The Genotype and Phenotypes in Families (GPF) platform manages the large and complex data at SFARI.

The exploration of genotypic variants impacting phenotypes is a cornerstone in genetics research. The emergence of vast collections containing deeply genotyped and phenotyped families has made it possible to pursue the search for variants associated with complex diseases. However, managing these large-scale datasets requires specialized computational tools tailored to organize and analyze the extensive data. GPF (Genotypes and Phenotypes in Families) is an open-source platform ( https://github.com/iossifovlab/gpf ) that manages genotypes and phenotypes derived from collections of families. The GPF interface allows interactive exploration of genetic variants, enrichment analysis for de novo mutations, and phenotype/genotype association tools. In addition, GPF allows researchers to share their data securely with the broader scientific community. GPF is used to disseminate two large-scale family collection datasets (SSC, SPARK) for the study of autism funded by the SFARI foundation. However, GPF is versatile and can manage genotypic data from other small or large family collections. Our GPF-SFARI GPF instance ( https://gpf.sfari.org/ ) provides protected access to comprehensive genotypic and phenotypic data for the SSC and SPARK. In addition, GPF-SFARI provides public access to an extensive collection of de novo mutations identified in individuals with autism and related disorders and to gene-level statistics of the protected datasets characterizing the genes' roles in autism. Here, we highlight the primary features of GPF within the context of GPF-SFARI.

EPERCAS study (Strategies for Preventing Medication Administration Errors in Nursing Homes). Preparation of a list of strategies to prevent the most frequent medication administration errors in the residential care environment.

Medication administration errors are one of the most frequent types of errors. There are different safety guides and recommendations to prevent medication errors generally directed to the hospital environment. However, specific recommendations for the management process in the residential care environment are lacking. The main objective of this study was to develop a list of recommendations to aid in preventing the most important medication errors that occur during the administration process in nursing homes (NHs), such as not administering doses or administering medication to the wrong patient. The effectiveness and feasibility of the strategies proposed were evaluated by a panel of experts. The conventional Delphi method was applied. The first round in our study was a face-to-face questionnaire; the second round included an online questionnaire based on the results of the first round. Finally, eight strategies were included in the EPERCAS List: one professional in charge per shift; one professional commissioned by the residential unit; avoid interruptions; avoid medication outside of meal times; personalized medication drawer for each resident including oral medication from a bag and laxatives, inhalers, syrups, eye drops, etc.; identification of the resident and their medication; visual check that everything has been administered; and signature to verify medication administration. The great continual challenge for NH is to define safe and affordable procedures. Minimum safety recommendations for administering the medications, such as those included in this study, should be employed. Our next stage is to implement these strategies in one of our NH and subsequently, evaluate its effectiveness and consider expanding it to the rest of the NH.

Altered neutrophil-to-lymphocyte ratio in sepsis secondary to canine parvoviral enteritis treated with and without an immunomodulator in puppies.

Neutrophil-to-lymphocyte ratio (NLR) is a cheap and easy-to-obtain biomarker that mirrors the balance between innate and adaptive immunity. Cortisol and catecholamines have been identified as major drivers of NLR. High cortisol levels increase neutrophils while simultaneously decreasing lymphocyte counts. Likewise, endogenous catecholamines may cause leukocytosis and lymphopenia. Thus, NLR allows us to monitor patient severity in conditions such as sepsis. Twenty-six puppies with sepsis secondary to canine parvoviral enteritis were treated with and without an immunomodulator. Our group determined the NLR and the plasmatic cortisol levels by chemiluminescence, and norepinephrine (NE) and epinephrine (E) by HPLC during the first 72 h of clinical follow-up. Our results showed that at admission puppies presented an NLR value of 1.8, cortisol of 314.9 nmol/L, NE 3.7, and E 3.3 pmol/mL. Both treatments decreased admission NLR values after 24 h of treatment. However, only the puppies treated with the immunomodulator (I) remained without significant changes in NLR (0.7-1.4) compared to the CT group, and that showed a significant difference (P < 0.01) in their NLR value (0.4-4.6). In addition, we found significant differences in the slope values between the admission and final values of NLR (P < 0.005), cortisol (P < 0.02), and E (P < 0.05) between treatments. Then, our data suggest that the immunomodulator positively affects the number of lymphocytes and neutrophils involved in NLR as well as major drivers like cortisol and epinephrine, which is reflected in clinical parameters and survival.

Tamizaje con oximetría de pulso en el diagnóstico de cardiopatías congénitas críticas en recién nacidos / Pulse oximetry screening in the diagnosis of critical congenital heart diseases in newborns

Resumen Objetivo Describir los resultados del tamizaje con oximetría de pulso en el diagnóstico de cardiopatías congénitas críticas en recién nacidos a término y asintomáticos, en una institución de salud de la ciudad de Cúcuta, durante el año 2018. Método: Se llevó a cabo un estudio de tipo descriptivo, de corte transversal, con recolección de información de manera prospectiva, en el cual se tomó oximetría de pulso a 438 recién nacidos a término, asintomáticos, que se encontraban en el quinto piso del Hospital Universitario Erasmo Meoz entre las 18 y las 48 horas de vida. Resultados El tamizaje fue negativo en un 99.1% de los recién nacidos y positivo en el 0.91%; este porcentaje corresponde a cuatro pacientes a quienes se les solicitó valoración por cardiología pediátrica y ecocardiograma transtorácico, de los cuales uno de ellos fue diagnosticado con transposición de grandes arterias y otro con hipertensión pulmonar moderada, y los dos pacientes restantes fueron sanos y dados de alta. Conclusiones La oximetría de pulso como prueba de tamizaje entre las 18 y las 48 horas de vida fue fundamental para diagnosticar una transposición de grandes arterias en un recién nacido asintomático, permitiéndole un tratamiento oportuno para una patología que representa un gran impacto en la morbimortalidad neonatal. Además, permitió el diagnóstico de hipertensión pulmonar en uno de los neonatos.

Abstract Objective To describe the results of pulse oximetry screening in the diagnosis of critical congenital heart diseases in newborns, in a health institution in Cucuta city, during 2018. Method A descriptive, cross-sectional study was conducted, with information collection prospectively, in which pulse oximetry was taken of 438 asymptomatic newborns at term who are on the fifth floor of the Erasmo Meoz University Hospital between 18 and 48 hours of life. Results Screening was negative in 99.1% of newborns and positive in 0.91%, this percentage corresponds to 4 patients who were asked for evaluation by pediatric cardiology and transthoracic echocardiogram; one of them was diagnosed with transposition of the great arteries, other with moderate pulmonary hypertension, the remaining two patients were healthy and discharged. Conclusions Pulse oximetry as a screening test between 18 and 48 hours of life was essential to diagnose a transposition of the great arteries in an asymptomatic newborn, allowing timely treatment for a pathology that represents a great impact on neonatal morbidity and mortality. Additionally, it allowed the diagnosis of pulmonary hypertension in one of the neonates.

Increased survival in puppies affected by Canine Parvovirus type II using an immunomodulator as a therapeutic aid.

Canine parvovirus type II (CPV-2) infection induces canine parvoviral enteritis (CPE), which in turn promotes sepsis and systemic inflammatory response syndrome (SIRS). Mortality in this disease is usually registered within 48-72 h post-hospitalization, the critical period of the illness. It has been recently described that the use of an immunomodulator, whose major component is monomeric ubiquitin (mUb) without the last two glycine residues (Ub∆GG), in pediatric human patients with sepsis augments survival. It is known that CXCR4 is the cell receptor of extracellular ubiquitin in humans. This work aimed to explore the effect of one immunomodulator (human Dialyzable Leukocyte Extract-hDLE) as a therapeutic auxiliary in puppies with sepsis and SIRS induced by CPE. We studied two groups of puppies with CPV-2 infection confirmed by polymerase chain reaction. The first group received conventional treatment (CT) and vehicle (V), while the second group received CT plus the immunomodulator (I). We assessed both groups' survival, clinical condition, number of erythrocytes, neutrophils, and lymphocytes during the hospitalization period. In addition, hematocrit, hemoglobin, plasma proteins and cortisol values, as well as norepinephrine/epinephrine and serotonin concentration were determined. Puppies treated with CT + I showed 81% survival, mild clinical signs, and a significant decrease in circulating neutrophils and lymphocytes in the critical period of the treatment. In contrast, the CT + V group presented a survival of 42%, severe clinical status, and no improvement of the parameters evaluated in the critical period of the disease. We determined in silico that human Ub∆GG can bind to dog CXCR4. In conclusion, the administration of a human immunomodulator (0.5 mg/day × 5 days) to puppies with CPE under six months of age reduces the severity of clinical signs, increases survival, and modulates inflammatory cell parameters. Further studies are necessary to take full advantage of these clinical findings, which might be mediated by the human Ub∆GG to canine CXCR4 interaction.

