Exploring the MEN1 dependent modulation of caspase 8 and caspase 3 in human pancreatic and murine embryo fibroblast cells

MEN1 mutation causes pancreatic neuroendocrine neoplasia and benign malignancies of the parathyroid, the adrenal cortex and pituitary gland. The transcriptional activity of its product menin promotes the expression of genes deputed to several cellular mechanism including cell death. Here, we focused on its implication in the activation of the initiator and executioner caspases after staurosporine mediated cell death in 2D and 3D human and murine cell models. The administration of staurosporine, a well-known inducer of apoptotic cell death, caused a significant reduction of BON1, QGP1 and HPSC2.2 cell viability. The transient knockdown of MEN1, performed by using a specific siRNA, caused a significant down-regulation of CDKN1A and TP53 transcripts. The treatment with 1 µM of staurosporine caused also a significant down-regulation of MEN1 and was able to restore the basal expression of TP53 only in QGP1 cells. Transient or permanent MEN1 inactivation caused a decrease of caspase 8 activity in BON1, HPSC2.2 cells and MEN1−/− MEFs treated with staurosporine. Caspase 3/7 activity was suppressed after administration of staurosporine in MEN1 knocked down HPSC2.2 and MEN1−/− MEFs as well. The cleaved caspase 8 and caspase 3 decreased in human cells after MEN1 knockdown and in MEN1−/− MEFs. The treatment with staurosporine caused a reduction of the size of MEN1+/+ MEFs spheroids. Instead, MEN1−/− MEFs spheroids did not show any significant reduction of their size. In conclusion, MEN1 controls the activity of the initiator caspase 8 and the executioner caspase 3 in human and murine cells. Restoring of a functional MEN1 and interfering with the apoptotic mechanism could represent a future strategy for the treatment of MEN1-related malignancies.

Reengineering of business processes Teta Food LLC

This article discusses the improvement of the work of an enterprise in the production sphere of LLC "TETA FOOD", which consists in increasing the efficiency of employees of the enterprise by reducing the time for the formation of a full package of documents (UPD) for submission to the tax office for the purpose of refunding VAT to the exporting enterprise. In the analytical part, the features of the VAT refund to the exporting company are analyzed in detail. To formalize and describe business processes, the notation IDEF0 and IDEF3 was chosen. In the design part, the ―AS IS‖ model was analyzed and the main problems of the model were identified. A strategy for the future strategy based on the IDEF0 methodology was developed.

OCULAR INJURY TREND IN COVID-19 ERA- A TERTIARY EYE CARE STUDY IN INDIA

Aim- To study the change in demography and injury pattern of ocular trauma during the lockdown period tothat of a similar period of the previous year. Materials & Methods- This is a retrospective analysis of the data of 362 patients with ocular trauma during the lockdown period from 25 March 2020 to 3 May 2020 and during a similar period of the previous year at a tertiary eye care center in India. Results- There was a decrease of 62.87% of patients of ocular trauma during the lockdown period because of the restricted lifestyle. Although home related and violence-related trauma increased, there was a decrease in trafc and sports-related trauma. Patients with chemical injury by sodium hypochlorite also had a sharp rise. Majority of the patients presented after two days during this period. Conclusion- Guidelines for mass health education and awareness about the risk of ocular trauma, morbidity caused by delayed presentation, and need to adopt safety or preventive strategies should be formulated so that future strategy can be planned to ght with the next pandemic or epidemic.

The “Hidden Story” about Change in Alcohol Use in India over the Past Two Decades: Insights from a Secondary Analysis of Data from the National Family Health Survey

Background: Studies and published reports have not commented on the change in the proportion of the Indian population that consumed alcohol over the years. Methods: We report the findings on changes in alcohol use in India over the past two decades, based on a secondary analysis of the data gathered over the successive National Family Health Surveys (NFHS-3 to 5). Results: There was a significant decline (P < 0.001) of around 8% and 45% for the current use of alcohol among men and women from NFHS-3 to NFHS-4. There was a decline in the proportion of men reporting alcohol use across all but one state in NFHS-5 compared to NFHS-3. The decline was statistically significant (P < 0.001) for all but one state. There was a decline in the proportion of women reporting alcohol use in 12 states and an increase in three states. Also, there was a significant (P < 0.001) decline in the proportion of men reporting alcohol use in all the states in NFHS-5 compared to NFHS-4. There was an increase in the proportion of women reporting alcohol use in nine states (statistically significant in six states) in NFHS-5 compared to NFHS-4. However, the proportions were more than NFHS-3 values in two states. Conclusions: These observations on changes in alcohol use in the country over the past two decades will help better understand the trends in alcohol consumption and help better plan the future strategy to address alcohol use and alcohol use disorders.

Mammalian Neuronal mRNA Transport Complexes: The Few Knowns and the Many Unknowns

Hundreds of messenger RNAs (mRNAs) are transported into neurites to provide templates for the assembly of local protein networks. These networks enable a neuron to configure different cellular domains for specialized functions. According to current evidence, mRNAs are mostly transported in rather small packages of one to three copies, rarely containing different transcripts. This opens up fascinating logistic problems: how are hundreds of different mRNA cargoes sorted into distinct packages and how are they coupled to and released from motor proteins to produce the observed mRNA distributions? Are all mRNAs transported by the same transport machinery, or are there different adaptors or motors for different transcripts or classes of mRNAs? A variety of often indirect evidence exists for the involvement of proteins in mRNA localization, but relatively little is known about the essential activities required for the actual transport process. Here, we summarize the different types of available evidence for interactions that connect mammalian mRNAs to motor proteins to highlight at which point further research is needed to uncover critical missing links. We further argue that a combination of discovery approaches reporting direct interactions, in vitro reconstitution, and fast perturbations in cells is an ideal future strategy to unravel essential interactions and specific functions of proteins in mRNA transport processes.

Exploring the Opinions of Irish Beef Farmers Regarding Dairy Beef Integration

Background: There has been very little previous research in Ireland on the opinions of farmers regarding dairy beef integration. The need for increased dairy beef integration has assumed a greater importance in Ireland in recent years due to a rapid expansion in dairy production, and associated increase in numbers of male dairy calves born on Irish farms. The objective of this study was to explore beef farmers' views on a broad range of issues related to dairy beef integration, using a survey methodology. The survey was distributed to approximately 4,250 beef farmers via email and 1,203 participated in the study.Results: The sample was composed almost entirely of beef farmers, although a very small proportion also had a dairy enterprise on their farm. Eighty percent of the farmers were concerned with the increase in the number of male dairy calves in recent years. Fifty seven percent of farmers responded that they were not willing to rear dairy bred calves for beef. Limousin, Aberdeen Angus and Hereford were the breeds farmers would be most willing to rear for beef. Good health, breed, and conformation were ranked as the main factors calf rearers consider when buying calves. Expectation of poor profit margin, expectation of poor-quality calves, and price volatility/market uncertainty were the top ranked factors dissuading farmers from rearing dairy calves for beef. The main themes arising from the qualitative question related to beef price/ability to make a profit, breed, and calf quality.Conclusions: While it is concerning that the majority of respondents expressed an unwillingness to rear dairy bred calves for beef, approximately a quarter of beef farmers indicated a willingness to rear beef-sired dairy calves for beef. In the qualitative responses, farmers described how their concerns about calf quality and their ability to make a profit from dairy bred calves would make it difficult for them to rear these calves for beef. Future strategy will have to consider how these challenges can be overcome and the issues of who bears the risks and costs associated with greater integration will have to be carefully considered.

A Study of Commuter’s Shift Behaviour Towards New Age Convenient Transport Services

This study identifies the determinants of commuter’s perception and shift behaviour towards new-age transport services. Convenience is an essential determinant in influencing consumer preferences. Multiple factors such as accessibility, convenience, cost of transport, number of transfers during the journey and waiting time are a few salient variables that influence the commuter’s shift to a new transport mode. Responses from ongoing commuters were collected by using a structured questionnaire from the users and non-users of the metro. The collected data were analysed. The study reveals that categorical variables such as age, gender and occupation have some degree of influence in commuters’ shift behaviour towards new-age transport services. The study will provide insights to formulate a future strategy to improve the acceptance of new-age transportation.

In-depth study of Netflix’s original content of fictional series. Forms, styles and trends in the new streaming scene

This article presents an analysis of the original content of fictional series created by one of the leading companies in the streaming television market, Netflix. This work aims at offering an in-depth study of the original series of the company Netflix, which will allow to classify these contents according to their strategic nature and, secondly, to offer a formal taxonomic overview on them. In addition, their forms, formats, languages, genres and thematic descriptors are analysed in order to establish a taxonomy for the classification of Netflix’s original content. To this end, this article is based on a quantitative method with qualitative contributions, adopting a descriptive but also exploratory approach. Its sample is made up of 490 series available on the Spanish version of the platform from its beginning in 2013 to 2019. The results lead to find a commitment to the production of fictional series with a global nature, but also focused on the local through alliances and productive methods with local businesses. Furthermore, the importance of in-house production as a present and medium-term future strategy is highlighted, together with the commitment to the division of production languages, considering local languages as a resource for the acceptance of the products. As for the predominant formats, a new trend marks how new audiovisual products are created by focusing, among other things, on reducing the duration and longevity of the series broadcast by the company.