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Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype-phenotype relationships1,2. Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies. The integration of HuRI with genome3, transcriptome4 and proteome5 data enables cellular function to be studied within most physiological or pathological cellular contexts. We demonstrate the utility of HuRI in identifying the specific subcellular roles of protein-protein interactions. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms that might underlie tissue-specific phenotypes of Mendelian diseases. HuRI is a systematic proteome-wide reference that links genomic variation to phenotypic outcomes.
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Proteoma/metabolismo , Espaço Extracelular/metabolismo , Humanos , Especificidade de Órgãos , Mapeamento de Interação de ProteínasRESUMO
In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.
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Reposicionamento de Medicamentos , Software , Reposicionamento de Medicamentos/métodos , Humanos , Internet , Descoberta de Drogas/métodos , Biologia de Sistemas/métodos , Biologia Computacional/métodosRESUMO
BACKGROUND: The presence of inorganic pollutants and heavy metals in industrial effluents has become a serious threat and environmental issues. Fungi have a remarkable ability to exclude heavy metals from wastewater through biosorption in eco-friendly way. Tannase plays an important role in bioconversion of tannin, a major constituent of tannery effluent, to gallic acid which has great pharmaceutical applications. Therefore, the aim of the current study was to exploit the potential of tannase from Aspergillus glaucus and fungal biomass waste for the bioremediation of heavy metals and tannin. RESULTS: Tannase from A. glaucus was partially purified 4.8-fold by ammonium sulfate precipitation (80%). The enzyme was optimally active at pH 5.0 and 40 °C and stable at this temperature for 1 h. Tannase showed high stability at different physiological conditions, displayed about 50% of its activity at 60 °C and pH range 5.0-6.0. Immobilization of tannase was carried out using methods such. as entrapment in Na-alginate and covalent binding to chitosan. The effects of Na-alginate concentrations on the beads formation and enzyme immobilization revealed that maximum immobilization efficiency (75%) was obtained with 3% Na-alginate. A potential reusability of the immobilized enzyme was showed through keeping 70% of its relative activity up to the fourth cycle. The best bioconversion efficiency of tannic acid to gallic acid by immobilized tannase was at 40 °C with tannic acid concentration up to 50 g/l. Moreover, bioremediation of heavy metal (Cr3+, Pb2+, Cu2+, Fe3+, and Mn2+) from aqueous solution using A. glaucus biomass waste was achieved with uptake percentage of (37.20, 60.30, 55.27, 79.03 and 21.13 respectively). The biomass was successfully used repeatedly for removing Cr3+ after using desorbing agent (0.1 N HCl) for three cycles. CONCLUSION: These results shed the light on the potential use of tannase from locally isolated A. glaucus in the bioremediation of industrial tanneries contained heavy metals and tannin.
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Aspergillus , Biodegradação Ambiental , Biomassa , Hidrolases de Éster Carboxílico , Enzimas Imobilizadas , Metais Pesados , Taninos , Taninos/metabolismo , Taninos/química , Aspergillus/enzimologia , Aspergillus/metabolismo , Metais Pesados/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Enzimas Imobilizadas/metabolismo , Enzimas Imobilizadas/química , Concentração de Íons de Hidrogênio , Temperatura , Estabilidade EnzimáticaRESUMO
INTRODUCTION: Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure typically developing in the first decade of life, congenital abnormalities, and an increased predisposition to malignancy. However, patients with FA can remain undiagnosed until adulthood and present with solid organ malignancies. Due to impaired DNA repair mechanisms, patients with FA are highly susceptible to severe bone marrow toxicity when treated with cisplatin. CASE REPORT: A 38-year-old woman, diagnosed with locally advanced squamous cell carcinoma (SCC) of the uterine cervix, underwent treatment with weekly cisplatin concurrent with radiotherapy. After the second week of cisplatin treatment, she presented with severe pancytopenia. The prolonged and severe pancytopenia following cisplatin and radiation, along with cervical SCC in the absence of risk factors and the presence of parental consanguinity, raised the possibility of FA as the underlying cause. Whole exome sequencing revealed a homozygous FANCI c.668A > C (p.Lys223Thr) missense variant confirming the diagnosis of FA. MANAGEMENT AND OUTCOME: The pancytopenia exhibited a protracted course, necessitating admission and supportive treatment with antibiotics, red blood cell and platelet transfusions, as well as filgrastim and eltrombopag. Eventually, the pancytopenia improved after approximately 40 days of hospitalization. DISCUSSION: SCC of the head and neck or gynecologic organs in a young adult without known risk factors should prompt consideration of FA. Cisplatin should be avoided in patients with FA.
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BACKGROUND: During scoliosis surgery, motor evoked potentials (MEP), and somatosensory evoked potentials (SSEP) have been reported to be affected by the use of higher doses of anesthetic agents. Dexmedetomidine, a sympatholytic agent, an alpha-2 receptor agonist, has been used as an adjunctive agent to lower anesthetic dose. However, there is conflicting evidence regarding the effects of dexmedetomidine on the intraoperative neurophysiological monitoring of MEP and SSEP during surgery, particularly among pediatric patients. OBJECTIVES: This systematic review aimed to determine whether, during spinal fusion surgery in pediatric patients with scoliosis, dexmedetomidine alters MEP amplitude or SSEP latency and amplitude and, if so, whether different doses of dexmedetomidine display different effects (PROSPERO registration number CRD42022300562). METHODS: We searched PubMed, Scopus, and Cochrane Library on January 1, 2022 and included randomized controlled trials, observational cohort and case-control studies and case series investigating dexmedetomidine in the population of interest and comparing against a standardized anesthesia regimen without dexmedetomidine or comparing multiple doses of dexmedetomidine. Animal and in vitro studies and conference abstracts were excluded. RESULTS: We found substantial heterogeneity in the risk of bias (per Cochrane-preferred tools) of the included articles (n = 5); results are summarized without meta-analysis. Articles with the lowest risk of bias indicated that dexmedetomidine was associated with MEP loss and that higher doses of dexmedetomidine increased risk. In contrast, articles reporting no association between dexmedetomidine and MEP loss suffered from higher risk of bias, including suspected or confirmed problems with confounding, outcome measurement, participant selection, results reporting, and lack of statistical transparency and power. CONCLUSION: Given the limitations of the studies available in the literature, it would be advisable to conduct rigorous randomized controlled trials with larger sample sizes to assess the effects of dexmedetomidine use of in scoliosis surgery in pediatric patients.
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Dexmedetomidina , Monitorização Neurofisiológica Intraoperatória , Escoliose , Humanos , Criança , Monitorização Neurofisiológica Intraoperatória/métodos , Dexmedetomidina/farmacologia , Escoliose/cirurgia , Potenciais Somatossensoriais Evocados/fisiologia , Potencial Evocado Motor/fisiologia , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Estudos RetrospectivosRESUMO
BACKGROUND: The direct quantitative measurement of donor and recipient pressures in patients with moyamoya vasculopathy (MMV) during superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery has yet to be reported in academic literature. METHOD: Using a wireless pressure wire, we describe our approach to measuring seven pressure parameters in MMV patients step-by-step. CONCLUSION: Direct intraluminal pressure measurement of donor and recipient arteries provides a practical and accurate means to quantify cerebral hemodynamic parameters in MMV patients, enhancing understanding of individualized hemodynamic changes pre- and post-surgery.
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Revascularização Cerebral , Doença de Moyamoya , Humanos , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/cirurgia , Hemodinâmica , Artéria Cerebral Média/cirurgia , Artérias Temporais/cirurgiaRESUMO
The study of gene expression variability, especially for cancer and cell differentiation studies, has become important. Here, we investigate transcriptome-wide scatter of 23 cell types and conditions across different levels of biological complexity. We focused on genes that act like toggle switches between pairwise replicates of the same cell type, i.e. genes expressed in one replicate and not expressed in the other, sometimes also referred as ON/OFF genes. The proportion of these toggle genes dramatically increases from unicellular to multicellular organization, especially for development and cancer cells. A relevant portion of toggle switches are non-coding genes: in unicellular systems the most represented classes are tRNA and rRNA, while multicellular systems more frequently show lncRNA, sncRNA and pseudogenes. Notably, disease associated microRNAs (miRNAs), pseudogenes and numerous uncharacterized transcripts are present in both development and cancer cells. On top of the known intrinsic and extrinsic factors, our work indicates toggle genes as a novel collective component creating transcriptome-wide variability. This requires further investigation for elucidating both evolutionary and disease processes.