Rates of contributory de novo mutation in high and low-risk autism families.

Autism arises in high and low-risk families. De novo mutation contributes to autism incidence in low-risk families as there is a higher incidence in the affected of the simplex families than in their unaffected siblings. But the extent of contribution in low-risk families cannot be determined solely from simplex families as they are a mixture of low and high-risk. The rate of de novo mutation in nearly pure populations of high-risk families, the multiplex families, has not previously been rigorously determined. Moreover, rates of de novo mutation have been underestimated from studies based on low resolution microarrays and whole exome sequencing. Here we report on findings from whole genome sequence (WGS) of both simplex families from the Simons Simplex Collection (SSC) and multiplex families from the Autism Genetic Resource Exchange (AGRE). After removing the multiplex samples with excessive cell-line genetic drift, we find that the contribution of de novo mutation in multiplex is significantly smaller than the contribution in simplex. We use WGS to provide high resolution CNV profiles and to analyze more than coding regions, and revise upward the rate in simplex autism due to an excess of de novo events targeting introns. Based on this study, we now estimate that de novo events contribute to 52-67% of cases of autism arising from low risk families, and 30-39% of cases of all autism.

Structure of crystalline and amorphous materials in the NASICON system Na1+xAlxGe2-x(PO4)3.

The structure of crystalline and amorphous materials in the sodium (Na) super-ionic conductor system Na1+xAlxGe2-x(PO4)3 with x = 0, 0.4, and 0.8 was investigated by combining (i) neutron and x-ray powder diffraction and pair-distribution function analysis with (ii) 27Al and 31P magic angle spinning (MAS) and 31P/23Na double-resonance nuclear magnetic resonance (NMR) spectroscopy. A Rietveld analysis of the powder diffraction patterns shows that the x = 0 and x = 0.4 compositions crystallize into space group-type R3̄, whereas the x = 0.8 composition crystallizes into space group-type R3̄c. For the as-prepared glass, the pair-distribution functions and 27Al MAS NMR spectra show the formation of sub-octahedral Ge and Al centered units, which leads to the creation of non-bridging oxygen (NBO) atoms. The influence of these atoms on the ion mobility is discussed. When the as-prepared glass is relaxed by thermal annealing, there is an increase in the Ge and Al coordination numbers that leads to a decrease in the fraction of NBO atoms. A model is proposed for the x = 0 glass in which super-structural units containing octahedral Ge(6) and tetrahedral P(3) motifs are embedded in a matrix of tetrahedral Ge(4) units, where superscripts denote the number of bridging oxygen atoms. The super-structural units can grow in size by a reaction in which NBO atoms on the P(3) motifs are used to convert Ge(4) to Ge(6) units. The resultant P(4) motifs thereby provide the nucleation sites for crystal growth via a homogeneous nucleation mechanism.

General paediatric practice in autism spectrum disorder screening in Ontario, Canada: Opportunities for improvement.

BACKGROUND: Screening is important for early identification of children with autism spectrum disorder (ASD), potentially leading to earlier intervention. Research has identified some barriers to early identification of ASD, however, information about ASD screening in Canadian general paediatric practice is lacking. OBJECTIVES: The aim of the study is to better understand ASD screening practice patterns by examining the use of ASD and general developmental screening tools by general paediatricians. METHODS: The research team conducted a cross-sectional survey of general paediatricians. RESULTS: Two-hundred and sixty-seven paediatricians responded and 132 were eligible for the study. Ninety-three per cent of the responders used a developmental screening tool. Eighty-five per cent of the responders used an ASD screening tool when there were concerns for ASD, and 15% never used one. The most commonly used ASD screening tool was the M-CHAT. Children suspected of having ASD were referred to specialists not only to confirm the diagnosis but also to facilitate access to resources. General paediatricians were keen to incorporate formal ASD screening tools in their practice but identified the need for clearer guidelines. CONCLUSION: Previous studies have shown that children at risk of ASD continue to be missed through developmental surveillance and targeted screening. Paediatricians are interested in implementing an ASD screening tool and cite brevity and forms that can be completed by parents as factors that would support the use of a screening tool. Clearer guidelines and tools to support ASD screening and access to resources are needed.

