SeqBreed : a python tool to evaluate genomic prediction in complex scenarios

Background: Genomic prediction (GP) is a method whereby DNA polymorphism information is used to predict breeding values for complex traits. Although GP can significantly enhance predictive accuracy, it can be expensive and difficult to implement. To help design optimum breeding programs and experiments, including genome-wide association studies and genomic selection experiments, we have developed SeqBreed, a generic and flexible forward simulator programmed in python3. Results: SeqBreed accommodates sex and mitochondrion chromosomes as well as autopolyploidy. It can simulate any number of complex phenotypes that are determined by any number of causal loci. SeqBreed implements several GP methods, including genomic best linear unbiased prediction (GBLUP), single-step GBLUP, pedigree-based BLUP, and mass selection. We illustrate its functionality with Drosophila genome reference panel (DGRP) sequence data and with tetraploid potato genotype data. Conclusions: SeqBreed is a flexible and easy to use tool that can be used to optimize GP or genome-wide association studies. It incorporates some of the most popular GP methods and includes several visualization tools. Code is open and can be freely modified. Software, documentation, and examples are available at https://github.com/miguelperezenciso/SeqBreed

Protein Discrimination Using a Fluorescence-Based Sensor Array of Thiacarbocyanine-GUMBOS

Sensitive and selective detection of proteins from complex samples has gained substantial interest within the scientific community. Early and precise detection of key proteins plays an important role in potential clinical diagnosis, treatment of different diseases, and proteomic research. In the study reported here, six different compounds belonging to a group of uniform materials based on organic salts (GUMBOS) have been synthesized using three thiacarbocyanine (TC) dyes and employed as fluorescent sensors. Fluorescence properties of micro- and nanoaggregates of these TC-based GUMBOS formed in phosphate buffer solutions are studied in the absence and presence of seven proteins. Fluorescence response patterns of these TC-based GUMBOS were analyzed by linear discriminant analysis (LDA). The constructed LDA model allowed discrimination of these seven proteins at various concentrations with 100% accuracy. The sensing and discrimination abilities of these TC-based GUMBOS were further evaluated in mixtures of two major proteins, i.e., human serum albumin and hemoglobin. Fluorescence response patterns of these mixtures were analyzed by LDA. This model allowed discrimination of various mixtures with 100% accuracy. Moreover, spiked urine samples were prepared and the responses of these sensors were collected and analyzed by LDA. Remarkably, discrimination of these seven proteins was also achieved with 100% accuracy

Psychiatric and social characterisation of suicide attempts treated at a children's clinic, 2003-2005.

OBJECTIVE: Psychiatrically and socially characterising suicide attempts treated at a children's clinic in Bogota, 2003-2005.METHODS: A retrospective series of 96 cases aged 11-18, using univariate and bivariate statistical analysis.RESULTS: 81,4 % of the cases were female. Mean age was 15,3 years and 70,9 % were aged 16 or younger. Low family income was found in 63,1 %. Poisoning was the suicide method in 96,9 % cases. Ambulatory care for two months or less was continued in 38 % cases. Only 13,2 % required anti-depressive or mood-modulator medicine. 87,9 % suffered family or scholastic stress. 83,5 % had a problematic relationship with parents and in 72,3 % of cases the parents had a conflictive relationship. 46,5 % were first-born children. Forty abuse situations were found. 27,2 % had attempted suicide previously. Adjustment disorders, family dysfunction and mood disorders were the main psychiatric diagnostics. 37,6 % had scholastic problems, suffered academic failure or had conflict with their teachers. Males were associated with aggressiveness, substance use, academic failure or romantic loss and females were associated with predominant anxiety and physical abuse.DISCUSSION: Being young, the overrepresentation of females and suffering scholastic and family conflict were noteworthy. Gender association with socio-cultural, behavioural and emotional profile is also worth noting. Socio-family and scholastic conflict is frequent in youth people's suicide attempts. The child-youth suicide problem must be made socially visible to prevent it

Psychiatric and social characterisation of suicide attempts treated at a children's clinic, 2003-2005

