Draft genome of Haloarcula rubripromontorii strain SL3, a novel halophilic archaeon isolated from the solar salterns of Cabo Rojo, Puerto Rico.

The genus Haloarcula belongs to the family Halobacteriaceae which currently has 10 valid species. Here we report the draft genome sequence of strain SL3, a new species within this genus, isolated from the Solar Salterns of Cabo Rojo, Puerto Rico. Genome assembly performed using NGEN Assembler resulted in 18 contigs (N50 = 601,911 bp), the largest of which contains 1,023,775 bp. The genome consists of 3.97 MB and has a GC content of 61.97%. Like all species of Haloarcula, the genome encodes heterogeneous copies of the small subunit ribosomal RNA. In addition, the genome includes 6 rRNAs, 48 tRNAs, and 3797 protein coding sequences. Several carbohydrate-active enzymes genes were found, as well as enzymes involved in the dihydroxyacetone processing pathway which are not found in other Haloarcula species. The NCBI accession number for this genome is LIUF00000000 and the strain deposit number is CECT9001

EFFECT OF PLANTING DATES AND FREQUENCIES OF INTERCROPPING ON YIELD AND INCOME OF BEAN AND BANANA

EFFECT OF PLANTING DATES AND FREQUENCIES OF INTERCROPPING ON YIELD AND INCOME OF BEAN AND BANAN

Funcionalidad física como indicador de disponibilidad de hábitat en Islas Marietas, Nayarit, México

Background. Few investigations use functional diversity and the reef functional index (IFA) to assess the sta-te of reef communities. Objectives. Evaluate physical functionality as an indicator of fish habitat availability and its relationship with functional diversity. Methods. The physical functionality of the reef was evaluated using the IFA, integrating data on coral cover, structural complexity, and calcification rate. The structure of the fish assemblages was analyzed by calculating functional diversity indices (richness, evenness, and divergen-ce) based on six functional traits (body size, mobility, activity period, type of aggregation, position in the water column, and diet). The relationship between functional diversity and IFA was evaluated using linear regression analysis. Results. Área de Restauración showed the highest values in the IFA; on the contrary, Túnel Amarra-dero presented the lowest values. In both sites, a greater presence of Pocillopora verrucosa was observed. Functional diversity presented the lowest values in the three functional indices in Área de Restauración. Linear regression analyses were not significant. Conclusions. No linear relationship was found between the IFA and functional diversity; this can be attributed to the fact that in sites with low coral cover, such as Islas Marietas, the functional diversity of fish presents a weak relationship with the three-dimensionality provided by corals since in sites with low coral cover, other structural elements (geologic features and rock substrates) could promote these three-dimensional structures.Antecedentes. Pocas investigaciones emplean la diversidad funcional y el Índice de Función Arrecifal (IFA) para evaluar el estado de las comunidades arrecifales. Objetivo. Evaluar la funcionalidad física como indica-dor de disponibilidad de hábitat de peces y su relación con la diversidad funcional. Métodos. La funcionalidad física del arrecife se evaluó mediante el IFA integrando datos de cobertura coralina, complejidad estructural y tasa de calcificación. La estructura de los ensamblajes de peces se analizó mediante el cálculo de índices de diversidad funcional (riqueza, equidad y divergencia) con base en seis atributos funcionales (tamaño corporal, movilidad, periodo de actividad, tipo de agregación, posición en la columna de agua y dieta). La relación entre la diversidad funcional del ensamblaje y el IFA se evaluó mediante un análisis de regresión lineal. Resultados. La Zona de Restauración presentó los valores más altos en el IFA; por el contrario, Túnel Amarradero presentó los valores másbajos. En ambos sitios se observó una mayor presencia de Pocillopora verrucosa. La diversidad funcional presentó los valores más bajos en los tres índices funcionales en la Zona de Restauración. Los análisis de regresión lineal no fueron significativos. Conclusiones. No se encontró una relación lineal entre el IFA y la diversidad funcional, esto puede atribuirse a que en sitios con baja cobertura coralina como Islas Marietas, la diversidad funcional de peces presenta una débil relación con la tridimen-sionalidad otorgada por los corales. Lo anterior debido a que, en sitios con baja cobertura coralina, otros elementos estructurales (características geológicas y sustratos rocosos) podrían proveer de esas estructuras tridimensionales

MKK6 deficiency promotes cardiac dysfunction through MKK3-p38γ/δ-mTOR hyperactivation.

