It isn't over ‘till it’s over: A continuing concern of the SARS-CoV-2 variants, and miRNAs targeting the S protein as a probable absolute cure

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak which still continues to affect the general population, has mutated day by day and new variants have emerged. More than 40 variants, usually caused by mutations in the spike (S) protein, have been recorded. Observation of S protein mutations in the development of t herapeutic agents will increase success rates. As we identify the three-dimensional (3D) conformation of viruses, it is more and more possible to work on models for understanding molecular interactions. Development of agents for arrays and 3D sequencing of proteins paves the way for potential therapeutic studies against variants. MicroRNAs (miRNAs) seemingly act as a potentially important group of biomolecules in combating uncontrolled cytokine release. Besides antiviral response, miRNAs promise to be  powerful therapeutic agents against infections. Studies have shown that miRNAs are able to inhibit the genome directly by miRNA-based treatments as they are sprecific to the SARS-CoV-2 genome. In order to expose this potential, in silico studies before continuing with lab studies are helpful. In our bioinformatics analysis, we proposed to compare the S protein similarities of Delta and Omicron, two of the most common variants, and to detect miRNAs targeting the S protein. The S proteins and coding sequences were compared between the two variants, and differences were determined. Within our analysis, 105 and 109 miRNAs for the Delta and Omicron variants, respectively, were detected. We believe that our study will be a potential guide for deciding on the miRNAs that may most likely have an effect on the management of the infection caused by both variants

Heart Rate Variability in Children with Tricyclic Antidepressant Intoxication

The aim of this study was to evaluate HRV in children requiring intensive care unit stays due to TCA poisoning between March 2009 and July 2010. In the time-domain nonspectral evaluation, the SDNN (P<0.001), SDNNi (P<0.05), RMSDD (P<0.01), and pNN50 (P<0.01) were found to be significantly lower in the TCA intoxication group. The spectral analysis of the data recorded during the first 5 minutes after intensive care unit admission showed that the values of the nLF (P<0.05) and the LF/HF ratio (P=0.001) were significantly higher in the TCA intoxication group, while the nHF (P=0.001) values were significantly lower. The frequency-domain spectral analysis of the data recorded during the last 5 minutes showed a lower nHF (P=0.001) in the TCA intoxication group than in the controls, and the LF/HF ratio was significantly higher (P<0.05) in the intoxication group. The LF/HF ratio was higher in the seven children with seizures (P<0.001). These findings provided us with a starting point for the value of HRV analysis in determining the risk of arrhythmia and convulsion in TCA poisoning patients. HRV can be used as a noninvasive testing method in determining the treatment and prognosis of TCA poisoning patients

Lithium promotes long-term neurological recovery after spinal cord injury in mice by enhancing neuronal survival, gray and white matter remodeling, and long-distance axonal regeneration

Spinal cord injury (SCI) induces neurological deficits associated with long-term functional impairments. Since the current treatments remain ineffective, novel therapeutic options are needed. Besides its effect on bipolar mood disorder, lithium was reported to have neuroprotective activity in different neurodegenerative conditions, including SCI. In SCI, the effects of lithium on long-term neurological recovery and neuroplasticity have not been assessed. We herein investigated the effects of intraperitoneally administered lithium chloride (LiCl) on motor coordination recovery, electromyography (EMG) responses, histopathological injury and remodeling, and axonal plasticity in mice exposed to spinal cord transection. At a dose of 0.2, but not 2.0 mmol/kg, LiCl enhanced motor coordination and locomotor activity starting at 28 days post-injury (dpi), as assessed by a set of behavioral tests. Following electrical stimulation proximal to the hemitransection, LiCl at 0.2 mmol/kg decreased the latency and increased the amplitude of EMG responses in the denervated hindlimb at 56 dpi. Functional recovery was associated with reduced gray and white matter atrophy rostral and caudal to the hemitransection, increased neuronal survival and reduced astrogliosis in the dorsal and ventral horns caudal to the hemitransection, and increased regeneration of long-distance axons proximal and distal to the lesion site in mice receiving 0.2 mmol/kg, but not 2 mmol/kg LiCl, as assessed by histochemical and immunohistochemical studies combined with anterograde tract tracing. Our results indicate that LiCl induces long-term neurological recovery and neuroplasticity following SCI.TUBA ; Istanbul Medipol University ; Turkish Academy of Science

