Keratin 6a marks mammary bipotential progenitor cells that can give rise to a unique tumor model resembling human normal-like breast cancer.

Progenitor cells are considered an important cell of origin of human malignancies. However, there has not been any single gene that can define mammary bipotential progenitor cells, and as such it has not been possible to use genetic methods to introduce oncogenic alterations into these cells in vivo to study tumorigenesis from them. Keratin 6a is expressed in a subset of mammary luminal epithelial cells and body cells of terminal end buds. By generating transgenic mice using the Keratin 6a (K6a) gene promoter to express tumor virus A (tva), which encodes the receptor for avian leukosis virus subgroup A (ALV/A), we provide direct evidence that K6a(+) cells are bipotential progenitor cells, and the first demonstration of a non-basal location for some biopotential progenitor cells. These K6a(+) cells were readily induced to form mammary tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding the polyoma middle T antigen. Tumors in this K6a-tva line were papillary and resembled the normal breast-like subtype of human breast cancer. This is the first model of this subtype of human tumors and thus may be useful for preclinical testing of targeted therapy for patients with normal-like breast cancer. These observations also provide direct in vivo evidence for the hypothesis that the cell of origin affects mammary tumor phenotypes

Meditation Awareness Training (MAT) for Work-related Wellbeing and Job Performance: A Randomised Controlled Trial

Due to its potential to concurrently improve work-related wellbeing (WRW) and job performance, occupational stakeholders are becoming increasingly interested in the applications of meditation. The present study conducted the first randomized controlled trial to assess the effects of meditation on outcomes relating to both WRW and job performance. Office-based middle-hierarchy managers (n = 152) received an eight-week meditation intervention (Meditation Awareness Training; MAT) or an active control intervention. MAT participants demonstrated significant and sustainable improvements (with strong effect sizes) over control-group participants in levels of work-related stress, job satisfaction, psychological distress, and employer-rated job performance. There are a number of novel implications: (i) meditation can effectuate a perceptual shift in how employees experience their work and psychological environment and may thus constitute a cost-effective WRW intervention, (ii) meditation-based (i.e., present-moment-focussed) working styles may be more effective than goal-based (i.e., future-orientated) working styles, and (iii) meditation may reduce the separation made by employees between their own interests and those of the organizations they work for

PEDRo: A database for storing, searching and disseminating experimental proteomics data

Abstract Background Proteomics is rapidly evolving into a high-throughput technology, in which substantial and systematic studies are conducted on samples from a wide range of physiological, developmental, or pathological conditions. Reference maps from 2D gels are widely circulated. However, there is, as yet, no formally accepted standard representation to support the sharing of proteomics data, and little systematic dissemination of comprehensive proteomic data sets. Results This paper describes the design, implementation and use of a Proteome Experimental Data Repository (PEDRo), which makes comprehensive proteomics data sets available for browsing, searching and downloading. It is also serves to extend the debate on the level of detail at which proteomics data should be captured, the sorts of facilities that should be provided by proteome data management systems, and the techniques by which such facilities can be made available. Conclusions The PEDRo database provides access to a collection of comprehensive descriptions of experimental data sets in proteomics. Not only are these data sets interesting in and of themselves, they also provide a useful early validation of the PEDRo data model, which has served as a starting point for the ongoing standardisation activity through the Proteome Standards Initiative of the Human Proteome Organisation

Induction of Protective Immunity against Chlamydia muridarum Intravaginal Infection with a Chlamydial Glycogen Phosphorylase

We evaluated 7 C. muridarum ORFs for their ability to induce protection against chlamydial infection in a mouse intravaginal infection model. These antigens, although encoded in C. muridarum genome, are transcriptionally regulated by a cryptic plasmid that is known to contribute to C. muridarum pathogenesis. Of the 7 plasmid-regulated ORFs, the chlamydial glycogen phosphorylase or GlgP, when delivered into mice intramuscularly, induced the most pronounced protective immunity against C. muridarum intravaginal infection. The GlgP-immunized mice displayed a significant reduction in vaginal shedding of live organisms on day 14 after infection. The protection correlated well with a robust C. muridarum-specific antibody and a Th1-dominant T cell responses, which significantly reduced the severity but not overall incidence of hydrosalpinx. The GlgP-induced partial protection against upper genital tract pathology suggests that GlgP may be considered a component for a multi-subunit vaccine. These results have demonstrated that intramuscular immunization of mice with purified proteins can be used to identify vaccine antigens for preventing intravaginal infection with C. trachomatis in humans

Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency

BACKGROUND: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors. METHODS: We measured three different types of biomarkers, including desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid. RESULTS: Effect of study medication on any of the biomarkers was not seen. Baseline desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05). Mean coefficient of variation within patients (CVi) for plasma and urine desmosines was 18.7 to 13.5%, respectively. Change in urinary desmosine levels correlated significantly with change in plasma desmosine levels (R = 0.84, p < 0.01). Mean CVi for fibrinogen fragments in plasma was 20.5% and for JM403 in urine was 27.8%. No correlations were found between fibrinogen fragments or JM403 epitope and desmosines. CONCLUSION: We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects

Addiction Treatment and Stable Housing among a Cohort of Injection Drug Users

Background: Unstable housing and homelessness is prevalent among injection drug users (IDU). We sought to examine whether accessing addiction treatment was associated with attaining stable housing in a prospective cohort of IDU in Vancouver, Canada. Methods: We used data collected via the Vancouver Injection Drug User Study (VIDUS) between December 2005 and April 2010. Attaining stable housing was defined as two consecutive ‘‘stable housing’ ’ designations (i.e., living in an apartment or house) during the follow-up period. We assessed exposure to addiction treatment in the interview prior to the attainment of stable housing among participants who were homeless or living in single room occupancy (SRO) hotels at baseline. Bivariate and multivariate associations between the baseline and time-updated characteristics and attaining stable housing were examined using Cox proportional hazard regression models. Principal Findings: Of the 992 IDU eligible for this analysis, 495 (49.9%) reported being homeless, 497 (50.1%) resided in SRO hotels, and 380 (38.3%) were enrolled in addiction treatment at the baseline interview. Only 211 (21.3%) attained stable housing during the follow-up period and of this group, 69 (32.7%) had addiction treatment exposure prior to achieving stable housing. Addiction treatment was inversely associated with attaining stable housing in a multivariate model (adjusted hazard ratio [AHR] = 0.71; 95 % CI: 0.52–0.96). Being in a partnered relationship was positively associated with the primary outcom

Temporal variability in shell mound formation at Albatross Bay, northern Australia

We report the results of 212 radiocarbon determinations from the archaeological excavation of 70 shell mound deposits in the Wathayn region of Albatross Bay, Australia. This is an intensive study of a closely co-located group of mounds within a geographically restricted area in a wider region where many more shell mounds have been reported. Valves from the bivalve Tegillarcca granosa were dated. The dates obtained are used to calculate rates of accumulation for the shell mound deposits. These demonstrate highly variable rates of accumulation both within and between mounds. We assess these results in relation to likely mechanisms of shell deposition and show that rates of deposition are affected by time-dependent processes both during the accumulation of shell deposits and during their subsequent deformation. This complicates the interpretation of the rates at which shell mound deposits appear to have accumulated. At Wathayn, there is little temporal or spatial consistency in the rates at which mounds accumulated. Comparisons between the Wathayn results and those obtained from shell deposits elsewhere, both in the wider Albatross Bay region and worldwide, suggest the need for caution when deriving behavioural inferences from shell mound deposition rates, and the need for more comprehensive sampling of individual mounds and groups of mounds

Cancer Stem Cell-Like Cells Derived from Malignant Peripheral Nerve Sheath Tumors

This study aims to examine whether or not cancer stem cells exist in malignant peripheral nerve sheath tumors (MPNST). Cells of established lines, primary cultures and freshly dissected tumors were cultured in serum free conditions supplemented with epidermal and fibroblast growth factors. From one established human MPNST cell line, S462, cells meeting the criteria for cancer stem cells were isolated. Clonal spheres were obtained, which could be passaged multiple times. Enrichment of stem cell-like cells in these spheres was also supported by increased expression of stem cell markers such as CD133, Oct4, Nestin and NGFR, and decreased expression of mature cell markers such as CD90 and NCAM. Furthermore, cells of these clonal S462 spheres differentiated into Schwann cells, smooth muscle/fibroblast and neurons-like cells under specific differentiation-inducing cultural conditions. Finally, subcutaneous injection of the spheres into immunodeficient nude mice led to tumor formation at a higher rate compared to the parental adherent cells (66% versus 10% at 2.5×105). These results provide evidence for the existence of cancer stem cell-like cells in malignant peripheral nerve sheath tumors

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd