Saharan dust electrification perceived by a triangle of atmospheric electricity stations in Southern Portugal

Atmospheric Electric Potential Gradient (PG) measurements were carried out in three sites forming a triangular array in Southern Portugal. The campaign was performed during the summer, characterized by Saharan dust outbreaks; 16th-17th July 2014 dust event is considered. Short time-scale oscillations of the PG at two of the stations and a mid time-scale suppression of the PG in the three stations are found. Results are interpreted as evidencing long-range dust electrification; attributed to the air-Earth electrical current creating a bipolar charge distribution inside of the dust layer. The relevance of using arrays of sensors, instead of single sited, is highlighted

SNAIL vs vitamin D receptor expression in colon cancer: therapeutics implications

Vitamin D analogues with reduced hypercalcemic activity are under clinical investigation for use against colon cancer and other neoplasias. However, only a subset of patients responds to this therapy, most probably due to loss of vitamin D receptor (VDR) expression during tumour progression. Recent data show that SNAIL transcription factor represses VDR expression, and thus abolishes the antiproliferative and prodifferentiation effects of VDR ligands in cultured cancer cells and their antitumour action in xenografted mice. Accordingly, upregulation of SNAIL in human colon tumours associates with downregulation of VDR. These findings suggest that SNAIL may be associated with loss of responsiveness to vitamin D analogues and may thus be used as an indicator of patients who are unlikely to respond to this therapy

A critique of Bernstein’s beyond objectivism and relativism: science, hermeneutics, and praxis

This analysis comments on Bernstein’s lack of clear understanding of subjectivity, based on his book, Beyond Objectivism and Relativism: Science, Hermeneutics, and Praxis. Bernstein limits his interpretation of subjectivity to thinkers such as Gadamer and Habermas. The authors analyze the ideas of classic scholars such as Edmund Husserl and Friedrich Nietzsche. Husserl put forward his notion of transcendental subjectivity and phenomenological ramifications of the relationship between subjectivity and objectivity. Nietzsche referred to subjectivity as “perspectivism,” the inescapable fact that any and all consciousnesses exist in space and time. Consciousness is fundamentally constituted of cultural, linguistic, and historical dimensions

Validity of the Postoperative Morbidity Survey after abdominal aortic aneurysm repair—a prospective observational study

BACKGROUND: Currently, there is no standardised tool used to capture morbidity following abdominal aortic aneurysm (AAA) repair. The aim of this prospective observational study was to validate the Postoperative Morbidity Survey (POMS) according to its two guiding principles: to only capture morbidity substantial enough to delay discharge from hospital and to be a rapid, simple screening tool. METHODS: A total of 64 adult patients undergoing elective infrarenal AAA repair participated in the study. Following surgery, the POMS was recorded daily, by trained research staff with the clinical teams blinded, until hospital discharge or death. We modelled the data using Cox regression, accounting for the competing risk of death, with POMS as a binary time-dependent (repeated measures) internal covariate. For each day for each patient, ‘discharged’ (yes/no) was the event, with the elapsed number of days post-surgery as the time variable. We derived the hazard ratio for any POMS morbidity (score 1–9) vs. no morbidity (zero), adjusted for type of repair (endovascular versus open), age and aneurysm size. RESULTS: The hazard ratio for alive discharge with any POMS-recorded morbidity versus no morbidity was 0.130 (95 % confidence interval 0.070 to 0.243). The median time-to-discharge was 13 days after recording any POMS morbidity vs. 2 days after scoring zero for POMS morbidity. Compliance with POMS completion was 99.5 %. CONCLUSIONS: The POMS is a valid tool for capturing short-term postoperative morbidity following elective infrarenal AAA repair that is substantial enough to delay discharge from hospital. Daily POMS measurement is recommended to fully capture morbidity and allow robust analysis. The survey could be a valuable outcome measure for use in quality improvement programmes and future research

The increase in cancer prevalence and hospital burden in Western Australia, 1992-2011

Purpose - To describe cancer prevalence and hospital service utilization by prevalent cancer patients in Western Australia from 1992 to 2011. Methods - This study was a population-based cohort study using the Western Australia (WA) Cancer Registry (1982 to 2011) as the source of incident cancer cases. These data were linked to mortality (1982 to 2011) and hospital morbidity (1998 to 2011) records via the WA Data Linkage System to ascertain complete and limited-duration prevalence and cancer-related hospitalizations over time. Prevalence rates were calculated using estimated residential population data from the Australian Bureau of Statistics. Results - In 2011, one in every 27 people living in WA had been diagnosed with cancer at some time in their lifetime, and one in 68 had been diagnosed within the previous five years. Between 1992 and 2011, complete cancer prevalence in Western Australia increased by a magnitude of 2.5-fold. Forty-five and 44% of the increase in complete cancer prevalence in males and females between 1992 and 2011 can be attributed to prostate and breast cancer, respectively. The absolute number of cancer-related bed days increased 81 and 74% in males and females, respectively, diagnosed within one year, between 1998 and 2011. Conclusions - The prevalence of cancer and the burden it places on hospitals continues to rise, demanding ongoing efforts to prevent cancer through modifiable risk factors and better, more efficient use of health resources. Steps should to be taken to understand and address overdiagnosis and overtreatmen

Effects of Clinically Relevant MPL Mutations in the Transmembrane Domain Revealed at the Atomic Level through Computational Modeling

BACKGROUND: Mutations in the thrombopoietin receptor (MPL) may activate relevant pathways and lead to chronic myeloproliferative neoplasms (MPNs). The mechanisms of MPL activation remain elusive because of a lack of experimental structures. Modern computational biology techniques were utilized to explore the mechanisms of MPL protein activation due to various mutations. RESULTS: Transmembrane (TM) domain predictions, homology modeling, ab initio protein structure prediction, and molecular dynamics (MD) simulations were used to build structural dynamic models of wild-type and four clinically observed mutants of MPL. The simulation results suggest that S505 and W515 are important in keeping the TM domain in its correct position within the membrane. Mutations at either of these two positions cause movement of the TM domain, altering the conformation of the nearby intracellular domain in unexpected ways, and may cause the unwanted constitutive activation of MPL's kinase partner, JAK2. CONCLUSIONS: Our findings represent the first full-scale molecular dynamics simulations of the wild-type and clinically observed mutants of the MPL protein, a critical element of the MPL-JAK2-STAT signaling pathway. In contrast to usual explanations for the activation mechanism that are based on the relative translational movement between rigid domains of MPL, our results suggest that mutations within the TM region could result in conformational changes including tilt and rotation (azimuthal) angles along the membrane axis. Such changes may significantly alter the conformation of the adjacent and intrinsically flexible intracellular domain. Hence, caution should be exercised when interpreting experimental evidence based on rigid models of cytokine receptors or similar systems

Iron: a target for the management of Kaposi's sarcoma?

BACKGROUND: Kaposi's sarcoma (KS) is a mesenchymal tumour associated with human herpesvirus-8 infection. However, the incidence of human herpesvirus-8 infection is far higher than the prevalence of KS, suggesting that viral infection per se is not sufficient for the development of malignancy and that one or more additional cofactors are required. DISCUSSION: Epidemiological data suggest that iron may be one of the cofactors involved in the pathogenesis of KS. Iron is a well-known carcinogen and may favour KS growth through several pathways. Based on the apoptotic and antiproliferative effect of iron chelation on KS cells, it is suggested that iron withdrawal strategies could be developed for the management of KS. Studies using potent iron chelators in suitable KS animal models are critical to evaluate whether iron deprivation may be a useful anti-KS strategy. SUMMARY: It is suggested that iron may be one of non-viral co-factors involved of KS pathogenesis and that iron withdrawal strategies might interfere with tumour growth in patients with KS

Dissection of QTL effects for root traits using a chromosome arm-specific mapping population in bread wheat

A high-resolution chromosome arm-specific mapping population was used in an attempt to locate/detect gene(s)/QTL for different root traits on the short arm of rye chromosome 1 (1RS) in bread wheat. This population consisted of induced homoeologous recombinants of 1RS with 1BS, each originating from a different crossover event and distinct from all other recombinants in the proportions of rye and wheat chromatin present. It provides a simple and powerful approach to detect even small QTL effects using fewer progeny. A promising empirical Bayes method was applied to estimate additive and epistatic effects for all possible marker pairs simultaneously in a single model. This method has an advantage for QTL analysis in minimizing the error variance and detecting interaction effects between loci with no main effect. A total of 15 QTL effects, 6 additive and 9 epistatic, were detected for different traits of root length and root weight in 1RS wheat. Epistatic interactions were further partitioned into inter-genomic (wheat and rye alleles) and intra-genomic (rye–rye or wheat–wheat alleles) interactions affecting various root traits. Four common regions were identified involving all the QTL for root traits. Two regions carried QTL for almost all the root traits and were responsible for all the epistatic interactions. Evidence for inter-genomic interactions is provided. Comparison of mean values supported the QTL detection

A Single Heterochromatin Boundary Element Imposes Position-Independent Antisilencing Activity in Saccharomyces cerevisiae Minichromosomes

Chromatin boundary elements serve as cis-acting regulatory DNA signals required to protect genes from the effects of the neighboring heterochromatin. In the yeast genome, boundary elements act by establishing barriers for heterochromatin spreading and are sufficient to protect a reporter gene from transcriptional silencing when inserted between the silencer and the reporter gene. Here we dissected functional topography of silencers and boundary elements within circular minichromosomes in Saccharomyces cerevisiae. We found that both HML-E and HML-I silencers can efficiently repress the URA3 reporter on a multi-copy yeast minichromosome and we further showed that two distinct heterochromatin boundary elements STAR and TEF2-UASrpg are able to limit the heterochromatin spreading in circular minichromosomes. In surprising contrast to what had been observed in the yeast genome, we found that in minichromosomes the heterochromatin boundary elements inhibit silencing of the reporter gene even when just one boundary element is positioned at the distal end of the URA3 reporter or upstream of the silencer elements. Thus the STAR and TEF2-UASrpg boundary elements inhibit chromatin silencing through an antisilencing activity independently of their position or orientation in S. cerevisiae minichromosomes rather than by creating a position-specific barrier as seen in the genome. We propose that the circular DNA topology facilitates interactions between the boundary and silencing elements in the minichromosomes