Utility investigation of automated techniques in hematopoietic progenitor cell count and viability assessment in the Good Manufacturing Practice (GMP) settingg

Aim: To compare our parameters as regards: i) cell count via two different automated cell count techniques, and ii) viability via automated trypan blue exclusion and 7-aminoactinomycin D (7-AAD) staining. Method: We used the trypan blue exclusion technique and an automated cell counter and for viability testing, and the trypan blue exclusion technique and the 7-AAD evaluation by flow cytometry. The trypan blue exclusion and the radio frequency techniques were used for automated cell counting. Flow cytometric analysis was performed by evaluating the yielded cellular products for 7-AAD uptake during the cell count of CD34+ cells. Results: The mean values for cell count were estimated as 3.44±1.22x106/ml (range, 2.48-5.71x106/ml) and 4.14±1.94x106/ml (range, 1.77-7.43x106/ml) for the trypan blue exclusion and radio frequency techniques, respectively. Additionally, the mean values for viability analyses via the automated trypan blue exclusion and 7-AAD were 93.38±6.09% (range, 79.00-98.00%) and 99.49±0.60% (range, 98.40-100.00%), respectively. Conclusions: Our study has responded to two fundamental questions: whether the results of both of the automated techniques for cell count correspond with each other, and whether the results of the automated viability assessment conform those of the 7-AAD technique during the manufacturing processes of cellular therapy products intended for clinical use. Even though we have the opportunity to use the hemocytometer in our laboratory setting, the automated trypan blue exclusion technique gives cell count results in concordance within the range of the expectations of our Quality Management System (QMS)

A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling

Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategie

Pre-service teachers' reflections on task design and implementation

International audienceIn this paper, we will present a part of findings of a larger study in which we investigated both pre-service teachers' pedagogical content knowledge and middle school students' mathematical skills. A total of 17 pre-service teachers worked with 7 th grade students on the mathematical tasks for a semester. The data was collected through inventories, videos of task implementations and written reflections. The analysis of inventories and written reflections revealed that the pre-service teachers had positive beliefs about using mathematical tasks in the lessons. They were able to evaluate the success or failure of a task by analyzing the implementation process. They recognized the importance of preparing appropriate tasks for students and implemented them as intended. They also noted that mathematical tasks provided them an opportunity to learn about students' mathematical understanding as well as to develop their scaffolding practices

Detection of Chronic Kidney Disease by Using Adaboost Ensemble Learning Approach

Chronic kidney disease can be detected with several automatic diagnosis systems. In this study, chronic kidney diseases are diagnosed with Adaboost ensemble learning algorithm. Decision tree based classifiers are used in the diagnosis. The classification performance are evaluated with kappa, mean absolute error (MAE), root mean squared error (RMSE) and area under curve (AUC) criterias. Considering the performance analyses, it is observed that adaboost ensemble learning algorithm provides better classification performance than individual classification

Mammographic Mass Detection using Wavelets as Input to Neural Networks

The objective of this paper is to demonstrate the utility of artificial neural networks, in combination with wavelet transforms for the detection of mammogram masses as malign or benign. A total of 45 patients who had breast masses in their mammography were enrolled in the study. The neural network was trained on the wavelet based feature vectors extracted from the mammogram masses for both benign and malign data. Therefore, in this study, Multilayer ANN was trained with the Backpropagation, Conjugate Gradient and Levenberg-Marquardt algorithms and ten-fold cross validation procedure was used. A satisfying sensitivity percentage of 89.2% was achieved with Levenberg-Marquardt algorithm. Since, this algorithm combines the best features of the Gauss-Newton technique and the other steepest-descent algorithms and thus it reaches desired results very fast

Multifont Ottoman character recognition using Support Vector Machine

In this study, an Optical Character Recognition (OCR) system, which implements segmentation, normalization, edge detection and recognition of the Ottoman script, is proposed. Each multifont Ottoman character is written with four different shapes according to its position in the word being at beginning, middle, at the end and in isolated form. We have used printed type of Ottoman scripts in image acquisition. Then image segmentation, normalization and finally edge detection are performed for feature extraction, where edge detection is achieved by Cellular Neural Network (CNN) approach. After these pre-proces steps, we recognize these multifont Ottoman characters using Support Vector Machine (SVM) technique. In SVM training, polynomial (linear and quadratic) and Gaussian Radial Basis Function kernels are chosen. The proposed recognition system has succeeded in classification up to 87.32% with quadratic kernel