Cellular uptake of taurine by lactating porcine mammary tissue

Milk taurine plays a critical role in neonatal development. Taurine uptake in lactating sow mammary tissue has not been characterized previously. The kinetic properties, ion dependence and substrate specificity of taurine uptake were characterized in mammary tissue collected from lactating sows at slaughter. Tissue explants were incubated in an isosmotic physiologic buffer with [³H]taurine tracer to measure taurine uptake. Taurine uptake was dependent upon the presence of extracellular sodium and chloride ions, which is consistent with the co-transport of sodium and chloride with taurine. Uptake was not dependent upon ion exchange mechanisms or upon furosemide-sensitive ion co-transport. Taurine uptake was saturable and exhibited an apparent K_m of 20 μM and a V_max of 386 μmol/kg cell water/30 min. Substrate specificity studies indicated a strong interaction of β-amino acids with the taurine transport system. Taurine transport in lactating sow mammary tissue is therefore a high affinity, sodium-dependent mechanism specific for β-amino acids, and is analogous to sodium-dependent taurine uptake in other tissues. The high affinity and high specificity of the taurine uptake system allows for concentration of taurine within the mammary cell and is ultimately responsible for provision of taurine required for neonatal development.     

Evolution: have wings come,gone and come again?

Can complex traits be re-evolved by lineages that have lost them? Phylogenetic study now suggests that wings may indeed have reappeared several times within the ancestrally wingless stick insects.     

A Gifted Amateur: The Case of George Washington Ellis

George Washington Ellis published Negro Culture in West Africa in 1914 in response to the social gospel prophets' racist and stereotypical perspectives of West Africa and Africans. In so doing. Ellis attempted to shift the discourse from one that emphasized African barbarism to one that repudiated the idea of African inferiority. Unwittingly, however, Ellis preached a brand of romantic racialism—a benign doctrine that was commonplace in the racial discourse of African American elites at the Turn of the Century. Asa consequence, his loyalties were divided between 19th-century ethnological science and the "new ethnology" of Franz Boas. [Keywords: George Washington Ellis, history of racism, antiracism, African American anthropology, social gospel prophets]     

New technologies in vitro for analysis of cell movement on or within collagen gels.

The movement of cells through extracellular matrix (ECM) is a critical component of many normal and pathological processes in vivo. Consequently, efforts to characterize motility-associated interactions between cells and ECM have led to the development of methods to observe and quantify (assay) the movement of cells under simplified conditions in vitro. In this report, we describe a novel method (the bullseye assay) and apparatus for the concentration of cells into small, precisely sized and shaped circular disks (bullseyes) that serve as starting points for migration of cells within ECM. The same apparatus is used to form the bullseyes and position them at the center of flat disks (windows) of gelled collagen that are supported at the edges by rings of nylon mesh. Complete assemblies, each consisting of a bullseye, collagen window and nylon mesh ring, are transferred to tissue culture wells for assay of cell migration either within or on top of the collagen window. Studies of the migratory responses of three different cell types to specific cytokines demonstrated that the bullseye assay was sensitive, rapid to set up, and easy to use. In conjunction with the bullseye assay, we developed a novel annular grayscale method for quantification of cell migration from digital images. The method is easily mastered, is derived from a measurement program in the public domain, is not subjective and is more discriminative than other techniques of measurement.     

The Effects of Superoxide and the Peripheral Benzodiazepine Receptor Ligands on the Mitochondrial Processing of Manganese-Dependent Superoxide Dismutase

The mitochondrion imports and processes the vast majority of the proteins that constitute its structural elements and metabolic pathways. To study mitochondrial precursor processing in the context of the cellular environment, we employed the baculovirus expression system to overexpress the prototypical precursor protein, human manganese-dependent superoxide dismutase (hMn-SOD). It was found that superoxide produced by hyperoxic culture conditions (95% O₂atm) or the redox cycling agent paraquat caused a lesion of the import/processing of precursor hMn-SOD in the baculovirus model. The oxidation of key sulfhydryl groups as a component of the mitochondrial processing lesion was implicated by the observation that the sulfhydryl reducing agent dithiothreitol was completely effective in preventing the block of hMn-SOD processing induced by paraquat. Interestingly, the peripheral benzodiazepine receptor (PBzR) agonists PK11194, Ro5-4864, and protoporphyrin IX were all found to enhance mitochondrial processing of the hMn-SOD precursor protein, suggesting a role for the PBzR in the regulation of mitochondrial import of proteins. Collectively, our results suggest a possible redox-regulated mechanism of mitochondrial protein import that may lead to less efficient precursor protein uptake by mitochondria under severely oxidizing conditions.     

Differences in Breast Cancer Survival between Public and Private Care in New Zealand: Which Factors Contribute?

BackgroundPatients who received private health care appear to have better survival from breast cancer compared to those who received public care. This study investigated if this applied to New Zealand women and identified factors that could explain such disparities.MethodsThis study involved all women who were diagnosed with primary breast cancer in two health regions in New Zealand, covering about 40% of the national population, between June 2000 and May 2013. Patients who received public care for primary treatment, mostly surgical treatment, were compared with those who received private care in terms of demographics, mode of presentation, disease factors, comorbidity index and treatment factors. Cox regression modelling was performed with stepwise adjustments, and hazards of breast cancer specific mortality associated with the type of health care received was assessed.ResultsOf the 14,468 patients, 8,916 (61.6%) received public care. Compared to patients treated in private care facilities, they were older, more likely to be Māori, Pacifika or Asian and to reside in deprived neighbourhoods and rural areas, and less likely to be diagnosed with early staged cancer and to receive timely cancer treatments. They had a higher risk of mortality from breast cancer (hazard ratio: 1.95; 95% CI: 1.75, 2.17), of which 80% (95% CI: 63%, 100%) was explained by baseline differences, particularly related to ethnicity, stage at diagnosis and type of loco-regional therapy. After controlling for these demographic, disease and treatment factors, the risk of mortality was still 14% higher in the public sector patients.ConclusionsEthnicity, stage at diagnosis and type of loco-regional therapy were the three key contributors to survival disparities between patients treated in public and private health care facilities in New Zealand. The findings underscore the need for more efforts to improve the quality, timeliness and equitability of public cancer care services.     

Mouse Model for Protein Tyrosine Phosphatase D (PTPRD) Associations with Restless Leg Syndrome or Willis-Ekbom Disease and Addiction: Reduced Expression Alters Locomotion,Sleep Behaviors and Cocaine-Conditioned Place Preference

The receptor type protein tyrosine phosphatase D (PTPRD) gene encodes a cell adhesion molecule likely to influence development and connections of addiction-, locomotion- and sleep-related brain circuits in which it is expressed. The PTPRD gene harbors genome-wide association signals in studies of restless leg syndrome (Willis-Ekbom disease [WED]/restless leg syndrome [RLS]; p < 10⁻⁸) and addiction-related phenotypes (clusters of nearby single nucleotide polymorphisms [SNPs] with 10⁻² > p > 10⁻⁸ associations in several reports). We now report work that seeks (a) association between PTPRD genotypes and expression of its mRNA in postmortem human brains and (b) RLS-related, addiction-related and comparison behavioral phenotypes in hetero- and homozygous PTPRD knockout mice. We identify associations between PTPRD SNPs and levels of PTPRD mRNA in human brain samples that support validity of mouse models with altered PTPRD expression. Knockouts display less behaviorally defined sleep at the end of their active periods. Heterozygotes move more despite motor weakness/impersistence. Heterozygotes display shifted dose-response relationships for cocaine reward. They display greater preference for places paired with 5 mg/kg cocaine and less preference for places paired with 10 or 20 mg/kg. The combined data provide support for roles for common, level-of-expression PTPRD variation in locomotor, sleep and drug reward phenotypes relevant to RLS and addiction. Taken together, mouse and human results identify PTPRD as a novel therapeutic target for RLS and addiction phenotypes.