Wiskott Aldrich syndrome protein regulates non-selective autophagy and mitochondrial homeostasis in human myeloid cells.

The actin cytoskeletal regulator Wiskott Aldrich syndrome protein (WASp) has been implicated in maintenance of the autophagy-inflammasome axis in innate murine immune cells. Here, we show that WASp deficiency is associated with impaired rapamycin-induced autophagosome formation and trafficking to lysosomes in primary human monocyte-derived macrophages (MDMs). WASp reconstitution in vitro and in WAS patients following clinical gene therapy restores autophagic flux and is dependent on the actin-related protein complex ARP2/3. Induction of mitochondrial damage with CCCP, as a model of selective autophagy, also reveals a novel ARP2/3-dependent role for WASp in formation of sequestrating actin cages and maintenance of mitochondrial network integrity. Furthermore, mitochondrial respiration is suppressed in WAS patient MDMs and unable to achieve normal maximal activity when stressed, indicating profound intrinsic metabolic dysfunction. Taken together, we provide evidence of new and important roles of human WASp in autophagic processes and immunometabolic regulation, which may mechanistically contribute to the complex WAS immunophenotype

Temporal dynamics of aquatic communities and implications for pond conservation

Conservation through the protection of particular habitats is predicated on the assumption that the conservation value of those habitats is stable. We test this assumption for ponds by investigating temporal variation in macroinvertebrate and macrophyte communities over a 10-year period in northwest England. We surveyed 51 ponds in northern England in 1995/6 and again in 2006, identifying all macrophytes (167 species) and all macroinvertebrates (221 species, excluding Diptera) to species. The alpha-diversity, beta-diversity and conservation value of these ponds were compared between surveys. We find that invertebrate species richness increased from an average of 29. 5 species to 39. 8 species between surveys. Invertebrate gamma-diversity also increased between the two surveys from 181 species to 201 species. However, this increase in diversity was accompanied by a decrease in beta-diversity. Plant alpha-, beta and gamma-diversity remained approximately constant between the two periods. However, increased proportions of grass species and a complete loss of charophytes suggests that the communities are undergoing succession. Conservation value was not correlated between sampling periods in either plants or invertebrates. This was confirmed by comparing ponds that had been disturbed with those that had no history of disturbance to demonstrate that levels of correlation between surveys were approximately equal in each group of ponds. This study has three important conservation implications: (i) a pond with high diversity or high conservation value may not remain that way and so it is unwise to base pond conservation measures upon protecting currently-speciose habitats; (ii) maximising pond gamma-diversity requires a combination of late and early succession ponds, especially for invertebrates; and (iii) invertebrate and plant communities in ponds may require different management strategies if succession occurs at varying rates in the two groups

Accessory muscle in the forearm: a clinical and embryological approach

Muscular variations of the flexor compartment of forearm are usual and can result in multiple clinical conditions limiting the functions of forearm and hand. The variations of the muscles, especially accessory muscles may simulate soft tissue tumors and can result in nerve compressions. During a routine dissection of the anterior region of the forearm and hand, an unusual muscle was observed on the left side of a 65-year-old male cadaver. The anomalous muscle belly arose from the medial epicondyle approxiamately 1 cm posterolateral to origin of normal flexor carpi ulnaris muscle (FCU), and from proximal part of the flexor digitorum superficialis muscle. It inserted to the triquetral, hamate bones and flexor retinaculum. Passive traction on the tendon of accessory muscle resulted in flexion of radiocarpal junction. The FCU which had one head, inserted to the pisiform bone hook of hamate and palmar aponeurosis. Its contiguous muscles displayed normal morphology. Knowledge of the existence of muscle anomalies as well as the location of compression is useful in determining the pathology and appropriate treatment for compressive neuropathies. In this study, a rare accessory muscle has been described

Are orthodontic educational opportunities adequate?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32251/1/0000313.pd

Unpopular Culture: Ecological Dissonance and Sustainable Futures in Media-Induced Tourism

The article deconstructs media-induced tourist development’s relationship with “sustainability,” “ecology” and the “popular”. I highlight the interconnected, but often competing interpretations of “ecology” as interactions among technics (representational regimes), technological regimes and institutions (media, tourism), social agents (media/tourism experts, fan tourists and their hosts), and the natural and built environment in which these take place. Constitutive of contemporary economic and sociocultural complexities in which media-induced “popular cultures” are produced and consumed, these ecological landscapes are increasingly in conflict between and within themselves. Such conflicts destabilize “popular culture” as ritualized behavior or experiential domain, enmeshing it into populist reactions against tourists/guests/strangers

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Investigating the great crested newt landscape in a pond rich environment : developing a landscape scale management perspective

