CDK5 interacts with STK3

The Hippo-YAP/TAZ pathway is the most prevalent evolutionary conserved pathway from Drosophila to mammals and plays a key role in controlling organ size, cell growth, self-renewal, and tissue homeostasis. Hippo pathway consists of MST/LATS kinase module and YAP/TAZ-TEAD transcription module and is generally regulated by transcriptional activity of YAP and TAZ. YAP and TAZ are mechanosensory proteins that read a broad range of mechanical clues from shear stress of cell shape, contact, extracellular matrix rigidity and stiffness. In general, the Hippo pathway kinases are generally considered tumour suppressors while YAP/TAZ are considered Oncoproteins. Activation of transcription co-activators YAP/TAZ is inhibited by phosphorylation caused by LATS1/2 and MST1/2 kinases which results in cytoplasmic sequestration and degradation of YAP/TAZ. While unphosphorylated, YAP/TAZ translocate to the nucleus and bind to TEAD family transcription factors to induce gene expression. Hippo pathway is widely dysregulated in cancer and mechano-transduction of YAP and TAZ is critical for driving expression of genes involved in cancer progression and growth. Cyclin-dependent kinase 5 is an unusual member of the family of cyclin-dependent kinases, which is activated upon binding to non-cyclin p35 and p39 proteins. It is known to be widely involved in tumorigenic processes. Through yeast two hybrid system we found a novel interaction between MST2 (STK3) and CDK5 which was further confirmed by co-immunoprecipitation experiments. In the current study, we aim to shed a light on the involvement of CDK5 in the Hippo pathway via interaction with MST2. We try to understand the relationship between CDK5 and Hippo kinases and how CDK5 influences the Hippo pathway cascade without being directly involved in it. We show how active YAP activity changes with CDK5 knockdown and overexpression. CDK5 also influences the expression of phosphorylated levels of upstream kinases of Hippo Pathway especially pLATS1 (thr1079). Expression of YAP target genes also get influenced where cells find a way to compensate for the reduced YAP activity by upregulating other mechanosensory pathways such as MRTF/.SRF. Our findings illustrate that it is not the kinase activity of CDK5 that is involved in the process. However, it does act like a scaffold bringing the other proteins together and providing a platform for Hippo pathway cascade. Phosphoproteomics analysis brings the same picture out and shed light to the overall phospho changes with CDK5 knockdown and overexpression. Further phosphoproteomics results also reveal that CDK5 interact with DLG5 another upstream kinase and regulates the Hippo pathway via cross talk with several other signalling pathways especially MAPK signalling. Finally, CDK5 not only acts as a scaffold protein but also is involved assisting cross talk of Hippo pathway with other signalling cascades. Our findings might be useful for developing novel drugs which can target CDK5 and regulate Hippo signalling

The Healing Power of Teacher-Student Relationships in Repairing Childhood Abuse: Commonalities and Differences with Clinical Social Work Practice

Research indicates survivors of childhood abuse are able to form the same quality relationships with teachers as non-abused children (Armstrong, Hasket & Hawkins, 2017). However, there is little research indicating what factors within the teacher-student relationship help build this resiliency. This study looks to clinical social work practice as a basis for understanding what qualities of the therapeutic relationship can extend to or overlap with non-clinical relationships with students who have a trauma history, within the teaching field. To better understand experiences within these relationships, semi-structured interviews were conducted with both a clinical social worker who has teaching experience at the post-secondary level, and the study enlisted the researcher as a participant to ascertain the student/ client perspective. Effectively a researcher self-study, findings indicated qualities of safety, empathy and client/student empowerment, albeit in different ways, helped to correct and repair some of the damage of childhood abuse within both therapeutic and teacher-student relationships

A Empirical Study Related To Preference Of Salaried Individuals Towards Different Investment Avenues

The financial knowledge about the various financial products and services impact the understanding, preference and behaviour of the various salaried individuals towards them. The anticipation of such preferences towards these products and services becomes really important for the growth of business of these products and the market structure accommodating the salaried individuals who are the key part of this society an plays a major role. This research paper covers the most of the investment options available in the market such as share, debentures, term deposits, insurance, mutual funds, real estate etc. and the factors influencing the investment behaviour of salaried individuals towards them. In this paper major factors such as demographic, socio economic factors etc influencing the investment decisions of salaried individuals have been covered. Through this study its being trying to drive a medium to understand the sense of judgement of the various financial objectives of the salaried class people with their determination of the desire for the investment returns over various investment avenues available in the market. Further this information could  help to unwrap the various prospects for predicting the preferences towards various investment avenues available and the future of various financial players in the market and the Indian Economy

Urban Resilience and Urban Sustainability

The urban system has been a subject of much attention and inquiry, more so in the past two or so decades. The design of urban systems and juxtaposition of humans with nature has been scrutinized and critically examined by several means and modes. To replicate the natural systems’ balance post human intervention on thus is what societies have strived for, for a long time now (Redman, 2010). The emergence of sustainability in the realm of urban living and more recently the attention imparted to the long known concept of resilient living have been a corollary of this quest. The trend in sustainable development and resilient systems planning of devising frameworks and drawing indicators to help define these vast concepts and help make their manifestation and measurement more tangible is evolving and developing more and more in academic circles and planning disciplines alike (see Alberti, 2012; Arup, 2015). However, the lack of a definite norm and basic sustainability and resilience requirements worldwide has made it more and more difficult for built and planning manifestations to respond directly to these broad-ended goals. It is hypothesized thus that a required innovative framework that incorporates the concepts of sustainability, resilience, a balanced ecological living and an efficient urban system be coined so that these concepts are reflected in manifestations of urban living and not lost in translation. An analysis of existing indicators and frameworks created by both academics and practitioners that currently define sustainability and resilience in urban development are used in identifying gaps in the current methodology adopted by cities in planning for sustainable-resilient living. A new framework and approach is attempted by incorporating the missing links. It is expected that this integrative framework - measuring and defining a resilient, sustainable and more responsible urban systems living - is a paradigmatic shift in the way planning policies are ideated and manifested in cities

The prevalence and under-reporting of needle-stick injuries among dental healthcare workers in Pakistan: a systematic review

Needlestick injuries (NSIs) are a major occupational health problem among dental healthcare workers (HCWs) in Pakistan, which places them at a significant risk of acquiring blood-borne infections. However, not all NSIs are reported, leading to an underestimation of the actual prevalence. The harmful impacts of NSIs on the healthcare delivery necessitate an urgent need to measure its actual prevalence. Objectives. The aim of this study was to review literature to estimate the prevalence and reporting rates of NSIs among dental-HCWs in Pakistan. Methods. 713 potentially relevant citations were identified by electronic databases and hand searching of articles. Nine primary studies were subsequently identified to be included in the review. Results. The results of the included studies indicate that the prevalence of NSIs among Pakistani dental-HCWs was between 30% and 73%. The rate of reporting of NSIs was between 15% and 76%, and the most common reason was found to be the lack of awareness regarding the reporting system, or of the need to report NSIs. Conclusion. It is evident from the review of the included studies that there is a significantly high prevalence and a low rate of reporting of NSIs among dental-HCWs in Pakistan, suggesting the need to setup an occupational health department in dental settings, for preventing, managing, recording, and monitoring NSIs

Influence of Salary Package and Promotion Opportunities on Job Satisfaction; A Study on the Employees of Retail Sector in Pakistan

This research was conducted during 2017-2018 in a private retail organization. Two independent variables were considered including pay and promotion and their impact was checked on the dependent variable “job satisfaction”. Data was collected from 30 respondents using a structured questionnaire. Judgemental sampling technique was used for data collection. Data was analyzed using SPSS and AMOS. Results indicate that there is a significant impact of pay and promotion on job satisfaction. It was also found that there are some other factors that can have their positive impact of job satisfaction including free medical facility, education facility employees’ children and insurance policies provided by the organizations

Coronavirus (CoV) Infection: The Pandemic Public Health Issue

The headlines hitting the news worldwide are talking about the recent outbreak of the coronavirus infection (COVID-19) that started as an epidemic in China by the end of year 2019 and became a public health emergency after a pandemic spread within a span of few weeks. With no curative measure in hand, this ailment is killing victims at the rate of almost 2% of the affected ones. This review focuses on general information regarding coronavirus, pathological findings from biopsy sample of a previously published case and the standard preventive recommendations prescribed by various researchers and health authorities