The Eco - Geo - Clim model: explaining Madagascar’s endemism

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Efficacy and safety of zibotentan and dapagliflozin in patients with chronic kidney disease: study design and baseline characteristics of the ZENITH-CKD trial

Background: Sodium–glucose co-transporter 2 inhibitors (SGLT2is) are part of the standard of care for patients with chronic kidney disease (CKD), both with and without type 2 diabetes. Endothelin A (ETA) receptor antagonists have also been shown to slow progression of CKD. Differing mechanisms of action of SGLT2 and ETA receptor antagonists may enhance efficacy. We outline a study to evaluate the effect of combination zibotentan/dapagliflozin versus dapagliflozin alone on albuminuria and estimated glomerular filtration rate (eGFR). // Methods: We are conducting a double-blind, active-controlled, Phase 2b study to evaluate the efficacy and safety of ETA receptor antagonist zibotentan and SGLT2i dapagliflozin in a planned 415 adults with CKD (Zibotentan and Dapagliflozin for the Treatment of CKD; ZENITH-CKD). Participants are being randomized (1:2:2) to zibotentan 0.25 mg/dapagliflozin 10 mg once daily (QD), zibotentan 1.5 mg/dapagliflozin 10 mg QD and dapagliflozin 10 mg QD alone, for 12 weeks followed by a 2-week off-treatment wash-out period. The primary endpoint is the change in log-transformed urinary albumin-to-creatinine ratio (UACR) from baseline to Week 12. Other outcomes include change in blood pressure from baseline to Week 12 and change in eGFR the study. The incidence of adverse events will be monitored. Study protocol–defined events of special interest include changes in fluid-related measures (weight gain or B-type natriuretic peptide). // Results: A total of 447 patients were randomized and received treatment in placebo/dapagliflozin (n = 177), zibotentan 0.25 mg/dapagliflozin (n = 91) and zibotentan 1.5 mg/dapagliflozin (n = 179). The mean age was 62.8 years, 30.9% were female and 68.2% were white. At baseline, the mean eGFR of the enrolled population was 46.7 mL/min/1.73 m2 and the geometric mean UACR was 538.3 mg/g. // Conclusion: This study evaluates the UACR-lowering efficacy and safety of zibotentan with dapagliflozin as a potential new treatment for CKD. The study will provide information about an effective and safe zibotentan dose to be further investigated in a Phase 3 clinical outcome trial. // Clinical Trial Registration Number: NCT0472483

Physicochemical properties and structural characteristics of whole grain Oryza sativa L. with different treatments

