303 research outputs found
Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells
Previous work has shown that some cancer cells are highly dependent on serine/glycine uptake for proliferation. Although serine and glycine can be interconverted and either might be used for nucleotide synthesis and one-carbon metabolism, we show that exogenous glycine cannot replace serine to support cancer cell proliferation. Cancer cells selectively consumed exogenous serine, which was converted to intracellular glycine and one-carbon units for building nucleotides. Restriction of exogenous glycine or depletion of the glycine cleavage system did not impede proliferation. In the absence of serine, uptake of exogenous glycine was unable to support nucleotide synthesis. Indeed, higher concentrations of glycine inhibited proliferation. Under these conditions, glycine was converted to serine, a reaction that would deplete the one-carbon pool. Providing one-carbon units by adding formate rescued nucleotide synthesis and growth of glycine-fed cells. We conclude that nucleotide synthesis and cancer cell proliferation are supported by serineârather than glycineâconsumption
Furthering the understanding of silicate-substitution in α-tricalcium phosphate : an X-ray diffraction, X-ray fluorescence and solid-state nuclear magnetic resonance study
High-purity (SupT) and reagent-grade (ST), stoichiometric and silicate-containing α-tricalcium phosphate (α-TCP: ST0/SupT0 and Si-TCP x = 0.10: ST10/SupT10) were prepared by solid-state reaction based on the substitution mechanism Ca3(PO4)(2-x)(SiO4)x. Samples were determined to be phase pure by X-ray diffraction (XRD), and Rietveld analysis performed on the XRD data confirmed inclusion of Si in the α-TCP structure as determined by increases in unit cell parameters; particularly marked increases in the b-axis and ÎČ-angle were observed. X-ray fluorescence (XRF) confirmed the presence of expected levels of Si in Si-TCP compositions as well as significant levels of impurities (Mg, Al and Fe) present in all ST samples; SupT samples showed both expected levels of Si and a high degree of purity. Phosphorus (31P) magic-angle-spinning solid-state nuclear magnetic resonance (MAS NMR) measurements revealed that the high-purity reagents used in the synthesis of SupT0 can resolve the 12 expected peaks in the 31P spectrum of α-TCP compared to the low-purity ST0 that showed significant spectral line broadening; line broadening was also observed with the inclusion of Si which is indicative of induced structural disorder. Silicon (29Si) MAS NMR was also performed on both Si-TCP samples which revealed Q0 species of Si with additional Si Q1/Q2 species that may indicate a potential charge-balancing mechanism involving the inclusion of disilicate groups; additional Q4 Si species were also observed, but only for ST10. Heating and cooling rates were briefly investigated by 31P MAS NMR which showed no significant line broadening other than that associated with the emergence of ÎČ-TCP which was only realised with the reagent-grade sample ST0. This study provides an insight into the structural effects of Si-substitution in α-TCP and could provide a basis for understanding how substitution affects the physicochemical properties of the material
Fractal Properties of Robust Strange Nonchaotic Attractors in Maps of Two or More Dimensions
We consider the existence of robust strange nonchaotic attractors (SNA's) in
a simple class of quasiperiodically forced systems. Rigorous results are
presented demonstrating that the resulting attractors are strange in the sense
that their box-counting dimension is N+1 while their information dimension is
N. We also show how these properties are manifested in numerical experiments.Comment: 9 pages, 14 figure
Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress
A functional genomics study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. Comparative metabolomics and lipidomics demonstrated that acetate is used as a nutritional source by cancer cells in an ACSS2-dependent manner, and supplied a significant fraction of the carbon within the fatty acid and phospholipid pools. ACSS2 expression is upregulated under metabolically stressed conditions and ACSS2 silencing reduced the growth of tumor xenografts. ACSS2 exhibits copy-number gain in human breast tumors, and ACSS2 expression correlates with disease progression. These results signify a critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment
Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR)
Introduction Severe cutaneous adverse reactions (SCAR) are a group of T cell-mediated hypersensitivities associated with significant morbidity, mortality and hospital costs. Clinical phenotypes include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). In this Australasian, multicentre, prospective registry, we plan to examine the clinical presentation, drug causality, genomic predictors, potential diagnostic approaches, treatments and long-term outcomes of SCAR in Australia and New Zealand.
Methods and analysis Adult and adolescent patients with SCAR including SJS, TEN, DRESS, AGEP and another T cell-mediated hypersensitivity, generalised bullous fixed drug eruption, will be prospectively recruited. A waiver of consent has been granted for some sites to retrospectively include cases which result in early mortality. DNA will be collected for all prospective cases. Blood, blister fluid and skin biopsy sampling is optional and subject to patient consent and site capacity. To develop culprit drug identification and prevention, genomic testing will be performed to confirm human leukocyte antigen (HLA) type and ex vivo testing will be performed via interferon-Îł release enzyme linked immunospot assay using collected peripheral blood mononuclear cells. The long-term outcomes of SCAR will be investigated with a 12-month quality of life survey and examination of prescribing and mortality data.
Ethics and dissemination This study was reviewed and approved by the Austin Health Human Research Ethics Committee (HREC/50791/Austin-19). Results will be published in peer-reviewed journals and presented at relevant conferences
Conservation conundrum â red listing of subtropical-temperate coastal forested wetlands of South Africa
Africaâs range-restricted and transitional subtropical-temperate coastal forested wetlands are facing interlinking
threats of climate and anthropogenic pressures. We assessed their conservation status using the criteria of the
International Union for Conservation of Nature (IUCN). Their total areal extent was hind-casted to the reference
epoch 2000, followed by the quantification of subsequent total losses in areal extents for the epochs 2005, 2008,
2011 and 2017. South Africa had 120 km2 of coastal swamp and floodplain forests in 2000 of which the majority
(116.5 km2) occurred on the Maputaland Coastal Plain (MCP). By 2011, 20% of the areal extent was lost, and at
the lowest rate of decline we estimate that â„ 80% of the rest will be lost in the next 50 years. An ecosystem
collapse assessment therefore indicated that the habitat is very likely Critically Endangered. Fragmentation and
types of transformations were used as degradation indices to show functional collapse. These results showed that forest patches became increasingly fragmented, from 511 to 1 145 patches between 2000 and 2017 and that >
23% of the areal extent showed severe transformation. Several faunal species, with a close association to the
forested wetlands of the MCP, are considered threatened with numbers declining because of transformation to
timber plantations or agriculture and coupled with a prolonged drought. Of these, a sub-species of the Samango
monkey, Cercopithecus mitis erythrarchus, considered to be a primary ecosystem engineer of the habitat, was red
listed with a restricted distribution, being endemic, Near Threatened and declining. Also under pressure, because
of habitat fragmentation and degradation is the Peregrine crab (Varuna litterata), a euryhaline species requiring
connectivity across the land-seascape, ranging from freshwater forested wetlands to estuarine and off-shore
environments. Functionally, these coastal forested wetlands are therefore also considered Critically Endangered.
The final IUCN conservation status of South Africaâs subtropical-temperate coastal forested wetlands are
recommended to be very likely Critically Endangered. Irrespective of 62% of the areal extent of these forested
wetlands being within protected areas, severe degradation (metrics of fragmentation and transformation) were
observed even inside these areas for the past two decades. The conservation conundrum is that despite existing
legislation and management measures, there has been no stop or reversal of the negative trends to date. As a
supplementary method, we therefore recommend a transdisciplinary community-based approach to conservation
practice, continued and improved monitoring of the habitat losses, the identifying priority areas for rehabilitation
and addressing data deficiencies in important species associations.CSIRâs Parliamentary Grant Project P1BEO00/P1CCS02, titled âMarine Observational and Predictive System Capabilities (MAROPS)â; as well as the African Union Commission (AUC) Global Monitoring for Environment and Security (GMES) MARCOSOUTH (K8MARCO). The Department of Science and Innovation (DSI) and National Research Foundation (NRF) Chair in Shallow Water Ecosystems (UID 84375) supported time of Prof. Janine Adams.https://www.elsevier.com/locate/ecolindam2022Geography, Geoinformatics and Meteorolog
The Drosophila melanogaster Genetic Reference Panel
A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics
Measurement of the CP-Violating Asymmetry Amplitude sin2
We present results on time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 million Y(4S) --> B Bbar decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B0 or B0bar from its decay products. The amplitude of the CP-violating asymmetry, which in the Standard Model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta = 0.741 +/- 0.067 (stat) +/- 0.033 (syst) and |lambda| = 0.948 +/- 0.051 (stat) +/- 0.017 (syst). The magnitude of lambda is consistent with unity, in agreement with the Standard Model expectation of no direct CP violation in these modes
Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at âNN = 5.02 TeV
The second-order Fourier coefficients (Ï
) characterizing the azimuthal distributions of ΄(1S) and ΄(2S) mesons produced in PbPb collisions at = 5.02 TeV are studied. The ΄mesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb. The scalar product method is used to extract the Ï
coefficients of the azimuthal distributions. Results are reported for the rapidity range |y| < 2.4, in the transverse momentum interval 0 < p < 50 GeV/c, and in three centrality ranges of 10â30%, 30â50% and 50â90%. In contrast to the J/Ï mesons, the measured Ï
values for the ΄ mesons are found to be consistent with zero
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