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Ping Guo, Mendwas Dzingina, Alice M Firth, Joanna M Davies, Abdel Douiri, Suzanne M O'Brien, Cathryn Pinto, Sophie Pask, Irene J Higginson, Kathy Eagar, Fliss E M Murtagh
INTRODUCTION: Provision of palliative care is inequitable with wide variations across conditions and settings in the UK. Lack of a standard way to classify by case complexity is one of the principle obstacles to addressing this. We aim to develop and validate a casemix classification to support the prediction of costs of specialist palliative care provision. METHODS AND ANALYSIS: Phase I: A cohort study to determine the variables and potential classes to be included in a casemix classification...
March 17, 2018: BMJ Open
Axel H Newton, Frantisek Spoutil, Jan Prochazka, Jay R Black, Kathryn Medlock, Robert N Paddle, Marketa Knitlova, Christy A Hipsley, Andrew J Pask
The Tasmanian tiger or thylacine ( Thylacinus cynocephalus ) was an iconic Australian marsupial predator that was hunted to extinction in the early 1900s. Despite sharing striking similarities with canids, they failed to evolve many of the specialized anatomical features that characterize carnivorous placental mammals. These evolutionary limitations are thought to arise from functional constraints associated with the marsupial mode of reproduction, in which otherwise highly altricial young use their well-developed forelimbs to climb to the pouch and mouth to suckle...
February 2018: Royal Society Open Science
Fan Huang, Jianli Tang, Lian He, Xuezhi Ding, Shaoya Huang, Youming Zhang, Yunjun Sun, Liqiu Xia
BACKGROUND: Syringolin, synthesized by a mixed non-ribosomal peptide synthetase/polyketide synthetase in Pseudomonas syringae pv. syringae (Pss) B728a, is a novel eukaryotic proteasome inhibitor. Meanwhile, directly modifying large fragments in the PKS/NRPS gene cluster through traditional DNA engineering techniques is very difficult. In this study, we directly cloned the syl gene cluster from Pss B301D-R via Red/ET recombineering to effectively express syringolin in heterologous hosts...
February 26, 2018: Microbial Cell Factories
Sophie Pask, Cathryn Pinto, Katherine Bristowe, Liesbeth van Vliet, Caroline Nicholson, Catherine J Evans, Rob George, Katharine Bailey, Joanna M Davies, Ping Guo, Barbara A Daveson, Irene J Higginson, Fliss Em Murtagh
BACKGROUND: Palliative care patients are often described as complex but evidence on complexity is limited. We need to understand complexity, including at individual patient-level, to define specialist palliative care, characterise palliative care populations and meaningfully compare interventions/outcomes. AIM: To explore palliative care stakeholders' views on what makes a patient more or less complex and insights on capturing complexity at patient-level. DESIGN: In-depth qualitative interviews, analysed using Framework analysis...
February 1, 2018: Palliative Medicine
Dóra Marosvári, Noémi Nagy, Csilla Kriston, Beáta Deák, Melinda Hajdu, Csaba Bödör, Irén Csala, Attila G Bagó, Zoltán Szállási, Anna Sebestyén, Lilla Reiniger
The primary aim of this study was to determine mTOR-pathway activity in primary central nervous system lymphoma (PCNSL), which could be a potential target for therapy. After demonstrating that p-S6 positivity largely exceeded mTOR activity, we aimed to identify other pathways that may lead to S6 phosphorylation. We measured mTOR activity with immunohistochemistry for p-mTOR and its downstream effectors p(T389)-p70S6K1, p-S6, and p-4E-BP1 in 31 cases of PCNSL and 51 cases of systemic diffuse large B-cell lymphoma (DLBCL) and evaluated alternative S6 phosphorylation pathways with p-RSK, p(T229)-p70S6K1, and PASK antibodies...
January 19, 2018: Journal of Neuropathology and Experimental Neurology
Juan Li, Daniel Prins, Hyun Jung Park, Jacob Grinfeld, Carlos Gonzalez-Arias, Stephen Loughran, Oliver M Dovey, Thorsten Klampfl, Cavan Bennett, Tina L Hamilton, Dean C Pask, Rachel Sneade, Matthew Williams, Juliet Aungier, Cedric Ghevaert, George S Vassiliou, David G Kent, Anthony R Green
Somatic mutations in the endoplasmic reticulum chaperone calreticulin (CALR) are detected in approximately 40% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF). Multiple different mutations have been reported, but all result in a +1bp frame shift and generate a novel protein C-terminus. In this study, we generated a conditional mouse knock-in model of the most common CALR mutation, a 52bp deletion. The mutant novel human C-terminal sequence is integrated into the otherwise intact mouse CALR gene and results in mutant CALR expression under the control of the endogenous mouse locus...
