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Summary: GlycoStore is a curated chromatographic, electrophoretic and mass-spectrometry composition database of N-, O-, glycosphingolipid (GSL) glycans and free oligosaccharides associated with a range of glycoproteins, glycolipids and biotherapeutics. The database is built on publicly available experimental datasets from GlycoBase developed in the Oxford Glycobiology Institute and then the National Institute for Bioprocessing Research and Training (NIBRT). It has now been extended to include recently published and in-house data collections from the Bioprocessing Technology Institute (BTI) A*STAR, Macquarie University and Ludger Ltd. GlycoStore provides access to approximately 850 unique glycan structure entries supported by over 8500 retention positions determined by: (i) hydrophilic interaction chromatography (HILIC) ultra-high performance liquid chromatography (U/HPLC) and reversed phase (RP)-U/HPLC with fluorescent detection; (ii) porous graphitized carbon (PGC) chromatography in combination with ESI-MS/MS detection; and (iii) capillary electrophoresis with laser induced fluorescence detection (CE-LIF). GlycoStore enhances many features previously available in GlycoBase while addressing the limitations of the data collections and model of this popular resource. GlycoStore aims to support detailed glycan analysis by providing a resource that underpins current workflows. It will be regularly updated by expert annotation of published data and data obtained from the project partners. Availability and implementation: http://www.glycostore.org. Supplementary information: Supplementary data are available at Bioinformatics online.
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Bases de Datos de Compuestos Químicos , Glicómica/métodos , Oligosacáridos/química , Polisacáridos/química , Cromatografía Líquida de Alta Presión , Electroforesis Capilar , Glucolípidos , Glicoproteínas , Interacciones Hidrofóbicas e Hidrofílicas , Estructura Molecular , Oligosacáridos/metabolismo , Polisacáridos/metabolismo , Espectrometría de Masas en TándemRESUMEN
Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns of DNA amplifications and deletions across diverse cancer types. These patterns are suggestive of conserved selection pressures during tumor evolution but cannot be fully explained by known oncogenes and tumor suppressor genes. Using a pan-cancer analysis of CNA data from patient tumors and experimental systems, here we show that principal component analysis-defined CNA signatures are predictive of glycolytic phenotypes, including 18F-fluorodeoxy-glucose (FDG) avidity of patient tumors, and increased proliferation. The primary CNA signature is enriched for p53 mutations and is associated with glycolysis through coordinate amplification of glycolytic genes and other cancer-linked metabolic enzymes. A pan-cancer and cross-species comparison of CNAs highlighted 26 consistently altered DNA regions, containing 11 enzymes in the glycolysis pathway in addition to known cancer-driving genes. Furthermore, exogenous expression of hexokinase and enolase enzymes in an experimental immortalization system altered the subsequent copy number status of the corresponding endogenous loci, supporting the hypothesis that these metabolic genes act as drivers within the conserved CNA amplification regions. Taken together, these results demonstrate that metabolic stress acts as a selective pressure underlying the recurrent CNAs observed in human tumors, and further cast genomic instability as an enabling event in tumorigenesis and metabolic evolution.
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Variaciones en el Número de Copia de ADN , Perfilación de la Expresión Génica/métodos , Glucólisis , Neoplasias/genética , Línea Celular Tumoral , Evolución Molecular , Amplificación de Genes , Eliminación de Gen , Regulación Neoplásica de la Expresión Génica , Inestabilidad Genómica , Humanos , Redes y Vías Metabólicas , Análisis de Componente Principal , Selección GenéticaRESUMEN
OBJECTIVES: Antibiotics for acute respiratory illness (ARI) constitute most pediatric medication use and contribute to the emergence of antimicrobial resistance. We investigated antibiotic prescription risk factors for ARI in pediatric clinics and clinical follow-up in individuals prescribed and not prescribed antibiotics. METHODS: In this observational study, we enrolled children ages 2 to 17 years old presenting with ARI with fever to two academic pediatric primary care outpatient clinics during influenza season 2013-2014. We collected information on demographics, initial symptoms, medical conditions, laboratory tests, discharge diagnoses, treatments, and 30 days of follow-up medical encounters. Factors associated with antibiotic prescription receipt were evaluated using logistic regression. RESULTS: Of 206 consented and enrolled children, 59 (29%) were prescribed antibiotics, 51 of 59 (86%) for indicated diagnoses: 34 for streptococcal pharyngitis, 15 for acute otitis media (AOM), and 2 for pneumonia. Discharge diagnoses were the only factors independently associated with an antibiotic prescription. Of children prescribed/not prescribed an antibiotic, 17%/17% received follow-up telephone calls and 27%/17% had follow-up visits related to ARI within 30 days. Two children with AOM were prescribed a second antibiotic during follow-up, and one developed Clostridium difficile colitis. Eighteen of 206 (9%) additional children were prescribed antibiotics within 30 days for ARI symptoms, 17 for streptococcal pharyngitis, AOM, pneumonia, or sinusitis; one was prescribed antibiotics for influenza-like illness. CONCLUSIONS: Among study children 2 to 17 years old with outpatient ARI, 29% were prescribed antibiotics at the initial visit and another 9% were prescribed antibiotics during the 30-day follow-up (most were for appropriate indications). Further decreasing antibiotic use in similar settings will likely require wider implementation of watchful waiting for AOM, a change in guidelines for pharyngitis management, and/or reductions in these diseases.
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Antibacterianos/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Otitis Media/tratamiento farmacológico , Faringitis/tratamiento farmacológico , Neumonía/tratamiento farmacológico , Adolescente , Niño , Preescolar , Continuidad de la Atención al Paciente , Femenino , Humanos , Masculino , Factores de Riesgo , TennesseeRESUMEN
In recent years, a role for epigenetic modifications in the pathophysiology of disease has received significant attention. Many studies are now beginning to explore the gene-environment interactions, which may mediate early-life exposure to risk factors, such as nutritional deficiencies and later development of behavioral problems in children and adults. In this paper, we review the current literature on the role of epigenetics in the development of psychopathology, with a specific focus on the potential for epigenetic modifications to link nutrition and brain development. We propose a conceptual framework whereby epigenetic modifications (e.g., DNA methylation) mediate the link between micro- and macro-nutrient deficiency early in life and brain dysfunction (e.g., structural aberration, neurotransmitter perturbation), which has been linked to development of behavior problems later on in life.
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Encéfalo/fisiopatología , Trastornos de la Nutrición del Niño/complicaciones , Trastornos de la Nutrición del Niño/fisiopatología , Epigénesis Genética , Interacción Gen-Ambiente , Psicopatología , Adulto , Trastorno de Personalidad Antisocial/epidemiología , Trastorno de Personalidad Antisocial/genética , Trastorno de Personalidad Antisocial/fisiopatología , Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Niño , Trastornos de la Nutrición del Niño/epidemiología , Trastornos de la Nutrición del Niño/genética , Metilación de ADN , Humanos , Psicopatología/métodos , Factores de Riesgo , Conducta SocialRESUMEN
BACKGROUND: Despite the body of literature that links anemia with poorer cognition in children and the evidence that the severity of the effects of anemia on children's cognition vary in different populations, few studies have investigated the effects of anemia on the cognitive development of Chinese children. METHODS: This longitudinal cohort included 171 children from a developing region of China. Hemoglobin (Hb) and iron levels were taken when the children were 4 years old. At age 6, the children's cognition was tested with the Chinese Wechsler Preschool and Primary Scale of Intelligence. Psychosocial information was also used in analyses. RESULTS: Results showed that the children who had low Hb levels had significantly lower scores in performance IQ (PIQ), but not verbal IQ. Although blood Fe levels were not shown to moderate the link between Hb levels and IQ, we found children who performed the best on IQ tests exhibited low iron levels concurrent with high Hb levels, whereas the group who performed the worst exhibited high iron but low Hb levels. We also found that psychosocial adversity did not differ significantly between children who had normal or low Hb levels, although the effect of Hb on PIQ became only suggestive after controlling for psychosocial adversity, therefore the correlation is not causal but only a suggestive association. CONCLUSION: Our findings are in agreement with literature on the negative effects of anemia on children's cognition and point to the possibility that the portions of the brain associated with PIQ components are particularly affected by low Hb during crucial periods of development.
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Anemia/sangre , Anemia/psicología , Trastornos del Conocimiento/sangre , Cognición , Hemoglobinas/análisis , Inteligencia , Hierro/sangre , Pueblo Asiatico , Niño , Preescolar , China , Estudios de Cohortes , Femenino , Humanos , Pruebas de Inteligencia , Estudios Longitudinales , Masculino , Encuestas y CuestionariosRESUMEN
GlycoStore ( http://www.glycostore.org ) is an open access chromatographic and electrophoretic retention database of glycans characterized from glycoproteins, glycolipids, and biotherapeutics. It is a continuation of the GlycoBase project (Oxford Glycobiology Institute and National Institute for Bioprocessing Research and Training, Ireland) but addresses many of the technological limitations that impacted the growth of GlycoBase, in particular, improvements to the bioinformatics architecture, enhancing data annotations and coverage, and improving connectivity with external resources. The first release of GlycoStore (October 2017) contains over 850 glycan entries accompanied by 8500+ retention positions including data from: (1) fluorescently labelled released glycans determined using hydrophilic interaction chromatography (HILIC) ultrahigh-performance liquid chromatography (U/HPLC) and reversed phase (RP)-U/HPLC; (2) porous graphitized carbon chromatography (PGC) interfaced with ESI-MS/MS; and (3) capillary electrophoresis with laser induced fluorescence detection (CE-LIF). In this chapter, we outline the objectives of GlycoStore, and describe a selection of step-by-step workflows for navigating and browsing the information available. We also provide a short description of informatics tools available to query the database using Semantic technologies. The information presented in this chapter supplements our documentation knowledge base that describes interface improvements, new features and tools, and content updates ( https://unicarbkb.freshdesk.com/ ).
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Electroforesis Capilar , Glicómica , Cromatografía Líquida de Alta Presión , Glicoproteínas , Polisacáridos , Espectrometría de Masas en TándemRESUMEN
Glycosylation is important in biology, contributing to both protein conformation and function. Structurally, glycosylation is complex and diverse. This complexity is reflected in the topology, composition, monosaccharide linkages, and isomerism of each oligosaccharide. Glycoanalytics is a discipline that addresses the understanding and characterization of this complexity and its correlation with biology. It includes analytical steps such as sample preparation, instrument measurements, and data analyses. Of these, data analysis has emerged as a critical bottleneck because data collection has increasingly become high-throughput. This has resulted in data-rich workflows that lack rapid and automated data analytics. To address this issue, the field has been developing software for interpretation of quantitative glycomics studies. Here, we describe a protocol using available informatics tools for analysis of data from analysis of released glycans using high-/ultraperformance liquid chromatography (H/UPLC) coupled with mass spectrometry (MS).
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Glicómica , Cromatografía Líquida de Alta Presión , Glicosilación , Espectrometría de Masas , PolisacáridosRESUMEN
The conformation space occupied by different classes of biomolecules measured by ion mobility-mass spectrometry (IM-MS) is described for utility in the characterization of complex biological samples. Although the qualitative separation of different classes of biomolecules on the basis of structure or collision cross section is known, there is relatively little quantitative cross-section information available for species apart from peptides. In this report, collision cross sections are measured for a large suite of biologically salient species, including oligonucleotides (n = 96), carbohydrates (n = 192), and lipids (n = 53), which are compared to reported values for peptides (n = 610). In general, signals for each class are highly correlated, and at a given mass, these correlations result in predicted collision cross sections that increase in the order oligonucleotides < carbohydrates < peptides < lipids. The specific correlations are described by logarithmic regressions, which best approximate the theoretical trend of increasing collision cross section as a function of increasing mass. A statistical treatment of the signals observed within each molecular class suggests that the breadth of conformation space occupied by each class increases in the order lipids < oligonucleotides < peptides < carbohydrates. The utility of conformation space analysis in the direct analysis of complex biological samples is described, both in the context of qualitative molecular class identification and in fine structure examination within a class. The latter is demonstrated in IM-MS separations of isobaric oligonucleotides, which are interpreted by molecular dynamics simulations.
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Carbohidratos/análisis , Lípidos/análisis , Oligonucleótidos/análisis , Péptidos/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Conformación MolecularRESUMEN
Experimental techniques to identify and quantify glycan structures in a given sample are continuously improving. However, as they advance data analysis and annotation seems to become more complex. To address this issue, much progress has been made in developing software for interpretation of quantitative glycan profiles. Here, we focus on these informatics tools for high/ultra performance liquid chromatography (H/UPLC), mass spectrometry (MS), tandem mass spectrometry (MSn) and combinations thereof. Software for biomarker discovery, pathway, genomic and disease analysis and a final note on some future prospects for glycoinformatics are also mentioned.
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Glicómica/métodos , Glicopéptidos/metabolismo , Polisacáridos/metabolismo , Animales , Humanos , Programas InformáticosRESUMEN
BACKGROUND: Still considered one of the most prevalent nutritional problems in the world, anemia has been shown in many studies to have deleterious effects on neurobehavioral development. While most research efforts have focused on investigating the effects of anemia on social and emotional development of infants by using a cross-sectional design, research is still needed to investigate whether early childhood anemia, beyond infantile years, is linked with behavioral problems. OBJECTIVE: This study assessed whether (1) hemoglobin (Hb) levels in early childhood are associated with externalizing behavior; and (2) this relationship is confounded by social adversity. METHODS: Hemoglobin levels were taken from children (N = 98) of the China Jintan Cohort Study at age 4 years, and externalizing behaviors (attention and aggression) were assessed with the Child Behavior Checklist (ASEBA-CBCL) at age 6 years (mean age 5.77 ± 0.39 years old). RESULTS: Compared with other children in the sample, children with relatively lower Hb levels at age 4 had more behavioral problems in both attention and aggression at age 6, independent of social adversity. For boys, this association was significant for attention problems, which did not interact with social adversity. For girls, the association was significant for aggression, which interacted with social adversity. While girls on average exhibited higher social adversity than boys, the main effect of Hb was only significant in girls with low social adversity. CONCLUSIONS: These results indicate that there is an inverse association between hemoglobin levels and later behavioral problems. Findings of this study suggest that regular monitoring of children's hemoglobin levels and appropriate intervention may help with early identification of behavioral problems.
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Agresión/fisiología , Anemia/complicaciones , Anemia/epidemiología , Atención/fisiología , Hemoglobinas/metabolismo , Problema de Conducta , Niño , Preescolar , China/epidemiología , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , MasculinoRESUMEN
Glycosylation of therapeutic proteins has a profound impact on their safety and efficacy. Many factors shape the glycosylation of biotherapeutics, ranging from expression systems and cell culture processes to downstream purification strategies. Various analytical technologies have been developed to address questions concerning different aspects of glycosylation. Informatics tools are also crucial for a systematic understanding of the glycosylation processes. Hence, an integrated approach is required to harness glycosylation for the production of optimal and consistent glycoprotein-based therapeutic drugs. Here, we review the latest developments and challenges in glycosylation analysis and control in the context of bioprocessing monoclonal antibodies.
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Descubrimiento de Drogas , Animales , Anticuerpos Monoclonales/farmacología , Línea Celular , Glicoproteínas/metabolismo , Glicosilación , HumanosRESUMEN
Previous research supports the link among malnutrition, cognitive dysfunction, and behavioral outcomes; however, less research has focused on micronutrient deficiencies. This study investigates whether micronutrient deficiencies, specifically blood zinc and iron levels, will be associated with increased behavior problem scores, including internalizing and externalizing behaviors. 1314 Children (55% boys and 45% girls) from the Jintan Preschool Cohort in China participated in this study. Venous blood samples were collected and analyzed for zinc and iron when the children were 3-5 years old. Behavior problems were measured with the Child Behavior Checklist (CBCL), which was completed by the parents when children were in their last months of preschool (mean age 5.6 years). General linear multivariate modeling was used, with adjustment for important sociodemographic variables. The results indicate that low zinc levels alone (p = 0.024) and combined low zinc and iron levels (p = 0.022) are significantly associated with increased reports of total behavior problems. We did not find an association between low iron and behavior problems. With regards to sociodemographics, living in the suburbs is associated with increased internalizing problems, while higher mother's education and being female were associated with decreased externalizing problems. This study suggests that micronutrient deficiencies and sociodemographic facts are associated with behavior problems in preschoolers.
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Trastornos de la Conducta Infantil/epidemiología , Conducta Infantil , Hierro/sangre , Zinc/sangre , Niño , Trastornos de la Conducta Infantil/sangre , Preescolar , China , Estudios de Cohortes , Femenino , Humanos , Masculino , Micronutrientes/sangre , Micronutrientes/deficiencia , Factores SocioeconómicosRESUMEN
The importance of interprofessional training in healthcare to improve quality of care and health outcomes has been increasingly recognized. This pilot study used an interprofessional and interdisciplinary team of undergraduate health and pre-health students to establish a unique community partnership with a local elementary school in developing and implementing a nutrition/exercise educational intervention. Our results suggest that children as young as 8 years old are capable of learning new information related to the benefits of particular food groups, are capable of retaining this knowledge for 6 months, and that an intervention program as short as one hour every few months stand to make significant impact on children's knowledge about proper nutrition and healthy lifestyles. Our results suggest the potential benefits of further expanding the short-term intervention into a longer-term community-based curriculum targeting a younger age group previously or currently practiced.. Furthermore, this pilot study suggests that undergraduate health and pre-health students can form an interprofessional and collaborative team to take an active role in the dissemination of nutrition knowledge in the community.