The cannabinoid CB receptor positive allosteric modulator EC21a exhibits complicated pharmacology .

Schizophrenia is a complex disease involving the dysregulation of numerous brain circuits and patients exhibit positive symptoms (hallucinations, delusions), negative symptoms (anhedonia), and cognitive impairments. We have shown that the antipsychotic efficacy of positive allosteric modulators (PAMs) of both the M muscarinic receptor and metabotropic glutamate receptor 1 (mGlu) involve the retrograde activation of the presynaptic cannabinoid type-2 (CB) receptor, indicating that CB activation or potentiation could result in a novel therapeutic strategy for schizophrenia. We used two complementary assays, receptor-mediated phosphoinositide hydrolysis and GIRK channel activation, to characterize a CB PAM scaffold, represented by the compound EC21a, to explore its potential as a starting point to optimize therapeutics for schizophrenia.

Optical control of 4 orbital state in rare-earth metals.

A change of orbital state alters the coupling between ions and their surroundings drastically. Orbital excitations are hence key to understand and control interaction of ions. Rare-earth elements with strong magneto-crystalline anisotropy (MCA) are important ingredients for magnetic devices.

Fieldworker effects on quality of data collected on sensitive questions in National Family Health Surveys: An analysis based on intimate partner violence in India.

National Family Health Survey (NFHS) has played a pivotal role in formulating policies and programs by providing nationally representative data on a wide range of monitoring and impact evaluation indicators in population, health and nutrition. However, due to measurement errors resulting in misreporting, the collection of accurate data on sensitive issues in sample surveys has always been a matter of concern. This study examines the fieldworker effect on the reporting of physical, sexual, and emotional Intimate Partner Violence (IPV) using fifth round of NFHS (2019-21) data in India.

Role of seasonality variation in prevalence and trend of childhood wasting in India: An empirical analysis using National Family Health Surveys, 2005-2021.

Background: Wasting develops over a short period and can be reversed with short-term interventions. The prevalence of wasting typically varies from season to season-becoming higher during the monsoon (June to September) season as compared to the winter (October to January) and summer (February to May) seasons every year in a cyclical fashion. However, to the best of our knowledge, using nationally representative demographic surveys to extensively study the impact of the timing of the survey on the results and trends around wasting has not been done so far.

Survey implementation process and interviewer effects on skipping sequence of maternal and child health indicators from National Family Health Survey: An application of cross-classified multilevel model.

Implementing a large-scale survey involves a string of intricate procedures exposed to numerous types of survey errors. Uniform and systematic training protocols, comprehensive survey manuals, and multilayer supervision during survey implementation help reduce survey errors, providing a consistent fieldwork environment that should not result in any variation in the quality of data collected across interviewers and teams. With this background, the present study attempts to delineate the effect of field investigator (FI) teams and survey implementation design on the selected outcomes.

Histone deacetylase 6 inhibition restores leptin sensitivity and reduces obesity.

The adipose tissue-derived hormone leptin can drive decreases in food intake while increasing energy expenditure. In diet-induced obesity, circulating leptin levels rise proportionally to adiposity. Despite this hyperleptinemia, rodents and humans with obesity maintain increased adiposity and are resistant to leptin's actions.

Using the photoinduced resonance shift in Fe and Ni as time reference for ultrafast experiments at low flux soft x-ray sources.

We study the optical-pump induced ultrafast transient change of x-ray absorption at absorption resonances of the transition metals Ni and Fe in the FeNi alloy. We find the effect for both elements to occur simultaneously on a femtosecond timescale. This effect may hence be used as a handy cross correlation scheme, providing a time-zero reference for ultrafast optical-pump soft x-ray-probe measurement.

Ten-Year Retrospective of the Vanderbilt Institute of Chemical Biology Chemical Synthesis Core.

Chemical synthesis has been described as a central science. Its practice provides access to the chemical structures of known and/or designed function. In particular, human health is greatly impacted by synthesis that enables advancements in both basic science discoveries in chemical biology as well as translational research that can lead to new therapeutics.

Optimization of ether and aniline based inhibitors of lactate dehydrogenase.

Lactate dehydrogenase (LDH) is a critical enzyme in the glycolytic metabolism pathway that is used by many tumor cells. Inhibitors of LDH may be expected to inhibit the metabolic processes in cancer cells and thus selectively delay or inhibit growth in transformed versus normal cells. We have previously disclosed a pyrazole-based series of potent LDH inhibitors with long residence times on the enzyme.

Pyrazole-Based Lactate Dehydrogenase Inhibitors with Optimized Cell Activity and Pharmacokinetic Properties.

Lactate dehydrogenase (LDH) catalyzes the conversion of pyruvate to lactate, with concomitant oxidation of reduced nicotinamide adenine dinucleotide as the final step in the glycolytic pathway. Glycolysis plays an important role in the metabolic plasticity of cancer cells and has long been recognized as a potential therapeutic target. Thus, potent, selective inhibitors of LDH represent an attractive therapeutic approach.

Synthesis of tetranor-PGE: a urinary metabolite of prostaglandins E and E.

Prostaglandin E is produced in response to inflammation, often associated with human disease. As prostaglandins are rapidly metabolized, quantification of end urinary metabolites depend on chemical synthesis of isotopically labeled standards to support metabolite quantification. A concise synthesis of tetranor-PGE is described including a late stage incorporation of an isotopically labeled side-chain.

Revisiting Goodenough-Kanamori rules in a new series of double perovskites LaSrCaNiReO.

The magnetic ground states in highly ordered double perovskites LaSrCaNiReO (x = 0.0, 0.5, 1.

Dual inhibition of Kif15 by oxindole and quinazolinedione chemical probes.

The mitotic spindle is a microtubule-based machine that segregates a replicated set of chromosomes during cell division. Many cancer drugs alter or disrupt the microtubules that form the mitotic spindle. Microtubule-dependent molecular motors that function during mitosis are logical alternative mitotic targets for drug development.

Total Synthesis and Biological Activity of the Arachidonic Acid Metabolite Hemiketal E.

The total synthesis of hemiketal E (HKE) has been accomplished using a gold(I)-mediated cycloisomerization followed by oxidation of the enol ether product to introduce a unique keto-hemiketal, the core structure of HKE. Synthetic hemiketal E reproduced biosynthetically derived HKE in the inhibition of human platelet aggregation.

Studies of the synthesis of providencin: construction and assembly of two major subunits.

The "northern" sector of the cembranoid diterpene providencin containing a tetrasubstituted cyclobutane was synthesized from the bis(acetonide) of d-glucose using dicyclopentadienylzirconium(0)-mediated oxygen abstraction from a furanose. Oxidative scission of the vinyl substituent of this cyclobutane gave an aldehyde, which was reacted with an alkynylstannane to provide an allenol. Cyclization of the derived allenone with silver nitrate led to a cyclobutylfuran comprising the northern subunit of providencin.

The synthesis of indoline and benzofuran scaffolds using a Suzuki-Miyaura coupling/oxidative cyclization strategy.

The generation of indolines and benzofurans from the combination of Suzuki-Miyaura coupling reactions with oxidative cyclizations is described.

Multifunctional Doped Semiconductor Nanocrystals.

Multifunctional nanomaterials with combined magnetic and optical properties remain one of the most demanded materials in upcoming research. To obtain these materials, we report here several doped semiconductor nanocrystals that simultaneously show tunable emission in a visible and NIR spectral window, above-room-temperature ferromagnetism, and improved conductivity. These nanocrystals are designed by inserting Ni(II) as a dopant in various semiconducting hosts with binary, alloyed, and ternary composition, and the induced multifunctional properties are observed to be stable and reproducible.

Spin-valve-type magnetoresistance: a generic feature of ferromagnetic double perovskites.

An unusual magnetoresistance (MR) behavior in Sr(2)FeMoO(6), recently termed as spin-valve-type MR (SVMR), presents several anomalies that are little understood so far. The formation of a magnetically distorted skin layer around every soft, ferromagnetic grain seems to be the reason behind such an unprecedented tunneling MR (TMR) response. However, initially it appeared that Sr(2)FeMoO(6) is an exclusive TMR material showing an unusual SVMR effect, while other well-known magnetoresistive compounds do not exhibit such behavior.

Synthesis of the cyclobutylfuran sector of providencin via zirconium-mediated oxygen abstraction from a furanoside.

A portion of the macrocyclic cembrenoid diterpene providencin possessing conjoined cyclobutane and furancarboxylate units was synthesized from D-glucose using deoxygenative ring contraction methodology to construct the tetrasubstituted cyclobutane and a Knoevenagel condensation of glyceraldehyde to fabricate the trisubstituted furan.