E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity

A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.     

Review on recent advances of zinc substituted cobalt ferrite nanoparticles: Synthesis characterization and diverse applications

Researchers have taken a prodigious consideration in characterizing and synthesizing zinc substituted cobalt ferrite nanoparticles because of their substantial applications across diverse technological and industrial fields. Zinc substituted cobalt ferrite nanoparticles are a class of lenient magnetic nanomaterials, which have potentially high magnetic, optical, electrical, and dielectric properties. These properties include a high value of permeability, low power losses, permittivity, saturation magnetization, coercivity, resistivity, and other beneficial properties that make them promise candidates for applications in various fields. These ferrites are also used in biomedical areas such as MRI and cancer treatments. In electronic fields, zinc substituted cobalt ferrite nanoparticles are used to make transducers, transformers, biosensors, and sensors. Apart from these advantages, they are found in our everyday electronic and electrical appliances like LED bulb, refrigerator, mobile charger, TV, microwave oven, juicer, washing machine, mixer, iron, printer, laptop, mobile, desktop, etc. Hence, the current review reports some properties of these spinel ferrites and emphasizes the different synthesis techniques that can be used to prepare them. Afterward, the impact of dopant on the materials' properties, the characterization techniques, and the momentous application in the present era have been well discussed.     

Effect of two different rubbers as secondary binders on the friction and wear characteristics of non-asbestos organic (NAO) brake friction materials

Binder provides structural integrity by holding all ingredients in the composition of a brake friction material. The modified binders have played a major role in improving the frictional performance and thermal resistance of the friction material. The present research work evaluates the influence of secondary binders (Nitrile Butadiene rubber (NBR) and Styrene Butadiene rubber (SBR)) on the tribological performance of the friction material using a full-scale inertia brake dynamometer as per JASO C406 standard. Three brake pads were developed by varying the type and composition of secondary rubber binder (5%NBR, 5%SBR and 2.5%NBR + 2.5%SBR) with rest of the ingredients kept unaltered. It was found that the quantity of SBR rubber powder present as secondary binder improved dry and wet recovery. Friction coefficient (μ) exhibited better stability during the fade with the inclusion of both the rubber powders. The friction material with the inclusion of both the NBR and SBR rubber powders exhibited overall better performance than compared to the inclusion of only one secondary binder rubber in the composition. The worn-out surface of the developed friction materials and the counter discs were characterised using FESEM.     

Mu-opioid receptor (OPRM1) variation, oxytocin levels and maternal attachment in free-ranging rhesus macaques Macaca mulatta.

Understanding the genetic and neuroendocrine basis of the mother-infant bond is critical to understanding mammalian affiliation and attachment. Functionally similar nonsynonymous mu-opioid receptor (OPRM1) SNPs have arisen and been maintained in humans (A118G) and rhesus macaques Macaca mulatta (C77G). In rhesus macaques, variation in OPRM1 predicts individual differences in infant affiliation for mothers. Specifically, infants carrying the G allele show increased distress on separation from their mothers, and spend more time with them upon reunion, than individuals homozygous for the C allele. In humans, individuals possessing the G allele report higher perceptions of emotional pain on receiving rejection by social partners. We studied maternal behavior over the course of a year among free-ranging female rhesus macaques on Cayo Santiago, Puerto Rico. We then trapped females and collected blood samples from which we assessed OPRM1 genotype; we also collected cerebrospinal fluid samples from which we measured oxytocin (OT) levels. We show that females possessing the G allele restrain their infants more (i.e., prevent infants from separating from them by pulling them back) than females homozygous for the C allele. Females possessing the G allele also show higher OT levels when lactating, and lower OT levels when neither lactating nor pregnant, than females homozygous for the C allele. This is the first study to demonstrate an association between OPRM1 genotype and maternal attachment for infants, and is one of the first studies of any free-ranging primate population to link functional genetic variation to behavior via potentially related neuroendocrine mechanisms. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Isomerization of 9c11t/10t12c CLA in Triacylglycerols

Isomers of conjugated linoleic acid from 7t9c through 12t14t can be induced by thermal treatment of triacylglycerol samples of 9c11t or 10t12c fatty acids in glass tubes. The formation of conjugated linoleic acids (CLAs) has been observed during thermal induction of the above-mentioned triacylglycerols at 250, 280 and 320°C. The concentrations of isomers formed in the mixture varied depending on the temperature and duration of the heating experiments. The objective of this study was to find a suitable thermal induction temperature and time that can produce most of the isomers of CLAs from the above-mentioned triacylglycerols. Such a mixture would give researchers a reference standard that can be used in the identification of CLAs in GC analyses of relevant samples. Fifteen-microlitre portions of the triacylglycerol samples containing 9c11t/10t12c fatty acid were placed in micro-glass ampoules, sealed under nitrogen and then subjected to thermal treatment. The glass ampoules were removed at regular time intervals, cut open, and part of the samples was analysed by infrared spectroscopy using attenuated internal reflectance technique. The remainder of the samples was subjected to derivatisation into their methyl esters. The methyl esters of the isomerised fatty acids were then analysed by gas chromatography after appropriate dilution in heptane. The results show that the thermally induced glyceride samples of 9c11t/10t12c fatty acids gave CLA profiles containing isomers ranging from 7t9c to 12t14t. However, the concentrations of the isomers are different depending on the duration of the thermal induction. It appears that [1,5] sigmatropic rearrangements and positional isomerisations take place in the heated mixtures. The rearrangements and positional isomerisations are accelerated by increasing temperature. The glyceride samples heated to 325°C form isomers within 30 min and provide a mixture of CLA isomers that can be used as reference sample containing the methyl esters of CLAs.     

The Relation Between Television Exposure and Theory of Mind Among Preschoolers

This study explored the relation between preschoolers' television exposure and one important indicator of cognitive processing called theory of mind (ToM). A total of 107 preschoolers and their parents provided data on the preschoolers' television exposure (including both intentional viewing and exposure via background television), parent–child discussion of television, and preschoolers' ToM. The results indicated that preschoolers who were exposed to more background television and who had a television in their bedroom performed more poorly on ToM assessments compared with other children. Parent–child discussion of television was positively related to ToM performance, however. These results have implications for how we understand the effects of television on preschoolers.     

Survival and Metabolic Activity of Listeria monocytogenes on Ready‐to‐Eat Roast Beef Stored at 4 °C

Three brands of commercial roast beef were purchased and artificially inoculated with a 5‐strain Listeria monocytogenes cocktail at 2 inoculation levels (approximately 3 and 6 Log CFU/g). Although all 3 brands contained sodium diacetate and sodium lactate, inoculated Listeria cocktail survived for 16 d in all 3 brands; significant increases in L. monocytogenes numbers were seen on inoculated Brand B roast beef on days 12 and 16. Numbers of L. monocytogenes increased to 4.14 Log CFU/g for the 3 Log CFU/g inoculation level and increased to 7.99 Log CFU/g for the 6 Log CFU/g inoculation level by day 16, with the pH values being 5.4 and 5.8 respectively. To measure the cell viability in potential biofilms formed, an Alamar blue assay was conducted. Brand B meat homogenate had the highest metabolic activities (P < 0.05). By comparing its metabolic activities to Brands A and C and the inoculated autoclaved meat homogenates, results indicated that the microflora present in Brand B may be the reason for high metabolic activities. Based on the denaturing gradient gel electrophoresis and the Shannon–Wiener diversity index analysis, the “Brand” factor significantly impacted the diversity index (P = 0.012) and Brand B had the highest microflora diversity (Shannon index 1.636 ± 0.011). Based on this study, results showed that antimicrobials cannot completely inhibit the growth of L. monocytogenes in ready‐to‐eat roast beef. Native microflora (both diversity and abundance), together with product formula, pH, antimicrobial concentrations, and storage conditions may all impact the survival and growth of L. monocytogenes.     

Effects of age on cerebrospinal fluid oxytocin levels in free-ranging adult female and infant rhesus macaques.

There is growing interest in examining oxytocin and social functioning in human and non-human primates. Studies of human oxytocin biology are typically restricted to peripheral assessments because opportunities to collect cerebrospinal fluid (CSF) are rare. Several studies have examined CSF oxytocin levels in captive adult primates, but none to our knowledge have been conducted under free-ranging conditions and inclusive of infants. The main goal of this study was to establish feasibility of quantifying CSF oxytocin levels in free-ranging adult female and infant rhesus monkeys living on Cayo Santiago, PR. CSF oxytocin levels were examined in relation to individuals' demographic and reproductive characteristics as well as plasma cortisol levels. CSF oxytocin concentrations ranged from 36.02 to 134.41 pg/ml in adult females (ages 7–26 years; N = 31) and 35.94 to 77.3 pg/ml in infants (ages 38–134 days; N = 17). CSF oxytocin levels were positively correlated with adult female age and negatively correlated with infant age. The former correlation was driven by reproductive status. CSF oxytocin levels were unrelated to dominance rank or plasma cortisol levels. In contrast to a previous study of plasma oxytocin concentrations in this population, CSF oxytocin levels did not differ significantly between lactating and non-lactating females. These findings: 1) provide feasibility data for examining CSF oxytocin levels in free-ranging non-human primates and 2) indicate that CSF oxytocin levels may be a biomarker of age-related central nervous system changes across lifespan development. Research is now required to examine CSF oxytocin levels in the context of social functioning in free-ranging rhesus monkeys. (PsycINFO Database Record (c) 2010 APA, all rights reserved)