Aspects of the biology of the freshwater crayfish Euastacus spinifer (Heller) (Decapoda: parastacidae)

A study of the freshwater crayfish Ehastacus spinifer (Heller) was conducted near Sydney, N.S.W., with the aim of describing the reproduction, growth, population structure and feeding habits of this crayfish under natural conditions. Reproductive mechanisms were compared to those of other parastacids, and seasonal reproductive activity was determined from changes through time in the breeding condition of wild females. The gonopore setae of females and the genital papillae of males were established as field indicators of maturity by comparison with laboratory determinations of gonad weight and maturity, and, in the case of females, with breeding condition in the wild population. Sizes at the attainment of maturity were thus determined for both males and females, and two reproductive types of males were described. Population structure was interpreted from the composition of catches, according to the results of tests for equal average catchabilities of crayfish in different sex- and size-groups based on recapture data. Studies of growth were based primarily on the resuls of mark-recapture studies, and a number of statistical methods were combined to form a routine for the extraction of information on moult increments from mark—recapture data

The CBM-opathies—A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 Complex

The caspase recruitment domain family member 11 (CARD11 or CARMA1)—B cell CLL/lymphoma 10 (BCL10)—MALT1 paracaspase (MALT1) [CBM] signalosome complex serves as a molecular bridge between cell surface antigen receptor signaling and the activation of the NF-κB, JNK, and mTORC1 signaling axes. This positions the CBM complex as a critical regulator of lymphocyte activation, proliferation, survival, and metabolism. Inborn errors in each of the CBM components have now been linked to a diverse group of human primary immunodeficiency diseases termed “CBM-opathies.” Clinical manifestations range from severe combined immunodeficiency to selective B cell lymphocytosis, atopic disease, and specific humoral defects. This surprisingly broad spectrum of phenotypes underscores the importance of “tuning” CBM signaling to preserve immune homeostasis. Here, we review the distinct clinical and immunological phenotypes associated with human CBM complex mutations and introduce new avenues for targeted therapeutic intervention

IL-4Rα on CD4\u3csup\u3e+\u3c/sup\u3e T cells plays a pathogenic role in respiratory syncytial virus reinfection in mice infected initially as neonates

RSV is the major cause of severe bronchiolitis in infants, and severe bronchiolitis as a result of RSV is associated with subsequent asthma development. A biased Th2 immune response is thought to be responsible for neonatal RSV pathogenesis; however, molecular mechanisms remain elusive. Our data demonstrate, for the first time, that IL-4Rα is up-regulated in vitro on human CD4+ T cells from cord blood following RSV stimulation and in vivo on mouse pulmonary CD4+ T cells upon reinfection of mice, initially infected as neonates. Th cell-specific deletion of Il4ra attenuated Th2 responses and abolished the immunopathophysiology upon reinfection, including airway hyper-reactivity, eosinophilia, and mucus hyperproduction in mice infected initially as neonates. These findings support a pathogenic role for IL-4Rα on Th cells following RSV reinfection of mice initially infected as neonates; more importantly, our data from human cells suggest that the same mechanism occurs in humans

Influence of Common Non-Synonymous Toll-like Receptor 4 Polymorphisms on Bronchopulmonary Dysplasia and Prematurity in Human Infants

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease and major risk factor for severe respiratory syncytial virus (RSV) infection among preterm infants. The Toll-like receptor 4 (TLR4) is involved in oxidative injury responses in the lungs. Two non-synonymous single nucleotide polymorphisms in the TLR4 gene have been associated with RSV infection in children. However, it is unclear to what extent this association is confounded by BPD or prematurity. In this study, we analyzed two population-based cohorts of preterm infants at risk for BPD as well as ethnicity-matched infants born at term, to test whether the TLR4 polymorphisms Asp299Gly (rs4986790) and Thr399Ile (rs4986791) are independently associated with BPD or premature birth. In a Canadian cohort (n = 269) composed of a majority of Caucasian preterm infants (BPD incidence of 38%), the TLR4-299 heterozygous genotype was significantly under-represented in infants without BPD (1.6% of infants versus 12% in infants with severe BPD) after adjusting for twins, ethnicity, gestational age, birth weight and gender (p = 0.014). This association was not replicated in a Finnish cohort (n = 434) of premature singletons or first-born siblings of Caucasian descent, although the incidence of BPD was substantially lower in this latter population (15%). We did not detect a significant association (>2-fold) between TLR4 genotypes and prematurity (p>0.05). We conclude that these TLR4 genotypes may have, at best, a modest influence on BPD severity in some populations of high-risk preterm infants. Further studies are warranted to clarify how clinical heterogeneity may impact genetic susceptibility to BPD

IVIg and LPS Co-stimulation Induces IL-10 Production by Human Monocytes, Which Is Compromised by an FcγRIIA Disease-Associated Gene Variant

Intravenous Immunoglobulin (IVIg) is used to treat autoimmune or inflammatory diseases, but its mechanism of action is not completely understood. We asked whether IVIg can induce interleukin-10 (IL-10) and reduce pro-inflammatory cytokine production in human monocytes, and whether this response is reduced in monocytes from people with an Fcγ receptor IIA (FcγRIIA) gene variant, which is associated with increased risk of inflammatory diseases and poor response to antibody-based biological therapy. IVIg increased IL-10 production and reduced pro-inflammatory cytokine production in response to bacterial lipopolysaccharide (LPS), which required FcγRI and FcγRIIB and activation of MAPKs, extracellular signal-regulated kinase 1/2 (ERK1/2), and p38. IL-10 production was lower and pro-inflammatory cytokine production was higher in monocytes from people with the FcγRIIA risk variant and the risk variant prevented IL-10 production in response to (IVIg+LPS). Finally, we show that IVIg did not induce MAPK activation in monocytes from people with the risk variant. Our results demonstrate that IVIg can skew human monocytes to an anti-inflammatory, IL-10-producing activation state, which is compromised in monocytes from people with the FcγRIIA risk variant. This research has profound implications for the use of IVIg because 25% of the population is homozygous for the FcγRIIA risk variant and its efficacy may be reduced in those individuals. In addition, this research may be useful to develop new therapeutic strategies to replace IVIg by cross-linking FcγRIs and FcγRIIBs to promote anti-inflammatory macrophage activation, independent of the FcγRIIA genotype

Comparison of Questionnaire Responses with Biomarkers of Tobacco Smoke Exposure in A Canadian Birth Cohort at Three Months of Age

Background Exposure to tobacco smoke increases the risk for several adverse health effects in children including wheeze, asthma, and asthma exacerbation. Accurately assessing tobacco smoke exposure is important for understanding and preventing these health effects. Questionnaires are a flexible and relatively inexpensive method of assessing exposure, but biomarkers of tobacco smoke exposure are considered more accurate. We developed questionnaire-based exposure models predicting urinary levels of biomarkers cotinine and trans-3’-hydroxycotinine (3HC) (metabolites of nicotine) in 3-month old infants using parent-reported questionnaire responses about tobacco smoke exposure from the Canadian Healthy Infant Longitudinal Development (CHILD) Study. Methods We used a manual model building process to build multiple linear regression models predicting urinary concentrations of cotinine, 3HC, and the sum of cotinine and 3HC on a molar basis (Cot+3HC) for 987, 1003, and 983 infants, respectively. Questions were included on the infant’s exposure assessed at 3 months of age and tobacco smoke odour in the home. We also included questions on maternal smoking status and history, passive exposure, and family socio-economic status assessed during pregnancy, as potential indirect measures of the infant’s exposure at 3 months. Adjusted R2 values were maximized in the final models. Results During pregnancy, the prevalence of maternal smoking was 2.4 %, and 115 (11.4 %) mothers reported smoking by at least 1 person at home. Of the 144 (14.3 %) infants whose mothers reported that smoking occurred at home when their child was 3 months, 129 (89.6%) and 136 (94.4%) had cotinine and 3HC levels above the detection limit (0.03 ng/mL), respectively. Of the 811 infants who had no parent-reported exposure at 3 months, 538 (66.3%) and 715 (88.2%) had detectable cotinine and 3HC levels, respectively. After correcting for urine dilution, the geometric mean levels were 0.085 ng/mL for cotinine, 0.20 ng/mL for 3HC, and 1.62 picomole/mL for Cot+3HC. The final questionnaire models explained 43.4%, 41.0%, and 42.9% of the variance in cotinine, 3HC, and Cot+3HC levels, respectively. Conclusions Our results indicate that exposure of these infants to tobacco smoke is not completely captured by questionnaires, suggesting that exposure assessment could be improved by using a combination of biomarker and questionnaire methods. Though more detectable, the inclusion of 3HC did not increase the ability of the questionnaires to explain variance in metabolite levels, but 3HC may be important since the ratio of 3HC to cotinine can be used to quantify the rate of nicotine metabolism and variation within population

Ethnic differences in maternal diet in pregnancy and infant eczema

Background The global prevalence of childhood eczema has increased over the last few decades, with a marked increase in high-income countries. Differences in prevalence of childhood eczema between countries and ethnicities suggest that genetic and early modifiable environmental factors, such as dietary intake, may underlie this observation. To investigate the association between pregnancy diet and infant eczema in a consortium of prospective Canadian birth cohorts predominantly comprised of white Europeans and South Asians. Methods We evaluated the association of maternal dietary patterns reported during pregnancy (assessed at 24–28 weeks gestation using a semi-quantitiative food-frequency questionnaire) with parent-reported physician-diagnosed infant eczema at 1-year from 2,160 mother-infant pairs. Using three dietary patterns (“Western”, “plant-based”, and “Balanced”) previously derived in this cohort using principal component analysis, we used multivariable logistic regression to determine the association of these dietary patterns with infant eczema, adjusted for potential confounders. Results We observed a lower odds of eczema in the full sample combining white Europeans and South Asians with greater adherence to a plant-based (OR = 0.65; 95% CI: 0.55, 0.76; <0.001) and Western dietary pattern (OR = 0.73; 95% CI: 0.60, 0.89; P<0.01), after adjusting for other known predictors of eczema, including ethnicity, which was not significant. No associations were observed for the balanced diet. An interaction between the Western diet and ethnicity was observed (P<0.001). Following stratification by ethnicity, a protective association between the plant-based diet and infant eczema was confirmed in both white Europeans (OR = 0.59; 95% CI: 0.47, 0.74; P<0.001) and South Asians (OR = 0.77; 95% CI: 0.61, 0.97; P = 0.025). In white Europeans only, a Western diet was associated with a lower odds of infant eczema (OR = 0.69; 95% CI: 0.56, 0.87; P = 0.001) while a balanced diet increased the odds of infant eczema (OR = 1.23; 95% CI: 1.02, 1.49; P = 0.03). Beyond a plant-based diet, no significant associations with other dietary patterns were observed in South Asians. Conclusion A plant-based diet during pregnancy is associated with a lowered odds of infant eczema at 1 year in all participants. Future studies of the components of plant-based diet which underlie the lower risk of eczema are needed