Quantitative High-Throughput Screening Identifies 8-Hydroxyquinolines as Cell-Active Histone Demethylase Inhibitors

Small molecule modulators of epigenetic processes are currently sought as basic probes for biochemical mechanisms, and as starting points for development of therapeutic agents. N(epsilon)-Methylation of lysine residues on histone tails is one of a number of post-translational modifications that together enable transcriptional regulation. Histone lysine demethylases antagonize the action of histone methyltransferases in a site- and methylation state-specific manner. N(epsilon)-Methyllysine demethylases that use 2-oxoglutarate as co-factor are associated with diverse human diseases, including cancer, inflammation and X-linked mental retardation; they are proposed as targets for the therapeutic modulation of transcription. There are few reports on the identification of templates that are amenable to development as potent inhibitors in vivo and large diverse collections have yet to be exploited for the discovery of demethylase inhibitors

Neuron-glial Interactions

Although lagging behind classical computational neuroscience, theoretical and computational approaches are beginning to emerge to characterize different aspects of neuron-glial interactions. This chapter aims to provide essential knowledge on neuron-glial interactions in the mammalian brain, leveraging on computational studies that focus on structure (anatomy) and function (physiology) of such interactions in the healthy brain. Although our understanding of the need of neuron-glial interactions in the brain is still at its infancy, being mostly based on predictions that await for experimental validation, simple general modeling arguments borrowed from control theory are introduced to support the importance of including such interactions in traditional neuron-based modeling paradigms.Junior Leader Fellowship Program by “la Caixa” Banking Foundation (LCF/BQ/LI18/11630006

Neuron-Glial Interactions

Although lagging behind classical computational neuroscience, theoretical and computational approaches are beginning to emerge to characterize different aspects of neuron-glial interactions. This chapter aims to provide essential knowledge on neuron-glial interactions in the mammalian brain, leveraging on computational studies that focus on structure (anatomy) and function (physiology) of such interactions in the healthy brain. Although our understanding of the need of neuron-glial interactions in the brain is still at its infancy, being mostly based on predictions that await for experimental validation, simple general modeling arguments borrowed from control theory are introduced to support the importance of including such interactions in traditional neuron-based modeling paradigms.Comment: 43 pages, 2 figures, 1 table. Accepted for publication in the "Encyclopedia of Computational Neuroscience," D. Jaeger and R. Jung eds., Springer-Verlag New York, 2020 (2nd edition

A miniaturized screen for inhibitors of Jumonji histone demethylases.

2-Oxoglutarate- and Fe(ii)-dependent oxygenases are a major class of N(epsilon)-methyl lysine demethylases that are involved in epigenetic regulation. Assays suitable for implementation in a high-throughput manner have been lacking for these enzymes. Here, we describe the design and implementation of a robust and miniaturized high-throughput kinetic assay for inhibitors of JMJD2E using a formaldehyde dehydrogenase-coupled reaction with real-time fluorescence detection. Reactant compatibility studies resulted in simplification of the assay scheme to the mixing of two reagent solutions, both of which were stable overnight. The assay was miniaturized to a 4 microL volume in 1536-well format and was used to screen the library of pharmacologically active compounds (LOPAC(1280)). Inhibitors identified by the screen were further characterized in secondary assays including FDH counterscreen and demethylation assays that monitored demethylation by MALDI-TOF MS. The assay developed here will enable the screening of large compound libraries against the Jumonji demethylases in a robust and automated fashion

May Measurement Month 2019: an analysis of blood pressure screening results from India (vol 23, pg B73, 2021)

[This corrects the article DOI: 10.1093/eurheartjsupp/suab047.]

May Measurement Month 2019: an analysis of blood pressure screening results from India

Aims: May Measurement Month is a global screening campaign to raise awareness regarding elevated blood pressure (BP). With the growing burden of hypertension, it is imperative to regularly assess the disease's prevalence, risk factors, and awareness levels in a country. The current prevalence of hypertension in India as per the National Family Health Survey Data stands at 25.3%. May Measurement Month mobilizes healthcare professionals and sensitizes them to regularly measure BP, and impart lifestyle modification advice to the community. It also complements the deficiency in screening programmes at a national and international level. Methods and results: May Measurement Month was carried out in May 2019 as an opportunistic screening campaign for adults (≥18 years). It was carried out by over 5000 trained volunteers across approximately 1000 screening sites (hospitals, public places, pharmacies, villages, and malls) in India. A total of 362 708 (57% males and 42.7% females) people were screened, among whom 68.1% had never measured their BP, and 29.4% (n = 106 522) were found to have hypertension. Of these, only 42.0% were on antihypertensive medication and 23.3% had controlled hypertension. Conclusion: Almost a third of the screened population had hypertension, and less than half of those with hypertension were aware of it or on treatment for it. Among those on antihypertensive drugs, BP was controlled in only half of them. These results support the need for greater impetus on BP screening initiatives to detect hypertension early in the community and prevent complications due to uncontrolled BP

Extrusion-Spheronization of Talc using Microcrystalline Cellulose as a Pellet Aid: Part I

NoThe aims of the present work were to pelletize talc by extrusion-spheronization technique using microcrystalline cellulose (MCC) as a pelletization aid and to study its performance as a neutral substrate for coating. A 32 factorial design was used to study the effect of independent variables (X1, amount of talc, and X2, MCC) on pellet properties

Components of all-solid-state ion-selective electrodes

An electrochemical sensor is a qualitative and quantitative device that converts a chemical signal to a measurable electrical signal (Yogeswaran and Shen-Ming 2008). Electrochemical sensors can be divided into three classes: potentiometric, amperometric, and conductometric (Stradiotto et al. 2003). A potentiometric sensor measures an electrical potential when no current is present, while an amperometric sensor produces current when a potential is applied between two electrodes. A conductometric sensor assesses conductivity by measuring the electrical resistance of a sample solution. Ion-selective electrodes (ISEs) are potentiometric ion sensors and a subgroup of electrochemical sensors; they are widely used in various fields of biomedical, environmental, and chemical analysis, and physiological sensing (Bobacka et al. 2003; Bakker et al. 2008; Hu et al. 2016). ISEs are classified into three groups, depending on the nature of the membrane material: glass, polymeric or liquid, and crystal or solid (Fig. 16.1) (Faridbod et al. 2007)