Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153088/1/feb213699.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153088/2/feb213699_am.pd

Motivation and incentives of rural maternal and neonatal health care providers: a comparison of qualitative findings from Burkina Faso, Ghana and Tanzania.

In Burkina Faso, Ghana and Tanzania strong efforts are being made to improve the quality of maternal and neonatal health (MNH) care. However, progress is impeded by challenges, especially in the area of human resources. All three countries are striving not only to scale up the number of available health staff, but also to improve performance by raising skill levels and enhancing provider motivation. In-depth interviews were used to explore MNH provider views about motivation and incentives at primary care level in rural Burkina Faso, Ghana and Tanzania. Interviews were held with 25 MNH providers, 8 facility and district managers, and 2 policy-makers in each country. Across the three countries some differences were found in the reasons why people became health workers. Commitment to remaining a health worker was generally high. The readiness to remain at a rural facility was far less, although in all settings there were some providers that were willing to stay. In Burkina Faso it appeared to be particularly difficult to recruit female MNH providers to rural areas. There were indications that MNH providers in all the settings sometimes failed to treat their patients well. This was shown to be interlinked with differences in how the term 'motivation' was understood, and in the views held about remuneration and the status of rural health work. Job satisfaction was shown to be quite high, and was particularly linked to community appreciation. With some important exceptions, there was a strong level of agreement regarding the financial and non-financial incentives that were suggested by these providers, but there were clear country preferences as to whether incentives should be for individuals or teams. Understandings of the terms and concepts pertaining to motivation differed between the three countries. The findings from Burkina Faso underline the importance of gender-sensitive health workforce planning. The training that all levels of MNH providers receive in professional ethics, and the way this is reinforced in practice require closer attention. The differences in the findings across the three settings underscore the importance of in-depth country-level research to tailor the development of incentives schemes

Charlie-is-so-“English”-like: Nationality and the branded-celebrity person in the age of YouTube

The YouTube celebrity is a novel social phenomenon. YouTube celebrities have implications for the social and cultural study of celebrity more generally but in order to illustrate the features of vlogging celebrity and its wider dimensions, this article focuses upon one case-study – Charlie McDonnell and his video ‘How to be English’. The premise of YouTube – ‘Broadcast Yourself’ – begs the question ‘but what self?’ The article argues the YouTube celebrity is able to construct a celebrity persona by appealing to aspects of identity, such as nationality, and use them as a mask(s) to perform with. By situating Charlie’s ‘How to be English’ in the context of establishing celebrity, the article argues that the processes of celebrification and ‘self-branding’ utilise the power of identity myths to help assist the construction of a celebrity persona. Use of masks and myths allows for one to develop various aspects of their persona into personae. One such persona for Charlie is his ‘Englishness’. As the social experience of ‘Broadcasting Yourself’ necessarily asks one to turn ordinary aspects of their person into extra-ordinary qualities, Charlie’s use of Englishness allows ‘being English’ to become a mythological device to overcome the problem of ‘self-promotion’

Comparable endocrine and neuromuscular adaptations to variable vs. constant gravity-dependent resistance training among young women.

BACKGROUND:Variable resistance has been shown to induce greater total work and muscle activation when compared to constant resistance. However, little is known regarding the effects of chronic exposure to variable resistance training in comparison with constant resistance training. The aim of the present study was therefore to examine the effects of chain-loaded variable and constant gravity-dependent resistance training on resting hormonal and neuromuscular adaptations. METHODS:Young women were randomly assigned to variable resistance training (VRT; n = 12; age, 23.75 ± 3.64 years; and BMI, 26.80 ± 4.21 kg m-2), constant resistance training (CRT; n = 12; age, 23.58 ± 3.84 years; BMI, 25.25 ± 3.84 kg m-2), or control (Con; n = 12; age, 23.50 ± 2.93 years; BMI, 27.12 ± 12 kg m-2) groups. CRT performed 8-week total-body free-weight training three times per week with moderate-to-high intensity (65-80% 1RM; periodized). VRT was the same as CRT but included variable resistance via chains (15% of total load). Resting serum samples were taken before and after the 8-week intervention for GH, IGF-1, cortisol, myostatin, and follistatin analyses. RESULTS:Both VRT and CRT groups displayed moderate-to-large significant increases in GH (197.1%; ES = 0.78 vs. 229.9%; ES = 1.55), IGF-1 (82.3%; ES = 1.87 vs. 66%; ES = 1.66), and follistatin (58.8%; ES = 0.80 vs. 49.15%; ES = 0.80) and decreases in cortisol (- 19.9%; ES = - 1.34 vs. - 17.1%; ES = - 1.05) and myostatin (- 26.9%; ES = - 0.78 vs. - 23.2%; ES = - 0.82). Also, VRT and CRT resulted in large significant increases in bench press (30.54%; ES = 1.45 vs. 25.08%; ES = 1.12) and squat (30.63%; ES = 1.28 vs. 24.81%; ES = 1.21) strength, with no differences between groups. CONCLUSIONS:Implementing chain-loaded VRT into a periodized resistance training program can be an effective alternative to constant loading during free-weight RT among untrained young women

The Induction of MicroRNA Targeting IRS-1 Is Involved in the Development of Insulin Resistance under Conditions of Mitochondrial Dysfunction in Hepatocytes

BACKGROUND: Mitochondrial dysfunction induces insulin resistance in myocytes via a reduction of insulin receptor substrate-1 (IRS-1) expression. However, the effect of mitochondrial dysfunction on insulin sensitivity is not understood well in hepatocytes. Although research has implicated the translational repression of target genes by endogenous non-coding microRNAs (miRNA) in the pathogenesis of various diseases, the identity and role of the miRNAs that are involved in the development of insulin resistance also remain largely unknown. METHODOLOGY: To determine whether mitochondrial dysfunction induced by genetic or metabolic inhibition causes insulin resistance in hepatocytes, we analyzed the expression and insulin-stimulated phosphorylation of insulin signaling intermediates in SK-Hep1 hepatocytes. We used qRT-PCR to measure cellular levels of selected miRNAs that are thought to target IRS-1 3' untranslated regions (3'UTR). Using overexpression of miR-126, we determined whether IRS-1-targeting miRNA causes insulin resistance in hepatocytes. PRINCIPAL FINDINGS: Mitochondrial dysfunction resulting from genetic (mitochondrial DNA depletion) or metabolic inhibition (Rotenone or Antimycin A) induced insulin resistance in hepatocytes via a reduction in the expression of IRS-1 protein. In addition, we observed a significant up-regulation of several miRNAs presumed to target IRS-1 3'UTR in hepatocytes with mitochondrial dysfunction. Using reporter gene assay we confirmed that miR-126 directly targeted to IRS-1 3'UTR. Furthermore, the overexpression of miR-126 in hepatocytes caused a substantial reduction in IRS-1 protein expression, and a consequent impairment in insulin signaling. CONCLUSIONS/SIGNIFICANCE: We demonstrated that miR-126 was actively involved in the development of insulin resistance induced by mitochondrial dysfunction. These data provide novel insights into the molecular basis of insulin resistance, and implicate miRNA in the development of metabolic disease

The degree of segmental aneuploidy measured by total copy number abnormalities predicts survival and recurrence in superficial gastroesophageal adenocarcinoma

