Combination of DROOL rules and Protégé knowledge bases in the ONTO-H annotation tool

ONTO-H is a semi-automatic collaborative tool for the semantic annotation of documents, built as a Protégé 3.0 tab plug-in. Among its multiple functionalities aimed at easing the document annotation process, ONTO-H uses a rule-based system to create cascading annotations out from a single drag and drop operation from a part of a document into an already existing concept or instance of the domain ontology being used for annotation. It also gives support to the detection of name conflicts and instance duplications in the creation of the annotations. The rule system runs on top of the open source rule engine DROOLS and is connected to the domain ontology used for annotation by means of an ad-hoc programmed Java proxy

The strength of the association between heterozygosity and probability of interannual local recruitment increases with environmental harshness in blue tits

The extent of inbreeding depression and the magnitude of heterozygosity–fitness correlations (HFC) have been suggested to depend on the environmental context in which they are assayed, but little evidence is available for wild populations. We combine extensive molecular and capture–mark–recapture data from a blue tit (Cyanistes caeruleus) population to (1) analyze the relationship between heterozygosity and probability of interannual adult local recruitment and (2) test whether environmental stress imposed by physiologically suboptimal temperatures and rainfall influence the magnitude of HFC. To address these questions, we used two different arrays of microsatellite markers: 14 loci classified as neutral and 12 loci classified as putatively functional. We found significant relationships between heterozygosity and probability of interannual local recruitment that were most likely explained by variation in genomewide heterozygosity. The strength of the association between heterozygosity and probability of interannual local recruitment was positively associated with annual accumulated precipitation. Annual mean heterozygosity increased over time, which may have resulted from an overall positive selection on heterozygosity over the course of the study period. Finally, neutral and putatively functional loci showed similar trends, but the former had stronger effect sizes and seemed to better reflect genomewide heterozygosity. Overall, our results show that HFC can be context dependent, emphasizing the need to consider the role of environmental heterogeneity as a key factor when exploring the consequences of individual genetic diversity on fitness in natural populations.Peer reviewe

An overview of the ciao multiparadigm language and program development environment and its design philosophy

We describe some of the novel aspects and motivations behind the design and implementation of the Ciao multiparadigm programming system. An important aspect of Ciao is that it provides the programmer with a large number of useful features from different programming paradigms and styles, and that the use of each of these features can be turned on and off at will for each program module. Thus, a given module may be using e.g. higher order functions and constraints, while another module may be using objects, predicates, and concurrency. Furthermore, the language is designed to be extensible in a simple and modular way. Another important aspect of Ciao is its programming environment, which provides a powerful preprocessor (with an associated assertion language) capable of statically finding non-trivial bugs, verifying that programs comply with specifications, and performing many types of program optimizations. Such optimizations produce code that is highly competitive with other dynamic languages or, when the highest levéis of optimization are used, even that of static languages, all while retaining the interactive development environment of a dynamic language. The environment also includes a powerful auto-documenter. The paper provides an informal overview of the language and program development environment. It aims at illustrating the design philosophy rather than at being exhaustive, which would be impossible in the format of a paper, pointing instead to the existing literature on the system

Evaluación de cuatro genotipos de pasto elefante en Calabozo estado Guárico, Venezuela

The elephant grass (Pennisetum purpureum) is one of the main cutting grasses used for animal feeding in intensive farms inVenezuela, lacking sufficient research, which allows its use as alternative forage. The research work was carried out in theINIA-Guárico, in the Banks of San Pedro, Calabozo Guárico State. The objectives that thought about in this investigationwere: Evaluate four grass genotypes, [Clone Cuba (G1), purple Maralfalfa (G2) (Taiwan), Maralfalfa green (G3) and KingGrass (G4)]. Evaluate the effect on yield of three levels of nitrogen fertilization N) in the reabsorption, T1: 150 Kg.ha-1 ofurea: T2: 15000 Kg.ha-1[69 KgN], T3: 20000 Kg.ha-1 [92 Kg N] cow manure; T4: 0 Kg.ha-1 were used; Evaluate morphometricvariables in four grass genotypes: number of stalks (NS), number of leaves (NL), plant height (PH), stem diameter (SD),weight of leaves (WL), weight of stalks (WS), number of stakes (NST), weight of cuttings (WC), total weight (TW = WL +WS). The area used was 684 m2, divided into 48 plots. It was used a randomized block design with three replications. Theresults show that the N, regardless of the source, was highly significant (p <0.01) for variables: NL, SD, WL, TW. Similarly,for genotypes, but with the variables: NL, SD, PH, WL, WC and TW. Results were well adjusted to the mathematic model:Y(TW)= - 0.14798+0.85903(WL)+0.20362(WC)+0.00145(NL)+0.00995(SD)+0.03369(PH), R2=0.9482 and (p<0.01).Protein content of 8 to 10 % was found, with Taiwan and king grass standing out. Nitrogen fertilization positively influencedforage production yield and morphmetric variables of the three elephant grass genotypes (Clon Cuba, Maralfalfa purple(Taiwan) y Maralfalfa green).El pasto elefante (Pennisetum purpureum) una de las principales gramíneas de corte utilizadas para la alimentación animalen las explotaciones intensivas en Venezuela, no contando con suficiente investigación, que permita su utilización comoalternativa forrajera. El trabajo de investigación se realizó en el INIA-Guárico, en los Bancos de San Pedro, Calabozo estadoGuárico. Los objetivos que se plantearon en este trabajo fueron: Evaluar cuatro genotipos del pasto, [Clon Cuba (G1), Maralfalfamorado (G2) (Taiwan), Maralfalfa verde (G3) y King Grass (G4)]. Se evaluó el efecto sobre el rendimiento de tresniveles de fertilización nitrogenada (N) en el reabono [T1: 150 Kg.ha-1 (urea), T2: 15000 Kg.ha-1, T3: 20000 Kg.ha-1 deestiércol de bovino y T4: (0 Kg.ha-1), Evaluando las siguientes variables morfométricas en los cuatro genotipos de pasto:número tallos (NT), número de hojas (NH), altura planta (AP), grosor del tallo (GT), número estacas (NE), peso hojas (PH),peso de tallos (PT), peso esquejes (PE) y peso total (Ptotal=PH+PT). La superficie utilizada fue 684 m2, dividida en 48parcelas. Se empleó un diseño experimental de bloques completos al azar, con tres repeticiones. La evaluación se realizócada 30 días, durante 3 meses consecutivos. Los resultados demuestran que los materiales presentaron diferencias significativas(p<0.01) para todas las variables evaluadas, no se presentaron diferencias entre los materiales y los tratamientos, el Nindependientemente de la fuente, fue altamente significativo para las variables: NH, GT, PH, PT, Ptotal. Del mismo modo,para los genotipos y para las variables: NH, GT, AP, PH, PT y Ptotal. Los resultados se ajustaron al modelo matemático:Y(Ptotal)= -0.14798 + 0.85903(PH) + 0.20362(PE) + 0.00145(NH) +0.00995(GT)+ 0.03369(AP), R2=0.9482 (p<0.01).El contenido proteico fue de 8 a 10%, sobresaliendo los materiales Taiwan y King Grass. La fertilización con nitrógenoinfluyó positivamente en la producción de forraje, rendimiento y las variables relacionadas en tres de los genotipos de pasto(Clon Cuba, Maralfalfa morado (Taiwan) y Maralfalfa verde)

Does the use of nest materials in a ground-nesting bird result from a compromise between the risk of egg overheating and camouflage?

Many studies addressing the use of nest materials by animals have focused on only one factor to explain its function. However, the consideration of more than one factor could explain the apparently maladaptive choice of nest materials that make nests conspicuous to predators. We experimentally tested whether there is a trade-off in the use of nest materials between the risks of egg predation versus protection from overheating. We studied the ground-nesting Kentish plover, Charadrius alexandrinus, in southern Spain. We added materials differing in thermal properties and coloration to the nests, thus affecting rates of egg heating, nest temperature and camouflage. Before these manipulations, adults selected materials that were lighter than the microhabitat, probably to buffer the risk of egg overheating. However, the adults did not keep the lightest experimental materials, probably because they reduced camouflage, and this could make the nests even more easily detectable to predators. In all nests, adults removed most of the experimental materials independently of their properties, so that egg camouflage returned to the original situation within a week of the experimental treatments. Although the thermal environment may affect the choice of nest materials by plovers, ambient temperatureswere not so high at our study site as to determine the acceptance of the lightest experimental materials

Characterization of mutant versions of the R-RAS2/TC21 GTPase found in tumors

The R-RAS2 GTP hydrolase (GTPase) (also known as TC21) has been traditionally considered quite similar to classical RAS proteins at the regulatory and signaling levels. Recently, a long-tail hotspot mutation targeting the R-RAS2/TC21 Gln72 residue (Q72L) was identified as a potent oncogenic driver. Additional point mutations were also found in other tumors at low frequencies. Despite this, little information is available regarding the transforming role of these mutant versions and their relevance for the tumorigenic properties of already-transformed cancer cells. Here, we report that many of the RRAS2 mutations found in human cancers are highly transforming when expressed in immortalized cell lines. Moreover, the expression of endogenous R-RAS2Q72L is important for maintaining optimal levels of PI3K and ERK activities as well as for the adhesion, invasiveness, proliferation, and mitochondrial respiration of ovarian and breast cancer cell lines. Endogenous R-RAS2Q72L also regulates gene expression programs linked to both cell adhesion and inflammatory/immune-related responses. Endogenous R-RAS2Q72L is also quite relevant for the in vivo tumorigenic activity of these cells. This dependency is observed even though these cancer cell lines bear concurrent gain-of-function mutations in genes encoding RAS signaling elements. Finally, we show that endogenous R-RAS2, unlike the case of classical RAS proteins, specifically localizes in focal adhesions. Collectively, these results indicate that gain-of-function mutations of R-RAS2/TC21 play roles in tumor initiation and maintenance that are not fully redundant with those regulated by classical RAS oncoproteins

Functional specificity of the members of the Sos family of Ras-GEF Activators: Novel role of Sos2 in control of epidermal stem cell homeostasis

© 2021 by the authors.Prior reports showed the critical requirement of Sos1 for epithelial carcinogenesis, but the specific functionalities of the homologous Sos1 and Sos2 GEFs in skin homeostasis and tumorigenesis remain unclear. Here, we characterize specific mechanistic roles played by Sos1 or Sos2 in primary mouse keratinocytes (a prevalent skin cell lineage) under different experimental conditions. Functional analyses of actively growing primary keratinocytes of relevant genotypes—WT, Sos1-KO, Sos2-KO, and Sos1/2-DKO—revealed a prevalent role of Sos1 regarding transcriptional regulation and control of RAS activation and mechanistic overlapping of Sos1 and Sos2 regarding cell proliferation and survival, with dominant contribution of Sos1 to the RAS-ERK axis and Sos2 to the RAS-PI3K/AKT axis. Sos1/2-DKO keratinocytes could not grow under 3D culture conditions, but single Sos1-KO and Sos2-KO keratinocytes were able to form pseudoepidermis structures that showed disorganized layer structure, reduced proliferation, and increased apoptosis in comparison with WT 3D cultures. Remarkably, analysis of the skin of both newborn and adult Sos2-KO mice uncovered a significant reduction of the population of stem cells located in hair follicles. These data confirm that Sos1 and Sos2 play specific, cell-autonomous functions in primary keratinocytes and reveal a novel, essential role of Sos2 in control of epidermal stem cell homeostasis.The E.S. group was supported by grants from ISCIII-MCUI (FIS PI19/00934), JCyL (SA264P18-UIC 076), Areces Foundation (CIVP19A5942), Solorzano-Barruso Foundation (FS/32-2020), and by ISCIII-CIBERONC (group CB16/12/00352). Research was co-financed by FEDER funds. The J.M.P. lab is co-funded by European Regional Development Fund (FEDER) grants from Science and Innovation (SAF2015-66015-R and PID2019-110758RB-I00 to J.M.P.) and Instituto de Salud Carlos III (CIBERONC no. CB16/12/00228 to J.M.P.). The XRB lab is funded by “la Caixa” Banking Foundation (HR20-00164), the Castilla-León autonomous government (CSI252P18, CSI145P20, CLC-2017-01), the Spanish Ministry of Science and Innovation (MSI) (RTI2018-096481-B-100), and the Spanish Association against Cancer (GC16173472GARC). The CIC is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia of the Castilla-León autonomous government (CLC-2017-01). L.F.L.-M. and N.F.-P. contracts have been supported by funding from the Spanish Ministry of Universities (FPU13/02923, FPU17/03912) and, in the case of L.F.L.M., by CLC-2017-01 grant

Plasma coenzyme Q10 status is impaired in selected genetic conditions.

Identifying diseases displaying chronic low plasma Coenzyme Q10 (CoQ) values may be important to prevent possible cardiovascular dysfunction. The aim of this study was to retrospectively evaluate plasma CoQ concentrations in a large cohort of pediatric and young adult patients. We evaluated plasma CoQ values in 597 individuals (age range 1 month to 43 years, average 11 years), studied during the period 2005-2016. Patients were classified into 6 different groups: control group of healthy participants, phenylketonuric patients (PKU), patients with mucopolysaccharidoses (MPS), patients with other inborn errors of metabolism (IEM), patients with neurogenetic diseases, and individuals with neurological diseases with no genetic diagnosis. Plasma total CoQ was measured by reverse-phase high-performance liquid chromatography with electrochemical detection and ultraviolet detection at 275 nm. ANOVA with Bonferroni correction showed that plasma CoQ values were significantly lower in the PKU and MPS groups than in controls and neurological patients. The IEM group showed intermediate values that were not significantly different from those of the controls. In PKU patients, the Chi-Square test showed a significant association between having low plasma CoQ values and being classic PKU patients. The percentage of neurogenetic and other neurological patients with low CoQ values was low (below 8%). In conclusión, plasma CoQ monitoring in selected groups of patients with different IEM (especially in PKU and MPS patients, but also in IEM under protein-restricted diets) seems advisable to prevent the possibility of a chronic blood CoQ suboptimal status in such groups of patients

Static Analysis-based Debugging, Certification, Testing, and Optimization with CiaoPP

Facilitate the development of safe, efficient programs. Approach: •Next-generation, higher-level, multiparadigm prog. languages. •Improved program development environments. •A framework (CiaoPP) which integrates: •Debugging. •Verification and certification. •Testing. •Optimization (optimized compilation, parallelization, ...

Differential role of the RasGEFs Sos1 and Sos2 in mouse skin homeostasis and carcinogenesis

Using Sos1 knockout (Sos1-KO), Sos2-KO, and Sos1/2 double-knockout (Sos1/2-DKO) mice, we assessed the functional role of Sos1 and Sos2 in skin homeostasis under physiological and/or pathological conditions. Sos1 depletion resulted in significant alterations of skin homeostasis, including reduced keratinocyte proliferation, altered hair follicle and blood vessel integrity in dermis, and reduced adipose tissue in hypodermis. These defects worsened significantly when both Sos1 and Sos2 were absent. Simultaneous Sos1/2 disruption led to severe impairment of the ability to repair skin wounds, as well as to almost complete ablation of the neutrophil-mediated inflammatory response in the injury site. Furthermore, Sos1 disruption delayed the onset of tumor initiation, decreased tumor growth, and prevented malignant progression of papillomas in a DMBA (7,12-dimethylbenz[α]anthracene)/TPA (12-O-tetradecanoylphorbol-13-acetate)-induced skin carcinogenesis model. Finally, Sos1 depletion in preexisting chemically induced papillomas resulted also in decreased tumor growth, probably linked to significantly reduced underlying keratinocyte proliferation. Our data unveil novel, distinctive mechanistic roles of Sos 1 and Sos2 in physiological control of skin homeostasis and wound repair, as well as in pathological development of chemically induced skin tumors. These observations underscore the essential role of Sos proteins in cellular proliferation and migration and support the consideration of these RasGEFs as potential biomarkers/therapy targets in Ras-driven epidermal tumors.This study was supported by grants FIS PI16/02137 from ISCIII (MINECO), SA043U16 (UIC 076) from JCyL, and AECC Spain (to E.S.); by MINECO grant SAF2015-66015-R; and by MSyC grants ISCIII-RETIC RD12/0036/0009, PIE 15/00076, and CB/16/00228 (to J.M.P.). This research was cofinanced by FEDER fund