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Cytotoxic T lymphocytes (CTLs) mediate host defense against viral and intracellular bacterial infections and tumors. However, the magnitude of CTL response and their function needed to confer heterosubtypic immunity against influenza virus infection are unknown. We addressed the role of CD8+ T cells in the absence of any cross-reactive antibody responses to influenza viral proteins using an adenoviral vector expressing a 9mer amino acid sequence recognized by CD8+ T cells. Our results indicate that both CD8+ T cell frequency and function are crucial for heterosubtypic immunity. Low morbidity, lower viral lung titers, low to minimal lung pathology, and better survival upon heterosubtypic virus challenge correlated with the increased frequency of NP-specific CTLs. NP-CD8+ T cells induced by differential infection doses displayed distinct RNA transcriptome profiles and functional properties. CD8+ T cells induced by a high dose of influenza virus secreted significantly higher levels of IFN-γ and exhibited higher levels of cytotoxic function. The mice that received NP-CD8+ T cells from the high-dose virus recipients through adoptive transfer had lower viral titers following viral challenge than those induced by the low dose of virus, suggesting differential cellular programming by antigen dose. Enhanced NP-CD8+ T-cell functions induced by a higher dose of influenza virus strongly correlated with the increased expression of cellular and metabolic genes, indicating a shift to a more glycolytic metabolic phenotype. These findings have implications for developing effective T cell vaccines against infectious diseases and cancer. IMPORTANCE: Cytotoxic T lymphocytes (CTLs) are an important component of the adaptive immune system that clears virus-infected cells or tumor cells. Hence, developing next-generation vaccines that induce or recall CTL responses against cancer and infectious diseases is crucial. However, it is not clear if the frequency, function, or both are essential in conferring protection, as in the case of influenza. In this study, we demonstrate that both CTL frequency and function are crucial for providing heterosubtypic immunity to influenza by utilizing an Ad-viral vector expressing a CD8 epitope only to rule out the role of antibodies, single-cell RNA-seq analysis, as well as adoptive transfer experiments. Our findings have implications for developing T cell vaccines against infectious diseases and cancer.
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Linfócitos T CD8-Positivos , Infecções por Orthomyxoviridae , Linfócitos T Citotóxicos , Animais , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Camundongos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T Citotóxicos/imunologia , Camundongos Endogâmicos C57BL , Feminino , Transferência Adotiva , Interferon gama/imunologia , Interferon gama/metabolismo , Proteínas do Nucleocapsídeo/imunologia , Pulmão/imunologia , Pulmão/virologia , Proteínas de Ligação a RNA/imunologia , Proteínas de Ligação a RNA/genética , Nucleoproteínas/imunologia , Nucleoproteínas/genética , Proteínas do Core Viral/imunologia , Proteínas do Core Viral/genéticaRESUMO
Liver transplantation is considered to be the only curative treatment for decompensated liver disease. Shortage of liver allografts is a major impediment to the widespread application of this procedure. ABO-incompatible (ABO-I) grafts have been used successfully, thereby increasing the living donor liver transplantation (LDLT) donor pool. However, ABO-I liver transplantation is associated with complications like acute liver rejection, hepatic artery thrombosis, and higher biliary stricture rates, leading to transplant failure, retransplantations, or sepsis-related complications. Various desensitization strategies have been adopted to improve outcomes. Biologically related donor-recipient pairs have the theoretical advantage of favorable HLA (human leukocyte antigen) match. We have analyzed the outcomes of ABO-I LDLT and compared the results of HLA-matched (biologically related) and HLA-unmatched (biologically unrelated) donor-recipient pairs. Retrospective data of 90 cases of ABO-I liver transplant recipients: HLA-matched (n = 35) and HLA-unmatched (n = 55) for comparison of preoperative and postoperative data. Peak bilirubin levels in HLA-unmatched recipients were higher. Platelet count was lower than HLA-matched recipients (7.3 vs. 8.9 mg/dL). No significant difference in days-to-normal bilirubin, peak International Normalised Ratio, hospital stay, and discharge-day from transplant between both groups. Postoperatively, HLA-unmatched recipients required more pulse-steroids therapy than HLA-matched: 21/55 (38.2%) versus 11/35 (31.4%). Biliary complications and interventions were more prevalent in the HLA-unmatched group (12/55, 21.8%) than in the HLA-matched group (4/35, 11.4%). Renal complications requiring postoperative hemodialysis were more prevalent in the HLA-unmatched group than the HLA-matched group (9/55 [16.4%] vs. 3/35 [8.6%]). The incidence of vascular complications was similar. ABO-I LDLT is an effective and safe method for increasing the donor pool in the absence of an ABO-compatible liver donor. Long-term outcomes of recipients with biologically related donors are marginally better than biologically unrelated ABO-I LDLT recipients. However, the incidence of antibody-mediated graft rejection and biliary complications is higher in biologically unrelated ABO-I liver recipients.
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Bouveret's syndrome is an uncommon cause of gastric outlet obstruction caused by the impaction of large gallstones in the duodenal lumen. The gallstones pass into the duodenal lumen through a cholecystogastric or a cholecystoduodenal fistula. Endoscopic retrieval with or without lithotripsy is the first line of management, often with variable success. We present a case of a woman in her 70s who presented with signs of gastric outlet obstruction and was diagnosed with Bouveret's syndrome with a 5 cm diameter gallstone in the third part of her duodenum. Following several unsuccessful attempts of endoscopic extraction, she underwent successful jejunal enterotomy with fragmentation and extraction of the calculus using an Allis tissue holding forceps. Postoperative recovery was uneventful.
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Cálculos Biliares , Obstrução da Saída Gástrica , Humanos , Feminino , Obstrução da Saída Gástrica/cirurgia , Obstrução da Saída Gástrica/etiologia , Cálculos Biliares/complicações , Cálculos Biliares/cirurgia , Cálculos Biliares/diagnóstico por imagem , Idoso , SíndromeRESUMO
BACKGROUND: Evidence suggests that hypothyroidism may be associated with an increased risk of acute coronary syndrome (ACS). The data regarding the influence of hypothyroidism on cardiovascular disease in the Asian population is conflicting. Therefore, we undertook this study to assess the overall prevalence of hypothyroidism in Acute Coronary Syndrome (ACS) patients and determine if there is a relationship between hypothyroidism, both sub-clinical and overt and other significant risk factors of ACS in an Indian population. METHODS: We studied 487 hospitalized patients between March 2018 and February 2021 with a diagnosis of ACS to determine the prevalence of hypothyroidism, both clinical and sub-clinical and their relationship with other known coronary risk factors. Thyroid function Tests - free T3, free T4 and TSH were collected from all the patients within 24 h of their admission to the coronary care unit (CCU) of 2 major hospitals in New Delhi and Imphal (Manipur). RESULTS: Subclinical hypothyroidism was prevalent in 44 (9 %), followed by overt hypothyroidism in 25 (5.2 %). Subclinical hypothyroidism was more common in females, whereas overt hypothyroidism was more common in males. ST Elevation Myocardial Infarction (STEMI) (52 %), followed by Non-ST-Elevation Myocardial Infarction (NSTEMI) (25 %), was the commonest diagnosis at presentation. Patients with overt hypothyroidism showed a higher proportion of increased triglyceride levels. Patients with hypothyroidism had no differences in the prevalence of concomitant diabetes hypertension and other coronary risk factors. CONCLUSIONS: Patients with ACS without known thyroid disorders should be screened for hypothyroidism since it is found frequently. There might be a case to treat their thyroid dysfunction appropriately.
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Síndrome Coronariana Aguda , Hipotireoidismo , Infarto do Miocárdio sem Supradesnível do Segmento ST , Doenças da Glândula Tireoide , Masculino , Feminino , Humanos , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Estudos Prospectivos , Índia/epidemiologia , Hipotireoidismo/complicações , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/epidemiologiaRESUMO
Diabetes Mellitus, one of the leading causes of death worldwide, has no cure to date and can lead to severe health complications, such as retinopathy, limb amputation, cardiovascular diseases, and neuronal disease, if left untreated. Consequently, it becomes crucial to be able to monitor and predict the incidence of diabetes. Machine learning approaches have been proposed and evaluated in the literature for diabetes prediction. This paper proposes an IoT-edge-Artificial Intelligence (AI)-blockchain system for diabetes prediction based on risk factors. The proposed system is underpinned by blockchain to obtain a cohesive view of the risk factors data from patients across different hospitals and ensure security and privacy of the user's data. We provide a comparative analysis of different medical sensors, devices, and methods to measure and collect the risk factors values in the system. Numerical experiments and comparative analysis were carried out within our proposed system, using the most accurate random forest (RF) model, and the two most used state-of-the-art machine learning approaches, Logistic Regression (LR) and Support Vector Machine (SVM), using three real-life diabetes datasets. The results show that the proposed system predicts diabetes using RF with 4.57% more accuracy on average in comparison with the other models LR and SVM, with 2.87 times more execution time. Data balancing without feature selection does not show significant improvement. When using feature selection, the performance is improved by 1.14% for PIMA Indian and 0.02% for Sylhet datasets, while it is reduced by 0.89% for MIMIC III.
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Sustainable agriculture faces major challenges under abiotic stress conditions owing to extensive application of chemical fertilizers which pollute water, soil and atmosphere. Biostimulants (BSs), comprising of naturally derived complex mixtures of uncharacterized biomolecules, pure biochemicals and nanomaterials, enhance nutrient use efficiency (NUE) and trigger crop's natural defense mechanisms. While it is difficult to specify the metabolic effects of uncharacterized natural mixtures (seaweed extract, protein hydrolyzates, etc.), exogenous application of pure biochemicals and nanomaterials offers an edge as BSs since their physiological roles and mechanisms of action are decipherable. Foliar application or seed treatment of some amino acids, polyamines and biopolymers (chitosan, lipochitin oligosaccharides and thuricin 17) enable plants to overcome drought and salinity stress via activation of mechanisms for reactive oxygen species (ROS) scavenging, osmolyte regulation and chlorophyll accumulation. Interaction of nitric oxide (NO) with some vitamins and melatonin exhibits potential significance as BSs for mitigating stress by ROS scavenging and maintenance of intracellular ionic balance and membrane integrity. Near future is likely to see wide applications of nanoparticles (NPs) and nanomaterials (NMs) as BSs in view of their biphasic mode of action (bio-physical activation of membrane receptors followed by gradual release of BS into the plant cells).
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Nanoestruturas , Espécies Reativas de Oxigênio , Agricultura , Estresse Fisiológico , PlantasRESUMO
Flexible paper-based thermoelectric generators (PTEGs) have drawn significant interest in recent years due to their various advantages such as flexibility, adaptability, environment friendliness, low cost, and easy fabrication process. However, the reported PTEG's output performance still lags behind the performance of other flexible devices as it is not so easy to obtain a compact film on a paper-based substrate with desirable power output with the standard thermoelectric (TE) materials that have been previously utilized. In this direction, Cu2SnS3 (CTS), an earth-abundant, ternary sulfide, can be a good choice p-type semiconductor, when paired with a suitable n-type TE material. In this article, CTS nanocubes are synthesized via a simple hot injection method and a thick film device on emery paper was prepared and optimized. Furthermore, a flexible, 20-pair PTEG is fabricated with p-type CTS legs and traced and pressed n-type bismuth legs assembled using Kapton tape that produced a significantly high output power of 2.18 µW (output power density â¼0.85 nW cm-2 K-1) for a temperature gradient of ΔT = 80 K. The TE properties are also supported by finite element simulation. The bending test conducted for the PTEG suggests device stability for up to 800 cycles with <0.05% change in the internal resistance. A proof-of-concept field-based demonstration for energy harvesting from waste heat of a motorbike exhaust is shown recovering an output power of â¼42 nW for ΔT = 20 K, corroborating the experimental and theoretical results.
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Metabolite genome-wide association studies (mGWASs) are increasingly used to discover the genetic basis of target phenotypes in plants such as Populus trichocarpa, a biofuel feedstock and model woody plant species. Despite their growing importance in plant genetics and metabolomics, few mGWASs are experimentally validated. Here, we present a functional genomics workflow for validating mGWAS-predicted enzyme-substrate relationships. We focus on uridine diphosphate-glycosyltransferases (UGTs), a large family of enzymes that catalyze sugar transfer to a variety of plant secondary metabolites involved in defense, signaling, and lignification. Glycosylation influences physiological roles, localization within cells and tissues, and metabolic fates of these metabolites. UGTs have substantially expanded in P. trichocarpa, presenting a challenge for large-scale characterization. Using a high-throughput assay, we produced substrate acceptance profiles for 40 previously uncharacterized candidate enzymes. Assays confirmed 10 of 13 leaf mGWAS associations, and a focused metabolite screen demonstrated varying levels of substrate specificity among UGTs. A substrate binding model case study of UGT-23 rationalized observed enzyme activities and mGWAS associations, including glycosylation of trichocarpinene to produce trichocarpin, a major higher-order salicylate in P. trichocarpa. We identified UGTs putatively involved in lignan, flavonoid, salicylate, and phytohormone metabolism, with potential implications for cell wall biosynthesis, nitrogen uptake, and biotic and abiotic stress response that determine sustainable biomass crop production. Our results provide new support for in silico analyses and evidence-based guidance for in vivo functional characterization.
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Circular polarized luminescence (CPL) sensitive two-dimensional organic inorganic halide perovskites have versatile applications in optical displays, encrypted transmission and quantum communications. Here, a new chiral hybrid [MePh3P]2CdCl4 (PCC) single crystal (SC) is synthesized using an achiral phosphonium cation by a solvent evaporation process at room temperature (rt). SC x-ray study reveals a non-centrosymmetric point group 23, with 21-screw optical axes providing a chiral Sohncke space group. Hirshfeld surface analysis suggests long-range H-bonding and ionic interactions (~ 3-9 kJ mol-1) and short-range Van der Waals and dispersion interactions (â¼0.4-4 kJ mol-1). Both the PCC thin films and SCs exhibit prominent circular dichroism (CD) and remarkably superior CPL activity at rt (|gCD| ≈ 5 × 10-3 and |glum| ≈ 4.3 × 10-2).
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Cerebral palsy (CP) is a neurological disorder that affects muscle tone, movement, and motor skills in children. One of the most common symptoms of cerebral palsy is spasticity, which is characterised by involuntary muscle contractions and stiffness. Both botulinum toxin and casting have been used as standalone treatments for spasticity in cerebral palsy, but which is better is still unclear. The aim of the present meta-analysis was to compare the effects on spasticity of serial casting and/or botulinum toxin type A (BoNT-A) in conjunction with or as independent therapies. Studies up to February 2022 were identified in four separate databases. The inclusion criteria were randomised controlled trials (RCTs) that compared different therapies (Botulinum toxin A, or BoNT-A, and casting) and assessed spasticity improvement in children with spastic cerebral palsy who were younger than 18 years old and were published in English. With a 95% confidence interval (CI), the standardised mean difference (SMD) was utilised to calculate treatment effects. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist was followed to undertake the current study. The search for relevant literature in four databases generated 147 results. After the abstract and full-text screening, five publications with a total of 190 cerebral palsy patients were included in this systematic review and meta-analysis. In patients with cerebral palsy, both methods - botulinum toxin and casting- apply globally; our systematic review tries to find out the most effective treatment between the two but does not show any significant difference in these methods. As we know, botulinum toxin is expensive, and the casting method is time-consuming and poorly accepted by patients. There is a need for an excellent study to examine the impact of casting and botulinum toxin type A.
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Exosomal microRNA (ExomiRs) serves as potential cargo molecules responsible for post-translation of gene expression and intracellular communication playing a vital role in acting as clinically relevant prognostic biomarkers for identifying pregnancy-associated complications in patients. ExomiRs are associated with Gestational Diabetes Mellitus (GDM) as potential targets for understanding the pathophysiology of beta-cell dysfunction. ExomiRs (ExomiR 122, ExomiR 16-5p, ExomiR 215-5p, ExomiR 450b-3p, ExomiR 122-5p) aid to act as biomarkers and regulate the progression of diabetes and its related complication. These ExomiRshave been reported to interfere with the regulation of various genes such as ZEB2, IRS1, IRS2, GLUT1, GLUT4, etc. and inhibition of several pathways like PI3K/AKT, Wnt, and mTOR signaling pathways leading to the modulation in the development of GDM affecting the clinical and pathological features of women. These ExomiRs have also been associated with other pregnancy-associated complications, including preeclampsia, hypothyroidism, pregnancy loss, and ectopic pregnancies. On the other hand, overexpression of certain ExomiRs such as Exomir-515-5p, ExomiR-221, and ExomiR-96 serve a regulatory role in overcoming insulin resistance. Taken together, the current review focuses on the prospective capabilities of ExomiRs for diagnosis and clinical prognosis of GDM women with respect to pregnancy outcomes.
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Diabetes Gestacional , MicroRNAs , Complicações na Gravidez , Gravidez , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/genética , Resultado da Gravidez , Prognóstico , Fosfatidilinositol 3-Quinases , Estudos Prospectivos , BiomarcadoresRESUMO
Covid 19 pandemic has severe implications on health and life of people. Asia being the most populous region has higher fatalities burden. Health infrastructure, stringent preventive measures by the government and public participation through adhering to social distancing have influence to check on fatalities' burden. The level of Social capital as well as voters' participation in a particular country can have influence on containment of COVID cases and fatalities. In this context, the main objectives of this study are to analyse pattern and trend of death burden for 45 Asian countries and impact of stringency measures by government, and voters' turnout ratio on death burden. However, for regression analysis only 32 countries are taken into account considering the availability of data for all variables. Multiple linear regression analysis is employed in a cross-sectional framework and Ordinary least square estimation technique with heteroscedastic adjusted standard errors have been used for estimation of coefficients. The results show that southern Asia contributes the highest share of fatality cases in total fatality cases of Asia with 71.43% share. It also has the highest share of confirmed cases in total confirmed cases of Asia with 71.72%. However, when we take the population into account, Western Asia leads in the share of confirmed COVID-19 cases and its associated fatality cases per million populations in Asia as compared to other Asian regions. The factors like health infrastructure and voters' turnover ratio are found to be significant and potential in reducing the new deaths per million populations. Though the coefficient of Stringency index has been negative and it did not emerge to be significant in Asian countries. The COVID related fatalities in Asian region are urban centric and urbanization proxy is found to be positive and significant. Diabetes prevalence rate has some heterogeneous result and in the present study its coefficient is not in the hypothesized direction. . The Countries should ramp up health infrastructure and necessary preparedness to deal with the subsequent waves and COVID related fatalities. Importance need to be given people's participation and their shared responsibilities in dealing with COVID cases and checking on fatalities. The realisation of social responsibility among the masses can lead to community participation and adhering to the protocols imposed by the government and helps in checking on spread of virus and associated death.
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Abuso de Idosos , Idoso , Abuso de Idosos/prevenção & controle , Humanos , Alocação de RecursosRESUMO
Crassulacean acid metabolism (CAM) plants exhibit elevated drought and heat tolerance compared to C3 and C4 plants through an inverted pattern of day/night stomatal closure and opening for CO2 assimilation. However, the molecular responses to water-deficit conditions remain unclear in obligate CAM species. In this study, we presented genome-wide transcription sequencing analysis using leaf samples of an obligate CAM species Kalanchoë fedtschenkoi under moderate and severe drought treatments at two-time points of dawn (2-h before the start of light period) and dusk (2-h before the dark period). Differentially expressed genes were identified in response to environmental drought stress and a whole genome wide co-expression network was created as well. We found that the expression of CAM-related genes was not regulated by drought stimuli in K. fedtschenkoi. Our comparative analysis revealed that CAM species (K. fedtschenkoi) and C3 species (Arabidopsis thaliana, Populus deltoides 'WV94') share some common transcriptional changes in genes involved in multiple biological processes in response to drought stress, including ABA signaling and biosynthesis of secondary metabolites.
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Metabolismo Ácido das Crassuláceas , Secas , Dióxido de Carbono/metabolismo , Metabolismo Ácido das Crassuláceas/genética , Genômica , Fotossíntese/genética , Plantas/metabolismo , Água/metabolismoRESUMO
Exosomes are extracellular vesicles produced by various cell types and extensively distributed in physiological fluids. Because of their significant role in cancer progression, they have been a focal point for the novel cancer therapy approach. Exosomes are highly efficient at transporting proteins, RNAs, and small drugs into cancer cells for therapeutic purposes. In addition to their prominent role as potential biomarkers for transporting targeted information from their progenitor cells, exosomes have also emerged as a new avenue for developing more effective clinical diagnostics and therapeutic techniques, also known as exosome theranostics. Lipids, proteins, and nucleic acids transported by exosomes were investigated as potential biomarkers for cancer diagnosis, prognosis, and future cancer treatment targets. The unique mechanism of exosomes and their therapeutic as well as diagnostic uses, also known as theranostic applications of exosomes in malignancies, are discussed in this review.
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BACKGROUND: Lifetime prevalence of Acute Appendicitis is about 6-7%.The seasonal variation is nearly an established fact with most of the studies suggesting that cases are more in summer and during the rainy season. There are few studies globally for evaluating the impact of altitude and temperature on the incidence of acute appendicitis. In India no such study has been reported. With this in view, a study was conducted on the incidence of acute appendicitis to evaluate the effect of absolute temperature in high altitudes >10000 ft. METHODS: Retrospective data collected for a period of five years from 2015 to 2019 for the three centres of Armed Forces, located at high altitude 10,500, 11,500 and 12,000 ft respectively and the three temperature categories viz.< 0 °C, 0-20 °C and >20 °C were made to infer if there is any correlation between these parameters. RESULTS: A total of 317 cases were operated in a period of 05 yrs at the three centres. In the three categories of temperature viz < 0 °C, 0-20 °C and >20 °C the total number of cases were 84,124 and 109 respectively over period of 5 yrs. The proportion of cases were maximum at altitude of 12000 ft. On evaluation of the effect of altitude and absolute temperature positive correlation is found. CONCLUSION: The analysis of the maiden study that was conducted for high altitude and extreme cold climate in India indicated a positive correlation of the altitude and the effect of absolute temperature on the occurrence of cases of Acute Appendicitis.
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Orphan genes are characteristic genomic features that have no detectable homology to genes in any other species and represent an important attribute of genome evolution as sources of novel genetic functions. Here, we identified 445 genes specific to Populus trichocarpa. Of these, we performed deeper reconstruction of 13 orphan genes to provide evidence of de novo gene evolution. Populus and its sister genera Salix are particularly well suited for the study of orphan gene evolution because of the Salicoid whole-genome duplication event which resulted in highly syntenic sister chromosomal segments across the Salicaceae. We leveraged this genomic feature to reconstruct de novo gene evolution from intergenera, interspecies, and intragenomic perspectives by comparing the syntenic regions within the P. trichocarpa reference, then P. deltoides, and finally Salix purpurea. Furthermore, we demonstrated that 86.5% of the putative orphan genes had evidence of transcription. Additionally, we also utilized the Populus genome-wide association mapping panel, a collection of 1,084 undomesticated P. trichocarpa genotypes to further determine putative regulatory networks of orphan genes using expression quantitative trait loci (eQTL) mapping. Functional enrichment of these eQTL subnetworks identified common biological themes associated with orphan genes such as response to stress and defense response. We also identify a putative cis-element for a de novo gene and leverage conserved synteny to describe evolution of a putative transcription factor binding site. Overall, 45% of orphan genes were captured in trans-eQTL networks.
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Populus , Evolução Molecular , Duplicação Gênica , Genoma de Planta , Estudo de Associação Genômica Ampla , Filogenia , Populus/genéticaRESUMO
Superoxide radicals and other reactive oxygen species (ROS) are implicated in influenza A virus-induced inflammation. In this in vitro study, we evaluated the effects of TG6-44, a novel quinazolin-derived myeloperoxidase-specific ROS inhibitor, on influenza A virus (A/X31) infection using THP-1 lung monocytic cells and freshly isolated peripheral blood mononuclear cells (PBMC). TG6-44 significantly decreased A/X31-induced ROS and virus-induced inflammatory mediators in THP-1 cells (IL-6, IFN-γ, MCP-1, TNF-α, MIP-1ß) and in human PBMC (IL-6, IL-8, TNF-α, MCP-1). Interestingly, TG6-44-treated THP-1 cells showed a decrease in percent cells expressing viral nucleoprotein, as well as a delay in translocation of viral nucleoprotein into the nucleus. Furthermore, in influenza A virus-infected cells, TG6-44 treatment led to suppression of virus-induced cell death as evidenced by decreased caspase-3 activation, decreased proportion of Annexin V+PI+ cells, and increased Bcl-2 phosphorylation. Taken together, our results demonstrate the anti-inflammatory and anti-infective effects of TG6-44.
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Mediadores da Inflamação/farmacologia , Inflamação/tratamento farmacológico , Vírus da Influenza A/efeitos dos fármacos , Peroxidase/antagonistas & inibidores , Espécies Reativas de Oxigênio/antagonistas & inibidores , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CCL2/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/patologia , Inflamação/virologia , Vírus da Influenza A/patogenicidade , Interleucina-6/genética , Interleucina-8/genética , Leucócitos Mononucleares/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Peroxidase/genética , Quinazolinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/genéticaRESUMO
Influenza infections cause several million cases of severe respiratory illness, hospitalizations, and hundreds of thousands of deaths globally. Secondary infections are a leading cause of influenza's high morbidity and mortality, and significantly factored into the severity of the 1918, 1968, and 2009 pandemics. Furthermore, there is an increased incidence of other respiratory infections even in vaccinated individuals during influenza season. Putative mechanisms responsible for vaccine failures against influenza as well as other respiratory infections during influenza season are investigated. Peripheral blood mononuclear cells (PBMCs) are used from influenza vaccinated individuals to assess antigen-specific responses to influenza, measles, and varicella. The observations made in humans to a mouse model to unravel the mechanism is confirmed and extended. Infection with influenza virus suppresses an ongoing adaptive response to vaccination against influenza as well as other respiratory pathogens, i.e., Adenovirus and Streptococcus pneumoniae by preferentially infecting and killing activated lymphocytes which express elevated levels of sialic acid receptors. These findings propose a new mechanism for the high incidence of secondary respiratory infections due to bacteria and other viruses as well as vaccine failures to influenza and other respiratory pathogens even in immune individuals due to influenza viral infections.
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Imunidade Adaptativa/imunologia , Influenza Humana/imunologia , Animais , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB CRESUMO
There is considerable association of thyroid function and the cardiovascular system during various acute systemic illnesses. It is well established that the normal thyroid homeostasis is known to alter in disease states including the acute coronary syndromes (ACS). Abnormal thyroid hormonal status has been shown to be related to worse outcomes and prognosis. This review focuses on the relationship of alterations in thyroid function and its influence on the pathophysiological mechanisms and cardiovascular hemodynamics in ACS and based upon the literature, summarises all the existing evidence to this date on this subject. The data largely points out that low levels of triiodothyronine (T3) levels seen in ACS might be useful in prognosticating the outcomes of ACS.