Sex specific retinoic acid signaling is required for the initiation of urogenital sinus bud development

The mammalian urogenital sinus (UGS) develops in a sex specific manner, giving rise to the prostate in the male and the sinus vagina in the embryonic female. Androgens, produced by the embryonic testis, have been shown to be crucial to this process. In this study we show that retinoic acid signaling is required for the initial stages of bud development from the male UGS. Enzymes involved in retinoic acid synthesis are expressed in the UGS mesenchyme in a sex specific manner and addition of ligand to female tissue is able to induce prostate-like bud formation in the absence of androgens, albeit at reduced potency. Functional studies in mouse organ cultures that faithfully reproduce the initiation of prostate development indicate that one of the roles of retinoic acid signaling in the male is to inhibit the expression of Inhba, which encodes the βA subunit of Activin, in the UGS mesenchyme. Through in vivo genetic analysis and culture studies we show that inhibition of Activin signaling in the female UGS leads to a similar phenotype to that of retinoic acid treatment, namely bud formation in the absence of androgens. Our data also reveals that both androgens and retinoic acid have extra independent roles to that of repressing Activin signaling in the development of the prostate during fetal stages. This study identifies a novel role for retinoic acid as a mesenchymal factor that acts together with androgens to determine the position and initiation of bud development in the male UGS epithelia.     

Faunal response to benthic and hyporheic sedimentation varies with direction of vertical hydrological exchange

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A survey of entodiniomorphid ciliates in chimpanzees and bonobos

Intestinal entodiniomorphid ciliates are commonly diagnosed in the feces of wild apes of the genera Pan and Gorilla. Although some authors previously considered entodiniomorphid ciliates as possible pathogens, a symbiotic function within the intestinal ecosystem and their participation in fiber fermentation has been proposed. Previous studies have suggested that these ciliates gradually disappear under captive conditions. We studied entodiniomorphid ciliates in 23 captive groups of chimpanzees, three groups of captive bonobos and six populations of wild chimpanzees. Fecal samples were examined using Sheather's flotation and Merthiolate‐Iodine‐Formaldehyde Concentration (MIFC) methods. We quantified the number of ciliates per gram of feces. The MIFC method was more sensitive for ciliate detection than the flotation method. Ciliates of genus Troglodytella were detected in 13 groups of captive chimpanzees, two groups of bonobos and in all wild chimpanzee populations studied. The absence of entodiniomorphids in some captive groups might be because of the extensive administration of chemotherapeutics in the past or a side‐effect of the causative or prophylactic administration of antiparasitic or antibiotic drugs. The infection intensities of ciliates in captive chimpanzees were higher than in wild ones. We suppose that the over‐supply of starch, typical in captive primate diets, might induce an increase in the number of ciliates. In vitro studies on metabolism and biochemical activities of entodiniomorphids are needed to clarify their role in ape digestion. Am J Phys Anthropol 2010. © 2009 Wiley‐Liss, Inc.     

The Kimberley Assessment of Depression of Older Indigenous Australians: Prevalence of Depressive Disorders,Risk Factors and Validation of the KICA-dep Scale

Objective

This study aimed to develop a culturally acceptable and valid scale to assess depressive symptoms in older Indigenous Australians, to determine the prevalence of depressive disorders in the older Kimberley community, and to investigate the sociodemographic, lifestyle and clinical factors associated with depression in this population.

Methods

Cross-sectional survey of adults aged 45 years or over from six remote Indigenous communities in the Kimberley and 30% of those living in Derby, Western Australia. The 11 linguistic and culturally sensitive items of the Kimberley Indigenous Cognitive Assessment of Depression (KICA-dep) scale were derived from the signs and symptoms required to establish the diagnosis of a depressive episode according to the DSM-IV-TR and ICD-10 criteria, and their frequency was rated on a 4-point scale ranging from ‘never’ to ‘all the time’ (range of scores: 0 to 33). The diagnosis of depressive disorder was established after a face-to-face assessment with a consultant psychiatrist. Other measures included sociodemographic and lifestyle factors, and clinical history.

Results

The study included 250 participants aged 46 to 89 years (mean±SD = 60.9±10.7), of whom 143 (57.2%) were women. The internal reliability of the KICA-dep was 0.88 and the cut-point 7/8 (non-case/case) was associated with 78% sensitivity and 82% specificity for the diagnosis of a depressive disorder. The point-prevalence of a depressive disorder in this population was 7.7%; 4.0% for men and 10.4% for women. Heart problems were associated with increased odds of depression (odds ratio = 3.3, 95% confidence interval = 1.2,8.8).

Conclusions

The KICA-dep has robust psychometric properties and can be used with confidence as a screening tool for depression among older Indigenous Australians. Depressive disorders are common in this population, possibly because of increased stressors and health morbidities.     

Extensive diversity of intestinal trichomonads of non-human primates

Despite the fact that the non-human primates are our closest relatives and represent a species-rich mammalian group, little is known about their intestinal protistan parasites/commensals. Particularly, the intestinal trichomonads represent a neglected part of the fauna of the primate digestive system. We have established 30 trichomonad strains isolated from feces of 11 primate species kept in 3 Czech zoos and performed an analysis of their SSU rDNA and ITS1-5·8S rDNA-ITS2. Our results showed that intestinal trichomonads are rather common among non-human primates. Molecular phylogenetic analysis showed that the strains are unexpectedly diversified, belonging to 8 or 9 distinct species. Interestingly, the vast majority of the strains from non-human primates belonged to the genus Tetratrichomonas while no member of this genus has been found in the human intestine so far. In addition, hominoid and non-hominoid primates differed in their intestinal trichomonads. Our results suggest that captive primates possibly may be infected by intestinal trichomonads of other vertebrates such as pigs, cattle, birds, tortoises and lizards.     

Species Determination and Quantitation in Mixtures Using MRM Mass Spectrometry of Peptides Applied to Meat Authentication

We describe a simple protocol for identifying and quantifying the two components in binary mixtures of species possessing one or more similar proteins. Central to the method is the identification of ''corresponding proteins'' in the species of interest, in other words proteins that are nominally the same but possess species-specific sequence differences. When subject to proteolysis, corresponding proteins will give rise to some peptides which are likewise similar but with species-specific variants. These are ''corresponding peptides''. Species-specific peptides can be used as markers for species determination, while pairs of corresponding peptides permit relative quantitation of two species in a mixture. The peptides are detected using multiple reaction monitoring (MRM) mass spectrometry, a highly specific technique that enables peptide-based species determination even in complex systems. In addition, the ratio of MRM peak areas deriving from corresponding peptides supports relative quantitation. Since corresponding proteins and peptides will, in the main, behave similarly in both processing and in experimental extraction and sample preparation, the relative quantitation should remain comparatively robust. In addition, this approach does not need the standards and calibrations required by absolute quantitation methods. The protocol is described in the context of red meats, which have convenient corresponding proteins in the form of their respective myoglobins. This application is relevant to food fraud detection: the method can detect 1% weight for weight of horse meat in beef. The corresponding protein, corresponding peptide (CPCP) relative quantitation using MRM peak area ratios gives good estimates of the weight for weight composition of a horse plus beef mixture.     

Community Attitudes and Practices of Urban Residents Regarding Predation by Pet Cats on Wildlife: An International Comparison

International differences in practices and attitudes regarding pet cats'' interactions with wildlife were assessed by surveying citizens from at least two cities in Australia, New Zealand, the UK, the USA, China and Japan. Predictions tested were: (i) cat owners would agree less than non-cat owners that cats might threaten wildlife, (ii) cat owners value wildlife less than non-cat owners, (iii) cat owners are less accepting of cat legislation/restrictions than non-owners, and (iv) respondents from regions with high endemic biodiversity (Australia, New Zealand, China and the USA state of Hawaii) would be most concerned about pet cats threatening wildlife. Everywhere non-owners were more likely than owners to agree that pet cats killing wildlife were a problem in cities, towns and rural areas. Agreement amongst non-owners was highest in Australia (95%) and New Zealand (78%) and lowest in the UK (38%). Irrespective of ownership, over 85% of respondents from all countries except China (65%) valued wildlife in cities, towns and rural areas. Non-owners advocated cat legislation more strongly than owners except in Japan. Australian non-owners were the most supportive (88%), followed by Chinese non-owners (80%) and Japanese owners (79.5%). The UK was least supportive (non-owners 43%, owners 25%). Many Australian (62%), New Zealand (51%) and Chinese owners (42%) agreed that pet cats killing wildlife in cities, towns and rural areas was a problem, while Hawaiian owners were similar to the mainland USA (20%). Thus high endemic biodiversity might contribute to attitudes in some, but not all, countries. Husbandry practices varied internationally, with predation highest where fewer cats were confined. Although the risk of wildlife population declines caused by pet cats justifies precautionary action, campaigns based on wildlife protection are unlikely to succeed outside Australia or New Zealand. Restrictions on roaming protect wildlife and benefit cat welfare, so welfare is a better rationale.     

Complex modulation of peptidolytic activity of cathepsin D by sphingolipids

Cathepsin D is an aspartic peptidase involved in cellular processes including proliferation and apoptosis and implicated in human pathologies such as cancer and neurodegeneration. Our knowledge about the relationship between proteolysis and bioactive sphingolipids is still very limited. Here, we describe a complex pattern of modulation of the peptidolytic activity of cathepsin D by sphingolipids. A panel of sphingolipid derivatives was screened in a FRET-based assay; these molecules demonstrated negative or positive modulation of cathepsin D peptidolytic activity, depending on the sphingolipid structure. Certain sphingosines and ceramides inhibited cathepsin D in the submicromolar range, and structural requirements for this inhibitory effect were evaluated. The interaction of cathepsin D with sphingolipids was also demonstrated by fluorescence polarization measurements and determined to follow a competitive inhibition mode. In contrast, monoester phosphosphingolipids, especially ceramide-1-phosphate, were identified as activators of cathepsin D peptidolytic activity at submicromolar concentrations. Thus, sphingolipids and phosphosphingolipids, known to be antagonistic in their cell-signaling functions, displayed opposite modulation of cathepsin D. Sphingolipid-based modulators of cathepsin D are potentially involved in the control of cathepsin D-dependent processes and might serve as a scaffold for the development of novel regulators of this therapeutic target.     

Genetic determinants of serum testosterone concentrations in men

Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone''s high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10⁻⁴¹ and rs6258, p = 2.3×10⁻²²). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10⁻¹⁶). The rs6258 polymorphism in exon 4 of SHBG affected SHBG''s affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.