Stress-activated p38 kinases control a plethora of functions, and their dysregulation has been linked to the development of steatosis, obesity, immune disorders, and cancer. Therefore, they have been identified as potential targets for novel therapeutic strategies. There are four p38 family members (p38α, p38β, p38γ, and p38δ) that are activated by MKK3 and MKK6. Here, we demonstrate that lack of MKK6 reduces the lifespan in mice. Longitudinal study of cardiac function in MKK6 KO mice showed that young mice develop cardiac hypertrophy which progresses to cardiac dilatation and fibrosis with age. Mechanistically, lack of MKK6 blunts p38α activation while causing MKK3-p38γ/δ hyperphosphorylation and increased mammalian target of rapamycin (mTOR) signaling, resulting in cardiac hypertrophy. Cardiac hypertrophy in MKK6 KO mice is reverted by knocking out either p38γ or p38δ or by inhibiting the mTOR pathway with rapamycin. In conclusion, we have identified a key role for the MKK3/6-p38γ/δ pathway in the development of cardiac hypertrophy, which has important implications for the clinical use of p38α inhibitors in the long-term treatment since they might result in cardiotoxicity.We thank S Bartlett and F Chanut for English editing. We are grateful to RJ Davis, A Padmanabhan, M Costa and C López-Otín for critical reading of the manuscript. We thank Dr. RJ Davis for the MKK3 and MKK6 KO animals and Dr. Erwin F Wagner for the p38α flox mice. We thank AC Silva (ana@anasilva illustrations.com) for help with figure editing and design. This work was funded by a CNIC Intramural Project Severo Ochoa (Expediente 12–2016 IGP) to GS and JJ and PID2019-104399RB-I00 funded by MCIN/AEI/10.13039/501100011033 to GS. BGT was a fellow of FPI Severo Ochoa CNIC Program (SVP-2013-067639) and is an American Heart Association Postdoctoral Fellow (18POST34080175). RRB is a fellow of the FPU Program (FPU17/03847). The following grants provided additional funding: GS is granted by funds from European Regional Development Fund (ERDF): EFSD/Lilly European Diabetes Research Programme Dr Sabio, Fundación AECC PROYE19047SABI and Comunidad de Madrid IMMUNOTHERCAN-CM B2017/BMD-3733; US National Heart, Lung, and Blood Institute (R01 Grant HL122352), Fondos FEDER, Madrid, Spain, and Fundación Bancaria “La Caixa (project HR19/52160013); Fundación La Marató TV3: Ayudas a la investigación en enfermedades raras 2020 (LA MARATO-2020); and Instituto de Salud Carlos III to JJ. IN was funded by EFSD/Lilly grants (2017 and 2019), the CNIC IPP FP7 Marie Curie Programme (PCOFUND-2012–600396), EFSD Rising Star award (2019), JDC-2018-Incorporación (MIN/JDC1802). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC FoundationS

