Genome-wide Integrative Analysis of Zika-Virus-Infected Neuronal Stem Cells Reveals Roles for MicroRNAs in Cell Cycle and Stemness.

Zika virus (ZIKV) infection is implicated in severe fetal developmental disorders, including microcephaly. MicroRNAs (miRNAs) post-transcriptionally regulate numerous processes associated with viral infection and neurodegeneration, but their contribution to ZIKV pathogenesis is unclear. We analyzed the mRNA and miRNA transcriptomes of human neuronal stem cells (hNSCs) during infection with ZIKV MR766 and Paraiba strains. Integration of the miRNA and mRNA expression data into regulatory interaction networks showed that ZIKV infection resulted in miRNA-mediated repression of genes regulating the cell cycle, stem cell maintenance, and neurogenesis. Bioinformatics analysis of Argonaute-bound RNAs in ZIKV-infected hNSCs identified a number of miRNAs with predicted involvement in microcephaly, including miR-124-3p, which dysregulates NSC maintenance through repression of the transferrin receptor (TFRC). Consistent with this, ZIKV infection upregulated miR-124-3p and downregulated TFRC mRNA in ZIKV-infected hNSCs and mouse brain tissue. These data provide insights into the roles of miRNAs in ZIKV pathogenesis, particularly the microcephaly phenotype

The impact of human capital outsourcing on human capital management practices in Karachi pharmaceutical industry

Purpose: The aim of this research is to examine relationship between Human Capital Management (HRM) and Human Resource (HR) Outsourcing in the Pharmaceutical sector. The specific objective is to find out that how important is HRM for an Organization to perform its operations more efficiently, and at what level Human Resource Outsourcing is affecting it. Literature review: Literature review shows that HR outsourcing has positive impact on HRM for an Organization to perform its operations more efficiently. Methods: In order to conduct this research the methodology that has been used is quantitative in nature and closed ended Questionnaire was used to collect data. The universe of study was the employees of Pharmaceutical industry in Karachi Pakistan. The responses of each respondent were thoroughly analyzed by using SPSS software, and the results show that there is a negative relationship between the Human Capital Management (Gaining Knowledge, Current Trend of Business Environment, Organization Managing Their Human Asset and Practices and Policies Regarding Human Resource) and HR Outsourcing. Conclusions: It is concluded that all Independent Variables have the strongest Positive correlation with each other. There are lots of constraints, which any organization faces in terms of time, finance and, in some cases factors like strategic focus.Human Capital Management, Karachi, Pharmaceutical, Outsourcing

Zika virus infection reprograms global transcription of host cells to allow sustained infection.

Zika virus (ZIKV) is an emerging virus causally linked to neurological disorders, including congenital microcephaly and Guillain-Barré syndrome. There are currently no targeted therapies for ZIKV infection. To identify novel antiviral targets and to elucidate the mechanisms by which ZIKV exploits the host cell machinery to support sustained replication, we analyzed the transcriptomic landscape of human microglia, fibroblast, embryonic kidney and monocyte-derived macrophage cell lines before and after ZIKV infection. The four cell types differed in their susceptibility to ZIKV infection, consistent with differences in their expression of viral response genes before infection. Clustering and network analyses of genes differentially expressed after ZIKV infection revealed changes related to the adaptive immune system, angiogenesis and host metabolic processes that are conducive to sustained viral production. Genes related to the adaptive immune response were downregulated in microglia cells, suggesting that ZIKV effectively evades the immune response after reaching the central nervous system. Like other viruses, ZIKV diverts host cell resources and reprograms the metabolic machinery to support RNA metabolism, ATP production and glycolysis. Consistent with these transcriptomic analyses, nucleoside metabolic inhibitors abrogated ZIKV replication in microglia cells

Identifying Factors Playing Important Role in the Increasing Employees’ Turnover Rate: A Case of Telecom Industry in Pakistan

The objective of this study is to know about the practices of Telecom industry, regarding their employees and to know how they keep up with the intense competition in the industry. The study focuses on factors effecting employees’ turnover and those that factors play an important role in retaining the employees of Telecom industry. The universe of this study was all the employees of Telecom industry in Islamabad, Karachi and Lahore. For this purpose survey method was used by using questionnaire as a tool for data collection. The results have shown that Salary, Working environment and Benefits are three significant factors effecting employees’ turnover and correlated with each other. The study was faced by certain limitations, which include time constraints and resources constraints, which limit this research to only Islamabad, Karachi and Lahore offices of the organizations in telecom industry of Pakistan. The present study found support for an independent variable with Employees turnover. Significant negative correlations have been found for the Salary, Work environment and Benefits. Therefore, organizations need to focus on how to develop better Salary plan and reduce strain in the workplace. If staff voluntarily leaves, it is a great loss to the telecom industry. It is expensive to hire, train, and “bring up to speed” new replacements. It is, therefore, important to understand the antecedents of turnover intent of employees before they decide to quit.Employee’s Turnover, Telecom Industry; Pakistan; Factors.

Role of Quality Management in Pharmaceutical Development: Evidence from Islamabad and Lahore

The aim of this paper is to investigate the employee’s perceptions of the impact, of Total Quality Management (TQM), on their roles within the organization and how they perceived the effectiveness of the quality processes in Pakistan Pharmaceutical industry. The universe of this study was the employees of Pharmaceutical industry in Islamabad and Lahore. For this purpose survey method was used by using questionnaire as a tool for data collection. The results have shown that Employee Training and Development, Employee Performance, Quality Process and Team Work are significant factors with the Total Quality Management and correlated with each others. The result shows the application of TQM principles addresses some of the key challenges facing the organization. The study was faced by certain limitations and included time constraints and resources constraints which limited this research to only Islamabad and Lahore offices, of the Pharmaceutical companies. The present study found support that pharmaceutical companies faced the same difficulties with TQM implementations as experienced in other industries. These include achieving a culture of continuous improvement, overcoming a lack of trust and understanding the TQM process itself, and what they were, as a company, trying to achieve. These problems are not new and many companies have difficulties in implementing TQM. Pharmaceutical companies also followed the path of achieving a quality certification; namely, ISO 9000 accreditation, in the pursuit of excellence.Quality Management; pharmaceutical Development; Pakistan; Employee’s Perceptions

Human Retroviral Host Restriction Factors APOBEC3G and APOBEC3F Localize to mRNA Processing Bodies

APOBEC3G is an antiviral host factor capable of inhibiting the replication of both exogenous and endogenous retroviruses as well as hepatitis B, a DNA virus that replicates through an RNA intermediate. To gain insight into the mechanism whereby APOBEC3G restricts retroviral replication, we investigated the subcellular localization of the protein. Herein, we report that APOBEC3G localizes to mRNA processing (P) bodies, cytoplasmic compartments involved in the degradation and storage of nontranslating mRNAs. Biochemical analysis revealed that APOBEC3G localizes to a ribonucleoprotein complex with other P-body proteins which have established roles in cap-dependent translation (eIF4E and eIF4E-T), translation suppression (RCK/p54), RNA interference–mediated post-transcriptional gene silencing (AGO2), and decapping of mRNA (DCP2). Similar analysis with other APOBEC3 family members revealed a potential link between the localization of APOBEC3G and APOBEC3F to a common ribonucleoprotein complex and P-bodies with potent anti–HIV-1 activity. In addition, we present evidence suggesting that an important role for HIV-1 Vif, which subverts both APOBEC3G and APOBEC3F antiviral function by inducing their degradation, could be to selectively remove these proteins from and/or restrict their localization to P-bodies. Taken together, the results of this study reveal a novel link between innate immunity against retroviruses and P-bodies suggesting that APOBEC3G and APOBEC3F could function in the context of P-bodies to restrict HIV-1 replication

Assessment on serum CRP and serum ferritin level in COVID-19 patients of Dehradun Uttarakhand, India

Background: Since being declared a global pandemic, COVID-19 has ravaged many countries worldwide and has over-whelmed many healthcare systems. The pandemic has also resulted in the loss of livelihoods due to prolonged shutdowns, which have had a rippling effect on the global economy. Even though substantial progress in clinical research has led to a better understanding of SARS-CoV-2 and the management of COVID-19, limiting the continuing spread of this virus and its variants has become an issue of increasing concern, as SARS-CoV-2 continues to wreak havoc across the world, with many countries enduring a second or third wave of out-breaks of this viral illness attributed mainly due to the emergence of mutant variants of the virus. Our study tried to evaluate the fact regarding CRP and feritin parameters concentration efficacy in the detection and evaluation of inflammatory disorders, tissue injury and infections. Methods: CRP concentration measurements are useful in the detection and evaluation of inflammatory disorders, tissue injury and infections. The VITROS CRP slide method is performed using the VITROS 5600 integrated system. The VITROS CRP slide is a multi-layered, analytical element coated on a polyester support. The immune-rate format for CRP is based on enzymatic heterogeneous, sandwich immunoassay format. In this format a derivative of phosphorylcholine (PC) is covalently bound to polystyrene polymer beads and in the presence of calcium serves as a capture agent, monoclonal anti-CRP antibody conjugated to horseradish peroxidase (HRP) serves as a signal generator. Results: A total of 175 patients were selected for the study for estimate levels of C-reactive protein and serum ferritin in COVID-19 patients. The data obtained was coded and entered into Microsoft Excel Worksheet. Data was analysed and results were tabulated. In our study, serum CRP and serum ferritin values were found to be elevated in patients infected with COVID-19. Conclusions: CRP levels were positively correlated with lung lesions. CRP levels could reflect disease severity and should be used as a key indicator for disease monitoring. Serum ferritin was found to be elevated among the COVID-19 patients who could not survive the treatment as compared to the recovered patients. Therefore, serum concentrations of ferritin could be used as a prognostic marker in the management of COVID-19 patients which is easily available and cost effective too

Lipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply.

Lipoprotein lipase (LPL) mediates hydrolysis of triglycerides (TGs) to supply free fatty acids (FFAs) to tissues. Here, we show that LPL activity is also required for hematopoietic stem progenitor cell (HSPC) maintenance. Knockout of Lpl or its obligatory cofactor Apoc2 results in significantly reduced HSPC expansion during definitive hematopoiesis in zebrafish. A human APOC2 mimetic peptide or the human very low-density lipoprotein, which carries APOC2, rescues the phenotype in apoc2 but not in lpl mutant zebrafish. Creating parabiotic apoc2 and lpl mutant zebrafish rescues the hematopoietic defect in both. Docosahexaenoic acid (DHA) is identified as an important factor in HSPC expansion. FFA-DHA, but not TG-DHA, rescues the HSPC defects in apoc2 and lpl mutant zebrafish. Reduced blood cell counts are also observed in Apoc2 mutant mice at the time of weaning. These results indicate that LPL-mediated release of the essential fatty acid DHA regulates HSPC expansion and definitive hematopoiesis

Modulating HIV-1 replication by RNA interference directed against human transcription elongation factor SPT5

BACKGROUND: Several cellular positive and negative elongation factors are involved in regulating RNA polymerase II processivity during transcription elongation in human cells. In recruiting several of these regulatory factors to the 5' long terminal repeat (LTR) promoter during transcription elongation, HIV-1 modulates replication of its genome in a process mediated by the virus-encoded transactivator Tat. One particular cellular regulatory factor, DSIF subunit human SPT5 (hSpt5), has been implicated in both positively and negatively regulating transcriptional elongation but its role in Tat transactivation in vivo and in HIV-1 replication has not been completely elucidated. RESULTS: To understand the in vivo function of hSpt5 and define its role in Tat transactivation and HIV-1 replication, we used RNA interference (RNAi) to specifically knockdown hSpt5 expression by degrading hSpt5 mRNA. Short-interfering RNA (siRNA) designed to target hSpt5 for RNAi successfully resulted in knockdown of both hSpt5 mRNA and protein levels, and did not significantly affect cell viability. In contrast to hSpt5 knockdown, siRNA-mediated silencing of human mRNA capping enzyme, a functionally important hSpt5-interacting cellular protein, was lethal and showed a significant increase in cell death over the course of the knockdown experiment. In addition, hSpt5 knockdown led to significant decreases in Tat transactivation and inhibited HIV-1 replication, indicating that hSpt5 was required for mediating Tat transactivation and HIV-1 replication. CONCLUSIONS: The findings presented here showed that hSpt5 is a bona fide positive regulator of Tat transactivation and HIV-1 replication in vivo. These results also suggest that hSpt5 function in transcription regulation and mRNA capping is essential for a subset of cellular and viral genes and may not be required for global gene expression