20 research outputs found
RhoA GTPase inhibition organizes contraction during epithelial morphogenesis
During morphogenesis, contraction of the actomyosin cytoskeleton within individual cells drives cell shape changes that fold tissues. Coordination of cytoskeletal contractility is mediated by regulating RhoA GTPase activity. Guanine nucleotide exchange factors (GEFs) activate and GTPase-activating proteins (GAPs) inhibit RhoA activity. Most studies of tissue folding, including apical constriction, have focused on how RhoA is activated by GEFs to promote cell contractility, with little investigation as to how GAPs may be important. Here, we identify a critical role for a RhoA GAP, Cumberland GAP (C-GAP), which coordinates with a RhoA GEF, RhoGEF2, to organize spatiotemporal contractility during Drosophila melanogaster apical constriction. C-GAP spatially restricts RhoA pathway activity to a central position in the apical cortex. RhoGEF2 pulses precede myosin, and C-GAP is required for pulsation, suggesting that contractile pulses result from RhoA activity cycling. Finally, C-GAP expression level influences the transition from reversible to irreversible cell shape change, which defines the onset of tissue shape change. Our data demonstrate that RhoA activity cycling and modulating the ratio of RhoGEF2 to C-GAP are required for tissue folding.American Cancer Society (125792-RSG-14-039-01-CSM
Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
Background:
Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.
Methods:
We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.
Findings:
Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group.
Interpretation:
In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes.
Funding:
GlaxoSmithKline
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Late-Spring Herbage Production on Shortgrass Rangeland
This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202
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Seasonal Variations in Protein and Mineral Content of Fringed Sagewort [Artemisia frigida]
Fringed sagewort (Artemisia frigida) was collected biweekly from May 15 through October 4, 1979, from a loamy range site near Cheyenne, Wyo. Crude protein, calcium, iron, potassium, magnesium, manganese, phosphorus, sodium, and zinc were determined on the collected plant material. After July 12, leaves and flowers were stripped from the stems and analyzed separately. Crude protein and mineral concentrations in the (fringed sagewort) plant material generally decreased with the advance of the growing season. Except for phosphorus and crude protein content in the stems after late July, the nutritional value was adequate. Fringed sagewort is considered to be of minor importance but is an important forage plant for wildlife and, to a lesser extent, for livestock use.This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202
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Mechanical Renovation of Rangelands for Increased Forage Production and Carrying Capacity
This material was digitized as part of a cooperative project between the Society for Range Management, the National Agricultural Library, and the University of Arizona Libraries.The Rangelands archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform March 202
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Mineral and Protein Contents of Blue Grama and Western Wheatgrass
Mineral and crude protein contents of blue grama and western wheatgrass were influenced by stage of maturity and precipitation at the Archer Substation near Cheyenne, Wyoming during the growing season in 1965. Mineral and crude protein levels of the two grasses generally declined with maturity./Este estudio se llevó a cabo en la Subestación de ARCHER cerca de Cheyenne, Wyoming, EUA. El contenido de proteína de cada especie declinó generalmente con el desarrollo. Sin embargo, el navajita azul mostró variaciones en el contenido de proteína por el crecimiento nuevo después de las lluvias aún durante el otoño y después de algunos días con heladas. Se observó un aumento rápido en el contenido de proteína con el crecimiento nuevo pero éste no ocurrió para el Western Wheatgrass. A mediados de agosto el contenido de fósforo en ambas especies declinó por abajo de los requisitos alimenticios dados por el National Research Council (NRC). Esto sugiere la necesidad de empezar la suplementación de fósforo en agosto. El contenido de cobre en el mes de julio para ambas especies estuvo abajo de los requisitos alimenticios del NRC, pero los borregos no mostraron síntomas de deficiencias. Cada especie tuvo bastante calcio, manganeso, magnesio y hierro para toda la estación de pastoreo.This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202