December 27, 2017: Blood
Charles Y Feigin, Axel H Newton, Liliya Doronina, Jürgen Schmitz, Christy A Hipsley, Kieren J Mitchell, Graham Gower, Bastien Llamas, Julien Soubrier, Thomas N Heider, Brandon R Menzies, Alan Cooper, Rachel J O'Neill, Andrew J Pask
The Tasmanian tiger or thylacine (Thylacinus cynocephalus) was the largest carnivorous Australian marsupial to survive into the modern era. Despite last sharing a common ancestor with the eutherian canids ~160 million years ago, their phenotypic resemblance is considered the most striking example of convergent evolution in mammals. The last known thylacine died in captivity in 1936 and many aspects of the evolutionary history of this unique marsupial apex predator remain unknown. Here we have sequenced the genome of a preserved thylacine pouch young specimen to clarify the phylogenetic position of the thylacine within the carnivorous marsupials, reconstruct its historical demography and examine the genetic basis of its convergence with canids...
January 2018: Nature Ecology & Evolution
Anna C Lewis, Katrina J Rankin, Andrew J Pask, Devi Stuart-Fox
Stress is an important potential factor mediating a broad range of cellular pathways, including those involved in condition-dependent (i.e., honest) color signal expression. However, the cellular mechanisms underlying the relationship between stress and color expression are largely unknown. We artificially elevated circulating corticosterone levels in male tawny dragon lizards, Ctenophorus decresii, to assess the effect of stress on the throat color signal. Corticosterone treatment increased luminance (paler throat coloration) and decreased the proportion of gray, thereby influencing the gray reticulations that produce unique patterning...
October 2017: Ecology and Evolution
Gregory M Pask, Jesse D Slone, Jocelyn G Millar, Prithwiraj Das, Jardel A Moreira, Xiaofan Zhou, Jan Bello, Shelley L Berger, Roberto Bonasio, Claude Desplan, Danny Reinberg, Jürgen Liebig, Laurence J Zwiebel, Anandasankar Ray
Eusocial insects use cuticular hydrocarbons as components of pheromones that mediate social behaviours, such as caste and nestmate recognition, and regulation of reproduction. In ants such as Harpegnathos saltator, the queen produces a pheromone which suppresses the development of workers' ovaries and if she is removed, workers can transition to a reproductive state known as gamergate. Here we functionally characterize a subfamily of odorant receptors (Ors) with a nine-exon gene structure that have undergone a massive expansion in ants and other eusocial insects...
August 17, 2017: Nature Communications
Thomas Moreau, Amanda L Evans, Louella Vasquez, Marloes R Tijssen, Ying Yan, Matthew W Trotter, Daniel Howard, Maria Colzani, Meera Arumugam, Wing Han Wu, Amanda Dalby, Riina Lampela, Guenaelle Bouet, Catherine M Hobbs, Dean C Pask, Holly Payne, Tatyana Ponomaryov, Alexander Brill, Nicole Soranzo, Willem H Ouwehand, Roger A Pedersen, Cedric Ghevaert
This corrects the article DOI: 10.1038/ncomms11208.
July 28, 2017: Nature Communications
Andrew J Lee, David J Spence, Helen M Pask
We detail the operation of a THz laser source based on non-linear stimulated polariton scattering (SPS) in Mg:LiNbO<sub>3</sub>. This system utilizes a fundamental wavelength of 1342 nm to completely avoid the negative effect of free-carrier generation within high-resistivity silicon (Si) prisms used to extract THz radiation from the Mg:LiNbO<sub>3</sub> crystal. THz power of up to 23.6 μW (62.3 μW when chopped at 50% duty cycle) was detected at 1.33 THz, and frequency tunability across the range 1...
July 15, 2017: Optics Letters
Jesse D Slone, Gregory M Pask, Stephen T Ferguson, Jocelyn G Millar, Shelley L Berger, Danny Reinberg, Jürgen Liebig, Anandasankar Ray, Laurence J Zwiebel
Animals use a variety of sensory modalities-including visual, acoustic, and chemical-to sense their environment and interact with both conspecifics and other species. Such communication is especially critical in eusocial insects such as honey bees and ants, where cooperation is critical for survival and reproductive success. Various classes of chemoreceptors have been hypothesized to play essential roles in the origin and evolution of eusociality in ants, through their functional roles in pheromone detection that characterizes reproductive status and colony membership...
August 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
Kristina Kirschner, Tamir Chandra, Vladimir Kiselev, David Flores-Santa Cruz, Iain C Macaulay, Hyun Jun Park, Juan Li, David G Kent, Rupa Kumar, Dean C Pask, Tina L Hamilton, Martin Hemberg, Wolf Reik, Anthony R Green
Aging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced stem cell function, the molecular basis of which is largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation of old HSCs carrying a p53 signature indicative of stem cell decline alongside pro-proliferative JAK/STAT signaling. To investigate the relationship between JAK/STAT and p53 signaling, we challenged HSCs with a constitutively active form of JAK2 (V617F) and observed an expansion of the p53-positive subpopulation in old mice...
May 23, 2017: Cell Reports
A Solini, G Sebastiani, L Nigi, E Santini, C Rossi, F Dotta
AIM: SGLT2 inhibitors reduce renal glucose uptake through an insulin-independent mechanism. They also increase glucagon concentration, although the extent to which this is due to a direct effect on pancreatic alpha cells remains unclear. METHODS: In the present work, αTC1 cells treated with the SGLT2 inhibitor dapagliflozin (Dapa) were analyzed for glucose transporters, molecular mediators of hormone secretion, glucagon and GLP-1 release, and the effects of somatostatin...
May 9, 2017: Diabetes & Metabolism
Axel H Newton, Charles Y Feigin, Andrew J Pask
BACKGROUND: Runt-related transcription factor 2 (RUNX2) is a transcription factor essential for skeletal development. Variation within the RUNX2 polyglutamine / polyalanine (QA) repeat is correlated with facial length within orders of placental mammals and is suggested to be a major driver of craniofacial diversity. However, it is not known if this correlation exists outside of the placental mammals. RESULTS: Here we examined the correlation between the RUNX2 QA repeat ratio and facial length in the naturally evolving sister group to the placental mammals, the marsupials...
May 4, 2017: BMC Evolutionary Biology
Yu Chen, Hongshi Yu, Andrew J Pask, Geoff Shaw, Marilyn B Renfree
Sex determination and sexual differentiation pathways are highly conserved between marsupials and eutherians. There are 2 different pathways of prostaglandin D2 (PGD2) synthesis: prostaglandin D synthase (PTGDS) and haematopoietic prostaglandin D synthase (HPGDS). PGD2 regulates the subcellular localization of SOX9 during gonadal sexual differentiation. To investigate the function of PGD2 in the tammar gonad, we cultured undifferentiated male gonads in the presence of the HPGDS inhibitor HQL-79 and female gonads with exogenous PGD2 to mimic activation of the PTGDS-PGD2 pathway...
2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
Ondrej Kitzler, Jipeng Lin, Helen M Pask, Richard P Mildren, Stephen C Webster, Nils Hempler, Graeme P A Malcolm, David J Spence
We demonstrate a single-longitudinal-mode ring diamond Raman laser, pumped by a tunable single-mode Ti:sapphire laser. Two methods to achieving unidirectional operation have been demonstrated: increasing gain for one direction using a reinjecting mirror and increasing loss for one direction using sum frequency mixing in BBO. Both methods result in a stable single-longitudinal-mode operation.
April 1, 2017: Optics Letters
Hali Bordelon, Keersten M Ricks, Megan E Pask, Patricia K Russ, Francesca Solinas, Mark L Baglia, Philip A Short, Andrew Nel, Jonathan Blackburn, Keertan Dheda, Carlos Zamudio, Tatiana Cáceres, David W Wright, Frederick R Haselton, April C Pettit
Urine samples are increasingly used for diagnosing infections including Escherichia coli, Ebola virus, and Zika virus. However, extraction and concentration of nucleic acid biomarkers from urine is necessary for many molecular detection strategies such as polymerase chain reaction (PCR). Since urine samples typically have large volumes with dilute biomarker concentrations making them prone to false negatives, another impediment for urine-based diagnostics is the establishment of appropriate controls particularly to rule out false negatives...
May 2017: Journal of Microbiological Methods
Sonia Pina-Pedrero, Àlex Olvera, Albert Bensaid
Trimeric autotransporters are surface-exposed proteins of Gram-negative bacteria belonging to the type V secretion system. They are involved in virulence and are targets for vaccine and diagnostic tool development, so optimal systems for their expression and purification are required. In the present study, the impact of the extended leader peptide of the Haemophilus parasuis virulence-associated trimeric autotransporters (VtaA) in its production as recombinant proteins in Escherichia coli was evaluated. The 13 genes encoding the VtaA1 to VtaA13 passenger domains of the strain Nagasaki were cloned in the pASK-IBA33plus plasmid and expressed in E...
May 2017: Protein Expression and Purification
Tiago A Ortega, Helen M Pask, David J Spence, Andrew J Lee
An enhancement in the performance of a THz polariton laser based on an intracavity magnesium-doped lithium niobate crystal (Mg:LiNbO<sub>3</sub>) in surface-emitted (SE) configuration is demonstrated resulting from the deposition of a protective Teflon coating on the total internal reflection surface of the crystal. In this cavity geometry the resonating fields undergo total internal reflection (TIR) inside the lithium niobate, and laser damage to that surface can be a limiting factor in performance...
February 20, 2017: Optics Express
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