Design and evaluation of a panel os single-nucleotide polymorphisms in microRNA genomic regions for association studies in human disease

MicroRNAs (miRNA) are recognized posttranscriptional gene repressors involved in the control of almost every biological process. Allelic variants in these regions may be an important source of phenotypic diversity and contribute to disease susceptibility. We analyzed the genomic organization of 325 human miRNAs (release 7.1, miRBase) to construct a panel of 768 single-nucleotide polymorphisms (SNPs) covering approximately 1 Mb of genomic DNA, including 131 isolated miRNAs (40%) and 194 miRNAs arranged in 48 miRNA clusters, as well as their 5-kb flanking regions. Of these miRNAs, 37% were inside known protein-coding genes, which were significantly associated with biological functions regarding neurological, psychological or nutritional disorders. SNP coverage analysis revealed a lower SNP density in miRNAs compared with the average of the genome, with only 24 SNPs located in the 325 miRNAs studied. Further genotyping of 340 unrelated Spanish individuals showed that more than half of the SNPs in miRNAs were either rare or monomorphic, in agreement with the reported selective constraint on human miRNAs. A comparison of the minor allele frequencies between Spanish and HapMap population samples confirmed the applicability of this SNP panel to the study of complex disorders among the Spanish population, and revealed two miRNA regions, hsa-mir-26a-2 in the CTDSP2 gene and hsa-mir-128-1 in the R3HDM1 gene, showing geographical allelic frequency variation among the four HapMap populations, probably because of differences in natural selection. The designed miRNA SNP panel could help to identify still hidden links between miRNAs and human disease.

Catholic Confession of Sins as Third-Party Moral Enforcement

Catholicism has built up a legalistic religion based on two pillars: salvation by works and 'auricular' confession of sins to a priest with judicial functions. Since the Reformation, many consider auricular confession inferior to less institutional and more individual conceptions of faith. This article analyzes how all these historical solutions trade off specialization advantages against exchange costs to produce moral enforcement. After showing the behavioral foundations of confession and the adaptiveness of its historical evolution, it tests hypotheses on its efficacy, exploitation and opportunity cost. Econometric evidence supports the efficacy but not the exploitative character of Catholic confession. It also explains its secular decline as a consequence of two factors. First, the rise in education, which makes moral self-enforcement less costly. Second, the productivity gap suffered by confession, given its necessarily interpersonal nature.

Supplemental nursing staff´s experiences at a Spanish hospital: Qualitative phenomenology research

The objective of this study was to describe the Supplemental Nursing Staff´s experiences at different hospital units. A qualitative phenomenological approach was conducted; a purposeful and theoretical sampling was implemented with supplemental nursing staff at Santa Barbara Hospital of Soria (Spain), to gain a more in-depth understanding of the Supplemental Nursing Staff ´s experience. Data were collected by in-depth interviews and through a field notebook. Data were analyzed using the Giorgi proposal. Twenty-one nurses with a mean age of 46 years were included. Three main topics emerged from the data analysis: building the first contact, carving out a niche and establishing interprofessional/interpersonal relationships. We conclude that the experience of hosting the supplemental nursing staff in changing clinical environments is conditioned by various factors. It is necessary for nurses and hospital managers to establish clear objectives with regard to the supplemental nursing staff´s role in the units.

Usability of computerized nursing process from the ICNP® in intensive care units

OBJECTIVE To analyze the usability of Computerized Nursing Process (CNP) from the ICNP® 1.0 in Intensive Care Units in accordance with the criteria established by the standards of the International Organization for Standardization and the Brazilian Association of Technical Standards of systems. METHOD This is a before-and-after semi-experimental quantitative study, with a sample of 34 participants (nurses, professors and systems programmers), carried out in three Intensive Care Units. RESULTS The evaluated criteria (use, content and interface) showed that CNP has usability criteria, as it integrates a logical data structure, clinical assessment, diagnostics and nursing interventions. CONCLUSION The CNP is a source of information and knowledge that provide nurses with new ways of learning in intensive care, for it is a place that provides complete, comprehensive, and detailed content, supported by current and relevant data and scientific research information for Nursing practices.

Effect of reducing sensory and environmental stimuli during hospitalized premature infant sleep

OBJECTIVETo compare the total sleep time of premature infant in the presence or absence of reducing sensory and environmental stimuli in the neonatal unit.METHODLongitudinal study in a Neonatal Intermediate Care Unit of a public hospital in Sao Paulo. The sample consisted of 13 premature infants. We used polysomnograph and unstructured observation for data collection. We analyzed 240 and 1200 minutes corresponding to the periods of the presence and absence of environmental management, respectively. Data were compared in proportion to the total sleep time in the two moments proposed by the study.RESULTSThe total sleep time in periods without environmental management was on average 696.4 (± 112.1) minutes and with management 168.5 (± 27.9) minutes, proportionally premature infant slept an average of 70.2% during periods with no intervention and 58.0% without management (p=0.002).CONCLUSIONReducing stimulation and handling of premature infant environment periods was effective to provide greater total sleep time.

