CCS Imaging of the Starless Core L1544: An Envelope with Infall and Rotation

We have carried out observations of the starless core L1544 in the CCS (J_N=3_2-2_1) line at 9 millimeters wavelength using the BIMA array. The maps show an elongated condensation, 0.15 x 0.045 pc in size, with stronger emission at the edges. The appearance is consistent with a flattened, ringlike structure viewed at high inclination to the line of sight. The CCS molecule is likely heavily depleted in the inner part of the core. The position velocity diagram along the major axis shows a remarkable pattern, a "tilted ellipse", that can be reproduced by a simple model ring with motions of both infall and rotation. The models suggest comparable velocities for infall and rotation, ~0.1 km/s, in the outermost envelope, at radius 15000 AU.Comment: 14 pages, 4 figures, AAS-LaTex v4.0, will be published in ApJ

Cysteamine inhibits lysosomal oxidation of low density lipoprotein in human macrophages and reduces atherosclerosis in mice

Background and aims: We have shown previously that low density lipoprotein (LDL) aggregated by vortexing is internalised by macrophages and oxidised by iron in lysosomes to form the advanced lipid/protein oxidation product ceroid. We have now used sphingomyelinase-aggregated LDL, a more pathophysiological form of aggregated LDL, to study lysosomal oxidation of LDL and its inhibition by antioxidants, including cysteamine (2-aminoethanethiol) which concentrates in lysosomes by several orders of magnitude. We have also investigated the effect of cysteamine on atherosclerosis in mice. Methods: LDL was incubated with sphingomyelinase, which increased its average particle diameter from 26 to 170 nm, and was then incubated for up to 7 days with human monocyte-derived macrophages. LDL receptor-deficient mice were fed a Western diet (19-22 per group) and some given cysteamine in their drinking water at a dose equivalent to that used in cystinosis patients. The extent of atherosclerosis in the aortic root and the rest of the aorta was measured. Results: Confocal microscopy revealed lipid accumulation in lysosomes in the cultured macrophages. Large amounts of ceroid were produced, which colocalised with the lysosomal marker LAMP2. The antioxidants cysteamine, butylated hydroxytoluene, amifostine and its active metabolite WR-1065, inhibited the production of ceroid. Cysteamine at concentrations well below those expected to be present in lysosomes inhibited the oxidation of LDL by iron ions at lysosomal pH (pH 4.5) for prolonged periods. Finally, we showed that the extent of atherosclerotic lesions in the aortic root and arch of mice was significantly reduced by cysteamine. Conclusions: These results support our hypothesis that lysosomal oxidation of LDL is important in atherosclerosis and hence antioxidant drugs that concentrate in lysosomes might provide a novel therapy for this disease

q-Space Imaging Yields a Higher Effect Gradient to Assess Cellularity than Conventional Diffusion-weighted Imaging Methods at 3.0 T : A Pilot Study with Freshly Excised Whole-Breast Tumors

N.S. supported by Biotechnology and Biological Sciences Research Council (1654748, BB/M010996/1). Study supported by the National Health Service Grampian Endowment Fund (15/1/052).Peer reviewedPublisher PD

Vitamin C Protects Human Arterial Smooth Muscle Cells Against Atherogenic Lipoproteins

Abstract —Glutathione (GSH) plays a key role in cellular antioxidant defenses by scavenging reactive oxygen species and reducing lipid peroxides. Intracellular GSH levels are regulated by transport of its precursor l -cystine via system x c − , which can be induced by oxidant stress. As oxidatively modified low density lipoproteins (LDLs) contribute to impaired vascular reactivity and the formation of atherosclerotic lesions, we have examined the effects of oxidized LDL and the antioxidant vitamins C and E on the l -cystine–GSH pathway in human umbilical artery smooth muscle cells (HUASMCs). Oxidized LDL, but not native LDL, elevated intracellular GSH levels and l -cystine transport via system x c − in a time-dependent (up to 24 hours) and dose-dependent (10 to 100 μg · mL −1 ) manner. These increases were dependent on protein synthesis and the extent of LDL oxidation, but the induction of l -cystine transport activity was independent of GSH synthesis. Pretreatment of HUASMCs for 24 hours with vitamin E (100 μmol/L) attenuated oxidized LDL–mediated increases in GSH, whereas pretreatment with vitamin C depressed basal levels and abolished oxidized LDL–induced increases in GSH and l -cystine transport in a time-dependent (3 to 24 hours) and dose-dependent (10 to 100 μmol/L) manner. Pretreatment of cells with dehydroascorbate had no effect on oxidized LDL–mediated increases in l -cystine transport and only marginally attenuated increases in GSH. Our findings provide the first evidence that vitamin C spares endogenous adaptive antioxidant responses in human vascular smooth muscle cells exposed to atherogenic oxidized LDL. </jats:p

Investigating brain alterations in the Dp1Tyb mouse model of Down syndrome

Down syndrome (DS) is one of the most common birth defects and the most prevalent genetic form of intellectual disability. DS arises from trisomy of chromosome 21, but its molecular and pathological consequences are not fully understood. In this study, we compared Dp1Tyb mice, a DS model, against their wild-type (WT) littermates of both sexes to investigate the impact of DS-related genetic abnormalities on the brain phenotype. We performed in vivo whole brain magnetic resonance imaging (MRI) and hippocampal 1H magnetic resonance spectroscopy (MRS) on the animals at 3 months of age. Subsequently, ex vivo MRI scans and histological analyses were conducted post-mortem. Our findings unveiled the following neuroanatomical and biochemical alterations in the Dp1Tyb brains: a smaller surface area and a rounder shape compared to WT brains, with DS males also presenting smaller global brain volume compared with the counterpart WT. Regional volumetric analysis revealed significant changes in 26 out of 72 examined brain regions, including the medial prefrontal cortex and dorsal hippocampus. These alterations were consistently observed in both in vivo and ex vivo imaging data. Additionally, high-resolution ex vivo imaging enabled us to investigate cerebellar layers and hippocampal subregions, revealing selective areas of decrease and remodelling in these structures. An analysis of hippocampal metabolites revealed an elevation in glutamine and the glutamine/glutamate ratio in the Dp1Tyb mice compared to controls, suggesting a possible imbalance in the excitation/inhibition ratio. This was accompanied by the decreased levels of taurine. Histological analysis revealed fewer neurons in the hippocampal CA3 and DG layers, along with an increase in astrocytes and microglia. These findings recapitulate multiple neuroanatomical and biochemical features associated with DS, enriching our understanding of the potential connection between chromosome 21 trisomy and the resultant phenotype

Forestry and environmental conditions as determinants of pine marten Martes martes occurrence in Norway

The European pine marten Martes martes is often associated with late seral stage coniferous forest stands. Earlier research has indicated that this species may be negatively influenced by clearcutting practices. However, the effects of current clearcutting methods on pine marten occurrence in conjunction with changing environmental conditions are not well known. In this study, we combined four complete years of nationwide data collected during a long-term camera trap (CT) monitoring program in Norway. We employed a multi-scale occupancy model to investigate the relationship of pine marten occurrence to clearcuts (regenerating stands & LE; 10 years old) and forests & GE; 120 years old. We also examined pine marten detection in relation to habitat features (i.e. dominant microsite characteristics) and to varying snow depths and temperatures. We found no relationship between pine marten occurrence and the proportions of old forest and clearcuts at the landscape scale. At the habitat-patch scale, pine marten occurrence was positively associated with the presence of old forest patches and terrain ruggedness, but not with clearcuts & LE; 100 m from sites. At CT sites near clearcuts, the detection probability was negatively correlated with snow depth. In contrast, pine marten occurrence was positively associated with snow depth at CT sites > 100 m from clearcuts. Furthermore, the detection probability increased with temperature and the presence of boulders at CT sites. Boulders may provide important access points for foraging, and cover for resting and predator avoidance. While previous studies indicate that pine martens prefer older forest and avoid clearcuts, the current level and scale of clearcutting in Norway does not appear to influence its occurrence at the landscape scale

Intracranial injection of dengue virus induces interferon stimulated genes and CD8(+) T cell infiltration by sphingosine kinase 1 independent pathways

We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain. Body weight loss and DENV RNA level tended to be greater in SK1-/- compared with wildtype (WT) mice. Brain infection with DENV-2 is associated with the induction of interferon-β (IFN-β) and IFN-stimulated gene (ISG) expression including viperin, Ifi27l2a, IRF7, and CXCL10 without any significant differences between WT and SK1-/- mice. The SK2 and sphingosine-1-phosphate (S1P) levels in the brain were unchanged by DENV infection or the lack of SK1. Histological analysis demonstrated the presence of a cellular infiltrate in DENV-infected brain with a significant increase in mRNA for CD8 but not CD4 suggesting this infiltrate is likely CD8+ but not CD4+ T-lymphocytes. This increase in T-cell infiltration was not affected by the lack of SK1. Overall, DENV-infection in the brain induces IFN and T-cell responses but does not influence the SK/S1P axis. In contrast to our observations in vitro, SK1 has no major influence on these responses following DENV-infection in the mouse brain.Wisam H. Al-Shujairi, Jennifer N. Clarke, Lorena T. Davies, Mohammed Alsharifi, Stuart M. Pitson, Jillian M. Car

Aspectos cronobiológicos na enxaqueca episódica e crônica

Altered melatonin secretion and circadian, seasonal variations have been shown in migraine patients, but little is known about migraine chronobiological features. Two hundred migraine patients were studied. Headaches were reported to occur after changes in patients sleep schedule (46%), shift work (86%) and traveling across time zones (79%). Patients significantly delayed their sleep phase, 54% shifted their sleep phase. Chronobiology is a relevant aspect in migraine patients.Secreção alterada de melatonina e as variações sazonais têm sido demonstrado em pacientes com enxaqueca, mas pouco é sabido sobre as características cronobiológicas na enxaqueca. Duzentos pacientes com enxaqueca foram estudados. Dores de cabeça foram relatadas ocorrer após as alterações do horário do sono em pacientes (46%), trabalho por turnos trocados (86%) e viajar através dos fusos horários (79%). Pacientes atrasaram significativamente a fase do sono, 54% alteraram a fase de sono. Cronobiologia é um aspecto relevante em pacientes com enxaqueca

Investigating low-velocity fluid flow in tumours using convection-MRI

Several distinct fluid flow phenemena occur in solid tumours, including intravascular blood flow and interstitial convection. To probe low-velocity flow in tumors resulting from raised interstitial fluid pressure, we have developed a novel magnetic resonance imaging (MRI) technique named convection-MRI. It uses a phase-contrast acquisition with a dual-inversion vascular nulling preparation to separate intra- and extra-vascular flow. Here, we report the results of experiments in flow phantoms, numerical simulations and tumor xenograft models to investigate the technical feasibility of convection-MRI. We report a good correlation between estimates of effective fluid pressure from convection-MRI with gold-standard, invasive measurements of interstitial fluid pressure in mouse models of human colorectal carcinoma and show that convection-MRI can provide insights into the growth and response to vascular-targeting therapy in colorectal cancers