The Case for a Reparations Clinic: A Proposal for Investigation, Documentation, and Remediation of Historic Housing Discrimination Through the Law School Clinic Model

Article published in the Michigan State Law Review

Direct and indirect influences of executive functions on mathematics achievement

Achievement in mathematics is predicted by an individual’s domain-specific factual knowledge, procedural skill and conceptual understanding as well as domain-general executive function skills. In this study we investigated the extent to which executive function skills contribute to these three components of mathematical knowledge, whether this mediates the relationship between executive functions and overall mathematics achievement, and if these relationships change with age. Two hundred and ninety-three participants aged between 8 and 25 years completed a large battery of mathematics and executive function tests. Domain-specific skills partially mediated the relationship between executive functions and mathematics achievement: Inhibitory control within the numerical domain was associated with factual knowledge and procedural skill, which in turn was associated with mathematical achievement. Working memory contributed to mathematics achievement indirectly through factual knowledge, procedural skill and, to a lesser extent, conceptual understanding. There remained a substantial direct pathway between working memory and mathematics achievement however, which may reflect the role of working memory in identifying and constructing problem representations. These relationships were remarkably stable from 8 years through to young adulthood. Our findings help to refine existing multi-component frameworks of mathematics and understand the mechanisms by which executive functions support mathematics achievement

The Case for a Reparations Clinic: A Proposal for Investigation, Documentation, and Remediation of Historic Housing Discrimination Through the Law School Clinic Model

Article published in the Michigan State Law Review

First report of Lyme borreliosis leading to cardiac bradydysrhythmia in two cats

Case series summary:Two cats were presented for investigation of bradyarrhythmia detected by their referring veterinarians during routine examination. Both cats had extensive investigations, including haematology, serum biochemistry with electrolytes and thyroxine concentrations, systolic blood pressure measurement, echocardiography, electrocardiography and infectious disease testing. Infectious disease testing included serology for Toxoplasma gondii, Ehrlichia canis, Anaplasma phagocytophilum and Borrelia burgdorferi, and PCR for B burgdorferi antigen in both cats. Case 1 was also assessed by PCR for Bartonella henselae antigen and case 2 was assessed for Dirofilaria immitis by serology. All infectious disease tests, other than for B burgdorferi, were negative. Case 1 was diagnosed with Lyme carditis based on marked bradydysrhythmia, positive B burgdorferi serology, a structurally normal heart and clinical resolution with appropriate treatment with a 4-year follow-up. Case 2 was diagnosed with Lyme carditis based on marked bradydysrhythmia and positive B burgdorferi PCR; however, this cat had structural heart disease that did not resolve with treatment. Relevance and novel information:This small case series describes two B burgdorferi positive cats presenting with newly diagnosed cardiac abnormalities consistent with those found in humans and dogs with Lyme carditis. Both cats were asymptomatic as perceived by their owners; the arrhythmia was detected by their veterinarians

Anatomical localization of progenitor cells in human breast tissue reveals enrichment of uncommitted cells within immature lobules

Introduction: Lineage tracing studies in mice have revealed the localization and existence of lineage-restricted mammary epithelial progenitor cells that functionally contribute to expansive growth during puberty and differentiation during pregnancy. However, extensive anatomical differences between mouse and human mammary tissues preclude the direct translation of rodent findings to the human breast. Therefore, here we characterize the mammary progenitor cell hierarchy and identify the anatomic location of progenitor cells within human breast tissues. Methods: Mammary epithelial cells (MECs) were isolated from disease-free reduction mammoplasty tissues and assayed for stem/progenitor activity in vitro and in vivo. MECs were sorted and evaluated for growth on collagen and expression of lineages markers. Breast lobules were microdissected and individually characterized based on lineage markers and steroid receptor expression to identify the anatomic location of progenitor cells. Spanning-tree progression analysis of density-normalized events (SPADE) was used to identify the cellular hierarchy of MECs within lobules from high-dimensional cytometry data. Results: Integrating multiple assays for progenitor activity, we identified the presence of luminal alveolar and basal ductal progenitors. Further, we show that Type I lobules of the human breast were the least mature, demonstrating an unrestricted pattern of expression of luminal and basal lineage markers. Consistent with this, SPADE analysis revealed that immature lobules were enriched for basal progenitor cells, while mature lobules consisted of increased hierarchal complexity of cells within the luminal lineages. Conclusions: These results reveal underlying differences in the human breast epithelial hierarchy and suggest that with increasing glandular maturity, the epithelial hierarchy also becomes more complex. Electronic supplementary material The online version of this article (doi:10.1186/s13058-014-0453-3) contains supplementary material, which is available to authorized users

Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life

Mapping the cellular and molecular heterogeneity of normal and malignant breast tissues and cultured cell lines

Introduction: Normal and neoplastic breast tissues are comprised of heterogeneous populations of epithelial cells exhibiting various degrees of maturation and differentiation. While cultured cell lines have been derived from both normal and malignant tissues, it remains unclear to what extent they retain similar levels of differentiation and heterogeneity as that found within breast tissues. Methods: We used 12 reduction mammoplasty tissues, 15 primary breast cancer tissues, and 20 human breast epithelial cell lines (16 cancer lines, 4 normal lines) to perform flow cytometry for CD44, CD24, epithelial cell adhesion molecule (EpCAM), and CD49f expression, as well as immunohistochemistry, and in vivo tumor xenograft formation studies to extensively analyze the molecular and cellular characteristics of breast epithelial cell lineages. Results: Human breast tissues contain four distinguishable epithelial differentiation states (two luminal phenotypes and two basal phenotypes) that differ on the basis of CD24, EpCAM and CD49f expression. Primary human breast cancer tissues also contain these four cellular states, but in altered proportions compared to normal tissues. In contrast, cultured cancer cell lines are enriched for rare basal and mesenchymal epithelial phenotypes, which are normally present in small numbers within human tissues. Similarly, cultured normal human mammary epithelial cell lines are enriched for rare basal and mesenchymal phenotypes that represent a minor fraction of cells within reduction mammoplasty tissues. Furthermore, although normal human mammary epithelial cell lines exhibit features of bi-potent progenitor cells they are unable to differentiate into mature luminal breast epithelial cells under standard culture conditions. Conclusions: As a group breast cancer cell lines represent the heterogeneity of human breast tumors, but individually they exhibit increased lineage-restricted profiles that fall short of truly representing the intratumoral heterogeneity of individual breast tumors. Additionally, normal human mammary epithelial cell lines fail to retain much of the cellular diversity found in human breast tissues and are enriched for differentiation states that are a minority in breast tissues, although they do exhibit features of bi-potent basal progenitor cells. These findings suggest that collections of cell lines representing multiple cell types can be used to model the cellular heterogeneity of tissues