597 research outputs found
Identifying and prioritising services in European terrestrial and freshwater ecosystems
Ecosystems are multifunctional and provide humanity with a broad array of vital services. Effective management of services requires an improved evidence base, identifying the role of ecosystems in delivering multiple services, which can assist policy-makers in maintaining them. Here, information from the literature and scientific experts was used to systematically document the importance of services and identify trends in their use and status over time for the main terrestrial and freshwater ecosystems in Europe. The results from this review show that intensively managed ecosystems contribute mostly to vital provisioning services (e.g. agro-ecosystems provide food via crops and livestock, and forests provide wood), while semi-natural ecosystems (e.g. grasslands and mountains) are key contributors of genetic resources and cultural services (e.g. aesthetic values and sense of place). The most recent European trends in human use of services show increases in demand for crops from agro-ecosystems, timber from forests, water flow regulation from rivers, wetlands and mountains, and recreation and ecotourism in most ecosystems, but decreases in livestock production, freshwater capture fisheries, wild foods and virtually all services associated with ecosystems which have considerably decreased in area (e.g. semi-natural grasslands). The condition of the majority of services show either a degraded or mixed status across Europe with the exception of recent enhancements in timber production in forests and mountains, freshwater provision, water/erosion/natural hazard regulation and recreation/ecotourism in mountains, and climate regulation in forests. Key gaps in knowledge were evident for certain services across all ecosystems, including the provision of biochemicals and natural medicines, genetic resources and the regulating services of seed dispersal, pest/disease regulation and invasion resistance
Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study
Introduction The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of ‘isotoxic’ radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable.
Methods and analysis Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years.
Ethics and dissemination The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West—Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally.
Trial registration number NCT01836692; Pre-result
Highly controlled, reproducible measurements of aerosol emissions from combustion of a common African biofuel source
Particulate emissions from biomass burning can both alter the atmosphere's radiative
balance and cause significant harm to human health. However, due to the large
effect on emissions caused by even small alterations to the way in which
a fuel burns, it is difficult to study particulate production of biomass
combustion mechanistically and in a repeatable manner. In order to address
this gap, in this study, small wood samples sourced from Côte D'Ivoire in
West Africa were burned in a highly controlled laboratory environment. The
shape and mass of samples, available airflow and surrounding thermal
environment were carefully regulated. Organic aerosol and refractory black
carbon emissions were measured in real time using an Aerosol Mass
Spectrometer and a Single Particle Soot Photometer, respectively. This
methodology produced remarkably repeatable results, allowing aerosol
emissions to be mapped directly onto different phases of combustion.
Emissions from pyrolysis were visible as a distinct phase before flaming was
established. After flaming combustion was initiated, a black-carbon-dominant
flame was observed during which very little organic aerosol was produced,
followed by a period that was dominated by organic-carbon-producing
smouldering combustion, despite the presence of residual flaming. During
pyrolysis and smouldering, the two phases producing organic aerosol, distinct
mass spectral signatures that correspond to previously reported variations in
biofuel emissions measured in the atmosphere are found. Organic aerosol
emission factors averaged over an entire combustion event were found to be
representative of the time spent in the pyrolysis and smouldering phases,
rather than reflecting a coupling between emissions and the mass loss of the
sample. Further exploration of aerosol yields from similarly carefully
controlled fires and a careful comparison with data from macroscopic fires
and real-world emissions will help to deliver greater constraints on the
variability of particulate emissions in atmospheric systems
Revealing the chemical characteristics of Arctic low-level cloud residuals – in situ observations from a mountain site
The role aerosol chemical composition plays in Arctic
low-level cloud formation is still poorly understood. In this study we
address this issue by combining in situ observations of the chemical
characteristics of cloud residuals (dried liquid cloud droplets or ice
crystals) and aerosol particles from the Zeppelin Observatory in
Ny-Ålesund, Svalbard (approx. 480 m a.s.l.). These measurements were
part of the 1-year-long Ny-Ã…lesund Aerosol and Cloud Experiment
2019–2020 (NASCENT). To obtain the chemical composition of cloud residuals
at molecular level, we deployed a Filter Inlet for Gases and AEROsols
coupled to a Chemical Ionization Mass Spectrometer (FIGAERO-CIMS) with
iodide as the reagent ion behind a ground-based counterflow virtual impactor
(GCVI). The station was enshrouded in clouds roughly 15 % of the time
during NASCENT, out of which we analyzed 14 cloud events between December
2019 and December 2020. During the entire year, the composition of the cloud
residuals shows contributions from oxygenated organic compounds, including
organonitrates, and traces of the biomass burning tracer levoglucosan. In
summer, methanesulfonic acid (MSA), an oxidation product of dimethyl sulfide
(DMS), shows large contributions to the sampled mass, indicating marine
natural sources of cloud condensation nuclei (CCN) and ice nucleating
particle (INP) mass during the sunlit part of the year. In addition, we
also find contributions of the inorganic acids nitric acid and sulfuric acid,
with outstanding high absolute signals of sulfuric acid in one cloud
residual sample in spring and one in late summer (21 May and 12 September 2020), probably caused by high anthropogenic sulfur emissions near the
Barents Sea and Kara Sea. During one particular cloud event, on 18 May 2020,
the air mass origin did not change before, during, or after the
cloud. We therefore chose it as a case study to investigate cloud impact on
aerosol physicochemical properties. We show that the overall chemical
composition of the organic aerosol particles was similar before, during, and
after the cloud, indicating that the particles had already undergone one or
several cycles of cloud processing before being measured as residuals at the
Zeppelin Observatory and/or that, on the timescales of the observed cloud event, cloud
processing of the organic fraction can be neglected. Meanwhile, there were on
average fewer particles but relatively more in the accumulation mode after
the cloud. Comparing the signals of sulfur-containing compounds of cloud
residuals with aerosols during cloud-free conditions, we find that sulfuric
acid had a higher relative contribution to the cloud residuals than to
aerosols during cloud-free conditions, but we did not observe an increase in
particulate MSA due to the cloud. Overall, the chemical composition,
especially of the organic fraction of the Arctic cloud residuals, reflected
the overall composition of the general aerosol population well. Our results
thus suggest that most aerosols can serve as seeds for low-level clouds in
the Arctic.</p
Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes
BACKGROUND: Mouse and human skeletal muscle transcriptome profiles vary by muscle type, raising the question of which mouse muscle groups have the greatest molecular similarities to human skeletal muscle. METHODS: Orthologous (whole, sub-) transcriptome profiles were compared among four mouse-human transcriptome datasets: (M) six muscle groups obtained from three mouse strains (wildtype, mdx, mdx(5cv)); (H1) biopsied human quadriceps from controls and Duchenne muscular dystrophy patients; (H2) four different control human muscle types obtained at autopsy; and (H3) 12 different control human tissues (ten non-muscle). RESULTS: Of the six mouse muscles examined, mouse soleus bore the greatest molecular similarities to human skeletal muscles, independent of the latters' anatomic location/muscle type, disease state, age and sampling method (autopsy versus biopsy). Significant similarity to any one mouse muscle group was not observed for non-muscle human tissues (dataset H3), indicating this finding to be muscle specific. CONCLUSION: This observation may be partly explained by the higher type I fiber content of soleus relative to the other mouse muscles sampled
Arctic observations of hydroperoxymethyl thioformate (HPMTF) – seasonal behavior and relationship to other oxidation products of dimethyl sulfide at the Zeppelin Observatory, Svalbard
Dimethyl sulfide (DMS), a gas produced by phytoplankton, is the largest
source of atmospheric sulfur over marine areas. DMS undergoes oxidation in
the atmosphere to form a range of oxidation products, out of which sulfuric
acid (SA) is well known for participating in the formation and growth of
atmospheric aerosol particles, and the same is also presumed for
