Managerial Work in a Practice-Embodying Institution - The role of calling, the virtue of constancy

What can be learned from a small scale study of managerial work in a highly marginal and under-researched working community? This paper uses the ‘goods-virtues-practices-institutions’ framework to examine the managerial work of owner-directors of traditional circuses. Inspired by MacIntyre’s arguments for the necessity of a narrative understanding of the virtues, interviews explored how British and Irish circus directors accounted for their working lives. A purposive sample was used to select subjects who had owned and managed traditional touring circuses for at least 15 years, a period in which the economic and reputational fortunes of traditional circuses have suffered badly. This sample enabled the research to examine the self-understanding of people who had, at least on the face of it, exhibited the virtue of constancy. The research contributes to our understanding of the role of the virtues in organizations by presenting evidence of an intimate relationship between the virtue of constancy and a ‘calling’ work orientation. This enhances our understanding of the virtues that are required if management is exercised as a domain-related practice

The Effects of Vitamin D Receptor Silencing on the Expression of LVSCC-A1C and LVSCC-A1D and the Release of NGF in Cortical Neurons

Recent studies have suggested that vitamin D can act on cells in the nervous system. Associations between polymorphisms in the vitamin D receptor (VDR), age-dependent cognitive decline, and insufficient serum 25 hydroxyvitamin D(3) levels in Alzheimer's patients and elderly people with cognitive decline have been reported. We have previously shown that amyloid β (Aβ) treatment eliminates VDR protein in cortical neurons. These results suggest a potential role for vitamin D and vitamin D-mediated mechanisms in Alzheimer's disease (AD) and neurodegeneration. Vitamin D has been shown to down-regulate the L-type voltage-sensitive calcium channels, LVSCC-A1C and LVSCC-A1D, and up-regulate nerve growth factor (NGF). However, expression of these proteins when VDR is repressed is unknown. The aim of this study is to investigate LVSCC-A1C, LVSCC-A1D expression levels and NGF release in VDR-silenced primary cortical neurons prepared from Sprague-Dawley rat embryos.qRT-PCR and western blots were performed to determine VDR, LVSCC-A1C and -A1D expression levels. NGF and cytotoxicity levels were determined by ELISA. Apoptosis was determined by TUNEL. Our findings illustrate that LVSCC-A1C mRNA and protein levels increased rapidly in cortical neurons when VDR is down-regulated, whereas, LVSCC-A1D mRNA and protein levels did not change and NGF release decreased in response to VDR down-regulation. Although vitamin D regulates LVSCC-A1C through VDR, it may not regulate LVSCC-A1D through VDR.Our results indicate that suppression of VDR disrupts LVSCC-A1C and NGF production. In addition, when VDR is suppressed, neurons could be vulnerable to aging and neurodegeneration, and when combined with Aβ toxicity, it is possible to explain some of the events that occur during neurodegeneration

A new family of diprotodontian marsupials from the latest Oligocene of Australia and the evolution of wombats, koalas, and their relatives (Vombatiformes)

We describe the partial cranium and skeleton of a new diprotodontian marsupial from the late Oligocene (~26–25 Ma) Namba Formation of South Australia. This is one of the oldest Australian marsupial fossils known from an associated skeleton and it reveals previously unsuspected morphological diversity within Vombatiformes, the clade that includes wombats (Vombatidae), koalas (Phascolarctidae) and several extinct families. Several aspects of the skull and teeth of the new taxon, which we refer to a new family, are intermediate between members of the fossil family Wynyardiidae and wombats. Its postcranial skeleton exhibits features associated with scratch-digging, but it is unlikely to have been a true burrower. Body mass estimates based on postcranial dimensions range between 143 and 171 kg, suggesting that it was ~5 times larger than living wombats. Phylogenetic analysis based on 79 craniodental and 20 postcranial characters places the new taxon as sister to vombatids, with which it forms the superfamily Vombatoidea as defined here. It suggests that the highly derived vombatids evolved from wynyardiid-like ancestors, and that scratch-digging adaptations evolved in vombatoids prior to the appearance of the ever-growing (hypselodont) molars that are a characteristic feature of all post-Miocene vombatids. Ancestral state reconstructions on our preferred phylogeny suggest that bunolophodont molars are plesiomorphic for vombatiforms, with full lophodonty (characteristic of diprotodontoids) evolving from a selenodont morphology that was retained by phascolarctids and ilariids, and wynyardiids and vombatoids retaining an intermediate selenolophodont condition. There appear to have been at least six independent acquisitions of very large (>100 kg) body size within Vombatiformes, several having already occurred by the late Oligocene

HIV Protease Inhibitors Sensitize Human Head and Neck Squamous Carcinoma Cells to Radiation by Activating Endoplasmic Reticulum Stress

Background Human head and neck squamous cell carcinoma (HNSCC) is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs) have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that HIV PIs induce cell apoptosis via activation of endoplasmic reticulum (ER) stress. The aim of this study was to examine the role of ER stress in HIV PI-induced radiosensitivity in human HNSCC. Methodology and Principal Findings HNSCC cell lines, SQ20B and FaDu, and the most commonly used HIV PIs, lopinavir and ritonavir (L/R), were used in this study. Clonogenic assay was used to assess the radiosensitivity. Cell viability, apoptosis and cell cycle were analyzed using Cellometer Vision CBA. The mRNA and protein levels of ER stress-related genes (eIF2α, CHOP, ATF-4, and XBP-1), as well as cell cycle related protein, cyclin D1, were detected by real time RT-PCR and Western blot analysis, respectively. The results demonstrated that L/R dose-dependently sensitized HNSCC cells to irradiation and inhibited cell growth. L/R-induced activation of ER stress was correlated to down-regulation of cyclin D1 expression and cell cycle arrest under G0/G1 phase. Conclusion and Significance HIV PIs sensitize HNSCC cells to radiotherapy by activation of ER stress and induction of cell cycle arrest. Our results provided evidence that HIV PIs can be potentially used in combination with radiation in the treatment of HNSCC

Epigenetically-Inherited Centromere and Neocentromere DNA Replicates Earliest in S-Phase

Eukaryotic centromeres are maintained at specific chromosomal sites over many generations. In the budding yeast Saccharomyces cerevisiae, centromeres are genetic elements defined by a DNA sequence that is both necessary and sufficient for function; whereas, in most other eukaryotes, centromeres are maintained by poorly characterized epigenetic mechanisms in which DNA has a less definitive role. Here we use the pathogenic yeast Candida albicans as a model organism to study the DNA replication properties of centromeric DNA. By determining the genome-wide replication timing program of the C. albicans genome, we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome. Importantly, epigenetic formation of new ectopic centromeres (neocentromeres) was accompanied by shifts in replication timing, such that a neocentromere became the first to replicate and became associated with origin recognition complex (ORC) components. Furthermore, changing the level of the centromere-specific histone H3 isoform led to a concomitant change in levels of ORC association with centromere regions, further supporting the idea that centromere proteins determine origin activity. Finally, analysis of centromere-associated DNA revealed a replication-dependent sequence pattern characteristic of constitutively active replication origins. This strand-biased pattern is conserved, together with centromere position, among related strains and species, in a manner independent of primary DNA sequence. Thus, inheritance of centromere position is correlated with a constitutively active origin of replication that fires at a distinct early time. We suggest a model in which the distinct timing of DNA replication serves as an epigenetic mechanism for the inheritance of centromere position

Molecular characterization of glucose-6-phosphate dehydrogenase deficient variants in Baghdad city - Iraq

Background: Although G6PD deficiency is the most common genetically determined blood disorder among Iraqis, its molecular basis has only recently been studied among the Kurds in North Iraq, while studies focusing on Arabs in other parts of Iraq are still absent. Methods: A total of 1810 apparently healthy adult male blood donors were randomly recruited from the national blood transfusion center in Baghdad. They were classified into G6PD deficient and non-deficient individuals based on the results of methemoglobin reduction test (MHRT), with confirmation of deficiency by subsequent enzyme assays. DNA from deficient individuals was studied using a polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) for four deficient molecular variants, namely G6PD Mediterranean (563 C®T), Chatham (1003 G®A), A- (202 G®A) and Aures (143 T®C). A subset of those with the Mediterranean variant, were further investigated for the 1311 (C®T) silent mutation. Results: G6PD deficiency was detected in 109 of the 1810 screened male individuals (6.0%). Among 101 G6PD deficient males molecularly studied, the Mediterranean mutation was detected in 75 cases (74.3%), G6PD Chatham in 5 cases (5.0%), G6PD A- in two cases (2.0%), and G6PD Aures in none. The 1311 silent mutation was detected in 48 out of the 51 G6PD deficient males with the Mediterranean variant studied (94.1%). Conclusions: Three polymorphic variants namely: the Mediterranean, Chatham and A-, constituted more than 80% of G6PD deficient variants among males in Baghdad. Iraq. This observation is to some extent comparable to othe

Prevalence and molecular characterization of Glucose-6-Phosphate dehydrogenase deficient variants among the Kurdish population of Northern Iraq

<p>Abstract</p> <p>Background</p> <p>Glucose-6-Phosphate dehydrogenase (G6PD) is a key enzyme of the pentose monophosphate pathway, and its deficiency is the most common inherited enzymopathy worldwide. G6PD deficiency is common among Iraqis, including those of the Kurdish ethnic group, however no study of significance has ever addressed the molecular basis of this disorder in this population. The aim of this study is to determine the prevalence of this enzymopathy and its molecular basis among Iraqi Kurds.</p> <p>Methods</p> <p>A total of 580 healthy male Kurdish Iraqis randomly selected from a main regional premarital screening center in Northern Iraq were screened for G6PD deficiency using methemoglobin reduction test. The results were confirmed by quantitative enzyme assay for the cases that showed G6PD deficiency. DNA analysis was performed on 115 G6PD deficient subjects, 50 from the premarital screening group and 65 unrelated Kurdish male patients with documented acute hemolytic episodes due to G6PD deficiency. Analysis was performed using polymerase chain reaction/restriction fragment length polymorphism for five deficient molecular variants, namely G6PD Mediterranean (563 C→T), G6PD Chatham (1003 G→A), G6PD A- (202 G→A), G6PD Aures (143 T→C) and G6PD Cosenza (1376 G→C), as well as the silent 1311 (C→T) mutation.</p> <p>Results</p> <p>Among 580 random Iraqi male Kurds, 63 (10.9%) had documented G6PD deficiency. Molecular studies performed on a total of 115 G6PD deficient males revealed that 101 (87.8%) had the G6PD Mediterranean variant and 10 (8.7%) had the G6PD Chatham variant. No cases of G6PD A-, G6PD Aures or G6PD Cosenza were identified, leaving 4 cases (3.5%) uncharacterized. Further molecular screening revealed that the silent mutation 1311 was present in 93/95 of the Mediterranean and 1/10 of the Chatham cases.</p> <p>Conclusions</p> <p>The current study revealed a high prevalence of G6PD deficiency among Iraqi Kurdish population of Northern Iraq with most cases being due to the G6PD Mediterranean and Chatham variants. These results are similar to those reported from neighboring Iran and Turkey and to lesser extent other Mediterranean countries.</p

