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Plant homeodomain leucine zipper IV (HD-Zip IV) transcription factors (TFs) contain an evolutionarily conserved steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain. While the START domain is required for TF activity, its presumed role as a lipid sensor is not clear. Here we used tandem affinity purification from Arabidopsis cell cultures to demonstrate that PROTODERMAL FACTOR2 (PDF2), a representative member that controls epidermal differentiation, recruits lysophosphatidylcholines (LysoPCs) in a START-dependent manner. Microscale thermophoresis assays confirmed that a missense mutation in a predicted ligand contact site reduces lysophospholipid binding. We additionally found that PDF2 acts as a transcriptional regulator of phospholipid- and phosphate (Pi) starvation-related genes and binds to a palindromic octamer with consensus to a Pi response element. Phospholipid homeostasis and elongation growth were altered in pdf2 mutants according to Pi availability. Cycloheximide chase experiments revealed a role for START in maintaining protein levels, and Pi starvation resulted in enhanced protein destabilization, suggesting a mechanism by which lipid binding controls TF activity. We propose that the START domain serves as a molecular sensor for membrane phospholipid status in the epidermis. Our data provide insights toward understanding how the lipid metabolome integrates Pi availability with gene expression.
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GLABRA2 (GL2), a class IV homeodomain leucine-zipper (HD-Zip IV) transcription factor (TF) from Arabidopsis, is a developmental regulator of specialized cell types in the epidermis. GL2 contains a monopartite nuclear localization sequence (NLS) that is conserved in most HD-Zip IV members across the plants. We demonstrate that NLS mutations affect nuclear transport and result in a loss-of-function phenotypes. NLS fusions to EYFP show that it is sufficient for nuclear localization in roots and trichomes. Despite partial overlap of the NLS with the homeodomain, genetic dissection indicates that nuclear localization and DNA binding are separable functions. Affinity purification of GL2 from plants followed by MS-based proteomics identified Importin α (IMPα) isoforms as potential GL2 interactors. NLS structural prediction and molecular docking studies with IMPα-3 revealed major interacting residues. Cytosolic yeast two-hybrid assays and co-immunoprecipitation experiments with recombinant proteins verified NLS-dependent interactions between GL2 and several IMPα isoforms. IMPα triple mutants (impα-1,2,3) exhibit abnormal trichome formation and defects in GL2 nuclear localization in trichomes, consistent tissue-specific and redundant functions of IMPα isoforms. Taken together, our findings provide mechanistic evidence for IMPα-dependent nuclear localization of GL2 in Arabidopsis, a process that is critical for cell-type differentiation of the epidermis.
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Gut microbes are important and may play important role in spreading cancers specially the gastrointestinal malignancies preferably colorectal cancers. Gut microbes and diet can influence the tissues in gastrointestinal tract increasing the risk of cancer spread. Insufficient nutrient intake and imbalance diet can disturb the microbiome of gastrointestinal tract causing metabolism of xenobiotics which is beneficial as well as detrimental. Dietary imbalance may also weaken the immune system which is another reason for spreading and development of cancers. The triage of gut microbiome, host immune system, and dietary patterns may help the initiation of mechanism of carcinogenesis. In addition to its role in carcinogenesis and tumor development, there is still growing evidence as to how intestinal microflora influences the efficacy and toxicity of chemotherapy and immunotherapy by the gut microbiome. It can therefore be used as a biomarker to predict treatment response or poor response and can also be modified to improve cancer treatment.
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Dieta , Microbioma Gastrointestinal , Neoplasias , Humanos , Microbioma Gastrointestinal/fisiología , Neoplasias/microbiología , AnimalesRESUMEN
BACKGROUND: Globally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy. METHODS: This prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied. RESULTS: A total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P Ë0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P Ë0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction. CONCLUSION: Pretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.
