Comparative Analysis of Teleost Genome Sequences Reveals an Ancient Intron Size Expansion in the Zebrafish Lineage

We have developed a bioinformatics pipeline for the comparative evolutionary analysis of Ensembl genomes and have used it to analyze the introns of the five available teleost fish genomes. We show our pipeline to be a powerful tool for revealing variation between genomes that may otherwise be overlooked with simple summary statistics. We identify that the zebrafish, Danio rerio, has an unusual distribution of intron sizes, with a greater number of larger introns in general and a notable peak in the frequency of introns of approximately 500 to 2,000 bp compared with the monotonically decreasing frequency distributions of the other fish. We determine that 47% of D. rerio introns are composed of repetitive sequences, although the remainder, over 331 Mb, is not. Because repetitive elements may be the origin of the majority of all noncoding DNA, it is likely that the remaining D. rerio intronic sequence has an ancient repetitive origin and has since accumulated so many mutations that it can no longer be recognized as such. To study such an ancient expansion of repeats in the Danio, lineage will require further comparative analysis of fish genomes incorporating a broader distribution of teleost lineages

Wolbachia Infections in Anopheles gambiae Cells: Transcriptomic Characterization of a Novel Host-Symbiont Interaction

The endosymbiotic bacterium Wolbachia is being investigated as a potential control agent in several important vector insect species. Recent studies have shown that Wolbachia can protect the insect host against a wide variety of pathogens, resulting in reduced transmission of parasites and viruses. It has been proposed that compromised vector competence of Wolbachia-infected insects is due to up-regulation of the host innate immune system or metabolic competition. Anopheles mosquitoes, which transmit human malaria parasites, have never been found to harbor Wolbachia in nature. While transient somatic infections can be established in Anopheles, no stable artificially-transinfected Anopheles line has been developed despite numerous attempts. However, cultured Anopheles cells can be stably infected with multiple Wolbachia strains such as wAlbB from Aedes albopictus, wRi from Drosophila simulans and wMelPop from Drosophila melanogaster. Infected cell lines provide an amenable system to investigate Wolbachia-Anopheles interactions in the absence of an infected mosquito strain. We used Affymetrix GeneChip microarrays to investigate the effect of wAlbB and wRi infection on the transcriptome of cultured Anopheles Sua5B cells, and for a subset of genes used quantitative PCR to validate results in somatically-infected Anopheles mosquitoes. Wolbachia infection had a dramatic strain-specific effect on gene expression in this cell line, with almost 700 genes in total regulated representing a diverse array of functional classes. Very strikingly, infection resulted in a significant down-regulation of many immune, stress and detoxification-related transcripts. This is in stark contrast to the induction of immune genes observed in other insect hosts. We also identified genes that may be potentially involved in Wolbachia-induced reproductive and pathogenic phenotypes. Somatically-infected mosquitoes had similar responses to cultured cells. The data show that Wolbachia has a profound and unique effect on Anopheles gene expression in cultured cells, and has important implications for mechanistic understanding of Wolbachia-induced phenotypes and potential novel strategies to control malaria

Engineering Chimeric Antigen Receptor T-Cells for Racing in Solid Tumors: Don't Forget the Fuel.

T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation. CAR therapy targeting CD19 has yielded extraordinary clinical responses against some hematological tumors. Solid tumors, however, remain an important challenge to CAR T-cells due to issues of homing, tumor vasculature and stromal barriers, and a range of obstacles in the tumor bed. Protumoral immune infiltrate including T regulatory cells and myeloid-derived suppressor cells have been well characterized for their ability to upregulate inhibitory receptors and molecules that hinder effector T-cells. A critical role for metabolic barriers in the tumor microenvironment (TME) is emerging. High glucose consumption and competition for key amino acids by tumor cells can leave T-cells with insufficient energy and biosynthetic precursors to support activities such as cytokine secretion and lead to a phenotypic state of anergy or exhaustion. CAR T-cell expansion protocols that promote a less differentiated phenotype, combined with optimal receptor design and coengineering strategies, along with immunomodulatory therapies that also promote endogenous immunity, offer great promise in surmounting immunometabolic barriers in the TME and curing solid tumors

Gender, Work and Wages in Industrial Revolution Britain

A major new study of the role of women in the labor market of Industrial Revolution Britain. It is well known that men and women usually worked in different occupations, and that women earned lower wages than men. These differences are usually attributed to custom but Joyce Burnette here demonstrates instead that gender differences in occupations and wages were instead largely driven by market forces. Her findings reveal that rather than harming women competition actually helped them by eroding the power that male workers needed to restrict female employment and minimizing the gender wage gap by sorting women into the least strength-intensive occupations. Where the strength requirements of an occupation made women less productive than men, occupational segregation maximized both economic efficiency and female incomes. She shows that women's wages were then market wages rather than customary and the gender wage gap resulted from actual differences in productivity.Includes bibliographical references and index.Introduction -- Women's occupations -- Women's wages -- Explaining occupational sorting -- Testing for occupational barriers in agriculture -- Barriers to women's employment -- Occupational barriers in self-employment -- Women's labour force participation -- Conclusion -- Appendix to chapter three -- Appendix to chapter four.A major new study of the role of women in the labor market of Industrial Revolution Britain. It is well known that men and women usually worked in different occupations, and that women earned lower wages than men. These differences are usually attributed to custom but Joyce Burnette here demonstrates instead that gender differences in occupations and wages were instead largely driven by market forces. Her findings reveal that rather than harming women competition actually helped them by eroding the power that male workers needed to restrict female employment and minimizing the gender wage gap by sorting women into the least strength-intensive occupations. Where the strength requirements of an occupation made women less productive than men, occupational segregation maximized both economic efficiency and female incomes. She shows that women's wages were then market wages rather than customary and the gender wage gap resulted from actual differences in productivity

The Paradox of Progress : the Emergence of Wage Discrimination in US Manufacturing

This article tests for wage discrimination in US manufacturing during the nineteenth century and in 2002 by estimating the female-to-male productivity ratio and comparing it to the wage ratio. This method will not identify all forms of discrimination, but will determine whether women were paid wages commensurate with their productivity. There was no significant difference between the wage ratio and the productivity ratio in the nineteenth century, but in 1900 there is evidence of gender discrimination among white-collar workers. In 2002 the female-to-male productivity ratio was higher than in the nineteenth century, and the wage ratio was also higher, but the wage ratio was significantly lower than the productivity ratio, at least for workers older than thirty-five. The movement from the spot labor markets of the nineteenth century to the internal labor markets has allowed for the emergence of gender wage discrimination

How skilled were English agricultural labourers in the early nineteenth century? -super-1

Using the wage accounts of two different farms in the 1830s and 1840s, matched with census records to determine the age of the workers, this article estimates age-wage profiles for male and female agricultural labourers. Females earned less than males, and had less wage growth over their life cycles. Male wage profiles peaked at age 30–5, earlier than the wage profiles of workers today. Before the age of 30 wage growth was more rapid than increases in strength, but less rapid than wage growth among factory workers. If wage increases after the age of 20 indicate skill acquisition, then male agricultural labourers acquired a significant amount of skill, but less skill than contemporaneous factory workers