Getting a Full Dose? Reconsidering Sex Chromosome Dosage Compensation in the Silkworm, Bombyx mori

Dosage compensation—equalizing gene expression levels in response to differences in gene dose or copy number—is classically considered to play a critical role in the evolution of heteromorphic sex chromosomes. As the X and Y diverge through degradation and gene loss on the Y (or the W in female-heterogametic ZW taxa), it is expected that dosage compensation will evolve to correct for sex-specific differences in gene dose. Although this is observed in some organisms, recent genome-wide expression studies in other taxa have revealed striking exceptions. In particular, reports that both birds and the silkworm moth (Bombyx mori) lack dosage compensation have spurred speculation that this is the rule for all female-heterogametic taxa. Here, we revisit the issue of dosage compensation in silkworm by replicating and extending the previous analysis. Contrary to previous reports, our efforts reveal a pattern typically associated with dosage compensated taxa: the global male:female expression ratio does not differ between the Z and autosomes. We believe the previous report of unequal male:female ratios on the Z reflects artifacts of microarray normalization in conjunction with not testing a major assumption that the male:female global expression ratio was unbiased for autosomal loci. However, we also find that the global Z chromosome expression is significantly reduced relative to autosomes, a pattern not expected in dosage compensated taxa. This combination of male:female parity with an overall reduction in expression for sex-linked loci is not consistent with the prevailing evolutionary theory of sex chromosome evolution and dosage compensation

Who Benefits from KIPP?

The nation's largest charter management organization is the Knowledge is Power Program (KIPP). KIPP schools are emblematic of the No Excuses approach to public education, a highly standardized and widely replicated charter model that features a long school day, an extended school year, selective teacher hiring, strict behavior norms, and a focus on traditional reading and math skills. No Excuses charter schools are sometimes said to focus on relatively motivated high achievers at the expense of students who are most diffiult to teach, including limited English proficiency (LEP) and special education (SPED) students, as well as students with low baseline achievement levels. We use applicant lotteries to evaluate the impact of KIPP Academy Lynn, a KIPP school in Lynn, Massachusetts that typifies the KIPP approach. Our analysis focuses on special needs students that may be underserved. The results show average achievement gains of 0.36 standard deviations in math and 0.12 standard deviations in reading for each year spent at KIPP Lynn, with the largest gains coming from the LEP, SPED, and low-achievement groups. The average reading gains are driven almost completely by SPED and LEP students, whose reading scores rise by roughly 0.35 standard deviations for each year spent at KIPP Lynn.human capital, charter schools, achievement

Sex Chromosome Dosage Compensation in Heliconius Butterflies: Global yet Still Incomplete?

The evolution of heterogametic sex chromosomes is often-but not always-accompanied by the evolution of dosage compensating mechanisms that mitigate the impact of sex-specific gene dosage on levels of gene expression. One emerging view of this process is that such mechanisms may only evolve in male-heterogametic (XY) species but not in female-heterogametic (ZW) species, which will consequently exhibit "incomplete" sex chromosome dosage compensation. However, recent results suggest that at least some Lepidoptera (moths and butterflies) may prove to be an exception to this prediction. Studies in bombycoid moths indicate the presence of a chromosome-wide epigenetic mechanism that effectively balances Z chromosome gene expression between the sexes by reducing Z-linked expression in males. In contrast, strong sex chromosome dosage effects without any reduction in male Z-linked expression were previously reported in a pyralid moth, suggesting a lack of any such dosage compensating mechanism. Here we report an analysis of sex chromosome dosage compensation in Heliconius butterflies, sampling multiple individuals for several different adult tissues (head, abdomen, leg, mouth, and antennae). Methodologically, we introduce a novel application of linear mixed-effects models to assess dosage compensation, offering a unified statistical framework that can estimate effects specific to chromosome, to sex, and their interactions (i.e., a dosage effect). Our results show substantially reduced Z-linked expression relative to autosomes in both sexes, as previously observed in bombycoid moths. This observation is consistent with an increasing body of evidence that some lepidopteran species possess an epigenetic dosage compensating mechanism that reduces Z chromosome expression in males to levels comparable with females. However, this mechanism appears to be imperfect in Heliconius, resulting in a modest dosage effect that produces an average 5-20% increase in male expression relative to females on the Z chromosome, depending on the tissue. Thus our results in Heliconius reflect a mixture of previous patterns reported for Lepidoptera. In Heliconius, a moderate pattern of incomplete dosage compensation persists apparently despite the presence of an epigenetic dosage compensating mechanism. The chromosomal distributions of sex-biased genes show an excess of male-biased and a dearth of female-biased genes on the Z chromosome relative to autosomes, consistent with predictions of sexually antagonistic evolution.This research was supported in part by a NSF postdoctoral fellowshiptoJ.R.W. (DBI-0905698). RNA sequencing was funded by the “Capacity and Capability Challenge Program” from The Genome Analysis Centre, Norwich, UK. The computing for this project was performed on the Community Cluster at the Center for Research Computing at the University of Kansas. Luiqi (Aloy) Gu provided valuable comments on the manuscript.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/gbe/evv156

Sex Chromosome Dosage Compensation in Heliconius Butterflies: Global yet Still Incomplete?

The evolution of heterogametic sex chromosomes is often—but not always—accompanied by the evolution of dosage compensating mechanisms that mitigate the impact of sex-specific gene dosage on levels of gene expression. One emerging view of this process is that such mechanisms may only evolve in male-heterogametic (XY) species but not in female-heterogametic (ZW) species, which will consequently exhibit “incomplete” sex chromosome dosage compensation. However, recent results suggest that at least some Lepidoptera (moths and butterflies) may prove to be an exception to this prediction. Studies in bombycoid moths indicate the presence of a chromosome-wide epigenetic mechanism that effectively balances Z chromosome gene expression between the sexes by reducing Z-linked expression in males. In contrast, strong sex chromosome dosage effects without any reduction in male Z-linked expression were previously reported in a pyralid moth, suggesting a lack of any such dosage compensating mechanism. Here we report an analysis of sex chromosome dosage compensation in Heliconius butterflies, sampling multiple individuals for several different adult tissues (head, abdomen, leg, mouth, and antennae). Methodologically, we introduce a novel application of linear mixed-effects models to assess dosage compensation, offering a unified statistical framework that can estimate effects specific to chromosome, to sex, and their interactions (i.e., a dosage effect). Our results show substantially reduced Z-linked expression relative to autosomes in both sexes, as previously observed in bombycoid moths. This observation is consistent with an increasing body of evidence that some lepidopteran species possess an epigenetic dosage compensating mechanism that reduces Z chromosome expression in males to levels comparable with females. However, this mechanism appears to be imperfect in Heliconius, resulting in a modest dosage effect that produces an average 5–20% increase in male expression relative to females on the Z chromosome, depending on the tissue. Thus our results in Heliconius reflect a mixture of previous patterns reported for Lepidoptera. In Heliconius, a moderate pattern of incomplete dosage compensation persists apparently despite the presence of an epigenetic dosage compensating mechanism. The chromosomal distributions of sex-biased genes show an excess of male-biased and a dearth of female-biased genes on the Z chromosome relative to autosomes, consistent with predictions of sexually antagonistic evolution

Who Benefits from KIPP?

