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Japanese encephalitis virus (JEV), a single-stranded, enveloped RNA virus, is a health concern across Asian countries, associated with severe neurological disorders, especially in children. Primarily, pigs, bats, and birds are the natural hosts for JEV, but humans are infected incidentally. JEV requires a few host proteins for its entry and replication inside the mammalian host cell. The endoplasmic reticulum (ER) plays a significant role in JEV genome replication and assembly. During this process, the ER undergoes stress due to its remodelling and accumulation of viral particles and unfolded proteins, leading to an unfolded protein response (UPR). Here, we review the overall strategy used by JEV to infect the host cell and various cytopathic effects caused by JEV infection. We also highlight the role of JEV structural proteins (SPs) and non-structural proteins (NSPs) at various stages of the JEV life cycle that are involved in up- and downregulation of different host proteins and are potentially relevant for developing efficient therapeutic drugs.
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Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Animales , Línea Celular , Niño , Virus de la Encefalitis Japonesa (Especie)/genética , Humanos , Mamíferos , Porcinos , Respuesta de Proteína Desplegada , Replicación ViralRESUMEN
Zika virus (ZIKV) has been characterized as one of many potential pathogens and placed under future epidemic outbreaks by the WHO. However, a lack of potential therapeutics can result in an uncontrolled pandemic as with other human pandemic viruses. Therefore, prioritized effective therapeutics development has been recommended against ZIKV. In this context, the present study adopted a strategy to explore the lead compounds from Azadirachta indica against ZIKV via concurrent inhibition of the NS2B-NS3 protease (ZIKVpro) and NS5 RNA dependent RNA polymerase (ZIKVRdRp) proteins using molecular simulations. Initially, structure-based virtual screening of 44 bioflavonoids reported in Azadirachta indica against the crystal structures of targeted ZIKV proteins resulted in the identification of the top four common bioflavonoids, viz. Rutin, Nicotiflorin, Isoquercitrin, and Hyperoside. These compounds showed substantial docking energy (-7.9 to -11.01 kcal/mol) and intermolecular interactions with essential residues of ZIKVpro (B:His51, B:Asp75, and B:Ser135) and ZIKVRdRp (Asp540, Ile799, and Asp665) by comparison to the reference compounds, O7N inhibitor (ZIKVpro) and Sofosbuvir inhibitor (ZIKVRdRp). Besides, long interval molecular dynamics simulation (500 ns) on the selected docked poses reveals stability of the respective docked poses contributed by intermolecular hydrogen bonds and hydrophobic interactions. The predicted complex stability was further supported by calculated end-point binding free energy using molecular mechanics generalized born surface area (MM/GBSA) method. Consequently, the identified common bioflavonoids are recommended as promising therapeutic inhibitors of ZIKVpro and ZIKVRdRp against ZIKV for further experimental assessment.
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Azadirachta , Infección por el Virus Zika , Virus Zika , Antivirales/química , Azadirachta/química , Flavonoides/química , Humanos , Plomo/farmacología , Simulación del Acoplamiento Molecular , Péptido Hidrolasas/farmacología , Inhibidores de Proteasas/química , ARN Polimerasa Dependiente del ARN , Proteínas no Estructurales Virales/metabolismo , Infección por el Virus Zika/tratamiento farmacológicoRESUMEN
The advent and persistence of the Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2)-induced Coronavirus Disease (COVID-19) pandemic since December 2019 has created the largest public health emergency in over a century. Despite the administration of multiple vaccines across the globe, there continues to be a lack of approved efficacious non-prophylactic interventions for the disease. Flavonoids are a class of phytochemicals with historically established antiviral, anti-inflammatory and antioxidative properties that are effective against cancers, type 2 diabetes mellitus, and even other human coronaviruses. To identify the most promising bioactive flavonoids against the SARS-CoV-2, this article screened a virtual library of 46 bioactive flavonoids against three promising targets in the SARS-CoV-2 life cycle: human TMPRSS2 protein, 3CLpro, and PLpro. By examining the effects of glycosylation and other structural-activity relationships, the presence of sugar moiety in flavonoids significantly reduces its binding energy. It increases the solubility of flavonoids leading to reduced toxicity and higher bioavailability. Through protein-ligand contact profiling, it was concluded that naringin formed more hydrogen bonds with TMPRSS2 and 3CLpro. In contrast, hesperidin formed a more significant number of hydrogen bonds with PLpro. These observations were complimented by the 100 ns molecular dynamics simulation and binding free energy analysis, which showed a considerable stability of docked bioflavonoids in the active site of SARS-CoV-2 target proteins. Finally, the binding affinity and stability of the selected docked complexes were compared with the reference ligands (camostat for TMPRSS2, GC376 for 3CLpro, and GRL0617 for PLpro) that strongly inhibit their respective SARS-COV-2 targets. Overall analysis revealed that the selected flavonoids could be potential therapeutic agents against SARS-CoV-2. Naringin showed better affinity and stability for TMPRSS2 and 3CLpro, whereas hesperidin showed a better binding relationship and stability for PLpro.
