Conservation of Complex Nuclear Localization Signals Utilizing Classical and Non-Classical Nuclear Import Pathways in LANA Homologs of KSHV and RFHV

ORF73 latency-associated nuclear antigen (LANA) of the Kaposi's sarcoma-associated herpesvirus (KSHV) is targeted to the nucleus of infected cells where it binds to chromatin and mediates viral episome persistence, interacts with cellular proteins and plays a role in latency and tumorigenesis. A structurally related LANA homolog has been identified in the retroperitoneal fibromatosis herpesvirus (RFHV), the macaque homolog of KSHV. Here, we report the evolutionary and functional conservation of a novel bi-functional nuclear localization signal (NLS) in KSHV and RFHV LANA. N-terminal peptides from both proteins were fused to EGFP or double EGFP fusions to examine their ability to induce nuclear transport of a heterologous protein. In addition, GST-pull down experiments were used to analyze the ability of LANA peptides to interact with members of the karyopherin family of nuclear transport receptors. Our studies revealed that both LANA proteins contain an N-terminal arginine/glycine (RG)-rich domain spanning a conserved chromatin-binding motif, which binds directly to importin β1 in a RanGTP-sensitive manner and serves as an NLS in the importin β1-mediated non-classical nuclear import pathway. Embedded within this domain is a conserved lysine/arginine-(KR)-rich bipartite motif that binds directly to multiple members of the importin α family of nuclear import adaptors in a RanGTP-insensitive manner and serves as an NLS in the classical importin α/β-mediated nuclear import pathway. The positioning of a classical bipartite kr-NLS embedded within a non-classical rg-NLS is a unique arrangement in these viral proteins, whose nuclear localization is critical to their functionality and to the virus life cycle. The ability to interact with multiple import receptors provides alternate pathways for nuclear localization of LANA. Since different import receptors can import cargo to distinct subnuclear compartments, a multifunctional NLS may provide LANA with an increased ability to interact with different nuclear components in its multifunctional role to maintain viral latency

Biofeedback for training balance and mobility tasks in older populations: a systematic review

<p>Abstract</p> <p>Context</p> <p>An effective application of biofeedback for interventions in older adults with balance and mobility disorders may be compromised due to co-morbidity.</p> <p>Objective</p> <p>To evaluate the feasibility and the effectiveness of biofeedback-based training of balance and/or mobility in older adults.</p> <p>Data Sources</p> <p>PubMed (1950-2009), EMBASE (1988-2009), Web of Science (1945-2009), the Cochrane Controlled Trials Register (1960-2009), CINAHL (1982-2009) and PsycINFO (1840-2009). The search strategy was composed of terms referring to biofeedback, balance or mobility, and older adults. Additional studies were identified by scanning reference lists.</p> <p>Study Selection</p> <p>For evaluating effectiveness, 2 reviewers independently screened papers and included controlled studies in older adults (i.e. mean age equal to or greater than 60 years) if they applied biofeedback during repeated practice sessions, and if they used at least one objective outcome measure of a balance or mobility task.</p> <p>Data Extraction</p> <p>Rating of study quality, with use of the Physiotherapy Evidence Database rating scale (PEDro scale), was performed independently by the 2 reviewers. Indications for (non)effectiveness were identified if 2 or more similar studies reported a (non)significant effect for the same type of outcome. Effect sizes were calculated.</p> <p>Results and Conclusions</p> <p>Although most available studies did not systematically evaluate feasibility aspects, reports of high participation rates, low drop-out rates, absence of adverse events and positive training experiences suggest that biofeedback methods can be applied in older adults. Effectiveness was evaluated based on 21 studies, mostly of moderate quality. An indication for effectiveness of visual feedback-based training of balance in (frail) older adults was identified for postural sway, weight-shifting and reaction time in standing, and for the Berg Balance Scale. Indications for added effectiveness of applying biofeedback during training of balance, gait, or sit-to-stand transfers in older patients post-stroke were identified for training-specific aspects. The same applies for auditory feedback-based training of gait in older patients with lower-limb surgery.</p> <p>Implications</p> <p>Further appropriate studies are needed in different populations of older adults to be able to make definitive statements regarding the (long-term) added effectiveness, particularly on measures of functioning.</p

420,000 year assessment of fault leakage rates shows geological carbon storage is secure

Carbon capture and storage (CCS) technology is routinely cited as a cost effective tool for climate change mitigation. CCS can directly reduce industrial CO2 emissions and is essential for the retention of CO2 extracted from the atmosphere. To be effective as a climate change mitigation tool, CO2 must be securely retained for 10,000 years (10 ka) with a leakage rate of below 0.01% per year of the total amount of CO2 injected. Migration of CO2 back to the atmosphere via leakage through geological faults is a potential high impact risk to CO2 storage integrity. Here, we calculate for the first time natural leakage rates from a 420 ka paleo-record of CO2 leakage above a naturally occurring, faulted, CO2 reservoir in Arizona, USA. Surface travertine (CaCO3) deposits provide evidence of vertical CO2 leakage linked to known faults. U-Th dating of travertine deposits shows leakage varies along a single fault and that individual seeps have lifespans of up to 200 ka. Whilst the total volumes of CO2 required to form the travertine deposits are high, time-averaged leakage equates to a linear rate of less than 0.01%/yr. Hence, even this natural geological storage site, which would be deemed to be of too high risk to be selected for engineered geologic storage, is adequate to store CO2 for climate mitigation purposes

Familial and cultural perceptions and beliefs of oral hygiene and dietary practices among ethnically and socio-economically diverse groups

Objective: The aim of this international study was to develop a valid and reliable psychometric measure to examine the extent to which parents' attitudes about engaging in twice-daily tooth brushing and controlling sugar snacking predict these respective behaviours in their children. A supplementary objective was to assess whether ethnic group, culture, level of deprivation or children's caries experience impact upon the relationships between oral health related behaviours, attitudes to these respective behaviours and to dental caries. Clinical setting: nurseries, health centres and dental clinics in 17 countries. Participants: 2822 children aged 3 to 4 years and their parents. Main outcome measures: Dental examination of children and questionnaire to parents. Results: factor analysis identified 8 coherent attitudes towards toothbrushing, sugar snacking and childhood caries. Attitudes were significantly different in families from deprived and non-deprived backgrounds and in families of children with and without caries. Parents' perception of their ability to control their children's toothbrushing and sugar snacking habits were the most significant predictors of whether or not favourable habits were reported. Some differences were found by site and ethnic group. Conclusions: this study supports the hypothesis that parental attitudes significantly impact on the establishment of habits favourable to oral health. An appreciation of the impact of cultural and ethnic diversity is important in understanding how parental attitudes to oral health vary. Further research should examine in a prospective intervention whether enhancing parenting skills is an effective route to preventing childhood caries.link_to_subscribed_fulltex

Pulses of carbon dioxide emissions from intracrustal faults following climatic warming

Carbon capture and geological storage represents a potential means of managing atmospheric carbon dioxide levels. Understanding the role of faults, as either barriers or conduits to the flow of carbon dioxide, is crucial for predicting the long-term integrity of geological storage sites. Of particular concern is the influence of geochemical reactions on the sealing behaviour of faults and the impact of seismicity and stress regime on fault stability. Here, we examine a 135,000-year palaeorecord of carbon dioxide leakage from a faulted, natural carbon dioxide reservoir in Utah. We assess the isotope and trace-element composition of U-Th-dated carbonate veins, deposited by carbon-dioxide-rich fluids. Temporal changes in vein geochemistry reveal pulses of carbon dioxide injection into the reservoir from deeper formations. Surface leakage rates increase by several orders of magnitude following these pulses. We show that each pulse occurs around 100-2,000 years after the onset of significant local climatic warming, at glacial to interglacial transitions. We suggest that carbon dioxide leakage rates increase as a result of fracture opening, potentially caused by changes in groundwater hydrology, the intermittent presence of a buoyant gas cap and postglacial crustal unloading of regions surrounding the fault