Cdk5 activity in the brain - multiple paths of regulation

Cyclin dependent kinase-5 (Cdk5), a family member of the cyclin-dependent kinases, plays a pivotal role in the central nervous system. During embryogenesis, Cdk5 is indispensable for brain development and, in the adult brain, it is essential for numerous neuronal processes, including higher cognitive functions such as learning and memory formation. However, Cdk5 activity becomes deregulated in several neurological disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, which leads to neurotoxicity. Therefore, precise control over Cdk5 activity is essential for its physiological functions. This Commentary covers the various mechanisms of Cdk5 regulation, including several recently identified protein activators and inhibitors of Cdk5 that control its activity in normal and diseased brains. We also discuss the autoregulatory activity of Cdk5 and its regulation at the transcriptional, post-transcriptional and post-translational levels. We finally highlight physiological and pathological roles of Cdk5 in the brain. Specific modulation of these protein regulators is expected to provide alternative strategies for the development of effective therapeutic interventions that are triggered by deregulation of Cdk5. © 2014. Published by The Company of Biologists Ltd

Pediatric Spasticity

Children with special health care needs (CSHCN) are increasingly prevalent in US hospitals. The pediatric hospitalist is often the primary provider of inpatient care for these patients. However, exposure to this patient population during training varies from provider to provider. No published educational curricula are specific to the inpatient care of this population. The purpose of this project is to build a multi-modal educational curriculum for providers with the overall goal of improving inpatient care for this at-risk population. This curriculum is primarily composed of a series of topic-specific learning modules. Asynchronous learning modules, utilized appropriately, can augment learning by providing individualized instruction and mastery of fundamentals. This particular resource was created to provide pediatricians with educational materials related to care of the medically complex child with spasticity. This module was distributed to our division. So far, seventeen colleagues have participated in this learning module with favorable results. Comments included good pathophysiology reminders and this was very informative and very well organized. On a 5-point Likert scale evaluation, over 90% of respondents felt that this learning module was A. relevant to my clinical practice, B. will change my clinical practice, C. increase my comfort with teaching this topic to trainees. The average pre-test score was 64% and post-test score was 82% which was statistically significant (p\u3c0.05). This module will be distributed to resident physicians within our institution this academic year. AAMC MedEdPORTAL publication ID 9282. Link to original

A review on determinants and barriers affecting the transition from curative care to palliative care in patients suffering from terminal cancer

The integration of palliative care into comprehensive cancer care has become increasingly recognized as an essential aspect of cancer treatment. Palliative care can improve patient outcomes, symptom management, and overall satisfaction with care. However, despite the benefits of palliative care, several barriers exist that prevent its widespread implementation, including lack of awareness and understanding of palliative care, lack of access to palliative care services, and stigma associated with palliative care. The decision to transition from curative to palliative care is complex and influenced by several factors, including patient preferences, disease stage, and prognosis, symptom burden, comorbidities, and social support. Effective communication between healthcare providers, patients, and families is essential in ensuring that patients are informed about their options and can make informed decisions about their care. This literature review aims to explore the factors that influence the decision to transition to palliative care and to identify the barriers to the implementation of palliative care in cancer patients. The review also discusses strategies to overcome these barriers and highlights the importance of integrating palliative care into cancer care from the time of cancer diagnosis.

A Study on Identifying Mutual Fund as an asset class for Alternative Investment with special reference to Mutual Fund amongst Generation Z

The word Savings and Investments are interchangeable in nature which plays an utmost importance in every person's life. Savings on one hand is to put money safely in a bank account while investing on other hand is to create a gradual increase in the wealth. There are various types of investment avenues available in India. People across various generations depending upon their objectives invest their money into various avenues available. Generation Z who are from mid 1990 to 2010 are the targeted population undertaken in this study. The study is an attempt to understand the awareness and the perception level of Generation Z population towards mutual funds as an investment objective. The sample chosen were from Mumbai city using simple random as the sampling technique. The three major variables studied were risk, returns and liquidity with respect to awareness and perception. The data was analyzed using regression and ANOVA technique. The study showed the investment pattern dependency was more on liquidity

Sex versus non-sex versus cheaters

Cheating is known to be a potential threat to cooperation. We examine the fitness of a cheater allele in an asexual-haploid versus a sexual-diploid population using three different models. The first model depicts small cooperative groups in which the altruist and cheater are distributed randomly, the second simulates large cooperative groups with varying degrees of spatial aggregation and the third simulates a hymenopteran society with cheater workers. In all the models sex helps stabilize cooperation. The results are not affected by dominance or recessiveness of the cheater allele. In either case, sexual diploidy increases the variance across groups and thus enhances group selection. As a result sex and cooperation can coevolve under conditions when cooperation offers substantial fitness gains and cheaters threaten cooperation. The model predicts that cooperation should be more common in sexually reproducing organisms than asexuals. Among organisms where diploid as well as haploid life-cycle stages are present, cooperation should be seen more commonly in the diploid stage

Reduced Activity of Nitrate Reductase Under Heavy Metal Cadmium Stress in Rice: An in silico Answer

Cadmium is a well known toxic heavy metal, which has various detrimental effects on plant system. In plants an important enzyme involved in the production of nitric oxide, nitrate reductase, is also affected by cadmium toxicity. According to many studies cadmium has an inhibitory effect on nitrate reductase activity. Similar effect of cadmium was found in our study where an inhibitory effect of cadmium on nitrate reductase activity was noted. However, the mechanism behind this inhibition has not been explored. With the help of homology, 3-D structure of rice-nitrate reductase is modeled in this study. Its binding with nitrate, nitrite and cadmium metal in silico has been explored. The bonds formed between the enzyme-substrate complex, enzyme-cadmium and differences in interactions in presence of cadmium has been studied in detail. The present study should help in understanding the modeled structure of rice-nitrate reductase in 3-D which may in turn guide enzyme related studies in silico. The present study also provides an insight as to how cadmium interacts with nitrate reductase to alter the enzyme activity