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BACKGROUND: Transcription factor (TF) binding motifs are identified by high throughput sequencing technologies as means to capture Protein-DNA interactions. These motifs are often represented by consensus sequences in form of position weight matrices (PWMs). With ever-increasing pool of TF binding motifs from multiple sources, redundancy issues are difficult to avoid, especially when every source maintains its own database for collection. One solution can be to cluster biologically relevant or similar PWMs, whether coming from experimental detection or in silico predictions. However, there is a lack of efficient tools to cluster PWMs. Assessing quality of PWM clusters is yet another challenge. Therefore, new methods and tools are required to efficiently cluster PWMs and assess quality of clusters. RESULTS: A new Python package Affinity Based Clustering for Position Weight Matrices (abc4pwm) was developed. It efficiently clustered PWMs from multiple sources with or without using DNA-Binding Domain (DBD) information, generated a representative motif for each cluster, evaluated the clustering quality automatically, and filtered out incorrectly clustered PWMs. Additionally, it was able to update human DBD family database automatically, classified known human TF PWMs to the respective DBD family, and performed TF motif searching and motif discovery by a new ensemble learning approach. CONCLUSION: This work demonstrates applications of abc4pwm in the DNA sequence analysis for various high throughput sequencing data using ~ 1770 human TF PWMs. It recovered known TF motifs at gene promoters based on gene expression profiles (RNA-seq) and identified true TF binding targets for motifs predicted from ChIP-seq experiments. Abc4pwm is a useful tool for TF motif searching, clustering, quality assessment and integration in multiple types of sequence data analysis including RNA-seq, ChIP-seq and ATAC-seq.
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Sequenciamento de Cromatina por Imunoprecipitação , Fatores de Transcrição , Sítios de Ligação/genética , Análise por Conglomerados , Humanos , Motivos de Nucleotídeos , Matrizes de Pontuação de Posição Específica , Ligação Proteica , Análise de Sequência de DNA/métodos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
In the detection of coronary heart diseases amongst the non-invasive techniques the role of myocardial perfusion imaging is indexed. The rationale of this study was to compare the different parameters and the association between the exercise MPI and vasodilator MPI in the detection of coronary artery disease (that is prolonged Qt interval with the size of perfusion defects). It was a cross-sectional prospective study with purposive non-probability sampling technique which was conducted in a tertiary care hospital from January 2020 to June 2020 for a period of 6 months. All patients regardless of gender were included in this study and age ranging from 30 to 80 years with comorbidities ranging from diabetes, hypertension and smokers were also included. A total of 100 patients were included in this study out of which 81% were male, 50% were diabetics, 69% were hypertensive, 39% had a history of coronary artery disease, 25% were smokers and 63% had hyperlipidemia. For statistical analysis SPSS 21 was applied and significant association was observed between DTS treadmill score and the perfusion defect in vasodilator MPI, corrected Qt interval and DTS tread mill score and between corrected Qt and size of the perfusion defect (P value < 0.001). It was thus seen that the different components of the noninvasive nuclear stress test tend to co-relate and thus aid in the detection of coronary artery disease increasing the accuracy of results.
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Doença da Artéria Coronariana/fisiopatologia , Teste de Esforço/métodos , Síndrome do QT Longo/fisiopatologia , Imagem de Perfusão do Miocárdio/métodos , Vasodilatadores , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/diagnóstico por imagem , Dipiridamol , Eletrocardiografia , Feminino , Humanos , Síndrome do QT Longo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The photodegradation of bifenthrin and deltamethrin was studied in the presence of Cu salts and two different solvents, methanol and acetonitrile. Results of the study showed that in the absence of any metal salt, the two pesticides degraded more rapidly in acetonitrile than in methanol. After 24 h of UV irradiation, 70% of deltamethrin had degraded in acetonitrile, while only 41% bifenthrin degraded in this solvent. In methanol, bifenthrin degraded at a much enhanced rate than in acetonitrile while the rate of degradation of deltamethrin was comparable to that in acetonitrile. The photodegradation was further enhanced by the addition of copper to the solution of bifenthrin and deltamethrin in acetonitrile. The rate of photodegradation of deltamethrin increased from 2.4 × 10-2 to 3.5 × 10-2 h-1 in acetonitrile and 2.5 × 10-2 to 3.4 × 10-2 h-1 in methanol after the addition of copper. Similarly, the rate of photodegradation of bifenthrin was increased from 5.0 × 10-3 to 9.0 × 10-3 h-1 in acetonitrile and 7.0 × 10-3to 9.05 × 10-3 h-1 in methanol with the addition of copper. Thus, copper has the potential to enhance the photodegradation of bifenthrin and deltamethrin in both the solvents.
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Acetonitrilas/química , Monitoramento Ambiental , Metanol/química , Nitrilas/metabolismo , Fotólise , Piretrinas/metabolismo , Cobre/química , Praguicidas/metabolismoRESUMO
A 41-year-old woman presented with a 3.5-month history of fever, weakness, productive cough, and burning micturition along with generalized weakness and significant weight loss. Chest X-ray revealed bilateral infiltrates and bilateral pleural effusion, and the workup suggested community-acquired pneumonia (CAP). However, the course was complicated by persistent fevers, elevated inflammatory markers, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), and pelvic fluid collection. Extensive investigations, including bronchoscopy and lung biopsy, failed to identify a specific pathogen. Pulmonary vasculitis and lymphoma were ruled out. Antibiotic and corticosteroid therapy resulted in clinical improvement. While the cause remains unknown, brucellosis and aspergillosis were considered but ruled out with advanced testing. The underlying etiology remains elusive, highlighting the diagnostic challenges in CAP with atypical presentations.
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Schnitzler syndrome (SS) is a rare autoinflammatory disorder characterized by a constellation of symptoms that include chronic urticarial rash, recurrent fever, arthralgias/arthritis, and monoclonal gammopathy, typically involving immunoglobulin M (IgM). However, cases with overlapping clinical features but lacking specific criteria fall under the umbrella of Schnitzler-like syndromes. This case report describes a 40-year-old male with Schnitzer-like syndrome and underscores the diagnostic complexities and therapeutic challenges of Schnitzer-like syndrome with IgG kappa monoclonal gammopathy, highlighting the need for a comprehensive diagnostic approach and targeted therapy.
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BACKGROUND: One of the major causes of cardiovascular morbidity and mortality is heart failure. The study aims to assess the effect of heart rate on the incidence of rehospitalization in patients with heart failure and reduced ejection fraction. METHODS: It is a cross-sectional, analytical research conducted over six months, from June to December 2022, at the cardiology department of a tertiary care hospital. Patients who satisfied the modified Framingham heart failure criteria at admission and were discharged with an initial diagnosis of heart failure and those readmitted within 6 months or less of their discharge were included in the study. Pregnant women, patients diagnosed with cognitive impairment, and patients who had contraindications for taking any of the beta-blockers, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker /angiotensin receptor -neprilysin inhibitor, Sodium-Glucose co-transport inhibitor, and mineralocorticoid inhibitors were excluded from the study. RESULTS: A total of 77 patients were included in the study. At discharge, approximately 71 patients had a heart rate of less than 70 beats/min and had no readmissions whereas, 6 patients had a heart rate of greater than 70 beats/min with 5 patients requiring readmission in the following 6 months. This relationship was statistically significant with a p-value of 0.000. CONCLUSIONS: According to the study, heart rate is a significant factor in the rehospitalization of individuals with heart failure and a low ejection fraction. At discharge, if the heart rate is not optimized then the rate of readmissions is increased.
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Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Gravidez , Humanos , Feminino , Readmissão do Paciente , Alta do Paciente , Volume Sistólico/fisiologia , Frequência Cardíaca , Estudos Transversais , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , HospitaisRESUMO
A major challenge in human genetics is of the analysis of the interplay between genetic and epigenetic factors in a multifactorial disease like cancer. Here, a novel methodology is proposed to investigate genome-wide regulatory mechanisms in cancer, as studied with the example of follicular Lymphoma (FL). In a first phase, a new machine-learning method is designed to identify Differentially Methylated Regions (DMRs) by computing six attributes. In a second phase, an integrative data analysis method is developed to study regulatory mutations in FL, by considering differential methylation information together with DNA sequence variation, differential gene expression, 3D organization of genome (e.g., topologically associated domains), and enriched biological pathways. Resulting mutation block-gene pairs are further ranked to find out the significant ones. By this approach, BCL2 and BCL6 were identified as top-ranking FL-related genes with several mutation blocks and DMRs acting on their regulatory regions. Two additional genes, CDCA4 and CTSO, were also found in top rank with significant DNA sequence variation and differential methylation in neighboring areas, pointing towards their potential use as biomarkers for FL. This work combines both genomic and epigenomic information to investigate genome-wide gene regulatory mechanisms in cancer and contribute to devising novel treatment strategies.
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Due to its widespread applications and its ubiquitous occurrence in the environment, bisphenol A (BPA) and its alternatives have gained increasing attention, especially in terms of human safety. Like BPA, alternatives such as bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF) have also been identified to be endocrine-disrupting chemicals (EDCs). Hence, in this study, we reviewed the literature of BPA and its alternatives mainly published between the period 2018-2020, including their occurrences in the environment, human exposure, and adverse health effects. The review shows that bisphenols are prevalent in the environment with BPA, BPS, and BPF being the most ubiquitous in the environment worldwide, though BPA remains the most abundant bisphenol. However, the levels of BPS and BPF in different environmental media have been constantly increasing and their fates and health risks are being evaluated. The studies show that humans and animals are exposed to bisphenols in many different ways through inhalation and ingestion and the exposure can have serious health effects. Urinary bisphenols (BPs) levels were frequently reported to be positively associated with different health problems such as cancer, infertility, cardiovascular diseases, diabetes and neurodegenerative diseases. Our literature study also shows that BPs generate reactive oxygen species and disrupt various signalling pathways, which could lead to the development of chronic diseases. Activated carbon-based and chitosan-based sorbents have been widely utilized in the removal of BPA in aqueous solutions. In addition, enzymes and microorganisms have also been getting much attention due to their high removal efficiencies.
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Compostos Benzidrílicos , Disruptores Endócrinos , Animais , Compostos Benzidrílicos/toxicidade , Carvão Vegetal , Disruptores Endócrinos/toxicidade , Humanos , Fenóis , ÁguaRESUMO
The human genome is regulated in a multi-dimensional way. While biophysical factors like Non-specific Transcription factor Binding Affinity (nTBA) act at DNA sequence level, other factors act above sequence levels such as histone modifications and 3-D chromosomal interactions. This multidimensionality of regulation requires many of these factors for a proper understanding of the regulatory landscape of the human genome. Here, we propose a new biophysical model for estimating nTBA. Integration of nTBA with chromatin modifications and chromosomal interactions, using a new Integrative Genome Analysis Pipeline (IGAP), reveals additive effects of nTBA to regulatory DNA sequences and identifies three types of genomic zones in the human genome (Inactive Genomic Zones, Poised Genomic Zones, and Active Genomic Zones). It also unveils a novel long distance gene regulatory model: chromosomal interactions reduce the physical distance between the high occupancy target (HOT) regions that results in high nTBA to DNA in the area, which in turn attract TFs to such regions with higher binding potential. These findings will help to elucidate the three-dimensional diffusion process that TFs use during their search for the right targets.
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DNA methylation (5mC) and hydroxymethylation (5hmC) are chemical modifications of cytosine bases which play a crucial role in epigenetic gene regulation. However, cost, data complexity and unavailability of comprehensive analytical tools is one of the major challenges in exploring these epigenetic marks. Hydroxymethylation-and Methylation-Sensitive Tag sequencing (HMST-seq) is one of the most cost-effective techniques that enables simultaneous detection of 5mC and 5hmC at single base pair resolution. We present HMST-Seq-Analyzer as a comprehensive and robust method for performing simultaneous differential methylation analysis on 5mC and 5hmC data sets. HMST-Seq-Analyzer can detect Differentially Methylated Regions (DMRs), annotate them, give a visual overview of methylation status and also perform preliminary quality check on the data. In addition to HMST-Seq, our tool can be used on whole-genome bisulfite sequencing (WGBS) and reduced representation bisulfite sequencing (RRBS) data sets as well. The tool is written in Python with capacity to process data in parallel and is available at (https://hmst-seq.github.io/hmst/).
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Long-standing, heavy alcohol use can lead to alcohol dependence, which predisposes to alcohol withdrawal if alcohol consumption is suddenly decreased or stopped. Alcohol withdrawal syndrome is characterized by a hyperadrenergic response, with symptoms ranging from mild tremulousness to delirium tremens. We report a 55-year-old male presenting with hyperthermia, tachycardia, tachypnea, altered consciousness, tremors, rigidity, diaphoresis, elevated creatinine kinase, and myoglobinuria. The diagnosis of alcohol withdrawal was made due to a history of alcohol use disorder with the last drink two days ago and no history of any medication or drug intake prior to admission. He was treated with benzodiazepines with an improvement in his condition.
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Empyema is often caused by Streptococcus pneumoniae, Staphylococcus aureus, and a variety of gram-negative organisms as well as anaerobes. Streptococcus gordonii (S. gordonii) is among some of the initial colonizers of the periodontal environment that is recognized to cause bacterial endocarditis. However, there are only a few case reports of S. gordonii causing empyema in the literature. We report the case of a 75-year-old male who presented with coughing up blood-tinged sputum. Physical examination revealed decreased breath sounds in the right lung base. Chest X-ray demonstrated a lower, right-sided, loculated pleural effusion. He underwent ultrasound-guided chest tube placement. The pleural fluid culture grew S. gordonii. He was started on ampicillin/ sulbactam. The follow-up computed tomography (CT) scan showed no significant improvement. Given his inability to improve with antibiotics and chest tube drainage, he was referred to an advanced care center for decortication of lung tissue.