Shape stabilization and laser triggered shape transformation of magnetic particle functionalized liquid metal motors

Liquid metal motors made from biologically benign gallium are promising candidates for various applications ranging from drug delivery to targeting and killing cancer cells directly. One of the main problems with this novel technology is the need to utilize a membrane, making it possible to maintain a defined shape in order to perform the required functions. For magnetic remote guidance, liquid metal motors can be doped with magnetic iron microparticles, forming a transition magnetic liquid. In an alternative approach liquid metal structures are coated with magnetite nanoparticles. We hereby present an approach to laminate biologically benign gallium-based magnetic liquid metal motors with a biodegradable and biocompatible macromolecular thin film to retain the initial shape. Thanks to the polymer lamination and by the help of magnetic fields, the presented liquid metal motors can be remotely guided. The shape retaining macromolecular thin film can be liquefied by photothermal effects such as laser irradiation in order to change the shape of the liquid metal motor into a droplet due to surface energy minimization, allowing for penetration of structures smaller than the initial motor size. This work uses a relatively large technical demonstrator to show the technical realization and properties of this novel system, which opens up new paths and potential applications

Mechanistic Insight into the Reactivation of BCAII Enzyme from Denatured and Molten Globule States by Eukaryotic Ribosomes and Domain V rRNAs

In all life forms, decoding of messenger-RNA into polypeptide chain is accomplished by the ribosome. Several protein chaperones are known to bind at the exit of ribosomal tunnel to ensure proper folding of the nascent chain by inhibiting their premature folding in the densely crowded environment of the cell. However, accumulating evidence suggests that ribosome may play a chaperone role in protein folding events in vitro. Ribosome-mediated folding of denatured proteins by prokaryotic ribosomes has been studied extensively. The RNA-assisted chaperone activity of the prokaryotic ribosome has been attributed to the domain V, a span of 23S rRNA at the intersubunit side of the large subunit encompassing the Peptidyl Transferase Centre. Evidently, this functional property of ribosome is unrelated to the nascent chain protein folding at the exit of the ribosomal tunnel. Here, we seek to scrutinize whether this unique function is conserved in a primitive kinetoplastid group of eukaryotic species Leishmania donovani where the ribosome structure possesses distinct additional features and appears markedly different compared to other higher eukaryotic ribosomes. Bovine Carbonic Anhydrase II (BCAII) enzyme was considered as the model protein. Our results manifest that domain V of the large subunit rRNA of Leishmania ribosomes preserves chaperone activity suggesting that ribosome-mediated protein folding is, indeed, a conserved phenomenon. Further, we aimed to investigate the mechanism underpinning the ribosome-assisted protein reactivation process. Interestingly, the surface plasmon resonance binding analyses exhibit that rRNA guides productive folding by directly interacting with molten globule-like states of the protein. In contrast, native protein shows no notable affinity to the rRNA. Thus, our study not only confirms conserved, RNA-mediated chaperoning role of ribosome but also provides crucial insight into the mechanism of the process

Crop Updates 2000 - Oilseeds

This session covers seventeen papers from different authors: Introduction, Paul Carmody, Centre for Cropping Systems CANOLA AGRONOMY 2. Genotype, location and year influence the quality of canola grown across southern Australia, PingSi1, Rodney Mailer2, Nick Galwey1 and David Turner1, 1Plant Sciences, Faculty of Agriculture, The University of Western Australia, 2Agricultural Research Institute, New South Wales Agriculture 3. Development of Pioneer® Canola varieties for Australian market,Kevin Morthorpe, StephenAddenbrooke, Pioneer Hi-Bred Australia Pty Ltd 4. Canola, Erucic Acid, Markets and Agronomic Implications, Peter Nelson, The Grain Pool of Western Australia 5. The control of Capeweed in Clearfield Production System for Canola, Mike Jackson and ScottPaton, Cyanamid Agriculture Pty Ltd 6. Responsiveness of Canola to Soil Potassium Levels: How Low Do We Have To Go? Ross Brennan, Noeleen Edwards, Mike Bolland and Bill Bowden,Agriculture Western Australia 7. Adaption of Indian Mustard (Brassica juncea) in the Mediterranean Environment of South Western Australia, C.P. Gunasekera1, L.D. Martin1, G.H. Walton2 and K.H.M. Siddique2 1Muresk Institute of Agriculture, Curtin University of Technology, Northam, 2Agriculture Western Australia 8. Physiological Aspects of Drought Tolerance in Brassica napus and B.juncea, Sharon R. Niknam and David W. Turner, Plant Sciences, Faculty of Agriculture, The University of Western Australia 9. Cross resistance of chlorsulfuron-resistant wild radish to imidazolinones, Abul Hashem, Harmohinder Dhammu and David Bowran, Agriculture Western Australia 10. Canola Variety and PBR Update 2000, From The Canola Association of Western Australia 11. Development of a canola ideotype for the low rainfall areas of the western Australian wheat belt, Syed H. Zaheer, Nick W. Galwey and David W. Turner, Faculty of Agriculture, The University of Western Australia DISEASE MANAGEMENT 12. Evaluation of fungicides for the management of blackleg in canola, Ravjit Khangura and Martin J. Barbetti, Agriculture Western Australia 13. Impact-IFÒ: Intergral in the control of Blackleg, Peter Carlton, Trials Coordinator, Elders Limited 14. Forecasting aphid and virus risk in canola, Debbie Thackray, Jenny Hawkes and Roger Jones, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture 15. Beet western yellow virus in canola: 1999 survey results, wild radish weed reservoir and suppression by insecticide, Roger Jones and Brenda Coutts, Agriculture Western Australia 16. Are canola crops resilient to damage by aphids and diamond back moths? Françoise Berlandier, Agriculture Western Australia ECONOMIC OUTLOOK 17. Outlook for prices and implications for rotations, Ross Kingwell1,2, Michael O’Connell1 and Simone Blennerhasset11Agriculture Western Australia 2University of Western Australi

DNA instability in replicating Huntington's disease lymphoblasts

<p>Abstract</p> <p>Background</p> <p>The expanded CAG repeat in the Huntington's disease (HD) gene may display tissue-specific variability (e.g. triplet mosaicism) in repeat length, the longest mutations involving mitotic (germ and glial cells) and postmitotic (neurons) cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths.</p> <p>Results</p> <p>Although most lymphoblastoid cell lines (88%) showed little or no repeat instability even after six or more months culture, in lymphoblasts with large expansion repeats beyond 60 CAG repeats the mutation size and triplet mosaicism always increased during replication, implying that the repeat mutability for highly expanded mutations may quantitatively depend on the triplet expansion size. None of the investigated genetic factors, potentially acting <it>in cis </it>to the mutation, significantly influence the repeat changes. Finally, in our experiments certain drugs controlled triplet expansion in two prone-to-expand HD cell lines carrying large CAG mutations.</p> <p>Conclusion</p> <p>Our data support quantitative evidence that the inherited CAG length of expanded alleles has a major influence on somatic repeat variation. The longest triplet expansions show wide somatic variations and may offer a mechanistic model to study triplet drug-controlled instability and genetic factors influencing it.</p

