Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice

Biochemical studies have suggested conflicting roles for the E3 ubiquitin ligase constitutive photomorphogenesis protein 1 (Cop 1; also known as Rfwd2) in tumorigenesis, providing evidence for both the oncoprotein c-Jun and the tumor suppressor p53 as its targets. Here we present what we believe to be the first in vivo investigation of the role of Cop1 in cancer etiology. Using an innovative genetic approach to generate an allelic series of Cop1, we found that Cop1 hypomorphic mice spontaneously developed malignancy at a high frequency in the first year of life and were highly susceptible to radiation-induced lymphomagenesis. Further analysis revealed that c-Jun was a key physiological target for Cop1 and that Cop1 constitutively kept c-Jun at low levels in vivo and thereby modulated c-Jun/AP-1 transcriptional activity. Importantly, Cop1 deficiency stimulated cell proliferation in a c-Jun-dependent manner. Focal deletions of COP1 were observed at significant frequency across several cancer types, and COP1 loss was determined to be one of the mechanisms leading to c-Jun upregulation in human cancer. We therefore conclude that Cop1 is a tumor suppressor that functions, at least in part, by antagonizing c-Jun oncogenic activity. In the absence of evidence for a genetic interaction between Cop1 and p53, our data strongly argue against the use of Cop1-inhibitory drugs for cancer therapy

SDAV 1.0: A Low-Cost sEMG Data Acquisition & Processing System For Rehabilitatio

Over the last two decades, myoelectric signals have been widely used in fields including rehabilitation devices and human-machine interfaces. This study aimed to develop an algorithm for surface electromyography (sEMG) data acquisition utilizing low-cost hardware and validate its performance using English vowels as silent speech content. The sEMG data were collected from the three facial muscles of one healthy subject. The sEMG signals were pre-processed, and various time-domain and statistical features were extracted in real time. The raw data and features were then used to train and test three customized machine learning classifiers: k-nearest neighbor (KNN), support vector machine (SVM), and artificial neural network (ANN). All customized classifiers achieved almost equivalent accuracy rates of 0.83 ± 0.01 in recognizing the English vowels with an improvement of 27.27% (KNN), 3.75% (SVM), and 51.85% (ANN) utilizing the same low-cost data acquisition hardware. Our findings are substantially closers to the results of commercial hardware setups, which raise the possibility of potential usage of low-cost sEMG data acquisition systems with the proposed algorithm in place of commercial hardware setups for rehabilitation devices and other related sectors of human-machine interaction

Effect of Chandana Bala Lakshadi Taila Abhyanga with Poshaka Laddu & Nutri Recharge Powder in Bala Shosha (Kuposhana Janya Vyadhi)

Introduction: In Ayurveda Bala Shosha is known as Kuposhan Janya Vyadhi and it is viewed under Malnutritional or PEM disorder. Malnutrition is a common health problem in preschool children of developing countries including in India. As per WHO poor feeding of infant and young children resulting in under nutrition is the single and most important factor for diseases. The malnourished child needs proper Ahara and Aaushadh for normal growth and protecting disease. So, we have made suitable plan to a child.   Aim: To evaluate the effect of Candana Bala Lakshadi Taila Abhyanga, Poshaka Laddu, Nurticharge Powder internally in Bala Shosha (Kuposhana Janya Vyadhi). Material & Method: The clinical study was conducted in 30 Malnourished Children pre and post evaluation without control. The Study setting Department of Koumarbhritya (Bal-Roga), Shubhdeep Ayurved Medical College, Indore M.P. This study is come under the project of Govt. of M.P. in supervision of Indore collector and funded by Govt. of M.P. Result: The effect of Nuticharge powder, Poshak Laddu & Abhyanga on child weight and M.U.A.C is statistically significant (P= 0.01). It showed that the treatment significantly increases the weight and mid under arm circumference of malnourished children. Conclusion: Here in this study a small group was taken for the study which is equated with the PEM & Kuposhana Janya Vyadhi

Coordinated Siting and Sizing of Electric Taxi Charging Stations Considering Traffic and Power Systems Conditions

[EN] Electric Vehicles (EVs) have gained increased attention courtesy their potential to mitigate environmental issues associated with transportation. To integrate EVs in transportation and power networks, it is essential to properly perform the siting and sizing of charging stations. In particular, this task is more challenging for users that have more rigid schedules such as taxi drivers. This paper proposes a coordinated siting and sizing methodology for electric taxi (ET) charging stations considering both transportation and power system constraints. The case of Quito, Ecuador has been analyzed. The results indicate the optimal placement of the ET charging stations and the number of charging spots to be installed.This paper belongs to the project SIS.JCG.19.03 from Universidad de las Americas-Ecuador. The authors would like to thank Irvin Cedenos from BYD E-motors Ecuador for the fruitful discussions.Clairand, J.; González-Rodríguez, M.; Kumar, R.; Vyas, S.; Escrivá-Escrivá, G. (2021). Coordinated Siting and Sizing of Electric Taxi Charging Stations Considering Traffic and Power Systems Conditions. IEEE. 1-6. https://doi.org/10.1109/PowerTech46648.2021.9495003S1

Bronchiectasis in India:results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients ( 6518 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0\ub70001]) and more likely to be men (1249 [56\ub79%] of 2195). Previous tuberculosis (780 [35\ub75%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13\ub77%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1\ub717, 95% CI 1\ub703-1\ub732; p=0\ub7015), P aeruginosa infection (1\ub729, 1\ub710-1\ub750; p=0\ub7001), a history of pulmonary tuberculosis (1\ub720, 1\ub707-1\ub734; p=0\ub7002), modified Medical Research Council Dyspnoea score (1\ub732, 1\ub725-1\ub739; p<0\ub70001), daily sputum production (1\ub716, 1\ub703-1\ub730; p=0\ub7013), and radiological severity of disease (1\ub703, 1\ub701-1\ub704; p<0\ub70001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation

Virosome: A vector in vaccine delivery

These days vaccines are considered the best economical and effective technique for preventing and handling bacterial infections, like human papillomavirus (HPV) or meningitis, allergies, autoimmune Relevant Disorders, Microbial Infections, and many more viral diseases. Annually millions of lives are saved from death-causing infections and other relevant disorders with the help of proper immunization with the help of vaccines. But still, many diseases are not yet preventable by vaccines and there is a chance of the improvement of current vaccines with help of many approaches. One of these is a compound known as a virosome, which is produced when pure haemagglutinin and neuraminidase projections of the influenza virus surface are removed from viral envelope and deposited on the exterior of unilamellar liposomes.Studies have shown that in order to attain the desired therapeutic effect, a physical attachment between the target antigen and the virosomal carrier is necessary. A virosome can bind to and “infect” host cells and deliver the antigen directly into the processing pathway which is an Alternatively, the virosome may be phagocytosed by an APC. So Our review gives a novel idea of the vector technology for vaccine delivery, its properties, method of preparation, and importance as well as some applications of different virosomal vaccine discoveries

Mitochondrial Pharmacotherapeutics - Advancements and Applications

Mitochondria, known as the “powerhouse of the cell”, plays an important role in the occurrence of multiple diseases and disorders. Mitochondria are believed to come into existence from the synergistic relationship between the proto-eukaryotic and primitive prokaryotic efficient by oxidative phosphorylation. It is the major hub of Adenosine Tri Phosphate production through the implementation of oxidative phosphorylation. It is the processing unit of the “Electron transport chain”. Mitochondria is useful in dealing with various cancers, cardiovascular problems, fatty-acid oxidation disorders, and several kinds of tumours and also several cancers

Ligand-activated BMP signaling inhibits cell differentiation and death to promote melanoma

Oncogenomic studies indicate that copy number variation (CNV) alters genes involved in tumor progression; however, identification of specific driver genes affected by CNV has been difficult, as these rearrangements are often contained in large chromosomal intervals among several bystander genes. Here, we addressed this problem and identified a CNV-targeted oncogene by performing comparative oncogenomics of human and zebrafish melanomas. We determined that the gene encoding growth differentiation factor 6 (GDF6), which is the ligand for the BMP family, is recurrently amplified and transcriptionally upregulated in melanoma. GDF6-induced BMP signaling maintained a trunk neural crest gene signature in melanomas. Additionally, GDF6 repressed the melanocyte differentiation gene MITF and the proapoptotic factor SOX9, thereby preventing differentiation, inhibiting cell death, and promoting tumor growth. GDF6 was specifically expressed in melanomas but not melanocytes. Moreover, GDF6 expression levels in melanomas were inversely correlated with patient survival. Our study has identified a fundamental role for GDF6 and BMP signaling in governing an embryonic cell gene signature to promote melanoma progression, thus providing potential opportunities for targeted therapy to treat GDF6-positive cancers

Advancing sepsis clinical research: harnessing transcriptomics for an omics-based strategy - a comprehensive scoping review

Sepsis continues to be recognized as a significant global health challenge across all ages and is characterized by a complex pathophysiology. In this scoping review, PRISMA-ScR guidelines were adhered to, and a transcriptomic methodology was adopted, with the protocol registered on the Open Science Framework. We hypothesized that gene expression analysis could provide a foundation for establishing a clinical research framework for sepsis. A comprehensive search of the PubMed database was conducted with a particular focus on original research and systematic reviews of transcriptomic sepsis studies published between 2012 and 2022. Both coding and non-coding gene expression studies have been included in this review. An effort was made to enhance the understanding of sepsis at the mRNA gene expression level by applying a systems biology approach through transcriptomic analysis. Seven crucial components related to sepsis research were addressed in this study: endotyping (n = 64), biomarker (n = 409), definition (n = 0), diagnosis (n = 1098), progression (n = 124), severity (n = 451), and benchmark (n = 62). These components were classified into two groups, with one focusing on Biomarkers and Endotypes and the other oriented towards clinical aspects. Our review of the selected studies revealed a compelling association between gene transcripts and clinical sepsis, reinforcing the proposed research framework. Nevertheless, challenges have arisen from the lack of consensus in the sepsis terminology employed in research studies and the absence of a comprehensive definition of sepsis. There is a gap in the alignment between the notion of sepsis as a clinical phenomenon and that of laboratory indicators. It is potentially responsible for the variable number of patients within each category. Ideally, future studies should incorporate a transcriptomic perspective. The integration of transcriptomic data with clinical endpoints holds significant potential for advancing sepsis research, facilitating a consensus-driven approach, and enabling the precision management of sepsis