Gonadal hormones, but not sex, affect the acquisition and maintenance of a Go/No-Go odor discrimination task in mice

In mice, olfaction is crucial for identifying social odors (pheromones) that signal the presence of suitable mates. We used a custom-built olfactometer and a thirst-motivated olfactory discrimination Go/No-Go (GNG) task to ask whether discrimination of volatile odors is sexually dimorphic and modulated in mice by adult sex hormones. Males and females gonadectomized prior to training failed to learn even the initial phase of the task, which involved nose poking at a port in one location obtaining water at an adjacent port. Gonadally intact males and females readily learned to seek water when male urine (S+) was present but not when female urine (S−) was present; they also learned the task when non-social odorants (amyl acetate, S+; peppermint, S−) were used. When mice were gonadectomized after training the ability of both sexes to discriminate urinary as well as non-social odors was reduced; however, after receiving testosterone propionate (castrated males) or estradiol benzoate (ovariectomized females), task performance was restored to pre-gonadectomy levels. There were no overall sex differences in performance across gonadal conditions in tests with either set of odors; however, ovariectomized females performed more poorly than castrated males in tests with non-social odors. Our results show that circulating sex hormones enable mice of both sexes to learn a GNG task and that gonadectomy reduces, while hormone replacement restores, their ability to discriminate between odors irrespective of the saliency of the odors used. Thus, gonadal hormones were essential for both learning and maintenance of task performance across sex and odor type.We thank David Giese for help in programming the apparatus used in GNG testing and Alberto Cruz-Martin for comments on an early version of the manuscript. This work was supported by NIDCD grant DC008962 to JAC. (DC008962 - NIDCD grant)Accepted manuscrip

Genome-wide SNP identification, linkage map construction and QTL mapping for seed mineral concentrations and contents in pea (Pisum sativum L.)

Linkage map. This file contains the details of the linkage map. (XLSX 38 kb

How men view genetic testing for prostate cancer risk: findings from focus groups

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65567/1/j.1399-0004.2000.580303.x.pd

High-dose Cefepime vs Carbapenems for Bacteremia Caused by Enterobacterales With Moderate to High Risk of Clinically Significant AmpC β-lactamase Production

BACKGROUND: Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4-8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum β-lactamase (ESBL) concerns. METHODS: This was a retrospective cohort study of hospitalized patients with RESULTS: Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared with carbapenem therapy (adjusted hazard ratio [aHR], 1.45; 95% CI, 0.79-2.14), which was consistent for patients with cefepime SDD isolates (aHR, 1.19; 95% CI, 0.52-1.77). Multivariable weighted Cox models identified Pitt bacteremia score \u3e4 (aHR, 1.41; 95% CI, 1.04-1.92), deep infection (aHR, 2.27; 95% CI, 1.21-4.32), and ceftriaxone-resistant AmpC-E (aHR, 1.32; 95% CI, 1.03-1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged-infusion β-lactam was protective (aHR, 0.67; 95% CI, 0.40-0.89). CONCLUSIONS: Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high-dose cefepime or a carbapenem as definitive β-lactam therapy

Evidence of Extensive DNA Transfer between Bacteroidales Species within the Human Gut

ABSTRACT The genome sequences of intestinal Bacteroidales strains reveal evidence of extensive horizontal gene transfer. In vitro studies of Bacteroides and other bacteria have addressed mechanisms of conjugative transfer and some phenotypic outcomes of these DNA acquisitions in the recipient, such as the acquisition of antibiotic resistance. However, few studies have addressed the horizontal transfer of genetic elements between bacterial species coresident in natural microbial communities, especially microbial ecosystems of humans. Here, we examine the genomes of Bacteroidales species from two human adults to identify genetic elements that were likely transferred among these Bacteroidales while they were coresident in the intestine. Using seven coresident Bacteroidales species from one individual and eight from another, we identified five large chromosomal regions, each present in a minimum of three of the coresident strains at near 100% DNA identity. These five regions are not found in any other sequenced Bacteroidetes genome at this level of identity and are likely all integrative conjugative elements (ICEs). Such highly similar and unique regions occur in only 0.4% of phylogenetically representative mock communities, providing strong evidence that these five regions were transferred between coresident strains in these subjects. In addition to the requisite proteins necessary for transfer, these elements encode proteins predicted to increase fitness, including orphan DNA methylases that may alter gene expression, fimbriae synthesis proteins that may facilitate attachment and the utilization of new substrates, putative secreted antimicrobial molecules, and a predicted type VI secretion system (T6SS), which may confer a competitive ecological advantage to these strains in their complex microbial ecosystem

Satellite tracking highlights difficulties in the design of effective protected areas for Critically Endangered leatherback turtles Dermochelys coriacea during the inter-nesting period

The globally distributed leatherback turtle Der- mochelys coriacea is subject to fisheries bycatch throughout its range. Protection from fisheries within pelagic foraging habitats is difficult to achieve but may be more tractable when populations are concentrated near neritic breeding and nesting grounds. We used satellite telemetry to de- scribe patterns of habitat utilization during the inter- nesting period for seven leatherback turtles nesting at Mayumba National Park in Gabon on the equatorial West African coast. The National Park includes critical nesting grounds and a marine protected area to 15 km offshore. Turtles dispersed widely from the nesting beach spending a mean of 62 - SD 26% of tracking time outside the confines of the National Park. This propensity to disperse is likely to increase the chance of deleterious interactions with fisheries in the region. Patterns of habitat utilization indicate the need for wider spatial scale planning on the West African continental shelf to enhance protection of leatherback turtles when they are seasonally occupying these habitats in great numbers for breeding and nesting

Impact of Ceftolozane-Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections

INTRODUCTION: Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane-tazobactam (C/T) is a novel β-lactam-β-lactamase inhibitor combination now commonly used to treat MDR and XDR P. aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P. aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.). METHODS: We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P. aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy. RESULTS: Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P. aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3% reduction in clinical failure compared to those who received best alternative therapy (P \u3c 0.001). The number needed to harm with best alternative therapy was 3. CONCLUSION: Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P. aeruginosa LRTI

Characterization of Pfiesteria Ichthyocidal Activity

Letter to the Editor regarding article: Drgon, T., et al. 2005. Characterization of ichthyocidal activity of Pfiesteria piscicida: Dependence on the dinospore cell density. Appl. Environ. Microbiol. 71:519–52

Genome-wide Map of Quantified Epigenetic Changes during In vitro Chondrogenic Differentiation of Primary Human Mesenchymal Stem Cells

Background: For safe clinical application of engineered cartilage made from mesenchymal stem cells (MSCs), molecular mechanisms for chondrogenic differentiation must be known in detail. Changes in gene expression and extracellular matrix synthesis have been extensively studied, but the epigenomic modifications underlying these changes have not been described. To this end we performed whole-genome chromatin immunoprecipitation and deep sequencing to quantify six histone modifications, reduced representation bisulphite sequencing to quantify DNA methylation and mRNA microarrays to quantify gene expression before and after 7 days of chondrogenic differentiation of MSCs in an alginate scaffold. To add to the clinical relevance of our observations, the study is based on primary bone marrow-derived MSCs from four donors, allowing us to investigate inter-individual variations. Results: We see two levels of relationship between epigenetic marking and gene expression. First, a large number of genes ontogenetically linked to MSC properties and the musculoskeletal system are epigenetically prepatterned by moderate changes in H3K4me3 and H3K9ac near transcription start sites. Most of these genes remain transcriptionally unaltered. Second, transcriptionally upregulated genes, more closely associated with chondrogenesis, are marked by H3K36me3 in gene bodies, highly increased H3K4me3 and H3K9ac on promoters and 5' end of genes, and increased H3K27ac and H3K4me1 marking in at least one enhancer region per upregulated gene. Within the 7-day time frame, changes in promoter DNA methylation do not correlate significantly with changes in gene expression. Inter-donor variability analysis shows high level of similarity between the donors for this data set. Conclusions: Histone modifications, rather than DNA methylation, provide the primary epigenetic control of early differentiation of MSCs towards the chondrogenic lineage.Stem Cell and Regenerative Biolog