Use of leuprolide to treat endometriosis in a rhesus macaque.

Endometriosis was diagnosed in an aged dysmenorrheic rhesus monkey (Macaca mulatta) after biopsy of a 7 cm abdominal mass which could not be completely resected due to extensive adhesions. A 6-month course of treatment with leuprolide, a gonadotropin-releasing hormone agonist, resulted in cessation of menstrual cycles and marked clinical improvement. Dysmenorrhea and hypovolemic shock occurred 2 months after therapy was completed. Despite supportive treatment and resumption of leuprolide, the primate's clinical deterioration and abdominal mass enlargement necessitated euthanasia. To our knowledge, this is the first report of a case of endometriosis in a rhesus macaque treated with a gonadotropin-releasing hormone agonist. Although prolonged leuprolide therapy was clinically effective, its cost and the difficulty in early diagnosis of endometriosis may limit its use in nonhuman primate medicine.     

Is there Ca2+(Sr2+)-3-hydroxybutyrate symport in rat-liver mitochondria? A reappraisal

The observation in this laboratory that respiration and Sr2+ import were stimulated by the addition of 3-hydroxybutyrate to suspensions of N-ethylmaleimide-treated mitochondria respiring in state 6, after the addition of Sr2+, in a sucrose medium containing choline as substrate, led to the proposal by Moyle and Mitchell [(1977) FEBS Lett. 84, 135-140] that there is a Ca2+(Sr2+)-3-hydroxybutyrate symporter in rat liver mitochondria. However, experiments described in the present paper support a different interpretation. Under the conditions of the experiments by Moyle and Mitchell, the rate of respiration and the poise of Sr2+ accumulation are mainly limited, not by delta mu H+, but by lack of respiratory substrate. Even though N-ethylmaleimide is a potent inhibitor of 3-hydroxybutyrate dehydrogenase, we have found that, somewhat surprisingly, under the special conditions of these experiments, sufficient 3-hydroxybutyrate dehydrogenase activity remains available to account for the 3-hydroxybutyrate-dependent respiratory stimulation and Sr2+ import.     

Functional,Non-Clonal IgMa-Restricted B Cell Receptor Interactions with the HIV-1 Envelope gp41 Membrane Proximal External Region

The membrane proximal external region (MPER) of HIV-1 gp41 has several features that make it an attractive antibody-based vaccine target, but eliciting an effective gp41 MPER-specific protective antibody response remains elusive. One fundamental issue is whether the failure to make gp41 MPER-specific broadly neutralizing antibodies like 2F5 and 4E10 is due to structural constraints with the gp41 MPER, or alternatively, if gp41 MPER epitope-specific B cells are lost to immunological tolerance. An equally important question is how B cells interact with, and respond to, the gp41 MPER epitope, including whether they engage this epitope in a non-canonical manner i.e., by non-paratopic recognition via B cell receptors (BCR). To begin understanding how B cells engage the gp41 MPER, we characterized B cell-gp41 MPER interactions in BALB/c and C57BL/6 mice. Surprisingly, we found that a significant (∼7%) fraction of splenic B cells from BALB/c, but not C57BL/6 mice, bound the gp41 MPER via their BCRs. This strain-specific binding was concentrated in IgM^hi subsets, including marginal zone and peritoneal B1 B cells, and correlated with enriched fractions (∼15%) of gp41 MPER-specific IgM secreted by in vitro-activated splenic B cells. Analysis of Igh^a (BALB/c) and Igh^b (C57BL/6) congenic mice demonstrated that gp41 MPER binding was controlled by determinants of the Igh^a locus. Mapping of MPER gp41 interactions with IgM^a identified MPER residues distinct from those to which mAb 2F5 binds and demonstrated the requirement of Fc C_H regions. Importantly, gp41 MPER ligation produced detectable BCR-proximal signaling events, suggesting that interactions between gp41 MPER and IgM^a determinants may elicit partial B cell activation. These data suggest that low avidity, non-paratopic interactions between the gp41 MPER and membrane Ig on naïve B cells may interfere with or divert bnAb responses.     

Predation drives morphological convergence in the Gambusia panuco species group among lotic and lentic habitats

Fish morphology is often constrained by a trade‐off between optimizing steady vs. unsteady swimming performance due to opposing effects of caudal peduncle size. Lotic environments tend to select for steady swimming performance, leading to smaller caudal peduncles, whereas predators tend to select for unsteady swimming performance, leading to larger caudal peduncles. However, it is unclear which aspect of performance should be optimized across heterogeneous flow and predation environments and how this heterogeneity may affect parallel phenotypic evolution. We investigated this question among four Gambusia species in north‐eastern Mexico, specifically the riverine G. panuco, the spring endemics G. alvarezi and G. hurtadoi, and a fourth species, G. marshi, found in a variety of habitats with varying predation pressure in the Cuatro Ciénegas Basin and Río Salado de Nadadores. We employed a geometric morphometric analysis to examine how body shapes of both male and female fish differ among species and habitats and with piscivore presence. We found that high‐predation and low‐predation species diverged morphologically, with G. marshi exhibiting a variable, intermediate body shape. Within G. marshi, body morphology converged in high‐predation environments regardless of flow velocity, and fish from high‐predation sites had larger relative caudal peduncle areas. However, we found that G. marshi from low‐predation environments diverged in morphology between sub‐basins of Cuatro Ciénegas, indicating other differences among these basins that merit further study. Our results suggest that a morphological trade‐off promotes parallel evolution of body shape in fishes colonizing high‐predation environments and that changing predation pressure can strongly impact morphological evolution in these species.     

Chronic social stress induces DNA methylation changes at an evolutionary conserved intergenic region in chromosome X

Chronic stress resulting from prolonged exposure to negative life events increases the risk of mood and anxiety disorders. Although chronic stress can change gene expression relevant for behavior, molecular regulators of this change have not been fully determined. One process that could play a role is DNA methylation, an epigenetic process whereby a methyl group is added onto nucleotides, predominantly cytosine in the CpG context, and which can be induced by chronic stress. It is unknown to what extent chronic social defeat, a model of human social stress, influences DNA methylation patterns across the genome. Our study addressed this question by using a targeted-capture approach called Methyl-Seq to investigate DNA methylation patterns of the dentate gyrus at putative regulatory regions across the mouse genome from mice exposed to 14 days of social defeat. Findings were replicated in independent cohorts by bisulfite-pyrosequencing. Two differentially methylated regions (DMRs) were identified. One DMR was located at intron 9 of Drosha, and it showed reduced methylation in stressed mice. This observation replicated in one of two independent cohorts. A second DMR was identified at an intergenic region of chromosome X, and methylation in this region was increased in stressed mice. This methylation difference replicated in two independent cohorts and in Major Depressive Disorder (MDD) postmortem brains. These results highlight a region not previously known to be differentially methylated by chronic social defeat stress and which may be involved in MDD.     

Neutral and non-neutral factors shape an emergent plant–antagonist interaction

Discerning the mechanisms responsible for emergent evolutionary radiations, community assembly, and the maintenance of diversity is necessary for understanding the evolutionary ecology of species interactions in changing landscapes. These processes can be driven by stochastic (neutral) factors, such as genetic drift, or deterministic (non-neutral) factors, such as the external environment and heritable phenotypic variation. Neutral and non-neutral factors can shape species interactions, but the relative influence of these different processes on antagonistic relationships is not well understood. We leveraged the recent discovery of a novel herbivore (Caloptilia triadicae) on invasive Chinese tallow (Triadica sebifera) to investigate the nature and relative importance of different factors influencing plant–antagonist interactions. We assessed measures of host attributes, herbivore demography and herbivory across the North American range of Triadica according to geography, environmental variation, and host genetic variation. We found that leaf toughness corresponded to genetic variation in Triadica, longitude, and mean temperature. Genetic variation in Triadica was the strongest predictor of herbivore abundance, especially for the early leaf mining stages, though herbivore abundance also corresponded to longitude. Model variables did not explain leaf damage, which was driven by interactions with late-stage larvae. Trends in herbivore demography were not consistent with previously reported geographic patterns of Triadica genetic variation related to tannin defense, but were consistent with patterns revealed by other studies of Triadica phenolic compounds and C:N, as well as low sensitivity of endophagous herbivores to tannins in the absence of parasitoids. Our findings suggest that even simple geographic mosaics of genetic and environmental variation, as well as distance-dependent dispersal, can influence the establishment and trajectory of novel species interactions.     

Conserving rare species can have high opportunity costs for common species

Conservation practitioners face difficult choices in apportioning limited resources between rare species (to ensure their existence) and common species (to ensure their abundance and ecosystem contributions). We quantified the opportunity costs of conserving rare species of migratory fishes in the context of removing dams and retrofitting road culverts across 1,883 tributaries of the North American Great Lakes. Our optimization models show that maximizing total habitat gains across species can be very efficient in terms of benefits achieved per dollar spent, but disproportionately benefits common species. Conservation approaches that target rare species, or that ensure some benefits for every species (i.e., complementarity) enable strategic allocation of resources among species but reduce aggregate habitat gains. Thus, small habitat gains for the rarest species necessarily come at the expense of more than 20 times as much habitat for common ones. These opportunity costs are likely to occur in many ecosystems because range limits and conservation costs often vary widely among species. Given that common species worldwide are declining more rapidly than rare ones within major taxa, our findings provide incentive for triage among multiple worthy conservation targets.     

Comparison of Antistreptolysin O Latex Screening Test with the Antistreptolysin O Hemolytic Test

This report describes a comparison of the Behringwerke antistreptolysin O (ASO) latex screening test with the ASO hemolytic test. Agreement between the two tests was poor when Difco streptolysin O (SLO) reagent was employed in the hemolytic test; approximately 34% of the sera with ASO titers in the normal range of the hemolytic test gave false-positive latex test reactions. However, the percentage of false-positive latex test reactions was only 5% when Behringwerke SLO reagent was used in the hemolytic test. An assay of the Difco and Behringwerke SLO reagents against an ASO standard indicated that the Difco SLO reagent was more potent than the Behringwerke SLO reagent. The lack of agreement between the Behringwerke latex test and the hemolytic test using Difco SLO reagent is attributed to the potency of the SLO reagents.     

Acid-Precipitated M Protein Compared with a Column-Eluted M Protein Preparation from Type 12, Group A Streptococci

An M protein preparation of group A streptococci, precipitated with 0.03 m sodium acetate buffer (pH 4.0) was compared with a column-eluted M protein preparation. Absorption spectra and methyl pentose content were similar in both preparations. Acrylamide gel electrophoresis patterns were different. Gel diffusion demonstrated two lines of fusion in the preparations. More antigens could be demonstrated in both preparations by using immunoelectrophoresis. Neither the pH 4 precipitate nor the column-eluted preparation appeared to be a pure M protein preparation.