Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1

Muscle tissue is the major site for insulin-stimulated glucose uptake in vivo, due primarily to the recruitment of the insulin-sensitive glucose transporter (GLUT4) to the plasma membrane. Surprisingly, virtually all cultured muscle cells express little or no GLUT4. We show here that adenovirus-mediated expression of the transcriptional coactivator PGC-1, which is expressed in muscle in vivo but is also deficient in cultured muscle cells, causes the total restoration of GLUT4 mRNA levels to those observed in vivo. This increased GLUT4 expression correlates with a 3-fold increase in glucose transport, although much of this protein is transported to the plasma membrane even in the absence of insulin. PGC-1 mediates this increased GLUT4 expression, in large part, by binding to and coactivating the muscle-selective transcription factor MEF2C. These data indicate that PGC-1 is a coactivator of MEF2C and can control the level of endogenous GLUT4 gene expression in muscle.

In vivo restoration of laminin 5 ��3 expression and function in junctional epidermolysis bullosa

The blistering disorder, lethal junctional epidermolysis bullosa (JEB), can result from mutations in the LAMB3 gene, which encodes laminin 5 ��3 (��3). Appropriate expression of LAM��3 in JEB skin tissue could potentially ameliorate the symptoms of the underlying disease. To explore the utility of this therapeutic approach, primary keratinocytes from six unrelated JEB patients were transduced with a retroviral vector encoding ��3 and used to regenerate human skin on severe combined immunodeficient (SCID) mice. Tissue regenerated from ��3-transduced JEB keratinocytes produced phenotypically normal skin characterized by sustained ��3 expression and the formation of hemidesmosomes. Additionally, ��3 gene transfer corrected the distribution of a number of important basement membrane zone proteins including BPAG2, integrins ��4/��1, and laminins ��3/��2. Skin produced from ��3-negative (��3[���]) JEB cells mimicked the hallmarks of the disease state and did not exhibit any of the aforementioned traits. Therefore, by effecting therapeutic gene transfer to ��3-deficient primary keratinocytes, it is possible to produce healthy, normal skin tissue in vivo. These data support the utility of gene therapy for JEB and highlight the potential for gene delivery in the treatment of human genetic skin disease.

Negative pH, efflorescent mineralogy, and consequences for environmental restoration at the Iron Mountain Superfund site, California

The Richmond Mine of the Iron Mountain copper deposit contains some of the most acid mine waters ever reported. Values of pH have been measured as low as ���3.6, combined metal concentrations as high as 200 g/liter, and sulfate concentrations as high as 760 g/liter. Copious quantities of soluble metal sulfate salts such as melanterite, chalcanthite, coquimbite, rhomboclase, voltaite, copiapite, and halotrichite have been identified, and some of these are forming from negative-pH mine waters. Geochemical calculations show that, under a mine-plugging remediation scenario, these salts would dissolve and the resultant 600,000-m3 mine pool would have a pH of 1 or less and contain several grams of dissolved metals per liter, much like the current portal effluent water. In the absence of plugging or other at-source control, current weathering rates indicate that the portal effluent will continue for approximately 3,000 years. Other remedial actions have greatly reduced metal loads into downstream drainages and the Sacramento River, primarily by capturing the major acidic discharges and routing them to a lime neutralization plant. Incorporation of geochemical modeling and mineralogical expertise into the decision-making process for remediation can save time, save money, and reduce the likelihood of deleterious consequences.

Membrane healing and restoration of contractility after mechanical injury in isolated skeletal muscle fibers of the frog.

In single isolated skeletal muscle fibers of the frog, we studied (i) the recovery from large sarcolemmal mechanical injuries of the response to electric stimulation and (ii) the integrity of the sarcolemma under the light microscope. In Ringer's solution, the damaged cells stopped contracting and deteriorated completely within 1 hr. In the presence of phosphatidylcholine (0.025 g/ml in Ringer's solution), the injured cells initially responded with local twitches. Within 0.5 hr, contractility and membrane integrity started to recover and both were back to control levels within 3 hr. When these cells were placed back in normal Ringer's solution, they remained viable and active for several hours. Our results suggest that phosphatidylcholine can protect muscle fibers from the effects of sarcolemmal injury.

Restoration of surface IgM-mediated apoptosis in an anti-IgM-resistant variant of WEHI-231 lymphoma cells by HS1, a protein-tyrosine kinase substrate.

