Estudios genéticos y neurodesarrollo: De la utilidad al modelo genético / Genetic studies and neurodevelopment. From effectiveness to genetic models]

Los avances en la genética han podido apoyar la sospecha que aportaba la experiencia clínica sobre el gran componente hereditario de la mayor parte de estos trastornos del neurodesarrollo (TND). Los estudios iniciales de heredabilidad, ligamiento o asociación evidenciaron desde los inicios la gran contribución de la variación genotípica a la clínica en general, y a los TND en particular. No debe obviarse la utilidad de los estudios genéticos en el ejercicio clínico, encaminados al diagnóstico etiológico. La mayor parte de los mismos están protocolizados en el estudio de trastornos como la discapacidad intelectual y el autismo; dentro de éstos, la hibridación por arrays cromosómicos ha aportado una mayor rentabilidad diagnóstica respecto a técnicas citogenéticas históricas (3 vs. 10% respectivamente). Sin embargo, la irrupción y rentabilidad de técnicas de genética molecular por secuenciación, particularmente la exómica y genómica en trío, analizando a padres, (tasas diagnósticas del 30-50%), están condicionando la modificación de los algoritmos genéticos en el diagnóstico de trastornos graves del neurodesarrollo. El mayor conocimiento de variantes causales de discapacidad intelectual y autismo está igualmente modificando los modelos teóricos poligénicos establecidos hasta la fecha.

Advances in genetics have been able to support the clinical suspicion on the large hereditary component of most of these neurodevelopmental disorders (NDD). Initial studies on heritability, linkage or association showed from the beginning the great contribution of genotypic variation to the clinic in general, and to NDD in particular. The effectiveness of genetic studies in clinical practice, targeted to aetiological diagnosis, should not be ignored. Most of these are protocolized in the study of disorders such as intellectual disability and autism; within these, the array comparative genomic hybridization have supported a greater diagnostic effectiveness with respect to historical cytogenetic techniques (3 vs. 10% respectively). However, the irruption and success of molecular genetic sequencing techniques, particularly the exome and genome in trio, analyzing the parents (diagnostic rates of 30-50%), are conditioning the modification of the genetic algorithms in the diagnosis of different NDD. The greater knowledge of causal variants in intellectual disability and autism is also modifying the polygenic theoretical models established to date.

Insights into the evolution of extracellular leucine-rich repeats in metazoans with special reference to Toll-like receptor 4

The importance of the widely spread leucine-rich repeat (LRR) motif was studied considering TLRs, the LRR-containingprotein involved in animal immune response. The protein connects intracellular signalling with a chain of molecularinteractions through the presence of LRRs in the ectodomain and TIR in the endodomain. Domain analyses with humanTLR1-9 reported ectodomain with tandem repeats, transmembrane domain and TIR domain. The repeat number variedacross members of TLR and remained characteristic to a particular member. Analysis of gene structure revealed absence ofcodon interruption with TLR3 and TLR4 as exceptions. Extensive study with TLR4 from metazoans confirmed thepresence of 23 LRRs in tandem. Distinct clade formation using coding and amino acid sequence of individual repeatsillustrated independent evolution. Although ectodomain and endodomain exhibited differential selection pressure, withinthe ectodomain, however, the individual repeats displayed positive, negative and neutral selection pressure depending ontheir structural and functional significance.

Effect of Cochlear Implant Electrode Array Design on Electrophysiological and Psychophysical Measures: Lateral Wall versus Perimodiolar Types

BACKGROUND AND OBJECTIVES: The present study aims to investigate whether the cochlear implant electrode array design affects the electrophysiological and psychophysical measures. SUBJECTS AND METHODS: Eighty five ears were used as data in this retrospective study. They were divided into two groups by the electrode array design: lateral wall type (LW) and perimodiolar type (PM). The electrode site was divided into three regions (basal, medial, apical). The evoked compound action potential (ECAP) threshold, T level, C level, dynamic range (DR), and aided air conduction threshold were measured. RESULTS: The ECAP threshold was lower for the PM than for the LW, and decreased as the electrode site was closer to the apical region. The T level was lower for the PM than for the LW, and was lower on the apical region than on the other regions. The C level on the basal region was lower for the PM than for the LW whereas the C level was lower on the apical region than on the other regions. The DRs on the apical region was greater for the PM than for the LW whereas the DR was narrower on the apical region than on the other regions. The aided air conduction threshold was not different for the electrode design and frequency. CONCLUSIONS: The current study would support the advantages of the PM over the LW in that the PM had the lower current level and greater DR, which could result in more localized neural stimulation and reduced power consumption.

Portable Low-Cost MRI System Based on Permanent Magnets/Magnet Arrays

Portable low-cost magnetic resonance imaging (MRI) systems have the potential to enable “point-of-care” and timely MRI diagnosis, and to make this imaging modality available to routine scans and to people in underdeveloped countries and areas. With simplicity, no maintenance, no power consumption, and low cost, permanent magnets/magnet arrays/magnet assemblies are attractive to be used as a source of static magnetic field to realize the portability and to lower the cost for an MRI scanner. However, when taking the canonical Fourier imaging approach and using linear gradient fields, homogeneous fields are required in a scanner, resulting in the facts that either a bulky magnet/magnet array is needed, or the imaging volume is too small to image an organ if the magnet/magnet array is scaled down to a portable size. Recently, with the progress on image reconstruction based on non-linear gradient field, static field patterns without spatial linearity can be used as spatial encoding magnetic fields (SEMs) to encode MRI signals for imaging. As a result, the requirements for the homogeneity of the static field can be relaxed, which allows permanent magnets/magnet arrays with reduced sizes, reduced weight to image a bigger volume covering organs such as a head. It offers opportunities of constructing a truly portable low-cost MRI scanner. For this exciting potential application, permanent magnets/magnet arrays have attracted increased attention recently. A magnet/magnet array is strongly associated with the imaging volume of an MRI scanner, image reconstruction methods, and RF excitation and RF coils, etc. through field patterns and field homogeneity. This paper offers a review of permanent magnets and magnet arrays of different kinds, especially those that can be used for spatial encoding towards the development of a portable and low-cost MRI system. It is aimed to familiarize the readers with relevant knowledge, literature, and the latest updates of the development on permanent magnets and magnet arrays for MRI. Perspectives on and challenges of using a permanent magnet/magnet array to supply a patterned static magnetic field, which does not have spatial linearity nor high field homogeneity, for image reconstruction in a portable setup are discussed.

Real-time measurement of cell contractile force during activation of human hepatic stellate cell line LX-2 / 生物医学工程学杂志

The contractile force of hepatic stellate cells plays a very important role in liver damage, hepatitis and fibrosis. In this paper, a method based on polydimethylsiloxane (PDMS) thin micropillar arrays is proposed to measure the contractile force of human hepatic stellate cell line LX-2, which enables dynamic measurement of the subcellular distribution of force magnitude and direction. First, thin micropillar arrays on glass bottom dish were fabricated using two-step casting process in order to meet the working distance requirement of 100× objective lens. After hydrophilic treatment and protein imprint, cells were seeded on the micropillar arrays. LX-2 cells, which were quiesced by growth in serum-free medium, were activated by adding fetal bovine serum (FBS). The deflections of the micropillars were achieved by image processing technique, and then the contractile force of cells exerted on the micropillars was calculated according to mechanical simulation results, and was analyzed under both quiescent and activated conditions. The experimental results show that the average traction force of quiescent cells is about 20 nN, while the contractile force of activated cells increased to 110 nN upon adding FBS. This method can quantify the contractile force of LX-2 cell on subcellular scale in both quiescent and activated states, which may benefit pathology study and drug screen for chronic liver diseases resulted from liver fibrosis.

Chemoradiation therapy induces in vivo changes in gene promoter methylation & gene transcript expression in patients with invasive cervical cancer

Background & objectives: Invasive cervical cancer patients are primarily treated with chemoradiation therapy. The overall and disease-free survival in these patients is variable and depends on the tumoral response apart from the tumour stage. This study was undertaken to assess whether in vivo changes in gene promoter methylation and transcript expression in invasive cervical cancer were induced by chemoradiation. Hence, paired pre- and post-treatment biopsy samples were evaluated for in vivo changes in promoter methylation and transcript expression of 10 genes (ESR1, BRCA1, RASSF1A, MYOD1, MLH1, hTERT, MGMT, DAPK1, BAX and BCL2L1) in response to chemoradiation therapy. Methods: In patients with locally advanced invasive cervical cancer, paired pre- and post-treatment biopsies after 10 Gy chemoradiation were obtained. DNA/RNA was extracted and gene promoter methylation status was evaluated by custom-synthesized methylation PCR arrays, and the corresponding gene transcript expression was determined by absolute quantification method using quantitative reverse transcription PCR. Results: Changes in the gene promoter methylation as well as gene expression following chemoradiation therapy were observed. BAX promoter methylation showed a significant increase (P<0.01) following treatment. There was a significant increase in the gene transcript expression of BRCA1 (P<0.01), DAPK1 and ESR1 (P<0.05), whereas MYOD1 and MLH1 gene transcript expression was significantly decreased (P<0.05) following treatment. Interpretation & conclusions: The findings of our study show that chemoradiation therapy can induce epigenetic alterations as well as affect gene expression in tissues of invasive cervical cancer which may have implications in determining radiation response.

Antibacterial activity of TiO2 nanotube arrays on periodontal pathogens before and after loaded with minocycline hydrochloride / 中国病理生理杂志

AIM:To investigate the effects of titanium dioxide(TiO2)nanotube arrays on the early adhesion behavior of Porphyromonas gingivalis(Pg),Tannerella forsythia(Tf)and Actinobacillus actinomycetemcomitans(Aa)be-fore and after loaded with minocycline hydrochloride(MN).METHODS: TiO2nanotube arrays were prepared by ano-dization and loaded with MN.Titanium slices were divided into 3 groups according to different treatment methods: pure polishing titanium(Ti)group,TiO2nanotube titanium(TiO2)group, and MN(120 μg)TiO2nanotube titanium(MN TiO2)group.The antibacterial properties of the titanium tablets were evaluated by the bacteriostasis test.RESULTS:The Ti had no antibacterial activity.The antibacterial activity of TiO 2to Aa,Pg and Tf was poor,with only about 20%of anti-bacterial rate after 4 h.After loaded with MN,its antibacterial activity was enhanced,and the antibacterial rate was up to 77%after 4 h.CONCLUSION: No antibacterial activity in the Ti group was observed.If TiO2nanotube arrays were formed on the surface and MN was loaded,the antibacterial activity on periodontal pathogens was stronger.

Screening and validating the prognostic biomarkers of hepatocelluar carcinoma based on reverse phase protein arrays / 中华肝胆外科杂志

Objective To screen and validate the prognostic biomarkers of patients with hepatocelluar carcinoma (HCC) based on reverse phase protein array (RPPA).Methods All public RPPA data (HCC patients) in TCGA database before December 2017 were enrolled in this study.Univariate and multivariate Cox analysis were used to screen the target proteins with prognostic value.From January 2013 to January 2014,121 HCC patients who were treated in the Affiliated Hospital of North Sichuan Medical College were enrolled in the study.Prognostic related proteins screened from RPPA data were detected in these patients' tumor specimen.Then,the correlations between the expression of the screened protein and prognosis was further analyzed.Results In the 218 protein,23 was related with HCC patient prognosis.Multivariate Cox regression analysis showed that high expression of NOTCH1 (HR=1.515,95％ CI:1.287～1.845,P＜0.05) and high expression of AKT1 (HR=1.119,95％ CI:1.033～ 1.203,P＜0.05) increased the risk of death,while high expression of NF2 (HR=0.865,95％ CI:0.783～0.956,P＜0.05) decreased the risk of death.The results of clinical data analysis indicated that there were significant differences of NOTCH1,AKT1 and NF2 level between HCC and adjacent tissue.Further survival analysis revealed that high expression of NOTCH1 and AKT1 were significantly associated with poor prognosis.The expression of NF2 was correlated with prognosis,but the difference was not statistically significant (P＞0.05).Conclusion RPPA,as a high throughput protein expression quantitative technique,can be used for screening prognostic markers,and the reliability of the screening results is higher in general.

Subclassification and Detection of New Markers for the Discrimination of Primary Liver Tumors by Gene Expression Analysis Using Oligonucleotide Arrays

BACKGROUND/AIMS: The failure to correctly differentiate between intrahepatic cholangiocarcinoma (CC) and hepatocellular carcinoma (HCC) is a significant clinical problem, particularly in terms of the different treatment goals for both cancers. In this study a specific gene expression profile to discriminate these two subgroups of liver cancer was established and potential diagnostic markers for clinical use were analyzed. METHODS: To evaluate the gene expression profiles of HCC and intrahepatic CC, Oligonucleotide arrays (AffymetrixU133A) were used. Overexpressed genes were checked for their potential use as new markers for discrimination and their expression values were validated by reverse transcription polymerase chain reaction and immunohistochemistry analyses. RESULTS: 695 genes/expressed sequence tags (ESTs) in HCC (245 up-/450 down-regulated) and 552 genes/ESTs in CC (221 up-/331 down-regulated) were significantly dysregulated (p 2, ≥70%). Using a supervised learning method, and one-way analysis of variance a specific 270-gene expression profile that enabled rapid, reproducible differentiation between both tumors and non-malignant liver tissues was established. A panel of 12 genes (e.g., HSP90β, ERG1, GPC3, TKT, ACLY, and NME1 for HCC; SPT2, T4S3, CNX43, TTD1, HBD01 for CC) were detected and partly described for the first time as potential discrimination markers. CONCLUSIONS: A specific gene expression profile for discrimination of primary liver cancer was identified and potential marker genes with feasible clinical impact were described.

Genome-wide copy number variations analysis in 64 patients with unexplained intellectual disability / 中华实用儿科临床杂志

Objective To investigate the genetic basis of patients with intellectual disability,and to assess the application of single nucleotide polymorphisms (SNP)-array in the molecular diagnosis of intellectual disability.Methods Sixty-four patients with intellectual disability who were identified in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2013 to June of 2015 were enrolled.Genomic DNA was extracted from peripheral blood and was analyzed with Illumina Humancyto SNP-12 300K gene array chip.All identified copy number variants (CNVs) were analyzed with references from databases such as ClinVar,DECIPHER,OMIM and DGV(Database of Genomic Variants),as well as comprehensive literature review from PubMed database to determine the pathogenicity of CNVs.Results Sixteen cases of the above 64 patients were found to have CNVs with genomic alterations,including 6 cases microdeletions/microduplications associated with known syndromes,3 cases microdeletions and microduplications with clear clinical relevance (non-syndrome),1 case numerical chromosome aberration,1 case unbalanced translocation and 5 cases CNVs of unknown clinical significance.The detection rate was 25% (16/64 cases).Among these 16 abnormalities,6 cases of them could not be detected by using karyotyping analysis because their sizes were less than 5 Mb,and the smallest detected missing fragment was 0.53 Mb.Conclusion SNP-array gene chip technique with the advantages of higher efficiency,high-resolution and good accuracy,which can be applied to the genetic diagnosis of intellectual disability.

Clinical application value of flow cytometry in detection of related cytokines at the early stage of influenza / 国际检验医学杂志

Objective To establish a clinical cytokine test method based on flow multiple microarray technology,and discuss its clinical significance by observing the change of cytokines level in the early stage of influenza.Methods 54 cases of influenza A virus positive and 20 cases of influenza A virus negative influenza like patients were selected as influenza group.Among them,influenza A virus positive patients were divided into mild group and severe group,influenza A virus negative influenza like patients were as neg-ative group.In addition,35 healthy people were selected as the control group,and the cytokine of all the whole blood samples was detected and statistically analyzed.Results Interleukin-6(IL-6),interleukin-21(IL-21),interleukin-12p70(IL-12p70),interleukin-1 β(IL-1 β)and interleukin-10(IL-10),chemokine-10(IP-10),interleukin-2(IL-2),monocyte chemoattractant protein-1(MCP-1)lev-els were significantly higher in the patients with early onset of influenza,and the difference was statistically significant(P<0.05). The difference of interferon-γ(IFN-γ)between the influenza group and the control group was not statistically significant(P> 0. 05).The levels of IL-6 and IP-10 in the severe group were higher than that of the mild group and the negative group,and the differ-ence was statistically significant(P<0.05).Conclusion IL-6,IL-21,IL-12p70,IL-1 beta,IL-10,IP-10,IL-2 and MCP-1 levels can be used as clinical biological evaluation indicators of patients with fever,of which IL-6 and IP-10 can be used as important indicators for disease progression assessment.

Preparation and structural characterization of TiO2 nanotube arrays on surface of orthopaedic titanium plate / 国际生物医学工程杂志

Objective The TiO2 nanotube arrays,fabricated on the surface of orthopedics,was characterized,to provide carrier for orthopedics plant surface modification or coating,and seek a new way for the prevention and treatment of orthopedics plant infection.Methods By adjusting certain parameters,TiO2 nanotube arrays were fabricated on orthopedic titanium plate surface using the method of anodic oxidation,with glycerol system as electrolyte,orthopedics titanium plate as anode,and platinum electrode as cathode.TiO2 nanotube arrays were characterized.The element composition of TiO2 nanotube arrays was analyzed by X-ray photoelectron spectroscopy (XPS),and the morphological changes of TiO2 nanotube arrays was observed at high temperature (300 ℃) by X-ray diffractomer (XRD).Results With glycerol system as electrolyte,TiO2 nanotube array with diameter of about 100 to 200 nm and the length less than 3μm can be fabricated on orthopedic titanium plate surface using anodic oxidation of 24 h.The surface of orthopedic titanium plate was changed from silver white to deep blue in the macroscopic view.The TiO2 nanotube array on orthopedics titanium plate surface was mainly composed of Ti element (75.88％),O element (20.16％),and F element (3.96％) by XPS analysis.TiO2 nanotube arrays morphology was stable when it was heated to 300 ℃ by muffle furnace.Conclusions The method of anodic oxidation can be applied to manufacture TiO2 nanotubes array on titanium plate surface.The array with stable morphology,the inner hollow shape,the bottom sealing,and a large specific surface area,can withstand high temperature,which can provide carrier for orthopedics plant surface modification or coating.

HRL-Local Infinite Triangular Array Languages

ABSTRACT A new subclass of infinite triangular arrays called hrl-local infinite triangular arrays is introduced. We introduce infinite triangular domino systems to recognize the infinite triangular picture language. Also we introduce strictly domino testable ωω-triangular array languages.

Diagnóstico molecular de enfermedades genéticas: del diagnóstico genético al diagnóstico genómico con la secuenciación masiva / Molecular diagnosis of genetic diseases: from genetic to genomic diagnosis using next generation sequencing

En la actualidad se conocen 8.000 enfermedades genéticas monogénicas. La mayoría de ellas son heterogéneas, por lo que el diagnóstico molecular por técnicas convencionales de secuenciación suele ser largo y costoso debido al gran número de genes implicados. El tiempo estimado para el diagnóstico molecular se encuentra entre 1 y 10 años, y este retraso impide que los pacientes reciban medidas terapéuticas y de rehabilitación específicas, que sus familiares entren en programas preventivos y que reciban asesoramiento genético. La secuenciación masiva está cambiando el modelo de diagnóstico molecular de los afectos, sin embargo, los médicos y profesionales de la salud se enfrentan al dilema de la selección del método más eficiente, con el menor coste sanitario y con la mayor precisión de sus resultados. El objetivo de este trabajo es revisar la tecnología de secuenciación masiva y definir las ventajas y los problemas en su utilización.

Currently 8000 monogenic genetic diseases are known. Most of them are heterogeneous, so their molecular diagnosis by conventional sequencing techniques is labour intensive and time consuming due to the large number of genes involved. The estimated time is between 1 and 10 years for molecular diagnosis and this delay prevents patients from receiving therapy and rehabilitation measures, and their families from entering prevention programs and being given genetic counselling. Next generation sequencing (NGS) is changing the model of molecular diagnosis of patients; however, doctors and health professionals are faced with the dilemma of choosing the most efficient method, with lower health care costs and the most accurate results. The aim of this paper is to review the NGS technology and define the advantages and problems in the use of this technology.

Effects of Zhigancao Decoction medicated serum combined with myocardial tissue/silicon substrate micro-electrode technique on cardiac electrophysiology / 医学研究生学报

[Abstract ] Objective Modern pharmacological studies confirmed Zhigancao Decoction total extract, single active ingredients and their combinations could obviously inhibit arrhythmia.This study was to investigate the effects of Zhigancao Decoction medicated serum combined with myocardial tissue/silicon substrate microelectrode arrays (MEA) on rapid atrial pacing(RAP). Methods New Zealand white rabbits were randomly divided into normal control group, normal serum control group, Zhigancao Decoction medica-ted serum group and water decoction group, 8 in each group.After the establishment of an atrial fibrillation rabbit model, the field ac-tion potential duration ( fAPD) of the right atrial appendage ( RAA ) tissue was measured and the effections of Zhigancao Decoction medicated serum and water decoction on the fAPD of RAA were observed. Results The successful modeling of rapid atrial pacing induced atrial fibrillation in rabbits contributed to the significant shortening of fAPD 12 h after pacing compared to that before pacing ([174.30 ±1.36]ms vs[162.48 ±0.88]ms, P<0.05).After giving 10%~25% Zhigancao Decoction medicated serum and water decoction, the fAPDs of RAA tissue in rabbits with atrial fibrillation were prolonged, which represented positive dose-response relation-ship.The fAPDs of the rabbits given serum containing 10%, 15%, 20%and 25%Zhigancao Decoction were respectively (170.81 ± 0.61)ms, (171.00 ±0.46)ms, (179.08 ±0.67)ms, (179.76 ±2.26)ms, which were longer than those of water decoction group ([163.82 ±0.780]ms, [163.66 ±0.95]ms, [174.06 ±1.32]ms, [176.84 ±1.19]ms), and the difference was statistically sig-nificant (P<0.05). Conclusion The fAPD can be taken as one index of cardiac electrophysiological change, and 10%~25%Zh-igancao Decoction medicated serum can lead to fAPD extension in rabbit model of atrial fibrillation, which might be the electrophysio-logical mechanism of anti-atrial fibrillation.

Gene array analysis in 56 cases of children with growth retardation / 临床儿科杂志

Objective To investigate the genetic basis of the children with growth retardation. Methods From January to October 2013, the 56 patients with growth retardation were enrolled in this study. Genomic DNA was extracted from peripheral blood and was analyzed with gene array chips. Results Abnormalities were found in 12 patients (6 cases of sex chromosome abnormalities and 6 cases of autosomal aberration) and the detection rate was 21.4%. Four patients had the copy-number variations of smaller than 2.5Mb in size which could not be found by karyotyping analysis. Conclusions SNP-array gene chip could be used in the genetic diagnosis of growth retardation.

Colorimetric Determination of Lactate Dehydrogenase on Paper-Based Microwell Arrays Microfluidic Device / 分析化学

A low-cost, simple, sensitive detection method of lactate dehydrogense ( LDH) was developed on paper-based microwell arrays microfluidic device. The phenazine methyl sulfate/nitrotetrazolium blue chloride ( PMS/NBT) detection system was used for LDH detection and the colorimetric results were recorded by both Gel Documentation System and a common camera. Under the optimized conditions, the colorimetric intensity showed a linear correlation to the activity of LDH in the range of 10 to 150 U/L with a limit of detection (LOD) of 9. 44 U/L (3σ) by Gel Documentation System;and the linear range was 15-150 U/L by camera with a LOD of 12. 36 U/L (3σ). Foremost, it was found that human serum albumin (HSA) had an effect on the colorimetric enhancement in this detection system. This low-cost, portable paper-based analytical platform could be suitable for the application in the point-of-care with high sensitivity and reproducibility.

Methodology to Weight Evaluation Areas from Autism Spectrum Disorder ADOS-G Test with Artificial Neural Networks and Taguchi Method / Metodología para ponderar áreas de evaluación de la herramienta ADOS-G en trastorno del espectro autista con redes neuronales artificiales y método de Taguchi

Autism diagnosis requires validated diagnostic tools employed by mental health professionals with expertise in autism spectrum disorders. This conventionally requires lengthy information processing and technical understanding of each of the areas evaluated in the tools. Classifying the impact of these areas and proposing a system that can aid experts in the diagnosis is a complex task. This paper presents the methodology used to find the most significant items from the ADOS-G tool to detect Autism Spectrum Disorders through Feed-forward Artificial Neural Networks with back-propagation training. The number of cases for the network training data was determined by using the Taguchi method with Orthogonal Arrays reducing the sample size from 531,441 to only 27. The trained network provides an accuracy of 100% with 11 different cases used only for validation, which provides a specificity and sensitivity of 1. The network was used to classify the 12 items from the ADOS-G tool algorithm into three levels of impact for Autism diagnosis: High, Medium and Low. It was found that the items "Showing", "Shared enjoyment in Interaction" and "Frequency of vocalization directed to others", are the areas of highest impact for Autism diagnosis. The methodology here presented can be replicated to different Autism diagnosis tests to classify their impact areas as well.

El diagnóstico del autismo requiere del uso de herramientas de diagnóstico validadas internacionalmente que son utilizadas por los profesionales de la salud expertos en trastornos del espectro autista, lo cual requiere de procesamiento de mucha información y un entendimiento técnico de cada una de las áreas evaluadas en ellas. La clasificación del impacto que tienen cada una de estas áreas, así como la propuesta de un sistema que pueda ayudar a los expertos en el diagnóstico, es una tarea compleja, por lo que en este artículo se presenta una metodología utilizada para encontrar los elementos más significativos de la herramienta de diagnóstico de autismo ADOS-G a través de redes neuronales artificiales entrenadas con retropropagación del error. El número de casos para entrenamiento de la red se seleccionó utilizando el método de Taguchi con arreglos ortogonales, reduciendo el tamaño de la muestra de 531,441 a solo 27 casos. La red entrenada tiene una exactitud del 100% validada con 11 casos diferentes de niños evaluados para diagnóstico de trastorno del espectro autista con lo que se obtuvo una especificidad y sensibilidad de 1. La red neuronal artificial se utilizó para clasificar los 12 elementos del algoritmo de la herramienta ADOS-G en tres niveles de impacto: Alto, Medio y Bajo. Se encontró que los elementos "Mostrar", "Placer compartido durante la interacción" y "Frecuencia de vocalizaciones dirigidas a otros" son las áreas de mayor impacto para el diagnóstico de autismo. La metodología presentada puede ser replicada para diferentes herramientas de diagnóstico de autismo para clasificar sus áreas de mayor impacto también.

Interação genótipo x local x regime alimentar em bovinos nelore por meio de componentes principais de três modos

O principal objetivo deste estudo foi aplicar componentes principais com múltiplas matrizes de dados para verificar a interação tripla genótipo x local x regime alimentar no valor genético do efeito direto do peso, aos 205 dias de idade. Foram utilizados touros com filhos em três regiões de produção do Nordeste Brasileiro (Maranhão, Mata e Agreste, e Recôncavo Baiano) e criados nos regimes alimentares a pasto ou com suplementação. Não se evidenciou interação genótipo x local para a característica estudada, entretanto, constatou-se interação do genótipo x regime alimentar. A utilização dos touros deve ser direcionada de acordo com o regime alimentar de seus filhos.

The main objective of this study was to apply three-mode principal component analysis to assess the triple interaction (genotype x location x feeding) on direct genetic value for weight at 205 days of age. We used 60 sires with offspring in three regions of northeastern Brazil (Maranhão, Mata and Agreste, and Recôncavo Baiano) and raised on a pasture regime or with supplementation. There was no interaction between genotype and location, but there was a correlation between genotype and direct effect of feeding. The use of sires should be dictated according to the system of rearing of their offspring.

Use of Mutual Information Arrays to Predict Coevolving Sites in the Full Length HIV gp120 Protein for Subtypes B and C / 中国病毒学·英文版

It is well established that different sites within a protein evolve at different rates according to their role within the protein; identification of these correlated mutations can aid in tasks such as ab initio protein structure,structure function analysis or sequence alignment.Mutual Information is a standard measure for coevolution between two sites but its application is limited by signal to noise ratio.In this work we report a preliminary study to investigate whether larger sequence sets could circumvent this problem by calculating mutual information arrays for two sets of drug naive sequences from the HIV gp120 protein for the B and C subtypes.Our results suggest that while the larger sequences sets can improve the signal to noise ratio,the gain is offset by the high mutation rate of the HIV virus which makes it more difficult to achieve consistent alignments.Nevertheless,we were able to predict a number of coevolving sites that were supported by previous experimental studies as well as a region close to the C terminal of the protein that was highly variable in the C subtype but highly conserved in the B subtype.