methanesulfonic acid (MSA). Recently, a new oxidation product of DMS,
hydroperoxymethyl thioformate (HPMTF), was discovered and later also measured
in the atmosphere. Little is still known about the fate of this compound and
its potential to partition into the particle phase. In this study, we present
a full year (2020) of concurrent gas- and particle-phase observations of
HPMTF, MSA, SA and other DMS oxidation products at the Zeppelin Observatory
(Ny-Ã…lesund, Svalbard) located in the Arctic. This is the first time
HPMTF has been measured in Svalbard and attempted to be observed in
atmospheric particles. The results show that gas-phase HPMTF concentrations
largely follow the same pattern as MSA during the sunlit months
(April–September), indicating production of HPMTF around Svalbard. However,
HPMTF was not observed in significant amounts in the particle phase, despite
high gas-phase levels. Particulate MSA and SA were observed during the
sunlit months, although the highest median levels of particulate SA were
measured in February, coinciding with the highest gaseous SA levels with
assumed anthropogenic origin. We further show that gas- and particle-phase
MSA and SA are coupled in May–July, whereas HPMTF lies outside of this
correlation due to the low particulate concentrations. These results provide
more information about the relationship between HPMTF and other DMS
oxidation products, in a part of the world where these have not been explored
yet, and about HPMTF's ability to contribute to particle growth and cloud
formation.</p
Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to promote resolution of inflammation
Terminally differentiated neutrophils are short-lived but the key effector cells of the innate immune response, and have a prominent role in the pathogenesis and propagation of many inflammatory diseases. Delayed apoptosis, which is responsible for their extended longevity, is critically dependent on a balance of intracellular survival versus pro-apoptotic proteins. Here, we elucidate the mechanism by which the cyclin-dependent kinase (CDK) inhibitor drugs such as R-roscovitine and DRB (5,6-dichloro-1-beta--ribofuranosylbenzimidazole) mediate neutrophil apoptosis. We demonstrate (by a combination of microarray, confocal microscopy, apoptosis assays and western blotting) that the phosphorylation of RNA polymerase II by CDKs 7 and 9 is inhibited by R-roscovitine and that specific effects on neutrophil transcriptional capacity are responsible for neutrophil apoptosis. Finally, we show that specific CDK7 and 9 inhibition with DRB drives resolution of neutrophil-dominant inflammation. Thus, we highlight a novel mechanism that controls both primary human neutrophil transcription and apoptosis that could be targeted by selective CDK inhibitor drugs to resolve established inflammation
Characterization of the effects of cross-linking of macrophage CD44 associated with increased phagocytosis of apoptotic PMN
Control of macrophage capacity for apoptotic cell clearance by soluble mediators such as cytokines, prostaglandins and lipoxins, serum proteins, and glucocorticoids may critically determine the rate at which inflammation resolves. Previous studies suggested that macrophage capacity for clearance of apoptotic neutrophils was profoundly altered following binding of CD44 antibodies. We have used a number of different approaches to further define the mechanism by which CD44 rapidly and specifically augment phagocytosis of apoptotic neutrophils. Use of Fab ’ fragments unequivocally demonstrated a requirement for cross-linking of macrophage surface CD44. The molecular mechanism of CD44-augmented phagocytosis was shown to be opsonin-independent and to be distinct from the Mer/protein S pathway induced by glucocorticoids and was not functional for clearance of apoptotic eosinophils. CD44-cross-linking also altered macrophage migration and induced cytoskeletal re-organisation together with phosphorylation of paxillin and activation of Rac2. Investigation of signal transduction pathways that might be critical for CD44 augmentation of phagocytosis revealed that Ca 2+ signalling, PI-3 kinase pathways and altered cAMP signalling were not involved, but did implicate a key role for tyrosine phosphorylation events. Finally, although CD44 antibodies were able to augment phagocytosis of apoptotic neutrophils by murine peritoneal and bone marrow-derived macrophages, we did not observe a difference in the clearance of neutrophils following induction of peritonitis with thioglycollate in CD44-deficient animals. Together, these data demonstrate that CD4
Regulation of neutrophil senescence by microRNAs
Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease
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