Accounting for uncertainty in marine reserve design

Ecosystems and the species and communities within them are highly complex systems that defy predictions with any degree of certainty. Managing and conserving these systems in the face of uncertainty remains a daunting challenge, particularly with respect to developing networks of marine reserves. Here we review several modelling frameworks that explicitly acknowledge and incorporate uncertainty, and then use these methods to evaluate reserve spacing rules given increasing levels of uncertainty about larval dispersal distances. Our approach finds similar spacing rules as have been proposed elsewhere – roughly 20–200 km – but highlights several advantages provided by uncertainty modelling over more traditional approaches to developing these estimates. In particular, we argue that uncertainty modelling can allow for (1) an evaluation of the risk associated with any decision based on the assumed uncertainty; (2) a method for quantifying the costs and benefits of reducing uncertainty; and (3) a useful tool for communicating to stakeholders the challenges in managing highly uncertain systems. We also argue that incorporating rather than avoiding uncertainty will increase the chances of successfully achieving conservation and management goals.     

Effect of gastric bypass on spontaneous growth hormone and ghrelin release profiles

Objective : The purpose of this study was to analyze growth hormone (GH) concentrations in obese women before and after Roux‐en‐Y gastric bypass (RYGBP) and how resulting changes in weight, fat mass, ghrelin levels, and insulin sensitivity affect GH secretion. Research Methods and Procedures : Blood was sampled at 20‐minute intervals for 24 hours in 10 non‐diabetic premenopausal severely obese women before and 6 months after RYGBP. GH concentrations were measured in all samples, and serum ghrelin was collected at five time‐points. Results : After a 27% BMI drop (55.9 ± 6.2 to 40.7 ± 5.8 kg/m²), blunted GH profiles underwent partial recovery. Basal, postprandial, and mean ghrelin concentrations were not changed. A negative correlation was found between mean GH levels and insulin and homeostasis model assessment (p < 0.01). BMI accounted for 54% of GH variation. Discussion : Partial recovery of GH secretion after RYGBP‐induced weight loss suggests that a blunted secretion is not a causal factor of obesity but a consequence of the obese state and does not seem to be ghrelin‐level dependent.     

Skp2B attenuates p53 function by inhibiting prohibitin

The F‐box protein Skp2 and its isoform Skp2B are both overexpressed in breast cancers. Skp2 alters the activity of p53 by inhibiting its interaction with p300 and by promoting p300 degradation. Here, we report that Skp2B also attenuates the activity of p53; however, this effect is independent of p300, suggesting that another mechanism might be involved. Prohibitin, a protein reported to activate p53, was isolated in a two‐hybrid screen with the carboxy‐terminal domain unique to Skp2B. We observed that prohibitin is a new substrate of Skp2B and that the degradation of prohibitin is responsible for the attenuated activity of p53 in cells overexpressing Skp2B. Furthermore, we show that the activity of p53 is reduced in the mammary glands of Skp2B transgenic mice. This study indicates that both Skp2 and Skp2B attenuate p53 activity through different pathways, suggesting that amplification of the Skp2 locus represents a powerful mechanism to attenuate p53 function in cancer.     

Unexpected diversity and photoperiod dependence of the zebrafish melanopsin system

Animals have evolved specialized photoreceptors in the retina and in extraocular tissues that allow them to measure light changes in their environment. In mammals, the retina is the only structure that detects light and relays this information to the brain. The classical photoreceptors, rods and cones, are responsible for vision through activation of rhodopsin and cone opsins. Melanopsin, another photopigment first discovered in Xenopus melanophores (Opn4x), is expressed in a small subset of retinal ganglion cells (RGCs) in the mammalian retina, where it mediates non-image forming functions such as circadian photoentrainment and sleep. While mammals have a single melanopsin gene (opn4), zebrafish show remarkable diversity with two opn4x-related and three opn4-related genes expressed in distinct patterns in multiple neuronal cell types of the developing retina, including bipolar interneurons. The intronless opn4.1 gene is transcribed in photoreceptors as well as in horizontal cells and produces functional photopigment. Four genes are also expressed in the zebrafish embryonic brain, but not in the photoreceptive pineal gland. We discovered that photoperiod length influences expression of two of the opn4-related genes in retinal layers involved in signaling light information to RGCs. Moreover, both genes are expressed in a robust diurnal rhythm but with different phases in relation to the light-dark cycle. The results suggest that melanopsin has an expanded role in modulating the retinal circuitry of fish.     