The nation's largest charter management organization is the Knowledge is Power Program (KIPP). KIPP schools are emblematic of the No Excuses approach to public education, a highly standardized and widely replicated charter model that features a long school day, an extended school year, selective teacher hiring, strict behavior norms, and emphasizes traditional reading and math skills. No Excuses charter schools are sometimes said to target relatively motivated high achievers at the expense of students who are more difficult to teach, including limited English proficiency (LEP) and special education (SPED) students, as well as students with low baseline achievement levels. We use applicant lotteries to evaluate the impact of KIPP Academy Lynn, a KIPP school in Lynn, Massachusetts that typifies the KIPP approach. Our analysis focuses on special needs students that may be underserved. The results show average achievement gains of 0.36 standard deviations in math and 0.12 standard deviations in reading for each year spent at KIPP Lynn, with the largest gains coming from the LEP, SPED, and low-achievement groups. Average reading gains are driven almost entirely by SPED and LEP students, whose reading scores rise by roughly 0.35 standard deviations for each year spent at KIPP Lynn

A Systemically-Administered Small Molecule Antagonist of CCR9 Acts as a Tissue-Selective Inhibitor of Lymphocyte Trafficking

A goal for developers of immunomodulatory drugs has long been a systemically administered small molecule that can selectively inhibit inflammation in specific tissues. The chemokine receptor CCR9 is an attractive target for this approach, as entry of T cells into the small intestine from blood requires interaction between CCR9 and its ligand CCL25. We have tested the ability of a small molecule CCR9 antagonist, CCX8037, to inhibit antigen-mediated T cell accumulation in the intestine. This compound prevented accumulation of gut-imprinted antigen-specific CD8 T cells within epithelium of the small intestine. Interestingly, the antagonist did not affect the robust generation of gut-imprinted CD8 T cells within mesenteric lymph nodes. To distinguish “gut-selective” from “general” T cell inhibition, we tested the drug’s ability to influence accumulation of T cells within skin, a tissue in which CCR9 plays no known role, and we found no appreciable effect. This study demonstrates the feasibility of creating systemically-administered pharmaceuticals capable of tissue-selective immune modulation. This proof of concept is of utmost importance for designing effective treatments against various autoimmune disorders localized to a specific tissue

The Zwicky Transient Facility: Surveys and Scheduler

We present a novel algorithm for scheduling the observations of time-domain imaging surveys. Our Integer Linear Programming approach optimizes an observing plan for an entire night by assigning targets to temporal blocks, enabling strict control of the number of exposures obtained per field and minimizing filter changes. A subsequent optimization step minimizes slew times between each observation. Our optimization metric self-consistently weights contributions from time-varying airmass, seeing, and sky brightness to maximize the transient discovery rate. We describe the implementation of this algorithm on the surveys of the Zwicky Transient Facility and present its on-sky performance.Comment: Published in PASP Focus Issue on the Zwicky Transient Facility (https://dx.doi.org/10.1088/1538-3873/ab0c2a). 13 Pages, 11 Figure

A Model for Assessing the Visual Resources of River Basins as an Aid to Making Landuse Planning Decisions

The visual quality of a river basin and its associated properties can be identified, evaluated and integrated into the landscape planning process. The model developed provides a quantitative methodology for determining visual quality on the basis of available Geographic Information System factors. These factors are utilized to develop the preference attributes, COLOR, FORM, TEXTURE and LINE, which are associated with the assessment of visual quality. The preference attributes are then combined through a decision making process into a continuum of DISTINCTIVE, GOOD, AVERAGE and MINIMAL visual quality and is expressed digitally in map format. By providing visual quality information in a digital format it can be treated as a discrete component of the planning process similar to physical, cultural and economic attributes

Explorations in anatomy: the remains from Royal London Hospital

This paper considers the faunal remains from recent excavations at the Royal London Hospital. The remains date to the beginning of the 19th century and offer an insight into the life of the hospital's patients and practices of the attached medical school. Many of the animal remains consist of partially dissected skeletons, including the unique finds of Hermann's tortoise (Testudo hermanni) and Cercopithecus monkey. The hospital diet and developments in comparative anatomy are discussed by integrating the results with documentary research. They show that zooarchaeological study of later post-medieval material can significantly enhance our understanding of the exploitation of animals in this perio