The role of sex chromosomes and sex hormones in vocal learning systems.

Vocal learning is the ability to imitate and modify sounds through auditory experience, a rare trait found in only a few lineages of mammals and birds. It is a critical component of human spoken language, allowing us to verbally transmit speech repertoires and knowledge across generations. In many vocal learning species, the vocal learning trait is sexually dimorphic, where it is either limited to males or present in both sexes to different degrees. In humans, recent findings have revealed subtle sexual dimorphism in vocal learning/spoken language brain regions and some associated disorders. For songbirds, where the neural mechanisms of vocal learning have been well studied, vocal learning appears to have been present in both sexes at the origin of the lineage and was then independently lost in females of some subsequent lineages. This loss is associated with an interplay between sex chromosomes and sex steroid hormones. Even in species with little dimorphism, like humans, sex chromosomes and hormones still have some influence on learned vocalizations. Here we present a brief synthesis of these studies, in the context of sex determination broadly, and identify areas of needed investigation to further understand how sex chromosomes and sex steroid hormones help establish sexually dimorphic neural structures for vocal learning.

Estrogen and sex-dependent loss of the vocal learning system in female zebra finches.

Sex hormones alter the organization of the brain during early development and coordinate various behaviors throughout life. In zebra finches, song learning is limited to males, with the associated song learning brain pathways only maturing in males and atrophying in females. While this atrophy can be prevented by treating females with exogenous estrogen during early post-hatch development, the requirement of estrogen during normal male song system development is uncertain. For the first time in songbirds, we administered exemestane, a potent third generation estrogen synthesis inhibitor, from the day of hatching until adulthood in order to reassess the role of estrogen in song circuit development. We examined the behavior, brain anatomy, and transcriptomes of individual song nuclei in these pharmacologically manipulated animals. We found that males with long-term exemestane treatment had diminished male-specific plumage and impaired song learning, but minimal effect on song nuclei sizes and their specialized transcriptome. Consistent with prior findings, females with long-term estrogen treatment retained a functional song system with song nuclei that had specialized gene expression similar, but not identical to males. We also observed that different song nuclei responded to estrogen manipulation differently, with Area X in the striatum being the most altered by estrogen modulation. These findings support the hypothesis that song learning is an ancestral trait in both sexes that was subsequently suppressed in females of some species and that estrogen has come to play a critical role in modulating this suppression as well as refinement of song learning.

Efficacy of the fibrosis index for predicting end-stage renal disease in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: Kidney involvement is a major manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and may progress to end-stage renal disease (ESRD), requiring renal replacement therapy. Unfortunately, there is no reliable kidney-specific index for predicting the progression of renal disease to ESRD. The fibrosis index (FI) reflects the degree of fibrosis in chronic liver disease. This study aimed to investigate whether the FI at the time of diagnosis could predict the development of ESRD in AAV patients. METHODS: We retrospectively reviewed the medical records of 211 immunosuppressive drug-naïve AAV patients and extrapolated the cut-off FI value for predicting the development of ESRD using receiver operating characteristic curves. The associations between the FI and clinical outcomes, including mortality, relapse, and ESRD development, were determined. RESULTS: Overall, 39 (18.5%) patients developed ESRD owing to the progression of AAV-associated renal disease. The median FI was higher in AAV patients with ESRD than in those without (1.61 vs 1.04; P = .001). The FI cut-off was 1.72. The incidence of ESRD was higher in patients with FI ≥ 1.72 at the time of diagnosis than in those with an FI < 1.72 at the time of diagnosis (relative risk: 4.655; 95% confidence interval: 2.242-9.662; P < .001). Kaplan-Meier survival analysis revealed that patients with an FI ≥ 1.72 at the time of diagnosis exhibited significantly lower ESRD-free survival rates than those with an FI < 1.72 at the time of diagnosis (P < .001). CONCLUSION: FI ≥ 1.72 at the time of diagnosis may be an independent predictive marker for ESRD in AAV patients.

Esophageal microbiome in eosinophilic esophagitis.

OBJECTIVE: The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE) is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis. DESIGN: In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD) and normal mucosa using the Esophageal String Test (EST). Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease. RESULTS: Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects. CONCLUSIONS: Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD.