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1.
Microb Pathog ; 142: 104101, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32109568

RESUMO

The pond has a complex microbial ecosystem, including microorganisms in water and sediment, which plays an important role in the health of fish and water quality. The microbial community structure in the ponds can be easily affected by many factors. However, not much is known about the role of different aquaculture model and fish on the microbial community structure in ponds. The purpose of the study was to investigate the microbial diversity and composition of the ponds with different aquaculture model and fish by high-throughput sequencing. A total of 3835072 valid sequences were achieved from 60 samples. Additionally, 2064 and 1917 core OTUs were observed in water and sediment samples, respectively. Our results suggested that sediment samples have a higher abundance and diversity of microbial community than water samples. In all the samples, the four most dominant phyla were Proteobacteria, Cyanobacteria, Actinomycetes and Bacteroides. At the genus level, hgcI_clade and CL500-29_marine_group were the dominant bacteria shared by the water samples and sediment samples. In addition, more bacteria related to eutrophication were found in the group of BF, BC and HSB, which suggested that these ponds may have been eutrophicated. In conclusion, the present study revealed the differences in the structure and diversity of microbial communities in ponds with different aquaculture model and fish. Furthermore, changes in typical bacteria of the ponds contribute to detect water quality and prevent water eutrophication.

2.
Ecotoxicol Environ Saf ; 190: 110126, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31918251

RESUMO

Tetramethyl thiuram disulfide (thiram) is a dithiocarbamate pesticide used for crop protection and storage. But, it's widespread utilization is associated with deleterious growth plate cartilage disorder in broilers termed as avian tibial dyschondroplasia (TD). TD results in non-mineralized and less vascularized proximal tibial growth plate cartilage causing lameness and poor growth performance. This study investigated the therapeutic potential of puerarin against thiram toxicity in TD affected chickens. One-day-old broiler chickens (n = 240) were alienated into three equal groups i.e. control, TD and puerarin (n = 80) and were offered standard feed. Additionally, TD and puerarin groups were offered thiram at 50 mg/kg of feed from 4 to 7 days for TD induction followed by puerarin therapy at 120 mg/kg to puerarin group only from 8 to 18 days for TD treatment. Thiram feeding to TD and puerarin group chickens caused lameness, mortality, and increased the aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) levels and growth plate (GP) size and upregulated HIF-1α expression. Besides, the production parameters, alkaline phosphatase (ALP), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels and the expressions of TIMP-3 and BCL-2 were decreased (p < 0.05). Puerarin alleviated lameness, enhanced angiogenesis and growth performance and serum and antioxidant enzymes, decreased apoptosis and recuperated GP width by significantly downregulating HIF-1α and upregulating the TIMP-3 and BCL-2 mRNA and protein expressions in puerarin group chickens (p < 0.05). In conclusion, the toxic effects associated with thiram can be mitigated using puerarin.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31960246

RESUMO

Tetramethyl thiuram disulfide (thiram) is widely used in agricultural production as an insecticide and fungicide, which can also lead to tibial dyschondroplasia (TD) in poultry. TD is characterized by leg disorders and growth performance retardation, and no targeted drugs have been found to treat TD until now. Therefore, the objective of the present study was to explore the ameliorative effect of traditional Chinese medicine naringin on thiram-induced TD chickens. A total of 180 one-day-old Arbor Acres (AA) broiler chickens were randomly divided into three equal groups (n = 60): control group (standard diet), thiram-induced group (thiram 50 mg/kg from day 3 to day 7), and naringin-treated group (naringin 30 mg/kg from day 8 to day 18). During the 18-day experiment, the growth performance, tibial bone parameters, antioxidant property of liver, serum biochemical changes and clinical symptoms were recorded to evaluate the protective effect of naringin in thiram-induced TD broiler chickens. Additionally, mRNA expressions and protein levels of Ihh and PTHrP genes were determined via quantitative real-time polymerase chain reaction and western blot. Administration of naringin showed significant results by alleviating lameness, increased growth performance, recuperated growth plate (GP) width, and improved functions and antioxidant enzyme level of liver in broilers affected by TD. Moreover, naringin treatment restored the development of damaged tibia bone via downregulating Ihh and upregulating PTHrP mRNA and protein expressions. In conclusion, our study determines naringin could be used as an effective medicine to treat TD.

4.
Elife ; 92020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31939735

RESUMO

Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and function, through BUD23-dependent ribosome generation. BUD23 was required for ribosome maturation, normal 18S/28S stoichiometry and modulated the translation of mitochondrial transcripts in human A549 cells. Deletion of Bud23 in murine cardiomyocytes reduced mitochondrial content and function, leading to severe cardiomyopathy and death. We discovered that BUD23 selectively promotes ribosomal interaction with low GC-content 5'UTRs. Taken together we identify a critical role for BUD23 in bioenergetics gene expression, by promoting efficient translation of mRNA transcripts with low 5'UTR GC content. BUD23 emerges as essential to mouse development, and to postnatal cardiac function.

5.
Proc Natl Acad Sci U S A ; 117(3): 1543-1551, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31900362

RESUMO

The circadian clock regulates many aspects of immunity. Bacterial infections are affected by time of day, but the mechanisms involved remain undefined. Here we show that loss of the core clock protein BMAL1 in macrophages confers protection against pneumococcal pneumonia. Infected mice show both reduced weight loss and lower bacterial burden in circulating blood. In vivo studies of macrophage phagocytosis reveal increased bacterial ingestion following Bmal1 deletion, which was also seen in vitro. BMAL1-/- macrophages exhibited marked differences in actin cytoskeletal organization, a phosphoproteome enriched for cytoskeletal changes, with reduced phosphocofilin and increased active RhoA. Further analysis of the BMAL1-/- macrophages identified altered cell morphology and increased motility. Mechanistically, BMAL1 regulated a network of cell movement genes, 148 of which were within 100 kb of high-confidence BMAL1 binding sites. Links to RhoA function were identified, with 29 genes impacting RhoA expression or activation. RhoA inhibition restored the phagocytic phenotype to that seen in control macrophages. In summary, we identify a surprising gain of antibacterial function due to loss of BMAL1 in macrophages, associated with a RhoA-dependent cytoskeletal change, an increase in cell motility, and gain of phagocytic function.

6.
Environ Sci Pollut Res Int ; 27(6): 6628-6636, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31873907

RESUMO

Thiram is a widely known tibial dyschondroplasia (TD) inducer. TD, a common metabolic cartilage disease, presents in rapidly growing poultry birds. There are evidences that miRNAs are involved in diverse aspects of normal skeletal development, but very less is known about the role of miRNAs in TD. Therefore, this study aimed to determine which genes and pathways show differential expression between TD suffered chickens and normal chickens. We collected growth plates from ten-days-old TD chickens and control chickens and performed high-throughput RNA sequencing (RNA-Seq). Afterwards, target prediction, GO annotation and KEGG pathway analysis were carried out to understand the role of DEMs (differentially expressed microRNAs). We obtained 96,884,760 and 94,574,290 clean reads and identified 17 significant DEMs between the TD and control groups. Functional enrichment analysis of DEMs indicated that the putative targets of miRNAs were remarkably enriched in bone-related pathways, such as Notch, MAPK and Autophagy. Overall, this study provides detailed understanding about the pathogenesis of thiram induced TD and new insights towards the molecular mechanism of miRNAs.

7.
Biomolecules ; 9(12)2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31779199

RESUMO

Tibial dyschondroplasia (TD) negatively affects broilers all over the world, in which the accretion of the growth plate (GP) develops into tibial proximal metaphysis. Plastrum testudinis extract (PTE) is renowned as a powerful antioxidant, anti-inflammatory, and bone healing agent. The current study was conducted to evaluate the efficacy of PTE for the treatment of thiram-induced TD chickens. Broilers (day old; n = 300) were raised for 3 days with normal feed. On the 4th day, three groups (n = 100 each) were sorted, namely, the control (normal diet), TD, and PTE groups (normal diet+ thiram 50 mg/kg). On the 7th day, thiram was stopped in the TD and PTE group, and the PTE group received a normal diet and PTE (30 mg/kg/day). Plastrum testudinis extract significantly restored (p < 0.05) the liver antioxidant enzymes, inflammatory cytokines, serum biochemicals, GP width, and tibia weight as compared to the TD group. The PTE administration significantly increased (p < 0.05) growth performance, vascularization, AKT (serine/threonine-protein kinase), and PI3K expressions and the number of hepatocytes and chondrocytes with intact nuclei were enhanced. In conclusion, PTE has the potential to heal TD lesions and act as an antioxidant and anti-inflammatory drug in chickens exposed to thiram via the upregulation of AKT and PI3K expressions.