Time standards of nursing in Primary Health Care: an observational study

Abstract OBJECTIVE To determine time standards for interventions and activities conducted by nursing professionals in Family Health Units (FHU) in Brazil to substantiate the calculation of work force. METHOD This was an observational study carried out in 27 FHU, in 12 municipalities in 10 states, in 2013. In each unit, nursing professionals were observed every 10 minutes, for eight work hours, on five consecutive days via the work sampling technique. RESULTS A total of 32,613 observations were made, involving 47 nurses and 93 nursing technicians/assistants. Appointments were the main intervention carried out by nurses, with a mean time of 25.3 minutes, followed by record-keeping, which corresponded to 9.7%. On average, nursing technicians/assistants spent 6.3% of their time keeping records and 30.6 intervention minutes on immunization/vaccination control. CONCLUSION The study resulted in standard times of interventions carried out by the FHU nursing team, which can underpin the determination of nursing staff size and human resource policies. Furthermore, the study showed the panorama of interventions currently employed, allowing for the work process to be reviewed and optimized.

Gene expression profiling in the human pathogenic dermatophyte Trichophyton rubrum during growth on proteins.

Dermatophytes are highly specialized filamentous fungi which cause the majority of superficial mycoses in humans and animals. The high secreted proteolytic activity of these microorganisms during growth on proteins is assumed to be linked to their particular ability to exclusively infect keratinized host structures such as the skin stratum corneum, hair, and nails. Individual secreted dermatophyte proteases were recently described and linked with the in vitro digestion of keratin. However, the overall adaptation and transcriptional response of dermatophytes during protein degradation are largely unknown. To address this question, we constructed a cDNA microarray for the human pathogenic dermatophyte Trichophyton rubrum that was based on transcripts of the fungus grown on proteins. Profiles of gene expression during the growth of T. rubrum on soy and keratin protein displayed the activation of a large set of genes that encode secreted endo- and exoproteases. In addition, other specifically induced factors potentially implicated in protein utilization were identified, including heat shock proteins, transporters, metabolic enzymes, transcription factors, and hypothetical proteins with unknown functions. Of particular interest is the strong upregulation of key enzymes of the glyoxylate cycle in T. rubrum during growth on soy and keratin, namely, isocitrate lyase and malate synthase. This broad-scale transcriptional analysis of dermatophytes during growth on proteins reveals new putative pathogenicity-related host adaptation mechanisms of these human pathogenic fungi.

Adaptive sequence evolution in a color gene involved in the formation of the characteristic egg-dummies of male haplochromine cichlid fishes.

BACKGROUND: The exceptionally diverse species flocks of cichlid fishes in East Africa are prime examples of parallel adaptive radiations. About 80% of East Africa's more than 1 800 endemic cichlid species, and all species of the flocks of Lakes Victoria and Malawi, belong to a particularly rapidly evolving lineage, the haplochromines. One characteristic feature of the haplochromines is their possession of egg-dummies on the males' anal fins. These egg-spots mimic real eggs and play an important role in the mating system of these maternal mouthbrooding fish. RESULTS: Here, we show that the egg-spots of haplochromines are made up of yellow pigment cells, xanthophores, and that a gene coding for a type III receptor tyrosine kinase, colony-stimulating factor 1 receptor a (csf1ra), is expressed in egg-spot tissue. Molecular evolutionary analyses reveal that the extracellular ligand-binding and receptor-interacting domain of csf1ra underwent adaptive sequence evolution in the ancestral lineage of the haplochromines, coinciding with the emergence of egg-dummies. We also find that csf1ra is expressed in the egg-dummies of a distantly related cichlid species, the ectodine cichlid Ophthalmotilapia ventralis, in which markings with similar functions evolved on the pelvic fin in convergence to those of the haplochromines. CONCLUSION: We conclude that modifications of existing signal transduction mechanisms might have evolved in the haplochromine lineage in association with the origination of anal fin egg-dummies. That positive selection has acted during the evolution of a color gene that seems to be involved in the morphogenesis of a sexually selected trait, the egg-dummies, highlights the importance of further investigations of the comparative genomic basis of the phenotypic diversification of cichlid fishes.

Sustainability of the Peruvian anchoveta supply chains from sea to shelf: towards a new strategy for optimal use of resources

The research performed a sustainability assessment of supply chains of the anchoveta (Engraulis ringens) in Peru. The corresponding fisheries lands 6.5 million t per year, of which <2% is rendered into products for direct human consumption (DHC) and 98% reduced into feed ingredients (fishmeal and fish oil, FMFO), for export. Several industries compete for the anchoveta resources, generating local and global impacts. The need for understanding these dynamics, towards sustainability-improving management and policy recommendations, determined the development of a sustainability assessment framework: 1) characterisation and modelling of the systems under study (with Life Cycle Assessment and other tools) including local aquaculture, 2) calculation of sustainability indicators (i.e. energy efficiency, nutritional value, socio-economic performances), and 3) sustainability comparison of supply chains; definition and comparison of alternative exploitation scenarios. Future exploitation scenarios were defined by combining an ecosystem and a material flow models: continuation of the status quo (Scenario 1), shift towards increased proportion of DHC production (Scenario 2), and radical reduction of the anchoveta harvest in order for other fish stocks to recover and be exploited for DHC (Scenario 3). Scenario 2 was identified as the most sustainable. Management and policy recommendations include improving of: controls for compliance with management measures, sanitary conditions for DHC, landing infrastructure for small- and medium-scale (SMS) fisheries; the development of a national refrigerated distribution chain; and the assignation of flexible tolerances for discards from different DHC processes.

MALT1 and Caspase-10 : two cysteine proteases controlling lymphocyte activation

&#932; cell activation via the &#932; cell receptor (TCR) through antigen recognition is one of the key steps to initiate the adaptive immune response. The mechanisms controlling TCR-induced signaling pathways are the subject of intense research, since deregulated signaling in lymphocytes can lead to immunodeficiency, autoimmunity or lymphomas. In &#932; lymphocytes a complex composed of CARMA1, BCL10 and MALT1 has been identified to receive signals from TCR proximal events and to induce further signals crucial for &#932; cell activation. MALT1 is scaffold protein and a cysteine protease and both functions have been shown, among other effects, to be crucial to initiate the activation of the transcription factors of the nuclear factor &#954;&#914; (NF-&#954;&#914;) family after TCR-stimulation. Several proteolytic targets have been described recently and all of them play roles in modulating NF-&#954;&#914; activation or other aspects of &#932; cell activation. In this study, we describe a novel target of MALT1, Caspase-10. Two isoforms of Caspase-10 are cleaved by MALTI in &#932; and &#914; cells after antigen receptor stimulation. Caspases are a family of cysteine proteases that are known for their roles in cell death and certain immune functions. Caspase-10 has so far only been reported to be involved in the induction of apoptosis. However it is very closely related to the well-characterized Caspase-8 that has been reported to be involved in &#932; cell activation. In the present study, we describe a crucial role for Caspase-10, but not Caspase-8, in &#932; cell activation after TCR stimulation. Jurkat &#932; cells silenced for Caspase-10 expression exhibit a dramatic reduction in IL-2 production following stimulation. The data obtained revealed that this is due to severely reduced activation of activator protein-1 (AP-1), another transcription factor family with key functions in the process of &#932; cell activation. We observed strongly reduced expression levels of the AP-1 family member c-Fos after &#932; cell stimulation. This transcription factor is expressed upon TCR stimulation and is a crucial component of AP-1 transcription factor dimers required for &#932; cell activation. In further analysis, it was shown that this defect is not based on reduced transcription, as the c-Fos mRNA levels are not altered, but rather seems to be caused by a defect in translation or protein stability in the absence of Caspase-10. Furthermore, we report a potential interaction of the c-Fos protein and Caspsae-10. This role of Caspase-10 in AP-1 activation however is independent of its cleavage by MALT1, leaving the role of Caspase-10 cleavage in activated lymphocytes unclear. Taken together, these results give new insights into the complex matter of lymphocyte activation whose understanding is crucial for the development of new drugs modulating the immune response or inhibiting lymphoma progression.

Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs.

The function of most proteins is not determined experimentally, but is extrapolated from homologs. According to the "ortholog conjecture", or standard model of phylogenomics, protein function changes rapidly after duplication, leading to paralogs with different functions, while orthologs retain the ancestral function. We report here that a comparison of experimentally supported functional annotations among homologs from 13 genomes mostly supports this model. We show that to analyze GO annotation effectively, several confounding factors need to be controlled: authorship bias, variation of GO term frequency among species, variation of background similarity among species pairs, and propagated annotation bias. After controlling for these biases, we observe that orthologs have generally more similar functional annotations than paralogs. This is especially strong for sub-cellular localization. We observe only a weak decrease in functional similarity with increasing sequence divergence. These findings hold over a large diversity of species; notably orthologs from model organisms such as E. coli, yeast or mouse have conserved function with human proteins.

