Spire stimulates nucleation by Cappuccino and binds both ends of actin filaments.

The actin nucleators Spire and Cappuccino synergize to promote actin assembly, but the mechanism of their synergy is controversial. Together these proteins promote the formation of actin meshes, which are conserved structures that regulate the establishment of oocyte polarity. Direct interaction between Spire and Cappuccino is required for oogenesis and for in vitro synergistic actin assembly. This synergy is proposed to be driven by elongation and the formation of a ternary complex at filament barbed ends, or by nucleation and interaction at filament pointed ends. To mimic the geometry of Spire and Cappuccino in vivo, we immobilized Spire on beads and added Cappuccino and actin. Barbed ends, protected by Cappuccino, grow away from the beads while pointed ends are retained, as expected for nucleation-driven synergy. We found that Spire is sufficient to bind barbed ends and retain pointed ends of actin filaments near beads and we identified Spire's barbed-end binding domain. Loss of barbed-end binding increases nucleation by Spire and synergy with Cappuccino in bulk pyrene assays and on beads. Importantly, genetic rescue by the loss-of-function mutant indicates that barbed-end binding is not necessary for oogenesis. Thus, increased nucleation is a critical element of synergy both in vitro and in vivo

Longitudinal study of trachomatous trichiasis in The Gambia: barriers to acceptance of surgery.

PURPOSE: Investigation of compliance with surgery for trachomatous trichiasis has become a priority of the World Health Organization. This study was conducted to investigate attitudes toward trichiasis and its treatment and to determine the rate of surgical uptake in The Gambia. METHODS: A 1-year longitudinal study was performed in 190 subjects with trichiasis. Persons with major trichiasis (involving five lashes or more) were referred for surgery, and those with minor trichiasis were advised to epilate. Outcome measures included attitudes toward trichiasis and its treatment, reported barriers to surgical uptake, acceptance rates for surgery, and factors affecting acceptance. RESULTS: Twenty-three percent (95% confidence interval [CI] 16.5%-30.6%) of subjects with major trichiasis attended for surgery during the year. Degree of ignorance about surgery, symptoms impeding work, and a multiple income source for the head of household predicted attendance. Reported lack of time predicted nonattendance. Sixty-eight percent of patients who had undergone surgery were trichiasis free at last follow-up. CONCLUSIONS: Poor attendance for surgery remains a problem in The Gambia. Barriers include ignorance and lack of time and money. Health education and surgical delivery strategies are needed to overcome these barriers. Regular audit of surgical results is necessary, with retraining where indicated

Mathematical modelling of fibre-enhanced perfusion inside\ud a tissue-engineering bioreactor

We develop a simple mathematical model for forced flow of culture medium through a porous scaffold in a tissue- engineering bioreactor. Porous-walled hollow fibres penetrate the scaffold and act as additional sources of culture medium. The model, based on Darcy’s law, is used to examine the nutrient and shear-stress distributions throughout the scaffold. We consider several configurations of fibres and inlet and outlet pipes. Compared with a numerical solution of the full Navier–Stokes equations within the complex scaffold geometry, the modelling approach is cheap, and does not require knowledge of the detailed microstructure of the particular scaffold being used. The potential of this approach is demonstrated through quantification of the effect the additional flow from the fibres has on the nutrient and shear-stress distribution

Extraordinary runoff from the Greenland ice sheet in 2012 amplified by hypsometry and depleted firn retention

It has been argued that the infiltration and retention of meltwater within firn across the percolation zone of the Greenland ice sheet has the potential to buffer up to similar to 3.6aEuro-mm of global sea-level rise (Harper et al., 2012). Despite evidence confirming active refreezing processes above the equilibrium line, their impact on runoff and proglacial discharge has yet to be assessed. Here, we compare meteorological, melt, firn stratigraphy and discharge data from the extreme 2010 and 2012 summers to determine the relationship between atmospheric forcing and melt runoff at the land-terminating Kangerlussuaq sector of the Greenland ice sheet, which drains into the Watson River. The 6.8aEuro-km(3) bulk discharge in 2012 exceeded that in 2010 by 28aEuro-%, despite only a 3aEuro-% difference in net incoming melt energy between the two years. This large disparity can be explained by a 10aEuro-% contribution of runoff originating from above the long-term equilibrium line in 2012 caused by diminished firn retention. The amplified 2012 response was compounded by catchment hypsometry; the disproportionate increase in area contributing to runoff as the melt-level rose high into the accumulation area. Satellite imagery and aerial photographs reveal an extensive supraglacial network extending 140aEuro-km from the ice margin that confirms active meltwater runoff originating well above the equilibrium line. This runoff culminated in three days with record discharge of 3100aEuro-m(3)aEuro-s(-1) (0.27aEuro-GtaEuro-d(-1)) that peaked on 11 July and washed out the Watson River Bridge. Our findings corroborate melt infiltration processes in the percolation zone, though the resulting patterns of refreezing are complex and can lead to spatially extensive, perched superimposed ice layers within the firn. In 2012, such layers extended to an elevation of at least 1840aEuro-m and provided a semi-impermeable barrier to further meltwater storage, thereby promoting widespread runoff from the accumulation area of the Greenland ice sheet that contributed directly to proglacial discharge and global sea-level rise

