Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
2,246
result(s) for
"Stanley, Peter"
Sort by:
A redox switch in angiotensinogen modulates angiotensin release
A blood pressure control point
A 20-year effort has succeeded in identifying the initiating step in the molecular interactions that release the vasopressor peptide angiotensin, and hence control blood pressure. Angiotensins are generated by cleavage of a larger protein, angiotensinogen, by the enzyme renin. Crystal structures of angiotensinogen alone and bound to renin now show that a large conformational change is required to expose the renin cleavage site. This transition is regulated by oxidation, and women with pre-eclampsia — which is associated with high blood pressure — have higher levels of the more active oxidized form.
Angiotensins have a crucial role in blood pressure regulation and are generated by cleavage of a larger protein, angiotensinogen, by the enzyme renin. Structures of angiotensinogen alone and in complex with renin show that a large conformational change is required to expose the renin-cleavage site. The authors also show that this transition is regulated by oxidation and that women with pre-eclampsia have higher levels of the more active, oxidized, form.
Blood pressure is critically controlled by angiotensins
1
, which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen—a non-inhibitory member of the serpin family of protease inhibitors
2
,
3
. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1 Å resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4 Å structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia—the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child.
Journal Article
Redefining the situation : the writings of Peter McHugh
\"Peter McHugh (1929-2010) was an internationally known sociologist within the field of anti-positivist social theory. As the only selection of McHugh's sole-authored writings, Redefining the Situation presents a comprehensive yet surprising view of this key theorist's influence in this field. Redefining the Situation is a compendium of McHugh's published and unpublished short-form writings, along with three new essays on McHugh's work that include an original essay by his long-time collaborator and friend Alan Blum. The collection contributes to the project of reinventing social theory by providing a new perspective from which to imaginatively rethink the development of sociology over the last fifty years. It locates McHugh's work not only within the modern and postmodern sociological tradition but also within contemporary social theory broadly, including hermeneutics, critical theory, deconstruction, and Hannah Arendt's political theory. The essays and articles in this volume show the development of a method to analyze everyday behaviour in light of fundamental questions, exploring conflicts and connections between socialization and recidivism, fragmentation and ethnic cleansing, justice and affirmative action, teaching and university politics, and intimacy and aesthetics. It shows how we can move beyond contemporary debates about big data/postmodernism, and along the way develops convergences in Anglo-American and Continental thought. By tracing the development of the tradition of social inquiry, Analysis, from its beginnings until today, Redefining the Situation re-establishes a prominent sociologist as one of the leading intellectuals in the field of interpretive social theory. \"-- Provided by publisher.
BOOK
Farm production diversity, household dietary diversity, and nutrition: Evidence from Uganda’s national panel survey
Improved food security and nutrition remain a notable global challenge. Yet, food security and nutrition are areas of strategic importance regarding the United Nations’ Sustainable Development Goals. The increasingly weakening global food production systems pose a threat to sustainable improved food security and nutrition. Consequently, a significant population remains chronically hungry and severely malnourished. As a remedy, farm production diversity (FPD) remains a viable pathway through which household nutrition can be improved. However, evidence is mixed, or unavailable on how FPD is associated with key nutrition indicators like household dietary diversity, energy, iron, zinc, and vitamin A (micronutrients). We use the Uganda National Panel Survey (UNPS) data for rural households to analyze differential associations of sub-components of FPD on dietary diversity, energy, and micronutrient intake. Panel data models reveal that indeed crop species count, and animal species count (sub-components of FPD) are differently associated with household dietary diversity score (HDDS), energy, and vitamin A sourced from markets. Moreover, when volumes of these nutrition outcomes were disaggregated by source (own farm vs. markets), the animal species count was only positively significantly associated with nutrition outcomes sourced from consumption of produce from own farm. Associations were insignificant for nutrition indicators sourced from markets except vitamin A. The crop species count, however, consistently showed a strong positive and significant association with energy, and all studied micronutrients sourced from own farm produce consumption, as well as those sourced from markets except Vitamin A, which was negative but insignificant. Therefore, inclusive, pro-poor, and pro-nutrition rural policy initiatives in the context of rural Uganda and similar ones, could more widely improve household nutrition through prioritizing crop species diversification on own farms because crops fetch wider nutrition gains.
Journal Article
Help your kids with music : a unique step-by-step visual guide
Offers a simple, visual guide to helping children understand music with Carol Vorderman. Reduce the stress of studying music and help your child with their homework, Help Your Kids with Music is a unique visual guide to music theory which will demystify the subject for everyone. Including the latest updates to the UK National Curriculum, covering everything from semitones and note values, to harmony and music appreciation, Help Your Kids with Music helps you work through music step-by-step. Using clear, accessible pictures and diagrams you'll learn to approach even the most complex musical theory with confidence. Includes a glossary of key musical terms and symbols. Help Your Kids with Music is the perfect guide for every parent and child, who wants to understand music theory and put it into practice.
Book
Cross-domain inhibition of TACE ectodomain
Proteolytic release from the cell surface is an essential activation event for many growth factors and cytokines. TNF-α converting enzyme (TACE) is a membrane-bound metalloprotease responsible for solubilizing many pathologically significant membrane substrates and is an attractive therapeutic target for the treatment of cancer and arthritis. Prior attempts to antagonize cell-surface TACE activity have focused on small-molecule inhibition of the metalloprotease active site. Given the highly conserved nature of metalloprotease active sites, this paradigm has failed to produce a truly specific TACE inhibitor and continues to obstruct the clinical investigation of TACE activity. We report the bespoke development of a specific TACE inhibitory human antibody using \"two-step\" phage display. This approach combines calculated selection conditions with antibody variable-domain exchange to direct individual antibody variable domains to desired epitopes. The resulting \"cross-domain\" human antibody is a previously undescribed selective TACE antagonist and provides a unique alternative to small-molecule metalloprotease inhibition.
Journal Article
An evaluation of the quality of ear health services for Aboriginal children living in remote Australia: a cascade of care analysis
Background
In the Northern Territory (NT) the prevalence of otitis media (OM) in young Aboriginal children living in remote communities has persisted at around 90% over the last few decades. OM-associated hearing loss can cause developmental delay and adversely impact life course trajectories. This study examined the 5-year trends in OM prevalence and quality of ear health services in remote NT communities.
Methods
A retrospective analysis was performed on de-identified clinical data for 50 remote clinics managed by the NT Government. We report a 6-monthly cascade analysis of the proportions of children 0–16 years of age receiving local guideline recommendations for surveillance, OM treatment and follow-up at selected milestones between 2014 and 2018.
Results
Between 6,326 and 6,557 individual children were included in the 6-monthly analyses. On average, 57% (95%CI: 56–59%) of eligible children had received one or more ear examination in each 6-monthly period. Of those examined, 36% (95%CI: 33–40%) were diagnosed with some type of OM, of whom 90% had OM requiring either immediate treatment or scheduled follow-up according to local guidelines. Outcomes of treatment and follow-up were recorded in 24% and 23% of cases, respectively. Significant decreasing temporal trends were found in the proportion diagnosed with any OM across each age group. Overall, this proportion decreased by 40% over the five years (from 43 to 26%).
Conclusions
This cascade of care analysis found that ear health surveillance and compliance with otitis media guidelines for treatment and follow-up were both low. Further research is required to identify effective strategies that improve ear health services in remote settings.
Journal Article
Dialysis catheter malposition: blood gas analysis provides a clue
Correspondence to Dr Hannah Victoria Reynolds; hannah.reynolds@health.qld.gov.au Description Following surgical debridement for Fournier’s gangrene, a morbidly obese man (250 kg, Body Mass Index 87 kg/m2) was admitted to the intensive care unit (ICU) in septic shock and multiorgan failure. With the advent of bedside ultrasound and improved training, malposition of a central venous access device has been reduced but not eliminated.1 Confirming the position (or detecting malposition) of a central venous catheter may involve a conventional chest radiograph, transducing pressures or blood gas analysis on a sample from the catheter. In the literature, the incidence of partial anomalous pulmonary venous connections (PAPVC) are reported to be between 0.4% and 0.7%.2 3 Although dependent on the shunt fraction, the presence of a PAPVC is usually asymptomatic and its diagnosis is usually incidental during other investigations.4 In the critical care setting, incidental diagnosis of a partial anomalous pulmonary venous connections during dialysis catheter insertion has been well described5–7 but the utility of blood gas analysis to provide early insight to the diagnosis less so.8 Furthermore, this case highlights the benefits of accessing interventional radiology to both clarify the exact position and relocation for patients with limited other access sites.
Journal Article
Characterization of Infants’ General Movements Using a Commercial RGB-Depth Sensor and a Deep Neural Network Tracking Processing Tool: An Exploratory Study
Cerebral palsy, the most common childhood neuromotor disorder, is often diagnosed through visual assessment of general movements (GM) in infancy. This skill requires extensive training and is thus difficult to implement on a large scale. Automated analysis of GM performed using low-cost instrumentation in the home may be used to estimate quantitative metrics predictive of movement disorders. This study explored if infants’ GM may be successfully evaluated in a familiar environment by processing the 3D trajectories of points of interest (PoI) obtained from recordings of a single commercial RGB-D sensor. The RGB videos were processed using an open-source markerless motion tracking method which allowed the estimation of the 2D trajectories of the selected PoI and a purposely developed method which allowed the reconstruction of their 3D trajectories making use of the data recorded with the depth sensor. Eight infants’ GM were recorded in the home at 3, 4, and 5 months of age. Eight GM metrics proposed in the literature in addition to a novel metric were estimated from the PoI trajectories at each timepoint. A pediatric neurologist and physiatrist provided an overall clinical evaluation from infants’ video. Subsequently, a comparison between metrics and clinical evaluation was performed. The results demonstrated that GM metrics may be meaningfully estimated and potentially used for early identification of movement disorders.
Journal Article