Explore the vast range of titles available.

In nature, structural specificity in DNA and proteins is encoded differently: In DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here, we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen-bond networks. We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall, and the hydrogen-bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen-bond networks with atomic accuracy enables the programming of protein interaction specificity for a broad range of synthetic biology applications; more generally, our results demonstrate that, even with the tremendous diversity observed in nature, there are fundamentally new modes of interaction to be discovered in proteins.

Background Physical activity improves bone strength and reduces the risk for osteoporotic fractures. However, there are substantial gaps in our knowledge as to when, how and how much activity is optimal for bone health. Purpose In this cohort study, we examined developmental trajectories of objectively measured physical activity from childhood to adolescence to discern if moderate-and-vigorous intensity physical activity (MVPA) predicts bone strength. Methods Starting at age 5 and continuing at 8, 11, 13, 15 and 17 years, Iowa Bone Development Study participants (n=530) wore an accelerometer for 3–5 days. At age 17, we assessed dual X-ray energy absorptiometry outcomes of mass and estimated geometry (femoral neck cross-sectional area and section modulus). We also assessed geometric properties (bone stress index and polar moment of inertia) of the tibia using peripheral computer quantitative tomography. Latent class modelling was used to construct developmental trajectories of MVPA from childhood to late adolescence. General linear models were used to examine the trajectory groups as predictors of age 17 bone outcomes. Results Girls and boys who accumulated the most MVPA had greater bone mass and better geometry at 17 years when compared to less active peers. The proportion of participants achieving high levels of MVPA throughout childhood was very low (<6% in girls) and by late adolescence almost all girls were inactive. Conclusions Bone health benefits of physical activity are not being realised due to low levels of activity for most youth, especially in girls.

\"Here begins Arthur Curry's recollection of the epic journey that led him to become the mythical superhero we know as Aquaman. Since his dramatic debut in the 1940s, Aquaman has gone from admired hero to legendary icon. Able to breathe in both air and water, the King of the Seven Seas has fought villainy from the deepest depths of the oceans to the outer limits of the galaxy. He is unquestionably one of the greatest heroes the world has ever seen, but his rise to power was not easy.\"-- Provided by publisher.

Large, intact areas of tropical peatland are highly threatened at a global scale by the expansion of commercial agriculture and other forms of economic development. Conserving peatlands on a landscape scale, with their hydrology intact, is of international conservation importance to preserve their distinctive biodiversity and ecosystem services and maintain their resilience to future environmental change. We explored threats to and opportunities for conserving remaining intact tropical peatlands; thus, we excluded peatlands of Indonesia and Malaysia, where extensive deforestation, drainage, and conversion to plantations means conservation in this region can protect only small fragments of the original ecosystem. We focused on a case study, the Pastaza-Marañón Foreland Basin (PMFB) in Peru, which is among the largest known intact tropical peatland landscapes in the world and is representative of peatland vulnerability. Maintenance of the hydrological conditions critical for carbon storage and ecosystem function of peatlands is, in the PMFB, primarily threatened by expansion of commercial agriculture linked to new transport infrastructure that is facilitating access to remote areas. There remain opportunities in the PMFB and elsewhere to develop alternative, more sustainable land-use practices. Although some of the peatlands in the PMFB fall within existing legally protected areas, this protection does not include the most carbon-dense (domed pole forest) areas. New carbon-based conservation instruments (e.g., REDD+, Green Climate Fund), developing markets for sustainable peatland products, transferring land title to local communities, and expanding protected areas offer pathways to increased protection for intact tropical peatlands in Amazonia and elsewhere, such as those in New Guinea and Central Africa which remain, for the moment, broadly beyond the frontier of commercial development. Extensas e intactas áreas de turberas tropicales están severamente amenazadas a escala mundial, debido a la expansión de la agricultura comercial y a otras formas de desarrollo económico. La conservación de las turberas como parte del medio natural, con su hidrología no intervenida, es de importancia internacional para asegurar la conservación de su biodiversidad tan característica y de los servicios ambientales que ofrecen, y así mantener su resiliencia ante futuros cambios ambientales. Exploramos las amenazas y las oportunidades para conservar las turberas tropicales intactas y remanentes. Nuestro enfoque por lo tanto excluye las turberas de Indonesia y Malasia, donde la deforestación de forma extensiva y el drenado para el establecimiento de plantaciones hace que la conservación en estas regiones pueda proteger solo pequeños fragmentos del ecosistema original En este estudio, nos enfocamos en las cuencas del Pastaza Marañón (PMFB, siglas en inglés) en Perú, que comprende una de las turberas tropicales intactas más extensas del mundo y es representativa de la vulnerabilidad que las amenaza. El mantenimiento de las condiciones hidrológicas críticas para el almacenamiento de carbono y la función ambiental de las turberas está, en la PMFB, amenazada principalmente por la expansión de la agricultura comercial y las nuevas vías de transporte que facilitan el acceso a las áreas remotas. En la PMFB y en otros lugares aún hay oportunidades para desarrollar prácticas alternativas y sostenibles del uso del suelo. Aunque algunas de las turberas en la PMFB caen dentro de áreas naturales protegidas, esta protección no incluye las áreas con mayor densidad de carbono (varillal hidromórfico). Nuevas herramientas para la conservación basada en el carbono (p.e. REDD+, Fondo Verde para el Clima), el desarrollo de mercados para los productos de las turberas, la transferencia de títulos de propiedad de la tierra a las comunidades locales, y la expansión de las áreas protegidas ofrecen alternativas para una mayor protección de las turberas tropicales intactas en la Amazonia y en otros lugares, como las turberas de Nueva Guinea y África Central que permanecen, por el momento, alejadas de la frontera de desarrollo comercial.

Medulloblastomas and glioblastomas, the most common primary brain tumors in children and adults, respectively, are extremely difficult to treat. Efforts to identify novel proteins essential for the growth of these tumors may help to further our understanding of the biology of these tumors, as well as, identify targets for future therapies. The recent identification of multiple transcription factor-centric protein interaction landscapes in embryonic stem cells has identified numerous understudied proteins that are essential for the self-renewal of these stem cells. To identify novel proteins essential for the fate of brain tumor cells, we examined the protein interaction network of the transcription factor, SOX2, in medulloblastoma cells. For this purpose, Multidimensional Protein Identification Technology (MudPIT) identified >280 SOX2-associated proteins in the medulloblastoma cell line DAOY. To begin to understand the roles of SOX2-associated proteins in brain cancer, we focused on two SOX2-associated proteins, Musashi 2 (MSI2) and Ubiquitin Specific Protease 9x (USP9X). Recent studies have implicated MSI2, a putative RNA binding protein, and USP9X, a deubiquitinating enzyme, in several cancers, but not brain tumors. We demonstrate that knockdown of MSI2 significantly reduces the growth of DAOY cells as well as U87 and U118 glioblastoma cells. We also demonstrate that the knockdown of USP9X in DAOY, U87 and U118 brain tumor cells strongly reduces their growth. Together, our studies identify a large set of SOX2-associated proteins in DAOY medulloblastoma cells and identify two proteins, MSI2 and USP9X, that warrant further investigation to determine whether they are potential therapeutic targets for brain cancer.

Objective: To assess chlorhexidine absorption and skin tolerability in premature infants, following skin antisepsis with 2% aqueous chlorhexidine gluconate (CHG) prior to peripherally inserted central catheter (PICC) placement. Study Design: Neonates less than 32 weeks gestation had skin cleansed with CHG prior to PICC placement. CHG concentrations were measured on serial blood samples. Skin integrity was evaluated for 2 weeks after CHG exposure. Result: Twenty infants were enrolled; median gestational age was 28 2/7 weeks (range 24 3/7 to 31 4/7). Ten infants had detectable serum chlorhexidine concentrations (range 1.6 to 206 ng ml −1 ). Seven of these infants had their highest serum concentration 2 to 3 days following exposure. No CHG-related skin irritation occurred in any infant. Conclusion: CHG was detected in the blood of preterm infants receiving CHG skin antisepsis for PICC insertion. Highest serum concentrations occurred 2 to 3 days after exposure. Further investigation is needed to determine the clinical relevance of CHG absorption in preterm infants.

In the present protocol, we determined the presence and concentrations of bisphenol A (BPA) spiked in surface water samples using EEM fluorescence spectroscopy in conjunction with modelling using partial least squares (PLS) and parallel factor (PARAFAC). PARAFAC modelling of the EEM fluorescence data obtained from surface water samples contaminated with BPA unraveled four fluorophores including BPA. The best outcomes were obtained for BPA concentration (R2 = 0.996; standard deviation to prediction error’s root mean square ratio (RPD) = 3.41; and a Pearson’s r value of 0.998). With these values of R2 and Pearson’s r, the PLS model showed a strong correlation between the predicted and measured BPA concentrations. The detection and quantification limits of the method were 3.512 and 11.708 micro molar (µM), respectively. In conclusion, BPA can be precisely detected and its concentration in surface water predicted using the PARAFAC and PLS models developed in this study and fluorescence EEM data collected from BPA-contaminated water. It is necessary to spatially relate surface water contamination data with other datasets in order to connect drinking water quality issues with health, environmental restoration, and environmental justice concerns.

Ketogenic diets are low in carbohydrates and high in fat, which forces cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Relative to normal cells, cancer cells are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. In this study we tested the hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes. Mice bearing MIA PaCa-2 pancreatic cancer xenografts were fed either a ketogenic diet or standard rodent chow, treated with conventionally fractionated radiation (2 Gy/fraction), and tumor growth rates were assessed daily. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modfied proteins as a marker of oxidative stress. Based on this and another previously published preclinical study, phase 1 clinical trials in locally advanced NSCLC and pancreatic cancer were initiated, combining standard radiation and chemotherapy with a ketogenic diet for six weeks (NSCLC) or five weeks (pancreatic cancer). The xenograft experiments demonstrated prolonged survival and increased 4HNE-modfied proteins in animals consuming a ketogenic diet combined with radiation compared to radiation alone. In the phase 1 clinical trial, over a period of three years, seven NSCLC patients enrolled in the study. Of these, four were unable to comply with the diet and withdrew, two completed the study and one was withdrawn due to a dose-limiting toxicity. Over the same time period, two pancreatic cancer patients enrolled in the trial. Of these, one completed the study and the other was withdrawn due to a dose-limiting toxicity. The preclinical experiments demonstrate that a ketogenic diet increases radiation sensitivity in a pancreatic cancer xenograft model. However, patients with locally advanced NSCLC and pancreatic cancer receiving concurrent radiotherapy and chemotherapy had suboptimal compliance to the oral ketogenic diet and thus, poor tolerance.