The HS1 protein is one of the major substrates of non-receptor-type protein-tyrosine kinases and is phosphorylated immediately after crosslinking of the surface IgM on B cells. The mouse B-lymphoma cell line WEHI-231 is known to undergo apoptosis upon crosslinking of surface IgM by anti-IgM antibodies. Variants of WEHI-231 that were resistant to anti-IgM-induced apoptosis expressed dramatically reduced levels of HS1 protein. Expression of the human HS1 protein from an expression vector introduced into one of the variant cell lines restored the sensitivity of the cells to apoptosis induced by surface IgM crosslinking. These results suggest that HS1 protein plays a crucial role in the B-cell antigen receptor-mediated signal transduction pathway that leads to apoptosis.

Efetividade das ��reas protegidas para a conserva����o da natureza sob a abordagem dos servi��os ecossist��micos na bacia do rio Corumbata��

A sustentabilidade da paisagem trata-se de um tema central no que se refere ��s quest��es de conserva����o e desenvolvimento de paisagens altamente antropizadas. Est�� embasada nos conceitos tradicionais de desenvolvimento sustent��vel, que visam balancear o desenvolvimento humano com a prote����o ambiental, pautada na equidade intra e extra-gera����o. Considera, ainda, os conceitos de bem-estar humano nesta esfera. Paralelamente, os conceitos de servi��os ecossist��micos reconhecem a depend��ncia das atividades antr��picas e seu bem-estar �� qualidade dos ecossistemas, reacendendo os debates sobre capital natural e desenvolvimento sustent��vel. Neste contexto, este trabalho aborda a sustentabilidade da paisagem questionando a potencialidade dos remanescentes florestais em fornecer, de maneira equilibrada, diferentes servi��os ecossist��micos na bacia do rio Corumbata��. Para isso, o trabalho foi dividido em duas etapas. A primeira buscou analisar quest��es de demanda e oferta por m��ltiplos servi��os ecossist��micos (controle de eros��o, regula����o h��drica, regula����o microclim��tica, informa����o est��tica e qualidade de habitat). Isso baseado em indicadores da paisagem, como a din��mica do uso do solo e padr��es do meio f��sico e antr��pico. A segunda investigou a viabilidade de integrar o sinergismo entre os servi��os de controle de eros��o e qualidade de habitat ��s prioridades de conserva����o e restaura����o florestal. Isso baseado no cen��rio atual da paisagem e por meio de diferentes simula����es de incremento em 10% da cobertura florestal na paisagem, inserindo florestas nos locais de alta erodibilidade (situa����o criteriosa) ou de forma rand��mica. Os resultados demonstraram que, apesar do aumento de 60% na cobertura florestal durante os ��ltimos 30 anos, apenas 37% das florestas possuem alto potencial para ofertar servi��os ecossist��micos e que, quando ponderadas perante as demandas da paisagem, apenas 20% das florestas encontram-se em equil��brio. Al��m disso, foi verificado sinergismo entre os servi��os de controle de eros��o e qualidade de habitat em aproximadamente 80% da cobertura florestal. No entanto, nos cen��rios de restaura����o florestal, o sinergismo foi alcan��ado em todas as situa����es, sejam elas criteriosas ou rand��micas. Deste modo, ficou evidente o limite das florestas e ��reas protegidas como potenciais prestadoras de servi��os ecossist��micos na paisagem. Tamb��m ficou evidente que, em paisagens com alto grau de fragmenta����o e baixa propor����o florestal, os processos de restaura����o n��o necessariamente devem almejar o sinergismo entre servi��os ecossist��micos. Por fim, atribui-se grande import��ncia ao papel das ��reas agr��colas e pastagens para compensar demandas, restaurar servi��os ecossist��micos, almejando, portanto, a sustentabilidade da paisagem.

Pseudoscalar susceptibilities and quark condensates: chiral restoration and lattice screening masses

We derive the formal Ward identities relating pseudoscalar susceptibilities and quark condensates in three-flavor QCD, including consistently the 77-n' sector and the U-A(1) anomaly. These identities are verified in the low-energy realization provided by ChPT, both in the standard SU(3) framework for the octet case and combining the use of the SU(3) framework and the large-Nc expansion of QCD to account properly for the nonet sector and anomalous contributions. The analysis is performed including finite temperature corrections as well as the calculation of U(3) quark condensates and all pseudoscalar susceptibilities, which together with the full set of Ward identities, are new results of this work. Finally, the Ward identities are used to derive scaling relations for pseudoscalar masses which explain the behavior with temperature of lattice screening masses near chiral symmetry restoration.