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Anemia , Hepatitis C Crónica , Hepatitis C , Humanos , Ribavirina/efectos adversos , Sofosbuvir/efectos adversos , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/genética , Antivirales/efectos adversos , Inosina Trifosfatasa , Hepacivirus/genética , Estudios Prospectivos , Polimorfismo de Nucleótido Simple , Pirofosfatasas/genética , Pirofosfatasas/uso terapéutico , Anemia/inducido químicamente , Anemia/genética , Hepatitis C/tratamiento farmacológico , Genotipo , Hemoglobinas/genética , Resultado del TratamientoRESUMEN
STUDY DESIGN: Prospective observational qualitative study. OBJECTIVE: Cannabis is used by patients for the treatment of chronic pain, spasticity, sleep issues or mood disorders such as anxiety and depression. Since 2018, it has been authorised in the United Kingdom for medical use as an unlicensed medicine. This study aims to determine if patients are using cannabis for the management of symptoms related to spinal cord injury, and if so, whether they are using medical or illicit cannabis. METHODS: Spinal cord injury patients from the Yorkshire Regional Spinal Injuries Centre and SPINE Community in the United Kingdom were surveyed. Participants were sent a 7-point electronic survey. All results were anonymous, and confidentiality was maintained throughout the process. RESULTS: In total, 223 patients completed the survey. Not all patients answered every question. Of those who responded 65.35% (n = 132) were paraplegic and 34.65% (n = 70) were tetraplegic. Patients were suffering from chronic pain (longer than 3 months), spasticity, loss of/difficulty in sleeping or anxiety/depression. Almost 15% (14.93%, n = 33 out of 221) used cannabis to manage their symptoms, out of those the majority used street cannabis (79.41%, n = 27 out of 34) were using street cannabis. CONCLUSION: This study demonstrates that there are spinal cord injury patients in the UK using cannabis to treat their symptoms. A majority appear to be using illicit cannabis. Given that cannabis can interact with other medications, and that the quality and content of illicit cannabis can be highly variable and at times dangerous, it is important for physicians to discuss cannabis use with their patients. This can inform prescribing and allow them to educate patients on the dangers of medical cannabis and potential alternatives.
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Autoimmunity refers to an organism's immune response against its own healthy cells, tissues, or components, potentially leading to irreversible damage to vital organs. Central and peripheral tolerance mechanisms play crucial roles in preventing autoimmunity by eliminating self-reactive T and B cells. The disruption of immunological tolerance, characterized by the failure of these mechanisms, results in the aberrant activation of autoreactive lymphocytes that target self-tissues, culminating in the pathogenesis of autoimmune disorders. Genetic predispositions, environmental exposures, and immunoregulatory disturbances synergistically contribute to the susceptibility and initiation of autoimmune pathologies. Within the realm of immune therapies for autoimmune diseases, cytokine therapies have emerged as a specialized strategy, targeting cytokine-mediated regulatory pathways to rectify immunological imbalances. Proinflammatory cytokines are key players in inducing and propagating autoimmune inflammation, highlighting the potential of cytokine therapies in managing autoimmune conditions. This review discusses the etiology of autoimmune diseases, current therapeutic approaches, and prospects for future drug design.
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Enfermedades Autoinmunes , Autoinmunidad , Citocinas , Humanos , Citocinas/metabolismo , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/terapia , Animales , Tolerancia InmunológicaRESUMEN
BACKGROUND: Inflammation is a key biological reaction that comprises a complex network of signals that both initiate and stop the inflammation process. PURPOSE: This study targets to evaluate the anti-inflammatory potential of the leaves of the Plectranthus rugosus (P. rugosus) plant involving both in vitro and in vivo measures. The current available drugs exhibit serious side effects. Traditional medicines impart an essential role in drug development. P. rugosus is a plant used in traditional medicine of Tropical Africa, China, and Australia to treat various diseases. METHODS: Lipopolysaccharide (LPS), an endotoxin, kindles macrophages to discharge huge quantities of pro-inflammatory cytokines like TNF-α and IL-6. So, clampdown of macrophage stimulation may have a beneficial potential to treat various inflammatory disorders. The leaves of the P. rugosus are used for swelling purpose by local population; however, its use as an anti-inflammatory agent and associated disorders has no scientific evidence. RESULTS: The extracts of the plant Plectranthus rugosus ethanolic extract (PREE), Plectranthus rugosus ethyl acetate extract (PREAF), and the compound isolated (oleanolic acid) suppress the pro-inflammatory cytokines (IL-6 and TNF-α) and nitric oxide (NO), confirming its importance in traditional medicine. CONCLUSION: The pro-inflammatory cytokines are inhibited by P. rugosus extracts, as well as an isolated compound oleanolic acid without compromising cell viability.
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Antineoplásicos , Ácido Oleanólico , Plectranthus , Antioxidantes/uso terapéutico , Factor de Necrosis Tumoral alfa , Interleucina-6 , Ácido Oleanólico/uso terapéutico , Antiinflamatorios/uso terapéutico , Extractos Vegetales/uso terapéutico , Inflamación/tratamiento farmacológico , Citocinas , Antineoplásicos/uso terapéutico , Óxido Nítrico , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Lipopolisacáridos/farmacologíaRESUMEN
Fasciola hepatica is a trematode leading to heavy economic setbacks to the livestock sector globally. The population's genetic information and intimate kinship level are frequently assessed using analysis of mitochondrial DNA. In this analysis, we retrieved cox1 (n = 247) and nad1 (n = 357) sequences of F. hepatica from the NCBI GenBank database and aligned the sequences with the respective reference sequences using MEGA software. The median joining network was drawn using PopArt software while neutrality and diversity indices were estimated with the help of DnaSp software. Neighbor-joining phylogenetic tree was constructed using the MEGA software package. A total of 46 and 98 distinctive haplotypes were observed for cox1 and nad1 genes, respectively. Diversity indices indicated high haplotype and nucleotide diversities in both genes. Positive Tajima's D and Fu's Fs values were found for the entire population of both the genes under study. The cox1 and nad1 gene segments in this study showed high Tajima's D values, suggesting a low likelihood of future population growth. The Tajima's D value of the nad1 gene sequence is lower (2.14910) than that of the cox1 gene sequence (3.40314), which suggests that the former is growing at a slower rate. However, the region-wise analysis revealed that both the cox1 and nad1 genes showed deviation from neutrality suggesting a recent population expansion as a result of an excess of low-frequency polymorphism. Furthermore, the overall host-wise analysis showed positive and significant Tajima's D values for the cox1 and nad1 gene sequences. To the best of our knowledge, this is the first attempt to provide insights into genetic variations and population structure of F. hepatica at a global scale using cox1 and nad1 genes. Our findings suggest the existence of specific variants of F. hepatica in different parts of the world and provide information on the molecular ecology of F. hepatica. The results of this study also mark a critical development in upcoming epidemiological investigations on F. hepatica and will also contribute to understanding the global molecular epidemiology and population structure of F. hepatica.
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Fasciola hepatica , Animales , Fasciola hepatica/genética , Filogenia , Variación Genética , ADN Mitocondrial/genética , HaplotiposRESUMEN
BACKGROUND: A high-quality docking method tends to yield multifold gains with half pains for the new drug development. Over the past few decades, great efforts have been made for the development of novel docking programs with great efficiency and intriguing accuracy. AutoDock Vina (Vina) is one of these achievements with improved speed and accuracy compared to AutoDock4. Since it was proposed, some of its variants, such as PSOVina and GWOVina, have also been developed. However, for all these docking programs, there is still large room for performance improvement. RESULTS: In this work, we propose a parallel multi-swarm cooperative particle swarm model, in which one master swarm and several slave swarms mutually cooperate and co-evolve. Our experiments show that multi-swarm programs possess better docking robustness than PSOVina. Moreover, the multi-swarm program based on random drift PSO can achieve the best highest accuracy of protein-ligand docking, an outstanding enrichment effect for drug-like activate compounds, and the second best AUC screening accuracy among all the compared docking programs, but with less computation consumption than most of the other docking programs. CONCLUSION: The proposed multi-swarm cooperative model is a novel algorithmic modeling suitable for protein-ligand docking and virtual screening. Owing to the existing coevolution between the master and the slave swarms, this model in parallel generates remarkable docking performance. The source code can be freely downloaded from https://github.com/li-jin-xing/MPSOVina .
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Algoritmos , Proteínas , Ligandos , Investigación , Programas InformáticosRESUMEN
BACKGROUND Congenital gastrointestinal (GI) malformations are developmental disorders that can result in secondary intestinal failure. Nutrient intakes must be adapted according to the newborn's nutritional requirements based on frequent anthropometric and biochemical assessments. Deficiencies or excess of a macronutrient can hinder the growth of the newborn. MATERIAL AND METHODS To assess the clinical condition of newborns with GI malformations, together with the postoperative nutritional status of newborns who underwent surgery due to congenital GI malformations, we performed a case-control study. The study group comprised newborns with digestive malformations (n=51) and the control group consisted of newborns without digestive pathologies (n=102), matched by sex, gestational age, and weight at admission. RESULTS Bivariate comparisons and multiple logistic regression analyses were performed. A P value <0.05 was considered to be statistically significant; these were observed in abdominal distension, gastric residue, and vomiting. The duration of hospitalization was shorter in the case group, as on average, they were transferred to the Pediatric Surgery Department on the 6th day, where they further remained admitted to treat the underlying cause. Differences between groups in administration of breast milk versus formula were not statistically significant. CONCLUSIONS We concluded that the clinical examination had a major role in early detection of digestive malformations and in the effective management of specific necessary nutrition. Proper evaluation of when to start enteral feeding can help post-surgical cases to recover faster, minimizing complications. Further studies are required to assess how financial factors affect implementation of the standardized guidelines of nutrition in children and to find possible solutions to financial constraints.
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Tracto Gastrointestinal , Nutrientes , Niño , Femenino , Recién Nacido , Humanos , Estudios de Casos y Controles , Edad Gestacional , Leche HumanaRESUMEN
Currently, researchers are working to contribute to the emerging fields of cloud computing, edge computing, and distributed systems. The major area of interest is to examine and understand their performance. The major globally leading companies, such as Google, Amazon, ONLIVE, Giaki, and eBay, are truly concerned about the impact of energy consumption. These cloud computing companies use huge data centers, consisting of virtual computers that are positioned worldwide and necessitate exceptionally high-power costs to preserve. The increased requirement for energy consumption in IT firms has posed many challenges for cloud computing companies pertinent to power expenses. Energy utilization is reliant upon numerous aspects, for example, the service level agreement, techniques for choosing the virtual machine, the applied optimization strategies and policies, and kinds of workload. The present paper tries to provide an answer to challenges related to energy-saving through the assistance of both dynamic voltage and frequency scaling techniques for gaming data centers. Also, to evaluate both the dynamic voltage and frequency scaling techniques compared to non-power-aware and static threshold detection techniques. The findings will facilitate service suppliers in how to encounter the quality of service and experience limitations by fulfilling the service level agreements. For this purpose, the CloudSim platform is applied for the application of a situation in which game traces are employed as a workload for analyzing the procedure. The findings evidenced that an assortment of good quality techniques can benefit gaming servers to conserve energy expenditures and sustain the best quality of service for consumers located universally. The originality of this research presents a prospect to examine which procedure performs good (for example, dynamic, static, or non-power aware). The findings validate that less energy is utilized by applying a dynamic voltage and frequency method along with fewer service level agreement violations, and better quality of service and experience, in contrast with static threshold consolidation or non-power aware technique.
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Nube Computacional , Carga de Trabajo , Fenómenos FísicosRESUMEN
Host inflammatory responses are key to protection against injury; however, persistent inflammation is detrimental and contributes to morbidity and mortality. Herein, we demonstrated the anti-inflammatory role of Arteannuin-B (1) and its new spirocyclic-2-isoxazoline derivative JR-9 and their side effects in acute inflammatory condition in vivo using LPS-induced cytokines assay, carrageenan-induced paw edema, acetic acid-induced writhing and tail immersion. The results show that the spirocyclic-2-isoxazoline derivative is a potent anti-inflammatory agent with minimal cell toxicity as compared to Arteannuin-B. In addition, the efficacies of these compounds were also validated by flow cytometric, computational, and histopathological analysis. Our results show that the anti-inflammatory response of JR-9 significantly reduces the ability of mouse macrophages to produce NO, TNF-α, and IL-6 following LPS stimulation. Therefore, JR-9 is a prospective candidate for the development of anti-inflammatory drugs and its molecular mechanism is likely related to the regulation of NF-κB and MAPK signaling pathway.
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Lipopolisacáridos , FN-kappa B , Ratones , Animales , FN-kappa B/metabolismo , Lipopolisacáridos/farmacología , Regulación hacia Abajo , Ratones Endogámicos BALB C , Macrófagos , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Elsinoë ampelina is an ascomycetous fungus that causes grape anthracnose, a potentially devastating disease worldwide. In this study, a dual RNA-seq analysis was used to simultaneously monitor the fungal genes related to pathogenesis and grape genes related to defense during the interaction at 2, 3, 4, and 5 days postinoculation. Consistent with their potential roles in pathogenicity, genes for carbohydrate-active enzymes, secondary metabolite synthesis, pathogen-host interaction, and those encoding secreted proteins are upregulated during infection. Based on Agrobacterium tumefaciens-mediated transient assays in Nicotiana benthamiana, we further showed that eight and nine candidate effectors, respectively, suppressed BAX- and INF1-mediated programmed cell death. The host response was characterized by the induction of multiple defense systems against E. ampelina, including synthesis of phenylpropanoids, stilbenes, and terpenoid biosynthesis, cell-wall modifications, regulation by phytohormones, and expression of defense-related genes. Together, these findings offer new insights into molecular mechanisms underlying the grape-E. ampelina interaction.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
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Ascomicetos , Interacciones Huésped-Patógeno , Enfermedades de las Plantas , Transcriptoma , Vitis , Ascomicetos/genética , Ascomicetos/patogenicidad , Regulación de la Expresión Génica de las Plantas , Interacciones Huésped-Patógeno/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Transcriptoma/genética , Vitis/genética , Vitis/microbiologíaRESUMEN
Acute Kidney Injury (AKI) is a common manifestation of COVID-19 and several cases have been reported in the setting of the high-risk APOL1 genotype (common genetic variants). This increases the likelihood that African American people with the high-risk genotype APOL1 are at increased risk for kidney disease in the COVID-19 environment. Single-nucleotide polymorphisms (SNPs) are found in various microRNAs (miRNAs) and target genes change the miRNA activity that leads to different diseases. Evidence has shown that SNPs increase/decrease the effectiveness of the interaction between miRNAs and disease-related target genes. The aim of this study is not only to identify miRSNPs on the APOL1 gene and SNPs in miRNA genes targeting 3'UTR but also to evaluate the effect of these gene variations in kidney patients and their association with SARS-COV-2 infection. In 3'UTR of the APOL1 gene, we detected 96 miRNA binding sites and 35 different SNPs with 10 different online software in the binding sites of the miRNA (in silico). Also we studied gene expression of patients and control samples by using qRT-PCR (in vitro). In silico study, the binding site of miR-6741-3p on APOL1 has two SNPs (rs1288875001, G > C; rs1452517383, A > C) on APOL1 3'UTR, and its genomic sequence is the same nucleotide as rs1288875001. Similarly, two other SNPs (rs1142591, T > A; rs376326225, G > A) were identified in the binding sites of miR-6741-3p at the first position. Here, the miRSNP (rs1288875001) in APOL1 3'UTR and SNP (rs376326225) in the miR-6741-3p genomic sequence are cross-matched in the same binding region. In vitro study, the relative expression levels were calculated by the 2-ΔΔCt method & Mann-Whitney U test. The expression of APOL1 gene was different in chronic kidney patients along with COVID-19. By these results, APOL1 expression was found lower in patients than healthy (p < 0.05) in kidney patients along with COVID-19. In addition, miR-6741-3p targets many APOL1-related genes (TLR7, SLC6A19, IL-6,10,18, chemokine (C-C motif) ligand 5, SWT1, NFYB, BRF1, HES2, NFYB, MED12L, MAFG, GTF2H5, TRAF3, angiotensin II receptor-associated protein, PRSS23) by evaluating online software in the binding sites of the miR-6741-3p. miR-6741-3p has not previously shown any association with kidney diseases and SARS-COV-2 infection. It assures that APOL1 can have a significant consequence in kidney-associated diseases by different pathways. Henceforth, this study represents and demonstrates an effective association between miR-6741-3p and kidney diseases, i.e., collapsing glomerulopathy, chronic kidney disease (CKD), acute kidney injury (AKI), and tubulointerstitial lesions susceptibility to SARS-COV-2 infection via in silico and in vitro exploration and recommended to have better insight.
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Regiones no Traducidas 3'/genética , Apolipoproteína L1/genética , COVID-19/genética , Enfermedades Renales/genética , MicroARNs/genética , Polimorfismo de Nucleótido Simple/genética , Sitios de Unión/genética , Estudios de Casos y Controles , Genotipo , Humanos , Riñón/patología , SARS-CoV-2/patogenicidadRESUMEN
An advanced detection assay is important for clinical diagnosis of human immunodeficiency virus (HIV) infection in asymptomatic individuals. The first step in timely treatment and management of the infection is the early detection of HIV. In this study, we determined the prevalence of HIV in Islamabad for the first time using a chemiluminescent microparticle immunoassay (CMIA), which is an advanced serological diagnostic technique. A total of 3659 samples were obtained from the general public in Islamabad, Pakistan, and 85 of them were found to be positive for HIV infection (2.32% prevalence). Of the positive subjects, 78.82% (67/85) were male, 10.6% (9/85) were female, and 10.6% (9/85) were of unidentified gender. The results revealed a significant relationship between age groups and HIV status. The age group of 21- to 30-year-olds was found to have the highest rate of HIV infection, and the rate of HIV infection in males was higher than in females.
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Infecciones por VIH/virología , VIH/inmunología , Inmunoensayo/métodos , Mediciones Luminiscentes/métodos , Tamizaje Masivo/métodos , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Pakistán , Prevalencia , Adulto JovenRESUMEN
The transition from traditional to truly smart dynamically adaptable manufacturing demands the adoption of a high degree of autonomy within automation systems, with resultant changes in the role of the human, in both the manufacturing and logistics functions within the factory. In the context of smart manufacturing, this paper describes research towards the realization of adaptable autonomous automation systems from both the control and information perspectives. Key facets of the approach taken at WMG are described in relation to human-machine interaction, autonomous approaches to assembly and intra-logistics, integration and dynamic system-wide optimization. The progression from simple distributed behavioural components towards autonomous functional entities is described. Effective systems integration and the importance of interoperability in the realization of more distributed and autonomous automation systems are discussed, so that operational information can propagate seamlessly, eliminating the traditional boundary between operational technology and information technology systems, and as an enabler for global knowledge collection, analysis and optimization. This article is part of the theme issue 'Towards symbiotic autonomous systems'.
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Elsinoë ampelina is the main cause of grape anthracnose, and the majority of grapevine cultivars are susceptible to this fungus. Some Chinese wild grape cultivars are resistant, however. It is therefore apt to compare the pathogenesis and immune responses in susceptible and resistant cultivars of grapevine to explore the detailed molecular and biochemical mechanisms of resistance to this fungus. In this study, ultrastructural and histopathological observations were used to demonstrate the resistance responses to E.â¯ampelina in the resistant Chinese wild cultivar Vitis quinquangularis clone 'Shang-24' and the susceptible cultivars V. davidii 'Tangwei' and V. vinifera 'Thompson Seedless'. Seventy-two hours postinoculation (hpi) with E. ampelina, brown necrotic spots were clearly visible on the leaves of the susceptible 'Tangwei' and 'Thompson Seedless'. The infection was characterized by rapid colonization of the host cells by hyphae and massive spread of the pathogen in the intercellular spaces, ultimately leading to host cell collapse, cuticle dissolution, and extensive hyphal growth. In the resistant clone 'Shang-24', the conidia were lysed, a large quantity of electronically dense matter appeared, the hyphal growth was suppressed, and the host cells remained intact. In addition, six genes associated with disease resistance were differentially expressed in the susceptible and resistant cultivars. These disease-related genes were significantly up-regulated following infection with E.â¯ampelina. This study illustrates the differences in infection and colonization of E.â¯ampelina in resistant and susceptible grape leaves.
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Ascomicetos , Vitis , Inmunidad , Enfermedades de las PlantasRESUMEN
Objective: To assess the effect of chloroquine and hydroxychloroquine on cytokine release syndrome (CRS) in adult patients with coronavirus disease 2019 (COVID-19) having mild to moderate symptoms.Methods: This blinded, placebo-controlled, randomized study was conducted in the Department of Medicine, Pak Emirates Military Hospital Rawalpindi, from June 1-15, 2020. A total of 150 hospitalized patients were enrolled after diagnoses with COVID-19 through reverse transcription polymerase chain reaction (RT-PCR). They were divided into three groups: hydroxychloroquine plus general care (HGC, n=50), chloroquine plus general care (CGC, n=50); and only general care (OGC, n=50). The HGC group received treatment with hydroxychloroquine 400 mg every 12 hours for day one and 200 mg for the next 4 days. The CGC group received treatment with chloroquine 250 mg every 12 hours for 7 days. The OGC group was kept as a control with only general care. After 12 days, the patients were screened for development of CRS through detection of interleukin 6 (IL-6) in serum samples by using Roche cobas e411 electrochemiluminescence immunoassay analyzer.Results: The mean duration from onset of symptoms to randomization was 7.65 days (SD = 3.287 days; range, 2-15 days). The mean age of patients was 37.57 (range 19-63) years. Results showed that out of a total 150 patients, only 10 patients (6%, mean=1.93; CI=1.89-1.97, P=0.651) developed CRS in all study groups. Four patients (8%) developed CRS in the HGC group, 2 patients (4%) in the CGC group, and 4 patients (8%) in the OGC group. There was no significant difference in the mean level of CRS among study groups.Conclusion: Administration of hydroxychloroquine and chloroquine has no effect in reducing the development of CRS in patients with COVID-19 having mild to moderate symptoms.
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Tratamiento Farmacológico de COVID-19 , Hidroxicloroquina , Adulto , Antivirales/uso terapéutico , Cloroquina/uso terapéutico , Síndrome de Liberación de Citoquinas , Humanos , Hidroxicloroquina/uso terapéutico , Persona de Mediana Edad , SARS-CoV-2 , Resultado del Tratamiento , Adulto JovenRESUMEN
Adipogenesis has been extensively studied using in vitro models of cellular differentiation, enabling long-term regulation of fat cell metabolism in human adipose tissue (AT) material. Many studies promote the idea that manipulation of this process could potentially reduce the prevalence of obesity and its related diseases. It has now become essential to understand the molecular basis of fat cell development to tackle this pandemic disease, by identifying therapeutic targets and new biomarkers. This review explores murine cell models and their applications for study of the adipogenic differentiation process in vitro. We focus on the benefits and limitations of different cell line models to aid in interpreting data and selecting a good cell line model for successful understanding of adipose biology.
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Adipocitos/metabolismo , Adipogénesis/genética , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo/crecimiento & desarrollo , Obesidad/genética , Tejido Adiposo/metabolismo , Tejido Adiposo Pardo/crecimiento & desarrollo , Animales , Diferenciación Celular/genética , Humanos , Técnicas In Vitro , Ratones , Obesidad/metabolismo , Obesidad/patologíaRESUMEN
Organic manures are more preferred and environmentally friendly than chemical fertilizers for minimally contaminating soil, water and environmental resources, but the determination of right source of organic manures continues to remain an unexplored aspect. Considering the important issue, a multi-year field trial was carried out to determine the response of forage soybean to four sources of nutrients such as chemical fertilizers (IF), poultry litter (PL), bovine's farm yard slurry (BFYS) and sewage sludge (SS) and their seven binary combinations (PL+BFYS, PL+SS, PL+IF, BFYS+SS, BFYS+IF, SS+IF and PL+BFYS+SS). Supplementation of organic manures with mineral fertilizers remained superior to their sole application, particularly BFYS + IF was found significantly (p≤0.05) superior for yielding the highest fresh biomass (23.9, 26.4 and 25.7 t ha-1) with improved nutritional quality. The same combination of integrated fertilizer management also recorded higher sustainability as per sustainable forage yield index along with the highest net income and the benefit-cost ratio. PL and SS applied in conjunction with IF performed better than sole or binary application of organic manures. Therefore, BFYS + IF may be recommended for adoption to produce comparable forage yield and nutritional quality of soybean along with reducing dependency on chemical fertilizers.