Risky business: the combined effects of fishing and changes in primary productivity on fish communities

There is an increasing need to understand ecosystem responses to multiple stressors in that such complex responses depend not only on species-level responses, but also on species interactions and ecosystem structure. In this study, we used a multi-model ecosystem simulation approach to explore the combined effects of fishing and primary productivity on different components of the food-web across a suite of ecosystems and a range of model types. Simulations were carried out under different levels of primary productivity and various fishing scenarios. In addition to exploring synergistic, additive or antagonistic combined effects of multiple stressors, we included a fourth category “dampened”, which refers to less negative or less positive impacts compared to additive ones, and in contrast to previous studies, we explicitly considered the direction (positive or negative) of the combined effects. We focused on two specific combined effects (negative synergism and positive dampened) associated with the risk of resultant lower fish biomass than expected under additive effects. Through a meta-analysis of the multi-models' simulation results, we found that (i) the risk of negative synergism was generally higher for low-trophic-level (LTL) taxa, implying that following an increase of fishing pressure on a given LTL stock, the subsequent decrease of biomass under low primary productivity would be larger than expected under additive effects and (ii) the risk of positive dampened effects was generally higher for high-trophic-level (HTL) taxa, implying that given a management measure aimed at reducing the impact of fishing on HTL stocks, the subsequent rebuilding of these stocks would be slower than expected. Our approach to categorizing and exploring cumulative effects can be applied to evaluate other community properties, and provide guidance for fisheries management

Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio

BACKGROUND: Treatment records and follow-up data on 40 patients with primary and metastatic liver malignancies who underwent a single whole-liver treatment with Y-90 resin microspheres (SIR-Spheres(® )Sirtex Medical, Lake Forest, IL) were retrospectively reviewed. The objective of the study was to evaluate the anatomic and physiologic determinants of radiation dose distribution, and the dose response of tumor and liver toxicity in patients with liver malignancies who underwent hepatic arterial Y-90 resin microsphere treatment. METHODS: Liver and tumor volume calculations were performed on pre-treatment CT scans. Fractional tumor and liver flow characteristics and lung shunt fractions were determined using hepatic arterial Tc-99m MAA imaging. Absorbed dose calculations were performed using the MIRD equations. Liver toxicity was assessed clinically and by liver function tests. Tumor response to therapy was assessed by CT and/or tumor markers. RESULTS: Of the 40 patients, 5 had hepatocellular cancer (HCC), and 35 had metastatic liver tumors (15 colorectal cancer, 10 neuroendocrine tumors, 4 breast cancer, 2 lung cancer, 1 ovarian cancer, 1 endometrial cancer, and 2 unknown primary adenocarcinoma). All patients were treated in a salvage setting with a 3 to 80 week follow-up (mean: 19 weeks). Tumor volumes ranged from 15.0 to 984.2 cc (mean: 294.9 cc) and tumor to normal liver uptake ratios ranged from 2.8 to 15.4 (mean: 5.4). Average administered activity was 1.2 GBq (0.4 to 2.4 GBq). Liver absorbed doses ranged from 0.7 to 99.5 Gy (mean: 17.2 Gy). Tumor absorbed doses ranged from 40.1 to 494.8 Gy (mean: 121.5 Gy). None of the patients had clinical venoocclusive disease or therapy-induced liver failure. Seven patients (17.5 %) had transient and 7 patients (17.5 %) had persistent LFT abnormalities. There were 27 (67.5%) responders (complete response, partial response, and stable disease). Tumor response correlated with higher tumor flow ratio as measured by Tc-99m MAA imaging. CONCLUSION: Doses up to 99.5 Gy to uninvolved liver are tolerated with no clinical venoocclusive disease or liver failure. The lowest tumor dose producing a detectable response is 40.1 Gy. The utilization of MAA-based imaging techniques to determine tumor and liver blood flow for clinical treatment planning and the calculation of administered activity may improve clinical outcomes

Ascending central canal dilation and progressive ependymal disruption in a contusion model of rodent chronic spinal cord injury