The Relationship Between Weight Restoration and Maturity Fears in Women with Anorexica Nervosa

High maturity fears predict poor treatment outcomes in women with anorexia nervosa (AN). The purpose of this study was to determine if weight gain predicts decreases in maturity fears (MF) for AN patients. Fifty-six patients in an eating disorders partial hospitalization program were administered a series of psychological tests at intake and discharge. R2 values indicate that percent change in weight restoration will not accurately forecast the change in MF scores, although a positive trend was identified between the two variables. The weak predictive relationship suggests that weight restoration alone is not adequate to address the psychological components of AN.

Restoration Efforts and Prairie Dog Management at the Rocky Mountain Arsenal National Wildlife Refuge

The Rocky Mountain Arsenal National Wildlife Refuge is being re-seeded to native shortgrass prairie, but the effects of prairie dog colonization on some sites may be limiting successful native plant establishment. This Capstone Project compares vegetation monitoring data and prairie dog distributions in four refuge sites to evaluate the effects of prairie dog colonization on restoration. In general, native plant abundance has increased on study plots since initiation of restoration. Localized changes in plant abundance have occurred among transects, but prairie dog densities could not be correlated with the changes. Future prairie dog expansion is cause for concern due to intensified burrowing and grazing effects. Seven recommendations are presented to aid future restoration efforts.

The Rio Salado Riparian Habitat Restoration Area: Managing the Southwestern Willow Flycatcher

The following document identifies the impact to the current management plan of the Rio Salado Riparian Habitat Restoration Area in the event the endangered Southwestern Willow Flycatcher is found nesting at the project site. Rio Salado is managed by the City of Phoenix Parks and Recreation Department, and consists of a low-flow channel with native vegetation and wildlife along the Salt River. This paper analyzes the regulatory responsibilities of project site management and discusses the necessary adjustments to the management plan. Despite the current absence of the Southwestern Willow Flycatcher from Rio Salado, management should enter into a Safe Harbor Agreement with the U.S. Fish and Wildlife Service to legally protect themselves from the regulations stipulated in the Endangered Species Act.

Leading Safety Indicators: Proactively Monitoring Safety Performance

Traditional measures or indicators of workplace safety performance reflect unrecognized hazards, unsafe conditions, reckless behavior, and other safety program shortcomings only after a worker is injured or falls ill. In contrast to traditional or lagging indicators, leading indicators can predict poor safety performance to ensure that safety program failings are addressed before an occupational injury or illness actually occurs. This Capstone Project identified a variety of proactive safety management practices, policies, and activities shown to have a positive impact on workplace safety as leading safety indicators. The end result is a comprehensive framework of leading safety indicators that employers can use to proactively gauge safety program performance and address unrecognized hazards, unsafe conditions, reckless behavior, and other safety program deficiencies.

Effects of landscape spatial heterogeneity on dryland restoration success. The combined role of site conditions and reforestation techniques in southeastern Spain

In occidental Europe, Spain is one of countries the most severely affected by desertification (Arnalds & Arsher 2000). Particularly, South-eastern Spain is considered as one of the most threatened areas by desertification in Mediterranean Europe (Vallejo 1997). In 2003, the Valencia Regional Forest Service implemented a restoration demonstration project in this area. The project site is a small catchment (25 ha) located in the Albatera municipality. The catchment is highly heterogeneous, with terraced slopes, south-facing slopes and north-facing slopes. The restoration strategy was based on planting evergreen trees and shrubs which can grow quickly after disturbances, and on field treatments aimed at maximizing water collection (micro-catchments, planting furrows), organic amendment (compost), and conservation (tree shelters, mulching). On south landscape unit, the whole category of restoration treatments was applied: water micro-catchment + Tubex tree shelters + mulching & compost, while on north landscape unit: netting tree shelters + mulching & compost only were applied, while in terrace landscape unit: furrows + netting tree shelters + mulching & compost were applied. Survival and growth of the planted seedlings were used as metrics of restoration success. To assess the effects of the treatments applied for soil conservation, soil loss rates (from 2005 to 2009) were evaluated using the erosion pin method. We conclude that, despite the limiting conditions prevailing on the south unit, this landscape unit showed the highest survival and growth plant rates in the area. The best seedling performances on the south landscape unit were probably due to the highest technical efforts applied, consisting in the water micro-catchment installation and the Tubex plant shelters addition. In addition, soil loss rates followed decreasing trends throughout the assessment period. Soil loss rates were highest on south landscape unit in comparison with the other landscape units, due to the more accentuated relief. North landscape unit and terrace unit showed a net soil mass gain, probably reflecting the trapping of sediments produced by plantation works.

Indicators of obesity and the educational attainment of the Czech female population

The aim of this paper was to evaluate the relationship between selected indicators of obesity and the highest completed level of education in the adult female population of the Czech republic. As basic indicators of obesity, these following parameters were selected and measured via the bioimpedance method on the device InBody 720: BMI, WHR (waist-to-hip ratio), % body fat, % skeletal muscle mass, fitness score. The educational attainment of the tested women was inquired by a questionnaire. Based on the responses, we subsequently divided our sample into four categories according to the level of education: primary education, secondary education-apprenticeship, secondary education-graduate diploma, and university. The research was realized within the project CZ.1.07/2.3.00/20.0044. The measurements on the device InBody 720 and the accompanying survey were conducted between 2011-2013 in different regions of the Czech Republic. The sample consisted of 754 women divided into 3 age groups (18-39, 40-59, 60+ years). Based on the results (p<0.05), we can say that average values of the indicators obesity (BMI: 22.76, 24.88, 26.49 kg/m2, WHR: 0.85, 0.88, 0.90 and % body fat: 25.76, 30.23, 34.62%) increase with the increasing age of examined women. The average values of the fitness score (75.53, 73.86, 70.04 points) and % skeletal muscle mass (40.78, 38.15, 33.95%) decrease with increasing age. With regard to the educational attainment, women with secondary education-apprenticeship achieved the worst results. In contrast, the values in university educated women were the best in most indicators of obesity.

Indicators of success in the dietary management of overweight and��obesity: weight, body fat loss and quality

Concepts: %WL: Percentage of weight loss; %FL: Percentage of fat loss. Objective: evaluate which unit of measurement for weight loss could determine the success or failure of dietary treatment for overweight and obesity. Method: 4,625 consultations carried out on 616 patients in the southeast of Spain from 2006 to 2012. All of the patients were over 25 years of age and suffered from overweight or obesity. The consultations were carried out every fortnight, using the Mediterranean or low-calorie diet. The patients were divided into four groups according to their %WL and %FL. Results: most of the sample consisted of: women; participants between 25-45 years of age; attended consultations for over a month and a half; obese. 80% of the patients obtained a %FL ��� 5% (15.5 �� 12.8). The groups with a higher %FL obtained significant differences in weight loss (22.6 vs 11.2%, p = 0.000). The multinomial analysis shows significant differences between the groups with the highest %FL and the lowest %WL and %FL: sex (p = 0.006 vs p = 0.005), BMI (p = 0.010 vs p = 0.003) and attendance (p = 0.000 vs p = 0.000). Conclusion: the patients who lost < 5% of fat had higher initial parameters (percentage of weight and fat); most of the sample lost ��� 5% of fat. This means that the method of personalised dietary treatment results in a high fat loss; fat is an indicator of the quality loss obtained. Recommendations: use the measurement of fat as a complementary unit of measurement to weight loss; establish a limit of 5% to evaluate such loss; and increase this type of research in any method of weight loss.

Restoration of religious temples: intervention in the church ���Nuestra Se��ora de Bel��n��� in Crevillente (Alicante)

Heritage conservation has raised historical problems usually centered in defects resulting from water leaks. Thus, any intervention is presented as a difficult task, both due to building techniques to be used and the lack of economic resources in many cases. In relation to the temples existing in Alicante (Spain), water drainage is solved with pitched roofs on slope formation (in vaulted naves) or directly supported on the vaulted elements (in the domes). Since those construction systems are composed by brick and plaster, the presence of moisture is problematic, and represents a risk of losing the strength capacity and therefore the stability of the dome. An example of this problem is the dome of the church ���Nuestra Se��ora de Bel��n��� in Crevillente, built with solid bricks, it has the highest diameter of the province (18th century). This historic building has been restored on several occasions in the recent years due to moisture, cracks or fissures. The study of these works give an idea of the difficulties of maintenance, conservation and proper restoration of such kind of buildings as unique and valued constructions in our heritage.