Objetivos Caracterizar psiquiátrica y socialmente el intento suicida atendido en una clínica infantil de Bogotá, entre 2003 y 2005. Métodos Serie retrospectiva de 96 Casos de 11 a 18 años de edad. Se realizó análisis estadístico univariado y bivariado. Resultados: Las mujeres constituyeron 81,4 %. La edad promedio fue 15,3 años y 70,9 % tenía máximo 16 años. El 63,1 % de familias tenían bajos ingresos. La intoxicación fue el método suicida del 96,9 %. El 38 % tuvo seguimiento ambulatorio máximo por 2 meses. Sólo 13,2 % requirió medicina antidepresiva o moduladora del afecto. El 87,9 % tenía estresantes familiares o escolares. El 83,5 % tenía problemas con los padres, y en 72,3 %, los padres tenían relación conflictiva. Eran primogénitos 46,5 %. Se encontraron 40 situaciones de maltrato. El 27,2 % tuvo intento suicida previo. Los trastornos adaptativos, la disfunción familiar y los trastornos del afecto fueron los principales diagnósticos psiquiátricos. El 37,6 % tenía problemas escolares, pérdida escolar o conflictos con los maestros. El sexo masculino se asoció con agresividad, consumo de sustancias, fracasos escolares o sentimentales y el femenino con ansiedad predominante y maltrato físico. Discusión Se resalta la disminución de la edad, el exceso de representación femenina, la frecuencia alta de conflictos familiares o escolares y la asociación del sexo con perfiles específicos socioculturales, conductuales y emocionales. El conflicto sociofamiliar y escolar es frecuente en el intento suicida juvenil. Es necesario hacer visible la problemática suicida infanto-juvenil para su prevención.OBJECTIVE: Psychiatrically and socially characterising suicide attempts treated at a children's clinic in Bogota, 2003-2005.METHODS: A retrospective series of 96 cases aged 11-18, using univariate and bivariate statistical analysis.RESULTS: 81,4 % of the cases were female. Mean age was 15,3 years and 70,9 % were aged 16 or younger. Low family income was found in 63,1 %. Poisoning was the suicide method in 96,9 % cases. Ambulatory care for two months or less was continued in 38 % cases. Only 13,2 % required anti-depressive or mood-modulator medicine. 87,9 % suffered family or scholastic stress. 83,5 % had a problematic relationship with parents and in 72,3 % of cases the parents had a conflictive relationship. 46,5 % were first-born children. Forty abuse situations were found. 27,2 % had attempted suicide previously. Adjustment disorders, family dysfunction and mood disorders were the main psychiatric diagnostics. 37,6 % had scholastic problems, suffered academic failure or had conflict with their teachers. Males were associated with aggressiveness, substance use, academic failure or romantic loss and females were associated with predominant anxiety and physical abuse.DISCUSSION: Being young, the overrepresentation of females and suffering scholastic and family conflict were noteworthy. Gender association with socio-cultural, behavioural and emotional profile is also worth noting. Socio-family and scholastic conflict is frequent in youth people's suicide attempts. The child-youth suicide problem must be made socially visible to prevent it

The Sensitivity of HAWC to High-Mass Dark Matter Annihilations

The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC will observe gamma rays and cosmic rays with an array of water Cherenkov detectors. The full HAWC array is scheduled to be operational in Spring 2015. In this paper, we study the HAWC sensitivity to the gamma-ray signatures of high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be sensitive to diverse searches for dark matter annihilation, including annihilation from extended dark matter sources, the diffuse gamma-ray emission from dark matter annihilation, and gamma-ray emission from non-luminous dark matter subhalos. Here we consider the HAWC sensitivity to a subset of these sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the Galactic center. We simulate the HAWC response to gamma rays from these sources in several well-motivated dark matter annihilation channels. If no gamma-ray excess is observed, we show the limits HAWC can place on the dark matter cross-section from these sources. In particular, in the case of dark matter annihilation into gauge bosons, HAWC will be able to detect a narrow range of dark matter masses to cross-sections below thermal. HAWC should also be sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The constraints placed by HAWC on the dark matter cross-section from known sources should be competitive with current limits in the mass range where HAWC has similar sensitivity. HAWC can additionally explore higher dark matter masses than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR

The Homeodomain Derived Peptide Penetratin Induces Curvature of Fluid Membrane Domains

BACKGROUND:Protein membrane transduction domains that are able to cross the plasma membrane are present in several transcription factors, such as the homeodomain proteins and the viral proteins such as Tat of HIV-1. Their discovery resulted in both new concepts on the cell communication during development, and the conception of cell penetrating peptide vectors for internalisation of active molecules into cells. A promising cell penetrating peptide is Penetratin, which crosses the cell membranes by a receptor and metabolic energy-independent mechanism. Recent works have claimed that Penetratin and similar peptides are internalized by endocytosis, but other endocytosis-independent mechanisms have been proposed. Endosomes or plasma membranes crossing mechanisms are not well understood. Previously, we have shown that basic peptides induce membrane invaginations suggesting a new mechanism for uptake, "physical endocytosis". METHODOLOGY/PRINCIPAL FINDINGS:Herein, we investigate the role of membrane lipid phases on Penetratin induced membrane deformations (liquid ordered such as in "raft" microdomains versus disordered fluid "non-raft" domains) in membrane models. Experimental data show that zwitterionic lipid headgroups take part in the interaction with Penetratin suggesting that the external leaflet lipids of cells plasma membrane are competent for peptide interaction in the absence of net negative charges. NMR and X-ray diffraction data show that the membrane perturbations (tubulation and vesiculation) are associated with an increase in membrane negative curvature. These effects on curvature were observed in the liquid disordered but not in the liquid ordered (raft-like) membrane domains. CONCLUSIONS/SIGNIFICANCE:The better understanding of the internalisation mechanisms of protein transduction domains will help both the understanding of the mechanisms of cell communication and the development of potential therapeutic molecular vectors. Here we showed that the membrane targets for these molecules are preferentially the fluid membrane domains and that the mechanism involves the induction of membrane negative curvature. Consequences on cellular uptake are discussed

Variation in optineurin (OPTN) allele frequencies between and within populations

PURPOSE: To evaluate the extent to which mutations in the optineurin (OPTN) glaucoma gene play a role in glaucoma in different populations. METHODS: Case-controlled study of OPTN sequence variants in individuals with or without glaucoma in populations of different ancestral origins and evaluate previous OPTN reports. We analyzed 314 subjects with African, Asian, Caucasian and Hispanic ancestries included 229 cases of primary open-angle glaucoma, 51 cases of juvenile-onset open-angle glaucoma, 33 cases of normal tension glaucoma, and 371 controls. Polymerase chain reaction-amplified OPTN coding exons were resequenced and case frequencies were compared to frequencies in controls matched for ancestry. RESULTS: The E50K sequence variant was identified in one individual from Chile with normal tension glaucoma, and the 691_692insAG variant was found in one Ashkenazi Jewish individual from Russia. The R545Q variant was found in two Asian individuals with primary open-angle glaucoma; one of Filipino ancestry and one of Korean ancestry. In addition to presenting OPTN allele frequencies for Caucasian and Asian populations that have been the subject of previous reports, we also present information for populations of Hispanic and black African ancestries. CONCLUSIONS: Our study contributes additional evidence to support the previously reported association of the OPTN E50K mutation with glaucoma. After finding an additional 691_692insAG OPTN variant, we can still only conclude that this variant is rare. Combined analysis of our data with data from more than a dozen other studies indicates no association of R545Q with glaucoma in most populations. Those same studies disagree in their conclusions regarding the role of M98K in glaucoma. Our analysis of the combined data provides statistically significant evidence of association of M98K with normal tension glaucoma in Asian populations, but not in Caucasian populations; however, the validity of this conclusion is questionable because of large differences in allele frequencies between and within populations. It is currently not possible to tell how much of the underlying cause of the allele frequency difference is attributable to demographic, technical, or ascertainment differences among the studies