| 1131. |
- Moro, Marcos V., et al.
(författare)
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Stopping cross section of vanadium for H+ and He+ ions in a large energy interval deduced from backscattering spectra
- 2018
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Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier BV. - 0168-583X .- 1872-9584. ; 424, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- We have experimentally determined electronic stopping cross sections of vanadium for 50-2750 keV protons and for 250-6000 keV He ions by relative measurements in backscattering geometry. To check the consistency of the employed procedure we investigate how to define adequate reference stopping cross section data and chose different reference materials. To proof consistency of different reference data sets, an intercomparison is performed to test the reliability of the evaluation procedure for a wide range of energies. This process yielded consistent results. The resulting stopping cross section data for V are compared to values from the IAEA database, to the most commonly employed semi-empirical program SRIM, and to calculations according to CasP. For helium, our results show a significant deviation of up to 10% with respect to literature and to SRIM, but are in very good agreement with the CasP predictions, in particular when charge-exchange processes are included in the model.
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| 1132. |
- Mydy, Lisa S., et al.
(författare)
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Human Glycerol 3-Phosphate Dehydrogenase : X-ray Crystal Structures That Guide the Interpretation of Mutagenesis Studies
- 2019
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Ingår i: Biochemistry. - : AMER CHEMICAL SOC. - 0006-2960 .- 1520-4995. ; 58:8, s. 1061-1073
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Tidskriftsartikel (refereegranskat)abstract
- Human liver glycerol 3-phosphate dehydrogenase (hlGPDH) catalyzes the reduction of dihydroxyacetone phosphate (DHAP) to form glycerol 3-phosphate, using the binding energy associated with the nonreacting phosphodianion of the substrate to properly orient the enzyme-substrate complex within the active site. Herein, we report the crystal structures for unliganded, binary E.NAD, and ternary E.NAD.DHAP complexes of wild type hlGPDH, illustrating a new position of DHAP, and probe the kinetics of multiple mutant enzymes with natural and truncated substrates. Mutation of Lys120, which is positioned to donate a proton to the carbonyl of DHAP, results in similar increases in the activation barrier to hlGPDH-catlyzed reduction of DHAP and to phosphite dianion-activated reduction of glycolaldehyde, illustrating that these transition states show similar interactions with the cationic K120 side chain. The K120A mutation results in a 5.3 kcal/mol transition state destabilization, and 3.0 kcal/mol of the lost transition state stabilization is rescued by 1.0 M ethylammonium cation. The 6.5 kcal/mol increase in the activation barrier observed for the D260G mutant hlGPDH-catalyzed reaction represents a 3.5 kcal/mol weakening of transition state stabilization by the K120A side chain and a 3.0 kcal/mol weakening of the interactions with other residues. The interactions, at the enzyme active site, between the K120 side chain and the Q295 and R269 side chains were likewise examined by double-mutant analyses. These results provide strong evidence that the enzyme rate acceleration is due mainly or exclusively to transition state stabilization by electrostatic interactions with polar amino acid side chains.
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| 1133. |
- Neesse, Albrecht, et al.
(författare)
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Stromal biology and therapy in pancreatic cancer : ready for clinical translation?
- 2019
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 68:1, s. 159-171
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDA) is notoriously aggressive and hard to treat. The tumour microenvironment (TME) in PDA is highly dynamic and has been found to promote tumour progression, metastasis niche formation and therapeutic resistance. Intensive research of recent years has revealed an incredible heterogeneity and complexity of the different components of the TME, including cancer-associated fibroblasts, immune cells, extracellular matrix components, tumour vessels and nerves. It has been hypothesised that paracrine interactions between neoplastic epithelial cells and TME compartments may result in either tumour-promoting or tumour-restraining consequences. A better preclinical understanding of such complex and dynamic network systems is required to develop more powerful treatment strategies for patients. Scientific activity and the number of compelling findings has virtually exploded during recent years. Here, we provide an update of the most recent findings in this area and discuss their translational and clinical implications for basic scientists and clinicians alike.
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| 1134. |
- Ni, Wei-Xin, et al.
(författare)
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X-ray reciprocal space mapping studies of strain relaxation in thin SiGe layers (=100 nm) using a low temperature growth step
- 2001
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Ingår i: Journal of Crystal Growth. - 0022-0248 .- 1873-5002. ; 227-228, s. 756-760
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Relaxation of thin SiGe layers (~90 nm) grown by molecular beam epitaxy using a low temperature growth step (120-200°C) has been investigated using two-dimensional reciprocal space mapping of X-ray diffraction. The samples studied have been divided in two groups, depending on the substrate cooling process during the growth of the low temperature layer. It has been found that a higher degree of relaxation was easily achieved for the sample group without growth interruption. A process window for full relaxation of the Si0.74Ge0.26 layer has been observed in the range of 140-150°C. © 2001 Elsevier Science B.V.
