DNA Footprints: Using Parasites to Detect Elusive Animals, Proof of Principle in Hedgehogs

The Western European Hedgehog (Erinaceous europaeus) is a nocturnal animal that is in decline in much of Europe, but the monitoring of this species is subjective, prone to error, and an inadequate basis for estimating population trends. Here, we report the use of Crenosoma striatum, a parasitic nematode specific to hedgehogs as definitive hosts, to detect hedgehog presence in the natural environment. This is achieved through collecting and sampling the parasites within their intermediate hosts, gastropoda, a group much simpler to locate and sample in both urban and rural habitats. C. striatum and Crenosoma vulpis were collected post-mortem from the lungs of hedgehogs and foxes, respectively. Slugs were collected in two sessions, during spring and autumn, from Skomer Island (n = 21), which is known to be free of hedgehogs (and foxes); and Pennard, Swansea (n = 42), known to have a healthy hedgehog population. The second internal transcribed spacer of parasite ribosomal DNA was used to develop a highly specific, novel, PCR based multiplex assay. Crenosoma striatum was found only at the site known to be inhabited by hedgehogs, at an average prevalence in gastropods of 10% in spring and autumn. The molecular test was highly specific: One mollusc was positive for both C. striatum and C. vulpis, and differentiation between the two nematode species was clear. This study demonstrates proof of principle for using detection of specific parasite DNA in easily sampled intermediate hosts to confirm the presence of an elusive nocturnal definitive host species. The approach has great potential as an adaptable, objective tool to supplement and support existing ecological survey methods

High local substrate availability stabilizes a cooperative trait

Cooperative behavior is widely spread in microbial populations. An example is the expression of an extracellular protease by the lactic acid bacterium Lactococcus lactis, which degrades milk proteins into free utilizable peptides that are essential to allow growth to high cell densities in milk. Cheating, protease-negative strains can invade the population and drive the protease-positive strain to extinction. By using multiple experimental approaches, as well as modeling population dynamics, we demonstrate that the persistence of the proteolytic trait is determined by the fraction of the generated peptides that can be captured by the cell before diffusing away from it. The mechanism described is likely to be relevant for the evolutionary stability of many extracellular substrate-degrading enzymes

Effects of dietary Na+ deprivation on epithelial Na+ channel (ENaC), BDNF, and TrkB mRNA expression in the rat tongue

<p>Abstract</p> <p>Background</p> <p>In rodents, dietary Na⁺deprivation reduces gustatory responses of primary taste fibers and central taste neurons to lingual Na⁺stimulation. However, in the rat taste bud cells Na⁺deprivation increases the number of amiloride sensitive epithelial Na⁺channels (ENaC), which are considered as the "receptor" of the Na⁺component of salt taste. To explore the mechanisms, the expression of the three ENaC subunits (α, β and γ) in taste buds were observed from rats fed with diets containing either 0.03% (Na⁺deprivation) or 1% (control) NaCl for 15 days, by using <it>in situ </it>hybridization and real-time quantitative RT-PCR (qRT-PCR). Since BDNF/TrkB signaling is involved in the neural innervation of taste buds, the effects of Na⁺deprivation on BDNF and its receptor TrkB expression in the rat taste buds were also examined.</p> <p>Results</p> <p><it>In situ </it>hybridization analysis showed that all three ENaC subunit mRNAs were found in the rat fungiform taste buds and lingual epithelia, but in the vallate and foliate taste buds, only α ENaC mRNA was easily detected, while β and γ ENaC mRNAs were much less than those in the fungiform taste buds. Between control and low Na⁺fed animals, the numbers of taste bud cells expressing α, β and γ ENaC subunits were not significantly different in the fungiform, vallate and foliate taste buds, respectively. Similarly, qRT-PCR also indicated that Na⁺deprivation had no effect on any ENaC subunit expression in the three types of taste buds. However, Na⁺deprivation reduced BDNF mRNA expression by 50% in the fungiform taste buds, but not in the vallate and foliate taste buds. The expression of TrkB was not different between control and Na⁺deprived rats, irrespective of the taste papillae type.</p> <p>Conclusion</p> <p>The findings demonstrate that dietary Na⁺deprivation does not change ENaC mRNA expression in rat taste buds, but reduces BDNF mRNA expression in the fungiform taste buds. Given the roles of BDNF in survival of cells and target innervation, our results suggest that dietary Na⁺deprivation might lead to a loss of gustatory innervation in the mouse fungiform taste buds.</p