Evaluación de la actividad antimicrobiana in vitro de extractos de Persea americana (Aguacate) variedad Choquette sobre el crecimiento de Staphylococcus aureus y Escherichia coli / Evaluation of the in vitro antimicrobial activity of extracts of Persea americana (Avocado) variety Choquette on the growth of Staphylococcus aureus and Escherichia coli

Las enfermedades infecciosas se encuentran entre las primeras causas de muerte a nivel mundial y la situación se agravada por la aparición progresiva de resistencia a las terapias farmacológicas convencionales. La Persea americana (aguacate), posee sustancias activas que regulan la proliferación de algunos microorganismos patógenos. El objetivo de esta investigación fue evaluar la actividad antimicrobiana y concentración mínima inhibitoria de extractos de Persea americana variedad Choquette sobre el crecimiento de S. aureus ATCC 29213 y E. coli ATCC 25922. La presente fue una investigación de tipo experimental en la que se utilizaron extractos de la cáscara, pulpa y semilla a partir de solventes orgánicos. Se determinó la concentración mínima inhibidora (CMI) y bactericida (CMB) de cada extracto utilizando placas de agar Mueller Hinton las cuales fueron inoculadas con la suspensión bacteriana ajustada. La CMI y CMB para la E. coli. Tratada con la cáscara (solvente hexano y el cloroformo) fue de (1/2)1000 mg/ml; la CMI y CMB para el S. aureus (con los solventes cloroformo y acetato de etilo) fue de (1/2)1000 mg/ml, el extracto de la pulpa no presentó actividad antimicrobiana para ambos microorganismos. Los resultados reflejan actividad antimicrobiana en cascara y semilla, por lo que se propone desarrollar nuevas investigaciones orientadas hacia la caracterización de estos compuestos con miras al desarrollo de fármacos antimicrobianos

Infectious diseases are among the leading causes of death worldwide and the situation is aggravated by the progressive emergence of resistance to conventional drug therapies. The Persea americana (avocado), has active substances that regulate the proliferation of some pathogenic microorganisms. The objective of this research was to evaluate the antimicrobial activity and minimum inhibitory concentration of extracts of Persea americana variety Choquette on the growth of S. aureus ATCC 29213 and E. coli ATCC 25922. The present was an experimental investigation using extracts of the shell, pulp and seed from organic solvents. The minimum inhibitory (MIC) and bactericidal (MIB) concentration of each extract was determined using Mueller Hinton agar plates which were inoculated with the adjusted bacterial suspension. The MIC and CMB for E. coli. Treated with the shell (hexane solvent and chloroform) was (1/2)1000 mg/ml; the MIC and CMB for S. aureus (with the solvents chloroform and ethyl acetate) was (1/2)1000 mg/ml, the pulp extract did not present antimicrobial activity for both microorganisms. The results reflect antimicrobial activity in shell and seed, so it is proposed to develop further research aimed at the characterization of these compounds for the development of antimicrobial drugs

New Na1+xGe2(SiO4)x(PO4)3-x NASICON Series with Improved Grain and Grain Boundary Conductivities.

In this study, we synthesize glass-ceramics of the new Na1+xGe2(SiO4)x(PO4)3-x NASICON (Na super-ionic conductor) series to evaluate the effect of Si4+/P5+ substitution on the structural, microstructural, and electrical properties of the NaGe2(PO4)3 system. From X-ray diffraction, the presence of the NASICON phase is confirmed in all glass-ceramics. An expansion of the unit cell volume suggesting an increase in the bottleneck of the NASICON structure is also observed. Impedance spectroscopy allowed the separation of grain and grain boundary contributions. We observe that the grain conductivity is higher than the specific grain boundary conductivity in all of the investigated compositions (0 ≤ x ≤ 0.8). The Si4+/P5+ substitution causes an enhancement of about 2 and 3 orders of magnitude in the grain and specific grain boundary conductivities, respectively. This behavior is attributable to the introduction of new charge carriers (Na+) in the NASICON structure and a decrease in the activation energy. Finally, the lowest activation energy for grain (0.586 eV) is observed in the x = 0.6 sample, which indicates the easiest displacement of ions in the investigated series, suggesting that this composition presents the most suitable bottleneck size for (Na+) sodium ion conduction.

