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1.
Mol Cell Proteomics ; 22(12): 100679, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37979947

RESUMO

The ability of an organism to respond to environmental changes is paramount to survival across a range of conditions. The bacterial heme nitric oxide/oxygen binding proteins (H-NOX) are a family of biofilm-regulating gas sensors that enable bacteria to respond accordingly to the cytotoxic molecule nitric oxide. By interacting with downstream signaling partners, H-NOX regulates the production of the bacterial secondary messenger cyclic diguanylate monophosphate (c-di-GMP) to influence biofilm formation. The aquatic organism Caulobacter crescentus has the propensity to attach to surfaces as part of its transition into the stalked S-phase of its life cycle. This behavior is heavily influenced by intracellular c-di-GMP and thus poses H-NOX as a potential influencer of C. crescentus surface attachment and cell cycle. By generating a strain of C. crescentus lacking hnox, our laboratory has demonstrated that this strain exhibits a considerable growth deficit, an increase in biofilm formation, and an elevation in c-di-GMP. Furthermore, in our comprehensive proteome study of 2779 proteins, 236 proteins were identified that exhibited differential expression in Δhnox C. crescentus, with 132 being downregulated and 104 being upregulated, as determined by a fold change of ≥1.5 or ≤0.66 and a p value ≤0.05. Our systematic analysis unveiled several regulated candidates including GcrA, PopA, RsaA, FtsL, DipM, FlgC, and CpaE that are associated with the regulation of the cellular division process, surface proteins, flagellum, and pili assembly. Further examination of Gene Ontology and pathways indicated that the key differences could be attributed to several metabolic processes. Taken together, our data indicate a role for the HNOX protein in C. crescentus cell cycle progression.


Assuntos
Caulobacter crescentus , Hemeproteínas , Caulobacter crescentus/genética , Caulobacter crescentus/metabolismo , Óxido Nítrico/metabolismo , GMP Cíclico/metabolismo , Hemeproteínas/genética , Hemeproteínas/metabolismo , Oxigênio/metabolismo , Proteínas de Bactérias/metabolismo , Ciclo Celular , Heme/metabolismo , Regulação Bacteriana da Expressão Gênica
2.
Hum Genomics ; 17(1): 58, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420264

RESUMO

BACKGROUND: Wastewater-based epidemiological surveillance has been considered a powerful tool for early detection and monitoring of the dynamics of SARS-CoV-2 and its lineages circulating in a community. This study is aimed to investigate the complexity of SARS-CoV-2 infection dynamics in Dhaka city by examining its genetic variants in wastewater. Also, the study seeks to determine a connection between the SARS-CoV-2 variations detected in clinical testing and those found in wastewater samples. RESULTS: Out of 504 samples tested in RT-qPCR, 185 (36.7%) tested positive for SARS-CoV-2 viral RNA. The median log10 concentration of SARS-CoV-2 N gene copies/Liter of wastewater (gc/L) was 5.2, and the median log10 concentration of ORF1ab was 4.9. To further reveal the genetic diversity of SARS-CoV-2, ten samples with ORF1ab real-time RT-PCR cycle threshold (Ct) values ranging from 28.78 to 32.13 were subjected to whole genome sequencing using nanopore technology. According to clade classification, sequences from wastewater samples were grouped into 4 clades: 20A, 20B, 21A, 21J, and the Pango lineage, B.1, B.1.1, B.1.1.25, and B.1.617.2, with coverage ranging from 94.2 to 99.8%. Of them, 70% belonged to clade 20B, followed by 10% to clade 20A, 21A, and 21J. Lineage B.1.1.25 was predominant in Bangladesh and phylogenetically related to the sequences from India, the USA, Canada, the UK, and Italy. The Delta variant (B.1.617.2) was first identified in clinical samples at the beginning of May 2021. In contrast, we found that it was circulating in the community and was detected in wastewater in September 2020. CONCLUSION: Environmental surveillance is useful for monitoring temporal and spatial trends of existing and emerging infectious diseases and supports evidence-based public health measures. The findings of this study supported the use of wastewater-based epidemiology and provided the baseline data for the dynamics of SARS-CoV-2 variants in the wastewater environment in Dhaka, Bangladesh.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Bangladesh/epidemiologia , COVID-19/epidemiologia , Vigilância em Saúde Pública , Águas Residuárias , Proteínas do Sistema Complemento , RNA
3.
Environ Monit Assess ; 196(7): 641, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904844

RESUMO

The lack of quality water resources for irrigation is one of the main threats for sustainable farming. This pioneering study focused on finding the best area for farming by looking at irrigation water quality and analyzing its location using a fuzzy logic model on a Geographic Information System platform. In the tribal-prone areas of Khagrachhari Sadar Upazila, Bangladesh, 28 surface water and 39 groundwater samples were taken from shallow tube wells, rivers, canals, ponds, lakes, and waterfalls. The samples were then analyzed for irrigation water quality parameters like electrical conductivity (EC), total dissolved solids (TDS), sodium adsorption ratio (SAR), soluble sodium percentage (SSP), residual sodium bicarbonate (RSBC), magnesium hazard ratio (MHR), Kelley's ratio (KR), and permeability index (PI). Fuzzy Irrigation Water Quality Index (FIWQI) was employed to determine the irrigation suitability of water resources. Spatial maps for parameters like EC, KR, MH, Na%, PI, SAR, and RSBC were developed using fuzzy membership values for groundwater and surface water. The FIWQI results indicate that 100% of the groundwater and 75% of the surface water samples range in the categories of excellent to good for irrigation uses. A new irrigation suitability map constructed by overlaying all parameters showed that surface water (75%) and some groundwater (100%) in the northern and southwestern portions are fit for agriculture. The western and central parts are unfit for irrigation due to higher bicarbonate and magnesium contents. The Piper and Gibbs diagram also indicated that the water in the study area is magnesium-bicarbonate type and the primary mechanism of water chemistry is controlled by the weathering of rocks, respectively. This research pinpoints the irrigation spatial pattern for regional water resource practices, identifies novel suitable areas, and improves sustainable agricultural uses in tribal-prone areas.


Assuntos
Irrigação Agrícola , Monitoramento Ambiental , Lógica Fuzzy , Água Subterrânea , Recursos Hídricos , Bangladesh , Irrigação Agrícola/métodos , Água Subterrânea/química , Análise Espacial , Qualidade da Água , Poluentes Químicos da Água/análise
4.
BMC Health Serv Res ; 22(1): 1040, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35971120

RESUMO

BACKGROUND: Responsiveness of Physicians (ROP) is defined as the social actions by physicians aimed at meeting the legitimate expectations of healthcare users. Even though patients' expectations regarding ROP have increased during the COVID-19 pandemic, the psychometrically-validated ROP-Scale is difficult to apply in hospital settings. The goal of this study is to validate the existing ROP-Scale to measure the responsiveness of hospital physicians during the ongoing COVID-19 pandemic in Bangladesh. METHODS: We conducted a cross-sectional phone survey involving 213 COVID-19 hospital patients, randomly selected from the government database. We applied the Delphi method for content validity, exploratory and confirmatory factor analyses for construct validity, Cronbach's alpha and corrected item-total correlation for internal consistency reliability, and Pearson's correlation between the scale and overall patient satisfaction for concurrent validity. RESULTS: After removing survey items based on data sufficiency, collinearity, factor loading derived through exploratory factor analysis, and internal consistency, the final version of the COVID-19 ROP-Scale consisted of 7 items, grouped under Informativeness, Trustworthiness and Courteousness domains. The confirmatory factor analysis supported the three domains with acceptable model fit [Root mean squared error of approximation (RMSEA) = 0.028, Comparative fit index (CFI) = 0.997, Tucker-Lewis index (TLI) = 0.994)]. The corrected item-total correlation ranged between 0.45 and 0.71. Concurrent validity was ascertained by the high correlation (0.84) between patient satisfaction and the COVID-19 ROP-Scale. Based on the mean domain score, the highest- and the lowest-scoring responsiveness domains were 'Trustworthiness' (7.85) and 'Informativeness' (7.28), respectively, whereas the highest- and the lowest-scoring items were 'Not being involved in illegal activities' (7.97), and 'Service-oriented, not business-like attitude' (6.63), respectively. CONCLUSIONS: The 7-item COVID-19 ROP-Scale was demonstrated to be feasible, valid, and internally consistent. Therefore, its application can help amend past mistakes in health service provision and improve care for the hospitalised COVID-19 patients or other patients suffering from similar conditions. This study can contribute to the national decision-making regarding hospital care, open up further avenues in the health policy and system research, and eventually improve the quality of care provided to Bangladeshi patients seeking hospital services. Moreover, findings yielded by this study can be incorporated into doctors' medical education and in-service training.


Assuntos
COVID-19 , Médicos , Bangladesh/epidemiologia , COVID-19/epidemiologia , Estudos Transversais , Humanos , Pandemias , Satisfação do Paciente , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
5.
BMC Bioinformatics ; 22(1): 213, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33894739

RESUMO

BACKGROUND: In this research, an astute system has been developed by using machine learning and data mining approach to predict the risk level of cervical and ovarian cancer in association to stress. RESULTS: For functioning factors and subfactors, several machine learning models like Logistics Regression, Random Forest, AdaBoost, Naïve Bayes, Neural Network, kNN, CN2 rule Inducer, Decision Tree, Quadratic Classifier were compared with standard metrics e.g., F1, AUC, CA. For certainty info gain, gain ratio, gini index were revealed for both cervical and ovarian cancer. Attributes were ranked using different feature selection evaluators. Then the most significant analysis was made with the significant factors. Factors like children, age of first intercourse, age of husband, Pap test, age are the most significant factors of cervical cancer. On the other hand, genital area infection, pregnancy problems, use of drugs, abortion, and the number of children are important factors of ovarian cancer. CONCLUSION: Resulting factors were merged, categorized, weighted according to their significance level. The categorized factors were indexed using ranker algorithm which provides them a weightage value. An algorithm has been formulated afterward which can be used to predict the risk level of cervical and ovarian cancer in relation to women's mental health. The research will have a great impact on the low incoming country like Bangladesh as most women in low incoming nations were unaware of it. As these two can be described as the most sensitive cancers to women, the development of the application from algorithm will also help to reduce women's mental stress. More data and parameters will be added in future for research in this perspective.


Assuntos
Aprendizado de Máquina , Neoplasias , Algoritmos , Teorema de Bayes , Criança , Feminino , Humanos , Modelos Logísticos , Redes Neurais de Computação , Gravidez
6.
Opt Lett ; 46(24): 6031-6034, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34913911

RESUMO

We report self-sustained optical square-wave (SW) generation in a semiconductor laser diode subjected to delayed optoelectronic feedback on its injection current (J). This optoelectronic oscillator relies on nonlinear effects present in both the laser diode and in the optoelectronic feedback loop through amplifier saturation. The repetition rate of the SW is an integer multiple of the inverse of the loop delay, while the duty cycle can be tuned with J.

7.
BMC Cancer ; 21(1): 577, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016083

RESUMO

BACKGROUND: PDE9A (Phosphodiesterase 9A) plays an important role in proliferation of cells, their differentiation and apoptosis via intracellular cGMP (cyclic guanosine monophosphate) signaling. The expression pattern of PDE9A is associated with diverse tumors and carcinomas. Therefore, PDE9A could be a prospective candidate as a therapeutic target in different types of carcinoma. The study presented here was designed to carry out the prognostic value as a biomarker of PDE9A in Colorectal cancer (CRC). The present study integrated several cancer databases with in-silico techniques to evaluate the cancer prognosis of CRC. RESULTS: The analyses suggested that the expression of PDE9A was significantly down-regulated in CRC tissues than in normal tissues. Moreover, methylation in the DNA promoter region might also manipulate PDE9A gene expression. The Kaplan-Meier curves indicated that high level of expression of PDE9A gene was associated to higher survival in OS, RFS, and DSS in CRC patients. PDE9A demonstrated the highest positive correlation for rectal cancer recurrence with a marker gene CEACAM7. Furtheremore, PDE9A shared consolidated pathways with MAPK14 to induce survival autophagy in CRC cells and showed interaction with GUCY1A2 to drive CRPC. CONCLUSIONS: Overall, the prognostic value of PDE9A gene could be used as a potential tumor biomarker for CRC.


Assuntos
3',5'-AMP Cíclico Fosfodiesterases/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Regulação Neoplásica da Expressão Gênica , Recidiva Local de Neoplasia/epidemiologia , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Simulação por Computador , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Recidiva Local de Neoplasia/genética , Prognóstico , Intervalo Livre de Progressão , Transdução de Sinais/genética
8.
Molecules ; 26(23)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34885978

RESUMO

This study aims to investigate the potential analgesic properties of the crude extract of Monochoria hastata (MH) leaves using in vivo experiments and in silico analysis. The extract, in a dose-dependent manner, exhibited a moderate analgesic property (~54% pain inhibition in acetic acid-induced writhing test), which is significant (** p < 0.001) as compared to the control group. The complex inflammatory mechanism involves diverse pathways and they are inter-connected. Therefore, multiple inflammatory modulator proteins were selected as the target for in silico analysis. Computational analysis suggests that all the selected targets had different degrees of interaction with the phytochemicals from the extract. Rutin (RU), protocatechuic acid (PA), vanillic acid (VA), and ferulic acid (FA) could regulate multiple targets with a robust efficiency. None of the compounds showed selectivity to Cyclooxygenase-2 (COX-2). However, regulation of COX and lipoxygenase (LOX) cascade by PA can reduce non-steroidal analgesic drugs (NSAIDs)-related side effects, including asthma. RU showed robust regulation of cytokine-mediated pathways like RAS/MAPK and PI3K/NF-kB by inhibition of EGFR and IKBα (IKK), which may prevent multi-organ failure due to cytokine storm in several microbial infections, for example, SARS-CoV-2. Further investigation, using in vivo and in vitro experiments, can be conducted to develop multi-target anti-inflammatory drugs using the isolated compounds from the extract.


Assuntos
Anti-Inflamatórios/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Pontederiaceae/metabolismo , Animais , Citocinas/metabolismo , Feminino , Masculino , Camundongos , Folhas de Planta/metabolismo
9.
Hum Mol Genet ; 27(1): 120-134, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29088368

RESUMO

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant Parkinson's disease (PD). LRRK2 mutations typically give rise to Lewy pathology in the brains of PD subjects yet can induce tau-positive neuropathology in some cases. The pathological interaction between LRRK2 and tau remains poorly defined. To explore this interaction in vivo, we crossed a well-characterized human P301S-tau transgenic mouse model of tauopathy with human G2019S-LRRK2 transgenic mice or LRRK2 knockout (KO) mice. We find that endogenous or pathogenic LRRK2 expression has minimal effects on the steady-state levels, solubility and abnormal phosphorylation of human P301S-tau throughout the mouse brain. We next developed a new model of tauopathy by delivering AAV2/6 vectors expressing human P301S-tau to the hippocampal CA1 region of G2019S-LRRK2 transgenic or LRRK2 KO mice. P301S-tau expression induces hippocampal tau pathology and marked degeneration of CA1 pyramidal neurons in mice, however, this occurs independently of endogenous or pathogenic LRRK2 expression. We further developed new AAV2/6 vectors co-expressing human WT-tau and GFP to monitor the neuron-to-neuron transmission of tau within defined hippocampal neuronal circuits. While endogenous LRRK2 is not required for tau transmission, we find that G2019S-LRRK2 markedly enhances the neuron-to-neuron transmission of tau in mice. Our data suggest that mutant tau-induced neuropathology occurs independently of LRRK2 expression in two mouse models of tauopathy but identifies a novel pathogenic role for G2019S-LRRK2 in promoting the neuronal transmission of WT-tau protein. These findings may have important implications for understanding the development of tau neuropathology in LRRK2-linked PD brains.


Assuntos
Encéfalo/fisiologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Transmissão Sináptica/fisiologia , Proteínas tau/metabolismo , Animais , Encéfalo/metabolismo , Região CA1 Hipocampal/metabolismo , Modelos Animais de Doenças , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/biossíntese , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/deficiência , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Mutação , Neurônios/metabolismo , Doença de Parkinson/genética , Fosforilação , Proteínas tau/genética
10.
BMC Public Health ; 20(1): 1261, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811451

RESUMO

BACKGROUND: Worldwide people in disorder of sex development (DSD) faces multiple barriers while seeking their social rights, particularly healthcare services. We aimed to explore the healthcare opportunities available to them, using patterns of healthcare utilization and difficulties faced by DSD population in accessing healthcare services in Bangladesh. METHODS: Data from a total of 945 DSD population and 71 medical staff were analyzed, collected from three major divisions (Dhaka, Chittagong, and Rajshahi) in Bangladesh during the period of January to December of 2017. A structured questionnaire was used to collect data via face-to-face interviews. Descriptive statistic was used to determine the frequencies of the visit by the DSD population in healthcare facilities as well as to analyze difficulties experienced by the DSD population in getting healthcare services. Multivariate regression analysis was used to explore the association between perceived barriers in getting healthcare services and failures of the DSD population to receive the healthcare services. RESULTS: Present data revealed that around 80% of DSD population sought healthcare services from government healthcare facilities, where the overall success rate in getting healthcare services was less than 50%. The DSD population reported a number of reasons for failures in getting healthcare services, including non-friendly interaction by non-clinical hospital's staff, non-friendly interaction by physicians, public fright as general people do not want to mingle with a DSD person, undesirable excess public interest in DSD individuals, and limitation of the treatment opportunities of hospitals to merely male or female patients. Among the stated reasons, the most frequently reported reason was non-friendly interaction by physicians (50.27%), followed by undesirable excess public interest in DSD individuals (50.16%). CONCLUSION: DSD population in Bangladesh have limited access to healthcare facilities and facing multiple barriers to get healthcare services. Initiatives from the government and social organizations are important to ensure their access to healthcare services.


Assuntos
Transtornos do Desenvolvimento Sexual/terapia , Acessibilidade aos Serviços de Saúde , Diferenciação Sexual , Adolescente , Adulto , Bangladesh , Estudos Transversais , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto Jovem
11.
Environ Health Prev Med ; 25(1): 62, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054709

RESUMO

BACKGROUND: Tobacco consumption causes almost 638,000 premature deaths per year in India. This study sought to examine the prevalence and determinants of tobacco use among men in India. METHODS: We analyzed data from the fourth round of the National Family Health Survey in India. These nationally representative cross-sectional sample data were collected from January 20, 2015, to December 4, 2016. A total of 112,122 men aged 15-54 years were included in this study. Primary outcomes were tobacco use categorized into smoking, smokeless, any tobacco, and both smoked and smokeless tobacco use. Complex survey design and sampling weights were applied in both the descriptive analyses and logistic regression models. We present the findings using odds ratios. RESULTS: The prevalence of tobacco use among men in India for the studied period was 45.5% (95% CI 44.9-46.1), smoking was 24.6% (95% CI 24.1-25.1), smokeless tobacco use was 29.1% (95% CI 28.6-29.6), and both smoked and smokeless tobacco use was 8.4% (95% CI 8.1-8.7). The prevalence of tobacco use among men was higher among the elderly, separated/divorced/widowed individuals, those with lower education and wealth status, alcohol consumers, manual workers, and residents of the northeast region. Multivariate analysis showed that age, lower education, occupation, region, alcohol consumption, separated/divorced/widowed status, and economic status were substantially associated with tobacco use among Indian men. CONCLUSIONS: Innovative and cost-effective strategies targeting high-risk groups are crucial to curbing the tobacco epidemic in India. Anti-smoking campaigns should also focus on mitigating alcohol abuse. Reducing tobacco marketing and implementing formal education about the dangers of tobacco use, progressive taxing, packaging, and labeling of tobacco products and price strategies should be harmonized in legal provisions.


Assuntos
Fatores Socioeconômicos , Adolescente , Adulto , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Uso de Tabaco/epidemiologia , Adulto Jovem
12.
Hum Mol Genet ; 25(24): 5365-5382, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27794539

RESUMO

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset, autosomal dominant familial Parkinson`s disease (PD) and variation at the LRRK2 locus contributes to the risk for idiopathic PD. LRRK2 can function as a protein kinase and mutations lead to increased kinase activity. To elucidate the pathophysiological mechanism of the R1441C mutation in the GTPase domain of LRRK2, we expressed human wild-type or R1441C LRRK2 in dopaminergic neurons of Drosophila and observe reduced locomotor activity, impaired survival and an age-dependent degeneration of dopaminergic neurons thereby creating a new PD-like model. To explore the function of LRRK2 variants in vivo, we performed mass spectrometry and quantified 3,616 proteins in the fly brain. We identify several differentially-expressed cytoskeletal, mitochondrial and synaptic vesicle proteins (SV), including synaptotagmin-1, syntaxin-1A and Rab3, in the brain of this LRRK2 fly model. In addition, a global phosphoproteome analysis reveals the enhanced phosphorylation of several SV proteins, including synaptojanin-1 (pThr1131) and the microtubule-associated protein futsch (pSer4106) in the brain of R1441C hLRRK2 flies. The direct phosphorylation of human synaptojanin-1 by R1441C hLRRK2 could further be confirmed by in vitro kinase assays. A protein-protein interaction screen in the fly brain confirms that LRRK2 robustly interacts with numerous SV proteins, including synaptojanin-1 and EndophilinA. Our proteomic, phosphoproteomic and interactome study in the Drosophila brain provides a systematic analyses of R1441C hLRRK2-induced pathobiological mechanisms in this model. We demonstrate for the first time that the R1441C mutation located within the LRRK2 GTPase domain induces the enhanced phosphorylation of SV proteins in the brain.


Assuntos
Encéfalo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Doença de Parkinson/genética , Proteoma/genética , Animais , Animais Geneticamente Modificados , Encéfalo/patologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/patologia , Proteínas de Drosophila/biossíntese , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/biossíntese , Mutação , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Monoéster Fosfórico Hidrolases/biossíntese , Monoéster Fosfórico Hidrolases/genética , Fosforilação , Mapas de Interação de Proteínas , Vesículas Sinápticas/genética , Sinaptotagmina I/biossíntese , Sinaptotagmina I/genética , Sintaxina 1/biossíntese , Sintaxina 1/genética , Proteínas rab3 de Ligação ao GTP/biossíntese , Proteínas rab3 de Ligação ao GTP/genética
15.
BMC Public Health ; 18(1): 476, 2018 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-29642879

RESUMO

BACKGROUND: Healthy life expectancy (HALE) at birth is an important indicator of health status and quality of life of a country's population. However, little is known about the determinants of HALE as yet globally or even country-specific level. Thus, we examined the factors that are associated with HALE at birth in low- and lower-middle-income countries. METHODS: In accordance with the World Bank (WB) classification seventy-nine low- and lower-middle-income countries were selected for the study. Data on HALE, demographic, socioeconomic, social structural, health, and environmental factors from several reliable sources, such as the World Health Organization, the United Nations Development Program, Population Reference Bureau, WB, Heritage Foundation, Transparency International, Freedom House, and International Center for Prison Studies were obtained as selected countries. Descriptive statistics, correlation analysis, and regression analysis were performed to reach the research objectives. RESULTS: The lowest and highest HALE were observed in Sierra Leone (44.40 years) and in Sri Lanka (67.00 years), respectively. The mean years of schooling, total fertility rate (TFR), physician density, gross national income per capita, health expenditure, economic freedom, carbon dioxide emission rate, freedom of the press, corruption perceptions index, prison population rate, and achieving a level of health-related millennium development goals (MDGs) were revealed as the correlates of HALE. Among all the correlates, the mean years of schooling, TFR, freedom of the press, and achieving a level of health-related MDGs were found to be the most influential factors. CONCLUSION: To increase the HALE in low- and lower-middle-income countries, we suggest that TFR is to be reduced as well as to increase the mean years of schooling, freedom of the press, and the achievement of a level of health-related MDGs.


Assuntos
Países em Desenvolvimento , Expectativa de Vida/tendências , Determinantes Sociais da Saúde , Humanos , Qualidade de Vida , Fatores Socioeconômicos
16.
Biochem Soc Trans ; 45(1): 163-172, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28202670

RESUMO

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease (PD) with autosomal dominant inheritance. Accordingly, LRRK2 has emerged as a promising therapeutic target for disease modification in PD. Since the first discovery of LRRK2 mutations some 12 years ago, LRRK2 has been the subject of intense investigation. It has been established that LRRK2 can function as a protein kinase, with many putative substrates identified, and can also function as a GTPase that may serve in part to regulate kinase activity. Familial mutations influence both of these enzymatic activities, suggesting that they may be important for the development of PD. Many LRRK2 models have been established to understand the pathogenic effects and mechanisms of familial mutations. Here, we provide a focused discussion of the evidence supporting a role for kinase and GTPase activity in mediating the pathogenic effects of familial LRRK2 mutations in different model systems, with an emphasis on rodent models of PD. We also critically discuss the contribution and relevance of protein aggregation, namely of α-synuclein and tau-proteins, which are known to form aggregates in PD brains harboring LRRK2 mutations, to neurodegeneration in LRRK2 rodent models. We aim to provide a clear and unbiased review of some of the key mechanisms that are important for LRRK2-dependent neurodegeneration in PD.


Assuntos
GTP Fosfo-Hidrolases/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Mutação , Doenças Neurodegenerativas/genética , GTP Fosfo-Hidrolases/metabolismo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Modelos Genéticos , Doenças Neurodegenerativas/enzimologia , Doenças Neurodegenerativas/metabolismo , Agregados Proteicos , Agregação Patológica de Proteínas , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismo
17.
Ecotoxicol Environ Saf ; 141: 85-92, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28319863

RESUMO

The binding affinity of organophosphate hydrolase enzyme (OphB) with soil particles in relation to the isoelectric point (pI) was studied. Immobilization of OphB with soil particles was observed by confocal microscopy, Fourier transform infrared spectroscopy (FT-IR), and Atomic force microscopy (AFM). The calculated pI of OphB enzyme was increased from 8.69 to 8.89, 9.04 and 9.16 by the single, double and triple mutant of OphB enzyme, respectively through the replacement of negatively charged aspartate with positively charged histidine. Practically, the binding affinity was increased to 5.30%, 11.50%, and 16.80% for single, double and triple mutants, respectively. In contrast, enzyme activity of OphB did not change by the mutation of the enzyme. On the other hand, adhesion forces were gradually increased for wild type OphB enzyme (90 pN) to 96, 100 and 104 pN for single, double and triple mutants of OphB enzyme, respectively. There was an increasing trend of binding affinity and adhesion force by the increase of isoelectric point (pI) of OphB enzyme.


Assuntos
Organofosfatos/química , Resíduos de Praguicidas/química , Monoéster Fosfórico Hidrolases/química , Poluentes do Solo/química , Solo/química , Recuperação e Remediação Ambiental , Proteínas de Fluorescência Verde/genética , Histidina/genética , Ponto Isoelétrico , Microscopia de Força Atômica , Modelos Moleculares , Mutagênese Sítio-Dirigida , Mutação , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Ligação Proteica , Pseudomonas/enzimologia , Pseudomonas/genética , Espectroscopia de Infravermelho com Transformada de Fourier , Especificidade por Substrato
18.
Ecotoxicol Environ Saf ; 112: 193-200, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25463871

RESUMO

Arsenic (As) and cadmium (Cd) are noxious and carcinogenic pollutants that can be removed from water by using emerging, ecofriendly, phytofiltration technology that employs Micranthemum umbrosum. After culturing M. umbrosum for 7 days in a hydroponic experiment, accumulation of 1219±44.11 µg As g(-1) and 799.40±30.95 µg Cd g(-1) were observed in the leaves, from 1000 µg As L(-1) and 1000 µg Cd L(-1) of water, respectively. Plant and water samples were analyzed for assessing the As and Cd accumulations, translocations, phytotoxic effects, uptake mechanisms and kinetics, and for evaluating the potential of M. umbrosum in As and Cd phytofiltration. The uptake pattern was leaf>stem>root for both pollutants. The plant showed higher resistance to As than to that to Cd. Uptake of inorganic As species was much greater than that of organic As and was found at above the substrate concentration. However, Cd showed similar uptake pattern to that of inorganic As species, and the data was better fit to a non-linear than a linear model. Low molecular weight substances that have thiol group(s) may be responsible for the binding of As in plants whereas Cd showed a different mechanism to that of As. M. umbrosum showed good As phytofiltration capabilities without any phytotoxic effects, but it was found to be a moderate accumulator of Cd with some phytotoxic effect compare to some other previously studied plant.


Assuntos
Arsênio/metabolismo , Cádmio/metabolismo , Recuperação e Remediação Ambiental/métodos , Scrophulariaceae/metabolismo , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Cinética , Águas Residuárias/química
19.
Biol Res ; 47: 68, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25723319

RESUMO

BACKGROUND: Tribolium castaneum (Herbst) is a major pest of stored grain-based products, and cause severe damage to cereal grains throughout the world. The present investigation was aimed to determine the pesticidal and pest repellent activities of 2α,3ß,21ß,23,28-penta hydroxyl 12-oleanene against T. castaneum. The compound 2α,3ß,21ß,23,28-penta hydroxyl 12-oleanene is a triterpenoid which was isolated from the roots of Laportea crenulata Gaud. Surface film technique was used for pesticidal screening, whereas, pest repellency property of the triterpenoid was determined by filter paper disc method. RESULTS: At 24 hours of exposure duration, significant mortality records (80% and 86%) were observed at doses 0.88 and 1.77 mg/cm(2). No significant change in mortality records was observed when duration of exposure was increased up to 48 hours. The triterpenoid showed significant repellency activity at doses 0.47 and 0.94 mg/cm(2). CONCLUSION: These data suggest that the triterpenoid 2α,3ß,21ß,23,28-penta hydroxyl 12-oleanene possess both pesticidal and pest repellency activities against T. castaneum and can be used in controlling the pest of grain-based products.


Assuntos
Controle de Insetos/métodos , Repelentes de Insetos/farmacologia , Ácido Oleanólico/análogos & derivados , Tribolium/efeitos dos fármacos , Urticaceae/química , Animais , Dose Letal Mediana , Ácido Oleanólico/farmacologia , Praguicidas/farmacologia , Raízes de Plantas/química , Tribolium/classificação , Urticaceae/classificação
20.
Water Environ Res ; 86(4): 296-304, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24851325

RESUMO

Beta-cyclodextrin (beta-CD) cross-linked with epichlorohydrin to form water insoluble beta-cyclodextrin polymer (beta-CDP) has been shown to be an effective sorbent for sorption of organic particles, but the sorption of copper (Cu2+) in aqueous solutions by beta-CDP has not been conducted. The objective of this study was to explore the sorption mechanism of beta-CDP for copper. The effects of different experimental conditions such as pH, ionic strength, contact time, and temperature were inspected using a batch method. In addition, binding scheme was estimated by using Fourier transform infrared (FTIR) spectroscopy, Xray photoelectron spectroscopy (XPS), a scanning electron microscope (SEM), and Brunauer-Emmett-Teller (BET) analysis. The adsorption of Cu2+ was observed to be higher at pH 6.0. The kinetic study revealed that the adsorption is fitted well by the pseudo-second-order kinetic model. The maximum binding of Cu2+ was estimated to be 111.11 mg/g through the Langmuir isotherm model--much higher than the existing sorption technologies. Hence, the adsorption-desorption trends of epichlorohydrin cross-linked with beta-CD, along with its good recyclability, establish an alternative, effective, and novel remediation technology for the removal of Cu2+ from aqueous solutions.


Assuntos
Cobre/química , Epicloroidrina/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , beta-Ciclodextrinas/química , Adsorção , Cinética , Microscopia Eletrônica de Varredura , Modelos Teóricos , Espectroscopia Fotoeletrônica , Polímeros , Espectroscopia de Infravermelho com Transformada de Fourier , Eliminação de Resíduos Líquidos/economia , Eliminação de Resíduos Líquidos/instrumentação
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