Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis

Introduction  

The glucocorticoid receptor (GR) plays an important regulatory role in the immune system. Four polymorphisms in the GR gene are associated with differences in glucocorticoid (GC) sensitivity; the minor alleles of the polymorphisms N363 S and BclI are associated with relative hypersensitivity to GCs, while those of the polymorphisms ER22/23EK and 9β are associated with relative GC resistance. Because differences in GC sensitivity may influence immune effector functions, we examined whether these polymorphisms are associated with the susceptibility to develop Rheumatoid Arthritis (RA) and RA disease severity.     

A comparison of menotropin, highly-purified menotropin and follitropin alfa in cycles of intracytoplasmic sperm injection

Background  

Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency.     

Dynorphin(1-10)amide: a potent and selective analog of dynorphin(1-13)

Dynorphin(1-10)amide was more potent than Dynorphin(1-13) in inhibiting the twitch of the mouse vas deferens (IC50 of Dynorphin(1-10)amide = 0.3 nM and IC50 of Dynorphin (1-13) = 4.0 nM). Binding assays indicated that two opioid peptides had similar profiles in that they enhanced dihydromorphine (DHM) binding in picomolar concentrations but displaced DHM binding in nanomolar concentrations (IC50 for Dynorphin(1-10)amide = 5 nM). In the mouse tail-flick assay, however, Dynorphin(1-10)amide showed a more selective action on morphine-induced analgesia. Although Dynorphin(1-10)amide had no significant analgesic activity by itself, it differed from the (1-13) analog by neither potentiating nor antagonizing morphine in naive animals. In tolerant animals, on the other hand, 50 microgram of this analog administered icv shifted the ED50 of morphine from 43.0(33.0-55.9) to 17.0 (12.4-23.3). Thus, Dynorphin(1-10)amide appears to be a more potent and selective analog of Dynorphin(1-13).     

Relationships of water temperature and aquatic macroinvertebrate community structure with non-native riparian plant densities in the southern Cape,South Africa

Non-native vegetation in the riparian zone impacts on water temperatures, flow patterns, degree of shading, channel modification, and changes to natural sediment loads. Freshwater ecosystems in the Garden Route Initiative planning domain are of particular conservation value, because of the rich Gondwanaland relict aquatic macroinvertebrate fauna found in the rivers there, which are vulnerable to thermal changes. Data were collected during 2013 and 2014 at 19 sites on seven river systems between George and Knysna in the southern Cape, South Africa. These included 12 months of hourly water temperatures at all sites, and quantitative sampling of aquatic macroinvertebrates at ten sites. Each site was characterised in terms of water quality (pH, conductivity and turbidity) and general characteristics, including impacts such as density of non-native riparian trees. At the family level, aquatic macroinvertebrate communities showed variation between sites and seasons. Differences were more pronounced on the basis of natural land cover type (fynbos versus indigenous forest) than densities of non-native invasive riparian vegetation. Conservation of these river systems will depend on maintaining a mosaic of natural vegetation types.     

Glucocorticoid receptor gene polymorphisms and disease activity during pregnancy and the postpartum period in rheumatoid arthritis

Introduction

The mechanism underlying the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and the subsequent postpartum flare is incompletely understood, and the disease course varies widely between pregnant RA patients. In pregnancy, total and free levels of cortisol increase gradually, followed by a postpartum decrease to prepregnancy values. The glucocorticoid receptor (GR) polymorphisms BclI and N363S are associated with relatively increased glucocorticoid (GC) sensitivity, whereas the 9β and ER22/23EK polymorphisms of the GR gene are associated with a relatively decreased GC sensitivity. We examined the relation between the presence of these GR polymorphisms and level of disease activity and disease course of RA during pregnancy and postpartum.

Methods

We studied 147 participants of the PARA study (Pregnancy-Induced Amelioration of Rheumatoid Arthritis study), a prospective study investigating the natural improvement during pregnancy and the postpartum flare in women with RA. Patients were visited, preferably before pregnancy, at each trimester and at three postpartum time points. On all occasions, disease activity was scored by using DAS28. All patients were genotyped for the GR polymorphisms BclI, N363S, 9β, and ER22/23EK and divided in groups harboring either polymorphisms conferring increased GC sensitivity (BclI and N363S; GC-S patients) or polymorphisms conferring decreased GC sensitivity (9β or 9β + ER22/23EK; GC-I patients). Data were analyzed by using a mixed linear model, comparing GC-S patients with GC-I patients with respect to improvement during pregnancy and the postpartum flare. The cumulative disease activity was calculated by using time-integrated values (area under the curve, AUC) of DAS28 in GC-I patients versus GC-S patients. Separate analyses were performed according to the state of GC use.

Results

GC-S patients treated with GC had a significantly lower AUC of DAS28 in the postpartum period than did GC-I patients. This difference was not observed in patients who were not treated with GCs. During pregnancy, GC-S and GC-I patients had comparable levels of disease activity and course of disease.

Conclusions

Differences in relative GC sensitivity, as determined by GR polymorphisms, are associated with the level of disease activity in the postpartum period in GC-treated patients, but they do not seem to influence the course of the disease per se.     

Quantitative genomics of locomotor behavior in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Background  

Locomotion is an integral component of most animal behaviors, and many human health problems are associated with locomotor deficits. Locomotor behavior is a complex trait, with population variation attributable to many interacting loci with small effects that are sensitive to environmental conditions. However, the genetic basis of this complex behavior is largely uncharacterized.