Influencia del nacimiento pretérmino en procesos conductuales y emocionales de niños en etapa escolar primaria / Influence of preterm births on behavioral and emotional processes of primary school age children / Influência do nascimento prematuro nos processos comportamentais e emocionais de crianças de ensino básico

Resumen (analítico): En esta investigación buscamos establecer las principales características conductuales que pueden manifestarse en niños y niñas entre seis a diez años de edad, con antecedente de nacimiento prematuro. Utilizamos la batería de pruebas BASC (del inglés Behavior Assessment System for Children), la lista de chequeo de los criterios de hiperactividad del DSM-5 y la prueba Caras-R. Aplicamos las pruebas a una muestra de 80 niños y niñas nacidos pretérmino (muestra clínica) y a 80 niños y niñas nacidos a término (muestra control). Analizamos la información a través del software estadístico SPSSTM versión 22, y el software de apoyo para la evaluación neuropsicológica de la conducta humana. En relación con el TDAH, son más frecuentes los casos de inatención o impulsividad en los niños y niñas prematuros, los cuales son percibidos en sus hogares con mayores conductas atípicas, síntomas de hiperactividad, episodios de aislamiento y sintomatología característica de depresión y cuadros de somatización.

Abstract (analytical): This research aimed to establish the main behavioral characteristics that can be presented by children aged between 6-10 years old who were born prematurely. For this purpose, the study used the BASC (Behavior Assessment System for Children) set of tests, the DSM V hyperactivity checklist of and the Caras-R test. These tests were applied to a sample of 80 children who had a preterm birth (clinical sample), and 80 children were born at full term (control sample). The information collected was analyzed using the SPSSTM software Version 22 and additional supporting software for the neuropsychological assessment of human behavior. The results showed that there were more cases of inattention or impulsivity in those born prematurely. This is manifested in their homes through atypical behavior, hyperactivity symptoms, episodes of isolation and the typical symptomatology of depression and somatization.

Resumo (analítico): A pesquisa procurou determinar as principais características comportamentais que podem ocorrer em crianças na faixa etária de 6 a 10 anos de idade com nascimento prematuro. Foi utilizada a bateria de testes BASC (Do inglês Behavior Assessment System for Children), os critérios de verificação de hiperatividade do DSM-5 e o teste de Faces-R. A avaliação foi feita em 80 crianças prematuras (amostra clínica) e 80 crianças não prematuras (amostra controle). Os dados foram analisados utilizando o software estatístico SPSS versão 22 e o software de apoio para avaliação neuropsicológica da conduta humana. Em relação ao TDAH foram mais freqüentes os casos de desatenção ou impulsividade no grupo de crianças nascidas prematuramente, as quais são percebidas nas suas casas como crianças com comportamentos atípicos, com sintomas de hiperatividade, episódios de isolamento, sintomatologia relacionada com depressão e sintomas de somatização.

Evolution of transcriptional networks in yeast: alternative teams of transcriptional factors for different species.

BACKGROUND: The diversity in eukaryotic life reflects a diversity in regulatory pathways. Nocedal and Johnson argue that the rewiring of gene regulatory networks is a major force for the diversity of life, that changes in regulation can create new species. RESULTS: We have created a method (based on our new "ping-pong algorithm) for detecting more complicated rewirings, where several transcription factors can substitute for one or more transcription factors in the regulation of a family of co-regulated genes. An example is illustrative. A rewiring has been reported by Hogues et al. that RAP1 in Saccharomyces cerevisiae substitutes for TBF1/CBF1 in Candida albicans for ribosomal RP genes. There one transcription factor substitutes for another on some collection of genes. Such a substitution is referred to as a "rewiring". We agree with this finding of rewiring as far as it goes but the situation is more complicated. Many transcription factors can regulate a gene and our algorithm finds that in this example a "team" (or collection) of three transcription factors including RAP1 substitutes for TBF1 for 19 genes. The switch occurs for a branch of the phylogenetic tree containing 10 species (including Saccharomyces cerevisiae), while the remaining 13 species (Candida albicans) are regulated by TBF1. CONCLUSIONS: To gain insight into more general evolutionary mechanisms, we have created a mathematical algorithm that finds such general switching events and we prove that it converges. Of course any such computational discovery should be validated in the biological tests. For each branch of the phylogenetic tree and each gene module, our algorithm finds a sub-group of co-regulated genes and a team of transcription factors that substitutes for another team of transcription factors. In most cases the signal will be small but in some cases we find a strong signal of switching. We report our findings for 23 Ascomycota fungi species.

The coffee genome provides insight into the convergent evolution of caffeine biosynthesis.

Coffee is a valuable beverage crop due to its characteristic flavor, aroma, and the stimulating effects of caffeine. We generated a high-quality draft genome of the species Coffea canephora, which displays a conserved chromosomal gene order among asterid angiosperms. Although it shows no sign of the whole-genome triplication identified in Solanaceae species such as tomato, the genome includes several species-specific gene family expansions, among them N-methyltransferases (NMTs) involved in caffeine production, defense-related genes, and alkaloid and flavonoid enzymes involved in secondary compound synthesis. Comparative analyses of caffeine NMTs demonstrate that these genes expanded through sequential tandem duplications independently of genes from cacao and tea, suggesting that caffeine in eudicots is of polyphyletic origin.

Relación e impacto del consumo de sustancias psicoactivas sobre la salud en Colombia / Relationship and impact of the use of psychoactive substances on health in Colombia

Esta investigación tuvo como objetivo principal realizar una aproximación preliminar al examen de la relación entre el consumo de drogas y los problemas de salud en Colombia. Para ello se utilizó un cuestionario con 11 categorías de enfermedades o síndromes (respiratorios, piel, neurológico, psiquiátrico, hepático, autoinmune, cardíaco, traumas y accidentes, transmisión sexual, genito-urinario y otros) que se aplicó a 101 consumidores de drogas entre los 15 y los 64 años de edad y a 50 no consumidores entre 20 y 84 años. Cuatro grupos de trastornos (dificultades psiquiátricas, neurológicas, cardíacas y respiratorias) resultaron significativos entre consumidores de droga. Los trastornos psiquiátricos comprendían ataques de pánico, euforia excesiva, ansiedad general, desmotivación, depresión y alucinaciones; los problemas neurológicos, aumento o disminución de la sensibilidad, pérdida de memoria y dificultades motoras. Solamente un problema cardíaco (las arritmias) y uno respiratorio (tos crónica) fueron significativos. Este estudio sienta las bases para el futuro cálculo de las fracciones atribuibles salud-drogas...

The main objective of this study is to carry out a preliminary approach to the examination of the relationship between drug use and the health problems in Colombia. It was used a questionnaire with 11 categories of diseases or syndromes (respiratory, skin, neurological, psychiatric, liver, self-inmune, cardiac, traumas and accidents, sexually transmitted genitalurinary and others), which was applied at 101 drug users between 15 and 64 years of age and 50 non-consumers between 20 and 84 years old. Four groups of disorders (psychiatric, neurologic, cardiac, and respiratory difficulties) were significant among drug users. Psychiatric disorders included panic attacks, excessive euphoria, general anxiety, discouragement, depression and hallucinations; neurological problems, increase or decrease of sensitivity, memory loss and motor difficulties. Only a heart problem (arrhythmias) and one respiratory (chronic cough) were significantly present. This study lays the groundwork for the future calculations of health-drugs attributable fractions...

Detection of gene expression changes at chromosomal rearrangement breakpoints in evolution.

