RESUMO
Basophils are evolutionarily conserved in vertebrates, despite their small numbers and short life span, suggesting that they have beneficial roles in maintaining health. However, these roles are not fully defined. Here we demonstrate that basophil-deficient mice exhibit reduced bacterial clearance and increased morbidity and mortality in the cecal ligation and puncture (CLP) model of sepsis. Among the several proinflammatory mediators that we measured, tumor necrosis factor (TNF) was the only cytokine that was significantly reduced in basophil-deficient mice after CLP. In accordance with that observation, we found that mice with genetic ablation of Tnf in basophils exhibited reduced systemic concentrations of TNF during endotoxemia. Moreover, after CLP, mice whose basophils could not produce TNF, exhibited reduced neutrophil and macrophage TNF production and effector functions, reduced bacterial clearance, and increased mortality. Taken together, our results show that basophils can enhance the innate immune response to bacterial infection and help prevent sepsis.
Assuntos
Basófilos/imunologia , Endotoxemia/imunologia , Imunidade Inata , Fator de Necrose Tumoral alfa/imunologia , Transferência Adotiva , Animais , Basófilos/metabolismo , Ceco/microbiologia , Modelos Animais de Doenças , Endotoxemia/microbiologia , Endotoxemia/terapia , Microbioma Gastrointestinal , Humanos , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Taxa de Sobrevida , Fator de Necrose Tumoral alfa/genéticaRESUMO
Although widely used, assisted reproductive technologies (ARTs) are associated with adverse perinatal outcomes. To elucidate their underlying causes, we have conducted a longitudinal analysis of placental development and fetal growth using a mouse model to investigate the effects of individual ART procedures: hormone stimulation, in vitro fertilization (IVF), embryo culture and embryo transfer. We demonstrate that transfer of blastocysts naturally conceived without hormone stimulation and developed in vivo prior to transfer can impair early placentation and fetal growth, but this effect normalizes by term. In contrast, embryos cultured in vitro before transfer do not exhibit this compensation but rather display placental overgrowth, reduced fetal weight, reduced placental DNA methylation and increased levels of sFLT1, an anti-angiogenic protein implicated in causing the maternal symptoms of preeclampsia in humans. Increases in sFLT1 observed in this study suggest that IVF procedures could increase the risk for preeclampsia. Moreover, our results indicate that embryo culture is the major factor contributing to most placental abnormalities and should therefore be targeted for optimization.
Assuntos
Placenta/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Metilação de DNA , Transferência Embrionária , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário , Feminino , Fertilização in vitro , Masculino , Camundongos , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Pré-Eclâmpsia/veterinária , Gravidez , Risco , Simportadores/genética , Simportadores/metabolismo , Trofoblastos/citologia , Trofoblastos/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
RNA Polymerase II (RNAPII) transcription termination is regulated by the phosphorylation status of the C-terminal domain (CTD). The phosphatase Rtr1 has been shown to regulate serine 5 phosphorylation on the CTD; however, its role in the regulation of RNAPII termination has not been explored. As a consequence of RTR1 deletion, interactions within the termination machinery and between the termination machinery and RNAPII were altered as quantified by Disruption-Compensation (DisCo) network analysis. Of note, interactions between RNAPII and the cleavage factor IA (CF1A) subunit Pcf11 were reduced in rtr1Δ, whereas interactions with the CTD and RNA-binding termination factor Nrd1 were increased. Globally, rtr1Δ leads to decreases in numerous noncoding RNAs that are linked to the Nrd1, Nab3 and Sen1 (NNS) -dependent RNAPII termination pathway. Genome-wide analysis of RNAPII and Nrd1 occupancy suggests that loss of RTR1 leads to increased termination at noncoding genes. Additionally, premature RNAPII termination increases globally at protein-coding genes with a decrease in RNAPII occupancy occurring just after the peak of Nrd1 recruitment during early elongation. The effects of rtr1Δ on RNA expression levels were lost following deletion of the exosome subunit Rrp6, which works with the NNS complex to rapidly degrade a number of noncoding RNAs following termination. Overall, these data suggest that Rtr1 restricts the NNS-dependent termination pathway in WT cells to prevent premature termination of mRNAs and ncRNAs. Rtr1 facilitates low-level elongation of noncoding transcripts that impact RNAPII interference thereby shaping the transcriptome.
Assuntos
Códon de Terminação/genética , RNA Polimerase II/genética , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/genética , Transcrição Gênica/genética , DNA Helicases/genética , Regulação Fúngica da Expressão Gênica/genética , Proteínas Nucleares/genética , Fosfoproteínas Fosfatases/genética , Fosforilação/genética , RNA Helicases/genética , RNA Mensageiro/genética , RNA não Traduzido/genética , Saccharomyces cerevisiae/genéticaRESUMO
PURPOSE: To evaluate pre-implantation genetic testing for aneuploidy (PGT-A) outcomes in patients without infertility compared to infertile patients. METHODS: We performed a retrospective cohort study of all patients without an infertility diagnosis ("fertile" patients) who utilized PGT-A at a large university-affiliated fertility center between 2016 and 2021. Fertile patients were 1-to-3 matched to infertile controls by age and number of oocytes retrieved. The primary outcome was blastocyst aneuploidy rate. Secondary outcomes included ovarian reserve markers, laboratory outcomes, and other PGT-A outcomes [rates of euploidy, mosaicism, and potentially transferrable (euploid + mosaic) embryos]. RESULTS: 283 fertile and 849 infertile patients were included. Median age, anti-Mullerian hormone, and day 2 estradiol levels were equivalent among groups; day 2 follicle-stimulating hormone levels were higher in fertile patients (6.9 vs. 6.5 IU/mL, p < 0.01). The aneuploidy rate was similar among fertile and infertile patients (33.7% vs. 31.8%, p = 0.11); the euploidy rate was higher (50.8% vs. 47.0%, p < 0.01), and the mosaicism rate was lower in fertile patients (13.3% vs. 19.2%, p < 0.01). The rate of transferrable embryos was similar among groups (64.0% vs. 66.3%, p = 0.07), as was the percentage of patients yielding ≥ 1 euploid embryo (90.1% vs. 87.3%, p = 0.25). When controlling for significant covariates, multiple linear regression showed that aneuploidy rate was equivalent in both cohorts. CONCLUSION: Aneuploidy rate was similar in fertile and infertile patients. Fertile patients had slightly higher euploidy and lower mosaicism than infertile patients. Still, compared to fertile patients, infertile patients had equivalent rates of transferrable embryos and were just as likely to yield ≥ 1 euploid embryo.
Assuntos
Infertilidade , Diagnóstico Pré-Implantação , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Fertilização in vitro , Aneuploidia , Testes Genéticos , Blastocisto , MosaicismoRESUMO
The diverse population of microbes that live in our digestive system, known as the gut microbiota, remains essential for many physiological processes. It plays a role in obtaining energy from food and controls both regional and overall immunity. In addition, changes in the microbiota of the digestive tract are connected to the emergence of an extensive variety of illnesses, such as cancer, gastrointestinal problems, and metabolic disorders. From a metabolic perspective, the gut microbiota can affect processes like lipid accumulation, lipopolysaccharide satisfied, and short-chain fatty acid synthesis, all of which have an effect on food intake, inflammatory reactions, and insulin signaling. Prebiotics, probiotics, specialized anti-diabetic medications, and faecalmicrobiota implantation are a few of the ways that have been discovered to alter the gut microbiota; each has a different influence the human body's metabolism and the emergence of metabolic disorders. These therapies have been reported to be therapeutic strategies for enhancing general wellness and reestablishing a balanced gut flora.
Assuntos
Microbioma Gastrointestinal , Doenças Metabólicas , Síndrome Metabólica , Microbiota , Probióticos , Humanos , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal , Probióticos/uso terapêuticoRESUMO
Complex inflammatory skin disease with autoimmune roots is psoriasis. This disease affects various cell types, and the underlying signaling processes are complicated yet not fully understood. Extensive psoriatic lesions' proteome and transcriptome of several researches were combined to understand disease's underlying biological mechanisms. According to a network-based study, both transcriptomics and proteomics control were comparable. They discovered many pathways of signaling previously undiscovered and possibly involved in overexpression of psoriasis genes. They also found a collection of transcription factors in charge of this process. The functional overlap between the results of transcriptomics and proteomics was also examined. There created a network-based method for combining the analysis of many high-throughput data sources. Proteomic and transcriptome studies of psoriasis data sets demonstrated regulatory flexibility apparatus underpinning disease and complementary relationships within two cellular organizations.
Assuntos
Psoríase , Transcriptoma , Humanos , Proteômica/métodos , Queratinócitos/metabolismo , Perfilação da Expressão Gênica/métodos , Psoríase/genética , Pele/metabolismoRESUMO
Primary Immunodeficiency Disease (PID) represents a class of diverse illnesses marked by compromised immune system performance. For better patient outcomes, PIDs must be diagnosed and treated quickly. Medical graduates are essential to the detection and treatment of these illnesses. The purpose of this study was to evaluate medical students' knowledge about PIDs in different Indian medical colleges. To perform this analytical investigation, college students from Maharashtra-area universities were enlisted between March and April of 2023. The participants received a questionnaire from mediators from every institution. Of the 500 students in the study, 66% were between the ages of 22 and 24 and 52% were female. Their understanding ratings had an average of 16.3±6.2 and varied between 4 and 32. A set of students classified as below average (86%) and a mean/above average (14%), were separated among the students. The largest percentage of above-average knowledge was demonstrated by VI-year participants (p<0.05). This investigation emphasizes how critical it is to provide focused educational activities to improve medical students' comprehension of PIDs in India.
Assuntos
Doenças da Imunodeficiência Primária , Estudantes de Medicina , Humanos , Feminino , Adulto Jovem , Adulto , Masculino , Índia/epidemiologia , Inquéritos e Questionários , UniversidadesRESUMO
Separating aneurysmal arterial disease from atherosclerosis and further occlusive artery conditions, it is a vascular degenerative disorder. Within the vascular tree, there is a regionalization of the propensity to produce aneurysms and the different locations result in different clinical processes. As the predominant risk factor for ubrenal abdominal aortic aneurysm (AAA), smoking is one of the most common manifestations of aneurysmal illness. For AAA compared to atherosclerosis, smoking is a far bigger risk factor. Along with contributing to the pathophysiology of AAA, smoking raises the likelihood that established AAA will rupture as well as its rate of expansion. The development of improved models for animals that are reliant on smoke or smoke constituents is helping to determine the mechanistic connection between AAA and smoking. According to the processes, there are long-lasting changes in the function of inflammatory and vascular smooth muscle cells. Focused on AAA, this review looks at the medical, epidemiology and mechanical evidence that links smoking to aneurysms.
Assuntos
Aneurisma da Aorta Abdominal , Aterosclerose , Produtos do Tabaco , Animais , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/etiologia , Aterosclerose/complicações , Nicotina/toxicidade , Fumaça , HumanosRESUMO
A prevalent psychiatric disorder called Child Separation Anxiety Disorder (SAD) is characterized by extreme discomfort when a child gets separated from their primary carers. While SAD's quick consequences on kids are well-researched, its long-term implications for teenage psychopathology have received less attention. This longitudinal study aims to ascertain the connection between child SAD and future psychopathological consequences in adolescents. 500 adolescents were chosen as part of the adolescent depression project, and at the age of 17, we retrospectively evaluated past and present mental disorders. At ages 25 and 32, they conducted diagnostic evaluations of these people during adolescence while they continued to monitor them. Based on childhood/adolescent assessments, the participants were split into different groups: SAD (n=34), other forms of Anxiety (n=76), a control group with combined psychiatric conditions (n=205), and mentally sound control group (n=185). Statistics were evaluated by hierarchical multiple logistic regression after various illnesses and pertinent demographic variables were considered. It implies that SAD has a high risk (80.2%) of being a significant risk indicator for the emergence of mental illnesses in young adults. This study highlights the importance of early SAD management and therapy and the possible advantages of treating SAD in lowering the likelihood of developing other mental health problems in adolescence. It also emphasizes the value of continuous studies to comprehend these connections and enhance the effects on SAD sufferers' psychological well-being.
Assuntos
Transtornos de Ansiedade , Ansiedade de Separação , Humanos , Adolescente , Criança , Ansiedade de Separação/diagnóstico , Ansiedade de Separação/psicologia , Estudos Longitudinais , Estudos Retrospectivos , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , AnsiedadeRESUMO
Aim - determining the prevalence of anxiety disorders and their effect on disease progression and quality of life in adults with organic illnesses and functional disorders of the respiratory system treated in a pulmonology environment. A total of 135 young adults between the ages of 13 and 17 were analyzed. There were a total of 46 adolescents diagnosed with somatoform respiratory disorders (SRD), 45 adolescents diagnosed with bronchial asthma (BA), and 44 adolescents diagnosed with pneumonia. The Spielberger-Khanin anxiety questionnaire and the Nijmegen hyperventilation syndrome (HVS) scale were used for the research and diagnosis, respectively. The quality of life was measured using the asthma quality of life questionnaire (AQLQ). In comparison to adults with asthma (33.2%) and pneumonia (32.3%), adults with SRD (34.5%). There were mild immediate associations between the Spielberger scale and the Nijmegen HVS questionnaire for both trait and state anxiety, and mild inverse correlations between the Spielberger scale and the AQLQ for both state and trait anxiety. Adolescents with anxiety had a higher prevalence of trauma, pain, and social issues than their non-anxious counterparts who were referred to psychiatry. In adolescents, 5.1% had severe trait anxiety, and 19.3% had severe condition anxiety. Adolescents with SRD were twice as likely to suffer from extreme state and trait anxiety as the general population. It is hypothesized that anxiety problems are at the root of HVS and contribute to adults' dissatisfaction with their quality of life due to lung ailments. Although certain adolescents with anxiety disorders were referred for anxiety, this data nevertheless lends credence to the idea that using standardized and structured instruments regularly might help increase accuracy and detection rates in the clinic, regardless of the reason for referral. Complete evaluations are essential for this patient population due to the intricacy of their symptoms.
Assuntos
Asma , Pneumonia , Adulto Jovem , Humanos , Adolescente , Estudos Prospectivos , Qualidade de Vida , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Hiperventilação/diagnóstico , Hiperventilação/epidemiologia , Síndrome , Inquéritos e QuestionáriosRESUMO
BACKGROUND & OBJECTIVES: Kyasanur Forest Disease (KFD) is a vector borne haemorrhagic fever that is endemic in the Wayanad region located in Northern part of Kerala, India. The region is managing the outbreak well ever since the major epidemic of 2015. This was because of the successful implementation of One Health (OH) initiative concentrating on multisectoral collaboration between regional institutions involved in public, animal and environmental health domains. The article presents how OH was implemented for the first time in the district in the year 2015 and evaluates the degree OH-ness of the Initiative. METHODS: The OH approach involved trans-disciplinary stakeholder meetings and reviews, outbreak management and integrated surveillance targeting ticks, monkeys and humans. The degree of OH-ness used for addressing KFD during the year 2015 was evaluated following the protocol developed by the Network for Evaluation of One Health (NEOH). In detail, we (i) described the OH initiative and its system (Aim, stakeholders, action strategy) and (ii) scored different aspects of this initiative (i.e., OH-thinking, -planning, -working, -sharing, -learning, -organization), with values from 0 (=no OH approach) to 1 (=perfect OH approach). RESULTS: We obtained a median score for each aspect evaluated. We reached high scores for OH systemic organization (1.0), OH thinking (0.83) and OH working (0.83). Lower scores were attributed to OH planning (0.58), OH sharing (0.50) and OH learning (0.33). The OH index was 0.36 and OH ratio was 0.95, indicating a balance between the OH operations and supporting infrastructures. INTERPRETATION & CONCLUSION: With this we could high-light some critical issues related to communication on sharing data as well as learning gaps for consideration to control future outbreaks. The strengths and weaknesses detected may be used to refine the initiative, aiming to provide a basis for the development of shared recommendations in a more OH-oriented perspective. This model of evaluation criteria will serve to create a database of OH success stories in India that will in turn help to institutionalize the approach at ministerial level. Future India is moving towards implementing a One Health, hence, this study data will provide an ideal opportunity for all sectors to control any vector borne diseases.
Assuntos
Doença da Floresta de Kyasanur , Saúde Única , Animais , Surtos de Doenças/prevenção & controle , Vetores de Doenças , Índia/epidemiologia , Doença da Floresta de Kyasanur/epidemiologia , Doença da Floresta de Kyasanur/prevenção & controleRESUMO
Smarter and minimization of devices are consistently substantial to shape the energy landscape. Significant amounts of endeavours have come forward as promising steps to surmount this formidable challenge. It is undeniable that material scientists were contemplating smarter material beyond purely inorganic or organic materials. To our delight, metal-organic frameworks (MOFs), an inorganic-organic hybrid scaffold with unprecedented tunability and smart functionalities, have recently started their journey as an alternative. In this review, we focus on such propitious potential of MOFs that was untapped over a long time. We cover the synthetic strategies and (or) post-synthetic modifications towards the formation of conductive MOFs and their underlying concepts of charge transfer with structural aspects. We addressed theoretical calculations with the experimental outcomes and spectroelectrochemistry, which will trigger vigorous impetus about intrinsic electronic behaviour of the conductive frameworks. Finally, we discussed electrocatalysts and energy storage devices stemming from conductive MOFs to meet energy demand in the near future.
Assuntos
Estruturas Metalorgânicas , Condutividade Elétrica , EletrônicaRESUMO
INTRODUCTION: The identification and follow-up of ultra-short Barrett's esophagus (BE) is controversial. BE surveillance guidelines emphasize mainly on long-segment BE. However, in practice a substantial proportion of esophageal adenocarcinoma (EAC) are found close to the gastro-esophageal junction (GEJ). Our study aims to chart the length of BE when low-grade dysplasia (LGD), high-grade dysplasia (HGD) and EAC arise in BE. METHODS: Endoscopic findings from all cases with a diagnosis of LGD and HGD in BE between June 2014 and June 2019, and 100 consecutive cases of EAC diagnosed between June 2018 and August 2019, were reviewed. Additionally, 438 consecutive gastroscopies were reviewed to identify 100 cases of non-dysplastic BE. RESULTS: 99 cases of LGD and 61 cases of HGD were reviewed. LGD and HGD when diagnosed, was located in BE ≤ 1 cm in 20% and 18% cases, respectively. LGD and HGD when diagnosed, was located in BE ≤ 3 cm in 48.5% and 40.9% cases, respectively. LGD and HGD when diagnosed in BE ≤ 3 cm was found at index endoscopy in 67% and 42% cases, respectively. Of the 100 cases of EAC, only 23 had concurrent visible BE, with BE higher than the level of EAC in seven. EAC when found, had its proximal extent ≤ 1 cm from GEJ in 22% and ≤ 3 cm from GEJ in 40% cases. Of the 100 non-dysplastic BE, 53% were ≤ 1 cm and 78% were ≤ 3 cm long. CONCLUSION: Almost 20% of all dysplasia in BE occurs in BE < 1 cm. Over 40% occurs in BE < 3 cm. Similarly, 20% of EAC occurs within 1 cm of GEJ and 40% occur within 3 cm. A majority of dysplasia diagnosed within 3 cm of the GEJ is found on index endoscopy. We propose that all lengths of columnar lined epithelium above the GEJ are recognized as BE and subjected to a thorough biopsy protocol.
Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Lesões Pré-Cancerosas , Adenocarcinoma/epidemiologia , Biópsia , Progressão da Doença , Neoplasias Esofágicas/epidemiologia , HumanosRESUMO
Adults with stroke frequently experience executive dysfunction. Despite the range of assessments that examine the effects of executive dysfunction on daily tasks, there remains a paucity of literature that examines the influence of the environment on performance in the community. The MET-Home is an ecologically valid assessment for examining post-stroke executive dysfunction in the home environment. This qualitative study explores the relationship between the environment and MET-Home performance among home-dwelling adults with stroke and matched controls. Using a descriptive qualitative approach, we analysed video, interview, and observation notes from a MET-Home validation study. An overarching theme of interplay between everyday task performance and the home environment produced further themes: naturalistically emerging supports and barriers and environment as strategy. Within naturalistically emerging supports and barriers, five contextual sub-themes were discovered: physical environment, social environment, temporal context, virtual context, and personal context. Within environment as strategy, we identified four sub-themes: reducing distractions, using everyday technologies, planning in context, and seeking social support. These findings extend the conceptualisation of how we evaluate executive dysfunction in the context of the community to also consider the inherent influence of the environment.
Assuntos
Atividades Cotidianas , Disfunção Cognitiva/diagnóstico , Função Executiva , Testes Neuropsicológicos/normas , Desempenho Psicomotor , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Função Executiva/fisiologia , Feminino , Humanos , Masculino , Desempenho Psicomotor/fisiologia , Pesquisa Qualitativa , Reprodutibilidade dos Testes , Meio Social , Acidente Vascular Cerebral/fisiopatologiaRESUMO
Self-generated strategy use has substantial potential for improving community living outcomes in adults with impaired executive function after stroke. However, little is known about how self-generated strategies support task performance in people with post-stroke executive function impairments living in the community. We explored strategy use among home-dwelling persons with stroke and neurologically-healthy control participants during the Multiple Errands Test-Home Version (MET-Home), a context-specific assessment with evidence of ecological validity designed to examine how post-stroke executive dysfunction manifests during task performance in the home environment. For persons with stroke, significant associations were identified between planning and tasks accurately completed on the MET-Home. Significant associations were also identified among the control participants for self-monitoring, multitasking, and "using the environment" strategies. These associations are related to enhanced MET-Home performance on sub-scores for levels of accuracy, passes, and total time. Rehabilitation interventions that focus on reinforcing self-generated strategy use may support community living outcomes in persons with post-stroke executive function impairments, but this area needs additional investigation.
Assuntos
Atividades Cotidianas , Disfunção Cognitiva/fisiopatologia , Função Executiva/fisiologia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/fisiopatologia , Análise e Desempenho de Tarefas , Idoso , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/reabilitação , Feminino , Humanos , Vida Independente , Masculino , Avaliação de Resultados da Assistência ao Paciente , Integração Social , Participação Social , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapiaRESUMO
mRNA therapeutics hold great potential for treating a variety of diseases through protein-replacement, immunomodulation, and gene editing. However, much like siRNA therapy the majority of progress in mRNA delivery has been confined to the liver. Previously, we demonstrated that poly(ß-amino esters), a class of degradable polymers, are capable of systemic mRNA delivery to the lungs in mice when formulated into nanoparticles with poly(ethylene glycol)-lipid conjugates. Using experimental design, a statistical approach to optimization that reduces experimental burden, we demonstrate herein that these degradable polymer-lipid nanoparticles can be optimized in terms of polymer synthesis and nanoparticle formulation to achieve a multiple order-of-magnitude increase in potency. Furthermore, using genetically engineered Cre reporter mice, we demonstrate that mRNA is functionally delivered to both the lung endothelium and pulmonary immune cells, expanding the potential utility of these nanoparticles.
Assuntos
Endotélio/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Nanopartículas/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Animais , Endotélio/imunologia , Endotélio/patologia , Técnicas de Transferência de Genes , Humanos , Lipídeos/administração & dosagem , Lipídeos/química , Pulmão/imunologia , Pulmão/patologia , Camundongos , Nanopartículas/química , Polietilenoglicóis/química , Polímeros/química , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genéticaRESUMO
Using affinity purification MS approaches, we have identified a novel role for casein kinase II (CKII) in the modification of the polymerase associated factor complex (PAF-C). Our data indicate that the facilitates chromatin transcription complex (FACT) interacts with CKII and may facilitate PAF complex phosphorylation. Posttranslational modification analysis of affinity-isolated PAF-C shows extensive CKII phosphorylation of all five subunits of PAF-C, although CKII subunits were not detected as interacting partners. Consistent with this, recombinant CKII or FACT-associated CKII isolated from cells can phosphorylate PAF-C in vitro, whereas no intrinsic kinase activity was detected in PAF-C samples. Significantly, PAF-C purifications combined with stable isotope labeling in cells (SILAC) quantitation for PAF-C phosphorylation from wild-type and CKII temperature-sensitive strains (cka1Δ cka2-8) showed that PAF-C phosphorylation at consensus CKII sites is significantly reduced in cka1Δ cka2-8 strains. Consistent with a role of CKII in FACT and PAF-C function, we show that decreased CKII function in vivo results in decreased levels of histone H2B lysine 123 monoubiquitylation, a modification dependent on FACT and PAF-C. Taken together, our results define a coordinated role of CKII and FACT in the regulation of RNA polymerase II transcription through chromatin via phosphorylation of PAF-C.
Assuntos
Caseína Quinase II/metabolismo , Histonas/metabolismo , RNA Polimerase II/metabolismo , Saccharomyces cerevisiae/metabolismo , Transcrição Gênica/fisiologia , Ubiquitinação/fisiologia , Caseína Quinase II/genética , Cromatina/genética , Cromatina/metabolismo , Histonas/genética , Fosforilação/fisiologia , RNA Polimerase II/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiaeRESUMO
Postsynthetic modification is a promising tool for introducing multifunctional properties in metal-organic frameworks (MOFs). The effects of postsynthetic metal addition/exchange in a barium-based MOF have been well examined toward their magnetic and electrical properties. The rattling motion of the extraframework organic cation is responsible for the ferroelectric behavior. The strong magnetic frustration in Tb@1 is found to arise from the nearly triangular arrangement of Tb3+ ions in its secondary building unit along the chain direction.
RESUMO
BACKGROUND & OBJECTIVES: Foot length of the newborn has a good correlation with the birth weight and is recommended to be used as a proxy measure. There can be variations in the measurement of foot length. A study was, therefore, carried out to develop a foot length calliper for accurate foot length measurement and to find cut-off values for birth weight and gestational age groups to be used by primary healthcare workers. METHODS: This study was undertaken on 645 apparently healthy newborn infants with known gestational age. Nude birth weight was taken within 24 h of birth on a standard electronic weighing machine. A foot length calliper was developed. Correlation between foot length and birth weight as well as gestational age was calculated. Correctness of cut-off values was tested using another set of 133 observations on the apparently healthy newborns. Action-oriented colour coding was done to make it easy for primary healthcare workers to use it. RESULTS: There was a significant correlation of foot length with birth weight (r=0.75) and gestational age (r=0.63). Cut-off values for birth weight groups were 6.1, 6.8 and 7.3 cm and for gestational age of 6.1, 6.8 and 7.0 cm. Correctness of these cut-off values ranged between 77.1 and 95.7 per cent for birth weight and 60-93.3 per cent for gestational age. Considering 2.5 kg as cut-off between normal birth weight and low birth weight (LBW), cut-off values of 6.1, 6.8 and 7.3 were chosen. Action-oriented colour coding was done by superimposing the colours on the scale of the calliper, green indicating home care, yellow indicating supervised home care, orange indicating care at newborn care units at primary health centres and red indicating Neonatal Intensive Care Unit care for infants. INTERPRETATION & CONCLUSIONS: A simple device was developed so that the primary health care workers and trained Accredited Social Health Activist workers can identify the risk of LBW in the absence of accurate weighing facilities and decide on the type of care needed by the newborn and take action accordingly.
Assuntos
Antropometria/instrumentação , Peso ao Nascer/fisiologia , Pé/fisiologia , Recém-Nascido de Baixo Peso , Feminino , Pé/anatomia & histologia , Pessoal de Saúde , Humanos , Índia/epidemiologia , Masculino , GravidezRESUMO
In recent years, hygienic handling of fishery waste is demanded owing to the fact that the fishery waste is an ideal raw material for the preparation of bioactive compounds. In the present study, the effect of pre-processing storage (at 4 ± 2 °C) of whole tilapia waste (WTW) on the properties of its protein hydrolysate derived using pepsin was evaluated. Fish protein hydrolysates (FPH) were prepared from 0, 24 and 48 h old ice stored WTW and designated as FPH-0, FPH-1, and FPH-2, respectively. Total amino acids, total essential amino acids and total hydrophobic amino acids of FPH samples increased with the storage period of raw material (WTW). Antioxidant activities such as DPPH (2, 2 diphynyl-1-picrylhydrazyl) free radical scavenging activity and ferric reducing power of FPH samples were dose dependent. FPH-0 had better antioxidant properties including linoleic acid peroxidation inhibition activity than FPH-1 and FPH-2. The DNA nicking assay revealed the protective effect of FPH preparations against Fenton's reaction mediated oxidative damage. FPH-2 had better emulsifying properties and foaming stability whereas the FPH-0 had relatively good foaming capacity. SDS-PAGE indicated the presence of peptides ranging from 116 to < 14.4 kDa in FPH-0 and less than 18 kDa in FPH-1 and FPH-2. The present study, clearly demonstrated that whole tilapia waste can effectively be converted to FPH and could be a potential ingredient in functional food and as a rich source of high-quality protein in animal feed formulations.