Trichinella spiralis: macrophage activity and antibody response in chronic murine infection

The role of macrophages, their products, and the specific antibody response were examined during chronic Trichinella spiralis infection in BALB/c mice. Adult T. spiralis in intestines were detected from 5 to 20 dpi. Muscle larvae numbers peaked at 45 dpi and thereafter a reduction was noted. The highest numbers of macrophages in the peritoneal cavity of infected mice were obtained up to 30 dpi. The production of NO by macrophages in infected mice was suppressed at 5 dpi, and then NO release increased until 45 dpi. The levels of NO in plasma and urine were lower in infected mice during the entire experiment in comparison to control. The production of O(2)(-) in peritoneal macrophages was inhibited during the first two weeks after infection and then increased until 90 dpi. Circulating T. spiralis antigens in plasma and urine were detected from 5 to 30 dpi. Specific IgM and IgA in serum increased until 20 dpi. IgG, IgG(1), and IgG(2) levels in serum increased until 60 dpi.     

Waist circumference and BMI cut-off based on 10-year cardiovascular risk: evidence for "central pre-obesity"

Objective: The objective was to assess the waist circumference (WC) cut‐off point that best identifies a level of 10‐year cardiovascular disease (CVD) risk with optimal balance of sensitivity and specificity in Chinese subjects according to their predicted 10‐year CVD risk. Research Methods and Procedures: A community‐based cross‐sectional observational study involving 14,919 Hong Kong Chinese subjects. The 10‐year CVD risk based on various prediction models was calculated. The projected WC cut‐off points were then determined. Results: There were 4837 (32.4%) men and 10,082 (67.6%) women (mean age ± standard deviation, 47.3 ± 13.5 years; age range, 18 to 93 years; median age, 45.0 years). The mean optimal WC or BMI predicting a 15% to 30% 10‐year CVD risk were 83 to 88 cm and 25 kg/m² for men, and 76 cm and 23 kg/m² for women, respectively. With WC ≥90 cm in men and ≥80 cm in women, the likelihood ratio at various WC cut‐off points to develop a ≥20% 10‐year CVD risk is 1.5 to 2.0 in men and 3.0 in women. The likelihood ratio was 1.5 in men with WC at 84 cm and in women at 70 cm. Discussion: Our results agree with the present guidelines on the definition of general and central obesity in Asia‐Pacific regions. We propose the creation of an intermediate state of high WC, the “central pre‐obesity” for Chinese men with WC ≥84 to 90 cm (≥33 to 36 inches) and women with WC ≥74 to 80 cm (≥29 to 32 inches). People with central pre‐obesity, similar to those with overweight (BMI ≥23 to 25 kg/m²), already have an increased risk of co‐morbidities.     

Application of menthol to the skin of whole trunk in mice induces autonomic and behavioral heat-gain responses

When ambient temperature is decreased in mammals, autonomic and behavioral heat-gain responses occur to maintain their core temperatures. However, what molecules in cutaneous sensory nerve endings mediate cooling-induced responses is unclear. Recently, transient receptor potential melastatin-8 (TRPM8) has been identified in cell bodies of sensory neurons as low-temperature and menthol-activated cation channel. We hypothesized that TRPM8 mediates cooling-induced autonomic and behavioral heat-gain responses. To activate TRPM8 specifically, we applied 1-10% menthol to the skin of whole trunk in mice instead of cooling and measured core temperatures and autonomic and behavioral heat-gain responses. Solvent of menthol (100% ethanol) was used as control. Significant elevation of core temperatures was observed between 20 and 120 min after menthol application. Pretreatment with diclofenac sodium, an antipyretic drug, did not affect this hyperthermia, indicating that the menthol-induced hyperthermia is not fever. Menthol application induced a rise in oxygen consumption, shivering-like muscle activity, tail skin vasoconstriction (autonomic responses), and heat-seeking behavior. All of them are typical heat-gain responses. These results support the hypothesis that TRPM8 mediates cooling-induced autonomic and behavioral heat-gain responses.     

Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 1: Synthesis of triplet drugs with morphinan skeletons

We synthesized symmetrical and nonsymmetrical triplet drugs with 1,3,5-trioxazatriquinane skeletons. The isolation of key intermediates, oxazoline dimers, made it possible to effectively produce nonsymmetrical triplets. Among the synthesized triplets, KNT-93, composed of three identical opioid μ receptor agonists, showed dose-dependent antinociception via the μ receptor. The effect was 56-fold more potent than that of morphine, a representative μ agonist. The profound analgesic effect induced by KNT-93 might result from simultaneous occupation of three μ opioid receptors.     

Repeatability of nest predation in passerines depends on predator species and time scale

It has been proposed that some specific locations of bird's nests have higher intrinsic chances of being depredated than other locations. This predicts that fates of consecutive nesting attempts at the same site should be repeatable. We used 20 pairs of old thrush nests to simulate repeated nesting attempts at the same sites, both within and between breeding seasons (n=40  sites×2  trials×2  years=160). Each nest was monitored by a camera to record multiple predation events and to identify predators. Predation by all predator species was repeatable during a 15-day trial. Predation by principal predators (jay Garrulus glandarius , marten Martes martes / foina ) and total predation (all species combined) was not correlated within pairs of simultaneously exposed nests or within samples of nests from particular study plot, and not repeatable for individual nests between-trials or between-years. These findings suggest short-term effect of predator memory causing revisitation of previously depredated nests during a current nesting trial (all predators); do not support an effect of nest site features on multiple nest discoveries and/or an effect of nest location on repeated random encounters with the same nest (principal predators). Long-term repeatability and correlation within pairs of simultaneously exposed nests was detectable only in occasional predators (great spotted woodpecker Dendrocopos major , possibly also squirrel Sciurus vulgaris ), which suggests effect of nest location combined with site fidelity and individual foraging specialization of these predators. We conclude that repeatability of nest predation depends on the time scale considered and the local predator community. We caution against spurious findings of repeatable nest predation resulting simply from statistical properties of correlation in binary data (nest fates).     

Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2

Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR)?=?1.03, 95% CI 1.00-1.06, p?=?0.023). There was evidence for heterogeneity in the ORs among studies (I(2)?=?49.3%; p?=?<0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR?=?0.89, 95%CI 0.80-1.00, p?=?0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.     

Inference of gene pathways using mixture Bayesian networks

Background  

Inference of gene networks typically relies on measurements across a wide range of conditions or treatments. Although one network structure is predicted, the relationship between genes could vary across conditions. A comprehensive approach to infer general and condition-dependent gene networks was evaluated. This approach integrated Bayesian network and Gaussian mixture models to describe continuous microarray gene expression measurements, and three gene networks were predicted.