Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
Cell ; 185(23): 4409-4427.e18, 2022 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-36368308

RESUMEN

Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Humanos , Trastorno del Espectro Autista/genética , Predisposición Genética a la Enfermedad , Variaciones en el Número de Copia de ADN/genética , Genómica
2.
Environ Res ; 222: 115313, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36709025

RESUMEN

Agriculture is a very important economic sector that contributes to a nation's overall economic development. According to the UN Food and Agriculture Organization, with a rising population, the cereals demand will reach 3 billion tons by 2050. Also, the mission of Sustainable Development Goals (SDGs) is to provide zero hunger and sustainable agriculture by 2030. With a simultaneous decline in cultivable land and water scarcity, food production has to increase in order to achieve the above mission. Vertical farming is a current state of art agriculture technology to increase crop yield per unit area. This work focuses on designing and constructing an IoT-enabled smart vertical farming system with a controlled environment for plant growth. This system uses the hydroponic Deep Flow Technique (DFT), various sensors, and an auto pH and Total Dissolved Solids (TDS) balancing system. This paper provides a comparative analysis of IoT-based controlled environment vertical farming setup with the uncontrolled setup for Romaine lettuce in terms of plant growth parameters like plant height, maximum leaf length, maximum leaf width, and fresh and dry weight of the plant. The observed fresh weight of the aerial part for automated and unautomated setup is found to be 58.66 g and 48.81 g respectively. Also, the chemical analysis showed the plants possess the required optimum range of micro and macronutrients for both setups. The macronutrient results obtained for the controlled/automated (A setup), and uncontrolled/unautomated setup (U setup for Phosphorus (P), and Potassium (K) are (PA, PU) (5.91 g/Kg, 6.06 g/Kg), and (KA, KU) (67.03 g/Kg, 74.01 g/Kg) respectively.


Asunto(s)
Agricultura , Ambiente Controlado , Hidroponía/métodos , Granjas , Agricultura/métodos , Tecnología
3.
Neurobiol Dis ; 140: 104872, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32302674

RESUMEN

Altered gene expression related to Parkinson's Disease (PD) has not been described in the living brain, yet this information may support novel discovery pertinent to disease pathophysiology and treatment. This study compared the transcriptome in brain biopsies obtained from living PD and Control patients. To evaluate the novelty of this data, a comprehensive literature review also compared differentially expressed gene (DEGs) identified in the current study with those reported in PD cadaveric brain and peripheral tissues. RNA was extracted from rapidly cryopreserved frontal lobe specimens collected from PD and Control patients undergoing neurosurgical procedures. RNA sequencing (RNA-Seq) was performed and validated using quantitative polymerase chain reaction. DEG data was assessed using bioinformatics and subsequently included within a comparative analysis of PD RNA-Seq studies. 370 DEGs identified in living brain specimens reflected diverse gene groups and included key members of trophic signaling, apoptosis, inflammation and cell metabolism pathways. The comprehensive literature review yielded 7 RNA-Seq datasets generated from blood, skin and cadaveric brain but none from a living brain source. From the current dataset, 123 DEGs were identified only within the living brain and 267 DEGs were either newly found or had distinct directional change in living brain relative to other tissues. This is the first known study to analyze the transcriptome in brain tissue from living PD and Control patients. The data produced using these methods offer a unique, unexplored resource with potential to advance insight into the genetic associations of PD.


Asunto(s)
Biomarcadores/metabolismo , Encéfalo/metabolismo , Enfermedad de Parkinson/metabolismo , Estudios de Casos y Controles , Biología Computacional , Femenino , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , Humanos , Masculino , MicroARNs/metabolismo , Análisis de Secuencia de ARN/métodos , Transducción de Señal/genética , Transcriptoma
4.
J Anaesthesiol Clin Pharmacol ; 36(4): 500-505, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33840931

RESUMEN

BACKGROUND AND AIMS: Labor pain is one of the most severe pain that a woman experiences in her lifetime. Various methods are being used to relieve this pain and to achieve higher maternal satisfaction. One such technique is transcutaneous electrical nerve stimulation (TENS) that uses low-frequency electrotherapy. The aim of our study was to evaluate TENS by comparing it to an established labor analgesia technique, i.e., epidural analgesia in terms of maternal satisfaction. MATERIAL AND METHODS: This prospective study was conducted on 60 parturients in active stage of labor. The choice of analgesia was made by the parturient after informed consent. In group A (n = 30) TENS was used, while in group B (n = 30) epidural ropivacaine 0.125% + 2 µg/ml fentanyl was given. Continuous monitoring of maternal vitals, visual analogue score, and fetal heart rate (FHR) was done. Maternal satisfaction was scored considering pain relief, ability to move and experience of labor at the end of delivery and outcome was labeled as favorable and unfavorable. RESULTS: TENS was found to be favorable in 90% of parturients as compared to 96.6% in epidural (P 0.301). The number of highly satisfied parturients was 4 (13.3%) in TENS group and 17 (56.6%) in the epidural group (P= 0.000). Three patients in the epidural group had assisted delivery and two had cesarean section whereas all patients in TENS group delivered normally (P= 0.065). No significant difference was found in the fetal outcome. CONCLUSIONS: TENS is a good alternate choice for providing labor analgesia and may have a major role in future.

5.
J Anaesthesiol Clin Pharmacol ; 34(3): 335-340, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30386016

RESUMEN

BACKGROUND AND AIMS: Maintenance of adequate depth of anesthetic is crucial to prevent awareness and to reduce stress response associated with surgery. Goals of balanced general anesthetic are met by use of adjuvants to facilitate use of lower anesthetic dose, while ensuring adequate anesthetic depth. This study employed BIS monitoring to compare the anesthetic sparing effects of intravenous dexmedetomidine and magnesium sulphate on induction dose of propofol by maintaining a BIS value of 40-50. MATERIAL AND METHODS: One hundred and twenty ASA I and II patients undergoing elective surgery under general anesthetic were included in three groups of forty each. Group D received 1 µg/kg of dexmedetomidine, Group M was given 30 mg/kg of magnesium sulphate in 100 ml saline and Group N received 100 ml saline over 15-20 minutes 15 minutes before induction. Data compared were dose of propofol and vecuronium, Ramsay sedation score, BIS values and hemodynamic parameters intraoperatively. RESULTS: Propofol required in group D was significantly lower 101.3 ± 16.5 than group M and N with dose of 114 ± 15.5 and 160.50 ± 25.08 respectively (p <0.001). Dose requirement of vecuronium was significantly reduced in group M 5.4 ± 0.8 and group D 6.6 ± 1.2 as compared to N 7.9 ± 1.4 (p <0.001). No significant differences were seen regarding baseline hemodynamics, RSS and BIS values in all groups. After study drug infusion, RSS was 4.59 ± 0.75 in dexmedetomidine group compared to 1.9 ± 0.7 and 1.4 ± 0.5 in group M and N (p <0.001). During maintenance, significantly lower HR, MAP and BIS values were seen in group D and M than N (p <0.001). CONCLUSION: Our study showed that pretreatment with dexmedetomidine and magnesium sulphate significantly reduced the induction dose of propofol by maintaining a constant BIS in value at 40-50. However, both the drugs reduced the time to reach BIS 40-50 but sedation and sparing of propofol was more in dexmedetomidine group.

6.
Indian J Crit Care Med ; 20(12): 689-694, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28149025

RESUMEN

BACKGROUND: The patient-ventilator asynchrony is almost observed in all modes of ventilation, and this asynchrony affects lung mechanics adversely resulting in deleterious outcome. Innovations and advances in ventilator technology have been trying to overcome this problem by designing newer modes of ventilation. Pressure support ventilation (PSV) is a commonly used flow-cycled mode where a constant pressure is delivered by ventilator. Proportional assist ventilation (PAV) is a new dynamic inspiratory pressure assistance and is supposed to be better than PSV for synchrony and tolerance, but reports are still controversial. Moreover, most of these studies are conducted in chronic obstructive pulmonary disease patients with respiratory failure; the results of these studies may not be applicable to surgical patients. Thus, we proposed to do compare these two modes in surgical Intensive Care Unit (ICU) patients as a randomized crossover study. AIMS: Comparison of patient-ventilator asynchrony between PSV and PAV plus (PAV+) in surgical patients while weaning. SUBJECTS AND METHODS: After approval by the Hospital Ethics Committee, we enrolled twenty patients from surgical ICU of tertiary care institute. The patients were ventilated with pressure support mode (PSV) and PAV+ for 12 h as a crossover from one mode to another after 6 h while weaning. RESULTS: Average age and weight of patients were 41.80 ± 15.20 years (mean ± standard deviation [SD]) and 66.50 ± 12.47 (mean ± SD) kg, respectively. Comparing the asynchronies between the two modes, the mean number of total asynchronous recorded breaths in PSV was 7.05 ± 0.83 and 4.35 ± 5.62, respectively, during sleep and awake state, while the same were 6.75 ± 112.24 and 10.85 ± 11.33 in PAV+. CONCLUSION: Both PSV and PAV+ modes of ventilation performed similarly for patient-ventilator synchrony in surgical patients. In surgical patients with acute respiratory failure, dynamic inspiratory pressure assistance modalities are not superior to PSV with respect to cardiorespiratory function.

7.
BMC Genomics ; 16: 310, 2015 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-25924671

RESUMEN

BACKGROUND: Little is known about invertebrate responses to DNA viruses. Here, we infect a commercially important pest moth species Plodia interpunctella with its naturally infecting DNA virus. We sequenced, assembled and annotated the complete transcriptome of the moth, and a partial transcriptome of the virus. We then tested for differential gene expression between moths that were exposed to the virus and controls. RESULTS: We found 51 genes that were differentially expressed in moths exposed to a DNA baculovirus compared to controls. Gene set enrichment analysis revealed that cuticle proteins were significantly overrepresented in this group of genes. Interestingly, 6 of the 7 differentially expressed cuticle proteins were downregulated, suggesting that baculoviruses are able to manipulate its host's response. In fact, an additional 29 of the 51 genes were also downregulated in exposed compared with control animals, including a gram-negative binding protein. In contrast, genes involved in transposable element movement were upregulated after infection. CONCLUSIONS: We present the first experiment to measure genome-wide gene expression in an insect after infection with a natural DNA virus. Our results indicate that cuticle proteins might be key genes underpinning the response to DNA viruses. Furthermore, the large proportion of genes that were downregulated after viral exposure suggests that this virus is actively manipulating the insect immune response. Finally, it appears that transposable element activity might increase during viral invasion. Combined, these results provide much needed host candidate genes that respond to DNA viral invaders.


Asunto(s)
Baculoviridae/fisiología , Interacciones Huésped-Patógeno , Mariposas Nocturnas/genética , Mariposas Nocturnas/virología , Transcriptoma , Animales , Genoma , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Mariposas Nocturnas/metabolismo
8.
Genome Res ; 22(12): 2467-77, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22919073

RESUMEN

The α-proteobacterium Wolbachia is probably the most prevalent, vertically transmitted symbiont on Earth. In contrast with its wide distribution in arthropods, Wolbachia is restricted to one family of animal-parasitic nematodes, the Onchocercidae. This includes filarial pathogens such as Onchocerca volvulus, the cause of human onchocerciasis, or river blindness. The symbiosis between filariae and Wolbachia is obligate, although the basis of this dependency is not fully understood. Previous studies suggested that Wolbachia may provision metabolites (e.g., haem, riboflavin, and nucleotides) and/or contribute to immune defense. Importantly, Wolbachia is restricted to somatic tissues in adult male worms, whereas females also harbor bacteria in the germline. We sought to characterize the nature of the symbiosis between Wolbachia and O. ochengi, a bovine parasite representing the closest relative of O. volvulus. First, we sequenced the complete genome of Wolbachia strain wOo, which revealed an inability to synthesize riboflavin de novo. Using RNA-seq, we also generated endobacterial transcriptomes from male soma and female germline. In the soma, transcripts for membrane transport and respiration were up-regulated, while the gonad exhibited enrichment for DNA replication and translation. The most abundant Wolbachia proteins, as determined by geLC-MS, included ligands for mammalian Toll-like receptors. Enzymes involved in nucleotide synthesis were dominant among metabolism-related proteins, whereas the haem biosynthetic pathway was poorly represented. We conclude that Wolbachia may have a mitochondrion-like function in the soma, generating ATP for its host. Moreover, the abundance of immunogenic proteins in wOo suggests a role in diverting the immune system toward an ineffective antibacterial response.


Asunto(s)
Regulación Bacteriana de la Expresión Génica , Genoma Bacteriano , Onchocerca volvulus/microbiología , Simbiosis/genética , Wolbachia/genética , Animales , Antibacterianos/metabolismo , Cromatografía Liquida , Replicación del ADN , ADN de Helmintos/genética , Femenino , Masculino , Proteómica/métodos , Riboflavina/metabolismo , Análisis de Secuencia de ARN , Espectrometría de Masas en Tándem , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Transcriptoma , Regulación hacia Arriba , Wolbachia/inmunología
9.
Appl Microbiol Biotechnol ; 99(7): 3015-28, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25650327

RESUMEN

This study was conducted to enhance flavor characteristics of wine by malolactic fermentation using recombinant Pediococcus acidilactici BD16 (fcs (+)/ech (+)) encoding synthetic genes of feruloyl-CoA synthetase and enoyl-CoA hydratase. After malolactic fermentation, wine phenolics were characterized using LCMS-ESI technique and a significant improvement in the antioxidant activity and flavor characteristics of wine was observed due to increased concentration of cinnamic acid derivatives. This proof of concept study highlights the role of recombinant P. acidilactici BD16 (fcs (+)/ech (+)) in improving flavor as well as aroma of wine due to production of several phenolic derivatives during secondary fermentation. A novel metabolic pathway was predicted from mass spectral analysis data that indicates biotransformation of cinnamic acid and derivatives into apigenin, catechin, coniferyl aldehyde, cyanidin, hydroxybenzoic acids, laricitrin, luteolin, malvidin 3-glucoside, myricetin, naringenin, pelargonin, piceatannol, querecitin, and vanillin that not only increased the overall consumer appreciation but also improved nutritional and probably the therapeutic properties of wines. This is a first evidence-based study where role of recombinant P. acidilactici BD16 (fcs (+)/ech (+)) in the wine secondary fermentation has been elucidated.


Asunto(s)
Pediococcus/genética , Pediococcus/metabolismo , Vino/análisis , Antioxidantes/metabolismo , Benzaldehídos/análisis , Cinamatos/metabolismo , Citrus sinensis , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , Enoil-CoA Hidratasa/genética , Enoil-CoA Hidratasa/metabolismo , Fermentación , Microbiología de Alimentos/métodos , Redes y Vías Metabólicas , Fenoles/análisis , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Rosa , Espectrometría de Masa por Ionización de Electrospray , Vitis , Vino/microbiología
10.
JAMA ; 314(9): 895-903, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26325558

RESUMEN

IMPORTANCE: The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. OBJECTIVE: To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. DESIGN, SETTING, AND PARTICIPANTS: The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). EXPOSURES: All probands underwent CMA, with WES performed for 95 proband-parent trios. MAIN OUTCOMES AND MEASURES: The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. RESULTS: Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text]. CONCLUSIONS AND RELEVANCE: Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.


Asunto(s)
Trastornos Generalizados del Desarrollo Infantil/genética , Exoma , Análisis por Micromatrices/métodos , Técnicas de Diagnóstico Molecular/métodos , Síndrome de Asperger/diagnóstico , Síndrome de Asperger/genética , Trastorno Autístico/diagnóstico , Trastorno Autístico/genética , Niño , Trastornos Generalizados del Desarrollo Infantil/diagnóstico , Trastornos Generalizados del Desarrollo Infantil/patología , Preescolar , Femenino , Humanos , Masculino , Análisis por Micromatrices/estadística & datos numéricos , Técnicas de Diagnóstico Molecular/estadística & datos numéricos , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos/estadística & datos numéricos , Fenotipo , Análisis de Secuencia de ADN/métodos , Análisis de Secuencia de Proteína/métodos
11.
Indian J Anaesth ; 65(Suppl 1): S34-S40, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33814588

RESUMEN

BACKGROUND AND AIMS: Dexmedetomidine and ketamine are commonly used pre-medicants to propofol. Previous literature shows a delay in recovery with their use without any clarity on discharge. This study was planned to find out whether adding these premedicants to Bispectral index (BIS) guided propofol anaesthesia led to delayed discharge in minor gynaecological surgeries. METHODS: Totally, 120 adult females belonging to American Society of Anesthesiologists (ASA) physical status I and II undergoing minor gynaecological surgeries under general anaesthesia were randomly allocated to receive 1 µg/kg dexmedetomidine (Group D), 0.5 mg/kg ketamine (Group K) and normal saline (Group P) as premedication. Propofol 1% was used for induction and maintenance of anaesthesia keeping BIS between 55 and 70. After the procedure, patients were assessed primarily for discharge readiness using Modified Post Anaesthesia Discharge Scoring System (MPADSS).The secondary outcomes were Modified Aldrete Score (MAS), total dose of propofol used and haemodynamics. RESULTS: The percentage of patients ready for discharge were 22.5%, 30% and 15%at 1 hour in group D, K and P, respectively (p = 0.275). Median MAS was 5, 4 and 6 respectively for group D, K and P immediately post-surgery (p = 0.000). The mean dose of propofol used was 69.75 ± 12.56 mg in group D and 135.25 ± 9.2 mg in group P (p = 0.001). There were significant haemodynamic variations in group D (16.4% fall in heart rate at 5 minutes and 24.18% fall in mean arterial pressure at 15 minutes). CONCLUSION: Premedication with dexmedetomidine and ketamine in propofol anaesthesia does not delay discharge. However, stable haemodynamics and good analgesia with ketamine make it a better option.

12.
Artículo en Inglés | MEDLINE | ID: mdl-34062823

RESUMEN

Food insecurity is an important contributor to health and a factor in both underweight and malnutrition, and overweight and obesity. Countries where both undernutrition and overweight and obesity coexist are said to be experiencing a double burden of malnutrition. India is one example of a country experiencing this double burden. Women have been found to experience the negative impacts of food insecurity and obesity, however, the reasons that women experience the impact of malnutrition more so than men are complex and are under-researched. This current research employed a mixed methods approach to begin to fill this gap by exploring the dietary intake, anthropometric characteristics, and food security status of rural Indian women. In total, 78 household were surveyed. The average waist measurement, waist to hip ratio, and BMI were all above WHO recommendations, with two thirds of participants categorized as obese. Contributing to these findings was a very limited diet, high in energy, and low in protein and iron. The findings of this research suggest that the rural Indian women in this study have a lack of diet diversity and may be at risk of a range of non-communicable diseases.


Asunto(s)
Inseguridad Alimentaria , Desnutrición , Estudios Transversales , Dieta , Ingestión de Alimentos , Femenino , Abastecimiento de Alimentos , Humanos , India/epidemiología , Masculino , Población Rural
13.
Artículo en Inglés | MEDLINE | ID: mdl-32466486

RESUMEN

BACKGROUND: Despite significant growth and change in India over the past two decades, some public health indicators have failed to keep pace. One such indicator is food insecurity. India is home to the largest number of people experiencing hunger and food insecurity. Food security is described as "a situation that exists when all people, at all times, have physical, social and economic access to sufficient, safe and nutritious food that meets their dietary needs and food preferences for an active and healthy life". While there has been considerable research investigating the role of crop yields, policy interventions, and food production in alleviating food insecurity in India, there is insufficient research investigating the social and cultural influences of food insecurity, including the role of women. The primary aim of this research is to investigate the experience of food insecurity among women in India. The objectives of this research are (1) to determine the role of women in food production and its contribution to household food security; (2) to examine the gender roles within households and the decision-making processes that influence food security, and (3) to investigate household nutritional status and food insecurity experience. METHODS: Participants will include women who live in a village in Punjab, India. Interviews with 100 households, drawn from a convenience sample will be conducted. Interviews will be conducted in Punjabi with simultaneous English translation, and will include: food related experiences, anthropometric measurements (weight, height, waist, and hip) and dietary assessment (24-h diet recall, two non-consecutive days), dwelling facilities, agriculture related information, including household agriculture activities undertaken, food security status (via the United States Department of Agriculture Household Food Security Scale Measurement), and demographic information. DISCUSSION: This study aims to investigate a range of determinants of food insecurity among a rural population. It will allow for the identification of some of the components of household food insecurity among women in India and will go part of the way to understanding how and why India continues to experience food and nutritional insecurity despite growth and progress in a range of other indicators.


Asunto(s)
Composición Familiar , Abastecimiento de Alimentos , Estado Nutricional , Adulto , Estudios Transversales , Femenino , Humanos , India , Factores Socioeconómicos
14.
Stem Cell Reports ; 11(5): 1211-1225, 2018 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-30392976

RESUMEN

Autism spectrum disorder (ASD) is phenotypically and genetically heterogeneous. We present a CRISPR gene editing strategy to insert a protein tag and premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of ten ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NGN2)-directed induction of iPSCs allowed production of excitatory neurons, and mutant proteins were not detectable. RNA sequencing revealed convergence of several neuronal networks. Using both patch-clamp and multi-electrode array approaches, the electrophysiological deficits measured were distinct for different mutations. However, they culminated in a consistent reduction in synaptic activity, including reduced spontaneous excitatory postsynaptic current frequencies in AFF2/FMR2-, ASTN2-, ATRX-, KCNQ2-, and SCN2A-null neurons. Despite ASD susceptibility genes belonging to different gene ontologies, isogenic stem cell resources can reveal common functional phenotypes, such as reduced functional connectivity.


Asunto(s)
Trastorno Autístico/genética , Trastorno Autístico/fisiopatología , Edición Génica , Predisposición Genética a la Enfermedad , Neuronas/metabolismo , Neuronas/patología , Línea Celular , Electrodos , Técnicas de Inactivación de Genes , Células HEK293 , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Mutagénesis Insercional/genética , Fenotipo
15.
Science ; 360(6386): 327-331, 2018 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-29674594

RESUMEN

The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.


Asunto(s)
Trastorno del Espectro Autista/genética , Predisposición Genética a la Enfermedad , Variación Genética , Herencia Paterna , Regiones Promotoras Genéticas/genética , Exones , Regulación de la Expresión Génica , Genoma Humano , Humanos , Mutación , Linaje , ARN no Traducido/genética , Selección Genética , Eliminación de Secuencia , Factores de Transcripción/genética
16.
G3 (Bethesda) ; 7(2): 755-773, 2017 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-28087693

RESUMEN

The Canadian beaver (Castor canadensis) is the largest indigenous rodent in North America. We report a draft annotated assembly of the beaver genome, the first for a large rodent and the first mammalian genome assembled directly from uncorrected and moderate coverage (< 30 ×) long reads generated by single-molecule sequencing. The genome size is 2.7 Gb estimated by k-mer analysis. We assembled the beaver genome using the new Canu assembler optimized for noisy reads. The resulting assembly was refined using Pilon supported by short reads (80 ×) and checked for accuracy by congruency against an independent short read assembly. We scaffolded the assembly using the exon-gene models derived from 9805 full-length open reading frames (FL-ORFs) constructed from the beaver leukocyte and muscle transcriptomes. The final assembly comprised 22,515 contigs with an N50 of 278,680 bp and an N50-scaffold of 317,558 bp. Maximum contig and scaffold lengths were 3.3 and 4.2 Mb, respectively, with a combined scaffold length representing 92% of the estimated genome size. The completeness and accuracy of the scaffold assembly was demonstrated by the precise exon placement for 91.1% of the 9805 assembled FL-ORFs and 83.1% of the BUSCO (Benchmarking Universal Single-Copy Orthologs) gene set used to assess the quality of genome assemblies. Well-represented were genes involved in dentition and enamel deposition, defining characteristics of rodents with which the beaver is well-endowed. The study provides insights for genome assembly and an important genomics resource for Castoridae and rodent evolutionary biology.


Asunto(s)
Genoma , Roedores/genética , Transcriptoma/genética , Animales , Genómica , Anotación de Secuencia Molecular , Sistemas de Lectura Abierta/genética
18.
Appl Biochem Biotechnol ; 170(4): 854-67, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23615732

RESUMEN

Ferulic acid (FA) is widely used in foods, in beverages, and in various pharmaceutical industries as a precursor of vanillin. FA biotransformation can occur during the growth of lactic acid bacteria (LAB), and its conversion to other phenolic derivatives is observed by many scientists, where ferulic acid esterase (FAE) and ferulic acid decarboxylase (FDC) play significant roles. The present study aimed at screening a panel of LAB for their ability to release FA from rice bran, an agro waste material. FAE and FDC activities were analyzed for the preliminary screening of various dairy isolates. Two Pediococcus acidilactici isolates were selected for studying further the hydrolysis of FA from rice bran and its bioconversion into phenolic derivatives like 4-ethylphenol, vanillin, vanillic acid, and vanillyl alcohol. P. acidilactici M16, a probiotic isolate, has great potential for the production of FA from rice bran and could be exploited as starter culture in the food industry for the production of biovanillin.


Asunto(s)
Ácidos Cumáricos/metabolismo , Oryza/metabolismo , Pediococcus/enzimología , Proteínas Bacterianas/metabolismo , Benzaldehídos/metabolismo , Alcoholes Bencílicos/metabolismo , Biotransformación , Carboxiliasas/metabolismo , Hidrolasas de Éster Carboxílico/metabolismo , Productos Lácteos/microbiología , Industria de Alimentos/métodos , Hidrólisis , Pediococcus/aislamiento & purificación , Fenoles/metabolismo , Probióticos/metabolismo , Ácido Vanílico/metabolismo
19.
Worm ; 1(1): 42-50, 2012 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-24058822

RESUMEN

The sequencing of the complete genome of the nematode Caenorhabditis elegans was a landmark achievement and ushered in a new era of whole-organism, systems analyses of the biology of this powerful model organism. The success of the C. elegans genome sequencing project also inspired communities working on other organisms to approach genome sequencing of their species. The phylum Nematoda is rich and diverse and of interest to a wide range of research fields from basic biology through ecology and parasitic disease. For all these communities, it is now clear that access to genome scale data will be key to advancing understanding, and in the case of parasites, developing new ways to control or cure diseases. The advent of second-generation sequencing technologies, improvements in computing algorithms and infrastructure and growth in bioinformatics and genomics literacy is making the addition of genome sequencing to the research goals of any nematode research program a less daunting prospect. To inspire, promote and coordinate genomic sequencing across the diversity of the phylum, we have launched a community wiki and the 959 Nematode Genomes initiative (www.nematodegenomes.org/). Just as the deciphering of the developmental lineage of the 959 cells of the adult hermaphrodite C. elegans was the gateway to broad advances in biomedical science, we hope that a nematode phylogeny with (at least) 959 sequenced species will underpin further advances in understanding the origins of parasitism, the dynamics of genomic change and the adaptations that have made Nematoda one of the most successful animal phyla.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA