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Sustainability is an issue of worldwide concern. Twitter is one of the most popular social networks, which makes it particularly interesting for exploring opinions and characteristics related to issues of social preoccupation. This paper aims to gain a better understanding of the activity related to sustainability that takes place on twitter. In addition to building a mathematical model to identify account typologies (bot and human users), different behavioural patterns were detected using clustering analysis mainly in the mechanisms of posting tweets and retweets). The model took as explanatory variables, certain characteristics of the user's profile and her/his activity. A lexicon-based sentiment analysis in the period from 2006 to 2022 was also carried out in conjunction with a keyword study based on centrality metrics. We found that, in both bot and human users, messages showed mostly a positive sentiment. Bots had a higher percentage of neutral messages than human users. With respect to the used keywords certain commonalities but also slight differences between humans and bots were identified.
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Mídias Sociais , Humanos , Feminino , Comunicação , Software , Rede Social , HábitosRESUMO
We conducted qualitative research with family planning clients, potential clients, and service providers on barriers and opportunities for improving the quality of family planning services in the Philippines. The family planning service providers included the primary, secondary, and tertiary levels of the health system. Our goal was to aid in developing more effective family planning quality improvement (QI) programs. Our methods included focus groups, key informant interviews and thematic content analysis of the qualitative data. We found four themes: the components of quality of family planning care; factors influencing quality; challenges for improving quality; and provider bias in the types of family planning services offered to clients. We identified five implications for QI, including: reduce provider bias; level off the understanding of QI concepts and roles among the different family planning service providers; involve men more actively; design new digital communication strategies for reaching clients and potential clients; and explore collaborations with private sector pharmacies. The findings from this study can guide the development of a pilot family planning QI programme in the Philippines. The findings provide themes and practical insights for an intervention-focused theory of change on how to improve current programs, design new programs, be more responsive to the needs and concerns of clients and potential clients and be well-accepted and sustained by providers. This can lay the groundwork for improving family planning outcomes and reducing teenage pregnancy rates and the unmet need for family planning throughout the Philippines.
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Serviços de Planejamento Familiar , Setor Privado , Masculino , Gravidez , Feminino , Adolescente , Humanos , FilipinasRESUMO
The impact of COVID-19, both in quality and quantity, on the field of early childhood education, ECE is immeasurable. However, as research shows, its impact on family child care (FCC), has been worse than other sectors of ECE. FCC providers worldwide have always perceived their work as a service to families and children, yet FCC homes have not received much attention and recognition from researchers and policymakers compared to center-based ECE programs. This phenomenological inquiry with 20 FCC providers in a large urban county in California highlights the financial challenges that FCC providers faced during the early part of the pandemic before they received financial support from the state in the spring of 2021. The cost of running the program was quite high because of reduced enrollment and the regular purchase of sanitary materials. To keep their programs afloat, some participants had to lay off their staff, others kept them without salary, others had to exhaust their savings, and most incurred credit card debt. Most of them also experienced psychosocial stress. Their financial hardships during the pandemic would have been far worse without the emergency funding received from the state. However, as experts warn, the field of ECE needs a permanent solution and the situation could be even worse after the emergency funds run out in 2024. The nation has witnessed the dedicated service of FCC providers during the pandemic, especially to families of essential workers. Much work is needed at empirical and policy levels to support and celebrate the service of FCC providers.
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BACKGROUND: Due to the COVID-19 pandemic, many challenges in adolescent health have been exacerbated including increased cases of early marriages, domestic violence, higher rates of anxiety and depression, and reduced access to sexual and reproductive health services for adolescents. This study examines the impacts of the pandemic on adolescent health services utilization and potential adaptations in the Philippines. METHODS: The data used in this study was from a rapid telephone assessment survey of 148 adolescent-friendly health facilities (rural health units) in the Philippines. We employed a mixed-methods research approach comprising both quantitative and qualitative analyses in three phases. First, we conducted a descriptive analysis of the status of adolescent healthcare access and utilization during COVID-19. Next, we examined using multivariate ordered logistic regressions how staff availability and adolescent health (AH) service provision modalities influenced AH service utilization in terms of the average number of adolescents served per week during compared to before the pandemic. We also conducted a complementing qualitative analysis of the challenges and corresponding adaptive solutions to ensuring continuity of AH services in facilities. RESULTS: We find that two months into the pandemic, 79% of adolescent-friendly trained staff were reporting for duty and 64% of facilities reported no staff disruptions. However, only 13% of facilities were serving the same number of adolescents or greater than before COVID-19. The use of more modalities for AH service provision (including telehealth) by facilities was significantly associated with increased likelihood to report serving the same number of adolescent or greater than before COVID-19 compared to those who used only one modality. CONCLUSION: Investments in multiple modalities of care provision, such as telehealth could improve AH services utilization and help sustain connection with adolescents during shocks, including future outbreaks or other stressors that limit physical access to health facilities.
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Serviços de Saúde do Adolescente , COVID-19 , Adolescente , Humanos , COVID-19/epidemiologia , Pandemias , Filipinas/epidemiologia , Acessibilidade aos Serviços de SaúdeRESUMO
This paper applies Information and Communication Technologies (ICT) as well as data analysis to gain a better understanding of the existing perception on the education system. 45,278 tweets were downloaded and processed. Using a lexicon-based approach, examining the most frequently used words, and estimating similarities between terms, we detected that a predominantly negative perception of the education system exists in most of the analysed countries. A positive perception is identified in certain low-income nations. Men exhibit a more positive sentiment than women as well as a higher subjectivity in some countries. The countries that exhibit the most positive perceptions India, Canada, Pakistan, Australia, South Africa and Kenya are also those that manifest the highest subjectivity.
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There is significant global concern about the harmful effects of greenhouse gas and carbon monoxide emissions (deforestation, air pollution, global warming, etc.). The 2015 Paris Agreement on climate change aspires to reduce global warming by achieving a climate-neutral world. Research has been carried out to calculate and diminish the aforementioned emissions in waste, power industry, transport, building, in addition to other areas. The aim of this paper is to analyse the carbon and greenhouse gas emissions across countries around the globe in order to find patterns and correlate them to socio-economic indicators [gross national income (GNI), industrial production (IPI) and human development indexes (HDI)] as well as Twitter interactions regarding climate change. For this purpose, time series and socio-economic data have been downloaded from different repositories including EDGAR (Emissions Database for Global Atmospheric Research), World Bank and UNDP (United Nations Development Programme). Although classical clustering algorithms have already been used in the examination of some environmental issues, we use a non-parametric time series clustering method, which has been suggested in certain scientific literature as a more flexible approach, since any ad hoc parametric assumptions are required. The chosen socio-economic indicators have also demonstrated their relevance in pieces of research related to various fields. With respect to Twitter, which is one of the most popular social networks nowadays, significant analysis has also been performed on the basis of capturing citizens' perceptions on a multitude of matters. We found that several countries such as Brazil, India, China, Nigeria, Russia, United States, Spain, Andorra, Greece, and Qatar show differences in carbon and greenhouse gas emissions patterns. Besides, there does not seem to be a correlation between GNI, IPI and HDI as well as the above mentioned emissions ( correlation < 0.16 ) . Regarding Twitter interactions, a dissimilarity in the distribution of hashtags was detected between the aforementioned countries and the rest of the world. This research can help to identify countries in which more governmental measures are needed to reduce the type of emissions analysed in certain industrial sectors. In addition, it points out the topics related to climate change that seem to generate the most debate on Twitter for countries with an unusual pattern. Supplementary Information: The online version contains supplementary material available at 10.1007/s41742-023-00510-4.
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Displacements within urban spaces have attracted particular interest among researchers. We examine the journeys that happen in the Madrid Community considering 24 travel typologies and 1390 administrative areas. From an origin-destination (OD) matrix, four classes of major flows are characterised through coarse-graining: hotspot-non-hotspots, non-hotspot-hotspots, hotspots-hotspots, non-hotspot-non-hotspot. In order to make comparisons between them with respect to spatial and temporal patterns, several statistical tests are performed. The spatial activity as well as transition probabilities between administrative zones are also analysed. The mobility network's topology is examined (some parameters such as maximal connected components, average degree, betweenness, and assortativity as well as the k-cores are checked). A model describing the formation of links between zones (existence of at least one trip between them) is constructed based on certain measures of affinity between areas.
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Viagem , ProbabilidadeRESUMO
The morphological analysis of patterns in dried droplets has allowed the generation of efficient techniques for the detection of molecules of medical interest. However, the effectiveness of this method to reveal the coexistence of macromolecules of the same species, but different conformational states, is still unknown. To address this problem, we present an experimental study on pattern formation in dried droplets of bovine serum albumin (BSA), in folded and unfolded conformational states, in saline solution (NaCl). Folded proteins produce a well-defined coffee ring and crystal patterns all over the dry droplet. Depending on the NaCl concentration, the crystals can be small, large, elongated, entangled, or dense. Optical microscopy reveals that the relative concentration of unfolded proteins determines the morphological characteristics of deposits. At a low relative concentration of unfolded proteins (above 2%), small amorphous aggregates emerge in the deposits, while at high concentrations (above 16%), the "eye-like pattern", a large aggregate surrounded by a uniform coating, is produced. The radial intensity profile, the mean pixel intensity, and the entropy make it possible to characterize the patterns in dried droplets. We prove that it is possible to achieve 100% accuracy in identifying 4% of unfolded BSA contained in a protein solution.
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Soroalbumina Bovina , Cloreto de SódioRESUMO
Due to their role in controlling translation, microRNAs emerged as novel therapeutic targets to modulate post-stroke outcomes. We previously reported that miR-21 is the most abundantly induced microRNA in the brain of rodents subjected to preconditioning-induced cerebral ischemic tolerance. We currently show that intracerebral administration of miR-21 mimic decreased the infarct volume and promoted better motor function recovery in adult male and female C57BL/6 mice subjected to transient middle cerebral artery occlusion. The miR-21 mimic treatment is also efficacious in aged mice of both sexes subjected to focal ischemia. Mechanistically, miR-21 mimic treatment decreased the post-ischemic levels of several pro-apoptotic and pro-inflammatory RNAs, which might be responsible for the observed neuroprotection. We further observed post-ischemic neuroprotection in adult mice administered with miR-21 mimic intravenously. Overall, the results of this study implicate miR-21 as a promising candidate for therapeutic translation after stroke.
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Lesões Encefálicas , Isquemia Encefálica , MicroRNAs , Acidente Vascular Cerebral , Animais , Encéfalo , Isquemia Encefálica/tratamento farmacológico , Feminino , Infarto da Artéria Cerebral Média , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
Loss of lymphocytes, particularly T cell apoptosis, is a central pathological event after severe tissue injury that is associated with increased susceptibility for life-threatening infections. The precise immunological mechanisms leading to T cell death after acute injury are largely unknown. Here, we identified a monocyte-T cell interaction driving bystander cell death of T cells in ischemic stroke and burn injury. Specifically, we found that stroke induced a FasL-expressing monocyte population, which led to extrinsic T cell apoptosis. This phenomenon was driven by AIM2 inflammasome-dependent interleukin-1ß (IL-1ß) secretion after sensing cell-free DNA. Pharmacological inhibition of this pathway improved T cell survival and reduced post-stroke bacterial infections. As such, this study describes inflammasome-dependent monocyte activation as a previously unstudied cause of T cell death after injury and challenges the current paradigms of post-injury lymphopenia.
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Coinfecção/imunologia , Proteínas de Ligação a DNA/imunologia , Tolerância Imunológica/imunologia , Inflamassomos/imunologia , Transdução de Sinais/imunologia , Animais , Apoptose/imunologia , Infecções Bacterianas/imunologia , Queimaduras/imunologia , Queimaduras/microbiologia , Coinfecção/microbiologia , Humanos , Interleucina-1beta/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/microbiologia , Linfócitos T/imunologiaRESUMO
Degeneration of sympathetic innervation of the heart occurs in numerous diseases, including diabetes, idiopathic REM sleep disorder, and Parkinson's disease (PD). In PD, cardiac sympathetic denervation occurs in 80-90% of patients and can begin before the onset of motor symptoms. Today, there are no disease-modifying therapies for cardiac sympathetic neurodegeneration, and biomarkers are limited to radioimaging techniques. Analysis of expression levels of coding mRNA and noncoding RNAs, such as microRNAs (miRNAs), can uncover pathways involved in disease, leading to the discovery of biomarkers, pathological mechanisms, and potential drug targets. Whole blood in particular is a clinically relevant source of biomarkers, as blood sampling is inexpensive and simple to perform. Our research group has previously developed a nonhuman primate model of cardiac sympathetic denervation by intravenous administration of the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA). In this rhesus macaque (Macaca mulatta) model, imaging with positron emission tomography showed that oral administration of the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone (n = 5; 5 mg/kg daily) significantly decreased cardiac inflammation and oxidative stress compared to placebo (n = 5). Here, we report our analysis of miRNA and mRNA expression levels over time in the whole blood of these monkeys. Differential expression of three miRNAs was induced by 6-OHDA (mml-miR-16-2-3p, mml-miR-133d-3p, and mml-miR-1262-5p) and two miRNAs by pioglitazone (mml-miR-204-5p and mml-miR-146b-5p) at 12 weeks posttoxin, while expression of mRNAs involved in inflammatory cytokines and receptors was not significantly affected. Overall, this study contributes to the characterization of rhesus coding and noncoding RNA profiles in normal and disease-like conditions, which may facilitate the identification and clinical translation of biomarkers of cardiac neurodegeneration and neuroprotection.
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Macaca mulatta/metabolismo , MicroRNAs/sangue , Doenças Neurodegenerativas/metabolismo , PPAR gama/metabolismo , RNA Mensageiro/sangue , Animais , Biomarcadores/metabolismo , Citocinas/metabolismo , Coração , Inflamação , Macaca mulatta/genética , Masculino , MicroRNAs/efeitos dos fármacos , MicroRNAs/genética , Estresse Oxidativo , Oxidopamina/toxicidade , Doença de Parkinson/metabolismo , RNA Mensageiro/genética , TranscriptomaRESUMO
BACKGROUND: Hospitalized medical-surgical patients are at risk for adverse health outcomes due to immobility. Despite well-documented consequences, low mobility is prevalent. LOCAL PROBLEM: In a 547-bed hospital, medical-surgical patients were mobilized less frequently than expected. Physical therapists were inappropriately consulted 22% of the time for routine mobility of patients. A preimplementation survey of registered nurses indicated a lack of knowledge and confidence to safely mobilize patients. METHODS: This quality improvement project implemented a nurse-led mobility program in an effort to increase early mobilization, reduce physical therapy referrals for routine mobility, and reduce the sequelae of immobility. INTERVENTIONS: The Bedside Mobility Assessment Tool and standardized interventions were implemented on 5 medical-surgical units. RESULTS: Postimplementation, nurse-led patient mobilizations increased by 40%, inappropriate physical therapy orders decreased 14%, and no significant change in patient falls or pressure injuries was noted. CONCLUSION: A nurse-led mobility program was effective in increasing safe, early mobilization of patients and improving the culture of mobility.
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Deambulação Precoce/enfermagem , Enfermagem Médico-Cirúrgica/métodos , Idoso , Idoso de 80 Anos ou mais , California , Deambulação Precoce/tendências , Feminino , Humanos , Masculino , Enfermagem Médico-Cirúrgica/tendências , Pessoa de Meia-Idade , Desenvolvimento de Programas/métodos , Avaliação de Programas e Projetos de Saúde/métodos , Melhoria de Qualidade , Inquéritos e QuestionáriosRESUMO
Perception of our environment entirely depends on the close interaction between the central and peripheral nervous system. In order to communicate each other, both systems must develop in parallel and in coordination. During development, axonal projections from the CNS as well as the PNS must extend over large distances to reach their appropriate target cells. To do so, they read and follow a series of axon guidance molecules. Interestingly, while these molecules play critical roles in guiding developing axons, they have also been shown to be critical in other major neurodevelopmental processes, such as the migration of cortical progenitors. Currently, a major hurdle for brain repair after injury or neurodegeneration is the absence of axonal regeneration in the mammalian CNS. By contrasts, PNS axons can regenerate. Many hypotheses have been put forward to explain this paradox but recent studies suggest that hacking neurodevelopmental mechanisms may be the key to promote CNS regeneration. Here we provide a seminar report written by trainees attending the second Flagship school held in Alpbach, Austria in September 2018 organized by the International Society for Neurochemistry (ISN) together with the Journal of Neurochemistry (JCN). This advanced school has brought together leaders in the fields of neurodevelopment and regeneration in order to discuss major keystones and future challenges in these respective fields.
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Orientação de Axônios/fisiologia , Axônios/fisiologia , Encéfalo/ultraestrutura , Animais , Axônios/ultraestrutura , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Humanos , Regeneração Nervosa , Quiasma Óptico/crescimento & desenvolvimento , Sistema Nervoso Periférico/crescimento & desenvolvimento , Sistema Nervoso Periférico/fisiologia , Medula Espinal/crescimento & desenvolvimento , Medula Espinal/fisiologia , Medula Espinal/ultraestruturaRESUMO
Introducción: la epistaxis es uno de los principales motivos de consulta por urgencias en el servicio de otorrinolaringología (ORL). La mayoría de los episodios se originan en el septo nasal anterior y su tratamiento tiende a ser conservador. Objetivo: caracterizar la población que consulta por epistaxis al servicio de otorrinolaringología del Hospital Universitario Mayor Méderi (HUM) entre marzo de 2017 y febrero de 2018. Metodología: estudio observacional, descriptivo y de corte transversal, con una recolección de datos de forma retrospectiva de pacientes que ingresan a urgencias del HUM por epistaxis, registrados en la base de datos del servicio de otorrinolaringología. Se analizaron datos demográficos, localización del sangrado, tratamiento, comorbilidades, fármacos y cifras tensionales. Resultados: un total de 587 pacientes; el 57 % son mujeres, con un promedio de 66 años +/- 16,15 años. La comorbilidad más frecuente fue la hipertensión arterial (60 %) y el 26 % de los pacientes presentaron cifras tensionales >140/90 mm Hg. En antecedentes farmacológicos, el 64,9 % pertenecían al grupo de antihipertensivos y el 37,6 % a los antiagregantes. La localización de los sangrados fue anterior (> área II de Cottle). El principal tratamiento fue el taponamiento nasal anterior con gasa (36,4 %), seguido por la cauterización con nitrato de plata (36,1 %). Conclusiones: en el HUM, los pacientes que consultan por epistaxis son adultos de edad media y avanzada, cuyo sangrado nasal tiene una localización anterior, que solamente requirieron tratamiento médico. Se requieren otros estudios para determinar la modalidad de tratamiento más efectiva según la gravedad de la epistaxis.
Background: epistaxis is one of the main reasons for emergency consultations in the Otolaryngology department. Most episodes originate in the anterior nasal septum and their management tends to be conservative. Aim: characterize the population that consults by epistaxis to the Otolaryngology department of the Hospital Universitario Mayor Méderi (HUM) between March 2017 and February 2018. Methods: observational, descriptive, cross-sectional study, with retrospective data collection of patients admitted to the emergency department of the HUM by epistaxis, registered in the database of the Otolaryngology Department. Demographic data, location of bleeding, treatment, comorbidities, drugs, and blood pressure were analyzed. Results: a total of 587 patients; 57 % women with an average of 66 years +/- 16.15 years. The most frequent comorbidity was arterial hypertension (60 %) and 26 % of the patients presented blood pressure levels >140/90 mm Hg. In pharmacological history, 64.9 % belonged to the group of antihypertensives and 37.6 % to antiplatelet agents. The location of the bleeds was anterior (> Cottle area II). The main treatment was the anterior nasal gauze packing (36.4 %), followed by silver nitrate cauterization (36.1 %). Conclusions: in the HUM, patients who consult for epistaxis are middle-aged and elderly adults, with anterior localization of nasal bleeding, which only required medical management. Other studies are required to determine the most effective treatment modality according to the severity of epistaxis.
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Humanos , Epistaxe , Terapêutica , Demografia , HipertensãoAssuntos
Prescrições de Medicamentos/enfermagem , Licenciamento em Farmácia/normas , Profissionais de Enfermagem/legislação & jurisprudência , California , Prescrições de Medicamentos/estatística & dados numéricos , Humanos , Licenciamento em Farmácia/tendências , Profissionais de Enfermagem/tendências , Saúde Pública/métodos , Saúde Pública/tendênciasRESUMO
The World Trade Network (WTN) is a network of exchange flows among countries whose topological and statistical properties are a valuable source of information. Degree and strength (weighted degree) are key magnitudes to understand its structure and generative mechanisms. In this work, we describe a stochastic model that yields synthetic networks that closely mimic the properties of annual empirical data. The model combines two popular mechanisms of network generation: preferential attachment and multiplicative process. Agreement between empirical and synthetic networks is checked using the available series from 1962 to 2017.
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BACKGROUND: We compared the rates of intraoperative parathyroid hormone (PTH) decline using the Siemens Immulite® Turbo PTH and Roche Elecsys® short turnaround time PTH assays in 95 consecutive surgical patients to investigate analytical and turnaround time (TAT) differences between the tests performed in the operating room (OR) vs the central clinical chemistry laboratory (CCL). METHODS: Serial blood samples from 95 patients undergoing parathyroidectomy were collected and measured using the 2 immunoassays. Specimens from the first 15 patients were measured simultaneously in the OR and CCL and used for the TAT study. In addition to 2 baseline samples, specimens were collected at 5, 10, and 15 min (for some patients, >15 min) after parathyroidectomy. RESULTS: In the TAT study, a significant difference was observed (OR median 20 min vs CCL median 27 min; P < 0.05). Of the 95 patient series, slower rates of parathyroid hormone decrease were observed in approximately 20% of the patients when comparing the Roche with the Immulite immunoassay. CONCLUSIONS: There was a slightly longer TAT in the CCL compared with running the assay directly within the OR (median difference of approximately 7 min). For a majority of the patients, both methods showed equivalent rates of PTH decline; however, for approximately 20% of the patients, there was a slower rate of PTH decline using the Roche assay.
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Testes de Química Clínica/métodos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/cirurgia , Imunoensaio/métodos , Hormônio Paratireóideo/sangue , Paratireoidectomia/métodos , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-IdadeRESUMO
Background and Purpose- Epigenetics play a significant role in brain pathologies. We currently evaluated the role of a recently discovered brain-enriched epigenetic modification known as 5-hydroxymethylcytosine (5hmC) in regulating transcriptomic and pathogenic mechanisms after focal ischemic injury. Methods- Young and aged male and female mice were subjected to transient middle cerebral artery occlusion, and the peri-infarct region was analyzed at various times of reperfusion. Two days before middle cerebral artery occlusion, short-interfering RNA against an isoform of the 5hmC producing enzyme TET (ten-eleven translocase) was injected intracerebrally. Ascorbate was injected intraperitoneally at 5 minutes, 30 minutes, or 2 hours of reperfusion. Motor function was tested with rotarod and beam-walk test. Results- Focal ischemia rapidly induced the activity of TET, the enzyme that catalyzes the formation of 5hmC and preferentially increased expression of the TET3 isoform in the peri-infarct region of the ischemic cortex. Levels of 5hmC were increased in a TET3-dependent manner, and inhibition of TET3 led to wide-scale reductions in the postischemic expression of neuroprotective genes involved in antioxidant defense and DNA repair. TET3 knockdown in adult male and female mice further increased brain degeneration after focal ischemia, demonstrating a role for TET3 and 5hmC in endogenous protection against stroke. Ascorbate treatment after focal ischemia enhanced TET3 activity and 5hmC enrichment in the peri-infarct region. TET3 activation by ascorbate provided robust protection against ischemic injury in young and aged mice of both sexes. Moreover, ascorbate treatment improved motor function recovery in both male and female mice. Conclusions- Collectively, these results indicate the potential of TET3 and 5hmC as novel stroke therapeutic targets. Visual Overview- An online visual overview is available for this article.
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5-Metilcitosina/análogos & derivados , Encéfalo/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Acidente Vascular Cerebral/metabolismo , 5-Metilcitosina/metabolismo , Fatores Etários , Animais , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Epigênese Genética , Infarto da Artéria Cerebral Média/genética , Masculino , Camundongos , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Acidente Vascular Cerebral/genéticaRESUMO
MicroRNAs (miRNAs) are emerging as novel molecular tools for diagnosing and treating diseases. Rhesus monkeys (Macaca mulatta) are the most widely used nonhuman primate species for biomedical studies, yet only 912 mature miRNAs have been identified in this species compared to 2654 in humans and 1978 in mice. The aim of this project was to help bridge that gap in knowledge by evaluating circulating miRNA in naïve rhesus monkeys and comparing results with currently available databases in different species in order to identify novel, mature miRNAs. Total RNA was isolated from whole blood of ten healthy, adult rhesus macaques. After performing next generation sequencing (NGS), 475 novel, mature miRNAs were identified in rhesus macaques for the first time; of those, 423 were identified for the first time in any species. The most abundantly expressed novel rhesus macaque miRNA, hsa-miR-744-5p, has previously been described in humans. Database assessment of hsa-miR-744-5p potential gene targets showed that while the gene targets showed > 90% sequence similarity between rhesus and humans, many did not share the same consensus sequences. The identification of 475 novel miRNAs in the blood of rhesus macaque reflects the complexity and variety of miRNAs across species. Further NGS studies are needed to reveal novel miRNA that will inform on species-, tissue-, and condition-specific miRNAs.
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Macaca mulatta/genética , MicroRNAs/genética , MicroRNAs/isolamento & purificação , Animais , Ácidos Nucleicos Livres/análise , Ácidos Nucleicos Livres/genética , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
Background: Parkinson's disease (PD) patients frequently present gastrointestinal (GI) dysfunction that, in many cases, predates the onset of motor symptoms. In PD, the presynaptic protein alpha-synuclein (α-syn) undergoes pathological changes, including phosphorylation and aggregation leading to the formation of Lewy bodies, which can be found in neurons of the enteric nervous system (ENS). Inflammation has been proposed as a possible trigger of α-syn pathology. Interestingly, patients with inflammatory bowel disease and irritable bowel syndrome, conditions associated with GI inflammation, are at higher risk of developing PD. Captive common marmosets (Callithrix jacchus) develop colitis, providing a natural platform to assess the relationship between α-syn pathology and GI inflammation. Materials and Methods: Sections of proximal colon from marmosets with colitis (n=5; 5.3±2.3 years old; 4 male) and normal controls (n=5; 4.1±1.6 years old; 1 male) were immunostained against protein gene product 9.5 (PGP9.5), human leukocyte antigen DR (HLA-DR), cluster of differentiation 3 (CD3), cluster of differentiation 20 (CD20), glial fibrillary acidic protein (GFAP), 8-hydroxy-2'-deoxyguanosine (8-OHdG), α-syn, and serine 129 phosphorylated α-syn (p-α-syn). Immunoreactivity of each staining in the myenteric plexus was quantified using NIH ImageJ software. Results: Marmosets with colitis had significantly increased expression of inflammatory markers (HLA-DR, p<0.02; CD3, p<0.008), oxidative stress (8-OHdG, p<0.05), and p-α-syn (p<0.02) and decreased expression of α-syn (p<0.04) in the colonic myenteric ganglia compared to normal, healthy controls. Conclusion: Colonic inflammation is associated with changes in α-syn expression and phosphorylation in the myenteric plexus of common marmosets. Future evaluation of the vagus nerve and brain of animals with colitis will be key to assess the contribution of colitis-induced ENS α-syn pathology to PD-like pathology in the brain.