Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
5,370
result(s) for
"Murphy, Mark"
Sort by:
Effect of elexacaftor/tezacaftor/ivacaftor on airway and systemic inflammation in cystic fibrosis
Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to improve lung function in people with cystic fibrosis (PWCF). However, its biological effects remain incompletely understood. Here we describe alterations in pulmonary and systemic inflammation in PWCF following initiation of ETI. To address this, we collected spontaneously expectorated sputum and matching plasma from PWCF (n=30) immediately prior to ETI therapy, then again at 3 and 12 months. Within 3 months, PWCF demonstrated reduced activity of neutrophil elastase, proteinase three and cathepsin G, and decreased concentrations of interleukin (IL)−1β and IL-8 in sputum, accompanied by decreased Pseudomonas burden and restoration of secretory leukoprotease inhibitor levels. Once treated with ETI, all airway inflammatory markers studied in PWCF had reduced to levels found in matched non-CF bronchiectasis controls. In PWCF with advanced disease, ETI resulted in decreased plasma concentrations of IL-6, C-reactive protein and soluble TNF receptor one as well as normalisation of levels of the acute phase protein, alpha-1 antitrypsin. These data clarify the immunomodulatory effects of ETI and underscore its role as a disease modifier.
Journal Article
Metabolomics responses and tolerance of Pseudomonas aeruginosa under acoustic vibration stress
Sound has been shown to impact microbial behaviors. However, our understanding of the chemical and molecular mechanisms underlying these microbial responses to acoustic vibration is limited. In this study, we used untargeted metabolomics analysis to investigate the effects of 100-Hz acoustic vibration on the intra- and extracellular hydrophobic metabolites of P. aeruginosa PAO1. Our findings revealed increased levels of fatty acids and their derivatives, quinolones, and N -acylethanolamines upon sound exposure, while rhamnolipids (RLs) showed decreased levels. Further quantitative real-time polymerase chain reaction experiments showed slight downregulation of the rhlA gene (1.3-fold) and upregulation of fabY (1.5-fold), fadE (1.7-fold), and pqsA (1.4-fold) genes, which are associated with RL, fatty acid, and quinolone biosynthesis. However, no alterations in the genes related to the rpoS regulators or quorum-sensing networks were observed. Supplementing sodium oleate to P. aeruginosa cultures to simulate the effects of sound resulted in increased tolerance of P. aeruginosa in the presence of sound at 48 h, suggesting a potential novel response-tolerance correlation. In contrast, adding RL, which went against the response direction, did not affect its growth. Overall, these findings provide potential implications for the control and manipulation of virulence and bacterial characteristics for medical and industrial applications.
Journal Article
DMRT1 prevents female reprogramming in the postnatal mammalian testis
DMRT1 loss is cue for sex swap
The presence or absence of the Y-chromosome gene
Sry
determines whether precursor cells differentiate into testicular Sertoli cells or ovarian granulosa cells in the mammalian fetus. Loss of the transcription factor FOXL2 in the adult ovary can lead to transdifferentiation of granulosa cells into Sertoli cells, but in males the sex-determining decision was thought to be stable. This study shows that this is not the case: adult mouse testicular cells become ovarian cells if the
Dmrt1
gene is lost. In the absence of transcription factor DMRT1, FOXL2 is activated and Sertoli cells are reprogrammed as granulosa cells.
Sex in mammals is determined in the fetal gonad by the presence or absence of the Y chromosome gene
Sry
, which controls whether bipotential precursor cells differentiate into testicular Sertoli cells or ovarian granulosa cells
1
. This pivotal decision in a single gonadal cell type ultimately controls sexual differentiation throughout the body. Sex determination can be viewed as a battle for primacy in the fetal gonad between a male regulatory gene network in which
Sry
activates
Sox9
and a female network involving WNT/β-catenin signalling
2
. In females the primary sex-determining decision is not final: loss of the FOXL2 transcription factor in adult granulosa cells can reprogram granulosa cells into Sertoli cells
2
. Here we show that sexual fate is also surprisingly labile in the testis: loss of the DMRT1 transcription factor
3
in mouse Sertoli cells, even in adults, activates
Foxl2
and reprograms Sertoli cells into granulosa cells. In this environment, theca cells form, oestrogen is produced and germ cells appear feminized. Thus
Dmrt1
is essential to maintain mammalian testis determination, and competing regulatory networks maintain gonadal sex long after the fetal choice between male and female.