8.
Microb Pathog ; 137: 103760, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31562897

RESUMO

The aim of this study was to evaluate the antibacterial potential of Lactobacillus screened from Tibetan yaks on clinical symptoms and intestinal microflora in enteroinvasive Escherichia coli (EIEC) induced mice model. In vitro study, Lactobacillus reuteri (LR1) exhibited stronger resistance to acid and bile and inhibited the growth of EIEC than Lactobacillus mucosae (LM1). The mice were randomly divided into four groups i.e. the LR1 group (LR1 1 × 109 CFU/day), LM1 group (LM1 1 × 109 CFU/day), blank control group and control group. Mice in control, LR1, and LM1 groups were challenged with EIEC on day 23. The body weight in the control and LM1 groups were significantly decreased after the infection with EIEC (P < 0.05), whereas the body weight of mice in the LR1 group did not change significantly (P > 0.05). The lowest diarrhea rate was recorded in the LR1 group after infection with EIEC. The results showed that the number of pathogens in the control group was higher than that in the experimental groups. The sequence analysis and OTU classification showed that the duodenum, ileum, and cecum of mice in the LR1 group had the highest number of OTUs compared with other groups. Whereas, the diversity analysis showed that in duodenum, ileum and cecum of mice in the LR1 group had the highest abundance and diversity. The composition of intestinal microbes indicated the presence of high proportions of Firmicutes, Proteobacteria and Bacteroidetes. Heat map analysis indicated high abundance of Bdello vibrio in the duodenum of mice in the LR1 group, while many pathogens were found in the different part of intestines in the control group, such as Streptococcus, Clostridium and Pseudomonas. In conclusion, pre-supplementation of LR1 alleviate the clinical symptoms caused by E. coli, and promote a healthy gut flora.

9.
Microb Pathog ; 136: 103671, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31437575

RESUMO

Yaks are an aboriginal breed of the Qinghai-Tibet plateau (3000 m), which are highly adaptable to cold and hypoxic environments. It is noticed that hypoxia and hypothermia can induce changes in intestinal microbial structure in animals. Increasing evidences suggested that probiotics supplementation can improve the balance of gut microbiota of animals. However, so far, very few studies have emphasized on the probiotics isolated from yaks in the Qinghai-Tibet Plateau. Therefore, a potential probiotic strain Bacillus velezensis was isolated from yaks. In the present study, a total of 18 Kunming mice (15-18 g) were equally distributed into two groups; control and probiotic treated groups (1 × 109 CFU/day). During the experimental period, all the mice from both groups were given standard normal diet ad libitum. At the end of the experiment, mice were euthanized and the intestines (duodenum, jejunum, ileum, and cecum) were removed for high-throughput sequencing. The results demonstrated that Bacillus velezensis supplementation showed beneficial effects on the gut microbiota of mice. Specifically, Bacillus velezensis supplementation increased the population of Lactobacillus and Ruminococcus in the duodenum, and Candidatus Arthromitus in the jejunum. Additionally, Acinetobacter in the duodenum and Helicobacter in the cecum were decreased after feeding Bacillus velezensis. Altogether, these findings suggested that Bacillus velezensis isolated from Tibetan yaks can improve gut microbiota of mice.

10.
Antioxidants (Basel) ; 8(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443437

RESUMO

Avian tibial dyschondroplasia affects fast growing broiler chickens accounting for almost 30% of leg ailments in broilers. The present project was designed to assess the efficacy of osthole against avian tibial dyschondroplasia (TD). Two hundred and forty chickens were equally allocated into control, TD and osthole groups (n = 80). The TD and osthole group chickens were challenged with tetramethylthiuram disulfide (thiram) at 50 mg/kg of feed from 4-7 days, followed by osthole administration at 20 mg/kg orally to the osthole group only from 8-18 days. Thiram feeding resulted in lameness, increased mortality, and decreased production parameters, alkaline phosphatase (ALP), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-PX) levels, along with significantly increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) levels, and growth plate size. Moreover, the genes and protein expressions of BMP-2 and RUNX-2 were significantly down-regulated in TD affected chickens (p < 0.05). Osthole administration showed promising results by alleviating lameness; increased ALP, SOD, T-AOC, and GSH-Px levels; and decreased the AST, ALT, and MDA levels significantly. It restored the size of the growth plate and significantly up-regulated the BMP-2 and RUNX-2 expressions (p < 0.05). In conclusion, the oxidative stress and growth plate anomalies could be assuaged using osthole.

11.
Cell Rep ; 27(11): 3215-3227.e6, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31189106

RESUMO

Embryonic stem cells (ESCs) must transition through a series of intermediate cell states before becoming terminally differentiated. Here, we investigated the early events in this transition by determining the changes in the open chromatin landscape as naive mouse ESCs transition to epiblast-like cells (EpiLCs). Motif enrichment analysis of the newly opening regions coupled with expression analysis identified ZIC3 as a potential regulator of this cell fate transition. Chromatin binding and genome-wide transcriptional profiling following Zic3 depletion confirmed ZIC3 as an important regulatory transcription factor, and among its targets are genes encoding a number of transcription factors. Among these is GRHL2, which acts through enhancer switching to maintain the expression of a subset of genes from the ESC state. Our data therefore place ZIC3 upstream of a set of pro-differentiation transcriptional regulators and provide an important advance in our understanding of the regulatory factors governing the early steps in ESC differentiation.

12.
Nat Prod Res ; : 1-5, 2018 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-30582365

RESUMO

Using a dual culture antagonism assay, Aspergillus niger exhibited 51.5 ± 1.1% growth inhibition against Fusarium oxysporum f.sp. lycopersici, the wilt pathogen of tomato. For enhanced production of antifungal metabolites, nutrient optimization was performed and in vitro well-diffusion antifungal assays demonstrated that crude extract obtained from GPYB culture showed a maximum zone of inhibition (8.8 ± 0.4 mm) against the wilt pathogen, which is corroborated by the comparative LCMS profiles of the extracts from all three media i.e. GPYB, YEB and PDB. Two known compounds, Asperazine (m/z 665 [M + H]+) and Nigerone (m/z 571 [M + H]+), were isolated from A. niger and their antifungal activity is reported here for the first time. In MIC experiments, Asperazine and Nigerone inhibited the pathogen at 60 and 80 µg·mL-1 respectively. Molecular docking studies of Nigerone and Asperazine with F. oxysporum tomatinase showed five and six binding interactions respectively.

13.
Nutr Hosp ; 35(5): 1145-1152, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30307299

RESUMO

INTRODUCTION: it has previously been shown that parasitic infections (PI) have deleterious effects on the nutritional status of the host, particularly among young children. OBJECTIVE: the objective of this study was to estimate the severity of the problem of malnutrition and anemia in association with PI in preschool children and to identify the possible risk factors that contribute to these health problems. METHODS: four hundred and thirty-seven mother-child pairs were randomly selected from rural areas of Peshawar, Pakistan. Children with visible and invisible worms were identified. The nutritional status of the respondents was evaluated. Structured questionnaires were used to collect data on relevant parameters. Appropriate statistical tests were used to analyze the data. RESULTS: the average age of the children was 24 ± 10 months. A total of 120 (27.5%) fecal samples of children tested positive for several parasites. Of the total, 267 (61%), 205 (47%), 109 (25%) and 140 (32%) children were anemic, stunted, wasted and underweight, respectively. The majority of wasted children (59% wasted versus 41% normal) and anemic (66% anemic versus 34% non-anemic) were infected with parasites (p < 0.05). Independent factors related to child anemia included child age, family size, mothers' awareness of overall child healthcare, and PIs. PIs were independent risk factors for malnutrition and general child wasting. Sociodemographic, parental and child-related risk factors for PIs included mothers' poor nutritional status and awareness level regarding overall child healthcare, fathers' formal education, child's pica habit, child's age, open sewage system in the houses and family size. CONCLUSION: in general, malnutrition and anemia were highly prevalent in children in association with PI.


Assuntos
Anemia/epidemiologia , Desnutrição/epidemiologia , Doenças Parasitárias/epidemiologia , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Desnutrição/parasitologia , Estado Nutricional , Paquistão/epidemiologia , Doenças Parasitárias/parasitologia , Prevalência , Fatores de Risco , População Rural
14.
Nutr. hosp ; 35(5): 1145-1152, sept.-oct. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-179921

RESUMO

Introduction: it has previously been shown that parasitic infections (PI) have deleterious effects on the nutritional status of the host, particularly among young children. Objective: the objective of this study was to estimate the severity of the problem of malnutrition and anemia in association with PI in preschool children and to identify the possible risk factors that contribute to these health problems. Methods: four hundred and thirty-seven mother-child pairs were randomly selected from rural areas of Peshawar, Pakistan. Children with visible and invisible worms were identified. The nutritional status of the respondents was evaluated. Structured questionnaires were used to collect data on relevant parameters. Appropriate statistical tests were used to analyze the data. Results: the average age of the children was 24 ± 10 months. A total of 120 (27.5%) fecal samples of children tested positive for several parasites. Of the total, 267 (61%), 205 (47%), 109 (25%) and 140 (32%) children were anemic, stunted, wasted and underweight, respectively. The majority of wasted children (59% wasted versus 41% normal) and anemic (66% anemic versus 34% non-anemic) were infected with parasites (p < 0.05). Independent factors related to child anemia included child age, family size, mothers’ awareness of overall child healthcare, and PIs. PIs were independent risk factors for malnutrition and general child wasting. Sociodemographic, parental and child-related risk factors for PIs included mothers' poor nutritional status and awareness level regarding overall child healthcare, fathers' formal education, child's pica habit, child’s age, open sewage system in the houses and family size. Conclusion: in general, malnutrition and anemia were highly prevalent in children in association with PI


Introducción: se ha demostrado previamente que las infecciones parasitarias (IP) tienen efectos nocivos sobre el estado nutricional del huésped, particularmente entre los niños pequeños. Objetivo: el presente estudio tuvo como objetivo estimar la gravedad del problema de desnutrición y anemia en asociación con IP en niños en edad preescolar e identificar los posibles factores de riesgo que contribuyen a estos problemas de salud. Métodos: se seleccionaron al azar 437 parejas madre-hijo de zonas rurales de Peshawar, Pakistán. Se identificaron niños con gusanos visibles y no visibles. Se evaluó el estado nutricional de los encuestados. Se usaron cuestionarios estructurados para recopilar datos sobre parámetros relevantes y pruebas estadísticas apropiadas para analizar los datos. Resultados: la edad promedio de los niños fue de 24 ± 10 meses. Un total de 120 (27,5%) muestras fecales de niños dieron positivo para varios parásitos. Del total, 267 (61%), 205 (47%), 109 (25%) y 140 (32%) niños eran anémicos, presentaban atrofia, desgaste y bajo peso, respectivamente. Los factores independientes relacionados con la anemia infantil incluyen la edad del niño, el tamaño de la familia, el nivel de conciencia de las madres sobre el cuidado de la salud general del niño y los IP. Los IP fueron factores de riesgo independientes para la malnutrición y el desgaste general de los niños. Los factores de riesgo independientes para los IP incluyeron un estado nutricional deficiente de las madres, bajo nivel de conciencia de las madres con respecto a la atención médica general del niño, la educación formal de los padres, el patrón pica en niños, la edad, el sistema de alcantarillado abierto en las casas y el tamaño de la familia. Conclusión: en general, la malnutrición y la anemia fueron muy prevalentes en los niños en asociación con IP


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Anemia/epidemiologia , Desnutrição/epidemiologia , Doenças Parasitárias/epidemiologia , Estudos Transversais , Desnutrição/parasitologia , Estado Nutricional , Paquistão/epidemiologia , Doenças Parasitárias/parasitologia , Prevalência , Fatores de Risco , População Rural
15.
J Clin Invest ; 128(10): 4454-4471, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30179226

RESUMO

The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day. Temporal segregation of GC action was underpinned by a physical interaction of GR with the circadian transcription factor REVERBa and co-binding with liver-specific hepatocyte nuclear transcription factors (HNFs) on chromatin. REVERBa promoted efficient GR recruitment to chromatin during the day, acting in part by maintaining histone acetylation, with REVERBa-dependent GC responses providing segregation of carbohydrate and lipid metabolism. Importantly, deletion of Reverba inverted circadian liver GC sensitivity and protected mice from hepatosteatosis induced by chronic GC administration. Our results reveal a mechanism by which the circadian clock acts through REVERBa in liver on elements bound by HNF4A/HNF6 to direct GR action on energy metabolism.


Assuntos
Cromatina/metabolismo , Relógios Circadianos/efeitos dos fármacos , Fígado Gorduroso/metabolismo , Glucocorticoides/efeitos adversos , Fígado/metabolismo , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Animais , Cromatina/genética , Cromatina/patologia , Relógios Circadianos/genética , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Glucocorticoides/farmacologia , Células HEK293 , Humanos , Fígado/patologia , Camundongos , Camundongos Knockout , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo
16.
Pak J Pharm Sci ; 31(1(Suppl.)): 305-309, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29386158

RESUMO

Hymenolepiasis is a helminthic and occasionally fatal disease of human imposing heavy economic losses to human society. Present study was aimed to diagnose the school children for the prevalence and control of Hymenolepiasis. A school based cross-sectional analysis of stool samples collected from 188 children aged 06-15 years was carried out (February to June 2016). Two stool samples were collected from each student before diagnosing and after treatment. The samples were fixed in 10% formalin and observed under the light microscope using the methods of direct smear in Lugol's solution, normal saline and flotation techniques. On the basis of drugs accessibility all the H. nana infected children were divided in to 2- groups. Children in group A were treated with albendazole (bendazol) 400mg once orally, group B was treated with albendazole (zentel) 200mg orally. Eggs per gram of faeces were counted in each group before and after treatment. Of the 188 children, current study reveals only 6.08% (n=18/296) infection with H.nana and 10.5% (n=16/151) were diagnosed with co infections. The % efficacy of albendazole (Zentel) and albendazole (bendazol) against Hymenolepis nana infection was reported as 83% and 75% respectively. Present study was concluded that albendazole (zentel) is the drug of choice for the treatment of hymenolepiasis in children.


Assuntos
Albendazol/uso terapêutico , Anticestoides/uso terapêutico , Himenolepíase/tratamento farmacológico , Administração Oral , Adolescente , Albendazol/administração & dosagem , Animais , Anticestoides/administração & dosagem , Criança , Estudos Transversais , Fezes/parasitologia , Feminino , Humanos , Himenolepíase/epidemiologia , Hymenolepis nana/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Paquistão/epidemiologia , Cooperação do Paciente , Resultado do Tratamento
17.
PeerJ ; 5: e3742, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28970965

RESUMO

We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα), RNA polymerase (Pol II) and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimulated with estrogen. A Bayesian classifier was developed which uses the correlation of temporal binding patterns at enhancers and promoters and genomic proximity as features to predict interactions. This method was trained using experimentally determined interactions from the same system and was shown to achieve much higher precision than predictions based on the genomic proximity of nearest ERα binding. We use the method to identify a genome-wide confident set of ERα target genes and their regulatory enhancers genome-wide. Validation with publicly available GRO-Seq data demonstrates that our predicted targets are much more likely to show early nascent transcription than predictions based on genomic ERα binding proximity alone.

18.
Poult Sci ; 96(9): 3086-3095, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28854756

RESUMO

Mycoplasma synoviae (MS) is an important pathogen of domestic poultry and is prevalent in commercial layers. Avian influenza (AI; H9N2) infections are emerging respiratory problems causing huge economic losses to the poultry industry, especially in the presence of other co-infecting pathogens. The possible role of MS vaccination and response to AI (H9N2) virus in commercial layers was evaluated during this study. Experimental commercial layers were divided into different groups which were identified as follows: non-vaccinated non-challenged (NVNC), non-vaccinated challenged (NVC), vaccinated non-challenged (VNC), and vaccinated challenged (VC). The titer of AI antibodies was measured pre- and post-challenge to confirm experimental infection. Infected layers showed clinical signs of differing severity, with the most prominent disease signs and mortality (25%) appearing in layers of the VC group. Moreover, the layers in VC group showed a significant decrease in weight and enhanced gross lesions. All infected layers showed positive results for virus shedding; however, the pattern of virus shedding was different, with layers of VC group showing more pronounced virus excretion than the layers in the NVC group. In addition, layers of VC group showed significantly reduced antibody responses and interferon gene expression when compared with the layers of NVC group. The present study revealed that MS vaccine could facilitate replication of avian influenza viruses and thus avian influenza virus infections can be worse after MS vaccination, especially in AIV-endemic areas.


Assuntos
Vacinas Bacterianas/administração & dosagem , Galinhas , Imunidade Inata/efeitos dos fármacos , Vírus da Influenza A Subtipo H9N2/imunologia , Influenza Aviária/imunologia , Doenças das Aves Domésticas/imunologia , Replicação Viral/efeitos dos fármacos , Animais , Feminino , Mycoplasma synoviae/fisiologia , Distribuição Aleatória , Eliminação de Partículas Virais
19.
PLoS Comput Biol ; 13(9): e1005731, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28922354

RESUMO

The bacterial Lux system is used as a gene expression reporter. It is fast, sensitive and non-destructive, enabling high frequency measurements. Originally developed for bacterial cells, it has also been adapted for eukaryotic cells, and can be used for whole cell biosensors, or in real time with live animals without the need for euthanasia. However, correct interpretation of bioluminescent data is limited: the bioluminescence is different from gene expression because of nonlinear molecular and enzyme dynamics of the Lux system. We have developed a computational approach that, for the first time, allows users of Lux assays to infer gene transcription levels from the light output. This approach is based upon a new mathematical model for Lux activity, that includes the actions of LuxAB, LuxEC and Fre, with improved mechanisms for all reactions, as well as synthesis and turn-over of Lux proteins. The model is calibrated with new experimental data for the LuxAB and Fre reactions from Photorhabdus luminescens-the source of modern Lux reporters-while literature data has been used for LuxEC. Importantly, the data show clear evidence for previously unreported product inhibition for the LuxAB reaction. Model simulations show that predicted bioluminescent profiles can be very different from changes in gene expression, with transient peaks of light output, very similar to light output seen in some experimental data sets. By incorporating the calibrated model into a Bayesian inference scheme, we can reverse engineer promoter activity from the bioluminescence. We show examples where a decrease in bioluminescence would be better interpreted as a switching off of the promoter, or where an increase in bioluminescence would be better interpreted as a longer period of gene expression. This approach could benefit all users of Lux technology.


Assuntos
Proteínas de Bactérias/análise , Genes Reporter/genética , Substâncias Luminescentes/análise , Regiões Promotoras Genéticas/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biologia Computacional , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica/genética , Luciferases/análise , Luciferases/química , Luciferases/genética , Luciferases/metabolismo , Substâncias Luminescentes/química , Substâncias Luminescentes/metabolismo , Dinâmica não Linear , Espectrometria de Fluorescência
20.
Bioinformatics ; 33(23): 3776-3783, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961802

RESUMO

Motivation: Regulation of gene expression in prokaryotes involves complex co-regulatory mechanisms involving large numbers of transcriptional regulatory proteins and their target genes. Uncovering these genome-scale interactions constitutes a major bottleneck in systems biology. Sparse latent factor models, assuming activity of transcription factors (TFs) as unobserved, provide a biologically interpretable modelling framework, integrating gene expression and genome-wide binding data, but at the same time pose a hard computational inference problem. Existing probabilistic inference methods for such models rely on subjective filtering and suffer from scalability issues, thus are not well-suited for realistic genome-scale applications. Results: We present a fast Bayesian sparse factor model, which takes input gene expression and binding sites data, either from ChIP-seq experiments or motif predictions, and outputs active TF-gene links as well as latent TF activities. Our method employs an efficient variational Bayes scheme for model inference enabling its application to large datasets which was not feasible with existing MCMC-based inference methods for such models. We validate our method on synthetic data against a similar model in the literature, employing MCMC for inference, and obtain comparable results with a small fraction of the computational time. We also apply our method to large-scale data from Mycobacterium tuberculosis involving ChIP-seq data on 113 TFs and matched gene expression data for 3863 putative target genes. We evaluate our predictions using an independent transcriptomics experiment involving over-expression of TFs. Availability and implementation: An easy-to-use Jupyter notebook demo of our method with data is available at https://github.com/zhenwendai/SITAR. Contact: mudassar.iqbal@manchester.ac.uk. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Sítios de Ligação , Imunoprecipitação da Cromatina/métodos , Perfilação da Expressão Gênica/métodos , Regulação Bacteriana da Expressão Gênica , Modelos Biológicos , Mycobacterium tuberculosis/genética , Fatores de Transcrição/metabolismo , Teorema de Bayes , Biologia Computacional/métodos , Transcrição Genética
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