Reliability and tolerance comparison in water supply networks

The final publication is available at Springer via http://dx.doi.org/10.1007/s11269-010-9753-2Urban water supply is a high priority service and so looped networks are extensively used in order to considerably reduce the number of consumers affected by a failure. Looped networks may be redundant in connectivity and capacity. The concept of reliability has been introduced in an attempt to quantitatively measure the possibility of maintaining an adequate service for a given period. Numerous researchers have considered reliability as a measure of redundancy. This concept is usually implicit, but some researchers have even stated it explicitly. This paper shows why reliability cannot be considered a measure of redundancy given that branched networks can achieve high values of reliability and this would deny the fact that a looped network is more reliable than a branched network with a similar layout and size. To this end the paper discusses two quantitative indices for measuring expected network behavior: reliability and tolerance. These indices are calculated and a comparison is made between looped, branched, and mixed networks. © 2011 Springer Science+Business Media B.V.The authors wish to acknowledge the support received from project IDAWAS, DPI2009-11591, of the Directorate-General of Research at the Spanish Ministry of Education, the grant PAID-02-09 for a stay at the Universidad Politecnica de Valencia by the first author, and a grant MAEC-AECI 0000202066 awarded to the second author by the Ministerio de Asuntos Exteriores y Cooperacion of Spain. The use of English in this paper was revised by John Rawlins; and the revision was funded by the Universidad Politecnica de Valencia, Spain.Martínez-Rodríguez, JB.; Montalvo Arango, I.; Izquierdo Sebastián, J.; Pérez García, R. (2011). Reliability and tolerance comparison in water supply networks. Water Resources Management. 25(5):1437-1448. https://doi.org/10.1007/s11269-010-9753-2S14371448255Bao Y, Mays LW (1990) Model for water distribution system reliability. J Hydraul Eng ASCE 116(9):1119–1137Bouchart F, Goulter I (1991) Reliability improvements in design of water distribution networks recognizing valve location. Water Resour Res 27(12):3029–3040Carrión A, Solano H, Gamiz ML, Debón A (2010) Evaluation of the reliability of a water supply network from right-censored and left-truncated break data. Water Resour Manag, Springer Sci 24:2917–2935. Published online: 28 January 2010Chiong C (1985) Optimización de redes cerradas, Doctoral Thesis, CIH-CUJAE, Havana (in Spanish)Christodoulou SE (2010) Water network assessment and reliability analysis by use of survival analysis. Water Resour Manag, Springer Sci, Published online: 19 June 2010Cullinane MJ, Lansey KE, Mays LW (1992) Optimization-availability-based design of water distribution networks. J Hydraul Eng ASCE 118(3):420–441Duan N, Mays LW, Lansey KE (1990) Optimal reliability-based design of pumping and distribution systems. J Hydraul Eng ASCE 116(2):249–268Goulter I (1992) Systems analysis in water distribution network design: from theory to practice. J Water Resour Plan Manage ASCE 118(3):238–248Goulter I (1993) Modern concepts of a water distribution system. Policies for improvement of networks with shortcomings. In: Cabrera E, Martínez F (eds) Water supply systems: state of the art and future trends, Valencia (Spain). Comput Mech Publ, Southampton, pp 121–138Goulter I, Bouchart F (1990) Reliability-constrained pipe network model. J Hydraul Eng ASCE 116(2):211–229Gupta R, Bhave R (1994) Reliability analysis of water distribution systems. J Environ Eng ASCE 120(2):447–460Jacobs P, Goulter I (1991) Estimation of maximum cut-set size for water network failure. J Water Resour Plan Manage ASCE 117(5):588–605Jowitt P, Xu C (1993) Predicting pipe failure effects in water distribution networks. J Water Resour Plan Manage ASCE 119(l):18–31Kalungi P, Tanyimboh TT (2003) Redundancy model for water distribution systems. Rel Eng Syst Safety 82(3):275–286Khomsi D, Walters GA, Thorley ARD, Ouazar D (1996) Reliability tester for water-distribution networks. J Comput Civ Eng ASCE 10(l):10–9Lansey K, Duan N, Mays LW, Tung YK (1989) Water distribution system design under uncertainty. J Water Resour Plan Manage ASCE 115(5):630–645Loganathan GV, Shah MP, Sherali HP (1990) A two-phase network design heuristic for minimum cost water distribution systems under a reliability constraint. Eng Optim 15(4):311–336Martínez JB (2007) Quantifying the economy of water supply looped networks. J Hydraul Eng ASCE 133(1):88–97Martínez JB (2010) Cost and reliability comparison between branched and looped water supply networks. J Hydroinform IWA 12(2):150–160Morgan DR, Goulter IC (1985) Optimal urban water distribution design. Water Resour Res 21(5):642–652Park H, Leibman J (1993) Redundancy-constrained minimum-cost design of water distribution networks. J Water Resour Plan Manage ASCE 119(l):83–98Pinto J, Varum H, Bentes I, Agarwal J (2010) A theory of vulnerability of water pipe network. Water Resour Manag 24:4237–4254. Springer Science, Published online: 6 May 2010Quimpo R, Shamsi U (1991) Reliability-based distribution system maintenance. J Water Resour Plan Manage ASCE 117(3):321–339Su Y, Mays LW, Duan N, Lansey K (1987) Reliability based optimization model for water distribution systems. J Hydraul Eng ASCE 113(12):1539–1556Tanyimboh TT, Tabesh M, Burrows R (2001) Appraisal of source head methods for calculating reliability of water distribution networks. J Water Resour Plan Manage ASCE 127(4):206–213Walski TM, Weiler JS, Culver T (2006) Using criticality analysis to identify impact of valve location. In: Proc 8th annual water distrib systems analysis symposium, August 27–30, Cincinnati, Ohio, USA,Walters GA, Knezevic J (1989) Discussion of ‘Reliability based optimization model for water distribution systems’ by Su, Y., Mays, L. W. , Duan, N., and Lansey, K. J Hydraul Eng ASCE 115(8):1157–1158Xu C, Goulter I (1997) Simulation-based optimal design of reliable water distribution networks. In: Zayegh A (ed) Proc 3rd int conf on modeling and simulation. Victoria University of Technology, Melbourne, pp 107–112Xu C, Goulter I (1998) Probabilistic model for water distribution reliability. J Water Resour Plan Manage ASCE 124(4):218–228Xu C, Goulter I (1999) Reliability based optimal design of water distribution networks. J Water Resour Plan Manage ASCE 125(6):352–362Xu C, Goulter I (2000) A model for optimal design of reliable water distribution networks. In: Blain WR, Brebbia CA (eds) Hydraulic engineering software VIII. WIT, Southampton, pp 71–8

p38γ is essential for cell cycle progression and liver tumorigenesis

The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)–cyclin protein complex1. However, control of the G0-to-G1 transition is not completely understood. Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease

Prospectiva territorial SENA regional Valle al 2030

Prospectiva territorial SENA regional Valle al 2030 compatible con las propuestas de desarrollo regional en la cual mediante el acopio, revisión y análisis de información de las tendencias internacionales, nacionales, locales y de la organización se identificaron las principales direccionadores, productos, tecnologías y recursos evaluando el nivel de importancia y gobernabilidad de los factores organizacionales más críticos así como conclusiones y recomendaciones.SENA regional Valle territorial prospect by 2030 compatible with regional development proposals in which, through the collection, review and analysis of information on international, national, local and organizational trends, the main drivers, products, technologies and resources were identified, evaluating the level of importance and governance of the most critical organizational factors as well as conclusions and recommendations.Identificación de dimensiones, direccionadores y factores -- Mapa de trayectoria del sena regional Valle -- Matriz de importancia y gobernabilidad -- Mundo e incertidumbre -- Direccionador desarrollo económico, empleo y demografía -- Tendencias de América Latina -- Tendencias nacionales -- Tendencias regionales -- Tendencias locales -- Situación étnico-cultural -- Institucionalidad y gobernabilidad -- Escenario desarrollo económico, empleo y demografía -- Direccionador seguridad y soberanía alimentaria -- Principales tendencias de América Latina -- Principales tendencias locales, regionales y nacionales -- Escenario seguridad alimentaria en el SENA regional Valle -- Direccionador industria 4.0 -- Definición -- Tendencias mundiales -- Principales tendencias de América Latina -- Principales tendencias locales regionales y nacionales -- SENA regional Valle y la industria 4.0 -- Direccionador ambiente -- Tendencias de América Latina -- Principales tendencias locales, regionales y nacionales -- Línea de base direccionador ambiente en El SENA Regional Valle -- Covid-19 y el impacto ambiental en el Valle del cauca -- Escenarios direccionador ambiente -- Direccionador infraestructura sostenible -- Principales tendencias de América Latina -- Principales tendencias locales, regionales y nacionales -- Diagnóstico infraestructura sostenible -- Escenario infraestructura sostenible -- Debilidades, oportunidades, fortalezas y amenazas (DOFA) -- Conclusiones -- Escenario Apuesta -- Escenarios posibles -- Conclusiones -- RecomendacionesPrimera ediciónna197 página

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Dysregulation of Macrophage-Secreted Cathepsin B Contributes to HIV-1-Linked Neuronal Apoptosis

Chronic HIV infection leads to the development of cognitive impairments, designated as HIV-associated neurocognitive disorders (HAND). The secretion of soluble neurotoxic factors by HIV-infected macrophages plays a central role in the neuronal dysfunction and cell death associated with HAND. One potentially neurotoxic protein secreted by HIV-1 infected macrophages is cathepsin B. To explore the potential role of cathepsin B in neuronal cell death after HIV infection, we cultured HIV-1ADA infected human monocyte-derived macrophages (MDM) and assayed them for expression and activity of cathepsin B and its inhibitors, cystatins B and C. The neurotoxic activity of the secreted cathepsin B was determined by incubating cells from the neuronal cell line SK-N-SH with MDM conditioned media (MCM) from HIV-1 infected cultures. We found that HIV-1 infected MDM secreted significantly higher levels of cathepsin B than did uninfected cells. Moreover, the activity of secreted cathepsin B was significantly increased in HIV-infected MDM at the peak of viral production. Incubation of neuronal cells with supernatants from HIV-infected MDM resulted in a significant increase in the numbers of apoptotic neurons, and this increase was reversed by the addition of either the cathepsin B inhibitor CA-074 or a monoclonal antibody to cathepsin B. In situ proximity ligation assays indicated that the increased neurotoxic activity of the cathepsin B secreted by HIV-infected MDM resulted from decreased interactions between the enzyme and its inhibitors, cystatins B and C. Furthermore, preliminary in vivo studies of human post-mortem brain tissue suggested an upregulation of cathepsin B immunoreactivity in the hippocampus and basal ganglia in individuals with HAND. Our results demonstrate that HIV-1 infection upregulates cathepsin B in macrophages, increases cathepsin B activity, and reduces cystatin-cathepsin interactions, contributing to neuronal apoptosis. These findings provide new evidence for the role of cathepsin B in neuronal cell death induced by HIV-infected macrophages