BACKGROUND: We study the relation between genome rearrangements, breakpoints and gene expression. Genome rearrangement research has been concerned with the creation of breakpoints and their position in the chromosome, but the functional consequences of individual breakpoints remain virtually unknown, and there are no direct genome-wide studies of breakpoints from this point of view. A question arises of what the biological consequences of breakpoint creation are, rather than just their structural aspects. The question is whether proximity to the site of a breakpoint event changes the activity of a gene. RESULTS: We investigate this by comparing the distribution of distances to the nearest breakpoint of genes that are differentially expressed with the distribution of the same distances for the entire gene complement. We study this in data on whole blood tissue in human versus macaque, and in cerebral cortex tissue in human versus chimpanzee. We find in both data sets that the distribution of distances to the nearest breakpoint of "changed expression genes" differs little from this distance calculated for the rest of the gene complement. In focusing on the changed expression genes closest to the breakpoints, however, we discover that several of these have previously been implicated in the literature as being connected to the evolutionary divergence of humans from other primates. CONCLUSIONS: We conjecture that chromosomal rearrangements occasionally interrupt the regulatory configurations of genes close to the breakpoint, leading to changes in expression.

Identidad femenina y consumo de drogas: un estudio cualitativo / Feminine identity and drug use: qualitative research

Este estudio examina la relación entre identidad femenina (IF) y consumo de drogas. Setenta y seis mujeres de tres grupos de edades (jóvenes, adultas jóvenes y adultas mayores), de tres niveles socioeconómicos (alto, medio y bajo) y tres circunstancias de consumo (consumidoras, no consumidoras y ex consumidoras) fueron entrevistadas sobre seis aspectos: la definición de ser mujer y las diferencias con ser hombre; la autovaloración femenina; los factores que influyen en la construcción de la IF; la evolución de la IF; IF y consumo de drogas; factores protectores y de riesgo. Las entrevistadas consideraron que la mayor parte de los cambios recientes dentro de la sociedad occidental han mejorado sustancialmente la condición de la mujer, aun cuando algunos de esos cambios también han incrementado su vulnerabilidad y están asociados al notable aumento del consumo de drogas entre las mujeres. Varios de los factores mencionados no suelen aparecer en los estudios sobre este tema ("mal uso de la libertad", "abandono de responsabilidades", "conducta sexual inadecuada") probablemente porque sus autores temen que se les acuse de estar censurando a las mujeres contemporáneas; en este estudio se presentan las percepciones de las mujeres, no las interpretaciones de los autores.

This study examines the relationship between female identity and drug use. Seventy-six women of three age groups (young, young adults, and mature adults), three socio-economic levels (upper, medium, low) and three drug use conditions (non users, users and ex users) were interviewed on six aspects: definition of "being a woman"; womenÆs self evaluation; factors influencing the development of FI; FI and drug use; and risk and protective factors. The results show that the interviewees think that most of the changes that occurred in West society have substantially improved womenÆs condition; nevertheless, some of those changes have also increased vulnerability and are associated with the notorious increase of drug abuse among women. Some of such factors are rarely mentioned in current studies on these issues (for instance, "bad use of freedom", "lack of responsibility", "sexual misbehaviour") probably because authors are afraid of being accused of blaming women. In this study womenÆs perceptions are presented, rather than authorsÆ interpretations.

Different expression patterns of Ngb and EPOR in the cerebral cortex and hippocampus revealed distinctive therapeutic effects of intranasal delivery of Neuro-EPO for ischemic insults to the gerbil brain.

The purpose of this study was to evaluate the neuroprotective effects of intranasally delivered recombinant human neuronal erythropoietin (Neuro-EPO) on brain injury induced by unilateral permanent ischemia in the Mongolian gerbil. Expression of EPO receptor (EPOR) and neuroglobin (Ngb) over 5 weeks after intranasal treatment with Neuro-EPO was determined using immunohistochemistry. Mortality of Neuro-EPO-treated gerbils decreased after surgery, and the sensory and motor function was significantly improved. Histopathological mapping showed that Neuro-EPO significantly reduced delayed neuronal death in the brain. Expression of Ngb was upregulated in the cerebral cortex at most time points (expect for 10 min and 48 hr) and in the hippocampus at 10 min and from 48 hr to 5 weeks, whereas EPOR was almost downregulated or unchanged in the brain (expect for 48 hr). The 10 min and 48 hr seemed to be two time points for the brain to switch the expression of both Ngb and EPOR to early and late recovery phase, respectively. In addition, there were two phases, 10 min to 1 hr and 24 hr to 72 hr, respectively, closing to the "golden hour" of about 60 min and the "silver day" of 1 to 3 days, for the brain to recover from stroke onset with intranasal Neuro-EPO treatment. Therefore, the results suggest that the intranasal administration of Neuro-EPO is effective in the treatment of acute brain ischemia. The different expression patterns of Ngb and EPOR is probably due to ischemic tolerance in the cerebral cortex and ischemic sensitivity in the hippocampus.

Rearrangement phylogeny of genomes in contig form.

There has been a trend in increasing the phylogenetic scope of genome sequencing while decreasing the quality of the published sequence for each genome. With reduced finishing effort, there is an increasing number of genomes being published in contig form. Rearrangement algorithms, including gene order-based phylogenetic tools, require whole genome data on gene order, segment order, or some other marker order. Items whose chromosomal location is unknown cannot be part of the input. The question we address here is, for gene order-based phylogenetic analysis, how can we use rearrangement algorithms to handle genomes available in contig form only? Our suggestion is to use the contigs directly in the rearrangement algorithms as if they were chromosomes, while making a number of corrections, e.g., we correct for the number of extra fusion/fission operations required to make contigs comparable to full assemblies. We model the relationship between contig number and genomic distance, and estimate the parameters of this model using insect genome data. With this model, we use distance matrix methods to reconstruct the phylogeny based on genomic distance and numbers of contigs. We compare this with methods to reconstruct ancestral gene orders using uncorrected contig data.

Scaffold filling, contig fusion and comparative gene order inference.

BACKGROUND: There has been a trend in increasing the phylogenetic scope of genome sequencing without finishing the sequence of the genome. Increasing numbers of genomes are being published in scaffold or contig form. Rearrangement algorithms, however, including gene order-based phylogenetic tools, require whole genome data on gene order or syntenic block order. How then can we use rearrangement algorithms to compare genomes available in scaffold form only? Can the comparative evidence predict the location of unsequenced genes? RESULTS: Our method involves optimally filling in genes missing from the scaffolds, while incorporating the augmented scaffolds directly into the rearrangement algorithms as if they were chromosomes. This is accomplished by an exact, polynomial-time algorithm. We then correct for the number of extra fusion/fission operations required to make scaffolds comparable to full assemblies. We model the relationship between the ratio of missing genes actually absent from the genome versus merely unsequenced ones, on one hand, and the increase of genomic distance after scaffold filling, on the other. We estimate the parameters of this model through simulations and by comparing the angiosperm genomes Ricinus communis and Vitis vinifera. CONCLUSIONS: The algorithm solves the comparison of genomes with 18,300 genes, including 4500 missing from one genome, in less than a minute on a MacBook, putting virtually all genomes within range of the method.

Inhibition of alpha-synuclein fibrillization by dopamine is mediated by interactions with five C-terminal residues and with E83 in the NAC region.

The interplay between dopamine and alpha-synuclein (AS) plays a central role in Parkinson's disease (PD). PD results primarily from a severe and selective devastation of dopaminergic neurons in substantia nigra pars compacta. The neuropathological hallmark of the disease is the presence of intraneuronal proteinaceous inclusions known as Lewy bodies within the surviving neurons, enriched in filamentous AS. In vitro, dopamine inhibits AS fibril formation, but the molecular determinants of this inhibition remain obscure. Here we use molecular dynamic (MD) simulations to investigate the binding of dopamine and several of its derivatives onto conformers representative of an NMR ensemble of AS structures in aqueous solution. Within the limitations inherent to MD simulations of unstructured proteins, our calculations suggest that the ligands bind to the (125)YEMPS(129) region, consistent with experimental findings. The ligands are further stabilized by long-range electrostatic interactions with glutamate 83 (E83) in the NAC region. These results suggest that by forming these interactions with AS, dopamine may affect AS aggregation and fibrillization properties. To test this hypothesis, we investigated in vitro the effects of dopamine on the aggregation of mutants designed to alter or abolish these interactions. We found that point mutations in the (125)YEMPS(129) region do not affect AS aggregation, which is consistent with the fact that dopamine interacts non-specifically with this region. In contrast, and consistent with our modeling studies, the replacement of glutamate by alanine at position 83 (E83A) abolishes the ability of dopamine to inhibit AS fibrillization.