High Salt Intake Down-Regulates Colonic Mineralocorticoid Receptors, Epithelial Sodium Channels and 11β-Hydroxysteroid Dehydrogenase Type 2

Besides the kidneys, the gastrointestinal tract is the principal organ responsible for sodium homeostasis. For sodium transport across the cell membranes the epithelial sodium channel (ENaC) is of pivotal relevance. The ENaC is mainly regulated by mineralocorticoid receptor mediated actions. The MR activation by endogenous 11β-hydroxy-glucocorticoids is modulated by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Here we present evidence for intestinal segment specific 11β-HSD2 expression and hypothesize that a high salt intake and/or uninephrectomy (UNX) affects colonic 11β-HSD2, MR and ENaC expression. The 11β-HSD2 activity was measured by means of 3H-corticosterone conversion into 3H-11-dehydrocorticosterone in Sprague Dawley rats on a normal and high salt diet. The activity increased steadily from the ileum to the distal colon by a factor of about 3, an observation in line with the relevance of the distal colon for sodium handling. High salt intake diminished mRNA and protein of 11β-HSD2 by about 50% (p<0.001) and reduced the expression of the MR (p<0.01). The functionally relevant ENaC-β and ENaC-γ expression, a measure of mineralocorticoid action, diminished by more than 50% by high salt intake (p<0.001). The observed changes were present in rats with and without UNX. Thus, colonic epithelial cells appear to contribute to the protective armamentarium of the mammalian body against salt overload, a mechanism not modulated by UNX

Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors

Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous blood-brain tumor barrier of malignant brain tumor microvasculature. Small molecule systemic chemotherapy drugs maintain peak blood concentrations for only minutes, and therefore, do not accumulate to therapeutic concentrations within individual brain tumor cells. The physiologic upper limit of pore size in the blood-brain tumor barrier of malignant brain tumor microvasculature is approximately 12 nanometers. Spherical nanoparticles ranging between 7 nm and 10 nm in diameter maintain peak blood concentrations for several hours and are sufficiently smaller than the 12 nm physiologic upper limit of pore size in the blood-brain tumor barrier to accumulate to therapeutic concentrations within individual brain tumor cells. Therefore, nanoparticles bearing chemotherapy that are within the 7 to 10 nm size range can be used to deliver therapeutic concentrations of small molecule chemotherapy drugs across the blood-brain tumor barrier into individual brain tumor cells. The initial therapeutic efficacy of the Gd-G5-doxorubicin dendrimer, an imageable nanoparticle bearing chemotherapy within the 7 to 10 nm size range, has been demonstrated in the orthotopic RG-2 rodent malignant glioma model. Herein I discuss this novel strategy to improve the effectiveness of systemic chemotherapy for the treatment of malignant brain tumors and the therapeutic implications thereof

Seasonality in Human Zoonotic Enteric Diseases: A Systematic Review

BACKGROUND: Although seasonality is a defining characteristic of many infectious diseases, few studies have described and compared seasonal patterns across diseases globally, impeding our understanding of putative mechanisms. Here, we review seasonal patterns across five enteric zoonotic diseases: campylobacteriosis, salmonellosis, vero-cytotoxigenic Escherichia coli (VTEC), cryptosporidiosis and giardiasis in the context of two primary drivers of seasonality: (i) environmental effects on pathogen occurrence and pathogen-host associations and (ii) population characteristics/behaviour. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed published literature from 1960-2010, resulting in the review of 86 studies across the five diseases. The Gini coefficient compared temporal variations in incidence across diseases and the monthly seasonality index characterised timing of seasonal peaks. Consistent seasonal patterns across transnational boundaries, albeit with regional variations was observed. The bacterial diseases all had a distinct summer peak, with identical Gini values for campylobacteriosis and salmonellosis (0.22) and a higher index for VTEC (Gini  0.36). Cryptosporidiosis displayed a bi-modal peak with spring and summer highs and the most marked temporal variation (Gini = 0.39). Giardiasis showed a relatively small summer increase and was the least variable (Gini = 0.18). CONCLUSIONS/SIGNIFICANCE: Seasonal variation in enteric zoonotic diseases is ubiquitous, with regional variations highlighting complex environment-pathogen-host interactions. Results suggest that proximal environmental influences and host population dynamics, together with distal, longer-term climatic variability could have important direct and indirect consequences for future enteric disease risk. Additional understanding of the concerted influence of these factors on disease patterns may improve assessment and prediction of enteric disease burden in temperate, developed countries

ICAR: endoscopic skull‐base surgery

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Estrogen-dependent regulation of sodium/hydrogen exchanger-3 (NHE3) expression via estrogen receptor β in proximal colon of pregnant mice

Although constipation is very common during pregnancy, the exact mechanism is unknown. We hypothesized that the involvement of estrogen receptor (ER) in the regulation of electrolyte transporter in the colon leads to constipation. In this study, the intestines of normal female ICR mouse and pregnant mice were examined for the expression of ERβ and ERβ by immunohistochemistry and in situ hybridization. ERα, but not ERα, was expressed in surface epithelial cells of the proximal, but not distal, colon on pregnancy days 10, 15, and 18, but not day 5, and the number of ERα-positive cells increased signiWcantly during pregnancy. Expression of NHE3, the gene that harbors estrogen response element, examined by immunohistochemistry and western blotting, was localized in the surface epithelial cells of the proximal colon and increased in parallel with ERβ expression. In ovariectomized mice, NHE3 expression was only marginal and was up-regulated after treatment with 17- estradiol (E2), but not E 2 + ICI 182,780 (estrogen receptor antagonist). Moreover, knock-down of ERβ expression by electroporetically transfected siRNA resulted in a signiWcant reduction of NHE3 expression. These results indicate that ERβ regulates the expression of NHE3 in the proximal colon of pregnant mice through estrogen action, suggesting the involvement of increased sodium absorption by up-regulated NHE3 in constipation during pregnancy

Associação ecológica entre características dos municípios e o risco de homicídios em homens adultos de 20-39 anos de idade no Brasil, 1999-2010 Ecological association between characteristics of the municipalities and the risk of homicide in adult males aged 20 to 39 in Brazil: 1999-2010

No Brasil, a mortalidade por homicídios persiste como importante problema de saúde pública, principalmente entre homens adultos jovens. O objetivo do presente estudo foi analisar o risco de morte por homicídios entre homens de 20-39 anos de idade e sua associação com características sociodemográficas dos municípios brasileiros. Foi realizado estudo ecológico, tendo como unidades de análise todos os municípios do País. Foram estudadas as tendências temporais entre 1999-2010 e as associações do desfecho com indicadores dos municípios em análise transversal referente ao quatriênio 2007-2010. Entre os quatriênios 1999-2002 e 2007-2010, houve aumento das taxas medianas de mortalidade por homicídios entre homens de 20-39 anos, de 22,7 para 35,5 por 100 mil habitantes. No quatriênio 2007-2010, os riscos de homicídios foram estatisticamente superiores (p<0,001) nos municípios de maior porte populacional, maior taxa de fecundidade, baixa proporção de alfabetizados, maior desigualdade aferida pela renda 20/40 e maior urbanização. Para a proporção da população de baixa renda e renda média per capita, as associações indicam excessos nas estimativas de risco de homicídios nos municípios com valores intermediários desses indicadores. Os achados podem auxiliar na focalização de políticas públicas.<br>Homicide mortality remains a major public health problem in Brazil, especially among young adult males. The aim of this study was to assess the homicide mortality risk (HMR) among males aged 20 to 39, and its association with selected socio-demographic characteristics of the Brazilian municipalities. This is an ecologic study in which all the municipalities in Brazil were the unit of analysis. Time trends (from 1999-2002) and adjusted associations between HMR and socio-demographic characteristics of municipalities were estimated in a cross-sectional analysis for 2007-2010 in this study. Between 1999-2002 and 2007-2010, an increasing trend of mean HMR rates from 22.7 to 35.5 per 100,000 inhabitants was observed in Brazil. In 2007-2010, HMR rates were significantly higher (p<0.001) in the largest cities, with higher fertility rates, lower literacy rates, higher social inequality (as estimated by the 20/40 income ratio) and more-urbanized municipalities. Considering the proportion of low income population and the average per capita income, associations with HMR identified greater risks in the intermediary categories of these independent variables. Findings from this study may support the implementation of focal policies directed to more vulnerable municipalities