Whole-proteome genetic analysis of dependencies in assembly of a vertebrate kinetochore

Kinetochores orchestrate mitotic chromosome segregation. Here, we use quantitative mass spectrometry of mitotic chromosomes isolated from a comprehensive set of chicken DT40 mutants to examine the dependencies of 93 confirmed and putative kinetochore proteins for stable association with chromosomes. Clustering and network analysis reveal both known and unexpected aspects of coordinated behavior for members of kinetochore protein complexes. Surprisingly, CENP-T depends on CENP-N for chromosome localization. The Ndc80 complex exhibits robust correlations with all other complexes in a “core” kinetochore network. Ndc80 associated with CENP-T interacts with a cohort of Rod, zw10, and zwilch (RZZ)–interacting proteins that includes Spindly, Mad1, and CENP-E. This complex may coordinate microtubule binding with checkpoint signaling. Ndc80 associated with CENP-C forms the KMN (Knl1, Mis12, Ndc80) network and may be the microtubule-binding “workhorse” of the kinetochore. Our data also suggest that CENP-O and CENP-R may regulate the size of the inner kinetochore without influencing the assembly of the outer kinetochore.     

A new SNP-based vision of the genetics of sex determination in European sea bass (Dicentrarchus labrax)

Background

European sea bass (Dicentrarchus labrax) is one of the most important farmed species in Mediterranean aquaculture. The observed sexual growth and maturity dimorphism in favour of females adds value towards deciphering the sex determination system of this species. Current knowledge indicates the existence of a polygenic sex determining determination system that interacts with temperature. This was explored by restriction-site associated DNA (RAD) marker analysis in a test panel of 175 offspring that originated from a factorial cross between two dams and four sires from a single full-sib family.

Results

The first high-density single nucleotide polymorphism (SNP) based linkage map for sea bass was constructed, consisting of 6706 SNPs on 24 linkage groups. Indications for putative sex-determining QTL (quantitative trait loci) that were significant at the genome-wide threshold were detected on linkage groups 6, 11 and 18 to 21, although a genome-wide association study (GWAS) did not identify individual significant SNPs at a genome-wide threshold. A preliminary genomic prediction approach that tested the efficiency of SNP-based selection for female sea bass showed a slight advantage compared to traditional pedigree-based selection. However, when the same models were tested on the same animals for selection for greater length, a clear advantage of the SNP-based selection was observed.

Conclusions

Overall, the results of this study provide additional support to the polygenic sex determination hypothesis in sea bass. In addition, identification of sex-ratio QTL may provide new opportunities for sex-ratio control in sea bass.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-015-0148-y) contains supplementary material, which is available to authorized users.     

Coumarin derivatives protection against ROS production in cellular models of Abeta toxicities

The role of oxidative stress and free radicals in the development of Alzheimer's disease (AD) has been the focus of many recent studies. The role of hydrogen peroxide (H(2)O(2)) in AD is thought to be associated with Abeta (amyloid - beta) damage in cells. A number of coumarin derivatives were previously found to be potent anti-inflammatory and antioxidant agents. Herein, these coumarin derivatives were tested as H(2)O(2) scavengers with the DCF assay using two types of neuronal cells: (a) wild type (N2a) neuroblastoma cells and (b) APP/PS1 transgenic cell line expressing Abeta. Their scavenging activity was varied between the types of cell cultures and it was found to be concentration and time dependent in the mutant cells. Their protective role against cell death further supports this notion. These results suggest that these compounds could be used as a template in the design of new molecules with a possible role in AD.     

Zoonotic diagrams: mastering and unsettling human‐animal relations

This article approaches interspecies relations through an examination of the prevalent visual device employed in the representation of animal‐human infection in the life sciences: the zoonotic cycles diagram. After charting its emergence and development in the context of bubonic plague, I explore how this diagrammatic regime has been applied in two distinct practical contexts: a plague warning sign on the Grand Canyon National Park hiking trail; and the on‐line public information campaign launched by the US Centers for Disease Control and Prevention (CDC) in the wake of the Ebola outbreak of 2014‐16. The article demonstrates the principal ontological and biopolitical operations of these diagrams, arguing that, far from simply summarizing epidemiological narratives of animal‐human infection, they function both as pilots of human mastery over human‐animal relations and as crucial sites of unsettlement for the latter.     

Optimal Designs for Estimating the Percentiles of the Risk in Multistage Models of Carcinogenesis

The multistage carcinogenesis models describe a process by which a normal cell becomes malignant and gives rise to a tumor. This paper aims at evaluating the percentiles of the risk function derived as dose-response relationship in a multi-stage model. These percentiles have been known as “virtual safe dose” levels or risk specific dose levels. The optimal design theory is applied to estimate the appropriate percentile and the sequential approach of design is adopted through a stochastic approximation scheme. If the initial design is D-optimal the limit design is D-optimal as well and it is the one with the minimum entropy.