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1.
Braz. j. biol ; 84: e253106, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345544

RESUMO

Abstract This study aimed to develop and evaluate data driven models for prediction of forest yield under different climate change scenarios in the Gallies forest division of district Abbottabad, Pakistan. The Random Forest (RF) and Kernel Ridge Regression (KRR) models were developed and evaluated using yield data of two species (Blue pine and Silver fir) as an objective variable and climate data (temperature, humidity, rainfall and wind speed) as predictive variables. Prediction accuracy of both the models were assessed by means of root mean squared error (RMSE), mean absolute error (MAE), correlation coefficient (r), relative root mean squared error (RRMSE), Legates-McCabe's (LM), Willmott's index (WI) and Nash-Sutcliffe (NSE) metrics. Overall, the RF model outperformed the KRR model due to its higher accuracy in forecasting of forest yield. The study strongly recommends that RF model should be applied in other regions of the country for prediction of forest growth and yield, which may help in the management and future planning of forest productivity in Pakistan.


Resumo Este estudo teve como objetivo desenvolver e avaliar modelos baseados em dados para previsão da produção florestal em diferentes cenários de mudanças climáticas na divisão florestal Gallies do distrito de Abbottabad, Paquistão. Os modelos Random Forest (RF) e Kernel Ridge Regression (KRR) foram desenvolvidos e avaliados usando dados de produção de duas espécies (pinheiro-azul e abeto-prateado) como uma variável objetiva e dados climáticos (temperatura, umidade, precipitação e velocidade do vento) como preditivos variáveis. A precisão da previsão de ambos os modelos foi avaliada por meio de erro quadrático médio (RMSE), erro absoluto médio (MAE), coeficiente de correlação (r), erro quadrático médio relativo (RRMSE), Legates-McCabe's (LM), índice de Willmott (WI) e métricas Nash-Sutcliffe (NSE). No geral, o modelo RF superou o modelo KRR devido à sua maior precisão na previsão do rendimento florestal. O estudo recomenda fortemente que o modelo RF seja aplicado em outras regiões do país para previsão do crescimento e produtividade florestal, o que pode ajudar no manejo e planejamento futuro da produtividade florestal no Paquistão.


Assuntos
Mudança Climática , Paquistão
2.
Braz. j. biol ; 83: e246002, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285612

RESUMO

Abstract Economic valuation of ecosystem services is a new concept in forest management. Economic valuation provides basis for payment for ecosystem services (PES). Therefore, objective of this study was to evaluate eco-tourism and carbon stock services of the Maindam valley, District Swat, Pakistan. For the carbon stock calculation, a sample size of 155 plots of 0.1 hectare (Ha) was taken using preliminary survey at 95% confidence interval and 10% allowable error. The data for tourism services was collected from owners of all the hotels, 100 tourists and key informants of the area at 10% sampling intensity on pretested questionnaire for twenty years period (1997-2017). Results showed that Miandam valley has carbon stock worth US$ 16,306,000 while the value of eco-tourism was US$ 1,578,458 on annual basis. The results also showed that trend of tourism has drastically declined after the 9/11 incident for foreigners and locals and the situation was further deteriorated during the era of Talibanization or militancy from 2008-2011. This study recommends implementation of PES strategy at the rate of 5%, thus a total of US$ 78,922 can be earned from eco-tourism and carbon crediting in the study area annually, which could play important role in sustainable forest management.


Resumo A valoração econômica dos serviços ecossistêmicos é um novo conceito no manejo florestal. A avaliação econômica fornece base para o pagamento por serviços ecossistêmicos (PES). Portanto, o objetivo deste estudo foi avaliar o ecoturismo e os serviços de estoque de carbono do vale de Miandam, distrito Swat, Paquistão. Para o cálculo do estoque de carbono, um tamanho de amostra de 155 parcelas de 0,1 hectare (ha) foi tirado, usando pesquisa preliminar com intervalo de confiança de 95% e erro admissível de 10%. Os dados para serviços de turismo foram coletados de proprietários de todos os hotéis, 100 turistas e informantes-chave da área em 10% de intensidade de amostragem em questionário pré-testado para um período de 20 anos (1997-2017). Os resultados mostraram que o vale de Miandam tem estoque de carbono no valor de US$ 16.306.000, enquanto o valor do ecoturismo foi de US$ 1.578.458 anualmente. Os resultados também mostraram que a tendência do turismo diminuiu drasticamente para estrangeiros e locais após o incidente de 11 de Setembro, e a situação se agravou ainda mais durante a era da talibanização ou militância de 2008-2011. Este estudo recomenda a implementação da estratégia de PES na taxa de 5%, portanto um total de US$ 78.922 pode ser ganho com ecoturismo e crédito de carbono na área de estudo anualmente, o que pode desempenhar um papel importante no manejo florestal sustentável.


Assuntos
Ecossistema , Conservação dos Recursos Naturais , Paquistão , Carbono/análise , Florestas
3.
Philos Trans A Math Phys Eng Sci ; 380(2236): 20210352, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36154473

RESUMO

Numerous applied models used in the study of optimal control problems, inverse problems, shape optimization, machine learning, fractional programming, neural networks, image registration and so on lead to stochastic optimization problems in Hilbert spaces. Under a suitable convexity assumption on the objective function, a necessary and sufficient optimality condition for stochastic optimization problems is a stochastic variational inequality. This article presents a new stochastic regularized second-order iterative scheme for solving a variational inequality in a stochastic environment where the primary operator is accessed by employing sampling techniques. The proposed iterative scheme, which fits within the general framework of the stochastic approximation approach, has its almost-sure convergence analysis given in a Hilbert space. We test the feasibility and the efficacy of the proposed stochastic approximation approach for a stochastic optimal control problem and a stochastic inverse problem, both associated with a second-order stochastic partial differential equation. This article is part of the theme issue 'Non-smooth variational problems and applications'.

4.
J Plast Reconstr Aesthet Surg ; 75(9): 2955-2959, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35752588

RESUMO

BACKGROUND: Dual-consultant operating (DCO) has been introduced in a multitude of surgical specialities. This retrospective cohort comparison study seeks to delineate any benefits DCO may confer on list utilisation, patient safety and training opportunities. METHODS: A retrospective cohort comparison of all free-flap breast reconstruction cases conducted at a single centre by five consultant plastic surgeons in the period May 2016-May 2020. RESULTS: A total of 281 patient records were used for analysis; 146 cases were dual consultants compared with 135 single consultants, representing 186 and 158 free flaps, respectively. Patient demographics were near identical in terms of patient age, BMI and ASA grade. Operating times were significantly reduced for both unilateral (mean reduction 59.49 min) and bilateral cases (mean reduction 38.14 min) with the presence of dual consultants. The mean length of stay for dual-consultant cases was on average 0.35 days less than for single consultant cases (p = 0.04). Dual-consultant case complications were less severe than those of single consultant cases (mean Clavien-Dindo severity 1.35 vs 0.96, p = 0.05). The rates of trainee one-to-one consultant training were increased in dual-consultant cases when preparing vessels (0.08 vs 0.35, p=<0.01) and performing anastomosis (0.63 vs 0.77, p = 0.03). CONCLUSIONS: DCO for complex breast reconstruction confers significant benefits to operating time, list utility and patient safety whilst protecting training opportunities for trainees. Plastic surgery departments looking to redesign services in the post-SARS-CoV-19 era should consider its adoption into their enhanced recovery protocols.


Assuntos
Retalhos de Tecido Biológico , Mamoplastia , Cirurgiões , Consultores , Humanos , Mamoplastia/métodos , Estudos Retrospectivos
5.
Braz. j. biol ; 82: e242636, 2022. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285595

RESUMO

Abstract Cranes are the large and attractive Creatures of nature with long necks, legs, and life-span. Adults of both sexes are the same with similar color patterns. Demoiselle cranes spend most of their lifespan on dry grasses. They are also found around the stream, rivers, shallow lakes, natural wetlands, and depressions. To evaluate the current status of habitat use and major threats a study was conducted in tehsil Domel district Bannu. Line transect method and water quality tests (temperature, PH, contamination of E-coli bacteria) were used. To determine the major threats questionnaire method was used. The whole data was analyzed by using SPSS 21 version. Based on the distribution four study sites were selected and four water samples from each study site were taken. Most sites were moderate to highly degraded except Kashoo and kurram river mixing point which was low degraded with livestock grazing and human activities. Water quality tests showed PH ranges from 7-9, temperature 6.5-8.5, and contamination of E-coli in all samples. The social survey revealed that hunting, habitat degradation, and pollution as major threats. Effective long-term conservation and management in the study area are needed to focus on the protection of disturbance-free habitat.


Resumo Guindastes são a grande e atraente criatura da natureza com um pescoço longo, pernas e vida útil. Adultos de ambos os sexos são os mesmos com padrões de cores semelhantes. Guindastes Demoiselle passam a maior parte da vida em gramíneas secas. Também se encontram ao redor do córrego, rios, lagos rasos, pântanos naturais e depressões. Para avaliar o estado atual do uso do hábitat e as principais ameaças, um estudo foi realizado no distrito de Tehsil Domel, em Bannu. Foram utilizados o método transect e testes de qualidade da água (temperatura, pH, contaminação da bactéria E. coli). Para determinar as principais ameaçasfoi utilizado o método de questionário. Todos os dados foram analisados por meio da versão SPSS 21. Com base na distribuição, foram selecionados quatro locais de estudo e quatro amostras de água de cada local de estudo. A maioria dos locais estava moderada a altamente degradada, exceto no ponto de encontro dos rios Kashoo e Kurram, que teve baixa degradação com pastagem de gado e atividades humanas. Os testes de qualidade da água mostraram variação de pH de 7-9, temperatura 6,5-8,5 e contaminação de E. coli em todas as amostras. A pesquisa do questionário revelou que a caça, a degradação do hábitat e a poluição são as principais ameaças. Efetiva conservação e gestão a longo prazo na área de estudo são necessárias para se concentrar na proteção de um hábitat livre de distúrbios.


Assuntos
Humanos , Animais , Masculino , Feminino , Aves , Ecossistema , Paquistão , Rios , Áreas Alagadas
6.
Braz. j. biol ; 82: e242635, 2022. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1278477

RESUMO

Abstract Indian crested porcupine is the largest rodent pest that damages a wide variety of crops, vegetables, and tree species which ultimately causes huge economic loss in Pakistan, which is an agricultural country. It prefers to live in hilly terrain but common in temperate and tropical forests, shrublands, and grasslands. This study focused on the identification and assessment of crops damaged along with the main precautionary measures used by the local farmers. The data was collected from twenty-four villages of two union councils i.e. Chamhad and Slahad of district Abbottabad. Two types of data (primary and secondary) were collected from the study area. Primary data was collected for identification and estimation calculation of total crop damaged through direct field observation by taking random quadrates in each village of the study area. The damage in the crop was assessed by randomly selecting a quadrate of 1x1 m2 for the wheat, pearl millet, and Sorghum fields. While 4x4 m2 quadrates were taken for maize and vegetables. At least three quadrate samples were taken from each field including one quadrate taken from the center of the field area. In union council Chamhad, damage to maize (11.31%) and wheat (0.73%) by the Indian crested porcupine while in union council Salhad, damage of maize (6.95%) and wheat (1.6%) was observed. In the entire study area, overall damage to maize crop (8.01%) and wheat (0.88%) was calculated. Based on information obtained from the farmers, the Indian porcupine inflicted damage to potato, tomato, cauliflower, chili pepper, turnip, radish, pea, and onion, etc. Secondary data obtained through a questionnaire survey to explore the human porcupine conflict and precautionary measures used by the farmers and landowners. Open and close-ended questionnaires (159) highlighted the presence of Indian crested porcupine in the study area and 96% of the respondents have seen porcupine directly. Many types of precautionary measures were used by the farmers such as fencing, night stay, night firing, and dogs to decrease the crop damage, respondents (63.91%) use guns for hunting. however, due to the largely agricultural area and nocturnal behavior of Indian crested porcupine majority of the respondents (51.57%) did not use any precautionary measure. Biological control of Indian porcupine is recommended in the study area. Farmers should be encouraged and provide incentives and killing through current should be banned while proper hunting license should be issued to overcome overhunting. Scientific studies are required to control the reproduction of porcupine specifically in the more damaged areas.


Resumo O porco-espinho indiano é a maior praga de roedores que danifica uma grande variedade de culturas, vegetais e espécies de árvores, o que acaba por causar enormes perdas econômicas no Paquistão, que é um país agrícola. Prefere viver em terrenos montanhosos, mas comuns em florestas temperadas e tropicais, arbustos e pastagens. Este estudo concentrou-se na identificação e avaliação das lavouras danificadas, juntamente com as principais medidas de precaução utilizadas pelos agricultores locais. Os dados foram coletados de 24 aldeias de dois conselhos sindicais, ou seja, Chamhad e Slahad, do distrito de Abbottabad. Dois tipos de dados (primário e secundário) foram coletados da área de estudo. Foram coletados dados primários para identificação e cálculo de estimativa do total da cultura danificada por meio da observação direta do campo, tomando quadrantes aleatórios em cada aldeia da área de estudo. O dano na cultura foi avaliado pela seleção aleatória de um quadrante de 1x1 m2 para os campos de trigo, milheto pérola e sorgo, enquanto quadrantes de 4x4 m2 foram tomados para milho e legumes. Pelo menos três amostras de quadrante foram colhidas de cada campo, incluindo um quadrante retirado do centro da área do campo. No Conselho Sindical de Chamhad, houve danos ao milho (11,31%) e ao trigo (0,73%) pelo porco-espinho indiano, enquanto no Conselho Sindical de Salhad, danos ao milho (6,95%) e ao trigo (1,6%) foram observados. Em toda a área do estudo, danos gerais à cultura do milho (8,01%) e ao trigo (0,88%) foram calculados. Com base em informações obtidas dos agricultores, o porco-espinho indiano infligiu danos à batata, tomate, couve-flor, pimenta, nabo, rabanete, ervilha, cebola, etc. Dados secundários foram obtidos por meio de um questionário para explorar o conflito suíno humano e as medidas de precaução utilizadas pelos agricultores e proprietários de terras. Questionários abertos e fechados (159) destacaram a presença de porco-espinho indiano na área de estudo e 96% dos entrevistados viram o porco-espinho diretamente. Muitos tipos de medidas de precaução foram utilizados pelos agricultores, como esgrima, estadia noturna, fogo noturno e cães para diminuir os danos na lavoura. Dos entrevistados, 63,91% usaram armas para caçar. No entanto, devido à área ser em grande parte agrícola e ao comportamento noturno da maioria dos porcos-espinhos indianos, 51,57% não usaram nenhuma medida de precaução. O controle biológico do porco-espinho indiano é recomendado na área de estudo. Os agricultores devem ser encorajados e fornecer incentivos, e o uso da corrente para matar os animais deve ser banido, assim como deve ser emitida a licença de caça adequada para superar a caça excessiva. Estudos científicos são necessários para controlar a reprodução de porco-espinho, especificamente nas áreas mais danificadas.


Assuntos
Animais , Cães , Porcos-Espinhos , Paquistão , Árvores , Produtos Agrícolas , Agricultura
7.
Braz J Biol ; 84: e253106, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34730700

RESUMO

This study aimed to develop and evaluate data driven models for prediction of forest yield under different climate change scenarios in the Gallies forest division of district Abbottabad, Pakistan. The Random Forest (RF) and Kernel Ridge Regression (KRR) models were developed and evaluated using yield data of two species (Blue pine and Silver fir) as an objective variable and climate data (temperature, humidity, rainfall and wind speed) as predictive variables. Prediction accuracy of both the models were assessed by means of root mean squared error (RMSE), mean absolute error (MAE), correlation coefficient (r), relative root mean squared error (RRMSE), Legates-McCabe's (LM), Willmott's index (WI) and Nash-Sutcliffe (NSE) metrics. Overall, the RF model outperformed the KRR model due to its higher accuracy in forecasting of forest yield. The study strongly recommends that RF model should be applied in other regions of the country for prediction of forest growth and yield, which may help in the management and future planning of forest productivity in Pakistan.


Assuntos
Mudança Climática , Paquistão
8.
Braz J Biol ; 83: e246002, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34378665

RESUMO

Economic valuation of ecosystem services is a new concept in forest management. Economic valuation provides basis for payment for ecosystem services (PES). Therefore, objective of this study was to evaluate eco-tourism and carbon stock services of the Maindam valley, District Swat, Pakistan. For the carbon stock calculation, a sample size of 155 plots of 0.1 hectare (Ha) was taken using preliminary survey at 95% confidence interval and 10% allowable error. The data for tourism services was collected from owners of all the hotels, 100 tourists and key informants of the area at 10% sampling intensity on pretested questionnaire for twenty years period (1997-2017). Results showed that Miandam valley has carbon stock worth US$ 16,306,000 while the value of eco-tourism was US$ 1,578,458 on annual basis. The results also showed that trend of tourism has drastically declined after the 9/11 incident for foreigners and locals and the situation was further deteriorated during the era of Talibanization or militancy from 2008-2011. This study recommends implementation of PES strategy at the rate of 5%, thus a total of US$ 78,922 can be earned from eco-tourism and carbon crediting in the study area annually, which could play important role in sustainable forest management.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Carbono/análise , Florestas , Paquistão
9.
Braz J Biol ; 82: e242636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34346960

RESUMO

Cranes are the large and attractive Creatures of nature with long necks, legs, and life-span. Adults of both sexes are the same with similar color patterns. Demoiselle cranes spend most of their lifespan on dry grasses. They are also found around the stream, rivers, shallow lakes, natural wetlands, and depressions. To evaluate the current status of habitat use and major threats a study was conducted in tehsil Domel district Bannu. Line transect method and water quality tests (temperature, PH, contamination of E-coli bacteria) were used. To determine the major threats questionnaire method was used. The whole data was analyzed by using SPSS 21 version. Based on the distribution four study sites were selected and four water samples from each study site were taken. Most sites were moderate to highly degraded except Kashoo and kurram river mixing point which was low degraded with livestock grazing and human activities. Water quality tests showed PH ranges from 7-9, temperature 6.5-8.5, and contamination of E-coli in all samples. The social survey revealed that hunting, habitat degradation, and pollution as major threats. Effective long-term conservation and management in the study area are needed to focus on the protection of disturbance-free habitat.


Assuntos
Aves , Ecossistema , Animais , Feminino , Humanos , Masculino , Paquistão , Rios , Áreas Alagadas
10.
Braz J Biol ; 82: e242635, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34190803

RESUMO

Indian crested porcupine is the largest rodent pest that damages a wide variety of crops, vegetables, and tree species which ultimately causes huge economic loss in Pakistan, which is an agricultural country. It prefers to live in hilly terrain but common in temperate and tropical forests, shrublands, and grasslands. This study focused on the identification and assessment of crops damaged along with the main precautionary measures used by the local farmers. The data was collected from twenty-four villages of two union councils i.e. Chamhad and Slahad of district Abbottabad. Two types of data (primary and secondary) were collected from the study area. Primary data was collected for identification and estimation calculation of total crop damaged through direct field observation by taking random quadrates in each village of the study area. The damage in the crop was assessed by randomly selecting a quadrate of 1x1 m2 for the wheat, pearl millet, and Sorghum fields. While 4x4 m2 quadrates were taken for maize and vegetables. At least three quadrate samples were taken from each field including one quadrate taken from the center of the field area. In union council Chamhad, damage to maize (11.31%) and wheat (0.73%) by the Indian crested porcupine while in union council Salhad, damage of maize (6.95%) and wheat (1.6%) was observed. In the entire study area, overall damage to maize crop (8.01%) and wheat (0.88%) was calculated. Based on information obtained from the farmers, the Indian porcupine inflicted damage to potato, tomato, cauliflower, chili pepper, turnip, radish, pea, and onion, etc. Secondary data obtained through a questionnaire survey to explore the human porcupine conflict and precautionary measures used by the farmers and landowners. Open and close-ended questionnaires (159) highlighted the presence of Indian crested porcupine in the study area and 96% of the respondents have seen porcupine directly. Many types of precautionary measures were used by the farmers such as fencing, night stay, night firing, and dogs to decrease the crop damage, respondents (63.91%) use guns for hunting. however, due to the largely agricultural area and nocturnal behavior of Indian crested porcupine majority of the respondents (51.57%) did not use any precautionary measure. Biological control of Indian porcupine is recommended in the study area. Farmers should be encouraged and provide incentives and killing through current should be banned while proper hunting license should be issued to overcome overhunting. Scientific studies are required to control the reproduction of porcupine specifically in the more damaged areas.


Assuntos
Porcos-Espinhos , Agricultura , Animais , Produtos Agrícolas , Cães , Paquistão , Árvores
11.
Vet Med Int ; 2021: 8818308, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055283

RESUMO

This study was conducted to inactivate Salmonella enteriditis phage types (SE pt) and to determine the safety and efficacy of inactivated SE pt in chickens. SE pt 1, 3A, 6A, 7, and 35 were inactivated and inoculated (0.20 mL) in 124 chickens divided into 6 groups (CV1, CV3A, CV6A, CV7, CV35, and CV0 as a control). Sampling was conducted on day 14 after inoculation (pi). Eight chickens from each group were separated on day 14 pi for oral challenge with 0.20 mL/chicken (1010 cfu/mL) SE pt 6A and designated CV1C, CV3AC, CV6AC, CV7C, CV35C, and CV0C as control chickens. On days 7 and 14 postchallenge (pc), 4 chickens from every group were sacrificed for sampling. There was no significant difference in the body weight between different groups. In challenged groups, there was no significant association between different tissues and isolation of Salmonella on days 7 and 14 pc. There was significance (p < 0.05) in isolation of Salmonella when CV0C group was compared with other challenged groups. Significance was not observed between different tissues with respect to induction of microscopic changes. Significance was not observed between day 7 pc and day 14 pc with respect to scoring of lesions induced. Clinical signs and gross lesions were also recorded. ELISA was applied. Only in CV3AC group, the mean antibody titer was 1359 on day 14 pc. The conclusion was that inactivated SE pt 3A and 6A were safe and efficacious for protection against Salmonella enteriditis infection in chickens.

13.
Ir Med J ; 113(7): 125, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35575605

RESUMO

Identifying citation classics is a valuable metric of research performance. Ireland has a distinguished history of medical research, although Ireland's top-cited articles are unknown. The SCOPUS database identified all medical and surgical articles published by journals in the Republic of Ireland or Northern Ireland. The 100 top-cited articles were analysed. The most cited article received 240 citations. There is an observed trend of increasing number of authors over time (p<0.05). General medicine and public health are the most common topics. The majority of works originate from Irish institutions. Collaborative research and non-Irish research are poorly represented among the citation classics. The Irish medical literature contains multiple highly cited and influential articles.

15.
Hum Mutat ; 40(2): 162-176, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30461122

RESUMO

KCNE1 encodes a regulatory subunit of the KCNQ1 potassium channel-complex. Both KCNE1 and KCNQ1 are necessary for normal hearing and cardiac ventricular repolarization. Recessive variants in these genes are associated with Jervell and Lange-Nielson syndrome (JLNS1 and JLNS2), a cardio-auditory syndrome characterized by congenital profound sensorineural deafness and a prolonged QT interval that can cause ventricular arrhythmias and sudden cardiac death. Some normal-hearing carriers of heterozygous missense variants of KCNE1 and KCNQ1 have prolonged QT intervals, a dominantly inherited phenotype designated Romano-Ward syndrome (RWS), which is also associated with arrhythmias and elevated risk of sudden death. Coassembly of certain mutant KCNE1 monomers with wild-type KCNQ1 subunits results in RWS by a dominant negative mechanism. This paper reviews variants of KCNE1 and their associated phenotypes, including biallelic truncating null variants of KCNE1 that have not been previously reported. We describe three homozygous nonsense mutations of KCNE1 segregating in families ascertained ostensibly for nonsyndromic deafness: c.50G>A (p.Trp17*), c.51G>A (p.Trp17*), and c.138C>A (p.Tyr46*). Some individuals carrying missense variants of KCNE1 have RWS. However, heterozygotes for loss-of-function variants of KCNE1 may have normal QT intervals while biallelic null alleles are associated with JLNS2, indicating a complex genotype-phenotype spectrum for KCNE1 variants.


Assuntos
Surdez/genética , Síndrome de Jervell-Lange Nielsen/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Síndrome de Romano-Ward/genética , Adolescente , Adulto , Códon sem Sentido/genética , Surdez/patologia , Feminino , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Heterozigoto , Homozigoto , Humanos , Síndrome de Jervell-Lange Nielsen/patologia , Síndrome do QT Longo , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , Linhagem , Fenótipo , Síndrome de Romano-Ward/patologia , Adulto Jovem
16.
Mol Cell Biochem ; 412(1-2): 297-305, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26728996

RESUMO

The mammalian DNA mismatch repair (MMR) system consists of a number of proteins that play important roles in repair of base pair mismatch mutations and in maintenance of genomic integrity. A defect in this system can cause genetic instability, which can lead to carcinogenesis. For instance, a germline mutation in one of the mismatch repair proteins, especially MLH1 or MSH2, is responsible for hereditary non-polyposis colorectal cancer. These MMR proteins also play an important role in the induction of apoptosis. Accordingly, altered expression of or a defect in MLH1 or MSH2 may confer resistance to anti-cancer drugs used in chemotherapy. We hypothesized that the ability of these two MMR proteins to regulate apoptosis are interdependent. Moreover, a defect in either one may confer resistance to chemotherapy by an inability to trigger apoptosis. To this end, we studied three cell lines-SW480, LoVo, and HTC116. These cell lines were selected based on their differential expression of MLH1 and MSH2 proteins. SW480 expresses both MLH1 and MSH2; LoVo expresses only MLH1 but not MSH2; HCT116 expresses only MSH2 but not MLH1 protein. MTT assays, a measure of cytotoxicity, showed that there were different cytotoxic effects of an anti-cancer drug, etoposide, on these cell lines, effects that were correlated with the MMR status of the cells. Cells that are deficient in MLH1 protein (HCT116 cells) were resistant to the drug. Cells that express both MLH1 and MSH2 proteins (SW480 cells) showed caspase-3 cleavage, an indicator of apoptosis. Cells that lack MLH1 (HCT116 cells) did not show any caspase-3 cleavage. Expression of full-length MLH1 protein was decreased in MMR proficient (SW480) cells during apoptosis; it remained unchanged in cells that lack MSH2 (LoVo cells). The expression of MSH2 protein remained unchanged during apoptosis both in MMR proficient (SW480) and deficient (HCT116) cells. Studies on translocation of MLH1 protein from nucleus to cytosolic fraction, an indicator of apoptosis, showed that MLH1 translocation only occurred in MMR proficient (SW480) cells upon induction of apoptosis further suggested a MSH2 dependent role of MLH1 in apoptosis. These data suggest a role of MLH1 in mediation of apoptosis in a MSH2-dependent manner. Taken together, our data supported an interdependence of mismatch repair proteins, particularly MLH1 and MSH2, in the mediation of apoptosis in human colorectal carcinoma cell lines.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Apoptose/fisiologia , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , Proteína 2 Homóloga a MutS/fisiologia , Proteínas Nucleares/fisiologia , Antineoplásicos/uso terapêutico , Caspase 3/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Etoposídeo/uso terapêutico , Humanos , Proteína 1 Homóloga a MutL , Proteólise
17.
Oncogene ; 35(21): 2698-710, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26387537

RESUMO

MOF (MYST1, KAT8) is the major H4K16 lysine acetyltransferase (KAT) in Drosophila and mammals and is essential for embryonic development. However, little is known regarding the role of MOF in specific cell lineages. Here we analyze the differential role of MOF in proliferating and terminally differentiated tissues at steady state and under stress conditions. In proliferating cells, MOF directly binds and maintains the expression of genes required for cell cycle progression. In contrast, MOF is dispensable for terminally differentiated, postmitotic glomerular podocytes under physiological conditions. However, in response to injury, MOF is absolutely critical for podocyte maintenance in vivo. Consistently, we detect defective nuclear, endoplasmic reticulum and Golgi structures, as well as presence of multivesicular bodies in vivo in podocytes lacking Mof following injury. Undertaking genome-wide expression analysis of podocytes, we uncover several MOF-regulated pathways required for stress response. We find that MOF, along with the members of the non-specific lethal but not the male-specific lethal complex, directly binds to genes encoding the lysosome, endocytosis and vacuole pathways, which are known regulators of podocyte maintenance. Thus, our work identifies MOF as a key regulator of cellular stress response in glomerular podocytes.


Assuntos
Histona Acetiltransferases/genética , Estresse Fisiológico/genética , Animais , Pontos de Checagem do Ciclo Celular/genética , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Histona Acetiltransferases/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Podócitos/citologia , Podócitos/metabolismo , Podócitos/fisiologia , Receptores Depuradores Classe A/genética , Receptores Depuradores Classe A/metabolismo , Transcrição Genética
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