This thesis investigated graph theoretic analysis of connectivity and habitat availability for landscape scale management of Triturus cristatus, the Great Crested Newt. The ecological foundations of wider landscape management concepts and knowledge base on T. cristatus' habitat requirements, dispersal and migration were explored. Species presence, and aquatic and terrestrial habitat on the Cholmondeley Estate, Malpas, Cheshire, UK was mapped and land cover characterized for suitability and traversibility by T. cristatus. Habitat area available and accessible from ponds were identified. Analysis and modelling of pondscape connectivity using Probability of Connectivity (PC) and related indices, was carried out using Euclidean and Cost Weighted Distance and pond clustering at ecologically relevant scales was examined. Association or correlation of presence with proximity to breeding ponds, pond cluster size, proximity and available quantity of terrestrial habitat, proximity to roads and moving water, and connectivity of breeding ponds were examined at Cost Weighted and Euclidean distances. Connectivity, (PC index), pond count in clusters at 250 and 500m thresholds of connectivity, and proximity to core habitat (broad leaved woodland and rough grassland) using Cost Weighted distances were positively associated with breeding presence. Road proximity and density, proximity of core habitat at Euclidean distances and mean inter-pond distance were not significantly associated with breeding presence. Proximity to moving water was negatively associated with breeding presence. Resistance to movement of various land cover types has important implications for habitat availability and connectivity, , / and important questions are raised in terms of "rule of thumb" guidelines for estimation of connectivity between pond populations and habitat availability around breeding ponds. Graph analysis was used to identify priority areas for maintenance of landscape level connectivity, and enhancement of habitat connectivity and availability on the local population scale, with prioritization of pond creation/protection sites against their contribution to connectivity and habitat I availability, examining various scenarios.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Temporal dynamics of aquatic communities and implications for pond conservation

<p>Conservation through the protection of particular habitats is predicated on the assumption that the conservation value of those habitats is stable. We test this assumption for ponds by investigating temporal variation in macroinvertebrate and macrophyte communities over a 10-year period in northwest England. We surveyed 51 ponds in northern England in 1995/6 and again in 2006, identifying all macrophytes (167 species) and all macroinvertebrates (221 species, excluding Diptera) to species. The alpha-diversity, beta-diversity and conservation value of these ponds were compared between surveys. We find that invertebrate species richness increased from an average of 29.5 species to 39.8 species between surveys. Invertebrate gamma-diversity also increased between the two surveys from 181 species to 201 species. However, this increase in diversity was accompanied by a decrease in beta-diversity. Plant alpha-, beta- and gamma-diversity remained approximately constant between the two periods. However, increased proportions of grass species and a complete loss of charophytes suggests that the communities are undergoing succession. Conservation value was not correlated between sampling periods in either plants or invertebrates. This was confirmed by comparing ponds that had been disturbed with those that had no history of disturbance to demonstrate that levels of correlation between surveys were approximately equal in each group of ponds. This study has three important conservation implications: (i) a pond with high diversity or high conservation value may not remain that way and so it is unwise to base pond conservation measures upon protecting currently-speciose habitats; (ii) maximising pond gamma-diversity requires a combination of late and early succession ponds, especially for invertebrates; and (iii) invertebrate and plant communities in ponds may require different management strategies if succession occurs at varying rates in the two groups.</p

Environmental correlates of plant and invertebrate species richness in ponds

<p>Ponds (lentic water bodies <2 ha) constitute a considerable biodiversity resource. Understanding the environmental factors that underlie this diversity is important in protecting and managing the habitat. We surveyed 425 ponds for biological and physical characteristics with 78 of those also surveyed for chemical characteristics. A total of 277 invertebrate species and 265 plant species were found. Species richness varied between 2 and 99 (mean 27.2 ± 0.6 SE) for invertebrates and 1 and 58 (mean 20.8 ± 0.4 SE) for plants. Generalised additive models were used to investigate variables that correlate with the species richness of plants and invertebrates, with additional models to investigate insect, Coleoptera, Odonata, Hemiptera, Trichoptera and Mollusca species richness. Models performed reasonably well for invertebrates in general (R 2 = 30.3%) but varied between lower-order invertebrate taxa (12.7–34.7%). Ponds with lower levels of shading and no history of drying contained higher numbers of species of plants and all invertebrate groups. Aquatic plant coverage positively correlated with species richness in all invertebrate groups apart from Trichoptera and the presence of fish was associated with high invertebrate species richness in all groups apart from Coleoptera. The addition of chemistry variables suggested non-linear relationships between oxygen demand and phosphate concentration and higher-order richness. We demonstrate that the composition of biological communities varies along with their species richness and that less diverse ponds are more variable compared to more diverse ponds. Variables positively correlated with richness of one taxon may be negatively correlated with that of another, making comprehensive management recommendations difficult. Promoting a high landscape-level pond biodiversity will involve the management of a high diversity of pond types within that landscape.</p

Wiskott Aldrich syndrome protein regulates non-selective autophagy and mitochondrial homeostasis in human myeloid cells.

The actin cytoskeletal regulator Wiskott Aldrich syndrome protein (WASp) has been implicated in maintenance of the autophagy-inflammasome axis in innate murine immune cells. Here, we show that WASp deficiency is associated with impaired rapamycin-induced autophagosome formation and trafficking to lysosomes in primary human monocyte-derived macrophages (MDMs). WASp reconstitution in vitro and in WAS patients following clinical gene therapy restores autophagic flux and is dependent on the actin-related protein complex ARP2/3. Induction of mitochondrial damage with CCCP, as a model of selective autophagy, also reveals a novel ARP2/3-dependent role for WASp in formation of sequestrating actin cages and maintenance of mitochondrial network integrity. Furthermore, mitochondrial respiration is suppressed in WAS patient MDMs and unable to achieve normal maximal activity when stressed, indicating profound intrinsic metabolic dysfunction. Taken together, we provide evidence of new and important roles of human WASp in autophagic processes and immunometabolic regulation, which may mechanistically contribute to the complex WAS immunophenotype