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MicroRNAs , Neoplasias , RNA Longo não Codificante , Diferenciação Celular , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , TranscriptomaRESUMO
Many proteins involved in signal transduction contain peptide recognition modules (PRMs) that recognize short linear motifs (SLiMs) within their interaction partners. Here, we used large-scale peptide-phage display methods to derive optimal ligands for 163 unique PRMs representing 79 distinct structural families. We combined the new data with previous data that we collected for the large SH3, PDZ, and WW domain families to assemble a database containing 7,984 unique peptide ligands for 500 PRMs representing 82 structural families. For 74 PRMs, we acquired enough new data to map the specificity profiles in detail and derived position weight matrices and binding specificity logos based on multiple peptide ligands. These analyses showed that optimal peptide ligands resembled peptides observed in existing structures of PRM-ligand complexes, indicating that a large majority of the phage-derived peptides are likely to target natural peptide-binding sites and could thus act as inhibitors of natural protein-protein interactions. The complete dataset has been assembled in an online database (http://www.prm-db.org) that will enable many structural, functional, and biological studies of PRMs and SLiMs.
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Bases de Dados de Proteínas , Peptídeos/metabolismo , Inquéritos e Questionários , Sequência de Aminoácidos , Bacteriófagos/metabolismo , Humanos , Ligantes , Peptídeos/químicaRESUMO
OBJECTIVE: Cardiac surgery for repair of congenital heart defects poses unique hazards to the developing brain. Deep hypothermic circulatory arrest (DHCA) is a simple and effective method for facilitating a bloodless surgical field during congenital heart defect repair. There are, however, some concerns that prolonged DHCA increases the risk of nervous system injury. The electroencephalogram (EEG) is used in adult and, to a lesser extent, pediatric cardiac procedures as a neuromonitoring method. The present study was performed to assess outcomes following DHCA with EEG monitoring in the pediatric population. DESIGN: In this systematic review and meta-analysis, the PubMed, Cochrane Central Register of Controlled Trials, Scopus, Institute of Science Index, and Embase databases were searched from inception for relevant articles. A fixed- or random-effects model, as appropriate, was used. SETTING: Surgical setting. PARTICIPANTS: Pediatric population (≤18 y old). INTERVENTIONS: DHCA (18°C) with EEG monitoring. MEASUREMENTS AND MAIN RESULTS: Nineteen articles with 1,267 pediatric patients ≤18 years were included. The event rate of clinical and EEG seizures among patients who underwent DHCA was 12.9% and 14.9%, respectively. Mortality was found to have a 6.3% prevalence. A longer duration of DHCA was associated with a higher risk of EEG seizure and neurologic abnormalities. In addition, seizures were associated with increased neurologic abnormalities and neurodevelopmental delay. CONCLUSIONS: EEG and neurologic abnormalities were common after DHCA. A longer duration of DHCA was found to lead to more EEG seizure and neurologic abnormalities. Moreover, EEG seizures were more common than clinical seizures. Seizures were found to be associated with increased neurologic abnormalities and neurodevelopmental delay.
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Procedimentos Cirúrgicos Cardíacos , Parada Circulatória Induzida por Hipotermia Profunda , Encéfalo , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar , Criança , Parada Circulatória Induzida por Hipotermia Profunda/efeitos adversos , Eletroencefalografia , Humanos , Convulsões/diagnóstico , Convulsões/epidemiologia , Convulsões/etiologiaRESUMO
Aggression takes several forms and can be offensive or defensive. Aggression between animals of the same species or society aims to inflict harm upon another for the purpose of protecting a resource such as food, reproductive partners, territory, or status. This chapter explores the neurobiology of aggression. We summarize the behavior of aggression, rodent models of aggression, and the correlates of aggressive behavior in the context of neuroendocrinology, neurotransmitter systems, and neurocircuitry. Translational implications of rodent studies are briefly discussed, applying basic research to brain imaging data and therapeutic approaches to conditions where aggression is problematic.
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Agressão , Encéfalo/fisiologia , Neurobiologia , Animais , Modelos Animais , NeurotransmissoresRESUMO
Food intake and energy homeostasis determine survival of the organism and species. Information on total energy levels and metabolic state are sensed in the periphery and transmitted to the brain, where it is integrated and triggers the animal to forage, prey, and consume food. Investigating circuitry and cellular mechanisms coordinating energy balance and feeding behaviors has drawn on many state-of-the-art techniques, including gene manipulation, optogenetics, virus tracing, and single-cell sequencing. These new findings provide novel insights into how the central nervous system regulates food intake, and shed the light on potential therapeutic interventions for eating-related disorders such as obesity and anorexia.
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Encéfalo/fisiologia , Comportamento Alimentar/fisiologia , Animais , Ingestão de Alimentos , Metabolismo Energético , Homeostase , HumanosRESUMO
Apyrase is one of the essential platelet aggregation inhibitors in hematophagous arthropods due to its ability to hydrolyze ATP and ADP molecules. Here, an apyrase (TNapyrase) with antiplatelet aggregation activity was purified and characterized from the nymphs of the camel tick Hyalomma dromedarii through anion exchange and gel filtration columns. The homogeneity of TNapyrase was confirmed by native-PAGE, SDS-PAGE as well as with isoelectric focusing. Purified TNapyrase had a molecular mass of 25 kDa and a monomer structure. TNapyrase hydrolyzed various nucleotides in the order of ATP > PPi > ADP > UDP > 6GP. The Km value was 1.25 mM ATP and its optimum activity reached at pH 8.4. The influence of various ions on TNapyrase activity showed that FeCl2, FeCl3 and ZnCl2 are activators of TNapyrase. EDTA inhibited TNapyrase activity competitively with a single binding site on the molecule and Ki value of 2 mM. Finally, TNapyrase caused 70% inhibition of ADP-stimulated platelets aggregation and is a possible target for antibodies in future tick vaccine studies.
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Apirase/metabolismo , Proteínas de Artrópodes/metabolismo , Agregação Plaquetária , Carrapatos/enzimologia , Animais , Camelus , NinfaRESUMO
This paper documents the results of 12 months of monitoring of an upgraded hybrid moving bed biofilm reactor-conventional activated sludge wastewater treatment plant (MBBR-CAS WWTP). It also targets the assessment of the increment of the hydraulic load on existing treatment units with a zero construction and land cost. The influent flow to the plant was increased from 21,000 m3 d-1 to 30,000 m3 d-1, 40% of the existing CAS reactor volume was used for the MBBR zone with a carrier fill fraction of 47.62% and with Headworks Bio ActiveCell™ 515 used as media; no modifications were made for the primary and secondary tanks. The hybrid reactor showed high removal efficiencies for biochemical oxygen demand (BOD5), chemical oxygen demand (COD) and total suspended solids (TSS), with average effluent values recording 33.00 ± 8.87 mg L-1, 52.90 ± 9.65 mg L-1 and 29.50 ± 6.64 mg L-1 respectively. Nutrient removals in the hybrid modified biological reactor were moderate compared with carbon removal despite the high C/N ratio of 12.33. Findings in this study favor the application of MBBR in the upgrading of existing CAS plants with the plant BOD5 removal efficiency recording an increase of about 5% compared with the plant before upgrade and effluent values well within the legal requirements.
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Esgotos , Águas Residuárias , Biofilmes , Reatores Biológicos , Eliminação de Resíduos LíquidosRESUMO
Bacterial diseases are the main cause of high economic loss in aquaculture, particularly gram-negative bacteria. This study was conducted for the isolation and identification of Aeromonas and Pseudomonas spp. from diseased fish. Twenty-two Aeromonas and sixteen Pseudomonas isolates were recovered from diseased Nile tilapia (Oreochromis niloticus) raised in eight earthen ponds in Elhox, Metoubes, Kafrelsheikh, Egypt. The recovered isolates were further identified using PCR as 22 Aeromonas hydrophila, 11 Pseudomonas aeruginosa, and 5 Pseudomonas fluorescens isolates. The 22 A. hydrophila isolates were screened for the presence of four virulence genes. Sixteen of the isolates (72.72%) were positive for the aerolysin gene (aer); 4 (18.18%) harbored the cytotoxic enterotoxin gene (act); and 2 (9.09%) carried the hemolysin A gene (hylA) while the cytotonic heat-stable enterotoxin gene (ast) was absent from all the tested isolates. The pathogenicity test indicated the direct relationship between the mortality percentage and the genotype of the tested A. hydrophila isolates as the mortality rates were 63.3 and 73.3% for isolates with two virulence genes (aer+ & act+, and aer+ and hylA+, respectively), followed by 40, 53.3, and 56.6% for isolates with only one virulence gene (hylA, act, and aer, respectively) and 20% for isolates lacking virulence genes. Based on the sensitivity test, the multi-antibiotic resistance profiles were as follows: 90.9% of the A. hydrophila isolates were sensitive to florfenicol and doxycycline; then 68.18% were susceptible to oxytetracycline, norfloxacin, and ciprofloxacin; and 63.63% were susceptible to sulfamethoxazole-trimethoprim, while only 27.27 and 4.5% were sensitive to erythromycin and cephradine, respectively, and all the isolates were resistant to amoxicillin and ampicillin.
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Aeromonas hydrophila/genética , Proteínas de Bactérias/genética , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Fatores de Virulência/genética , Aeromonas hydrophila/metabolismo , Aeromonas hydrophila/patogenicidade , Animais , Proteínas de Bactérias/metabolismo , Ciclídeos/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Pseudomonas/genética , Pseudomonas/metabolismo , Pseudomonas/patogenicidade , Virulência , Fatores de Virulência/metabolismoRESUMO
BACKGROUND: Surgery for aortic coarctation requires special care during anesthesia due to severe pain during the lateral thoracotomy incision, intraoperative hemodynamic instability and the need for large doses of intra- and postoperative analgesics and vasodilators. Additionally, the postoperative care of patients is very important. AIMS: We aimed to compare ultrasound-guided paravertebral block performed using bupivacaine alone and bupivacaine with dexamethasone in terms of the intra- and postoperative analgesic requirements and hemodynamics, postoperative complications and ICU stay. STUDY DESIGN: This was a prospective, randomized, controlled, double-blinded study. METHODS: Fifty patients aged four to 12 months scheduled for aortic coarctation surgery were randomly divided into two equal groups (n = 25). Patients in group D (dexamethasone) received 0.5 mg/kg bupivacaine 0.25% mixed with 0.1 mg/kg dexamethasone diluted with isotonic saline and those in group C (control) received 0.5 mg/kg bupivacaine 0.25% diluted with isotonic saline (total volume 15 ml in each group). Intraoperative fentanyl consumption and hemodynamics (heart rate, arterial blood pressure) at baseline, 1 min after induction, at skin incision, after 30 min, after clamping, after declamping and at the end of the surgery were recorded, along with the objective pain score (OPS) immediately postoperatively and at 4 h, 8 h, 12 h and 24 h postoperatively and the time to the first request for pethidine. The intra- and postoperative vasodilator doses, time to extubation, ICU stay duration and postoperative complications were also recorded. RESULTS: The postoperative OPS was significantly lower at 12 and 24 h in group D than in group C. The time to the first request for analgesia was significantly longer in group D than in group C (3.9 ± 2.23 vs 8.6 ± 0.69). Additionally, the time to extubation was significantly shorter in group D. CONCLUSION: The use of dexamethasone as an adjuvant in ultrasound-guided paravertebral block in paediatric patients undergoing surgery for aortic coarctation increased the duration of postoperative analgesia with a prolonged time to the first request for analgesics It was also associated with a decreased incidence of postoperative complications. TRIAL REGISTRATION: Trial registration number: NCT03074773 . (Prospectively registered). The initial registration date was 9/3/2017.
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Anti-Inflamatórios/administração & dosagem , Coartação Aórtica/cirurgia , Bloqueio Nervoso Autônomo/métodos , Dexametasona/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Coartação Aórtica/diagnóstico por imagem , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Dor Pós-Operatória/diagnóstico por imagem , Estudos Prospectivos , Toracotomia/efeitos adversos , Toracotomia/métodos , Ultrassonografia de Intervenção/métodosRESUMO
Reversible protein-tyrosine phosphorylation is catalyzed by the antagonistic actions of protein-tyrosine kinases (PTKs) and phosphatases (PTPs), and represents a major form of cell regulation. Acute myeloid leukemia (AML) is an aggressive hematological malignancy that results from the acquisition of multiple genetic alterations, which in some instances are associated with deregulated protein-phosphotyrosine (pY) mediated signaling networks. However, although individual PTKs and PTPs have been linked to AML and other malignancies, analysis of protein-pY networks as a function of activated PTKs and PTPs has not been done. In this study, MS was used to characterize AML proteomes, and phospho-proteome-subsets including pY proteins, PTKs, and PTPs. AML proteomes resolved into two groups related to high or low degrees of maturation according to French-American-British classification, and reflecting differential expression of cell surface antigens. AML pY proteomes reflect canonical, spatially organized signaling networks, unrelated to maturation, with heterogeneous expression of activated receptor and nonreceptor PTKs. We present the first integrated analysis of the pY-proteome, activated PTKs, and PTPs. Every PTP and most PTKs have both positive and negative associations with the pY-proteome. pY proteins resolve into groups with shared PTK and PTP correlations. These findings highlight the importance of pY turnover and the PTP phosphatome in shaping the pY-proteome in AML.
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Leucemia Mieloide Aguda/metabolismo , Fosfotirosina/metabolismo , Proteínas Quinases/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Humanos , Leucemia Mieloide Aguda/enzimologia , Fosforilação , Transdução de SinaisRESUMO
Brain carbonic anhydrases (CAs) are known to modulate neuronal signalling. Using a novel CA VII (Car7) knockout (KO) mouse as well as a CA II (Car2) KO and a CA II/VII double KO, we show that mature hippocampal pyramidal neurons are endowed with two cytosolic isoforms. CA VII is predominantly expressed by neurons starting around postnatal day 10 (P10). The ubiquitous isoform II is expressed in neurons at P20. Both isoforms enhance bicarbonate-driven GABAergic excitation during intense GABAA-receptor activation. P13-14 CA VII KO mice show behavioural manifestations atypical of experimental febrile seizures (eFS) and a complete absence of electrographic seizures. A low dose of diazepam promotes eFS in P13-P14 rat pups, whereas seizures are blocked at higher concentrations that suppress breathing. Thus, the respiratory alkalosis-dependent eFS are exacerbated by GABAergic excitation. We found that CA VII mRNA is expressed in the human cerebral cortex before the age when febrile seizures (FS) occur in children. Our data indicate that CA VII is a key molecule in age-dependent neuronal pH regulation with consequent effects on generation of FS.
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Anidrase Carbônica II/metabolismo , Anidrases Carbônicas/metabolismo , Córtex Cerebral/citologia , Neurônios GABAérgicos/metabolismo , Convulsões Febris/enzimologia , Fatores Etários , Análise de Variância , Animais , Northern Blotting , Western Blotting , Anidrase Carbônica II/genética , Anidrases Carbônicas/genética , Córtex Cerebral/metabolismo , Diazepam/toxicidade , Eletroencefalografia , Fluorescência , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Knockout , Ratos , Convulsões Febris/induzido quimicamente , Convulsões Febris/metabolismoRESUMO
Decoding DNA symbols using next-generation sequencers was a major breakthrough in genomic research. Despite the many advantages of next-generation sequencers, e.g., the high-throughput sequencing rate and relatively low cost of sequencing, the assembly of the reads produced by these sequencers still remains a major challenge. In this review, we address the basic framework of next-generation genome sequence assemblers, which comprises four basic stages: preprocessing filtering, a graph construction process, a graph simplification process, and postprocessing filtering. Here we discuss them as a framework of four stages for data analysis and processing and survey variety of techniques, algorithms, and software tools used during each stage. We also discuss the challenges that face current assemblers in the next-generation environment to determine the current state-of-the-art. We recommend a layered architecture approach for constructing a general assembler that can handle the sequences generated by different sequencing platforms.
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DNA/química , Análise de Sequência de DNA/métodos , Algoritmos , Sequência de Bases , Genoma , Alinhamento de Sequência , SoftwareRESUMO
With the continuous increment in global population growth, compounded by post-pandemic food security challenges due to labor shortages, effects of climate change, political conflicts, limited land for agriculture, and carbon emissions control, addressing food production in a sustainable manner for future generations is critical. Microorganisms are potential alternative food sources that can help close the gap in food production. For the development of more efficient and yield-enhancing products, it is necessary to have a better understanding on the underlying regulatory molecular pathways of microbial growth. Nevertheless, as microbes are regulated at multiomics scales, current research focusing on single omics (genomics, proteomics, or metabolomics) independently is inadequate for optimizing growth and product output. Here, we discuss digital twin (DT) approaches that integrate systems biology and artificial intelligence in analyzing multiomics datasets to yield a microbial replica model for in silico testing before production. DT models can thus provide a holistic understanding of microbial growth, metabolite biosynthesis mechanisms, as well as identifying crucial production bottlenecks. Our argument, therefore, is to support the development of novel DT models that can potentially revolutionize microorganism-based alternative food production efficiency.
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Biologia de Sistemas , Inteligência Artificial , Metabolômica/métodos , Genômica , Bactérias/metabolismo , Bactérias/genéticaRESUMO
BACKGROUND: In bypass surgery for moyamoya disease (MMD), the superficial temporal artery's (STA) pressure needs to surpass that of the cortical M4 recipient of the middle cerebral artery (MCA), boosting cerebral blood flow into the MCA and enhancing cerebral circulation. This study investigates the STA-MCA arterial pressure parameters and gradients during bypass surgery, aiming to deepen our understanding of hemodynamic shifts pre- and post-operation. METHODS: DSA imaging data were prospectively collected from patients diagnosed with bilateral MMD who underwent STA-MCA bypass surgery between 2022 and 2023 and stratified according to the Suzuki stage. The mean arterial pressure (MAP) of the donor and recipient arteries was directly measured during the STA-MCA bypass procedure, and these data were statistically analyzed and evaluated. RESULTS: Among 48 MMD patients, Suzuki grading revealed that 43.8% were in early stages (II and III), while 56.2% were in advanced stages (IV, V, and VI). Predominantly, 77.1% presented with ischemic-type MMD and 22.9% with hemorrhagic type. Pre-bypass assessments showed that 62.5% exhibited antegrade blood flow direction, and 37.5% had retrograde. The mean recipient artery pressure was 35.0 ± 2.3 mmHg, with a mean donor-recipient pressure gradient (δP) of 46.4 ± 2.5 mmHg between donor and recipient arteries. Post-bypass, mean recipient artery pressure increased to 73.3 ± 1.6 mmHg. No significant correlation (r = 0.18, P = 0.21) was noted between δP and Suzuki staging. CONCLUSION: Our study elucidated that cerebral blood pressure significantly decreases beyond the moyamoya network at the distal M4 segment. Furthermore, we observed bidirectional flow in MCA territories and a significant positive pressure gradient between the STA and M4 segments. The lack of correlation between Suzuki stages and M4 pressures indicates that angiographic severity may not reflect hemodynamic conditions before surgery, highlighting the need for customized surgical approaches.