[EN] Physicochemical properties and structural characteristics of whole rice flours with different treatments (soaking, germination and extrusion cooking) were studied. Water solubility, water absorption, crystallinity, adsorption isotherms (BET and GAB models), and glass transition temperature of the samples were determined. Water solubility and water absorption were enhanced by extrusion cooking process (3.17 4.98 vs. 24.1 53.76 g/100 g and 2.77 3.05 vs. 4.46 7.04 ml/g, respectively), but crystallinity was decreased (30 33 vs. 4 16%). Adsorption isotherms showed that extruded samples exhibited higher equilibrium moisture content as compared with their corresponding non-extruded samples (5.0 19.2 vs. 4.0 16.1 g water/g solids). There were no changes in glass transition temperature values in the studied moisture range (3.8 16 g/100 g). These results allow the correct use of whole rice flours with different treatments in foods and also contributed to the knowledge of stabilization of the productsThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was partially financed by ANPCYT (PICT 1105) and ERASMUS MUNDUS ACTION 2 ARCOIRIS Fellowship.Albarracin, M.; Talens Oliag, P.; Martínez Navarrete, N.; González, RJ.; Drago, SR. (2016). Physicochemical properties and structural characteristics of whole grain Oryza sativa L. with different treatments. Food Science and Technology International. 22(4):1-10. doi:10.1177/1082013215600078S110224Albarracín, M., José González, R., & Drago, S. R. (2015). Soaking and extrusion effects on physicochemical parameters, phytic acid, nutrient content and mineral bio-accessibility of whole rice grain. International Journal of Food Sciences and Nutrition, 66(2), 210-215. doi:10.3109/09637486.2014.986070Björck, I., & Asp, N.-G. (1983). The effects of extrusion cooking on nutritional value — A literature review. Journal of Food Engineering, 2(4), 281-308. doi:10.1016/0260-8774(83)90016-xBrunauer, S., Deming, L. S., Deming, W. E., & Teller, E. (1940). On a Theory of the van der Waals Adsorption of Gases. Journal of the American Chemical Society, 62(7), 1723-1732. doi:10.1021/ja01864a025Donkor, O. N., Stojanovska, L., Ginn, P., Ashton, J., & Vasiljevic, T. (2012). Germinated grains – Sources of bioactive compounds. Food Chemistry, 135(3), 950-959. doi:10.1016/j.foodchem.2012.05.058Gonzalez, R. J., De Greef, D. M., Torres, R. L., Borras, F. S., & Robutti, J. (2004). Effects of endosperm hardness and extrusion temperature on properties of products obtained with grits from two commercial maize cultivars. LWT - Food Science and Technology, 37(2), 193-198. doi:10.1016/j.lwt.2003.07.004Gonzalez, R., Drago, S., Torres, R., & De Greef, D. (2013). Extrusion Cooking of Cereal-Based Products. Contemporary Food Engineering. doi:10.1201/b15246-13González, R. J., Pastor Cavada, E., Vioque Peña, J., Torres, R. L., De Greef, D. M., & Drago, S. R. (2013). Extrusion Conditions and Amylose Content Affect Physicochemical Properties of Extrudates Obtained from Brown Rice Grains. International Journal of Food Science, 2013, 1-8. doi:10.1155/2013/584148Herawat, H., Kusnandar, F., Adawiyah, D. R., Budijanto, S., & Rahman, M. S. (2014). Thermal characteristics and state diagram of extruded instant artificial rice. Thermochimica Acta, 593, 50-57. doi:10.1016/j.tca.2014.08.017Jones, J. M., & Engleson, J. (2010). Whole Grains: Benefits and Challenges. Annual Review of Food Science and Technology, 1(1), 19-40. doi:10.1146/annurev.food.112408.132746Kim, H. Y., Hwang, I. G., Kim, T. M., Woo, K. S., Park, D. S., Kim, J. H., … Jeong, H. S. (2012). Chemical and functional components in different parts of rough rice (Oryza sativa L.) before and after germination. Food Chemistry, 134(1), 288-293. doi:10.1016/j.foodchem.2012.02.138Lowry, R. R., & Tinsley, I. J. (1976). Rapid colorimetric determination of free fatty acids. Journal of the American Oil Chemists’ Society, 53(7), 470-472. doi:10.1007/bf02636814Matveev, Y. (2000). The plasticizing effect of water on proteins, polysaccharides and their mixtures. Glassy state of biopolymers, food and seeds. Food Hydrocolloids, 14(5), 425-437. doi:10.1016/s0268-005x(00)00020-5Perdon, A., Siebenmorgen, T. J., & Mauromoustakos, A. (2000). Glassy State Transition and Rice Drying: Development of a Brown Rice State Diagram. Cereal Chemistry Journal, 77(6), 708-713. doi:10.1094/cchem.2000.77.6.708ROOS, Y., & KAREL, M. (1991). Plasticizing Effect of Water on Thermal Behavior and Crystallization of Amorphous Food Models. Journal of Food Science, 56(1), 38-43. doi:10.1111/j.1365-2621.1991.tb07970.xRuiz-Ruiz, J., Martínez-Ayala, A., Drago, S., González, R., Betancur-Ancona, D., & Chel-Guerrero, L. (2008). Extrusion of a hard-to-cook bean (Phaseolus vulgaris L.) and quality protein maize (Zea mays L.) flour blend. LWT - Food Science and Technology, 41(10), 1799-1807. doi:10.1016/j.lwt.2008.01.005SIU, G. M., & DRAPER, H. H. (1978). A SURVEY OF THE MALONALDEHYDE CONTENT OF RETAIL MEATS AND FISH. Journal of Food Science, 43(4), 1147-1149. doi:10.1111/j.1365-2621.1978.tb15256.xSun, Z., Yang, W., Siebenmorgen, T., Stelwagen, A., & Cnossen, A. (2002). Thermomechanical Transitions of Rice Kernels. Cereal Chemistry Journal, 79(3), 349-353. doi:10.1094/cchem.2002.79.3.349Timmermann, E. O. (2003). Multilayer sorption parameters: BET or GAB values? Colloids and Surfaces A: Physicochemical and Engineering Aspects, 220(1-3), 235-260. doi:10.1016/s0927-7757(03)00059-1Tovar, J., Bjoerck, I. M., & Asp, N. G. (1990). Starch content and .alpha.-amylolysis rate in precooked legume flours. Journal of Agricultural and Food Chemistry, 38(9), 1818-1823. doi:10.1021/jf00099a00

Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade

Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits

Argument mining: A machine learning perspective

Argument mining has recently become a hot topic, attracting the interests of several and diverse research communities, ranging from artificial intelligence, to computational linguistics, natural language processing, social and philosophical sciences. In this paper, we attempt to describe the problems and challenges of argument mining from a machine learning angle. In particular, we advocate that machine learning techniques so far have been under-exploited, and that a more proper standardization of the problem, also with regards to the underlying argument model, could provide a crucial element to develop better systems

Mating with Stressed Males Increases the Fitness of Ant Queens

BACKGROUND: According to sexual conflict theory, males can increase their own fitness by transferring substances during copulation that increase the short-term fecundity of their mating partners at the cost of the future life expectancy and re-mating capability of the latter. In contrast, sexual cooperation is expected in social insects. Mating indeed positively affects life span and fecundity of young queens of the male-polymorphic ant Cardiocondyla obscurior, even though males neither provide nuptial gifts nor any other care but leave their mates immediately after copulation and die shortly thereafter. PRINCIPAL FINDINGS: Here, we show that mating with winged disperser males has a significantly stronger impact on life span and reproductive success of young queens of C. obscurior than mating with wingless fighter males. CONCLUSIONS: Winged males are reared mostly under stressful environmental conditions, which force young queens to disperse and found their own societies independently. In contrast, queens that mate with wingless males under favourable conditions usually start reproducing in the safety of the established maternal nest. Our study suggests that males of C. obscurior have evolved mechanisms to posthumously assist young queens during colony founding under adverse ecological conditions

Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset

Diabetes like many diseases and biological processes is not mono-causal. On the one hand multifactorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics

MetaboHunter: an automatic approach for identification of metabolites from 1H-NMR spectra of complex mixtures

<p>Abstract</p> <p>Background</p> <p>One-dimensional ¹H-NMR spectroscopy is widely used for high-throughput characterization of metabolites in complex biological mixtures. However, the accurate identification of individual compounds is still a challenging task, particularly in spectral regions with higher peak densities. The need for automatic tools to facilitate and further improve the accuracy of such tasks, while using increasingly larger reference spectral libraries becomes a priority of current metabolomics research.</p> <p>Results</p> <p>We introduce a web server application, called MetaboHunter, which can be used for automatic assignment of ¹H-NMR spectra of metabolites. MetaboHunter provides methods for automatic metabolite identification based on spectra or peak lists with three different search methods and with possibility for peak drift in a user defined spectral range. The assignment is performed using as reference libraries manually curated data from two major publicly available databases of NMR metabolite standard measurements (HMDB and MMCD). Tests using a variety of synthetic and experimental spectra of single and multi metabolite mixtures show that MetaboHunter is able to identify, in average, more than 80% of detectable metabolites from spectra of synthetic mixtures and more than 50% from spectra corresponding to experimental mixtures. This work also suggests that better scoring functions improve by more than 30% the performance of MetaboHunter's metabolite identification methods.</p> <p>Conclusions</p> <p>MetaboHunter is a freely accessible, easy to use and user friendly ¹H-NMR-based web server application that provides efficient data input and pre-processing, flexible parameter settings, fast and automatic metabolite fingerprinting and results visualization via intuitive plotting and compound peak hit maps. Compared to other published and freely accessible metabolomics tools, MetaboHunter implements three efficient methods to search for metabolites in manually curated data from two reference libraries.</p> <p>Availability</p> <p><url>http://www.nrcbioinformatics.ca/metabohunter/</url></p

Searching the protein structure database for ligand-binding site similarities using CPASS v.2

<p>Abstract</p> <p>Background</p> <p>A recent analysis of protein sequences deposited in the NCBI RefSeq database indicates that ~8.5 million protein sequences are encoded in prokaryotic and eukaryotic genomes, where ~30% are explicitly annotated as "hypothetical" or "uncharacterized" protein. Our Comparison of Protein Active-Site Structures (CPASS v.2) database and software compares the sequence and structural characteristics of experimentally determined ligand binding sites to infer a functional relationship in the absence of global sequence or structure similarity. CPASS is an important component of our Functional Annotation Screening Technology by NMR (FAST-NMR) protocol and has been successfully applied to aid the annotation of a number of proteins of unknown function.</p> <p>Findings</p> <p>We report a major upgrade to our CPASS software and database that significantly improves its broad utility. CPASS v.2 is designed with a layered architecture to increase flexibility and portability that also enables job distribution over the Open Science Grid (OSG) to increase speed. Similarly, the CPASS interface was enhanced to provide more user flexibility in submitting a CPASS query. CPASS v.2 now allows for both automatic and manual definition of ligand-binding sites and permits pair-wise, one versus all, one versus list, or list versus list comparisons. Solvent accessible surface area, ligand root-mean square difference, and Cβ distances have been incorporated into the CPASS similarity function to improve the quality of the results. The CPASS database has also been updated.</p> <p>Conclusions</p> <p>CPASS v.2 is more than an order of magnitude faster than the original implementation, and allows for multiple simultaneous job submissions. Similarly, the CPASS database of ligand-defined binding sites has increased in size by ~ 38%, dramatically increasing the likelihood of a positive search result. The modification to the CPASS similarity function is effective in reducing CPASS similarity scores for false positives by ~30%, while leaving true positives unaffected. Importantly, receiver operating characteristics (ROC) curves demonstrate the high correlation between CPASS similarity scores and an accurate functional assignment. As indicated by distribution curves, scores ≥ 30% infer a functional similarity. Software URL: <url>http://cpass.unl.edu</url>.</p

Genetic Relations Between the Aves Ridge and the Grenada Back-Arc Basin, East Caribbean Sea

The Grenada Basin separates the active Lesser Antilles Arc from the Aves Ridge, described as a Cretaceous‐Paleocene remnant of the “Great Arc of the Caribbean.” Although various tectonic models have been proposed for the opening of the Grenada Basin, the data on which they rely are insufficient to reach definitive conclusions. This study presents, a large set of deep‐penetrating multichannel seismic reflection data and dredge samples acquired during the GARANTI cruise in 2017. By combining them with published data including seismic reflection data, wide‐angle seismic data, well data and dredges, we refine the understanding of the basement structure, depositional history, tectonic deformation and vertical motions of the Grenada Basin and its margins as follows: (1) rifting occurred during the late Paleocene‐early Eocene in a NW‐SE direction and led to seafloor spreading during the middle Eocene; (2) this newly formed oceanic crust now extends across the eastern Grenada Basin between the latitude of Grenada and Martinique; (3) asymmetrical pre‐Miocene depocenters support the hypothesis that the southern Grenada Basin originally extended beneath the present‐day southern Lesser Antilles Arc and probably partly into the present‐day forearc before the late Oligocene‐Miocene rise of the Lesser Antilles Arc; and (4) the Aves Ridge has subsided along with the Grenada Basin since at least the middle Eocene, with a general subsidence slowdown or even an uplift during the late Oligocene, and a sharp acceleration on its southeastern flank during the late Miocene. Until this acceleration of subsidence, several bathymetric highs remained shallow enough to develop carbonate platforms