In the mammalian olfactory system, information from approximately 1000 different odorant receptor types is organized in the nose into four spatial zones. Each zone is a mosaic of randomly distributed ...neurons expressing different receptor types. In these studies, we have obtained evidence that information highly distributed in the nose is transformed in the olfactory bulb of the brain into a highly organized spatial map. We find that specific odorant receptor gene probes hybridize in situ to small, and distinct, subsets of olfactory bulb glomeruli. The spatial and numerical characteristics of the patterns of hybridization that we observe with different receptor probes indicate that, in the olfactory bulb, olfactory information undergoes a remarkable organization into a fine, and perhaps stereotyped, spatial map. In our view, this map is in essence an epitope map, whose approximately 1000 distinct components are used in a multitude of different combinations to discriminate a vast array of different odors.
A series of tetrahydropyrido4,3-
dpyrimidine-2,4-dione was selected in silico and evaluated as small molecules antagonists against the h-GnRH receptor. SAR is reported
The present article describes a ...selection of a new class of small molecule antagonists for the h-GnRH receptor, their preparation, and evaluation in vitro. Three computational methods were combined into a consensus score, to rank order virtual templates. The top 5% of templates were further evaluated in silico and assessed for novelty and synthetic accessibility. The tetrahydropyrido4,3-
dpyrimidine-2,4-dione core was selected for synthesis and evaluated in vitro. Using an array approach for analog design and synthesis, we were able to drive the binding below 10
nM for the h-GnRH receptor after two rounds of optimization.
Many nonpeptide antagonists of the gonadotropin-releasing hormone (GnRH) receptor, as well as other drug targets, possess a broad range of dissociation kinetic rate constants. Current methods to ...accurately define kinetic rate parameters such as K(on) and K(off) are time and labor intensive, prompting the development of a screening assay to identify slowly dissociating compounds for follow-up rate constant determination. The authors measured inhibition binding constants (K(i)) for GnRH receptor antagonists after 30 min and 10 h of incubation and observed several compounds with markedly decreased K(i) values over time (Ki(30 min)/Ki(10 h) > 6). They used scintillation proximity assay technology to perform these binding experiments because this homogeneous assay does not have a fixed termination end point as does filtration binding, permitting successive readings to be taken from the same assay plate over an extended period of time. They also used a quantitative method of kinetic rate analysis to confirm that a large disparity between a compound's K(i) value at 30 min and 10 h could identify compounds that dissociate slowly. Thus, the K(i) ratio can be used to screen for and select compounds to test using more quantitative, albeit lower throughput methods to accurately define kinetic rate constants.
Objective. To examine the effects of dietary experience and milk feeding regimen on acceptance of their first vegetable by 4- to 6-month-old infants. Design. Longitudinal study, of 26-days duration, ...observing infants aged 4 to 6 months at the start of the study. Random assignment to treatments, within-subject control. Setting. General community in a medium-sized midwestern town. Subjects. Thirty-six infants and their mothers. Subjects were solicited through birth records and advertisements in local newspapers. Interventions. Infants were randomly assigned to be fed one vegetable on 10 occasions, either salted or unsalted peas or green beans, for a 10-day period. Outcome measures. Infant intake of the vegetable consumed during the 10-day exposure period; intake of salted and unsalted versions: (1) before the 10-day exposure period, (2) immediately after the exposure period; and (3) after a 1-week period of delay. Intake of a control food was also measured before and after repeated consumption of the vegetable. Adult ratings of the infants' videotaped responses during test feedings were also obtained before and after the exposure period. Results. After 10 opportunities to consume the vegetable, all infants significantly increased their intake (P 0.001). Although they did not differ initially, infants fed breast milk showed greater increases in intake of the vegetable after exposure and had an overall greater level of intake than formula-fed infants. Adult ratings of the infants' nonverbal responses correlated positively with infant intake. Conclusions. Infants increase their acceptance (reflected both in changes in intake and in behavioral response) of a novel food after repeated dietary exposure to that food. Relative to formula-feeding, breast-feeding may facilitate the acceptance of solid foods. Pediatrics 1994;93:271-277; Infant feeding, solid foods, breast-feeding
Abstract
Objectives:
Research indicates that older adults’ (≥60 years) emotion recognition is worse than that of young adults, young and older men’s emotion recognition is worse than that of young ...and older women (respectively), older adults’ looking at mouths compared with eyes is greater than that of young adults. Nevertheless, previous research has not compared older men’s and women’s looking at emotion faces so the present study had two aims: (a) to examine whether the tendency to look at mouths is stronger amongst older men compared with older women and (b) to examine whether men’s mouth looking correlates with better emotion recognition.
Method:
We examined the emotion recognition abilities and spontaneous gaze patterns of young (n = 60) and older (n = 58) males and females as they labelled emotion faces.
Results:
Older men spontaneously looked more to mouths than older women, and older men’s looking at mouths correlated with their emotion recognition, whereas women’s looking at eyes correlated with their emotion recognition.
Discussion:
The findings are discussed in relation to a growing body of research suggesting both age and gender differences in response to emotional stimuli and the differential efficacy of mouth and eyes looking for men and women.
Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated ...variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression (GTEx) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
What is already known about this topic? Hepatitis A vaccination is recommended for men who have sex with men (MSM). What is added by this report? During January 1, 2017–October 31, 2018, a total of ...260 cases of hepatitis A occurred among MSM from eight states compared with 16 cases reported from 50 states during 2013─2015. Forty-eight percent (124 of 258) of MSM patients were hospitalized for a median of 3 days. No deaths were reported. What are the implications for public health practice? Targeted outreach to increase awareness about hepatitis A infection and improve access to vaccination services are needed to prevent outbreaks among MSM.
Mothers’ use of mental state talk (MST) is linked to young children’s performance on false belief tests of theory of mind (ToM) and to their behaviour in social contexts. However, little is known ...about MST beyond the early years. This investigation is the first to examine continuity in both mother and child MST from preschool (age 3–4 years) to middle childhood (age 10) and examines the role of early maternal MST in children’s later ToM and use of MST. We examine the novel association between MST and children’s behavioural adjustment from pre‐school into late childhood. Participants were mother–child dyads from a 7‐year longitudinal study. Measures of MST, ToM, and language were administered at home when children were 3 and 4 years old and again at the age of 10. Also at 10, behavioural adjustment was measured using the Strengths and Difficulties Questionnaire. Mother and child MST were highly stable from preschool to later childhood. Early maternal MST accounted for unique variance in later child MST and behavioural adjustment at 10 years of age; children whose mothers used more MST, specifically references to cognitions, when they were 3 or 4 experienced fewer behavioural difficulties (externalising behaviour) when they were 10 years old.
The CRF2 receptor is involved in stress responses, cardiovascular function and gastric motility. Endogenous agonists (urocortin (UCN) 2, UCN 3) and synthetic antagonists (astressin2-B, ...antisauvagine-30) are selective for CRF2 over the CRF1 receptor. Peptide ligand binding properties of the CRF2 receptor require further investigation, including ligand affinity for endogenously expressed receptors, the effect of receptor-G-protein coupling on ligand affinity, and the molecular basis of ligand selectivity. Ligand affinity for rat CRF(2a) in olfactory bulb and CRF(2b) in A7r5 cells was similar to that for the cloned human CRF(2a) receptor (within three-fold), except for oCRF (9.4- and 5.4-fold higher affinity in olfactory bulb and A7r5 cells, respectively). Receptor-G-protein uncoupling reduced agonist affinity only 1.2- to 6.5-fold (compared with 92-1300-fold for the CRF1 receptor). Ligand selectivity mechanisms were investigated using chimeric CRF2/CRF1 receptors. The juxtamembrane receptor domain determined selectivity of antisauvagine-30, the N-terminal-extracellular domain contributed to selectivity of UCN 3, and both domains contributed to selectivity of UCN 2 and astressin2-B. Therefore ligands differ in the contribution of receptor domains to their selectivity, and CRF2-selective antagonists bind the juxtamembrane domain. These findings will be important for identifying the CRF2 receptor in tissues and for developing ligands targeting the receptor, both of which will be useful in identifying the emerging physiological functions of the CRF2 receptor.
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