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1.
Chin J Integr Med ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586557

RESUMO

COVID-19 virus is a causative agent of viral pandemic in human beings which specifically targets respiratory system of humans and causes viral pneumonia. This unusual viral pneumonia is rapidly spreading to all parts of the world, currently affecting about 105 million people with 2.3 million deaths. Current review described history, genomic characteristics, replication, and pathogenesis of COVID-19 with special emphasis on Nigella sativum (N. sativum) as a treatment option. N. sativum seeds are historically and religiously used over the centuries, both for prevention and treatment of different diseases. This review summarizes the potential role of N. sativum seeds against COVID-19 infection at levels of in silico, cell lines and animal models.

2.
APMIS ; 129(10): 579-586, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34342074

RESUMO

Coronavirus disease 2019 (COVID-19) is a novel respiratory disease that has led to a global pandemic and created a havoc. The COVID-19 disease severity varies among individuals, depending on fluctuating symptoms. Many infectious diseases such as hepatitis B and dengue hemorrhagic fever have been associated with ABO blood groups. The aim of this study was to explore whether ABO blood groups might serve as a risk or a protective factor for COVID-19 infection. Moreover, the symptomatic variations of COVID-19 infection among the individuals with different blood groups were also analyzed. An online questionnaire-based survey was conducted in which 305 partakers were included, who had successfully recovered from coronavirus infection. The ABO blood groups of 1294 healthy individuals were also taken as a control. The results of the current study demonstrated that antibody A containing blood groups (blood group B, p-value: 0.049 and blood group O, p-value: 0.289) had a protective role against COVID-19 infection. The comparison of symptomatic variations among COVID-19-infected subjects showed that blood group O subjects had lower chances of experiencing severe symptoms relating to respiratory distress, while subjects with AB blood group were more prone to develop symptoms, but the differences in both groups were found to be statistically non-significant. In conclusion, subjects who do not have anti-A antibodies in their serum (i.e., subjects with group A and AB) are more likely to be infected with COVID-19. The current data showed that there was no significant association of signs and symptoms variations of COVID-19 infection among individuals with different blood groups.


Assuntos
Sistema ABO de Grupos Sanguíneos , COVID-19/sangue , Adolescente , Adulto , Distribuição por Idade , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Inquéritos e Questionários , Adulto Jovem
3.
Mol Cell ; 81(16): 3356-3367.e6, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34297910

RESUMO

RNA polymerase II (RNAP II) pausing is essential to precisely control gene expression and is critical for development of metazoans. Here, we show that the m6A RNA modification regulates promoter-proximal RNAP II pausing in Drosophila cells. The m6A methyltransferase complex (MTC) and the nuclear reader Ythdc1 are recruited to gene promoters. Depleting the m6A MTC leads to a decrease in RNAP II pause release and in Ser2P occupancy on the gene body and affects nascent RNA transcription. Tethering Mettl3 to a heterologous gene promoter is sufficient to increase RNAP II pause release, an effect that relies on its m6A catalytic domain. Collectively, our data reveal an important link between RNAP II pausing and the m6A RNA modification, thus adding another layer to m6A-mediated gene regulation.


Assuntos
Proteínas de Drosophila/genética , Complexos Multiproteicos/genética , Proteínas Nucleares/genética , RNA Polimerase II/genética , Transcrição Genética , Animais , Drosophila melanogaster/genética , Metiltransferases/genética , Regiões Promotoras Genéticas/genética
4.
Nat Commun ; 11(1): 480, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980599

RESUMO

Mutations in the actively expressed, maternal allele of the imprinted KCNK9 gene cause Birk-Barel intellectual disability syndrome (BBIDS). Using a BBIDS mouse model, we identify here a partial rescue of the BBIDS-like behavioral and neuronal phenotypes mediated via residual expression from the paternal Kcnk9 (Kcnk9pat) allele. We further demonstrate that the second-generation HDAC inhibitor CI-994 induces enhanced expression from the paternally silenced Kcnk9 allele and leads to a full rescue of the behavioral phenotype suggesting CI-994 as a promising molecule for BBIDS therapy. Thus, these findings suggest a potential approach to improve cognitive dysfunction in a mouse model of an imprinting disorder.


Assuntos
Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/metabolismo , Histonas/metabolismo , Deficiência Intelectual/genética , Deficiência Intelectual/metabolismo , Hipotonia Muscular/genética , Hipotonia Muscular/metabolismo , Canais de Potássio/genética , Animais , Comportamento Animal , Benzamidas , Encéfalo/metabolismo , Anormalidades Craniofaciais/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Impressão Genômica , Inibidores de Histona Desacetilases/farmacologia , Humanos , Deficiência Intelectual/tratamento farmacológico , Locus Cerúleo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hipotonia Muscular/tratamento farmacológico , Mutação , Fenótipo , Fenilenodiaminas/farmacologia , Canais de Potássio/deficiência , Canais de Potássio/metabolismo , Regulação para Cima/efeitos dos fármacos
5.
Comp Immunol Microbiol Infect Dis ; 66: 101345, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31476607

RESUMO

Campylobacter jejuni is a major cause of infectious diarrhea in humans. The bacterium can be transmitted through contaminated poultry meat and waste water. We report the presence of C. jejuni from potential transmission sources including egg shells, poultry waste, waste water and migratory bird droppings with a prevalence rate of 78%, 66%, 86% and 70% respectively. Antibiotic resistance profile showed high number of isolates resistant to multiple antibiotics including 4th generation cephalosporins. C. jejuni isolates were further screened for presence of T6SS, an important virulence factor. None of the C. jejuni isolates from migratory birds carried a T6SS, whereas highest prevalence of T6SS isolates was observed in waste water samples, followed by poultry waste and egg shells. To determine virulence potential of the isolates, hemolytic activity of isolates was compared. Although variation in hemolytic potential between isolates from different sources was noted, higher hemolytic activity was observed for isolates possessing hcp, a T6SS gene. Furthermore, presence of T6SS affords the bacterium some survival advantage when compared to T6SS competent Helicobacter pullorum which occupies the same niche. Taken together our findings indicate that C. jejuni with T6SS have a fitness advantage increasing their isolation frequency from waste water and poultry waste.


Assuntos
Antibacterianos/farmacologia , Infecções por Campylobacter/veterinária , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/patogenicidade , Sistemas de Secreção Tipo VI/genética , Migração Animal , Animais , Aves/microbiologia , Infecções por Campylobacter/transmissão , Campylobacter jejuni/genética , DNA Bacteriano/genética , Casca de Ovo/microbiologia , Aves Domésticas/microbiologia , Virulência , Águas Residuárias/microbiologia
6.
Elife ; 82019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31535971

RESUMO

Sensory systems sequentially extract increasingly complex features. ON and OFF pathways, for example, encode increases or decreases of a stimulus from a common input. This ON/OFF pathway split is thought to occur at individual synaptic connections through a sign-inverting synapse in one of the pathways. Here, we show that ON selectivity is a multisynaptic process in the Drosophila visual system. A pharmacogenetics approach demonstrates that both glutamatergic inhibition through GluClα and GABAergic inhibition through Rdl mediate ON responses. Although neurons postsynaptic to the glutamatergic ON pathway input L1 lose all responses in GluClα mutants, they are resistant to a cell-type-specific loss of GluClα. This shows that ON selectivity is distributed across multiple synapses, and raises the possibility that cell-type-specific manipulations might reveal similar strategies in other sensory systems. Thus, sensory coding is more distributed than predicted by simple circuit motifs, allowing for robust neural processing.


Assuntos
Drosophila/fisiologia , Interneurônios/fisiologia , Vias Visuais/fisiologia , Percepção Visual , Animais , Fármacos Atuantes sobre Aminoácidos Excitatórios/metabolismo , GABAérgicos/metabolismo , Modelos Neurológicos
7.
Life Sci Alliance ; 2(4)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31331983

RESUMO

Chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-Seq) is a powerful technique to study transcriptional regulation. However, the requirement of millions of cells to generate results with high signal-to-noise ratio precludes it in the study of small cell populations. Here, we present a tagmentation-assisted fragmentation ChIP (TAF-ChIP) and sequencing method to generate high-quality histone profiles from low cell numbers. The data obtained from the TAF-ChIP approach are amenable to standard tools for ChIP-Seq analysis, owing to its high signal-to-noise ratio. The epigenetic profiles from TAF-ChIP approach showed high agreement with conventional ChIP-Seq datasets, thereby underlining the utility of this approach.


Assuntos
Sequenciamento de Cromatina por Imunoprecipitação/métodos , Drosophila/genética , Histonas/metabolismo , Animais , Epigênese Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Células K562 , Razão Sinal-Ruído , Software , Sequenciamento Completo do Genoma
8.
Health Secur ; 17(3): 229-239, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31206321

RESUMO

Dual-use research poses a significant challenge for scientists in the biomedical field and for global health security in general. As the scientific knowledge and materials required for the development of biological agents become progressively more accessible and inexpensive, there is an increased need to understand and improve the governance of scientific research. Prevention of the misuse of facilities, equipment, agents, and scientific knowledge requires high levels of awareness of the concept of dual-use research, starting with early-career scientists and graduate students. In this study, the attitudes and level of awareness of postgraduate students in Pakistan toward the issues surrounding dual-use research were assessed through a survey containing both quantitative and qualitative questions in 32 universities in 4 provinces, federal area, and Azad Jammu and Kashmir regions of Pakistan; 933 students responded. Most (58.2%) had never heard of dual-use research of concern (DURC), while 18.5% had heard the term but were unsure of its meaning. Irrespective of prior knowledge, a higher percentage of students (68.6%) felt an obligation to report research misuse. Considering the need for DURC training, 94.1% of the respondents agreed that the principal investigator should take the responsibility to train students on DURC at the start of a research project. When experimental results having dual-use potential, 69.1% indicated they would publish with limited protocol, with 43.5% indicating they would publish the limited protocol only if there was a way for scientists to access their data. The survey results revealed limited DURC awareness among researchers across Pakistan. However, the respondents, although not formally educated about DURC, were quite aware of its impact. The information gained in this survey will be valuable in addressing country-specific awareness and training needs.


Assuntos
Pesquisa Biomédica/ética , Disseminação de Informação/ética , Estudantes/psicologia , Pesquisa Biomédica/normas , Bioterrorismo/prevenção & controle , Contenção de Riscos Biológicos/ética , Estudos Transversais , Humanos , Paquistão , Medidas de Segurança/ética , Medidas de Segurança/normas , Inquéritos e Questionários
9.
Nat Commun ; 10(1): 521, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30705266

RESUMO

Promoter-proximal pausing of RNA polymerase II (Pol II) is a widespread transcriptional regulatory step across metazoans. Here we find that the nuclear exon junction complex (pre-EJC) is a critical and conserved regulator of this process. Depletion of pre-EJC subunits leads to a global decrease in Pol II pausing and to premature entry into elongation. This effect occurs, at least in part, via non-canonical recruitment of pre-EJC components at promoters. Failure to recruit the pre-EJC at promoters results in increased binding of the positive transcription elongation complex (P-TEFb) and in enhanced Pol II release. Notably, restoring pausing is sufficient to rescue exon skipping and the photoreceptor differentiation defect associated with depletion of pre-EJC components in vivo. We propose that the pre-EJC serves as an early transcriptional checkpoint to prevent premature entry into elongation, ensuring proper recruitment of RNA processing components that are necessary for exon definition.


Assuntos
Éxons/genética , Animais , Núcleo Celular/genética , Núcleo Celular/metabolismo , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , Células HeLa , Humanos , Regiões Promotoras Genéticas/genética , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Splicing de RNA/genética
10.
Nature ; 540(7632): 242-247, 2016 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-27919077

RESUMO

N6-methyladenosine RNA (m6A) is a prevalent messenger RNA modification in vertebrates. Although its functions in the regulation of post-transcriptional gene expression are beginning to be unveiled, the precise roles of m6A during development of complex organisms remain unclear. Here we carry out a comprehensive molecular and physiological characterization of the individual components of the methyltransferase complex, as well as of the YTH domain-containing nuclear reader protein in Drosophila melanogaster. We identify the member of the split ends protein family, Spenito, as a novel bona fide subunit of the methyltransferase complex. We further demonstrate important roles of this complex in neuronal functions and sex determination, and implicate the nuclear YT521-B protein as a main m6A effector in these processes. Altogether, our work substantially extends our knowledge of m6A biology, demonstrating the crucial functions of this modification in fundamental processes within the context of the whole animal.


Assuntos
Adenosina/análogos & derivados , Drosophila melanogaster/fisiologia , Neurônios/fisiologia , Processos de Determinação Sexual/fisiologia , Adenosina/metabolismo , Processamento Alternativo , Animais , Comportamento Animal/fisiologia , Proteínas de Drosophila/química , Proteínas de Drosophila/deficiência , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/enzimologia , Feminino , Masculino , Metiltransferases/química , Metiltransferases/metabolismo , Sistema Nervoso/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fenótipo , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Proteínas de Ligação a RNA/genética , Processos de Determinação Sexual/genética
11.
Elife ; 42015 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-25779349

RESUMO

Divergent morphology of species has largely been ascribed to genetic differences in the tissue-specific expression of proteins, which could be achieved by divergence in cis-regulatory elements or by altering the binding specificity of transcription factors (TFs). The relative importance of the latter has been difficult to assess, as previous systematic analyses of TF binding specificity have been performed using different methods in different species. To address this, we determined the binding specificities of 242 Drosophila TFs, and compared them to human and mouse data. This analysis revealed that TF binding specificities are highly conserved between Drosophila and mammals, and that for orthologous TFs, the similarity extends even to the level of very subtle dinucleotide binding preferences. The few human TFs with divergent specificities function in cell types not found in fruit flies, suggesting that evolution of TF specificities contributes to emergence of novel types of differentiated cells.


Assuntos
Evolução Biológica , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Sítios de Ligação , Drosophila , Duplicação Gênica , Humanos , Camundongos , Filogenia , Técnica de Seleção de Aptâmeros , Homologia de Sequência de Aminoácidos
12.
Genes Dev ; 28(16): 1786-99, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25104425

RESUMO

The exon junction complex (EJC) is a highly conserved ribonucleoprotein complex that binds RNAs during splicing and remains associated with them following export to the cytoplasm. While the role of this complex in mRNA localization, translation, and degradation has been well characterized, its mechanism of action in splicing a subset of Drosophila and human transcripts remains to be elucidated. Here, we describe a novel function for the EJC and its splicing subunit, RnpS1, in preventing transposon accumulation in both Drosophila germline and surrounding somatic follicle cells. This function is mediated specifically through the control of piwi transcript splicing, where, in the absence of RnpS1, the fourth intron of piwi is retained. This intron contains a weak polypyrimidine tract that is sufficient to confer dependence on RnpS1. Finally, we demonstrate that RnpS1-dependent removal of this intron requires splicing of the flanking introns, suggesting a model in which the EJC facilitates the splicing of weak introns following its initial deposition at adjacent exon junctions. These data demonstrate a novel role for the EJC in regulating piwi intron excision and provide a mechanism for its function during splicing.


Assuntos
Proteínas Argonauta/metabolismo , Elementos de DNA Transponíveis/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila/genética , Drosophila/metabolismo , Splicing de RNA , Ribonucleoproteínas/metabolismo , Animais , Proteínas Argonauta/genética , DNA Complementar/metabolismo , Proteínas de Drosophila/genética , Feminino , Técnicas de Silenciamento de Genes , Inativação Gênica , Íntrons/genética , Mutação , Ovário/citologia , Ovário/metabolismo , Subunidades Proteicas/metabolismo , Ribonucleoproteínas/genética
13.
Appl Microbiol Biotechnol ; 98(3): 987-1000, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24292125

RESUMO

Production of succinic acid via separate enzymatic hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) are alternatives and are environmentally friendly processes. These processes have attained considerable positions in the industry with their own share of challenges and problems. The high-value succinic acid is extensively used in chemical, food, pharmaceutical, leather and textile industries and can be efficiently produced via several methods. Previously, succinic acid production via chemical synthesis from petrochemical or refined sugar has been the focus of interest of most reviewers. However, these expensive substrates have been recently replaced by alternative sustainable raw materials such as lignocellulosic biomass, which is cheap and abundantly available. Thus, this review focuses on succinic acid production utilizing lignocellulosic material as a potential substrate for SSF and SHF. SSF is an economical single-step process which can be a substitute for SHF - a two-step process where biomass is hydrolyzed in the first step and fermented in the second step. SSF of lignocellulosic biomass under optimum temperature and pH conditions results in the controlled release of sugar and simultaneous conversion into succinic acid by specific microorganisms, reducing reaction time and costs and increasing productivity. In addition, main process parameters which influence SHF and SSF processes such as batch and fed-batch fermentation conditions using different microbial strains are discussed in detail.


Assuntos
Biomassa , Lignina/metabolismo , Ácido Succínico/metabolismo , Fermentação , Hidrólise
14.
BMJ Case Rep ; 20122012 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-22962389

RESUMO

The authors present the case of a 45-year-old lady who presented to the emergency department with sudden onset of right hemiparesis, numbness, dysarthria, dysmetria, left upper motor neuron facial palsy and left extensor plantar. Initial laboratory investigations, ECG and MR angiography were normal. MRI brain revealed multiple ischaemic strokes in middle cerebral artery and posterior cerebral artery territory. Transthoracic echocardiography revealed large mobile mass in left atrium which was resected and the patient remained well postoperatively. Anticoagulants do not play any protective role making resection as the only effective treatment.


Assuntos
Isquemia Encefálica/etiologia , Átrios do Coração , Neoplasias Cardíacas/complicações , Mixoma/complicações , Acidente Vascular Cerebral/etiologia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Ecocardiografia , Feminino , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mixoma/diagnóstico por imagem , Mixoma/cirurgia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia
15.
Genome Biol ; 13(9): R49, 2012 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-22950968

RESUMO

BACKGROUND: Advances in sequencing technology have boosted population genomics and made it possible to map the positions of transcription factor binding sites (TFBSs) with high precision. Here we investigate TFBS variability by combining transcription factor binding maps generated by ENCODE, modENCODE, our previously published data and other sources with genomic variation data for human individuals and Drosophila isogenic lines. RESULTS: We introduce a metric of TFBS variability that takes into account changes in motif match associated with mutation and makes it possible to investigate TFBS functional constraints instance-by-instance as well as in sets that share common biological properties. We also take advantage of the emerging per-individual transcription factor binding data to show evidence that TFBS mutations, particularly at evolutionarily conserved sites, can be efficiently buffered to ensure coherent levels of transcription factor binding. CONCLUSIONS: Our analyses provide insights into the relationship between individual and interspecies variation and show evidence for the functional buffering of TFBS mutations in both humans and flies. In a broad perspective, these results demonstrate the potential of combining functional genomics and population genetics approaches for understanding gene regulation.


Assuntos
Drosophila/genética , Variação Genética , Genoma Humano , Genoma de Inseto , Fatores de Transcrição/metabolismo , Análise de Variância , Animais , Sítios de Ligação , Humanos , Modelos Genéticos , Anotação de Sequência Molecular , Mutação , Motivos de Nucleotídeos , Matrizes de Pontuação de Posição Específica , Sequências Reguladoras de Ácido Nucleico , Análise de Sequência de DNA/métodos
16.
BMJ Case Rep ; 20122012 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-22850564

RESUMO

We present the case of a 28-year-old gentleman who presented with weakness and wasting in the right arm. He complained about painful cramps in his left leg but there were no sensory, visual or swallowing problems. Neurological examination was significant for asymmetric weakness of both upper and lower limbs and deep tendon reflexes were asymmetrically brisk. Initial laboratory investigations, MRI brain and MRI spine were normal. Electromyography revealed active denervation and chronic neurogenic motor unit action potential. Myokymic discharges were noted in the left deltoid muscle.


Assuntos
Anticonvulsivantes/uso terapêutico , Músculo Deltoide/fisiopatologia , Doença dos Neurônios Motores/fisiopatologia , Cãibra Muscular/fisiopatologia , Espasticidade Muscular/fisiopatologia , Mioquimia/fisiopatologia , Riluzol/uso terapêutico , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Baclofeno/uso terapêutico , Aconselhamento Diretivo , Humanos , Imageamento por Ressonância Magnética , Masculino , Doença dos Neurônios Motores/diagnóstico , Doença dos Neurônios Motores/terapia , Cãibra Muscular/diagnóstico , Cãibra Muscular/tratamento farmacológico , Relaxantes Musculares Centrais/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Mioquimia/diagnóstico , Mioquimia/terapia , Quinina/uso terapêutico
17.
J Ayub Med Coll Abbottabad ; 17(1): 89-91, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15929541

RESUMO

Physicians are often confronted with patients who state that they are "allergic" to a drug. The goal of this review article is to help physicians to develop management plans for patients who present with drug induced diseases. It provides information that allows physicians to differentiate between reactions that are truly allergic in nature and those that are not immunologically mediated. The suggestions which may be helpful in the assessment are discussed and guidance is provided whether a drug may be safely readministered. Unfortunately until we are unable to thoroughly understand the mechanisms responsible for drug induced reactions, our management tools will remair limited.


Assuntos
Hipersensibilidade a Drogas/classificação , Hipersensibilidade a Drogas/diagnóstico , Humanos
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