<p>Abstract</p> <p>Background</p> <p>Chronic spinal cord injury (SCI) can lead to an insidious decline in motor and sensory function in individuals even years after the initial injury and is accompanied by a slow and progressive cytoarchitectural destruction. At present, no pathological mechanisms satisfactorily explain the ongoing degeneration.</p> <p>Methods</p> <p>Adult female Sprague-Dawley rats were anesthetized laminectomized at T10 and received spinal cord contusion injuries with a force of 250 kilodynes using an Infinite Horizon Impactor. Animals were randomly distributed into 5 groups and killed 1 (n = 4), 28 (n = 4), 120 (n = 4), 450 (n = 5), or 540 (n = 5) days after injury. Morphometric and immunohistochemical studies were then performed on 1 mm block sections, 6 mm cranial and 6 mm caudal to the lesion epicenter. The SPSS 11.5 t test was used to determine differences between quantitative measures.</p> <p>Results</p> <p>Here, we document the first report of an ascending central canal dilation and progressive ependymal disruption cranial to the epicenter of injury in a contusion model of chronic SCI, which was characterized by extensive dural fibrosis and intraparenchymal cystic cavitation. Expansion of the central canal lumen beyond a critical diameter corresponded with ependymal cell ciliary loss, an empirically predictable thinning of the ependymal region, and a decrease in cell proliferation in the ependymal region. Large, aneurysmal dilations of the central canal were accompanied by disruptions in the ependymal layer, periependymal edema and gliosis, and destruction of the adjacent neuropil.</p> <p>Conclusion</p> <p>Cells of the ependymal region play an important role in CSF homeostasis, cellular signaling and wound repair in the spinal cord. The possible effects of this ascending pathology on ependymal function are discussed. Our studies suggest central canal dilation and ependymal region disruption as steps in the pathogenesis of chronic SCI, identify central canal dilation as a marker of chronic SCI and provide novel targets for therapeutic intervention.</p

The retinoid anticancer signal: mechanisms of target gene regulation

Retinoids induce growth arrest, differentiation, and cell death in many cancer cell types. One factor determining the sensitivity or resistance to the retinoid anticancer signal is the transcriptional response of retinoid-regulated target genes in cancer cells. We used cDNA microarray to identify 31 retinoid-regulated target genes shared by two retinoid-sensitive neuroblastoma cell lines, and then sought to determine the relevance of the target gene responses to the retinoid anticancer signal. The pattern of retinoid responsiveness for six of 13 target genes (RARβ2, CYP26A1, CRBP1, RGS16, DUSP6, EGR1) correlated with phenotypic retinoid sensitivity, across a panel of retinoid-sensitive or -resistant lung and breast cancer cell lines. Retinoid treatment of MYCN transgenic mice bearing neuroblastoma altered the expression of five of nine target genes examined (RARβ2, CYP26A1, CRBP1, DUSP6, PLAT) in neuroblastoma tumour tissue in vivo. In retinoid-sensitive neuroblastoma, lung and breast cancer cell lines, direct inhibition of retinoid-induced RARβ2 expression blocked induction of only one of eight retinoid target genes (CYP26A1). DNA demethylation, histone acetylation, and exogenous overexpression of RARβ2 partially restored retinoid-responsive CYP26A1 expression in RA-resistant MDA-MB-231 breast, but not SK-MES-1 lung, cancer cells. Combined, rather than individual, inhibition of DUSP6 and RGS16 was required to block retinoid-induced growth inhibition in neuroblastoma cells, through phosphorylation of extracellular-signal-regulated kinase. In conclusion, sensitivity to the retinoid anticancer signal is determined in part by the transcriptional response of key retinoid-regulated target genes, such as RARβ2, DUSP6, and RGS16

Bias and Evolution of the Mutationally Accessible Phenotypic Space in a Developmental System

Genetic and developmental architecture may bias the mutationally available phenotypic spectrum. Although such asymmetries in the introduction of variation may influence possible evolutionary trajectories, we lack quantitative characterization of biases in mutationally inducible phenotypic variation, their genotype-dependence, and their underlying molecular and developmental causes. Here we quantify the mutationally accessible phenotypic spectrum of the vulval developmental system using mutation accumulation (MA) lines derived from four wild isolates of the nematodes Caenorhabditis elegans and C. briggsae. The results confirm that on average, spontaneous mutations degrade developmental precision, with MA lines showing a low, yet consistently increased, proportion of developmental defects and variants. This result indicates strong purifying selection acting to maintain an invariant vulval phenotype. Both developmental system and genotype significantly bias the spectrum of mutationally inducible phenotypic variants. First, irrespective of genotype, there is a developmental bias, such that certain phenotypic variants are commonly induced by MA, while others are very rarely or never induced. Second, we found that both the degree and spectrum of mutationally accessible phenotypic variation are genotype-dependent. Overall, C. briggsae MA lines exhibited a two-fold higher decline in precision than the C. elegans MA lines. Moreover, the propensity to generate specific developmental variants depended on the genetic background. We show that such genotype-specific developmental biases are likely due to cryptic quantitative variation in activities of underlying molecular cascades. This analysis allowed us to identify the mutationally most sensitive elements of the vulval developmental system, which may indicate axes of potential evolutionary variation. Consistent with this scenario, we found that evolutionary trends in the vulval system concern the phenotypic characters that are most easily affected by mutation. This study provides an empirical assessment of developmental bias and the evolution of mutationally accessible phenotypes and supports the notion that such bias may influence the directions of evolutionary change

Experimental mutation-accumulation on the X chromosome of Drosophila melanogaster reveals stronger selection on males than females

<p>Abstract</p> <p>Background</p> <p>Sex differences in the magnitude or direction of mutational effect may be important to a variety of population processes, shaping the mutation load and affecting the cost of sex itself. These differences are expected to be greatest after sexual maturity. Mutation-accumulation (MA) experiments provide the most direct way to examine the consequences of new mutations, but most studies have focused on juvenile viability without regard to sex, and on autosomes rather than sex chromosomes; both adult fitness and X-linkage have been little studied. We therefore investigated the effects of 50 generations of X-chromosome mutation accumulation on the fitness of males and females derived from an outbred population of <it>Drosophila melanogaster</it>.</p> <p>Results</p> <p>Fitness declined rapidly in both sexes as a result of MA, but adult males showed markedly greater fitness loss relative to their controls compared to females expressing identical genotypes, even when females were made homozygous for the X. We estimate that these mutations are partially additive (h ~ 0.3) in females. In addition, the majority of new mutations appear to harm both males and females.</p> <p>Conclusions</p> <p>Our data helps fill a gap in our understanding of the consequences of sexual selection for genetic load, and suggests that stronger selection on males may indeed purge deleterious mutations affecting female fitness.</p

Estimating Heritabilities and Genetic Correlations: Comparing the ‘Animal Model’ with Parent-Offspring Regression Using Data from a Natural Population

Quantitative genetic parameters are nowadays more frequently estimated with restricted maximum likelihood using the ‘animal model’ than with traditional methods such as parent-offspring regressions. These methods have however rarely been evaluated using equivalent data sets. We compare heritabilities and genetic correlations from animal model and parent-offspring analyses, respectively, using data on eight morphological traits in the great reed warbler (Acrocephalus arundinaceus). Animal models were run using either mean trait values or individual repeated measurements to be able to separate between effects of including more extended pedigree information and effects of replicated sampling from the same individuals. We show that the inclusion of more pedigree information by the use of mean traits animal models had limited effect on the standard error and magnitude of heritabilities. In contrast, the use of repeated measures animal model generally had a positive effect on the sampling accuracy and resulted in lower heritabilities; the latter due to lower additive variance and higher phenotypic variance. For most trait combinations, both animal model methods gave genetic correlations that were lower than the parent-offspring estimates, whereas the standard errors were lower only for the mean traits animal model. We conclude that differences in heritabilities between the animal model and parent-offspring regressions were mostly due to the inclusion of individual replicates to the animal model rather than the inclusion of more extended pedigree information. Genetic correlations were, on the other hand, primarily affected by the inclusion of more pedigree information. This study is to our knowledge the most comprehensive empirical evaluation of the performance of the animal model in relation to parent-offspring regressions in a wild population. Our conclusions should be valuable for reconciliation of data obtained in earlier studies as well as for future meta-analyses utilizing estimates from both traditional methods and the animal model

Evolution of Female Preference for Younger Males

Previous theoretical work has suggested that females should prefer to mate with older males, as older males should have higher fitness than the average fitness of the cohort into which they were born. However, studies in humans and model organisms have shown that as males age, they accumulate deleterious mutations in their germ-line at an ever-increasing rate, thereby reducing the quality of genes passed on to the next generation. Thus, older males may produce relatively poor-quality offspring. To better understand how male age influences female mate preference and offspring quality, we used a genetic algorithm model to study the effect of age-related increases in male genetic load on female mate preference. When we incorporate age-related increases in mutation load in males into our model, we find that females evolve a preference for younger males. Females in this model could determine a male's age, but not his inherited genotype nor his mutation load. Nevertheless, females evolved age-preferences that led them to mate with males that had low mutation loads, but showed no preference for males with respect to their somatic quality. These results suggest that germ-line quality, rather than somatic quality, should be the focus of female preference in good genes models

Interleukin-10 (IL-10) Pathway: Genetic Variants and Outcomes of HIV-1 Infection in African American Adolescents

promoter sequence have been reported to influence pathogenesis or acquisition of HIV-1 infection. T-cell increased by 31±0.9% and 17±8% every 3 months for AA and AG genotype, respectively. gene family to HIV-1/AIDS