2,429 research outputs found
Determining and interpreting correlations in lipidomic networks found in glioblastoma cells
Background: Intelligent and multitiered quantitative analysis of biological systems rapidly evolves to a key technique in studying biomolecular cancer aspects. Newly emerging advances in both measurement as well as bio-inspired computational techniques have facilitated the development of lipidomics technologies and offer an excellent opportunity to understand regulation at the molecular level in many diseases.
Results: We present computational approaches to study the response of glioblastoma U87 cells to gene- and chemo-therapy. To identify distinct biomarkers and differences in therapeutic outcomes, we develop a novel technique based on graph-clustering. This technique facilitates the exploration and visualization of co-regulations in glioblastoma lipid profiling data. We investigate the changes in the correlation networks for different therapies and study the success of novel gene therapies targeting aggressive glioblastoma.
Conclusions: The novel computational paradigm provides unique “fingerprints” by revealing the intricate interactions at the lipidome level in glioblastoma U87 cells with induced apoptosis (programmed cell death) and thus opens a new window to biomedical frontiers
Prevalence and Predictors of Vitamin D Insufficiency in Children: A Great Britain Population Based Study
Objectives
To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children In Great Britain.
Design
A nationally representative cross-sectional study survey of children (1102) aged 4–18 years (999 white, 570 male) living in private households (January 1997–1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L).
Results
Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4–63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53–59 degrees latitude had lower levels (compared with 50–53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14–18 years old), odds ratio (OR) = 3.6 (95%CI 1.8–7.2) compared with younger children (4–8 years); non white children (OR = 37 [95%CI 15–90]); blood levels taken December-May (OR = 6.5 [95%CI 4.3–10.1]); on income support (OR = 2.2 [95%CI 1.3–3.9]); not taking vitamin D supplementation (OR = 3.7 [95%CI 1.4–9.8]); being overweight (OR 1.6 [95%CI 1.0–2.5]); <1/2 hour outdoor exercise/day/week (OR = 1.5 [95%CI 1.0–2.3]); watched >2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0–2.4]).
Conclusion
We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children
Evaluating Promotional Approaches for Citizen Science Biological Recording: Bumblebees as a Group Versus Harmonia axyridis as a Flagship for Ladybirds
Over the past decade, the number of biological records submitted by members of the public have increased dramatically. However, this may result in reduced record quality, depending on how species are promoted in the media. Here we examined the two main promotional approaches for citizen science recording schemes: flagship-species, using one charismatic species as an umbrella for the entire group (here, Harmonia axyridis (Pallas) for Coleoptera: Coccinellidae), and general-group, where the group is promoted as a whole and no particular prominence is given to any one species (here, bumblebees, genus Bombus (Hymenoptera: Apidae)). Of the two approaches, the
general-group approach produced data that was not
biased towards any one species, but far fewer records
per year overall. In contrast, the flagship-species
approach generated a much larger annual dataset, but
heavily biased towards the flagship itself. Therefore,
we recommend that the approach for species promotion
is fitted to the result desired
SPARTAN: a global network to evaluate and enhance satellite-based estimates of ground-level particulate matter for global health applications
Ground-based observations have insufficient spatial coverage to assess long-term human exposure to fine particulate matter (PM2.5) at the global scale. Satellite remote sensing offers a promising approach to provide information on both short-and long-term exposure to PM2.5 at local-to-global scales, but there are limitations and outstanding questions about the accuracy and precision with which ground-level aerosol mass concentrations can be inferred from satellite remote sensing alone. A key source of uncertainty is the global distribution of the relationship between annual average PM2.5 and discontinuous satellite observations of columnar aerosol optical depth (AOD). We have initiated a global network of ground-level monitoring stations designed to evaluate and enhance satellite remote sensing estimates for application in health-effects research and risk assessment. This Surface PARTiculate mAtter Network (SPARTAN) includes a global federation of ground-level monitors of hourly PM2.5 situated primarily in highly populated regions and collocated with existing ground-based sun photometers that measure AOD. The instruments, a three-wavelength nephelometer and impaction filter sampler for both PM2.5 and PM10, are highly autonomous. Hourly PM2.5 concentrations are inferred from the combination of weighed filters and nephelometer data. Data from existing networks were used to develop and evaluate network sampling characteristics. SPARTAN filters are analyzed for mass, black carbon, water-soluble ions, and metals. These measurements provide, in a variety of regions around the world, the key data required to evaluate and enhance satellite-based PM2.5 estimates used for assessing the health effects of aerosols. Mean PM2.5 concentrations across sites vary by more than 1 order of magnitude. Our initial measurements indicate that the ratio of AOD to ground-level PM2.5 is driven temporally and spatially by the vertical profile in aerosol scattering. Spatially this ratio is also strongly influenced by the mass scattering efficiency.Fil: Snider, G.. Dalhousie University Halifax; CanadáFil: Weagle, C. L.. Dalhousie University Halifax; CanadáFil: Martin, R. V.. Dalhousie University Halifax; Canadá. University of Cambridge; Reino UnidoFil: van Donkelaar, A.. Dalhousie University Halifax; CanadáFil: Conrad, K.. Dalhousie University Halifax; CanadáFil: Cunningham, D.. Dalhousie University Halifax; CanadáFil: Gordon, C.. Dalhousie University Halifax; CanadáFil: Zwicker, M.. Dalhousie University Halifax; CanadáFil: Akoshile, C.. University of Ilorin; NigeriaFil: Artaxo, P.. Governo Do Estado de Sao Paulo; BrasilFil: Anh, N. X.. Vietnam Academy of Science and Technology. Institute of Geophysics; VietnamFil: Brook, J.. University of Toronto; CanadáFil: Dong, J.. Tsinghua University; ChinaFil: Garland, R. M.. North-West University; SudáfricaFil: Greenwald, R.. Rollins School of Public Health; Estados UnidosFil: Griffith, D.. Council for Scientific and Industrial Research; SudáfricaFil: He, K.. Tsinghua University; ChinaFil: Holben, B. N.. NASA Goddard Space Flight Center; Estados UnidosFil: Kahn, R.. NASA Goddard Space Flight Center; Estados UnidosFil: Koren, I.. Weizmann Institute Of Science Israel; IsraelFil: Lagrosas, N.. Manila Observatory, Ateneo de Manila University campus; FilipinasFil: Lestari, P.. Institut Teknologi Bandung; IndonesiaFil: Ma, Z.. Rollins School of Public Health; Estados UnidosFil: Vanderlei Martins, J.. University of Maryland; Estados UnidosFil: Quel, Eduardo Jaime. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rudich, Y.. Weizmann Institute Of Science Israel; IsraelFil: Salam, A.. University Of Dhaka; BangladeshFil: Tripathi, S. N.. Indian Institute Of Technology, Kanpur; IndiaFil: Yu, C.. Rollins School of Public Health; Estados UnidosFil: Zhang, Q.. Tsinghua University; ChinaFil: Zhang, Y.. Tsinghua University; ChinaFil: Brauer, M.. University of British Columbia; CanadáFil: Cohen, A.. Health Effects Institute; Estados UnidosFil: Gibson, M. D.. Dalhousie University Halifax; CanadáFil: Liu, Y.. Rollins School of Public Health; Estados Unido
Discovery of an unconventional centromere in budding yeast redefines evolution of point centromeres
Centromeres are the chromosomal regions promoting kinetochore assembly for chromosome segregation. In many eukaryotes, the centromere consists of up to mega base pairs of DNA. On such "regional centromeres," kinetochore assembly is mainly defined by epigenetic regulation [1]. By contrast, a clade of budding yeasts (Saccharomycetaceae) has a "point centromere" of 120-200 base pairs of DNA, on which kinetochore assembly is defined by the consensus DNA sequence [2, 3]. During evolution, budding yeasts acquired point centromeres, which replaced ancestral, regional centromeres [4]. All known point centromeres among different yeast species share common consensus DNA elements (CDEs) [5, 6], implying that they evolved only once and stayed essentially unchanged throughout evolution. Here, we identify a yeast centromere that challenges this view: that of the budding yeast Naumovozyma castellii is the first unconventional point centromere with unique CDEs. The N. castellii centromere CDEs are essential for centromere function but have different DNA sequences from CDEs in other point centromeres. Gene order analyses around N. castellii centromeres indicate their unique, and separate, evolutionary origin. Nevertheless, they are still bound by the ortholog of the CBF3 complex, which recognizes CDEs in other point centromeres. The new type of point centromere originated prior to the divergence between N. castellii and its close relative Naumovozyma dairenensis and disseminated to all N. castellii chromosomes through extensive genome rearrangement. Thus, contrary to the conventional view, point centromeres can undergo rapid evolutionary changes. These findings give new insights into the evolution of point centromeres
Lambda and Antilambda polarization from deep inelastic muon scattering
We report results of the first measurements of Lambda and Antilambda
polarization produced in deep inelastic polarized muon scattering on the
nucleon. The results are consistent with an expected trend towards positive
polarization with increasing x_F. The polarizations of Lambda and Antilambda
appear to have opposite signs. A large negative polarization for Lambda at low
positive x_F is observed and is not explained by existing models.A possible
interpretation is presented.Comment: 9 pages, 2 figure
Detailed Differentiation of Calbindin D-28k-Immunoreactive Cells in the Dentate Gyrus in C57BL/6 Mice at Early Postnatal Stages
The hippocampus makes new memories and is involved in mental cognition, and the hippocampal dentate gyrus (DG) is critical because neurogenesis, which occurs throughout life, occurs in the DG. We observed the differentiation of neuroblasts into mature neurons (granule cells) in the DG of C57BL/6 mice at various early postnatal (P) ages: P1, P7, P14, and P21 using doublecortin (DCX) immunohistochemistry (IHC) for neuroblasts and calbindin D-28k (CB) IHC for granule cells. DCX-positive cells decreased in the DG with age; however, CB+ cells increased over time. At P1, DCX and CB double-labeled (DCX+CB+) cells were scattered throughout the DG. At P7, DCX+CB+ cells (about 92% of CB+ cells) were seen only in the granule cell layer (GCL) of the dorsal blade. At P14, DCX+CB+ cells (about 66% of CB+ cells) were found in the lower half of the GCL of both blades. In contrast, at P21, about 18% of CB+ cells were DCX+CB+ cells, and they were mainly located only in the subgranular zone of the DG. These results suggest that the developmental pattern of DCX+CB+ cells changes with time in the early postnatal stages
A CsI(Tl) Scintillating Crystal Detector for the Studies of Low Energy Neutrino Interactions
Scintillating crystal detector may offer some potential advantages in the
low-energy, low-background experiments. A 500 kg CsI(Tl) detector to be placed
near the core of Nuclear Power Station II in Taiwan is being constructed for
the studies of electron-neutrino scatterings and other keV-MeV range neutrino
interactions. The motivations of this detector approach, the physics to be
addressed, the basic experimental design, and the characteristic performance of
prototype modules are described. The expected background channels and their
experimental handles are discussed.Comment: 34 pages, 11 figures, submitted to Nucl. Instrum. Method
Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.
G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology
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