Sex-role reversal revisited: choosy females and ornamented, competitive males in a pipefish

In the pipefish Syngnathus typhle sex roles are reversed, thatis, females compete more intensely than males over mates. However,competition over mates among individuals of one sex does notnecessarily prevent members of that same sex from being choosy,and choosiness in the other sex does not prevent competitionwithin it. In an experiment we allowed a female pipefish tochoose freely between two males, after which we released themales and let the three interact. Comparisons with earlier resultsshow that both sexes courted partners and competed with consexuals.However, females courted more often than did males, and courtshipwas more frequent in treatments involving large individualsthan in treatments with small individuals. Males competed amongthemselves for access to mates but for a shorter duration thanfemales in the same situation. Males displayed an ornament towardsfemales but not to males during mating competition. Females,however, used their ornament in both contexts. Females did notalways mate with the male of their previously made choice, whichwe interpret as females being constrained by male-male competition,male motivation to mate, or both. Thus, in this sex-role reversedspecies, mate choice in the more competitive sex may be circumventedand even overruled by mate competition and mating willingnessin the least competitive sex. Hence, sex roles should not beconsidered as sexes being either choosy or competitive but ratherthat males and females may exhibit different combinations ofchoice and competition.     

SHORT Syndrome with Partial Lipodystrophy Due to Impaired Phosphatidylinositol 3 Kinase Signaling

The phosphatidylinositol 3 kinase (PI3K) pathway regulates fundamental cellular processes such as metabolism, proliferation, and survival. A central component in this pathway is the p85α regulatory subunit, encoded by PIK3R1. Using whole-exome sequencing, we identified a heterozygous PIK3R1 mutation (c.1945C>T [p.Arg649Trp]) in two unrelated families affected by partial lipodystrophy, low body mass index, short stature, progeroid face, and Rieger anomaly (SHORT syndrome). This mutation led to impaired interaction between p85α and IRS-1 and reduced AKT-mediated insulin signaling in fibroblasts from affected subjects and in reconstituted Pik3r1-knockout preadipocytes. Normal PI3K activity is critical for adipose differentiation and insulin signaling; the mutated PIK3R1 therefore provides a unique link among lipodystrophy, growth, and insulin signaling.     

Purity and Corruption: Chinese Communist Party Applicants and the Problem of Evil

In contemporary China, university students play a key ideological role as the future vanguard of the nation and for this reason they are intensely courted by the Chinese Communist Party. This article addresses the moral ambiguities of this courtship for students, who face the paradox that while the party centre and collectivist authoritarian ideology invariably claims moral superiority, individual party cadres are frequently exposed as morally corrupt. The evil of cadre corruption becomes the nodal point for questioning party morality, a central stake in support of collectivist authoritarian ideology as well as in its denunciation. For students, the problem of evil within the force, representing the collective good is never resolved in either false consciousness or an unmasking of ideology. Doubt instead proceeds as two incommensurable interpretations of party morality persist in suggesting themselves, and this I suggest has important implications for our understanding of political legitimacy in authoritarian states.     

Mechanical Resistance in Unstructured Proteins

Single-molecule pulling experiments on unstructured proteins linked to neurodegenerative diseases have measured rupture forces comparable to those for stable folded proteins. To investigate the structural mechanisms of this unexpected force resistance, we perform pulling simulations of the amyloid β-peptide (Aβ) and α-synuclein (αS), starting from simulated conformational ensembles for the free monomers. For both proteins, the simulations yield a set of rupture events that agree well with the experimental data. By analyzing the conformations occurring shortly before rupture in each event, we find that the mechanically resistant structures share a common architecture, with similarities to the folds adopted by Aβ and αS in amyloid fibrils. The disease-linked Arctic mutation of Aβ is found to increase the occurrence of highly force-resistant structures. Our study suggests that the high rupture forces observed in Aβ and αS pulling experiments are caused by structures that might have a key role in amyloid formation.     

Elevated Tolerance to Aneuploidy in Cancer Cells: Estimating the Fitness Effects of Chromosome Number Alterations by In Silico Modelling of Somatic Genome Evolution

An unbalanced chromosome number (aneuploidy) is present in most malignant tumours and has been attributed to mitotic mis-segregation of chromosomes. However, recent studies have shown a relatively high rate of chromosomal mis-segregation also in non-neoplastic human cells, while the frequency of aneuploid cells remains low throughout life in most normal tissues. This implies that newly formed aneuploid cells are subject to negative selection in healthy tissues and that attenuation of this selection could contribute to aneuploidy in cancer. To test this, we modelled cellular growth as discrete time branching processes, during which chromosome gains and losses were generated and their host cells subjected to selection pressures of various magnitudes. We then assessed experimentally the frequency of chromosomal mis-segregation as well as the prevalence of aneuploid cells in human non-neoplastic cells and in cancer cells. Integrating these data into our models allowed estimation of the fitness reduction resulting from a single chromosome copy number change to an average of ≈30% in normal cells. In comparison, cancer cells showed an average fitness reduction of only 6% (p = 0.0008), indicative of aneuploidy tolerance. Simulations based on the combined presence of chromosomal mis-segregation and aneuploidy tolerance reproduced distributions of chromosome aberrations in >400 cancer cases with higher fidelity than models based on chromosomal mis-segregation alone. Reverse engineering of aneuploid cancer cell development in silico predicted that aneuploidy intolerance is a stronger limiting factor for clonal expansion of aneuploid cells than chromosomal mis-segregation rate. In conclusion, our findings indicate that not only an elevated chromosomal mis-segregation rate, but also a generalised tolerance to novel chromosomal imbalances contribute to the genomic landscape of human tumours.     

Immunohistochemical analysis of the vitellogenin response in the liver of Atlantic salmon exposed to environmental oestrogens

Induction of vitellogenin (Vtg) in oviparous vertebrates has been used as a biomarker of response for environmental oestrogens. This study reports the cellular localization of oestrogen- and xenoestrogen-induced Vtg synthesis in the liver of juvenile Atlantic salmon (Salmo salar). Paraffin-embedded liver sections were incubated with homologous monoclonal antibody against Atlantic salmon Vtg. Following intraperitoneal (ip) exposure of fish to estradiol-17beta E₂; 5 mg kg-1 or 4-nonylphenol NP; 125 mg kg-1, Vtg induction was primarily demonstrated immunohistochemically in the cytoplasm of hepatocytes, endothelial cells and within hepatic sinusoids. Vtg staining of hepatocytes was not evenly distributed, as there was a high degree of polarization toward the sinusoid. The intensity of positive Vtg staining was stronger in the liver sections of E₂-treated fish, compared with NP-treated fish. Hepatocytes of E₂-, NP- and vehicle (control)-treated fish showed normal cellular structures, thus showing no evidence of histopathological changes. In parallel, indirect enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis of plasma Vtg levels show significant induction of Vtg in E₂- and NP-treated fish, as compared with untreated (control) fish. The present study demonstrates the applicability of immunohistochemistry in studies of cellular structures, processes and responses of fish exposure to oestrogen and oestrogen-mimicking compounds.