Background: Prognostic biomarkers are needed for superficial gastroesophageal adenocarcinoma (EAC) to predict clinical outcomes and select therapy. Although recurrent mutations have been characterized in EAC, little is known about their clinical and prognostic significance. Aneuploidy is predictive of clinical outcome in many malignancies but has not been evaluated in superficial EAC. Methods: We quantified copy number changes in 41 superficial EAC using Affymetrix SNP 6.0 arrays. We identified recurrent chromosomal gains and losses and calculated the total copy number abnormality (CNA) count for each tumor as a measure of aneuploidy. We correlated CNA count with overall survival and time to first recurrence in univariate and multivariate analyses. Results: Recurrent segmental gains and losses involved multiple genes, including: HER2, EGFR, MET, CDK6, KRAS (recurrent gains); and FHIT, WWOX, CDKN2A/B, SMAD4, RUNX1 (recurrent losses). There was a 40-fold variation in CNA count across all cases. Tumors with the lowest and highest quartile CNA count had significantly better overall survival (p = 0.032) and time to first recurrence (p = 0.010) compared to those with intermediate CNA counts. These associations persisted when controlling for other prognostic variables. Significance: SNP arrays facilitate the assessment of recurrent chromosomal gain and loss and allow high resolution, quantitative assessment of segmental aneuploidy (total CNA count). The non-monotonic association of segmental aneuploidy with survival has been described in other tumors. The degree of aneuploidy is a promising prognostic biomarker in a potentially curable form of EAC. © 2014 Davison et al

Antineoplastic effects of rosiglitazone and PPARγ transactivation in neuroblastoma cells

Neuroblastoma (NB) is the most common extracranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. In the present study, we evaluated the role of the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (RGZ) in two NB cell lines (SK-N-AS and SH-SY5Y), which express PPARγ. Rosiglitazone decreased cell proliferation and viability to a greater extent in SK-N-AS than in SH-SY5Y. Furthermore, 20 μM RGZ significantly inhibited cell adhesion, invasiveness and apoptosis in SK-N-AS, but not in SH-SY5Y. Because of the different response of SK-N-AS and SH-SY5Y cells to RGZ, the function of PPARγ as a transcriptional activator was assessed. Noticeably, transient transcription experiments with a PPARγ responsive element showed that RGZ induced a three-fold increase of the reporter activity in SK-N-AS, whereas no effect was observed in SH-SY5Y. The different PPARγ activity may be likely due to the markedly lower amount of phopshorylated (i.e. inactive) protein observed in SK-N-AS. To our knowledge, this is the first demonstration that the differential response of NB cells to RGZ may be related to differences in PPARγ transactivation. This finding indicates that PPARγ activity may be useful to select those patients, for whom PPARγ agonists may have a beneficial therapeutic effect

Localization and function of the renal calcium-sensing receptor

The ability to monitor changes in the ionic composition of the extracellular environment is a crucial feature that has evolved in all living organisms. The cloning and characterization of the extracellular calcium-sensing receptor (CaSR) from the mammalian parathyroid gland in the early 1990s provided the first description of a cellular, ion-sensing mechanism. This finding demonstrated how cells can detect small, physiological variations in free ionized calcium (Ca 2+) in the extracellular fluid and subsequently evoke an appropriate biological response by altering the secretion of parathyroid hormone (PTH) that acts on PTH receptors expressed in target tissues, including the kidney, intestine, and bone. Aberrant Ca 2+ sensing by the parathyroid glands, as a result of altered CaSR expression or function, is associated with impaired divalent cation homeostasis. CaSR activators that mimic the effects of Ca 2+ (calcimimetics) have been designed to treat hyperparathyroidism, and CaSR antagonists (calcilytics) are in development for the treatment of hypercalciuric disorders. The kidney expresses a CaSR that might directly contribute to the regulation of many aspects of renal function in a PTH-independent manner. This Review discusses the roles of the renal CaSR and the potential impact of pharmacological modulation of the CaSR on renal function

The institutions of archaic post-modernity and their organizational and managerial consequences: The case of Portugal

The long march of modernization of the Western societies tends to be presented as following a regular sequence: societies and institutions were pre-modern, and then they were modernized, eventually becoming post-modern. Such teleology may provide an incomplete or distorted narrative of societal evolution in many parts of the world, even in the ‘post-modern heartland’ of Western Europe, with Portugal being a case in point. The concept of archaic post-modernity has been developed by a philosopher, José Gil, to show how Portuguese institutions and organizations combine elements of pre-modernity and post-modernity. The notion of an archaic post-modernity is advanced in order to provide an alternative account of the modernization process, which enriches discussion of the varieties of capitalism. Differences in historical experiences create singularities that may be considered in the analysis of culture, management and organization