Post-traumatic glenohumeral cartilage lesions: a systematic review

<p>Abstract</p> <p>Background</p> <p>Any cartilage damage to the glenohumeral joint should be avoided, as these damages may result in osteoarthritis of the shoulder. To understand the pathomechanism leading to shoulder cartilage damage, we conducted a systematic review on the subject of articular cartilage lesions caused by traumas where non impression fracture of the subchondral bone is present.</p> <p>Methods</p> <p>PubMed (MEDLINE), ScienceDirect (EMBASE, BIOBASE, BIOSIS Previews) and the COCHRANE database of systematic reviews were systematically scanned using a defined search strategy to identify relevant articles in this field of research. First selection was done based on abstracts according to specific criteria, where the methodological quality in selected full text articles was assessed by two reviewers. Agreement between raters was investigated using percentage agreement and Cohen's Kappa statistic. The traumatic events were divided into two categories: 1) acute trauma which refers to any single impact situation which directly damages the articular cartilage, and 2) chronic trauma which means cartilage lesions due to overuse or disuse of the shoulder joint.</p> <p>Results</p> <p>The agreement on data quality between the two reviewers was 93% with a Kappa value of 0.79 indicating an agreement considered to be 'substantial'. It was found that acute trauma on the shoulder causes humeral articular cartilage to disrupt from the underlying bone. The pathomechanism is said to be due to compression or shearing, which can be caused by a sudden subluxation or dislocation. However, such impact lesions are rarely reported. In the case of chronic trauma glenohumeral cartilage degeneration is a result of overuse and is associated to other shoulder joint pathologies. In these latter cases it is the rotator cuff which is injured first. This can result in instability and consequent impingement which may progress to glenohumeral cartilage damage.</p> <p>Conclusion</p> <p>The great majority of glenohumeral cartilage lesions without any bony lesions are the results of overuse. Glenohumeral cartilage lesions with an intact subchondral bone and caused by an acute trauma are either rare or overlooked. And at increased risk for such cartilage lesions are active sportsmen with high shoulder demand or athletes prone to shoulder injury.</p

Process evaluation of a participatory ergonomics programme to prevent low back pain and neck pain among workers

Background: Both low back pain (LBP) and neck pain (NP) are major occupational health problems. In the workplace, participatory ergonomics (PE) is frequently used on musculoskeletal disorders. However, evidence on the effectiveness of PE to prevent LBP and NP obtained from randomised controlled trials (RCTs) is scarce. This study evaluates the process of the Stay@Work participatory ergonomics programme, including the perceived implementation of the prioritised ergonomic measures.Methods: This cluster-RCT was conducted at the departments of four Dutch companies (a railway transportation company, an airline company, a steel company, and a university including its university medical hospital). Directly after the randomisation outcome, intervention departments formed a working group that followed the steps of PE during a six-hour working group meeting. Guided by an ergonomist, working groups identified and prioritised risk factors for LBP and NP, and composed and prioritised ergonomic measures. Within three months after the meeting, working groups had to implement the prioritised ergonomic measures at their department. Data on various process components (recruitment, reach, fidelity, satisfaction, and implementation components, i.e., dose delivered and dose received) were collected and analysed on two levels: department (i.e., working group members from intervention departments) and participant (i.e., workers from intervention departments).Results: A total of 19 intervention departments (n = 10 with mental workloads, n = 1 with a light physical workload, n = 4 departments with physical and mental workloads, and n = 4 with heavy physical workloads) were recruited for participation, and the reach among working group members who participated was high (87%). Fidelity and satisfaction towards the PE programme rated by the working group members was good (7.3 or higher). The same was found for the Stay@Work ergocoach training (7.5 or higher). In total, 66 ergonomic measures were prioritised by the working groups. Altogether, 34% of all prioritised ergonomic measures were perceived as implemented (dose delivered), while the workers at the intervention departments perceived 26% as implemented (dose received).Conclusions: PE can be a successful method to develop and to prioritise ergonomic measures to prevent LBP and NP. Despite the positive rating of the PE programme the implementation of the prioritised ergonomic measures was lower than expected. © 2010 Driessen et al; licensee BioMed Central Ltd