Inferring trackline detection probabilities,g(0), for cetaceans from apparent densities in different survey conditions

Visual line‐transect surveys are commonly used to estimate cetacean abundance. A key parameter in such studies is g(0), the probability of detecting an animal that is directly on the transect line. This is typically considered to be constant for a species across survey conditions. A method is developed to estimate the relative values of g(0) in different survey conditions (Beaufort state) by comparing Beaufort‐specific density estimates. The approach is based on fitting generalized additive models, with the presence of a sighting on a survey segment as the dependent variable, Beaufort state as the key explanatory variable, and year, latitude, and longitude as nuisance variables to control for real differences in density over time and space. Values of relative g(0) are estimated for 20 cetacean taxa using 175,000 km of line‐transect survey data from the eastern and central Pacific Ocean from 1986 to 2010. Results show that g(0) decreases as Beaufort state increases, even for visually conspicuous species. This effect is greatest for the least conspicuous species (rough‐toothed dolphins, beaked whales, minke whales, and dwarf and pygmy sperm whales). Ignoring these large effects results in a nontrivial bias in cetacean abundance estimates.     

Food web structure changes with elevation but not rainforest stratum

Changes in species richness along elevational gradients are well documented. However, little is known about how trophic interactions between species and, in particular, the food webs that these interactions comprise, change with elevation. Here we present results for the first comparison of quantitative food webs in forest understorey and canopy along an elevational gradient. Replicate quantitative food webs were constructed for assemblages involving 23 species of cavity‐nesting Hymenoptera and 12 species of their parasitoids and kleptoparasites in subtropical rainforest in Australia. A total of 1589 insects were collected using trap nests across 20 plots distributed at sites ranging from 300 to 1100 m a.s.l. Insect abundance, insect diversity and parasitism rate generally decreased with increasing elevation. Food web structure significantly changed with elevation. In particular, weighted quantitative measures of linkage density, interaction evenness, nestedness (weighted NODF) and potential for enemy mediated interactions (PAC) decreased with increasing elevation, and network specialisation (H₂′) increased with increasing elevation, even after controlling for matrix size; but there was no change in weighted connectance. Changes in forest type and temperature along the elevational gradient are likely to be, at least partly, responsible for the patterns observed. We found no significant differences in insect abundance, insect diversity or parasitism rate between canopy and understorey. Furthermore, there were no differences in food web structure between strata. These results contribute further evidence to studies revealing changes in food web structure along natural environmental gradients and provide information that can potentially be used for predicting how communities may respond to climate change.     

Tight coupling of primary production and marine mammal reproduction in the Southern Ocean

Polynyas are areas of open water surrounded by sea ice and are important sources of primary production in high-latitude marine ecosystems. The magnitude of annual primary production in polynyas is controlled by the amount of exposure to solar radiation and sensitivity to changes in sea-ice extent. The degree of coupling between primary production and production by upper trophic-level consumers in these environments is not well understood, which prevents reliable predictions about population trajectories for species at higher trophic levels under potential future climate scenarios. In this study, we find a strong, positive relationship between annual primary production in an Antarctic polynya and pup production by ice-dependent Weddell seals. The timing of the relationship suggests reproductive effort increases to take advantage of high primary production occurring in the months after the birth pulse. Though the proximate causal mechanism is unknown, our results indicate tight coupling between organisms at disparate trophic levels on a short timescale, deepen our understanding of marine ecosystem processes, and raise interesting questions about why such coupling exists and what implications it has for understanding high-latitude ecosystems.     

Symmetrical Dose-Dependent DNA-Methylation Profiles in Children with Deletion or Duplication of 7q11.23

Epigenetic dysfunction has been implicated in a growing list of disorders that include cancer, neurodevelopmental disorders, and neurodegeneration. Williams syndrome (WS) and 7q11.23 duplication syndrome (Dup7) are rare neurodevelopmental disorders with broad phenotypic spectra caused by deletion and duplication, respectively, of a 1.5-Mb region that includes several genes with a role in epigenetic regulation. We have identified striking differences in DNA methylation across the genome between blood cells from children with WS or Dup7 and blood cells from typically developing (TD) children. Notably, regions that were differentially methylated in both WS and Dup7 displayed a significant and symmetrical gene-dose-dependent effect, such that WS typically showed increased and Dup7 showed decreased DNA methylation. Differentially methylated genes were significantly enriched with genes in pathways involved in neurodevelopment, autism spectrum disorder (ASD) candidate genes, and imprinted genes. Using alignment with ENCODE data, we also found the differentially methylated regions to be enriched with CCCTC-binding factor (CTCF) binding sites. These findings suggest that gene(s) within 7q11.23 alter DNA methylation at specific sites across the genome and result in dose-dependent DNA-methylation profiles in WS and Dup7. Given the extent of DNA-methylation changes and the potential impact on CTCF binding and chromatin regulation, epigenetic mechanisms most likely contribute to the complex neurological phenotypes of WS and Dup7. Our findings highlight the importance of DNA methylation in the pathogenesis of WS and Dup7 and provide molecular mechanisms that are potentially shared by WS, Dup7, and ASD.     

A Kinetic Study of Ovalbumin Fibril Formation: The Importance of Fragmentation and End-Joining

The ability to control the morphologies of biomolecular aggregates is a central objective in the study of self-assembly processes. The development of predictive models offers the surest route for gaining such control. Under the right conditions, proteins will self-assemble into fibers that may rearrange themselves even further to form diverse structures, including the formation of closed loops. In this study, chicken egg white ovalbumin is used as a model for the study of fibril loops. By monitoring the kinetics of self-assembly, we demonstrate that loop formation is a consequence of end-to-end association between protein fibrils. A model of fibril formation kinetics, including end-joining, is developed and solved, showing that end-joining has a distinct effect on the growth of fibrillar mass density (which can be measured experimentally), establishing a link between self-assembly kinetics and the underlying growth mechanism. These results will enable experimentalists to infer fibrillar morphologies from an appropriate analysis of self-assembly kinetic data.     

Use of a small molecule cell cycle inhibitor to control cell growth and improve specific productivity and product quality of recombinant proteins in CHO cell cultures

The continued need to improve therapeutic recombinant protein productivity has led to ongoing assessment of appropriate strategies in the biopharmaceutical industry to establish robust processes with optimized critical variables, that is, viable cell density (VCD) and specific productivity (product per cell, qP). Even though high VCD is a positive factor for titer, uncontrolled proliferation beyond a certain cell mass is also undesirable. To enable efficient process development to achieve consistent and predictable growth arrest while maintaining VCD, as well as improving qP, without negative impacts on product quality from clone to clone, we identified an approach that directly targets the cell cycle G1‐checkpoint by selectively inhibiting the function of cyclin dependent kinases (CDK) 4/6 with a small molecule compound. Results from studies on multiple recombinant Chinese hamster ovary (CHO) cell lines demonstrate that the selective inhibitor can mediate a complete and sustained G0/G1 arrest without impacting G2/M phase. Cell proliferation is consistently and rapidly controlled in all recombinant cell lines at one concentration of this inhibitor throughout the production processes with specific productivities increased up to 110 pg/cell/day. Additionally, the product quality attributes of the mAb, with regard to high molecular weight (HMW) and glycan profile, are not negatively impacted. In fact, high mannose is decreased after treatment, which is in contrast to other established growth control methods such as reducing culture temperature. Microarray analysis showed major differences in expression of regulatory genes of the glycosylation and cell cycle signaling pathways between these different growth control methods. Overall, our observations showed that cell cycle arrest by directly targeting CDK4/6 using selective inhibitor compound can be utilized consistently and rapidly to optimize process parameters, such as cell growth, qP, and glycosylation profile in recombinant antibody production cultures. Biotechnol. Bioeng. 2015;112: 141–155. © 2014 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.