Control of utilization of L-arginine, L-ornithine, agmatine, and putrescine as nitrogen sources in Escherichia coli K-12.

The regulation of the synthesis of the enzymes involved in the utilization of L-arginine, L-ornithine, agmatine, and putrescine as a sole nitrogen source in Escherichia coli K-12 was examined. The synthesis of agmatine ureohydrolase, putrescine aminotransferase, and pyrroline dehydrogenase is dually controlled by catabolite repression and nitrogen availability. Catabolite repression of agmatine ureohydrolase, but not that of putrescine aminotransferase or pyrroline dehydrogenase, is relieved by the addition of cAMP. Agmatine ureohydrolase synthesis in addition is subject to induction by L-arginine and agmatine. Arginine decarboxylase and ornithine decarboxylase synthesis is not sensitive to catabolite repression or to stimulation by nitrogen limitation or subject to substrate induction.     

PLK1 depletion alters homologous recombination and synaptonemal complex disassembly events during mammalian spermatogenesis

Homologous recombination (HR) is an essential meiotic process that contributes to the genetic variation of offspring and ensures accurate chromosome segregation. Recombination is facilitated by the formation and repair of programmed DNA double-strand breaks. These DNA breaks are repaired via recombination between maternal and paternal homologous chromosomes and a subset result in the formation of crossovers. HR and crossover formation is facilitated by synapsis of homologous chromosomes by a proteinaceous scaffold structure known as the synaptonemal complex (SC). Recent studies in yeast and worms have indicated that polo-like kinases (PLKs) regulate several events during meiosis, including DNA recombination and SC dynamics. Mammals express four active PLKs (PLK1–4), and our previous work assessing localization and kinase function in mouse spermatocytes suggested that PLK1 coordinates nuclear events during meiotic prophase. Therefore, we conditionally mutated Plk1 in early prophase spermatocytes and assessed stages of HR, crossover formation, and SC processes. Plk1 mutation resulted in increased RPA foci and reduced RAD51/DMC1 foci during zygonema, and an increase of both class I and class II crossover events. Furthermore, the disassembly of SC lateral elements was aberrant. Our results highlight the importance of PLK1 in regulating HR and SC disassembly during spermatogenesis.     

Comparative genetics of sex determination: masculinizing mutations in Caenorhabditis briggsae

The nematodes Caenorhabditis elegans and C. briggsae independently evolved self-fertile hermaphroditism from gonochoristic ancestors. C. briggsae has variably divergent orthologs of nearly all genes in the C. elegans sex determination pathway. Their functional characterization has generally relied on reverse genetic approaches, such as RNA interference and cross-species transgene rescue and more recently on deletion mutations. We have taken an unbiased forward mutagenesis approach to isolating zygotic mutations that masculinize all tissues of C. briggsae hermaphrodites. The screens identified loss-of-function mutations in the C. briggsae orthologs of tra-1, tra-2, and tra-3. The somatic and germline phenotypes of these mutations are largely identical to those of their C. elegans homologs, including the poorly understood germline feminization of tra-1(lf) males. This overall conservation of Cb-tra phenotypes is in contrast to the fem genes, with which they directly interact and which are significantly divergent in germline function. In addition, we show that in both C. briggsae and C. elegans large C-terminal truncations of TRA-1 that retain the DNA-binding domain affect sex determination more strongly than somatic gonad development. Beyond these immediate results, this collection of mutations provides an essential foundation for further comparative genetic analysis of the Caenorhabditis sex determination pathway.