14,049 research outputs found
Tropical belt width proportionately more sensitive to aerosols than greenhouse gases
The tropical belt has widened during the last several decades, and both internal variability and anthropogenic forcings have contributed. Although greenhouse gases and stratospheric ozone depletion have been implicated as primary anthropogenic drivers of tropical expansion, the possible role of other drivers remains uncertain. Here, we analyze the tropical belt width response to idealized perturbations in multiple models. Our results show that absorbing black carbon (BC) aerosol drives tropical expansion, and scattering sulfate aerosol drives contraction. BC, especially from Asia, is more efficient per unit radiative forcing than greenhouse gases in driving tropical expansion, particularly in the Northern Hemisphere. Tropical belt expansion (contraction) is associated with an increase (decrease) in extratropical static stability induced by absorbing (scattering) aerosol. Although a formal attribution is difficult, scaling the normalized expansion rates to the historical time period suggests that BC is the largest driver of the Northern Hemisphere tropical widening but with relatively large uncertainty
A fln-2 mutation affects lethal pathology and lifespan in C. elegans
Differences in genetic background in model organisms can have complex effects on phenotypes of interest. We previously reported a difference in hermaphrodite lifespan between two wild-type lines widely used by C. elegans researchers (N2 hermaphrodite and male stocks). Here, using pathology-based approaches and genome sequencing, we identify the cause of this difference as a nonsense mutation in the filamin gene fln-2 in the male stock, which reduces early mortality caused by pharyngeal infection. We show how fln-2 variation explains previous discrepancies involving effects of sir-2.1 (sirtuin deacetylase) on ageing, and show that in a fln-2(+) background, sir-2.1 over-expression causes an FUDR (DNA synthesis inhibitor)-dependent reduction in pharyngeal infection and increase in lifespan. In addition we show how fln-2 variation confounds effects on lifespan of daf-2 (insulin/IGF-1 signalling), daf-12 (steroid hormone signalling), and eat-2 (putative dietary restriction). These findings underscore the importance of identifying and controlling genetic background variation
Increasing smoking intensity is associated with increased disease activity in axial spondyloarthritis.
A history of ever-smoking appears to be associated with a more severe disease phenotype in axial spondyloarthritis (axSpA). However, evidence is sparse for the effect of increased smoking exposure on disease outcomes or whether smoking reduction or cessation improves outcomes. The aim of this study was to explore whether a dose-response relationship exists between pack-years and disease activity and functional impairment in axSpA. Consecutive patients meeting ASAS criteria for axial SpA were recruited from a spondyloarthritis service. The associations between pack-years of smoking and: (1) disease activity (BASDAI/ASDAS), (2) spinal pain, (3) functional impairment (BASFI) and (4) inflammatory markers were explored using multivariable linear models, adjusted for age, gender and use of TNF inhibition (TNFi) therapy. Pack-years were categorised into four groups (40) and analysed with light smoking (40, β = 2.6 (0.54, 3.56)), higher BASFI (21-40, β = 2.1 (0.42, 4.80); >40, β = 3.2 (0.76, 5.71)), and higher ASDAS (21-40, β = 0.82 (0.14, 1.51)). This cross-sectional study demonstrated that smoking is associated with increased axSpA severity markers in a dose-response manner. Particular effort should be made to restrict smoking exposure early before accruing a significant number of pack-years
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Chemical characterization of water-soluble organic carbon aerosols at a rural site in the Pearl River Delta, China, in the summer of 2006
Online measurements of water-soluble organic carbon (WSOC) aerosols were made using a particle-into-liquid sampler (PILS) combined with a total organic carbon (TOC) analyzer at a rural site in the Pearl River Delta region, China, in July 2006. A macroporous nonionic (DAX-8) resin was used to quantify hydrophilic and hydrophobic WSOC, which are defined as the fractions of WSOC that penetrated through and retained on the DAX-8 column, respectively. Laboratory calibrations showed that hydrophilic WSOC (WSOCHPI) included low-molecular aliphatic dicarboxylic acids and carbonyls, saccharides, and amines, while hydrophobic WSOC (WSOCHPO) included longer-chain aliphatic dicarboxylic acids and carbonyls, aromatic acids, phenols, organic nitrates, cyclic acids, and fulvic acids. On average, total WSOC (TWSOC) accounted for 60% of OC, and WSOCHPO accounted for 60% of TWSOC. Both WSOC HIP and WSOCHPO increased with photochemical aging determined from the NOx/NOy ratio. In particular, the average WSOCHPO mass was found to increase by a factor of five within a timescale of ∼10 hours, which was substantially larger than that of WSOCHPI (by a factor of 2-3). The total increase in OC mass with photochemical aging was associated with the large increase in WSOCHPO mass. These results, combined with the laboratory calibrations, suggest that significant amounts of hydrophobic organic compounds (likely containing large carbon numbers) were produced by photochemical processing. By contrast, water-insoluble OC (WIOC) mass did not exhibit significant changes with photochemical aging, suggesting that chemical transformation of WIOC to WSOC was not a dominant process for the production of WSOC during the study period. Copyright 2009 by the American Geophysical Union
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Damaged axons promote OPC differentiation
Oligodendrocyte progenitor cell (OPC) differentiation is an important therapeutic target to promote remyelination in multiple sclerosis (MS). We previously reported hyperphosphorylated and aggregated microtubule-associated protein tau in MS lesions, suggesting its involvement in axonal degeneration. However, the influence of pathological tau-induced axonal damage on the potential for remyelination is unknown. Therefore, we investigated OPC differentiation in human P301S tau (P301S-htau) transgenic mice, both in vitro and in vivo following focal demyelination. In 2-month-old P301S-htau mice, which show hyperphosphorylated tau in neurons, we found atrophic axons in the spinal cord in the absence of prominent axonal degeneration. These signs of early axonal damage were associated with microgliosis and an upregulation of IL-1β and TNFα. Following in vivo focal white matter demyelination we found that OPCs differentiated more efficiently in P301S-htau mice than wild type (Wt) mice. We also found an increased level of myelin basic protein within the lesions, which however did not translate into increased remyelination due to higher susceptibility of P301S-htau axons to demyelination-induced degeneration compared to Wt axons. In vitro experiments confirmed higher differentiation capacity of OPCs from P301S-htau mice compared with Wt mice-derived OPCs. Because the OPCs from P301S-htau mice do not ectopically express the transgene, and when isolated from newborn mice behave like Wt mice-derived OPCs, we infer that their enhanced differentiation capacity must have been acquired through microenvironmental priming. Our data suggest the intriguing concept that damaged axons may signal to OPCs and promote their differentiation in the attempt at rescue by remyelination. GLIA 2016;64:457-471.This project was funded by the Multiple Sclerosis Society UK via the Cambridge Centre for Myelin Repair consortium, and core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute
Review of recent progress toward a fiberless, whole-scalp diffuse optical tomography system
The development of a whole-scalp, high sampling-density diffuse optical tomography (DOT) system is a critical next step in the evolution of the field of diffuse optics. To achieve this with optical fiber bundles is extremely challenging, simply because of the sheer number of bundles required, and the associated challenges of weight and ergonomics. Dispensing with optical fiber bundles and moving to head-mounted optoelectronics can potentially facilitate the advent of a new generation of wearable, whole-scalp technologies that will open up a range of new experimental and clinical applications for diffuse optical measurements. Here, we present a concise review of the significant progress that has been made toward achieving a wearable, fiberless, high-density, whole-scalp DOT system. We identify the key limitations of current technologies and discuss the possible opportunities for future development
The mechanics of reinforcement of polymers by graphene nanoplatelets
A detailed study has been undertaken of the mechanisms of stress transfer in polymeric matrices with different values of Young's modulus, Em, reinforced by graphene nanoplatelets (GNPs). For each material, the Young's modulus of the graphene filler, Ef, has been determined using the rule of mixtures and it is found to scale with the value of Em. Additionally stress-induced Raman bands shifts for the different polymer matrices show different levels of stress transfer from the polymer matrix to the GNPs, which again scale with Em. A theory has been developed to predict the stiffness of the bulk nanocomposites from the mechanics of stress transfer from the matrix to the GNP reinforcement based upon the shear-lag deformation of individual graphene nanoplatelets. Overall it is found that it is only possible to realise the theoretical Young's modulus of graphene of 1.05 TPa for discontinuous nanoplatelets as Em approaches 1 TPa; the effective modulus of the reinforcement will always be less for lower values of Em. For flexible polymeric matrices the level of reinforcement is independent of the graphene Young's modulus and, in general, the best reinforcement will be obtained in nanocomposites with strong graphene-polymer interfaces and aligned nanoplatelets with high aspect ratios
Influence of silencing the MC4R gene by lentivirusmediated RNA interference in bovine fibroblast cells
Melanocortin receptor 4 (MC4R) is a key element in the mechanisms used to regulate both aspects of keeping the balance between energy uptake and energy expenditure. MC4R was knocked down by lentivirus-mediated shRNA expressing plasmids, which were controlled by the U6 promoter in bovine fibroblast cells, and the expression of MC4R was examined by the real time-PCR and Western blot analysis. Real time-PCR analysis was used to characterize the expression of Leptin, POMC, AGRP, MC3R and NPY gene. The relative genes [leptin, proopiomelanocortin (POMC), agouti-related peptide (AGRP), MC3R and neuropeptide Y (NPY)] expression level seemed to be closely associated with the MC4R gene in bovine fibroblast cell lines (BFCs). The levels of both MC4R mRNA and protein were significantly reduced by RNA interference (RNAi) mediated knockdown of MC4R in BFCs cells transfected with plasmid-based MC4R-specific shRNAs. The finding of this study demonstrated that vector based siRNA expression systems were an efficient approach to the knockdown of the MC4R gene expression in bovine fibroblast cells and they provided a new molecular basis for understanding the relationship of MC4R and other genes, which were responsible for the regulation of energy homeostasis by the melanocortin system.Key words: Melanocortin receptor 4 (MC4R), RNAi, bovine fibroblast cells, energy homeostasis
cAMP-dependent protein kinase A (PKA) regulates angiogenesis by modulating tip cell behavior in a Notch-independent manner
cAMP-dependent protein kinase A (PKA) is a ubiquitously expressed serine/threonine kinase that regulates a variety of cellular functions. Here, we demonstrate that endothelial PKA activity is essential for vascular development, specifically regulating the transition from sprouting to stabilization of nascent vessels. Inhibition of endothelial PKA by endothelial cell-specific expression of dominant-negative PKA in mice led to perturbed vascular development, hemorrhage and embryonic lethality at mid-gestation. During perinatal retinal angiogenesis, inhibition of PKA resulted in hypersprouting as a result of increased numbers of tip cells. In zebrafish, cell autonomous PKA inhibition also increased and sustained endothelial cell motility, driving cells to become tip cells. Although these effects of PKA inhibition were highly reminiscent of Notch inhibition effects, our data demonstrate that PKA and Notch independently regulate tip and stalk cell formation and behavior
Towards cot-side mapping of the sensorimotor cortex in preterm and term infants with wearable high-density diffuse optical tomography
We are translating wearable HD-DOT to the neonatal clinic to investigate healthy and brain-injured infants and establish a model of the developmental trajectory of the infant sensorimotor system
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