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COVID-19 , Diabetes Mellitus Tipo 2 , Compuestos de Anilina , Animales , Benzamidas , Flavonoides/farmacología , Humanos , Estadios del Ciclo de Vida , Simulación del Acoplamiento Molecular , Naftalenos , SARS-CoV-2RESUMEN
Supercapacitor and hydrogen-based fuel cells are cheap and environmental-friendly next-generation energy storage devices that are intended to replace Lithium-ion batteries. Metal oxide nanostructures having perovskite crystal structure have been found to exhibit unique electrochemical properties owing to its unique electronic band structure and multiple redox-active ions. Herein, MgTiO3 nanoparticles (MTO-1) were synthesized by wet-chemical sol-gel technique with an average particle size of 50-55 nm, which exhibited superior supercapacitor performance of capacitance (C) = 25 F/g (at 0.25 A/g), energy density (ED) = 17 Wh/kg, power density (PD) = 275 W/kg and 82.41% capacitance retention (after 1000 cycles). Aqueous 1 M Mg(ClO4)2 solution was used as the electrolyte. MTO-1 revealed an overpotential () = 1.329 V and Tafel slope (b) = 374 mV/dec towards Oxygen Evolution Reaction (OER) electrocatalyst and exhibited = 0.914 V and b = 301.4 mV/dec towards Hydrogen Evolution Reaction (HER) electrocatalyst, both in presence of alkaline 1 M KOH solution, making these MgTiO3 nanoparticles very promising for potential use in various technologically important electrochemical applications.
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In recent years, solid solutions have shown promising results as functional materials for different applications. These materials have tunable physiochemical properties and electronic properties, and are being intensively studied for next generation electrochemical charge storage as well as noble metal free low cost electrocatalyts. In the present work, Magnesium Nickel Oxide (MgNiO2) solid solution is prepared by molten salt synthesis. MgNiO2 particles having octahedron shaped morphology with size of 550 nm with an agglomerative behavior was observed through morphological studies. Raman studies revealed presence of three two-phonon modes as well as two one-phonon modes, which confirm the phase purity of MgNiO2 sample. MgNiO2 particles behaved as a promising supercapacitor candidate by exhibiting a large specific capacitance of 76 F/g. It also revealed electrochemical stability over an expansive potential range under the presence of 0.5 mol L-1Sodium Sulfate (Na2SO4) electrolyte, having a high energy density of nearly 51 Wh/kg with a power density of nearly 825 w/kg. Further, MgNiO2 particle showed improved electrocatalytic potential towards Hydrogen Evolution Reaction (HER) in 1 mol L-1 Potassium Hydroxide (KOH) alkaline medium, by demonstrating an overpotential of 0.636 V with a Tafel slope of 0.22205 v/dec. Based on these observed promising results, it can be conclusively inferred that MgNiO2 solid solution is a potential candidate for environmental friendly high voltage supercapacitor and HER electrocatalyst applications.
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This study evaluated the plant growth and profenofos (PF) removal efficiency of Acinetobacter sp.33F and Comamonas sp. 51 F bacteria as individual strains and in combination F1. Plant growth-promoting activities such as indole 3 acetic acid (IAA) production, 1-aminocyclopropane-1-carboxylate (ACC) deaminase, phosphate solubilization, ammonia production, and exopolysaccharide (EPS) production were observed in Acinetobacter sp. 33 F and Comamonas sp. 51 F. However, PGP properties observed were higher in Acinetobacter sp. 33 F as compared to the Comamonas sp. 51 F. In pot sand and pot soil studies, the physiological parameters such as sprout length, shoot length, root length, chlorophyll a, chlorophyll b, and carotenoids were higher for combination F1. PF degradation in pot sand and pot soil resulted in highest degradation by combination F1. In pot soil study, soil enzyme activities such as cellulase, dehydrogenase, urease, protease, and phosphate activities and root cross-section area, total stele area and xylem vessel area were recorded higher for the formulation F1. The study demonstrated that the together Acinetobacter sp. 33 F and Comamonas sp. 51 F as formulation has higher plant growth-promoting activities as compared to the individual bacteria.
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Vigna , Bacterias , Biodegradación Ambiental , Clorofila A , Factores de Crecimiento Nervioso , Organotiofosfatos , Raíces de Plantas , Suelo , Microbiología del SueloRESUMEN
16S ribosomal RNA gene sequences are characteristically used as gold-standard genetic marker for the determination of bacterial and/or archaeal biodiversity, and community profiling of environmental samples. The 16S rRNA amplicon analysis till-date is taken as a standard method for investigation and identification of uncultivable bacteria in microbial diversity studies. The accuracy of these analyses strongly depends upon the choice of primers. It is presumed that these primers do not participate in non-specific amplifications. In the present study, by in silico, PCR and denaturing gradient gel electrophoresis (DGGE) analysis, we have shown that primers do cross-react with eukaryotic DNAs as well, eventually leading to overestimation of microbial biodiversity. We further demonstrated that the overestimation is not only due to cross-reaction with eukaryotic mitochondrial or plastid DNA, but also with eukaryotic chromosomal DNA, that is ubiquitous in environmental samples. We tried to establish methanogenic diversity in municipal solid waste (MSW) leachates and cow dung samples before and after enrichment of the prokaryotic DNA from eukaryotic ones. Results revealed that bands disappeared/get lightened in bacterial 16S rRNA-based DGGE community profiles, after prokaryotic DNA enrichment, but not in mcrA-based community profiles.
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Bacterias/clasificación , Bacterias/genética , Cartilla de ADN/genética , Eucariontes/genética , Hongos/clasificación , Hongos/genética , ARN Ribosómico 16S/genética , Animales , Bacterias/aislamiento & purificación , Bovinos , Enzimas de Restricción del ADN/metabolismo , ADN de Cloroplastos/genética , ADN Mitocondrial/genética , ADN Ribosómico/genética , Electroforesis en Gel de Gradiente Desnaturalizante , Heces/microbiología , Hongos/aislamiento & purificación , Perfilación de la Expresión Génica , Reacción en Cadena de la PolimerasaRESUMEN
OBJECTIVE: To identify sensitivity, specificity and predictive accuracy of quick sequential organ failure assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria to predict in-hospital mortality in hospitalized patients with suspected infection. METHODS: This meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group consensus statement for conducting and reporting the results of systematic review. PubMed and EMBASE were searched for the observational studies which reported predictive utility of qSOFA score for predicting mortality in patients with suspected or proven infection with the following search words: 'qSOFA', 'q-SOFA', 'quick-SOFA', 'Quick Sequential Organ Failure Assessment', 'quick SOFA'. Sensitivity, specificity, area under receiver operating characteristic (ROC) curves with 95% confidence interval (CI) of qSOFA and SIRS criteria for predicting in-hospital mortality was collected for each study and a 2â¯×â¯2 table was created for each study. RESULTS: Data of 406â¯802 patients from 45 observational studies were included in this meta-analysis. Pooled sensitivity (95% CI) and specificity (95% CI) of qSOFA ≥2 for predicting mortality in patients who were not in an intensive care unit (ICU) was 0.48 (0.41-0.55) and 0.83 (0.78-0.87), respectively. Pooled sensitivity (95% CI) of qSOFA ≥2 for predicting mortality in patients (both ICU and non-ICU settings) with suspected infection was 0.56 (0.47-0.65) and pooled specificity (95% CI) was 0.78 (0.71-0.83). CONCLUSION: qSOFA has been found to be a poorly sensitive predictive marker for in-hospital mortality in hospitalized patients with suspected infection. It is reasonable to recommend developing another scoring system with higher sensitivity to identify high-risk patients with infection.
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Puntuaciones en la Disfunción de Órganos , Sepsis/mortalidad , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/patología , Humanos , Estudios Observacionales como Asunto , Valor Predictivo de las PruebasRESUMEN
Dibutyl phthalate is (DBP) the top priority toxicant responsible for carcinogenicity, teratogenicity and endocrine disruption. This study demonstrates the DBP degradation capability of the two newly isolated bacteria from municipal solid waste leachate samples. The isolated bacteria were designated as Pseudomonas sp. V21b and Comamonas sp. 51F after scanning electron microscopy, transmission electron microscopy, Gram-staining, antibiotic sensitivity tests, biochemical characterization, 16S-rRNA gene identification and phylogenetic studies. They were able to grow on DBP, benzyl butyl phthalate, monobutyl phthalate, diisodecyl phthalate, dioctyl phthalate, and protocatechuate. It was observed that Pseudomonas sp. V21b was more efficient in DBP degradation when compared with Comamonas sp. 51F. It degraded 57% and 76% of the initial DBP in minimal salt medium and in DBP contaminated samples respectively. Kinetics for the effects of DBP concentration on Pseudomonas sp. V21b and Comamonas sp. 51F growth was also evaluated. Stoichiometry for DBP degradation and biomass formation were compared for both the isolates. Two major metabolites diethyl phthalate and monobutyl phthalates were identified using GC-MS in the extracts. Key genes were amplified from the genomes of Pseudomonas sp. V21b and Comamonas sp. 51F. DBP degradation pathway was also proposed.
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Two forms of vitellogenin (Vg: Vg1 and Vg2) were purified from the plasma of estradiol-17ß (E2)-treated Indian walking catfish, Clarias batrachus, by gel filtration and adsorption chromatography. Native Vg1 and Vg2 had apparent molecular masses of 375 and 450 kDa, respectively, and both Vgs resolved into two similar major bands (95 and 67 kDa) in SDS-PAGE under reducing condition. Polyclonal antisera raised against each form of Vg were absorbed with a combination of hypophysectomized male catfish serum proteins and alternate Vg to ensure specificity. Immunological analyses verified the presence of Vg1 and Vg2 in the plasma of female catfish. Homologous ELISAs were developed for Vg1 and Vg2 using their respective harvested antisera, which exhibited the detection limit of 100 ng ml-1 for Vg1 and 40 ng ml-1 for Vg2, and low level of cross-reactivity (not parallel to the standard) was found with alternate Vg in each assay. Treatment of male catfish with E2 induced both Vgs showing a proportionate ratio of Vg1 to Vg2 at 5.6:1. Plasma concentrations of both Vgs measured by ELISAs at different reproductive phases of field collected female catfish increased in accordance with the ovarian development, keeping the proportionate ratio of Vg1 to Vg2 at about 2:1 in fish undergoing vitellogenesis during prespawning period and 1:20 during spawning period, suggesting that Vg1 may be the major Vg to contribute in yolk formation, whereas Vg2, besides its role in yolk formation, may facilitate other physiological functions. The present study, thus, demonstrates the occurrence of two unequally synthesized Vgs in the catfish.
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Bagres/sangre , Proteínas de Peces , Vitelogeninas , Animales , Western Blotting , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Estradiol/farmacología , Femenino , Proteínas de Peces/sangre , Proteínas de Peces/inmunología , Proteínas de Peces/aislamiento & purificación , Sueros Inmunes/inmunología , Masculino , Vitelogeninas/sangre , Vitelogeninas/inmunología , Vitelogeninas/aislamiento & purificaciónRESUMEN
BACKGROUND: Dexamethasone is a potent anti-inflammatory, analgesic, and antiemetic drug. Individual randomized controlled trials found a possible benefit of epidural dexamethasone. The purpose of this meta-analysis is to estimate the benefit of epidural dexamethasone on postoperative pain and opioid consumption and to formulate a recommendation for evidence-based practice. MATERIALS AND METHODS: Prospective, randomized controlled trials comparing the analgesic efficacy of epidural local anesthetic and dexamethasone combination, with local anesthetic alone for postoperative pain management after abdominal surgery, were planned to be included in this meta-analysis. PubMed, PubMed Central, Scopus, and Central Register of Clinical Trials of the Cochrane Collaboration (CENTRAL) databases were searched for eligible controlled trials using the following search words: "Epidural", "dexamethasone", and "postoperative pain", until February 20, 2015. RESULTS: Data from five randomized control trials have been included in this meta-analysis. Epidural dexamethasone significantly decreased postoperative morphine consumption (mean difference -7.89 mg; 95% confidence interval [CI]: -11.66 to -3.71) and number of patients required postoperative rescue analgesic boluses (risk ratio: 0.51; 95% CI: 0.41-0.63). CONCLUSION: The present data shows that the addition of dexamethasone to local anesthetic in epidural is beneficial for postoperative pain management.
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Bacteria of the genus Methylobacillus are methanotrophs, a metabolic feature that is widespread in the phylum Proteobacteria. The study demonstrates the isolation and characterization of a newly isolated Methylobacillus sp. V29b. which grows on methanol, protocatechuate, monobutyl phthalate, dibutyl phthalate, diethyl phthalate, benzyl butyl phthalate, dioctyl phthalate and diisodecyl phthalate. Methylobacillus sp. V29b was characterized with scanning electron microscopy, transmission electron microscopy, Gram staining, antibiotics sensitivity tests and biochemical characterization. It degrades 70 % of the initial DBP in minimal salt medium and 65 % of the initial DBP in samples contaminated with DBP. DBP biodegradation kinetics was explained by the Monod growth inhibition model. Values for maximum specific growth rate (µ max) and half-velocity constant (K s) are 0.07 h-1 and 998.2 mg/l, respectively. Stoichiometry for DBP degradation was calculated for Methylobacillus sp. V29b. Four metabolic intermediates, dibutyl phthalate (DBP), monobutyl phthalate, phthalic acid and pyrocatechol, were identified. Based on the metabolic intermediates identified, a chemical pathway for DBP degradation was proposed. Six genes for phthalic acid degradation were identified from the genome of Methylobacillus sp. V29b.
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Methanogens, a key contributor in global carbon cycling, methane emission, and alternative energy production, generate methane gas via anaerobic digestion of organic matter. The methane emission potential depends upon methanogenic diversity and activity. Since they are anaerobes and difficult to isolate and culture, their diversity present in the landfill sites of Delhi and marshlands of Southern Assam, India, was analyzed using molecular techniques like 16S rDNA sequencing, DGGE, and qPCR. The sequencing results indicated the presence of methanogens belonging to the seventh order and also the order Methanomicrobiales in the Ghazipur and Bhalsawa landfill sites of Delhi. Sequences, related to the phyla Crenarchaeota (thermophilic) and Thaumarchaeota (mesophilic), were detected from marshland sites of Southern Assam, India. Jaccard analysis of DGGE gel using Gel2K showed three main clusters depending on the number and similarity of band patterns. The copy number analysis of hydrogenotrophic methanogens using qPCR indicates higher abundance in landfill sites of Delhi as compared to the marshlands of Southern Assam. The knowledge about "methanogenic archaea composition" and "abundance" in the contrasting ecosystems like "landfill" and "marshland" may reorient our understanding of the Archaea inhabitants. This study could shed light on the relationship between methane-dynamics and the global warming process.