Synoptic-scale controls on the δ18O in precipitation across Beringia

Oxygen isotope records of precipitation (δ18Oprecip) from Beringia are thought to reflect synoptic-scale circulation changes associated with the Aleutian Low. To delineate the spatial pattern of δ18Oprecip associated with the two dominant modes of Aleutian Low circulation, we combine modern δ18Oprecip and deuterium excess data with climate reanalysis and back-trajectory modelling. Aleutian Low strength and position are revealed to systematically affect regional moisture source and δ18Oprecip; whereby a strengthened Aleutian Low causes lower (higher) δ18Oprecip in western (eastern) Beringia. We compare a new 100-year-long δ18O record from the Aleutian Islands with the North Pacific Index, the primary indicator of Aleutian Low strength, and find a significant positive relationship (r = 0.43, p < 0.02, n = 28) that tracks late 20th century change. This study demonstrates synoptic-scale circulation controls on our isotope record, and provides a coherent framework for interpreting existing and emerging paleo-isotope data from the region

Elucidating Nature’s Solutions to Heart, Lung, and Blood Diseases and Sleep Disorders

Evolution has provided a number of animal species with extraordinary phenotypes. Several of these phenotypes allow species to survive and thrive in environmental conditions that mimic disease states in humans. The study of evolved mechanisms that responsible for these phenotypes may provide insights into the basis of human disease and guide the design of new therapeutic approaches. Examples include species that tolerate acute or chronic hypoxemia like deep-diving mammals and high-altitude inhabitants, as well as those that hibernate and interrupt their development when exposed to adverse environments. The evolved traits exhibited by these animal species involve modifications of common biological pathways that affect metabolic regulation, organ function, antioxidant defenses, and oxygen transport. In 2006, the National Heart, Lung, and Blood Institute (NHLBI) released a funding opportunity announcement to support studies that were designed to elucidate the natural molecular and cellular mechanisms of adaptation in species that tolerate extreme environmental conditions. The rationale for this funding opportunity is detailed in this Special Article, and the specific evolved mechanisms examined in the supported research are described. Also highlighted are past medical advances achieved through the study of animal species that have evolved extraordinary phenotypes as well as the expectations for new understanding of nature’s solutions to heart, lung, blood, and sleep disorders through future research in this area

Associations of Sitting Behavior Patterns With Cardiometabolic Risk in Children: The Sit Less for Health Cross-Sectional Study

Accepted author manuscript version reprinted, by permission, from Journal of Physical Activity and Health, 2019, volume 16 (issue 10): 836-842, https://doi.org/10.1123/jpah.2018-0469. © Human Kinetics, Inc

Elucidating Nature’s Solutions to Heart, Lung, and Blood Diseases and Sleep Disorders

Evolution has provided a number of animal species with extraordinary phenotypes. Several of these phenotypes allow species to survive and thrive in environmental conditions that mimic disease states in humans. The study of evolved mechanisms that responsible for these phenotypes may provide insights into the basis of human disease and guide the design of new therapeutic approaches. Examples include species that tolerate acute or chronic hypoxemia like deep-diving mammals and high-altitude inhabitants, as well as those that hibernate and interrupt their development when exposed to adverse environments. The evolved traits exhibited by these animal species involve modifications of common biological pathways that affect metabolic regulation, organ function, antioxidant defenses, and oxygen transport. In 2006, the National Heart, Lung, and Blood Institute (NHLBI) released a funding opportunity announcement to support studies that were designed to elucidate the natural molecular and cellular mechanisms of adaptation in species that tolerate extreme environmental conditions. The rationale for this funding opportunity is detailed in this Special Article, and the specific evolved mechanisms examined in the supported research are described. Also highlighted are past medical advances achieved through the study of animal species that have evolved extraordinary phenotypes as well as the expectations for new understanding of nature’s solutions to heart, lung, blood, and sleep disorders through future research in this area

The Impact of Trachomatous Trichiasis on Quality of Life: A Case Control Study.

BACKGROUND: Trachomatous trichiasis is thought to have a profound effect on quality of life (QoL), however, there is little research in this area. We measured vision and health-related QoL in a case-control study in Amhara Region, Ethiopia. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 1000 adult trichiasis cases and 200 trichiasis-free controls, matched to every fifth trichiasis case on age (+/- two years), sex and location. Vision-related quality of life (VRQoL) and health-related quality of life (HRQoL) were measured using the WHO/PBD-VF20 and WHOQOL-BREF questionnaires. Comparisons were made using linear regression adjusted for age, sex and socioeconomic status. Trichiasis cases had substantially lower VRQoL than controls on all subscales (overall eyesight, visual symptom, general functioning and psychosocial, p<0.0001), even in the sub-group with normal vision (p<0.0001). Lower VRQoL scores in cases were associated with longer trichiasis duration, central corneal opacity, visual impairment and poor contrast sensitivity. Trichiasis cases had lower HRQoL in all domains (Physical-health, Psychological, Social, Environment, p<0.0001), lower overall QoL (mean, 34.5 v 64.6; p<0.0001) and overall health satisfaction (mean, 38.2 v 71.7; p<0.0001). This association persisted in a sub-group analysis of cases and controls with normal vision. Not having a marriage partner (p<0.0001), visual impairment (p = 0.0068), daily labouring (p<0.0001), presence of other health problems (p = 0.0018) and low self-rated wealth (p<0.0001) were independently associated with lower overall QoL scores in cases. Among cases, trichiasis caused 596 (59%) to feel embarrassed, 913 (91.3%) to worry they may lose their remaining eyesight and 681 (68.1%) to have sleep disturbance. CONCLUSIONS/SIGNIFICANCE: Trachomatous trichiasis substantially reduces vision and health related QoL and is disabling, even without visual impairment. Prompt trichiasis intervention is needed both to prevent vision loss and to alleviate physical and psychological suffering, social exclusion and improve overall well-being. Implementation of the full SAFE strategy is needed to prevent the development of trachomatous trichiasis