A Microbial Strategy to Multiply in Macrophages: The Pregnant Pause

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72518/1/j.1600-0854.2002.030302.x.pd

Academic freedom: in justification of a universal ideal

This paper examines the justification for, and benefits of, academic freedom to academics, students, universities and the world at large. The paper surveys the development of the concept of academic freedom within Europe, more especially the impact of the reforms at the University of Berlin instigated by Wilhelm von Humboldt. Following from this, the paper examines the reasons why the various facets of academic freedom are important and why the principle should continue to be supported

The Wnt5a Receptor, Receptor Tyrosine Kinase-Like Orphan Receptor 2, Is a Predictive Cell Surface Marker of Human Mesenchymal Stem Cells with an Enhanced Capacity for Chondrogenic Differentiation

Multipotent mesenchymal stem cells (MSCs) have enormous potential in tissue engineering and regenerative medicine. However until now their development for clinical use has been severely limited as they are a mixed population of cells with varying capacities for lineage differentiation and tissue formation. Here we identify ROR2 as a cell surface marker expressed by those MSCs with an enhanced capacity for cartilage formation. We generated clonal human MSC populations with varying capacities for chondrogenesis. ROR2 was identified through screening for upregulated genes in the most chondrogenic clones. When isolated from un-cloned populations, ROR2+ve MSCs were significantly more chondrogenic than either ROR2-ve or unfractionated MSCs. In a sheep cartilage-repair model they produced significantly more defect filling with no loss of cartilage quality compared with controls. ROR2+ve MSCs/perivascular cells were present in developing human cartilage, adult bone marrow and adipose tissue. Their frequency in bone marrow was significantly lower in patients with osteoarthritis than in controls. However after isolation of these cells and their initial expansion in vitro, there was greater ROR2 expression in the population derived from osteoarthritis patients compared with controls. Furthermore, osteoarthritis-derived MSCs were better able to form cartilage than MSCs from control patients in a tissue engineering assay. We conclude that MSCs expressing high levels of ROR2 provide a defined population capable of predictably enhanced cartilage production. This article is protected by copyright. All rights reserved

Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis

Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors

Control and involvement HR practices in Indian call centres: Still searching for answers

Call centres were established primarily to reduce organizational costs while simultaneously providing high-quality customer service. To support this 'twin constraints' strategy, a range of human resource (HR) practices tends to be used in call centres that focus simultaneously on both control and involvement. To date, there has been a lack of empirical evidence concerning the outcome of such HR practices on call centre frontline staff (call centre representatives - CCRs). Consequently, this paper attempts to bridge this gap using a sample of 250 CCRs from Indian call centres. The findings show that, while the simultaneous use of involvement-and control-oriented HR practices had a positive impact on CCR job satisfaction, it also resulted in employee exhaustion and disengagement. These findings suggest that while involvement-oriented HR practices enhance CCR job satisfaction, they come at a cost which is potentially a key factor leading to high CCR turnover

Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma

BACKGROUND: Recent evidence suggests that progesterone metabolites play important roles in regulating breast cancer. Previous studies have shown that tumorous tissues have higher 5α-reductase (5αR) and lower 3α-hydroxysteroid oxidoreductase (3α-HSO) and 20α-HSO activities. The resulting higher levels of 5α-reduced progesterone metabolites such as 5α-pregnane-3,20-dione (5αP) in tumorous tissue promote cell proliferation and detachment, whereas the 4-pregnene metabolites, 4-pregnen-3α-ol-20-one (3αHP) and 4-pregnen-20α-ol-3-one (20αDHP), more prominent in normal tissue, have the opposite (anti-cancer-like) effects. The aim of this study was to determine if the differences in enzyme activities between tumorous and nontumorous breast tissues are associated with differences in progesterone metabolizing enzyme gene expression. METHODS: Semi-quantitative RT-PCR was used to compare relative expression (as a ratio of 18S rRNA) of 5αR type 1 (SRD5A1), 5αR type 2 (SRD5A2), 3α-HSO type 2 (AKR1C3), 3α-HSO type 3 (AKR1C2) and 20α-HSO (AKR1C1) mRNAs in paired (tumorous and nontumorous) breast tissues from 11 patients, and unpaired tumor tissues from 17 patients and normal tissues from 10 reduction mammoplasty samples. RESULTS: Expression of 5αR1 and 5αR2 in 11/11 patients was higher (mean of 4.9- and 3.5-fold, respectively; p < 0.001) in the tumor as compared to the paired normal tissues. Conversely, expression of 3α-HSO2, 3α-HSO3 and 20α-HSO was higher (2.8-, 3.9- and 4.4-fold, respectively; p < 0.001) in normal than in tumor sample. The mean tumor:normal expression ratios for 5αR1 and 5αR2 were about 35–85-fold higher than the tumor:normal expression ratios for the HSOs. Similarly, in the unmatched samples, the tumor:normal ratios for 5αR were significantly higher than the ratios for the HSOs. CONCLUSIONS: The study shows changes in progesterone metabolizing enzyme gene expression in human breast carcinoma. Expression of SRD5A1 (5αR1) and SRD5A2 (5αR2) is elevated, and expression of AKR1C1 (20α-HSO), AKR1C2 (3α-HSO3) and AKR1C3 (3α-HSO2) is reduced in tumorous as compared to normal breast tissue. The changes in progesterone metabolizing enzyme expression levels help to explain the increases in mitogen/metastasis inducing 5αP and decreases in mitogen/metastasis inhibiting 3αHP progesterone metabolites found in breast tumor tissues. Understanding what causes these changes in expression could help in designing protocols to prevent or reverse the changes in progesterone metabolism associated with breast cancer

Resident physician and hospital pharmacist familiarity with patient discharge medication costs

Objective Cost-related medication non-adherence is associated with increased health-care resource utilization and poor patient outcomes. Physicians-in-training generally receive little education regarding costs of prescribed therapy and may rely on hospital pharmacists for this information. However, little is documented regarding either of these health care providers’ familiarity with out-of pocket medication expenses borne by patients in the community. The purpose of this study was to evaluate and compare resident physician and hospital pharmacist familiarity with what patients pay for medications prescribed once discharged. Setting A major tertiary patient care and medical teaching centre in Canada. Method Internal medicine residents and hospital pharmacists within a specific health care organization were invited to participate in an online survey. Eight patient case scenarios and associated discharge therapeutic regimens were outlined and respondents asked to identify the costs patients would incur when having the prescription filled once discharged. Main Outcome Measure Total number and proportion of estimates above and below actual cost were calculated and compared between the groups using χ2 tests. Responses ±10% of the true cost were considered correct. Mean absolute values and standard deviation estimated costs, as well as cost increments above and below 10%, were calculated to assess the magnitude of the discrepancy between the respondent estimates and the actual total cost. Results Forty-four percent of physician residents and 26% of hospital pharmacists accessed the survey. Overall 39% and 47% of medication costs were under-estimated, 32% and 33% were overestimated, and 29% and 21% were correctly estimated by residents and pharmacists, respectively (P = NS). Incorrect estimates were evident across all therapeutic classes and medical indications presented in the survey. The greatest absolute cost discrepancy for both groups was under-estimation of linezolid ($800 and$400) and over-estimation of clopidogrel ($80) and bisoprolol therapy ($22) by residents and pharmacists, respectively. Conclusion Resident physicians and hospital pharmacists are unfamiliar with what patients must pay for drug therapy once discharged

Subjective well-being indicators for large-scale assessment of cultural ecosystem services

The substantial importance of cultural benefits as a source of human well-being is increasingly recognised in society-environment interactions. The integration of cultural ecosystem services (CES) into the ecosystem services framework remains a challenge due to the difficulties associated with defining, articulating and measuring CES. We operationalise a novel framework developed by the UK National Ecosystem Assessment that identifies CES as the interactions between environmental spaces (i.e. physical localities or landscapes), and the activities that occur there. We evaluate the benefits of the CES provided by 151 UK marine sites to recreational sea anglers and divers, using subjective well-being indicators. Factor analysis of an online questionnaire with 1220 participants revealed multiple CES benefits that contribute to human wellbeing e.g. including ‘engagement with nature’, ‘place identity’ and ‘therapeutic value’. In addition to regional differences, we also found that biophysical attributes of sites, such as the presence of charismatic species and species diversity, were positively associated with provision of CES benefits. The study provides evidence that could be used to inform designation of protected areas. The indicators used in the study may also be adapted for use across a range of marine and terrestrial spaces for improved integration of CES in environmental decisionmaking