Crop Updates 2005 - Lupins and Pulses

This session covers sixty five papers from different authors: 1. 2004 LUPIN AND PULSE INDUSTRY HIGHLIGHTS, Peter White Department of Agriculture 2. BACKGROUND, Peter White Department of Agriculture 2004 REGIONAL ROUNDUP 3. Northern Agricultural Region, Martin Harries, Department of Agriculture 4. Central Agricultural Region, Ian Pritchard, Department of Agriculture 5. Great Southern and Lakes, Rodger Beermier, Department of Agriculture 6. Esperance Port Zone, Mark Seymour, Department of Agriculture, and David Syme, The Grain Pool of WA LUPIN AND PULSE PRODUCTION AGRONOMY AND GENETIC IMPROVEMENT 7. Lupin, Martin Harries, Department of Agriculture 8. Narrow-leafed lupin breeding, Bevan Buirchell, Department of Agriculture 9. Yellow lupin breeding in Western Australia, Kedar Adhikari, Mark Sweetingham and Bevan Buirchell, Department of Agriculture 10. WALAB2000 - First Anthracnose resistant albus lupins, Kedar Adhikari, Bevan Buirchell, MarkSweetingham and Geoff Thomas, Department of Agriculture 11. Improving lupin grain quality and yield through genetic manipulation of key physiological traits, Jon Clements1 and Bevan Buirchell2,1CLIMA, The University of Western Australia 2Department of Agriculture 12. Lupin alkaloids in four Australian species, Shao Fang Wang, Chemistry Centre (WA), CLIMA, The University of Western Australia 13. Improving lupin tolerance to herbicides of metribuzin, isoxaflutole and carfentrazone-ethyl, Ping Si1, Mark Sweetingham12, Bevan Buirchell12, David Bowran2 and Huaan Yang12 , 1CLIMA, The University of Western Australia, 2Department of Agriculture 14. Combined cultural and shielded sprayer herbicide application for weed management, Martin Harries and Mike Baker Department of Agriculture 15. Field testing of lupin seed of various sources with and without post maturity, pre harvest rain for field establishment, Martin Harries, Wayne Parker, Mike Baker, Department of Agriculture 16. Lupin seed rate by wide row spacing, Martin Harries, Bob French, Damien Owen D’arcy, Department of Agriculture 17. How environment influences row spacing response in lupins, Bob French, Department of Agriculture 18. The effect of wider row spacing on lupin architecture, growth and nutrient uptake dynamics, Bill Bowden and Craig Scanlan, Department of Agriculture 19. Fertiliser placement and application rate in wide rows, Martin Harries, Damien Owen D’arcy, Department of Agriculture 20. The pros and cons of cowing lupins in ‘wide’ rows, Wayne Parker, Bob French and Martin Harries, Department of Agriculture 21. Investigation into the influence of row orientation in lupin crops, Jeff Russell1 and Angie Roe2, 1Department of Agriculture, 2Farm Focus Consultants 22. Making the most of Mandelup, Greg Shea and Chris Matthews, Department of Agriculture 23. The effect of wild radish density and lupin cultivars on their competition at Merredin, Shahab Pathan, Abul Hashem and Bob French, Department of Agriculture 24. The potential of pearl lupin (Lupinus mutabilis) for southern Australia, Jon Clements1, Mark Sweetingham2, Bevan Buirchell2, Sofia Sipsas2, Geoff Thomas2, John Quealy1, Roger Jones2, Clive Francis1, Colin Smith2 and Gordon Francis1, 1CLIMA, University of Western Australia 2Department of Agriculture 25. Field pea, Mark Seymour, Department of Agriculture 26. Breeding highlights, Tanveer. Khan and Bob French, Department of Agriculture 27. Variety evaluation, Tanveer Khan, Kerry Regan, Jenny Garlinge and Rod Hunter, Department of Agriculture 28. Large scale field pea variety trials, Martin Harries, Department of Agriculture 29. Kaspa demonstrations, Rodger Beermier, Mark Seymour, Ian Pritchard, Graham Mussell, Department of Agriculture 30. Field pea harvesting demonstration at Merredin, Glen Riethmuller, Greg Shea and Bob French, Department of Agriculture 31. Does Kaspa respond differently to disease, fungicides, time of sowing or seed rate, Mark Seymour, Department of Agriculture 32. Field pea response to foliar Manganese in mallee district, Mark Seymour, Department of Agriculture 33. Kaspa harvesting observations 2004, Mark Seymour, Ian Pritchard, Glen Riethmuller, Department of Agriculture 34. ‘Blackspot Manager’ for understanding blackspot of peas and ascochyta blight management, Moin Salam and Jean Galloway, Department of Agriculture 35. 250,000 ha of field pea in WA – Is it sustainable? Larn McMurray1 and Mark Seymour2, 1South Australian Research and Development Institute, 2Department of Agriculture 36. Desi chickpea, Wayne Parker, Department of Agriculture 37. Breeding highlights, Tanveer Khan1,2 and Kadambot Siddique2,1Department of Agriculture, 2CLIMA, The University of Western Australia 38. Variety evaluation, Tanveer Khan, Kerry Regan, Jenny Garlinge and Rod Hunter, Department of Agriculture 39. Large scale variety testing of desi chickpeas, Martin Harries, Greg Shea, Mike Baker, Dirranie Kirby, Department of Agriculture 40. Desi variety chickpea trial, Martin Harries and Murray Blyth, Department of Agriculture 41. Seeding rates and row spacing of chickpea desi, Martin Harries, MurrayBlyth, Damien Owen D’arcy, Department of Agriculture 42. Molecular characterisation of chickpea wild relatives, Fucheng Shan, Heather Clarke and Kadambot Siddique, CLIMA, The University of Western Australia 43. Plant phosphorus status has a limited influence on the concentration of phosphorus-mobilising carboxylates in the rhizosphere of chickpea, Madeleine Wouterlood, Hans Lambers and Erik Veneklaas, The University of Western Australia 44. Kabuli chickpea, Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 45. ‘Kimberly Large’ A high quality and high yielding new variety for the Ord River Irrigation Area, Kerry Regan1,2, Kadambot Siddique2, Peter White1,2, Peter Smith1 and Gae Plunkett1,1Department of Agriculture, 2CLIMA, University of Western Australia 46. Development of ascochyta resistant and high quality varieties for Australia, Kadambot Siddique1, Kerry Regan1,2, Tim Pope1 and Mike Baker2, 1CLIMA, The University of Western Australia 2Department of Agriculture 47. Towards double haploids in chickpeas and field pea, Janine Croser, Julia Wilson and Kadambot Siddique, CLIMA, The University of Western Australia 48. Crossing chickpea with wild Cicer relatives to introduce resistance to disease and tolerance to environmental stress, Heather Clarke and Kadambot Siddique, CLIMA, The University of Western Australia 49. Faba bean, Peter White, Department of Agriculture 50. Germplasm evaluation, Peter White1,2, Kerry Regan1,2, Tim Pope2, Martin Harries1, Mark Seymour1, Rodger Beermier1 and Leanne Young1, 1Department of Agriculture, 2CLIMA, The University of Western Australia 51. Lentil, Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 52. Variety and germplasm evaluation, Kerry Regan1,2, Tim Pope2, Leanne Young1, Martin Harries1, Murray Blyth1 and Michael Materne3, 1Department of Agriculture, 2CLIMA, University of Western Australia, 3Department of Primary Industries, Victoria 53. Lathyrus species, Kadambot Siddique1, Kerry Regan2, and Colin Hanbury2, 1CLIMA, the University of Western Australia, 2Department of Agricultur

Doxorubicin-induced chronic dilated cardiomyopathy—the apoptosis hypothesis revisited

The chemotherapeutic agent doxorubicin (DOX) has significantly increased survival rates of pediatric and adult cancer patients. However, 10% of pediatric cancer survivors will 10–20 years later develop severe dilated cardiomyopathy (DCM), whereby the exact molecular mechanisms of disease progression after this long latency time remain puzzling. We here revisit the hypothesis that elevated apoptosis signaling or its increased likelihood after DOX exposure can lead to an impairment of cardiac function and cause a cardiac dilation. Based on recent literature evidence, we first argue why a dilated phenotype can occur when little apoptosis is detected. We then review findings suggesting that mature cardiomyocytes are protected against DOX-induced apoptosis downstream, but not upstream of mitochondrial outer membrane permeabilisation (MOMP). This lack of MOMP induction is proposed to alter the metabolic phenotype, induce hypertrophic remodeling, and lead to functional cardiac impairment even in the absence of cardiomyocyte apoptosis. We discuss findings that DOX exposure can lead to increased sensitivity to further cardiomyocyte apoptosis, which may cause a gradual loss in cardiomyocytes over time and a compensatory hypertrophic remodeling after treatment, potentially explaining the long lag time in disease onset. We finally note similarities between DOX-exposed cardiomyocytes and apoptosis-primed cancer cells and propose computational system biology as a tool to predict patient individual DOX doses. In conclusion, combining recent findings in rodent hearts and cardiomyocytes exposed to DOX with insights from apoptosis signal transduction allowed us to obtain a molecularly deeper insight in this delayed and still enigmatic pathology of DC

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe