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1.
An Acad Bras Cienc ; 95(3): e20211594, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37851743

RESUMEN

Changes in the physical and biogeochemical properties of water columns are frequently associated with cold fronts and mesoscale convective systems due to increased cloud cover. The effects of low-level jet (LLJ) events on thermal stratification and water quality, however, remain undescribed, particularly for tropical reservoirs. Here, water temperature time series are combined with meteorological data, LIDAR observations, ERA5 reanalysis data, and hydrodynamical modeling to investigate the impact of an event of LLJ over the Furnas hydropower reservoir in Brazil. The LLJ event was characterized by dry, intense, and persistent winds (~10 m s-1) blowing for more than 12 hours over the main fetch of the reservoir. In the downwind side of the lake, the surface mixed layer depth increased by 50% during the LLJ event. The changes to the water column were produced by a combination of wind-induced upwelling, shear-driven mixing, and nocturnal convective overturning, different from the heat balance expected during passing cold fronts and mesoscale convective systems. The results suggest that both momentum and heat fluxes during LLJ events need to be accounted for in lake modelings to reproduce the vertical mixing process.


Asunto(s)
Frío , Viento , Temperatura , Lagos , Calor
2.
Trop Anim Health Prod ; 52(1): 31-39, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31289965

RESUMEN

Equine leptospirosis, although usually asymptomatic, has been associated with recurrent uveitis, abortion, and other systemic signs, constituting a major economic loss in the equine agribusiness sector. The occurrence of anti-Leptospira spp. agglutinins were investigated in 1200 serum samples of horses from 27 municipalities of the Recôncavo Baiano region, Bahia state (NE Brazil), besides the risk factors related to animals and their cattle farms. The microscopic agglutination test (MAT) was performed using 13 serogroups of Leptospira spp. as antigens. From 1200 analyzed equines, 97 (8%) were considered as positive, which obtained titer equal to or higher than 200. In 22 (78.6%) from the 28 properties, at least one animal was detected as seropositive. The most prevalent serogroup in animals, raised in stables, was the Australis (serovar Bratislava) 67%; in mounted police animals was the Sejroe (serovar Wolffi and Hardjobovis) 50%; and equestrian animals was the Australis (serovar Bratislava) 25% and Icterohaemorrhagiae (serovar Copenhageni) 25%. Equine leptospirosis is present in most cattle farms of the region studied. The risk factors of major importance regarded the semi-extensive livestock farming, the land topography of the cattle farm, the contact with animals in neighboring properties, and cohabitation with goats.


Asunto(s)
Enfermedades de los Caballos/epidemiología , Leptospirosis/veterinaria , Pruebas Serológicas/veterinaria , Pruebas de Aglutinación/veterinaria , Animales , Antígenos Bacterianos/sangre , Brasil/epidemiología , Bovinos , Granjas , Caballos , Factores de Riesgo , Estudios Seroepidemiológicos , Serogrupo
3.
An Acad Bras Cienc ; 89(2): 1189-1203, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28640356

RESUMEN

Currently, there is a lack of studies on the correct utilization of continuous distributions for dry tropical forests. Therefore, this work aims to investigate the diameter structure of a brazilian tropical dry forest and to select suitable continuous distributions by means of statistic tools for the stand and the main species. Two subsets were randomly selected from 40 plots. Diameter at base height was obtained. The following functions were tested: log-normal; gamma; Weibull 2P and Burr. The best fits were selected by Akaike's information validation criterion. Overall, the diameter distribution of the dry tropical forest was better described by negative exponential curves and positive skewness. The forest studied showed diameter distributions with decreasing probability for larger trees. This behavior was observed for both the main species and the stand. The generalization of the function fitted for the main species show that the development of individual models is needed. The Burr function showed good flexibility to describe the diameter structure of the stand and the behavior of Mimosa ophthalmocentra and Bauhinia cheilantha species. For Poincianella bracteosa, Aspidosperma pyrifolium and Myracrodum urundeuva better fitting was obtained with the log-normal function.


Asunto(s)
Bosques , Dispersión de las Plantas/fisiología , Árboles/crecimiento & desarrollo , Clima Tropical , Anacardiaceae/crecimiento & desarrollo , Aspidosperma/crecimiento & desarrollo , Bauhinia/crecimiento & desarrollo , Biodiversidad , Brasil , Caesalpinia/crecimiento & desarrollo , Mapeo Geográfico , Mimosa/crecimiento & desarrollo , Valores de Referencia , Estadísticas no Paramétricas , Árboles/clasificación
4.
An Acad Bras Cienc ; 89(3): 1815-1828, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28954167

RESUMEN

Dry tropical forests are a key component in the global carbon cycle and their biomass estimates depend almost exclusively of fitted equations for multi-species or individual species data. Therefore, a systematic evaluation of statistical models through validation of estimates of aboveground biomass stocks is justifiable. In this study was analyzed the capacity of generic and specific equations obtained from different locations in Mexico and Brazil, to estimate aboveground biomass at multi-species levels and for four different species. Generic equations developed in Mexico and Brazil performed better in estimating tree biomass for multi-species data. For Poincianella bracteosa and Mimosa ophthalmocentra, only the Sampaio and Silva (2005) generic equation was the most recommended. These equations indicate lower tendency and lower bias, and biomass estimates for these equations are similar. For the species Mimosa tenuiflora, Aspidosperma pyrifolium and for the genus Croton the specific regional equations are more recommended, although the generic equation of Sampaio and Silva (2005) is not discarded for biomass estimates. Models considering gender, families, successional groups, climatic variables and wood specific gravity should be adjusted, tested and the resulting equations should be validated at both local and regional levels as well as on the scales of tropics with dry forest dominance.


Asunto(s)
Biomasa , Bosques , Brasil , Monitoreo del Ambiente , México , Modelos Estadísticos , Clima Tropical
5.
Regul Toxicol Pharmacol ; 74: 170-7, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26522812

RESUMEN

The infusion of Baccharis trimera (Less) DC, popularly known as "carqueja" (broom), is popularly used in the treatment of hepatic and digestive problems. In this study, we evaluated the acute and sub-chronic oral toxicities of B. trimera tincture on male and female Wistar rats according to Organization for Economic Cooperation and Development (OECD, guidelines 423 e 407, respectively). The B. trimera tincture was administered by oral gavage in a single dose (2000 mg/kg) in doses of 100, 200 and 400 mg/kg daily for 28 days. Blood was collected to analyze hematological and biochemical parameters. Kidneys and liver were homogenized to determine lipid peroxidation and δ-aminolevulinate dehydratase (δ-ALA-D) and catalase (CAT) enzyme activities. In acute treatment, tincture did not induce any signs of toxicity or mortality. Daily oral administration produced no significant changes in the hematological and biochemical parameters, except for the hepatic enzymes alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) that showed a reduction in both sexes. Moreover, the B. trimera tincture did not increase lipid peroxidation or affected ALA-D and CAT activities. In conclusion, the tincture of B. trimera may be considered relatively safe in this protocol.


Asunto(s)
Baccharis/toxicidad , Extractos Vegetales/toxicidad , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Subcrónica , Administración Oral , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Baccharis/química , Biomarcadores/sangre , Catalasa/sangre , Femenino , Riñón/efectos de los fármacos , Riñón/enzimología , Riñón/patología , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Masculino , Fitoterapia , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Porfobilinógeno Sintasa/sangre , Ratas Wistar , Medición de Riesgo , Factores Sexuales , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factores de Tiempo
6.
An Acad Bras Cienc ; 87(2): 1041-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26062113

RESUMEN

American foulbrood (AFB) is a serious worldwide spreading disease in bees caused by Paenibacillus larvae. Plants extracts are known to decrease or inhibit the growth of these bacteria. The purpose of this study was to evaluate the antimicrobial activity of Calendula. officinalis, Cariniana domestica, and Nasturtium officinale extracts against the P. larvae and to evaluate the toxicity of the extracts in bees. In vitro activity against P. larvae of the extracts was evaluated by micro dilution method and the minimal inhibitory concentrations (MICs) were also determined. The concentrations used in the toxicity test were established based on the MIC values and by the spraying application method. The P. larvae was susceptible to the evaluated crude extract of C. officinalis and N. officinale. To C. domestica, only the ethyl acetate (EtAc) fraction and n-butanol (BuOH) fractions had activity against P. larvae. Toxicity analysis in bees showed no toxicity for N. officinale crude extract and for C. domestica BuOH fraction during 15 days of treatment, however, some deaths of bees occurred during the first three days of treatment with C. officinalis and C. domestica EtAc fraction. The results with these species were firstly described and showed that N. officinale crude extract and C. domestica BuOH fraction both presented not toxic effects in the concentration tested by the spraying application method, and can be a useful alternative for treatment or prevention of AFB.


Asunto(s)
Abejas/efectos de los fármacos , Calendula/química , Lecythidaceae/química , Nasturtium/química , Paenibacillus/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Cromatografía de Gases y Espectrometría de Masas , Larva/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/toxicidad , Pruebas de Toxicidad
7.
Cell Biochem Funct ; 32(5): 438-44, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24633892

RESUMEN

The mechanisms that lead to the onset of organoselenium intoxication are still poorly understood. Therefore, in the present study, we investigated the effect of acute administration of 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress and on the activity of creatine kinase (CK) in different brain areas and on the behaviour in the open field test of 90-day-old male rats. Animals (n = 10/group) were treated intraperitoneally with a single dose of the organoselenium (125, 250 or 500 µg kg(-1) ), and after 1 h of the drug administration, they were exposed to the open field test, and behaviour parameters were recorded. Immediately after they were euthanized, cerebral cortex, hippocampus and cerebellum were dissected for measurement of thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and CK activity. Our results showed that the dose of 500 µg kg(-1) of the organoselenium increased the locomotion and rearing behaviours in the open field test. Moreover, the organochalcogen enhanced TBARS in the cerebral cortex and cerebellum and increased the oxidation of proteins (carbonyl) only in the cerebral cortex. Sulfhydryl content was reduced in all brain areas, CAT activity enhanced in the hippocampus and reduced in the cerebellum and SOD activity increased in all brain structures. The organoselenium also inhibited CK activity in the cerebral cortex. Therefore, changes in motor behaviour, redox state and energy homeostasis in rats treated acutely with organoselenium support the hypotheses that the brain is a potential target for the organochalcogen action. Ltd.


Asunto(s)
Encéfalo/metabolismo , Compuestos de Organoselenio/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Encéfalo/enzimología , Catalasa/metabolismo , Creatina Quinasa/metabolismo , Masculino , Compuestos de Organoselenio/química , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo
8.
Scott Med J ; 59(1): 62-6, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24434856

RESUMEN

Clinical engagement can achieve lasting change in the delivery of healthcare. In October 2011, Healthcare Improvement Scotland formulated a clinical engagement strategy to ensure that a progressive and sustainable approach to engaging healthcare professionals is firmly embedded in its health improvement and public assurance activities. The strategy was developed using a 90-day process, combining an evidence base of best practice and feedback from semi-structured interviews and focus groups. The strategy aims to create a culture where clinicians view working with Healthcare Improvement Scotland as a worthwhile venture, which offers a number of positive benefits such as training, career development and research opportunities. The strategy works towards developing a respectful partnership between Healthcare Improvement Scotland, the clinical community and key stakeholders whereby clinicians' contributions are recognised in a non-financial reward system. To do this, the organisation needs a sustainable infrastructure and an efficient, cost-effective approach to clinical engagement. There are a number of obstacles to achieving successful clinical engagement and these must be addressed as key drivers in its implementation. The implementation of the strategy is supported by an action and resource plan, and its impact will be monitored by a measurement plan to ensure the organisation reviews its approaches towards clinical engagement.


Asunto(s)
Atención a la Salud/normas , Mejoramiento de la Calidad , Atención a la Salud/organización & administración , Prioridades en Salud , Humanos , Escocia
9.
Comput Biol Med ; 173: 108085, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38513393

RESUMEN

Glass Box Machine Learning is, in this study, a type of partially supervised data mining and prediction technique, like a neural network in which each weight or pattern of mutually relevant weights is now replaced by a meaningful "probabilistic knowledge element." We apply it to retrospective cohort studies using large numbers of structured medical records to help select candidate patients for future cohort studies and similar clinical trials. Here it is applied to aid analysis of approaches to aid Deep Learning, but the method lends itself well to direct computation of odds with "explainability" in study design that can complement "Black Box" Deep Learning. Cohort studies and clinical trials traditionally involved at least one 2 × 2 contingency table, but in the age of emerging personalized medicine and the use of machine learning to discover and incorporate further relevant factors, these tables can extend into many extra dimensions as a 2 × 2 x 2 × 2 x ….data structure by considering different conditional demographic and clinical factors of a patient or group, as well as variations in treatment. We consider this in terms of multiple 2 × 2 x 2 data substructures where each one is summarized by an appropriate measure of risk and success called DOR*. This is the diagnostic odds ratio DOR for a specified disease conditional on a favorable outcome divided by the corresponding DOR conditional on an unfavorable outcome. Bleeding peptic ulcer was chosen as a complex disease with many influencing factors, one that is still subject to controversy and that highlights the challenges of using Real World Data.


Asunto(s)
Úlcera Péptica , Humanos , Estudios Retrospectivos , Hemorragia , Aprendizaje Automático , Estudios de Cohortes , Registros Médicos
10.
J Water Health ; 11(3): 397-409, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23981869

RESUMEN

Specificity testing of two published polymerase chain reaction (PCR) markers for the detection of human faecal pollution, revealed 100% false-positive rates to brush-tailed possum faeces (n = 10), but low false-positive rates against other potential pollution sources. Cross-reaction with possums could be a problem with other human-specific markers; therefore, a possum PCR marker was developed for use in conjunction with human PCR markers. The possum PCR marker was based on Bacteroidales 16S ribosomal ribonucleic acid sequences, and was tested on 233 individual faecal samples from 11 other animal species. Sensitivity of the possum marker in possum faeces (n = 36) was high at 83.3%. Cross-reactivity of the possum marker was limited to black swan (7/20 samples), human (2/48 samples) and rabbit (1/10) faecal samples, all at marker concentrations at least four orders of magnitude lower than possum faeces. The possum marker was not detected in human sewage or the faeces of other animal species. Specificity of the possum PCR marker, therefore, was high at 95.7%. To exclude the possibility that only possum pollution is being detected, additional testing by other faecal source tracking methods is required where the water sample is positive for both human and possum markers.


Asunto(s)
Heces/química , Reacción en Cadena de la Polimerasa/métodos , Trichosurus/genética , Contaminantes del Agua/química , Animales , Bacteroidetes/genética , Teorema de Bayes , Reacciones Cruzadas , ADN/análisis , Reacciones Falso Positivas , Humanos , Nueva Zelanda , Sensibilidad y Especificidad
11.
Neurochem Res ; 37(5): 928-34, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22212881

RESUMEN

Selenium (Se) is an essential mineral for mammals. It is a nutrient related to the complex metabolic and enzymatic functions. Although Se has important physiological functions in the cells, organic compounds of Se can be extremely toxic, and may affect the central nervous system. This study aims to investigate the effect of the chronic treatment with the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress in the brain of rats. Animals received the vinyl chalcogenide (125, 250 or 500 µg/kg body weight) intraperitoneally once a day during 30 days. The cerebral cortex, the hippocampus, and the cerebellum were dissected and homogenized in KCl. Afterward, thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in the brain. Results showed that the organoselenium enhanced TBARS in the cerebral cortex of rats but the compound was not able to change carbonyl levels. Furthermore, the organoselenium reduced thiol groups measured by the sulfhydryl assay in all tissues studied. The activity of the antioxidant enzyme CAT was increased by the organochalcogen in the cerebral cortex and in the cerebellum, and the activity of SOD was increased in the hippocampus. On the other hand, the activity of the antioxidant enzyme GPx was reduced in all brain structures. Our findings indicate that this organoselenium compound induces oxidative stress in different brain regions of rats, corroborating to the fact that this tissue is a potential target for organochalcogen action.


Asunto(s)
Encéfalo/efectos de los fármacos , Compuestos de Organoselenio/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Encéfalo/enzimología , Encéfalo/metabolismo , Catalasa/metabolismo , Relación Dosis-Respuesta a Droga , Glutatión Peroxidasa/metabolismo , Masculino , NADP/metabolismo , Compuestos de Organoselenio/administración & dosificación , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
12.
Inform Med Unlocked ; 31: 100966, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35611320

RESUMEN

The author, the journal, Computers in Biology and Medicine (CBM), and Elsevier Press more generally, played a helpful very early role in responding to COVID-19. Within a few days of the appearance of the "Wuhan Seafood isolate" genome on GenBank, a bioinformatics study was posted by the present author in ResearchGate in January 2020, "Preliminary Bioinformatics Studies on the Design of Synthetic Vaccines and Preventative Peptidomimetic Antagonists against the Wuhan Seafood Market Coronavirus. Possible Importance of the KRSFIEDLLFNKV Motif" DOI: 10.13140/RG.2.2.18275.09761. On February 2nd, 2020, a more thorough analysis was submitted to CBM, e-published on February 26, and formally published in April 2020, at about the same time as the virus named as 2019n-CoV was identified as essentially SARS and renames SARS-COV-2. This was followed by four further papers describing in more detail some previously unreported aspects of the early investigation. The speed of research and writing of the papers was made possible by knowledge-gathering tools. Based on this and earlier experiences with fast responses to emerging epidemics such as HIV and Mad Cow Disease, it is possible to envisage the nature of a speedier response to emerging epidemics and new variants of concern in established epidemics.

14.
Water Sci Technol ; 63(8): 1744-51, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21866776

RESUMEN

This study determined whether human pathogenic viruses are present in two New Zealand surface waters that are used as drinking-water sources. Enteric viruses were concentrated using hollow-fibre ultrafiltration and detected using PCR for adenovirus (AdV), and reverse transcription PCR for norovirus (NOV) genogroups I-III, enterovirus, rotavirus (RoV) and hepatitis E virus (HEV). Target viruses were detected in 106/109 (97%) samples, with 67/109 (61%) samples positive for three or more viral types at any one time. AdV, NoV and ROV were detected the most frequently, and HEV the least frequently. Human NoV was not usually associated with animal NOV. Our results suggest that New Zealand would be well served by assessing the ability of drinking-water treatment plants to remove viruses from the source waters, and that this assessment could be based on the viral concentration of AdV-NoV-RoV. The long-term aim of our work is to use this information to estimate the risk of waterborne viral infection.


Asunto(s)
Gastroenteritis/epidemiología , Gastroenteritis/virología , Virus/clasificación , Microbiología del Agua , Abastecimiento de Agua/normas , ADN Viral/clasificación , ADN Viral/aislamiento & purificación , Humanos , Nueva Zelanda/epidemiología , Reacción en Cadena de la Polimerasa , ARN Viral/clasificación , ARN Viral/aislamiento & purificación , Virus/aislamiento & purificación
15.
Comput Biol Med ; 128: 104124, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33276271

RESUMEN

The aim of the present study is to discuss the design of peptide vaccines and peptidomimetics against SARS-COV-2, to develop and apply a method of protein structure analysis that is particularly appropriate to applying and discussing such design, and also to use that method to summarize some important features of the SARS-COV-2 spike protein sequence. A tool for assessing sidechain exposure in the SARS-CoV-2 spike glycoprotein is described. It extends to assessing accessibility of sidechains by considering several different three-dimensional structure determinations of SARS-CoV-2 and SARS-CoV-1 spike protein. The method is designed to be insensitive to a distance limit for counting neighboring atoms and the results are in good agreement with the physical chemical properties and exposure trends of the 20 naturally occurring sidechains. The spike protein sequence is analyzed with comment regarding exposable character. It includes studies of complexes with antibody elements and ACE2. These indicate changes in exposure at sites remote to those at which the antibody binds. They are of interest concerning design of synthetic peptide vaccines, and for peptidomimetics as a basis of drug discovery. The method was also developed in order to provide linear (one-dimensional) information that can be used along with other bioinformatics data of this kind in data mining and machine learning, potentially as genomic data regarding protein polymorphisms to be combined with more traditional clinical data.


Asunto(s)
Vacunas contra la COVID-19/química , Modelos Moleculares , Peptidomiméticos/química , Glicoproteína de la Espiga del Coronavirus/química , Simulación por Computador , Humanos , Vacunas de Subunidad/química
16.
Comput Biol Med ; 125: 103963, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32828990

RESUMEN

Knowledge management tools that assist in systematic review and exploration of scientific knowledge generally are of obvious potential importance in evidence based medicine in general, but also to the design of therapeutics based on the protein subsequences and fold motifs of virus proteins as considered here. Rapid access to bundles (clusters) of related elements of knowledge gathered from diverse sources on the Internet and from growing knowledge repositories seem particularly helpful when exploring less obvious therapeutic targets in viruses (for which knowledge new to the researcher is important), and when using the following concept. Subsequences of amino acid residue sequences of proteins that are conserved across strains and species are (a) more likely to be important targets and (b) less likely to exhibit escape mutations that would make them resistant to vaccines and therapeutic agents. However, the terms "conserved" and even "highly conserved" used by authors are matters of degree, depending on how distant from SARS-CoV-2 they wished to go in comparing other sequences. The binding site to the human ACE2 protein as virus receptor and human antibody CR3022 binding site on the spike glycoprotein are rather variable by the criteria used in the present and preceding studies. To look for more strongly conserved targets, open reading frames of SARS-CoV-2 were examined for extremely highly conserved regions, meaning recognizable across many viruses and organisms. Most prominent is a motif found in SARS-CoV-2 non-structural protein 3 (Nsp3). It relates to a fold called type called the macro domain and has remarkably wide distribution across organisms including humans with significant homologies involving three especially conserved subsequences (a) VVVNAANVYLKHGGGVAGALNK, (b) LHVVGPNVNKG, and (c) PLLSAGIFG. Careful study of the variations of these and of the more variable sequences between and around them might provide a finer "scalpel" to ensure inhibition of a vital function of the virus without impairing the functions of related host macro domains.


Asunto(s)
Inteligencia Artificial , Biología Computacional/métodos , Secuencia Conservada/genética , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Proteínas no Estructurales Virales , Secuencia de Aminoácidos , Betacoronavirus , Sitios de Unión , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Proteasas Similares a la Papaína de Coronavirus , Desarrollo de Medicamentos , Humanos , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , SARS-CoV-2 , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/genética
17.
Comput Biol Med ; 122: 103849, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32658736

RESUMEN

SARS-CoV and SARS-CoV-2 do not appear to have functions of a hemagglutinin and neuraminidase. This is a mystery, because sugar binding activities appear essential to many other viruses including influenza and even most other coronaviruses in order to bind to and escape from the glycans (sugars, oligosaccharides or polysaccharides) characteristic of cell surfaces and saliva and mucin. The S1 N terminal Domains (S1-NTD) of the spike protein, largely responsible for the bulk of the characteristic knobs at the end of the spikes of SARS-CoV and SARS-CoV-2, are here predicted to be "hiding" sites for recognizing and binding glycans containing sialic acid. This may be important for infection and the ability of the virus to locate ACE2 as its known main host cell surface receptor, and if so it becomes a pharmaceutical target. It might even open up the possibility of an alternative receptor to ACE2. The prediction method developed, which uses amino acid residue sequence alone to predict domains or proteins that bind to sialic acids, is naïve, and will be advanced in future work. Nonetheless, it was surprising that such a very simple approach was so useful, and it can easily be reproduced in a very few lines of computer program to help make quick comparisons between SARS-CoV-2 sequences and to consider the effects of viral mutations.


Asunto(s)
Betacoronavirus/química , Biología Computacional , Infecciones por Coronavirus/virología , Neumonía Viral/virología , Glicoproteína de la Espiga del Coronavirus/química , Algoritmos , Secuencias de Aminoácidos , Sitios de Unión , COVID-19 , Humanos , Conformación Molecular , Ácido N-Acetilneuramínico/química , Pandemias , Polisacáridos/química , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , SARS-CoV-2 , Triptófano/química
18.
Comput Biol Med ; 119: 103670, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32209231

RESUMEN

This paper concerns study of the genome of the Wuhan Seafood Market isolate believed to represent the causative agent of the disease COVID-19. This is to find a short section or sections of viral protein sequence suitable for preliminary design proposal for a peptide synthetic vaccine and a peptidomimetic therapeutic, and to explore some design possibilities. The project was originally directed towards a use case for the Q-UEL language and its implementation in a knowledge management and automated inference system for medicine called the BioIngine, but focus here remains mostly on the virus itself. However, using Q-UEL systems to access relevant and emerging literature, and to interact with standard publically available bioinformatics tools on the Internet, did help quickly identify sequences of amino acids that are well conserved across many coronaviruses including 2019-nCoV. KRSFIEDLLFNKV was found to be particularly well conserved in this study and corresponds to the region around one of the known cleavage sites of the SARS virus that are believed to be required for virus activation for cell entry. This sequence motif and surrounding variations formed the basis for proposing a specific synthetic vaccine epitope and peptidomimetic agent. The work can, nonetheless, be described in traditional bioinformatics terms, and readily reproduced by others, albeit with the caveat that new data and research into 2019-nCoV is emerging and evolving at an explosive pace. Preliminary studies using molecular modeling and docking, and in that context the potential value of certain known herbal extracts, are also described.


Asunto(s)
Betacoronavirus/inmunología , Betacoronavirus/fisiología , Biología Computacional , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Peptidomiméticos/química , Neumonía Viral/prevención & control , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Vacunas Virales , Secuencia de Aminoácidos , Animales , Betacoronavirus/química , Betacoronavirus/efectos de los fármacos , COVID-19 , Vacunas contra la COVID-19 , Simulación por Computador , Coronavirus/química , Infecciones por Coronavirus/tratamiento farmacológico , Diseño de Fármacos , Epítopos , Genoma Viral , Humanos , Modelos Moleculares , Peptidomiméticos/metabolismo , Peptidomiméticos/farmacología , Neumonía Viral/tratamiento farmacológico , Lenguajes de Programación , Conformación Proteica , Estructura Secundaria de Proteína , SARS-CoV-2 , Homología de Secuencia de Aminoácido , Programas Informáticos , Glicoproteína de la Espiga del Coronavirus/química , Vacunas Sintéticas , Vacunas Virales/química , Internalización del Virus , Tratamiento Farmacológico de COVID-19
19.
Comput Biol Med ; 121: 103749, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32568687

RESUMEN

This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2' spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles' heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried out suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding sites. The enzyme 11ß-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/prevención & control , Glicoproteína de la Espiga del Coronavirus/química , Vacunas Virales/inmunología , Secuencia de Aminoácidos , Enzima Convertidora de Angiotensina 2 , Animales , Antivirales/farmacología , Betacoronavirus/química , Betacoronavirus/genética , Betacoronavirus/inmunología , Sitios de Unión , COVID-19 , Vacunas contra la COVID-19 , Biología Computacional , Coronavirus/química , Coronavirus/genética , Coronavirus/inmunología , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Diseño de Fármacos , Farmacorresistencia Viral/genética , Interacciones Microbiota-Huesped/genética , Interacciones Microbiota-Huesped/inmunología , Humanos , Modelos Moleculares , Mutación , Peptidomiméticos/farmacología , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/virología , SARS-CoV-2 , Homología de Secuencia de Aminoácido , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Vacunas Virales/genética
20.
Curr Alzheimer Res ; 17(4): 365-372, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32442085

RESUMEN

BACKGROUND: Sedentary life-style is a significant public health issue. It increases the incidence of type-2 diabetes mellitus (DM2) and systemic arterial hypertension (SAH), which in turn may impair physical and mental health. In fact, disrupted glucose metabolism is characteristic of Alzheimer's dementia, and it is often dubbed as type-3 diabetes. OBJECTIVE: The purpose of this study was to assess the level of activity, body composition, cardiovascular risk and cognitive profile of patients with DM2 and/or SAH. The study was cross-sectional design. METHOD: The sample consisted of 120 individuals which 35% men and 65% women, with an average of 64±9 years old and 60±11 years old, respectively. Various parameters were evaluated such as anthropometric variables, pedometer recordings and brief cognitive screening battery (BCSB), which assesses the immediate memory, verbal fluency, learning, late memory and recognition. Chi-square and Fisher's exact test were applied to observe possible differences between men and women. In addition to Kruskall-Wallis, in the comparison between patients with SAH; DM2 and SAH + DM2. RESULTS: A high rate of physical inactivity was found among those enrolled in this project. Females were characterized by increased body fat, whereas men displayed visceral fat excess. BCSB demonstrated reduced verbal fluency, late memory and recognition, with women presenting significantly worse results. CONCLUSION: Low level of daily physical activity is apparently correlated with obesity, elevated cardiovascular risk, and cognitive dysfunction.


Asunto(s)
Enfermedades Cardiovasculares/fisiopatología , Disfunción Cognitiva/fisiopatología , Ejercicio Físico/fisiología , Ejercicio Físico/psicología , Factores de Riesgo de Enfermedad Cardiaca , Conducta Sedentaria , Anciano , Antropometría/métodos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/psicología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo
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