A critical role for Kalirin in NGF signaling through TrkA

Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low concentration of NGF. Furthermore, elevated Kalirin expression resulted in catalytic activation of TrkA, as demonstrated by in vitro kinase assays and increased NGF-stimulated cellular activation of Rac, Mek, and CREB. Domain mapping demonstrated that the N-terminal Kalirin pleckstrin homology domain mediates the interaction with TrkA. The effects of Kalirin on TrkA provide a molecular basis for the requirement of Kalirin in process extension from PC12 cells and for previously observed effects on axonal extension and dendritic maintenance. The interaction of TrkA with the pleckstrin homology domain of Kalirin may be one example of a general mechanism whereby receptor/Rho GEF pairings play an important role in receptor tyrosine kinase activation and signal transduction

Current Perspectives of Telomerase Structure and Function in Eukaryotes with Emerging Views on Telomerase in Human Parasites

Replicative capacity of a cell is strongly correlated with telomere length regulation. Aberrant lengthening or reduction in the length of telomeres can lead to health anomalies, such as cancer or premature aging. Telomerase is a master regulator for maintaining replicative potential in most eukaryotic cells. It does so by controlling telomere length at chromosome ends. Akin to cancer cells, most single-cell eukaryotic pathogens are highly proliferative and require persistent telomerase activity to maintain constant length of telomere and propagation within their host. Although telomerase is key to unlimited cellular proliferation in both cases, not much was known about the role of telomerase in human parasites (malaria, Trypanosoma, etc.) until recently. Since telomerase regulation is mediated via its own structural components, interactions with catalytic reverse transcriptase and several factors that can recruit and assemble telomerase to telomeres in a cell cycle-dependent manner, we compare and discuss here recent findings in telomerase biology in cancer, aging and parasitic diseases to give a broader perspective of telomerase function in human diseases

Molecular and Evolutionary Analysis of RNA–Protein Interactions in Telomerase Regulation

Telomerase is an enzyme involved in the maintenance of telomeres. Telomere shortening due to the end-replication problem is a threat to the genome integrity of all eukaryotes. Telomerase inside cells depends on a myriad of protein–protein and RNA–protein interactions to properly assemble and regulate the function of the telomerase holoenzyme. These interactions are well studied in model eukaryotes, like humans, yeast, and the ciliated protozoan known as Tetrahymena thermophila. Emerging evidence also suggests that deep-branching eukaryotes, such as the parasitic protist Trypanosoma brucei require conserved and novel RNA-binding proteins for the assembly and function of their telomerase. In this review, we will discuss telomerase regulatory pathways in the context of telomerase-interacting proteins, with special attention paid to RNA-binding proteins. We will discuss these interactors on an evolutionary scale, from parasitic protists to humans, to provide a broader perspective on the extensive role that protein–protein and RNA–protein interactions play in regulating telomerase activity in eukaryotes

Antenatal and maternal health care utilization: evidence from northeastern states of India

This article examines the role played by the various socio-economic and community level factors in determining the antenatal and maternal health care utilization pattern using the data from the National Family Health Survey carried out in India in 1998/99. Our analysis document that autonomy enjoyed by women and exposure to media has a significant impact on maternal heath care utilization even after controlling for other attributes, particularly their education and household economic status. Availability of a rural health facility in the village and other community level programme propagates the utilization of health care.

Synthesis of functionalized 1,2,3,4-tetrahydro-β-carboline derived enamines through bischler-napieralski type cyclization of polarized ketene N,S-acetals

Synthesis of functionalized 1,2,3,4-tetrahydro-β-carboline derived enaminones, esters and nitriles has been developed via trifluoroacetic acid induced Bischler-Napieralski type cyclization of newly prepared polarized ketene N,S-acetals from tryptamine and polarized ketene dithioacetals

ACR appropriateness criteria(®) on abnormal vaginal bleeding

Synthesis of novel highly functionalized 2-oxo-(1,2,3,4-tetrahydropyridin-3-yl)acetic acids has been described via aza-annulation of both acyclic and cyclic α -oxo- and α -nitro-N,S- and -N,N-ketene acetals with itaconic anhydride

Impact of socioeconomic status of family on the birth weight- A cross sectional study from Eastern India

Introduction: Despite a lot of progress in the field of neonatology in last few years, low birth weight babies still pose a challenge for an optimal outcome. Maternal socioeconomic status and malnutrition is directly or indirectly linked to the birthweight. We intended to study the effect of socioeconomic status of family with birthweight in eastern part of India. Objective: To assess the effect of socioeconomic status of family on birth weight and to assess the effect of anemia on birthweight. Materials and Methods: A cross-sectional study was conducted in Gouri Devi Institute of Medical Sciences and Hospital, Durgapur, West Bengal, from 1st March 2019 to 28th February 2020. Data was collected from the mothers who visited the Paediatrics OPD with their child during the study period. Mothers were asked to fill a pre-designated case record form. Details of antenatal, natal and postnatal records were sought and noted. For the purpose of assessment of socioeconomic status, education, occupation and income of family were recorded. Socioeconomic status family were classified in to 3 major categories; lower (lower and upper lower), middle (lower middle and upper middle) and upper as per modified Kuppuswamy classification. Maternal nutrition status was assessed by body mass index (BMI) and anemia. Results: Out of the 229 babies, 79 babies had low birthweight and 150 babies had normal birthweight. 35.5% of babies were found to have low birthweight. Babies born to mother with primary education (68.55%) were found to have more LBW babies than with higher education. Twenty eight (35.44%) LBW babies belong to middle class (class II and class III) and 51(64.56%) LBW babies were from lower class (P<0.05). Mothers of 194 (84.71%) out of 229 babies had anemia. Similarly only 5(6.33%) LBW babies belong to non-anemic mother where as 74(93.67%) of LBW babies were from mothers with low hemoglobin. Anemic mothers were more likely to deliver LBW baby. Conclusion: Low maternal education, low socio-economic status and maternal anemia were associated with increase in the risk of low birth weight babies

Epitranscriptomics in parasitic protists: Role of RNA chemical modifications in posttranscriptional gene regulation.

"Epitranscriptomics" is the new RNA code that represents an ensemble of posttranscriptional RNA chemical modifications, which can precisely coordinate gene expression and biological processes. There are several RNA base modifications, such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), and pseudouridine (Ψ), etc. that play pivotal roles in fine-tuning gene expression in almost all eukaryotes and emerging evidences suggest that parasitic protists are no exception. In this review, we primarily focus on m6A, which is the most abundant epitranscriptomic mark and regulates numerous cellular processes, ranging from nuclear export, mRNA splicing, polyadenylation, stability, and translation. We highlight the universal features of spatiotemporal m6A RNA modifications in eukaryotic phylogeny, their homologs, and unique processes in 3 unicellular parasites-Plasmodium sp., Toxoplasma sp., and Trypanosoma sp. and some technological advances in this rapidly developing research area that can significantly improve our understandings of gene expression regulation in parasites