Dmrt1
and
Foxl2
are conserved throughout vertebrates
4
,
5
and
Dmrt1
-related sexual regulators are conserved throughout metazoans
3
. Antagonism between
Dmrt1
and
Foxl2
for control of gonadal sex may therefore extend beyond mammals. Reprogramming due to loss of
Dmrt1
also may help explain the aetiology of human syndromes linked to
DMRT1
, including disorders of sexual differentiation
6
and testicular cancer
7
.
Journal Article
Knaves over queens
As the alien Xenovirus reaches Britain, Prime Minister Sir Winston Churchill, now gifted with extraordinary longevity, joins with Alan Turing to set up a special organization, the Order of the Silver Helix, to outmaneuver the terrifying mutations of the virus in Britain.
BOOK
Deciding between an X-Ray and 137Cs Irradiator – It's not just about Energy Spectra
Irradiators utilizing radioactive cesium-137 (137Cs) or cobalt-60 (60Co) gamma-ray sources have been used for biological applications for many decades. These applications include irradiation of much of the nation's blood supply and radiation biology research. In 2005, the U.S. Nuclear Regulatory Commission was assigned the task of preventing the misuse of radioactive materials by persons with malicious intentions; gamma-ray sources, in particular, were given high priority. This resulted in increased security requirements, including constant surveillance, controlled access and personnel background checks. As a result of such regulations being introduced, organizations considering the purchase of a gamma-ray irradiator for the first time or as a replacement to an existing one due to radioactive decay, are now looking into alternative technologies, primarily an X-ray irradiator. To make an educated decision on whether a particular type of X-ray irradiator is of sufficient equivalency to a particular type of 137Cs irradiator for specific applications, one must rely on relevant published comparison studies from other researchers, or perform the comparison studies on their own. This work focuses on the comparison of the radiation physics aspects of two 137Cs irradiator models and three X-ray irradiator models, for the purpose of determining whether the X-ray irradiator models could validly replace the 137Cs irradiator models for certain applications. Although evaluating the influence of relative biological effectiveness (RBE) differences among irradiators could be part of this study, that has been left for a related publication focused on the theoretical aspects of this topic. These evaluations were performed utilizing 47-g and 120-g tissue-equivalent rodent dosimetry phantoms. Our results indicate that, depending upon the user's dose uncertainty budget and maximum areal density of specimens to be irradiated, the RS 2000 160 kVp X-ray irradiator, X-RAD160 X-ray irradiator or X-RAD320 X-ray irradiator could successfully replace a 137Cs irradiator. Technically, any X-ray irradiator model providing similar irradiation geometry, and average energy similar to or higher than these three X-ray models, could also successfully replace a 137Cs irradiator. The results also reveal that differences in inherent source geometry, field geometry and irradiation geometry can counter some of the influence due to differences in energy spectrum. Our goal is that this publication be used as a guide for other similar studies, providing investigators with information on important details that can make the difference between strong and weak comparison conclusions.
Journal Article
Forest edges increase pollinator network robustness to extinction with declining area
Edge effects often exacerbate the negative effects of habitat loss on biodiversity. In forested ecosystems, however, many pollinators actually prefer open sunny conditions created by edge disturbances. We tested the hypothesis that forest edges have a positive buffering effect on plant-pollinator interaction networks in the face of declining forest area. In a fragmented land-bridge island system, we recorded ~20,000 plant-pollinator interactions on 41 islands over 3 yr. We show that plant richness and floral resources decline with decreasing forest area at both interior and edge sites, but edges maintain 10-fold higher pollinator abundance and richness regardless of area loss. Edge networks contain highly specialized species, with higher nestedness and lower modularity than interior networks, maintaining high robustness to extinction following area loss while forest interior networks collapse. Anthropogenic forest edges benefit community diversity and network robustness to extinction in the absence of natural gap-phase dynamics in small degraded forest remnants.
Analysing 20,000 plant-pollinator interactions over 3 yr in a fragmented island ecosystem, the authors show that forest edges benefit community diversity and network robustness to extinction in the face of declining forest area.
Journal Article