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1.
Saudi J Kidney Dis Transpl ; 31(2): 423-430, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32394915

RESUMO

There are only a few reports on the role of peritoneal dialysis (PD) in critically ill patients requiring continuous renal replacement therapies (RRT). This study aimed to determine the efficacy and outcome of intermittent PD in acute kidney injury (AKI) patients in intensive care unit setting and to assess the procedure-related complications. This was a prospective, observational study conducted from March 1, 2015, to February 29, 2016, which included patients of either sex, aged ≥18 years, diagnosed with AKI, and undergoing RRT with intermittent PD sessions with more than 48 h of hospital stay. Patients were later shifted to sustained low- efficiency dialysis or hemodialysis, when they became hemodynamically stable. Hence, the patients who received at least 48 h of PD were included in the study. A total of 75 patients were enrolled. Overall, the mean age was 55.75 years, and around 64% were men. The most common indication to start PD was metabolic acidosis, and the most common cause of AKI was sepsis. A total of 21 patients survived, and the mortality rate was 72%. The average peritoneal urea clearance and creatinine clearance were 14.81 mL/min and 12.59 mL/min, respectively. Of the 66 patients on inotropes, 28 patients were tapered from inotropic support. Thirty-nine patients had hyperkalemia, and 27 patients had correction within 1 day of the start of PD. Forty-seven patients had correction of acidosis, and 33 of these achieved pH ≥7.25 within one day of PD. The most common complication that occurred was peri-catheter leaks followed by peritonitis. Acute PD can be an effective, simple, and safe bridge RRT in hemodynamically unstable patients until the achievement of hemodynamic stability to shift them to other modalities of RRT.

2.
Alcohol Clin Exp Res ; 44(5): 1061-1074, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32154597

RESUMO

BACKGROUND: Liver is enriched in several innate-like unconventional T cells, but their role in alcohol-related liver disease (ALD) is not fully understood. Studies in several acute alcohol feeding models but not in chronic alcoholic steatohepatitis (ASH) model have shown that invariant natural killer T (iNKT) cells play a pathogenic role in ALD. Here, we investigated the activation of iNKT cells in an intragastric (iG) infusion model of chronic ASH as well as the frequency and cytokine phenotype of 3 different unconventional T cells: iNKT, mucosal-associated invariant T (MAIT), and CD8+ CD161hi Vα7.2- cells in peripheral blood of ALD patients. METHODS: Hepatic iNKT cells were investigated using the iG model of chronic ASH that combines feeding of high-cholesterol/high-fat diet (HCFD) with intragastric feeding of ethanol diet (HCFD + iG Alc). Human iNKT, MAIT, and CD8+ CD161hi Vα7.2- cells were examined by flow cytometry in peripheral blood of patients with severe alcoholic hepatitis (SAH) and chronic alcoholics (ChA) and compared with healthy controls. RESULTS: In the iG model of chronic ASH, IFNγ+ iNKT cells accumulate in their livers compared with pair-fed control mice and activated hepatic iNKT cells show high expression of Fas and FasL. Notably, IFNγ+ iNKT cells are also significantly increased in peripheral blood of ChA patients compared with SAH patients. MAIT cells are significantly reduced in all ALD patients, but CD8+ CD161hi Vα7.2- cells are increased in SAH patients. Although MAIT and CD8+ CD161hi Vα7.2- cells displayed a similar cytokine production profile, the production of IFNγ and TNFα is significantly increased in SAH patients, while significant IL-17A production is found in ChA patients. CONCLUSIONS: We found that the 3 unconventional T cells are activated in ALD patients showing interesting differences in their frequency and cytokine production profile between SAH and ChA patients. In the iG murine model of chronic ASH, iNKT cells are also activated secreting proinflammatory cytokines suggesting their involvement in liver disease.

3.
BMC Infect Dis ; 20(1): 188, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32122317

RESUMO

BACKGROUND: In recent times, Plasmodium vivax (P. vivax) has become a serious threat to public health due to its ability to cause severe infection with fatal outcomes. Its unique biology makes it resilient to control measures that are otherwise effective against P. falciparum. A deeper understanding of P. vivax biology and pathogenesis is, therefore, essential for developing the right control strategies. Proteomics of P. falciparum has been helpful in studying disease biology and elucidating molecular mechanisms involved in the development of disease. However, unlike P. falciparum, proteomics data for P. vivax infection is minimal due to the absence of a continuous culture system. The dependence on clinical samples and animal models has drastically limited P. vivax research, creating critical knowledge gaps in our understanding of the disease. This study describes an in-depth proteomics analysis of P. vivax-infected human plasma and parasite isolates, to understand parasite biology, pathogenesis, and to identify new diagnostic targets for P. vivax malaria. METHODS: A mass-spectrometry- (MS) based proteomics approach (Q Exactive) was applied to analyze human plasma and parasite isolates from vivax malaria patients visiting a primary health centre in India. Additionally, a targeted proteomics assay was standardized for validating unique peptides of most recurring parasite proteins. RESULTS: Thirty-eight P. vivax proteins were detected in human plasma with high confidence. Several glycolytic enzymes were found along with hypothetical, cytoskeletal, ribosomal, and nuclear proteins. Additionally, 103 highly abundant P. vivax proteins were detected in parasite isolates. This represents the highest number of parasite proteins to be reported from clinical samples so far. Interestingly, five of these; three Plasmodium exported proteins (PVX_003545, PVX_003555 and PVX_121935), a hypothetical protein (PVX_083555) and Pvstp1 (subtelomeric transmembrane protein 1, PVX_094303) were found in both plasma and parasite isolates. CONCLUSIONS: A parasite proteomics investigation is essential to understand disease pathobiology and design novel interventions. Control strategies against P. vivax also depend on early diagnosis. This work provides deeper insights into the biology of P. vivax by identifying proteins expressed by the parasite during its complex life-cycle within the human host. The study also reports antigens that may be explored as diagnostic candidates.

4.
Nucleic Acids Res ; 48(5): e26, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32009153

RESUMO

High-throughput chromosome conformation capture (Hi-C) technology enables the investigation of genome-wide interactions among chromosome loci. Current algorithms focus on topologically associating domains (TADs), that are contiguous clusters along the genome coordinate, to describe the hierarchical structure of chromosomes. However, high resolution Hi-C displays a variety of interaction patterns beyond what current TAD detection methods can capture. Here, we present BHi-Cect, a novel top-down algorithm that finds clusters by considering every locus with no assumption of genomic contiguity using spectral clustering. Our results reveal that the hierarchical structure of chromosome is organized as 'enclaves', which are complex interwoven clusters at both local and global scales. We show that the nesting of local clusters within global clusters characterizing enclaves, is associated with the epigenomic activity found on the underlying DNA. Furthermore, we show that the hierarchical nesting that links different enclaves integrates their respective function. BHi-Cect provides means to uncover the general principles guiding chromatin architecture.


Assuntos
Algoritmos , Cromossomos Humanos/química , DNA/genética , Linhagem Celular , Montagem e Desmontagem da Cromatina , Mapeamento Cromossômico , Cromossomos Humanos/ultraestrutura , DNA/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Loci Gênicos , Humanos , Família Multigênica
5.
JCI Insight ; 5(3)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32051339

RESUMO

Chronic alcohol abuse has a detrimental effect on the brain and liver. There is no effective treatment for these patients, and the mechanism underlying alcohol addiction and consequent alcohol-induced damage of the liver/brain axis remains unresolved. We compared experimental models of alcoholic liver disease (ALD) and alcohol dependence in mice and demonstrated that genetic ablation of IL-17 receptor A (IL-17ra-/-) or pharmacological blockade of IL-17 signaling effectively suppressed the increased voluntary alcohol drinking in alcohol-dependent mice and blocked alcohol-induced hepatocellular and neurological damage. The level of circulating IL-17A positively correlated with the alcohol use in excessive drinkers and was further increased in patients with ALD as compared with healthy individuals. Our data suggest that IL-17A is a common mediator of excessive alcohol consumption and alcohol-induced liver/brain injury, and targeting IL-17A may provide a novel strategy for treatment of alcohol-induced pathology.

6.
BMC Med Inform Decis Mak ; 20(1): 6, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914992

RESUMO

BACKGROUND: The ubiquity of electronic health records (EHR) offers an opportunity to observe trajectories of laboratory results and vital signs over long periods of time. This study assessed the value of risk factor trajectories available in the electronic health record to predict incident type 2 diabetes. STUDY DESIGN AND METHODS: Analysis was based on a large 13-year retrospective cohort of 71,545 adult, non-diabetic patients with baseline in 2005 and median follow-up time of 8 years. The trajectories of fasting plasma glucose, lipids, BMI and blood pressure were computed over three time frames (2000-2001, 2002-2003, 2004) before baseline. A novel method, Cumulative Exposure (CE), was developed and evaluated using Cox proportional hazards regression to assess risk of incident type 2 diabetes. We used the Framingham Diabetes Risk Scoring (FDRS) Model as control. RESULTS: The new model outperformed the FDRS Model (.802 vs .660; p-values <2e-16). Cumulative exposure measured over different periods showed that even short episodes of hyperglycemia increase the risk of developing diabetes. Returning to normoglycemia moderates the risk, but does not fully eliminate it. The longer an individual maintains glycemic control after a hyperglycemic episode, the lower the subsequent risk of diabetes. CONCLUSION: Incorporating risk factor trajectories substantially increases the ability of clinical decision support risk models to predict onset of type 2 diabetes and provides information about how risk changes over time.

7.
Environ Monit Assess ; 191(Suppl 3): 797, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989261

RESUMO

In this study, we investigated the relationship between soil properties and litter chemistry in three forest communities, i.e., Sal mixed forest (SMF), dry mixed forest (DMF), and teak plantation forest (TPF), in tropical deciduous forest ecosystem in North India. Fresh leaf litter and soil samples were collected at two soil depths (0-15 and 15-30 cm) from all these three forest communities. Litter bag experiment was also conducted to know differences in litter nutrients after its decomposition. The concentrations (mg kg-1) of different nutrients such as sodium (Na) 2.6, potassium (K) 38.5, calcium (Ca) 425, and carbon (C) 45.54% were highest in fresh litter collected from DMF. Total organic carbon (g kg-1) was significantly higher in SMF (19.23) in comparison to DMF (18.41) and TPF (13.61) at 0-15-cm soil depth. Na, K, Ca, available P, total P, available N, and total N were highest in DMF soil. We observed significantly positive correlation between all nutrients of litter and soil. Although soil bulk density (BD) and particle density (PD) showed their significant negative correlation with litter C, total porosity was positively correlated. Similarly, litter Na has its significant negative correlation with BD and positive correlation with PD. The litter chemistry played a significant role in changing soil pH and TOC. All litter nutrients, except total P, have their significant positive correlation with soil pH. Total P, C, and N of litter have their significant positive correlation with total soil organic carbon. This indicates that litter chemistry and soil properties have specific relation among them despite unique species composition in each forest community.


Assuntos
Ecossistema , Florestas , Solo , Carbono , Monitoramento Ambiental , Índia , Folhas de Planta , Árvores
8.
Environ Monit Assess ; 191(Suppl 3): 796, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989356

RESUMO

Environmental factors along with soil physico-chemical properties play a significant role on the diurnal trend of soil CO2 efflux. Soil CO2 efflux in Indian tropical forests is poorly studied. We studied the soil CO2 efflux in a representative tropical deciduous forest at Katerniaghat Wildlife Sanctuary (KWLS), Uttar Pradesh. The three forest communities namely dry mixed (DMF), Sal mixed (SMF), and Teak plantation (TPF) were selected for measuring soil CO2 efflux in the summer season during April to May 2017 using automated LI-COR 8100 soil CO2 flux system. Soil physico-chemical parameters were also studied in the three abovementioned forest communities. We also measured the different microclimatic variables at forest understorey in all three communities during the summer season. Total day time soil CO2 efflux of 826.70, 1089.24, and 828.94 (µmolCO2 m-2d-1) was observed in TPF, SMF, and DMF respectively. Soil CO2 efflux observed significant differences (P < 0.01) among the three forest communities studied for the summer season in tropical deciduous forest of Terai Himalaya. Average soil CO2 efflux rate (µmol CO2 m-2 s-1) of 4.06 ± 0.36, 5.03 ± 0.45, and 4.37 ± 0.79 was observed in TPF, SMF, and DMF, respectively, which is positively correlated with total organic carbon (TOC) and water holding capacity (WHC) among soil physico-chemical variables. Among microclimatic variables, soil temperature (ST, °C) and air temperature (AT, °C) observed strong positive correlation with day time soil CO2 efflux in all three communities. Significant increase in soil CO2 flux was observed with increasing air and soil temperature (AT and ST) in DMF and SMF. Maximum TOC of 19.23 g Kg-1 was observed in SMF among all communities in the summer season. The result showed that soil CO2 efflux is closely associated with TOC, WHC, AT, and ST for Indian deciduous forest ecosystems.


Assuntos
Dióxido de Carbono , Florestas , Solo , Ecossistema , Monitoramento Ambiental , Índia , Árvores
9.
J Biomol Struct Dyn ; 38(2): 511-523, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30767625

RESUMO

Diabetes is a foremost health problem globally susceptible to increased mortality and morbidity. The present therapies in the antidiabetic class have sound adverse effects and thus, emphasis on the further need to develop effective medication therapy. Peroxisome proliferator-activated receptor alpha-gamma dual approach represents an interesting target for developing novel anti-diabetic drug along with potential anti-hyperlipidimic activity. In the current study, the peroxisome proliferator-activated receptor alpha-gamma agonistic hits were screened by hierarchical virtual screening of drug like compounds followed by molecular dynamics simulation and knowledge-based structure-activity relation analysis. The key amino acid residues of binding pockets of both target proteins were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit. This dual targeted approach of structure based computational technique was undertaken to identify prevalent promising hits for both targets with binding energy and absorption distribution metabolism excretion prediction supported the analysis of their pharmacokinetic potential. In addition, stability analysis using molecular dynamics simulation of the target protein complexes was performed with the most promising dual targeted hit found in this study. Further, comparative analysis of binding site of both targets was done for the development of knowledge-based structure-activity relationship, which may useful for successful designing of dual agonistic candidates. AbbreviationsADMEabsorption distribution metabolism excretionHTVShighthroughput virtual screeningMDmolecular dynamicsMMGBSAmolecular mechanics generalized bonn solvation accessiblePDBprotein data bankPPARperoxisome proliferator-activated receptorRMSDRoot mean square deviationRMSFRoot mean square fluctuationSARstructural activity relationshipSPsimple precisionT2DMTypeII diabetes mellitusXPExtra precisionCommunicated by Ramaswamy H. Sarma.

10.
Mol Reprod Dev ; 87(1): 17-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31737970

RESUMO

Human endometrial epithelium (EE) is composed of a multitude of proteins, amongst which those localized on the plasma membrane [plasma membrane proteins (PMPs)] are of critical relevance in the early stages of implantation. Evidence supports the key role of few PMPs in implantation. However, many remain unidentified, as efforts have not been made till date to generate the plasma membrane proteome of human EE cells, using a gel-free approach. This study presents a protein catalog of the PMP enriched fraction of Ishikawa cell line; often used as an in vitro model for embryo-adhesive EE. Liquid chromatography with tandem mass spectrometry identified 3,598 proteins. Of these, 1,963 proteins were annotated for their membrane localization. Of 1,963 proteins, 1,321 were found to have a transmembrane domain and 43 proteins had glycophosphatidylinositol (GPI) anchor. Extensive data mining revealed endometrial expression of 943 proteins reported in humans and/or rodents. Further, quantitative alterations were observed in the plasma membrane proteome on the perturbation of intracellular trafficking. Silencing of Rab11a (known for its role in plasma membrane organization) expression caused alteration in the abundance of 74 proteins. Caveolin-1 and EpCAM levels were reduced whereas Rab4a abundance increased in the PMP extracts of Rab11a deficient cells, compared with control cells. Briefly, the study reports the identity of several novel plasma membrane-localized proteins. A major spin-off of the study is the identification of novel proteins trafficked by Rab11a to the plasma membrane. Targeted analysis of novel PMPs may reveal their specific roles in endometrial receptivity and implantation.

11.
Chemosphere ; 240: 124944, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726591

RESUMO

The present study explores the potential of two chromium tolerant and plant growth promoting bacterial strains, Klebsiella sp. and Enterobacter sp. in luxuriant growth of tomato plants under chromium stress conditions. For the assessment of potentiality of the two selected strains, a pot scale experiment was setup with tomato plant under different levels of chromium contamination. In pot experiment, different plant growth parameters, oxidative stress tolerance and chromium bioremediation potential were studied upon inoculation of the selected bacterial strains. The results of pot experiment showed that both the strains were effective in promotion of plant growth and enhanced the plant biomass but Enterobacter sp. was more prominent in enhancement of root length, shoot length, fresh and dry weight, and nutrient uptake in tomato plant. The enhancement of enzymes to combat oxidative stress in tomato plant under chromium stress was also observed for both the strains. Both strains enhanced the levels of superoxide dismutase, catalase, peroxidase, total phenolic, and ascorbic acid in tomato plant under different levels of chromium stress conditions. The chromium phytoremediation potential of tomato plant upon inoculation of both the strains was also studied. The results of phytoremediation showed greater chromium accumulation in roots with poor translocation in shoot upon inoculation of Klebsiella sp. while no significant enhancement in chromium uptake by tomato plant was observed on inoculation of Enterobacter sp. compared to control. Thus, these two strains can effectively be used in luxuriant growth of tomato plant under metal stress conditions.


Assuntos
Cromo/toxicidade , Enterobacter/fisiologia , Klebsiella/fisiologia , Lycopersicon esculentum/fisiologia , Poluentes do Solo/toxicidade , Biodegradação Ambiental , Biomassa , Catalase/metabolismo , Enterobacter/metabolismo , Klebsiella/metabolismo , Lycopersicon esculentum/efeitos dos fármacos , Lycopersicon esculentum/microbiologia , Estresse Oxidativo , Desenvolvimento Vegetal , Raízes de Plantas/metabolismo , Superóxido Dismutase/metabolismo
12.
Org Biomol Chem ; 17(48): 10245-10250, 2019 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-31793609

RESUMO

A general and simple metal-free protocol for expedient C-H functionalization leading to the regioselective generation of C-5 chalcogenated 8-aminoquinoline analogues in up to 90% yield at room temperature (25 °C) has been established. This methodology is an eco-friendly approach to the atom-economical utilization of diaryl/dialkyl chalcogenides for direct access to chalcogenated quinolines and is scalable to the gram scale without considerable decrease in the yield of the product. It represents a practical alternative to the existing metal-catalyzed functionalization of 8-aminoquinoline derivatives with broad functional group tolerance. The controlled experiments suggest that the reaction possibly proceeds through an ionic pathway at room temperature. Furthermore, the potentiality for the functionalization of free amines in chalcogenated-8-aminoquinolines provides an attractive perspective for further elaboration of the amine substituent through chemical manipulations. The applicability of the standardized method has been augmented through late-stage antimalarial drug diversification of primaquine analogues.


Assuntos
Aminoquinolinas/síntese química , Aminas/química , Catálise , Iodo/química , Estrutura Molecular , Oxirredução , Ácido Selênico/química , Solventes/química , Estereoisomerismo , Ácidos Sulfênicos/química
13.
Artigo em Inglês | MEDLINE | ID: mdl-31679802

RESUMO

The effectiveness of herbs for the management of chemically induced hepatotoxicity has been discussed by many researchers. However, there is a paucity of compressive literature on the significance of hepatoprotective plants for the management of anti-TB drug induced toxicity. Anti-TB drugs have been reported to causes hepatic damage, due to which, many patients across the globe discontinued the treatment. Medicinal plants have multiple therapeutic effects. The assessment of biological activity of plants against Mycobacterium and its use for hepatic recovery provides an effective treatment approach. Traditionally used medicinal plants are the rich source of phytochemicals and secondary metabolites. These compounds can restore normal function, enzymatic activity and structure of hepatic cells against anti-TB drug induced hepatotoxicity. The present review covers comprehensive details on different hepatoprotective and antimycobacterial plants studied during past few decades so that potential adjuvants can be studied for Tuberculosis chemotherapy.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31587164

RESUMO

Thermal power generating industries affect the surrounding environment in various ways. Fly ash escapes along with flue gases and can be found in undesirable quantities in soil and water sources in the region. The water quality of an area must be evaluated regularly to ensure the quality of potable water. The present study evaluates the pre-monsoon and post-monsoon concentrations of several important physico-chemical parameters and heavy-metal contents of groundwater samples collected from sites near the Koradi Thermal Power Plant, a major source of power generation in the Nagpur Region. The maximum amount of total dissolved solids observed during the two seasons studied were 1571 mg/l and 1591 mg/l which is within the desirable limit implying that fly ash contamination did not affect this water quality parameter. The total hardness of samples from GW-3, GW-5 and GW-9 were 844 mg/l, 775 mg/l and 675 mg/l during pre-monsoon season, while GW-3 and GW-5 along with GW-4 continued to show high levels of total hardness at 1015 mg/l, 741 mg/l and 650 mg/l, respectively. These values are higher than the permissible limit due to the high levels of ions of bicarbonate, calcium, sodium and sulphate derived from fly ash leachate. Statistical analysis showed that sulphides, total hardness, electrical conductivity and total dissolved solids were the significant water quality parameters of the region. The evaluation of the parameters found that the three water sources (GW-3, GW-5 and GW-9) out of 10 are the most affected groundwater sources of fly ash pollution.

15.
J Immunol ; 203(8): 2150-2162, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31554695

RESUMO

Hepatic immune system is uniquely challenged to mount a controlled effector response to pathogens while maintaining tolerance to diet and microbial Ags. We have identified a novel population of innate-like, unconventional CD8αα+TCRαß+ T cells in naive mice and in human peripheral blood, called CD8αα Tunc, capable of controlling effector T cell responses. They are NK1.1+ (CD161+ in human), express NK-inhibitory receptors, and express the promyelocytic leukemia zinc finger (PLZF) transcription factor that distinguishes them from conventional CD8+ T cells. These cells display a cytotoxic phenotype and use a perforin-dependent mechanism to control Ag-induced or T cell-mediated autoimmune diseases. CD8αα Tunc are dependent upon IL-15/IL-2Rß signaling and PLZF for their development and/or survival. They are Foxp3-negative and their regulatory activity is associated with a functionally distinct Qa-1b-dependent population coexpressing CD11c and CD244. A polyclonal TCR repertoire, an activated/memory phenotype, and the presence of CD8αα Tunc in NKT- and in MAIT-deficient as well as in germ-free mice indicates that these cells recognize diverse self-protein Ags. Our studies reveal a distinct population of unconventional CD8+ T cells within the natural immune repertoire capable of controlling autoimmunity and also providing a new target for therapeutic intervention.

16.
Nat Commun ; 10(1): 4274, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537791

RESUMO

Genetic interactions have been reported to underlie phenotypes in a variety of systems, but the extent to which they contribute to complex disease in humans remains unclear. In principle, genome-wide association studies (GWAS) provide a platform for detecting genetic interactions, but existing methods for identifying them from GWAS data tend to focus on testing individual locus pairs, which undermines statistical power. Importantly, a global genetic network mapped for a model eukaryotic organism revealed that genetic interactions often connect genes between compensatory functional modules in a highly coherent manner. Taking advantage of this expected structure, we developed a computational approach called BridGE that identifies pathways connected by genetic interactions from GWAS data. Applying BridGE broadly, we discover significant interactions in Parkinson's disease, schizophrenia, hypertension, prostate cancer, breast cancer, and type 2 diabetes. Our novel approach provides a general framework for mapping complex genetic networks underlying human disease from genome-wide genotype data.


Assuntos
Redes Reguladoras de Genes/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Modelos Genéticos , Neoplasias da Mama/genética , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Hipertensão/genética , Masculino , Transtornos Parkinsonianos/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética , Esquizofrenia/genética
17.
Chemistry ; 25(53): 12303-12307, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31373735

RESUMO

Triplex forming oligonucleotides are used as a tool for gene regulation and in DNA nanotechnology. By incorporating artificial nucleic acids, target affinity and biological stability superior to that of natural DNA may be obtained. This work demonstrates how a chimeric clamp consisting of acyclic (L)-threoninol nucleic acid (aTNA) and DNA can bind DNA and RNA by the formation of a highly stable triplex structure. The (L)-aTNA clamp is released from the target again by the addition of a releasing strand in a strand displacement type of reaction. It is shown that the clamp efficiently inhibits Bsu and T7 RNA polymerase activity and that polymerase activity is reactivated by displacing the clamp. The clamp was successfully applied to the regulation of luciferase expression by reversible binding to the mRNA. When targeting a sequence in the double stranded plasmid, 40 % downregulation of protein expression is achieved.


Assuntos
RNA Polimerases Dirigidas por DNA/química , DNA/química , Ácidos Nucleicos/química , RNA/química , Proteínas Virais/química , Amino Álcoois/química , Butileno Glicóis/química , RNA Polimerases Dirigidas por DNA/metabolismo , RNA Polimerases Dirigidas por DNA/farmacologia , Proteínas Virais/metabolismo , Proteínas Virais/farmacologia
18.
Stud Health Technol Inform ; 264: 288-292, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437931

RESUMO

Different analytic techniques operate optimally with different types of data. As the use of EHR-based analytics expands to newer tasks, data will have to be transformed into different representations, so the tasks can be optimally solved. We classified representations into broad categories based on their characteristics, and proposed a new knowledge-driven representation for clinical data mining as well as trajectory mining, called Severity Encoding Variables (SEVs). Additionally, we studied which characteristics make representations most suitable for particular clinical analytics tasks including trajectory mining. Our evaluation shows that, for regression, most data representations performed similarly, with SEV achieving a slight (albeit statistically significant) advantage. For patients at high risk of diabetes, it outperformed the competing representation by (relative) 20%. For association mining, SEV achieved the highest performance. Its ability to constrain the search space of patterns through clinical knowledge was key to its success.


Assuntos
Mineração de Dados , Registros Eletrônicos de Saúde
19.
Sci Rep ; 9(1): 10455, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31320739

RESUMO

It is reported that coal consumption in the Asia-Pacific region is going to increase to about 87.2 percent by 2035. Management of coal combustion residues (CCRs) generated by industries is a major bottleneck towards handling the repercussions of coal usage. The present study investigates a management technique for these potentially hazardous wastes by means of vermicomposting. In the present investigation, studies were made on the effects of various concentrations of vermicomposted fly ash (VCF) added to agricultural soil, on the growth and yield of tomato (Lycopersicon esculentum Mill.) and brinjal (Solanum melongena L.) plants. The toxicity of trace elements in VCF were estimated using coefficient of pollution and potential ecological risk index, which revealed no apparent risks to the environment. A gradual increase in VCF concentrations in the agricultural soil improved the physico-chemical properties, enzymatic activities, microbial biomass, carbon and microbial population upto 90 days after sowing of seeds. The VCF amendments significantly (p < 0.05) improved the soil quality (2.86% nitrogen and 1.05% Phosphorous) and germination percentage (82.22%) of seeds in L. esculentum and also in S. melongena. The results of this study reveal that, CCRs can be effectively managed in agriculture specially in developing economies.

20.
AMIA Jt Summits Transl Sci Proc ; 2019: 630-638, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31259018

RESUMO

The ability to assess data quality is essential for secondary use of EHR data and an automated Healthcare Data Quality Framework (HDQF) can be used as a tool to support a healthcare organization's data quality initiatives. Use of a general purpose HDQF provides a method to assess and visualize data quality to quickly identify areas for improvement. The value of the approach is illustrated for two analytics use cases: 1) predictive models and 2) clinical quality measures. The results show that data quality issues can be efficiently identified and visualized. The automated HDQF is much less time consuming than a manual approach to data quality and the framework can be rerun repeatedly on additional datasets without much effort.

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