Combinatorial Control of Light Induced Chromatin Remodeling and Gene Activation in Neurospora

Light is an important environmental cue that affects physiology and development of Neurospora crassa. The light-sensing transcription factor (TF) WCC, which consists of the GATAfamily TFs WC1 and WC2, is required for light-dependent transcription. SUB1, another GATA-family TF, is not a photoreceptor but has also been implicated in light-inducible gene expression. To assess regulation and organization of the network of light-inducible genes, we analyzed the roles of WCC and SUB1 in light-induced transcription and nucleosome remodeling. We show that SUB1 co-regulates a fraction of light-inducible genes together with the WCC. WCC induces nucleosome eviction at its binding sites. Chromatin remodeling is facilitated by SUB1 but SUB1 cannot activate light-inducible genes in the absence of WCC. We identified FF7, a TF with a putative O-acetyl transferase domain, as an interaction partner of SUB1 and show their cooperation in regulation of a fraction of light-inducible and a much larger number of non light-inducible genes. Our data suggest that WCC acts as a general switch for light-induced chromatin remodeling and gene expression. SUB1 and FF7 synergistically determine the extent of light-induction of target genes in common with WCC but have in addition a role in transcription regulation beyond light-induced gene expression

Investigation of potential biomarkers in prediction of acute myocardial infarction via explainable artificial intelligence

Remodeling of the left ventricle (LV) after myocardial infarction (MI) is a process of infarct enlargement. Despite the relevance of the inflammatory response and healing process in LV remodeling after MI, the mechanisms that begin and govern these processes remain unknown. Based on the important information highlighted in different studies, the current research aims to investigate potential biomarkers for left ventricular remodeling after acute MI based on the interpretation of the explainable artificial intelligence (XAI). The project research from which the public dataset was obtained was designed in an experimental type. A cohort study involving 66 patients with coronary heart disease and 34 healthy community controls provided the platelet samples for the current research, which used available omics data on those samples. For discovering significant mechanistic connections between metabolites and glycans, the metabolomics and glycomics datasets were analyzed using biostatistics/metabolomics and explainable artificial intelligence techniques. Metabolomics data of 100 patients (AMI=66; Control=34) including 75 males and 25 females were evaluated in this study. As a result of experimental omics analyses, 102 metabolite levels of the patients were obtained. When FC values were examined, creatinine and dl-pipecolic acid levels were 0.50 and 0.55-fold down-regulated and glutamine, myoinositol, and cytosine levels were 1.34, 1.33, and 1.53-fold up-regulated in the AMI group compared to the control group. Findings of metabolomics data and XAI analyses revealed that five lipid metabolites may be used as potential predictors of AMI. [Med-Science 2023; 12(2.000): 424-30

ENDODONTIC TREATMENT OF TYPE II DENS INVAGINATOS IN A MANDIBULAR LATERAL: INCISOR: A CASE REPORT

Dens invaginatus is a rare developmental malinformation or teeth possibly resulting from an invagination or the enough organ, This rase report presents the conventional treatment of it an Oehlers I IF invaginated mandibular lateral inciser. was a lathe chronic lession with an extroral fistula around ate mandibular right incisors and left central incisor All three teeth responded negatively to the vitality tests. The invaginatus in the #42 was removed)removed completely using various diamond Mars on an air turbine meter wager sooty. Alter a 1-month treatment well calcium hydroxide dressings,ILL extroral fistula (Wept:dissappeared and the rote canals of :all deed incisors were Piled Li laterally dare eondensed gutta percha and sealed go treat dens irivaginatus both conventional and,surgical endodontic: treatment techniques may he considered. In dens invaginanis:casses oases, success of the. treatments depends on the diagnose, of the mialformation and its type Thorough complte I,removal I Ut the malforamation groat thee rote debridement calcium lrydroxide medication and obturation. fistula disappeared and the wind Were asymprthomatic

The effects of pacing mode on development of chronic AF in patients undergoing pacemaker implantation due to AV block : A retrospective study

Permanent atrial fibrillation (AF) is the most prevalent arrhythmia among elderly patients. Permanent AF may cause thromboembolic events, heart failure, poor quality of life and recurrent hospitalizations. The effects of pacemaker mode on developing permanent AF have been investigated in several studies. In this study, we aimed to investigate the effects of physiological pacing (DDD) and non-physiological pacing (VVI) on the development of permanent AF in patients undergoing pacemaker implantation due to AV block who initially had a sinus rhythm and did not have significant coronary artery disease (CAD). We included 148 patients who underwent permanent cardiac pacemaker implantation (67 VVI and 81 DDD) due to AV block. All patients had P wave activity before pacemaker insertion, and none had significant CAD on coronary angiography. Trans thoracic echocardiography and a 12 lead ECG of each patient were performed. Of 148 patients who were included in the study, 81 had DDD pacemaker and 67 had VVI pacemaker. There were 72 women (48.6%) and 76 men (51.4%). The mean age was 67±7 years. Mean follow-up time was 5.7±1.8 years. Permanent AF developed in 16 (10.8%) patients. Age, gender, hypertension, diabetes mellitus, initial LA diameter, and LV ejection fraction were not statistically the difference between two groups. Pacemaker mode was the unique variable that reached statistical significance (p=0.003). Permanent AF developed in 13 (19.4%) patients and in 3 (3.7%) patients in VVI and DDD pacemaker groups, respectively (p=0.003). The comparison of initial and follow-up echocardiographic parameters such as change in LA diameters, LV ejection fractions, and LV end-systolic and end-diastolic diameters revealed that merely the change in LA diameters was statistically significant between the patients who developed permanent AF and who did not. In this study, we found that pacemaker mode significantly leads to the development of permanent AF. The risk of developing permanent AF was 7-8 times greater in the VVI group than that in the DDD group. Neither mode had effects on ventricular systolic functions. However, the mean left atrial diameter was significantly higher in the VVI group. According to these results, we suggest the insertion of a DDD pacemaker for the patient with P wave activity and AV block. [Med-Science 2022; 11(1.000): 48-52

Characterization of Lin(-)ALDH(bright) population using Ehrlich ascites tumor cells in mice

Cancer stem cells (CSCs)/tumor initiating cells have been shown to exist in recent studies; however, it is challenging to isolate these cells. The latest evidence suggests that elevated aldehyde dehydrogenase (ALDH) activity is a hallmark of CSCs. In this study, mice implanted with Ehrlich ascites tumor (EAT) cells were used to isolate cancer stem cells. Femoral bone marrow aspirations were performed 15 days after the injection of EAT cells and Lin(-)ALDH(bright) and Lin(-)ALDH(low) cell populations were isolated. Lin(-)ALDH(bright) cells isolated from EAT-bearingmice accounted for 11.08 +/- 10.52% of all the Lin-cell population. Analysis of hematopoietic stem cell markers showed that Sca-1, c-kit, and CD38 were expressed higher in the Lin(-)ALDH(bright) population compared with Lin(-)ALDH(low). The Lin(-)ALDH(bright) population expressed P-glycoprotein, a product of the multidrug resistance (MDR) gene. P-gp activity measured by rhodamine 123 (Rh123) and blocked by verapamil. Among the cells treated with doxorubicin for 48 h, the Lin(-)ALDH(bright) cell groups were more resistant and had higher overexpression of Bcl-2 protein than Lin(-)ALDH(low)

Assessment of Hematological Predictors via Explainable Artificial Intelligence in the Prediction of Acute Myocardial Infarction

Acute myocardial infarction (AMI) is the main cause of death in developed and developing countries. AMI is a serious medical problem that necessitates hospitalization and sometimes results in death. Patients hospitalized in the emergency department (ED) should therefore receive an immediate diagnosis and treatment. Many studies have been conducted on the prognosis of AMI with hemogram parameters. However, no study has investigated potential hemogram parameters for the diagnosis of AMI using an interpretable artificial intelligence-based clinical approach. The purpose of this research is to implement the principles of explainable artificial intelligence (XAI) in the analysis of hematological predictors for AMI. In this retrospective analysis, 477 (48.6%) patients with AMI and 504 (51.4%) healthy individuals were enrolled and assessed in predicting AMI. Of the patients with AMI, 182 (38%) had an ST-segment elevation MI (STEMI), and 295 (62%) had a non-ST-segment elevation MI (NSTEMI). Demographic and hematological information of the patients was analyzed to determine AMI. The XAI approach combined with machine learning approaches (Extreme Gradient Boosting, XGB; Adaptive Boosting, AB; Light Gradient Boosting Machine, LGBM) was applied for the estimation of AMI and distinguishing subgroups of AMI (STEMI and NSTEMI). The SHAP approach was used to explain the predictions intuitively. After selecting the 10 most important hematological parameters for AMI, the LGBM model achieved 83% and 74% accuracy for prediction of AMI, and distinguishing subgroups of AMI (STEMI and NSTEMI), respectively. SHAP results showed that neutrophil (NEU), white blood cell (WBC), platelet width of distribution (PDW), and basophil (BA) were the most important for AMI prediction. Mean corpuscular volume (MCV), BA, monocytes (MO), and lymphocytes (LY) were the most important hematological parameters that distinguish STEMI from NSTEMI. The proposed model serves as a valuable tool for physicians, facilitating the diagnosis, treatment, and follow-up of patients with AMI and distinguishing subgroups of AMI (STEMI and NSTEMI). Analyzing readily accessible hemogram parameters empowers medical professionals to make informed decisions and provide enhanced care to a wide range of individuals

Targeted Ablation of Primary Cilia in Differentiated Dopaminergic Neurons Reduces Striatal Dopamine and Responsiveness to Metabolic Stress

Mustafa R, Rawas C, Mannal N, et al. Targeted Ablation of Primary Cilia in Differentiated Dopaminergic Neurons Reduces Striatal Dopamine and Responsiveness to Metabolic Stress. Antioxidants. 2021;10(8): 1284.Primary cilia (PC) are microtubule-based protrusions of the cell membrane transducing molecular signals during brain development. Here, we report that PC are required for maintenance of Substantia nigra (SN) dopaminergic (DA) neurons highly vulnerable in Parkinson's disease (PD). Targeted blockage of ciliogenesis in differentiated DA neurons impaired striato-nigral integrity in adult mice. The relative number of SN DA neurons displaying a typical auto-inhibition of spontaneous activity in response to dopamine was elevated under control metabolic conditions, but not under metabolic stress. Strikingly, in the absence of PC, the remaining SN DA neurons were less vulnerable to the PD neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP). Our data indicate conserved PC-dependent neuroadaptive responses to DA lesions in the striatum. Moreover, PC control the integrity and dopamine response of a subtype of SN DA neurons. These results reinforce the critical role of PC as sensors of metabolic stress in PD and other disorders of the dopamine system

Epidemiology of atrial fibrillation in Turkey: preliminary results of the multicenter AFTER* study

Objectives: Although atrial fibrillation (AF) is one of the most common rhythm disorders observed in clinical practice, a multicenter epidemiological study has not been conducted in our country. This study aimed to assess our clinical approach to AF based upon the records of the first multicenter prospective Atrial Fibrillation in Turkey: Epidemiologic Registry (AFTER) study