Virtualització de servidors. Avantatges. Implantació en una PIME real

 En la societat d’avui dia, les empreses depenen en gran part dels seus recursos informàtics. La seva capacitat de supervivència i innovació en el mercat actual, on la competitivitat és cada dia més forta, passa per una infraestructura informàtica que els permeti, no només desplegar i implantar ordinadors i servidors de manera ràpida i eficient sinó que també les protegeixi contra parades del sistema informàtic, problemes amb servidors, caigudes o desastres físics de hardware.Per evitar aquests problemes informàtics susceptibles de poder parar el funcionament d’una empresa es va començar a treballar en el camp de la virtualització informàtica amb l’objectiu de poder trobar solucions a aquests problemes a la vegada que s’aprofitaven els recursos de hardware existents d’una manera més òptim a i eficient, reduint així també el cost de la infraestructura informàtica.L’objectiu principal d’aquest treball és veure en primer pla la conversió d’una empresa real amb una infraestructura informàtica del tipus un servidor físic -una funció cap a una infraestructura virtual del tipus un servidor físic -varis servidors virtual -vàries funcions. Analitzarem l’estat actual de l’empresa, servidors i funcions, adquirirem el hardware necessari i farem la conversió de tots els seus servidors cap a una nova infraestructura virtual.Faig especial atenció a les explicacions de perquè utilitzo una opció i no un altre i també procuro sempre donar vàries opcions. Igualment remarco en quadres verds observacions a tenir en compte complementàries al que estic explicant en aquell moment, i en quadres vermells temes en els que s’ha de posar especial atenció en el moment en que es fan. Finalment, un cop feta la conversió, veurem els molts avantatges que ens ha reportat aquesta tecnologia a nivell de fiabilitat, estabilitat, capacitat de tolerància a errades, capacitat de ràpid desplegament de noves màquines, capacitat de recuperació del sistema i aprofitament de recursos físics.

Patterns of positive selection in seven ant genomes.

The evolution of ants is marked by remarkable adaptations that allowed the development of very complex social systems. To identify how ant-specific adaptations are associated with patterns of molecular evolution, we searched for signs of positive selection on amino-acid changes in proteins. We identified 24 functional categories of genes which were enriched for positively selected genes in the ant lineage. We also reanalyzed genome-wide data sets in bees and flies with the same methodology to check whether positive selection was specific to ants or also present in other insects. Notably, genes implicated in immunity were enriched for positively selected genes in the three lineages, ruling out the hypothesis that the evolution of hygienic behaviors in social insects caused a major relaxation of selective pressure on immune genes. Our scan also indicated that genes implicated in neurogenesis and olfaction started to undergo increased positive selection before the evolution of sociality in Hymenoptera. Finally, the comparison between these three lineages allowed us to pinpoint molecular evolution patterns that were specific to the ant lineage. In particular, there was ant-specific recurrent positive selection on genes with mitochondrial functions, suggesting that mitochondrial activity was improved during the evolution of this lineage. This might have been an important step toward the evolution of extreme lifespan that is a hallmark of ants.

Relaxation times of non-Markovian processes

We consider a general class of non-Markovian processes defined by stochastic differential equations with Ornstein-Uhlenbeck noise. We present a general formalism to evaluate relaxation times associated with correlation functions in the steady state. This formalism is a generalization of a previous approach for Markovian processes. The theoretical results are shown to be in satisfactory agreement both with experimental data for a cubic bistable system and also with a computer simulation of the Stratonovich model. We comment on the dynamical role of the non-Markovianicity in different situations.

Structural changes in latosols of the cerrado region: II - soil compressive behavior and modeling of additional compaction

Currently in Brazil, as in other parts of the world, the concern is great with the increase of degraded agricultural soil, which is mostly related to the occurrence of soil compaction. Although soil texture is recognized as a very important component in the soil compressive behaviors, there are few studies that quantify its influence on the structural changes of Latosols in the Brazilian Cerrado region. This study aimed to evaluate structural changes and the compressive behavior of Latosols in Rio Verde, Goiás, through the modeling of additional soil compaction. The study was carried out using five Latosols with very different textures, under different soil compaction levels. Water retention and soil compression curves, and bearing capacity models were determined from undisturbed samples collected on the B horizons. Results indicated that clayey and very clayey Latosols were more susceptible to compression than medium-textured soils. Soil compression curves at density values associate with edaphic functions were used to determine the beneficial pressure (&#963; b) , i.e., pressure with optimal water retention, and critical pressure (&#963;crMAC), i.e., pressure with macroporosity below critical levels. These pressure values were higher than the preconsolidation pressure (&#963;p), and therefore characterized as additional compaction. Based on the compressive behavior of these Latosols, it can be concluded that the combined preconsolidation pressure, beneficial pressure and critical pressure allow a better understanding of compression processes of Latosols.