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Archaea/clasificación , Archaea/genética , Biodiversidad , Metano/metabolismo , Microbiología del Suelo , Instalaciones de Eliminación de Residuos , Humedales , Anaerobiosis , Archaea/metabolismo , Análisis por Conglomerados , ADN de Archaea/química , ADN de Archaea/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Electroforesis en Gel de Gradiente Desnaturalizante , India , Datos de Secuencia Molecular , Filogenia , ARN Ribosómico 16S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
Previous comparisons between the Ambu(®) AuraOnce(™) and other laryngeal mask airways have revealed different results across various clinical studies. We aimed to perform a systematic review with meta-analysis on the efficacy and safety of the AuraOnce compared with other laryngeal mask airways for airway maintenance in adults undergoing general anaesthesia. Our search of PubMed, PubMed Central, Scopus and the Central Register of Clinical Trials of the Cochrane Collaboration yielded nine randomised controlled trials eligible for inclusion. Comparator laryngeal mask airways were the LMA Unique(™) (four trials), the LMA Classic(®) (five trials) and the Portex(®) Soft Seal(®) (three trials). The AuraOnce provided an oropharyngeal leak pressure higher than the LMA Unique (304 participants, mean (95% CI) difference 3.1 (1.6-4.7) cmH2 O, p < 0.0001) and equivalent to the LMA Classic. The Soft Seal provided a higher leak pressure than the AuraOnce (229 participants, mean (95% CI) difference 3.5 (0.4-6.7) cmH2 O, p = 0.03). Insertion was significantly faster with the AuraOnce than the LMA Unique (304 participants, mean (95% CI) difference 5.4 (2.1-8.71) s, p = 0.001) and Soft Seal (229 participants, mean (95% CI) difference 9.5 (3.0-15.9) s, p = 0.004), but similar to the LMA Classic. The first-insertion success rate of the AuraOnce was equivalent to the LMA Unique, LMA Classic and Soft Seal. We found a higher likelihood of bloodstaining on the cuff with the Soft Seal and a higher incidence of sore throat with the LMA Classic. We conclude that the AuraOnce is an effective alternative to the LMA Classic and LMA Unique, and easier to insert than all three other devices studied.
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Anestesia General/efectos adversos , Anestesia General/instrumentación , Máscaras Laríngeas/efectos adversos , Adolescente , Adulto , Anciano , Presión del Aire , Femenino , Humanos , Laringe/lesiones , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Seguridad del Paciente , Faringitis/epidemiología , Faringitis/etiología , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Adulto JovenRESUMEN
STUDY DESIGN: Noggin protein levels and spinal fusion rates were compared in a rabbit model after application of siRNA against BMP antagonist noggin in paraspinal muscle. OBJECTIVE: To test whether endogenous BMPs are sufficient to form bone in the absence of their antagonists, using noggin siRNA to interrupt the negative feedback loop on endogenous BMP within the paraspinal muscles in rabbits. Unused Posterolateral lumbar fusion is a standard surgical treatment for many spinal disorders, yet even under ideal conditions the rate of non-fusion approaches 25 %. BMPs are effective in promoting bone formation, and are inhibited by antagonists such as noggin. We have previously shown that in this model, endogenous BMPs are present and endogenous BMP antagonist noggin is strongly increased during spinal fusion. Previous studies have found that noggin siRNA enhanced spinal fusion in combination with supra-physiological amounts of exogenous BMP; however, the effect of the siRNA alone remains unknown. METHODS: A posterolateral intertransverse rabbit lumbar fusion was utilized, as established by Boden et al. SiRNA against noggin was electroporated into paraspinal muscle to determine its effect on fusion. Outcome measures included noggin protein expression, and assessment of spinal fusion at 6 weeks. RESULTS: SiRNAs were effective in reducing overexpressed noggin in vitro. Noggin protein was successfully knocked down in vivo for the initial 7 days in our rabbit model and returned to detectable levels by 4 weeks and to normal levels by 6 weeks. The overall fusion rate was not significantly enhanced compared to established controls from our earlier work (Tang et al.). CONCLUSIONS: Early noggin suppression does not appear to enhance the BMP activity sufficiently to significantly affect final fusion rates in our model.
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Proteínas Morfogenéticas Óseas/metabolismo , Proteínas Portadoras/metabolismo , Vértebras Lumbares/cirugía , Músculos Paraespinales/metabolismo , Fusión Vertebral , Animales , Proteínas Portadoras/genética , Técnicas de Silenciamiento del Gen , Modelos Animales , ARN Interferente Pequeño , ConejosRESUMEN
Attention deficit hyperactivity disorder (ADHD) is the most frequently diagnosed behavioral disorder in children with a high frequency of co-morbid conditions like conduct disorder (CD) and oppositional defiant disorder (ODD). These traits are controlled by neurotransmitters like dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA), a mitochondrial enzyme involved in the degradation of amines, has been reported to be associated with aggression, impulsivity, depression, and mood changes. We hypothesized that MAOA can have a potential role in ADHD associated CD/ODD and analyzed 24 markers in a group of Indo-Caucasoid subjects. ADHD probands and controls (N = 150 each) matched for ethnicity and gender were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV. Appropriate scales were used for measuring CD and ODD traits. Markers were genotyped by PCR-based methods and data obtained analyzed using the Cocaphase program under UNPHASED. Only eight markers were found to be polymorphic. rs6323 "G" allele showed higher frequencies in ADHD (P = 0.0023), ADHD + CD (P = 0.03) and ADHD + ODD (P = 0.01) as compared to controls. Haplotype analysis revealed statistically significant difference for three haplotypes in ADHD cases (P < 0.02). Statistically significant differences were also noticed for haplotypes in ADHD + CD and ADHD + ODD cases (P < 0.01). LD analysis showed significant variation in different groups. Multidimensionality reduction analysis showed independent as well as interactive effects of markers. Genotypes showed correlation with behavioral problems in ADHD and ADHD + CD. We interpret that MAOA gene variants may contribute to the etiology of ADHD as well as associated co-morbid CD and ODD in this ethnic group.
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Trastorno por Déficit de Atención con Hiperactividad/genética , Monoaminooxidasa/genética , Trastorno por Déficit de Atención con Hiperactividad/enzimología , Déficit de la Atención y Trastornos de Conducta Disruptiva/enzimología , Déficit de la Atención y Trastornos de Conducta Disruptiva/genética , Comorbilidad , Trastorno de la Conducta/genética , Femenino , Haplotipos , Humanos , India , Masculino , Repeticiones de Minisatélite , Población Blanca/genéticaRESUMEN
The studies were carried out to find out transport parameters to predict leachate transport and contaminant plume profile underneath a municipal solid waste(MSW) dump. For this, both theoretical and practical avenues were explored. Batch experiments with disturbed soil were carried out with a tracer dye Brilliant Blue FCF to obtain the adsorption isotherm of the tracer. Column experiments with undisturbed realistic soil column were carried out to determine physico-chemical transport parameters using the tracer dye. MSW leachate transport were simulated and sensitivity analysis for MSW leachate transport was carried out for different Darcy velocity for pulse input.For determination of mass-transfer coefficient between the immobilized and mobilized water phase, we usedthe concept of number of transfer units (NTUs) and height of transfer units (HTUs) frequently used by Chemical Engineers. The obtained value of mass transfer coefficient calculated by this method was in excellent agreement with the value obtained from inverse calculation of parameter values by a standard software package (CXTFIT).
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Modelos Teóricos , Contaminantes del Suelo/química , Contaminantes Químicos del Agua/química , Adsorción , Bencenosulfonatos , SueloRESUMEN
Dengue is specially owing to inadequate water supply and poor solid waste management , which are favorable for multiplication of the main vectors including the Aedes ageypti coupled with lack of proven anti viral therapy and no proven efficient vaccine .there are many cases of both dengue shock syndrome and dengue haemmorhagic fever making it a major public health burden sending ominous signal resulting both rising morbidity & mortality, deleterious effect on DALY [disability adjusted life year] & QALY [quality adjusted life year] & though it affect all section of society ,still it affect the poor & underprivileged section more, thereby growing menace in public health in general & in developing countries in particular.
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Possible involvement of cyclic nucleotide dependent protein kinase (PKA) and MAP kinase (MAPK) pathways during oocyte maturation in Anabas testudineus was investigated. Pre-incubation with phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX), inhibited 17α, 20ß-DHP-induced GVBD dose dependently. PKA inhibitor, H89 could induce resumption of meiosis independent of 17α, 20ß-DHP, in dose and duration dependent manner. The maximum response was obtained with the dose of 10 µM of H89 and 95% of cells underwent GVBD within 18 h. Moreover, stimulation with 17α, 20ß-DHP inhibited endogenous PKA activity significantly within first hour and this effect was attenuated by PDE inhibitor IBMX at all time points. The pattern of PKA inhibition corresponded well with kinetics of histone H1 kinase activation and p34cdc2 phosphorylation. These results suggest physiological relevance of cAMP/PKA signaling in perch oocytes undergoing G2/M transition. MAPK was demonstrated as two distinct isoforms (ERK1 and ERK2) which resolved in the range of 42-44 kDa in immunoblot. Though total protein content did not show significant variation, H89 stimulation was able to stimulate phosphorylation of ERK1/2 from 5h onwards and the strongest response was observed between 10 and 18 h. MEK inhibitor, U0126 completely blocked PKA inhibition induced MAPK activation and GVBD. In addition, inhibition of endogenous PKA by a more selective peptide inhibitor [PKI-(6-22)-amide] was sufficient to resume GVBD and MAPK activation in intact perch oocytes. Also, significant ERK1/2 phosphorylation could be stimulated in cell-free extracts of perch oocytes supplemented with PKI-(6-22)-amide. The results suggest an interaction between cAMP/PKA and MAPK pathways in mediating meiosis resumption in perch oocyte.
Asunto(s)
Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Oocitos/citología , Oocitos/enzimología , Percas/metabolismo , Animales , Butadienos/farmacología , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Femenino , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Nitrilos/farmacologíaRESUMEN
Vitamin D regulates calcium and immune function. While vitamin D deficiency has been associated with periodontitis, little information exists regarding its effect on wound healing and periodontal surgery outcomes. This longitudinal clinical trial assessed outcomes of periodontal surgery and teriparatide administration in vitamin-D-sufficient and -insufficient individuals. Forty individuals with severe chronic periodontitis received periodontal surgery, daily calcium and vitamin D supplements, and self-administered teriparatide or placebo for 6 wks to correspond with osseous healing time. Serum 25(OH)D was evaluated at baseline, 6 wks, and 6 mos post-surgery. Clinical and radiographic outcomes were evaluated over 1 yr. Placebo patients with baseline vitamin D deficiency [serum 25(OH)D, 16-19 ng/mL] had significantly less clinical attachment loss (CAL) gain (-0.43 mm vs. 0.92 mm, p < 0.01) and probing depth (PPD) reduction (0.43 mm vs. 1.83 mm, p < 0.01) than vitamin-D-sufficient individuals. Vitamin D levels had no significant impact on CAL and PPD improvements in teriparatide patients at 1 yr, but infrabony defect resolution was greater in teriparatide-treated vitamin-D-sufficient vs. -deficient individuals (2.05 mm vs. 0.87 mm, p = 0.03). Vitamin D deficiency at the time of periodontal surgery negatively affects treatment outcomes for up to 1 yr. Analysis of these data suggests that vitamin D status may be critical for post-surgical healing. (ClinicalTrials.gov number, CT00277706).