An approach to solving problems of growth retardation in the child and teenager.

The physician who looks after children and teenagers is often confronted with the problem of short stature or growth failure. Common causes of growth failure include genetic background, intrauterine disease, malnutrition, chronic illness and hormonal disorders; some cases are attributed to mental retardation or primary central nervous system disease. A major concern in the evaluation of these patients is when, and how extensively, to investigate the problem. From a practical standpoint assessment can be related to height percentiles. The aims of treatment are a) to identify and treat appropriately the patients in whom there is an organic cause and b) to provide psychologic counselling and support.     

Nrf2b, novel zebrafish paralog of oxidant-responsive transcription factor NF-E2-related factor 2 (NRF2)

NF-E2-related factor 2 (NRF2; also called NFE2L2) and related NRF family members regulate antioxidant defenses by activating gene expression via antioxidant response elements (AREs), but their roles in embryonic development are not well understood. We report here that zebrafish (Danio rerio), an important developmental model species, possesses six nrf genes, including duplicated nrf1 and nrf2 genes. We cloned a novel zebrafish nrf2 paralog, nrf2b. The predicted Nrf2b protein sequence shares several domains with the original Nrf2 (now Nrf2a) but lacks the Neh4 transactivation domain. Zebrafish-human comparisons demonstrate conserved synteny involving nrf2 and hox genes, indicating that nrf2a and nrf2b are co-orthologs of human NRF2. nrf2a and nrf2b displayed distinct patterns of expression during embryonic development; nrf2b was more highly expressed at all stages. Embryos in which Nrf2a expression had been knocked down with morpholino oligonucleotides were more sensitive to tert-butylhydroperoxide but not tert-butylhydroquinone, whereas knockdown of Nrf2b did not affect sensitivity of embryos to either chemical. Gene expression profiling by microarray identified a specific role for Nrf2b as a negative regulator of several genes, including p53, cyclin G1, and heme oxygenase 1, in embryos. Nrf2a and Nrf2b exhibited different mechanisms of cross-talk with the Ahr2 signaling pathway. Together, these results demonstrate distinct roles for nrf2a and nrf2b, consistent with subfunction partitioning, and identify a novel negative regulatory role for Nrf2b during development. The identification of zebrafish nrf2 co-orthologs will facilitate new understanding of the multiple roles of NRF2 in protecting vertebrate embryos from oxidative damage.     

Co-selection of antibiotic and metal resistance

There is growing concern that metal contamination functions as a selective agent in the proliferation of antibiotic resistance. Documented associations between the types and levels of metal contamination and specific patterns of antibiotic resistance suggest that several mechanisms underlie this co-selection process. These co-selection mechanisms include co-resistance (different resistance determinants present on the same genetic element) and cross-resistance (the same genetic determinant responsible for resistance to antibiotics and metals). Indirect but shared regulatory responses to metal and antibiotic exposure such as biofilm induction also represent potential co-selection mechanisms used by prokaryotes. Metal contamination, therefore, represents a long-standing, widespread and recalcitrant selection pressure with both environmental and clinical importance that potentially contributes to the maintenance and spread of antibiotic resistance factors.     

Integrating the costs of plant toxins and predation risk in foraging decisions of a mammalian herbivore

Foraging herbivores must satisfy their nutrient requirements in a world of toxic plants while also avoiding predators. Plant toxins and perceived predation risk at food patches should both reduce patch residency time, but the relative strengths of these factors on feeding decisions has rarely been quantified. Using an arboreal generalist herbivore, the common brushtail possum Trichosurus vulpecula, we tested the effects on food intake of the plant toxin, cineole, and regurgitated pellets from one of its predators, the powerful owl Ninox strenua at the small spatial scale of the food patch. We used the giving-up density (GUD) framework, with animals harvesting food items (sultanas) in an inedible matrix (small pebbles). We ran two consecutive field experiments in a eucalypt woodland in eastern Australia, 1 month apart in the same location. In experiment 1, there was a significant interaction between cineole [at 17% of dry matter (DM)] and owl pellets. The GUD was lowest in the absence of both cineole and owl pellet, intermediate in the presence of owl pellet; and highest with cineole ± owl pellet. The effect of owl pellet diminished over time. In experiment 2, only cineole (at 10% DM) increased the GUD significantly. The difference in effect of owl pellet was probably due to both habituation and freshness of the cue. Our study demonstrates the importance of synthesising predator–prey and plant–herbivore ecology to better understand the complex set of constraints influencing foraging herbivores. The greater effect of toxin than fear on possums is likely to be due to its high, but ecologically relevant concentration. This highlights the need to explore the relative and net impacts of a range of concentrations of plant toxins and predation risks.