselves are more knowledgeable about IRS, and asking that community leaders encourage participation by their constituents rather than threatening punishment for noncompliance. While there are several rumours and misconceptions concerning IRS in Tanzania, acceptance is very high and continues to increase as positive results become apparent

Knowledge and behaviour of nurse/midwives in the prevention of vertical transmission of HIV in Owerri, Imo State, Nigeria: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Mother-to-Child Transmission (MTCT) of HIV remains the main mode of acquisition of HIV in children. Transmission of HIV may occur during pregnancy, delivery or breastfeeding. Studies have shown that some specific interventions help to reduce the transmission of the virus to the baby. In order to target safe, rational and effective intervention to reduce MTCT of HIV, it is necessary to ensure that the nurse/midwife has knowledge of the strategies for the prevention of vertical transmission of HIV.</p> <p>Method</p> <p>The cross-sectional design was utilized to determine the knowledge and behaviour of nurse/midwives in the prevention of vertical transmission of HIV in Owerri, Imo State, Nigeria. The study sample consisted of 155 nurse/midwives drawn from three selected hospitals through stratified random sampling method. Official permission was obtained from the institutions and consent from participants. Data was collected through the use of a self administered questionnaire. Information sought included respondents' demographic characteristics, knowledge about and behaviour of prevention of vertical transmission as well as factors influencing behaviour.</p> <p>Results</p> <p>Findings revealed that nurse/midwives had moderate level of knowledge with mean score of 51.4%. The mean score on behaviour was 52.5%, major factors that influence behaviour in these settings were mainly fear of getting infected, irregular supply of resources like gloves, goggles, sharp boxes, and water supply was not regular also. Hypotheses tested revealed that there is a positive relationship between knowledge and behaviour (r = 0.583, p = 0.00). Knowledge level of nurse/midwives who had educational exposure was not different from those who did not (t = 1.439, p = 0.152). There was a significant difference in the knowledge of nurse/midwives who had experience in managing pregnant women living with HIV/AIDS and those who did not (t = 2.142, p = 0.03). Also, there was a significant relationship between behaviour and availability of resources (r = 0.318, p = 0.000).</p> <p>Conclusion</p> <p>The study revealed that the nurse/midwives though moderately knowledgeable still had gaps in certain areas. Their behaviours were fairly appropriate. There is need for improved knowledge through structured educational intervention. Resources needed for practice should always be made available and the environment should be much more conducive for practice.</p

General distress, hopelessness-suicidal ideation and worrying in adolescence:concurrent and predictive validity of a symptom-level bifactor model for clinical diagnoses

BACKGROUND: Clinical disorders often share common symptoms and aetiological factors. Bifactor models acknowledge the role of an underlying general distress component and more specific sub-domains of psychopathology which specify the unique components of disorders over and above a general factor. METHODS: A bifactor model jointly calibrated data on subjective distress from The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale. The bifactor model encompassed a general distress factor, and specific factors for (a) hopelessness-suicidal ideation, (b) generalised worrying and (c) restlessness-fatigue at age 14 which were related to lifetime clinical diagnoses established by interviews at ages 14 (concurrent validity) and current diagnoses at 17 years (predictive validity) in a British population sample of 1159 adolescents. RESULTS: Diagnostic interviews confirmed the validity of a symptom-level bifactor model. The underlying general distress factor was a powerful but non-specific predictor of affective, anxiety and behaviour disorders. The specific factors for hopelessness-suicidal ideation and generalised worrying contributed to predictive specificity. Hopelessness-suicidal ideation predicted concurrent and future affective disorder; generalised worrying predicted concurrent and future anxiety, specifically concurrent generalised anxiety disorders. Generalised worrying was negatively associated with behaviour disorders. LIMITATIONS: The analyses of gender differences and the prediction of specific disorders was limited due to a low frequency of disorders other than depression. CONCLUSIONS: The bifactor model was able to differentiate concurrent and predict future clinical diagnoses. This can inform the development of targeted as well as non-specific interventions for prevention and treatment of different disorders

Plio-Pleistocene trends in ice rafted debris on the Lomonosov Ridge

Although more than 700 sediment cores exist from the Arctic Ocean, the Plio-Pleistocene evolution of the basin and its marginal seas remains virtually unknown. This is largely due the shallow penetration of most of these records, and difficulties associated with deriving chronologies for the recovered material. The Integrated Ocean Drilling Program’s (IODP) Expedition 302 (Arctic Coring Expedition, ACEX) recovered 197 m of Neogene/Quaternary sediment from the circumpolar regions of the Lomonosov Ridge. As detailed analyses of this material emerge, research is beginning to formulate a long-term picture of paleoceanographic changes in the central Arctic Ocean. This paper reviews the ACEX Plio-Pleistocene age model, identifies uncertainties, and addresses ways in which these may be eliminated. Within the established stratigraphic framework, a notable reduction in the abundance of ice rafted debris (IRD) occurs in the early part of the Pleistocene and persists until Marine Isotope Stage 6 (MIS 6). Therefore, while global oceanographic proxies indicate the gradual growth of terrestrial ice-sheets during this time, IRD delivery to the central Arctic Ocean remained comparatively low and stable. Within the resolution of existing data, the Pleistocene reduction in IRD is synchronous with predicted changes in both the inflow of North Atlantic and Pacific waters, which in modern times are known to exert a strong influence on sea ice stability

Sea ice dynamics across the Mid-Pleistocene transition in the Bering Sea.

Sea ice and associated feedback mechanisms play an important role for both long- and short-term climate change. Our ability to predict future sea ice extent, however, hinges on a greater understanding of past sea ice dynamics. Here we investigate sea ice changes in the eastern Bering Sea prior to, across, and after the Mid-Pleistocene transition (MPT). The sea ice record, based on the Arctic sea ice biomarker IP25 and related open water proxies from the International Ocean Discovery Program Site U1343, shows a substantial increase in sea ice extent across the MPT. The occurrence of late-glacial/deglacial sea ice maxima are consistent with sea ice/land ice hysteresis and land-glacier retreat via the temperature-precipitation feedback. We also identify interactions of sea ice with phytoplankton growth and ocean circulation patterns, which have important implications for glacial North Pacific Intermediate Water formation and potentially North Pacific abyssal carbon storage