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| 1135. |
- Nielsen, Henrietta M., et al.
(författare)
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Peripheral apoE isoform levels in cognitively normal APOE epsilon 3/epsilon 4 individuals are associated with regional gray matter volume and cerebral glucose metabolism
- 2017
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Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCarriers of the APOE epsilon 4 allele are at increased risk of developing Alzheimer's disease (AD), and have been shown to have reduced cerebral metabolic rate of glucose (CMRgl) in the same brain areas frequently affected in AD. These individuals also exhibit reduced plasma levels of apolipoprotein E (apoE) attributed to a specific decrease in the apoE4 isoform as determined by quantification of individual apoE isoforms in APOE epsilon 4 heterozygotes. Whether low plasma apoE levels are associated with structural and functional brain measurements and cognitive performance remains to be investigated.MethodsUsing quantitative mass spectrometry we quantified the plasma levels of total apoE and the individual apoE3 and apoE4 isoforms in 128 cognitively normal APOE epsilon 3/epsilon 4 individuals included in the Arizona APOE cohort. All included individuals had undergone extensive neuropsychological testing and 25 had in addition undergone FDG-PET and MRI to determine CMRgl and regional gray matter volume (GMV).ResultsOur results demonstrated higher apoE4 levels in females versus males and an age-dependent increase in the apoE3 isoform levels in females only. Importantly, a higher relative ratio of apoE4 over apoE3 was associated with GMV loss in the right posterior cingulate and with reduced CMRgl bilaterally in the anterior cingulate and in the right hippocampal area. Additional exploratory analysis revealed several negative associations between total plasma apoE, individual apoE isoform levels, GMV and CMRgl predominantly in the frontal, occipital and temporal areas. Finally, our results indicated only weak associations between apoE plasma levels and cognitive performance which further appear to be affected by sex.ConclusionsOur study proposes a sex-dependent and age-dependent variation in plasma apoE isoform levels and concludes that peripheral apoE levels are associated with GMV, CMRgl and possibly cognitive performance in cognitively healthy individuals with a genetic predisposition to AD.
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| 1136. |
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| 1137. |
- Nilsson, Emma C, 1979-, et al.
(författare)
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The GD1a glycan is a cellular receptor for adenoviruses causing epidemic keratoconjunctivitis (Letter)
- 2011
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 17:1, s. 105-109
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Tidskriftsartikel (refereegranskat)abstract
- Adenovirus type 37 (Ad37) is a leading cause of epidemic keratoconjunctivitis (EKC), a severe and highly contagious ocular disease. Whereas most other adenoviruses infect cells by engaging CD46 or the coxsackie and adenovirus receptor (CAR), Ad37 binds previously unknown sialic acid-containing cell surface molecules. By glycan array screening, we show here that the receptor-recognizing knob domain of the Ad37 fiber protein specifically binds a branched hexasaccharide that is present in the GD1a ganglioside and that features two terminal sialic acids. Soluble GD1a glycan and GD1a-binding antibodies efficiently prevented Ad37 virions from binding and infecting corneal cells. Unexpectedly, the receptor is constituted by one or more glycoproteins containing the GD1a glycan motif rather than the ganglioside itself, as shown by binding, infection and flow cytometry experiments. Molecular modeling, nuclear magnetic resonance and X-ray crystallography reveal that the two terminal sialic acids dock into two of three previously established sialic acid-binding sites in the trimeric Ad37 knob. Surface plasmon resonance analysis shows that the knob-GD1a glycan interaction has high affinity. Our findings therefore form a basis for the design and development of sialic acid-containing antiviral drugs for topical treatment of EKC.
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| 1138. |
- O'Connell, David, et al.
(författare)
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Integrated protein array screening and high throughput validation of 70 novel neural calmodulin binding proteins
- 2010
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Ingår i: Molecular & Cellular Proteomics. - 1535-9484. ; 9:6, s. 1118-1132
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Tidskriftsartikel (refereegranskat)abstract
- Calmodulin is an essential regulator of intracellular processes in response to extracellular stimuli mediated by a rise in Ca(2+) ion concentration. To profile protein-protein interactions of calmodulin in human brain, we probed a high content human protein array with fluorophore-labelled calmodulin in the presence of Ca(2+). This protein array contains 37,200 redundant proteins, incorporating over 10,000 unique human neural proteins from a human brain cDNA library. We designed a screen to find high affinity (K(D) = 1 muM) binding partners of calmodulin and identified 76 human proteins from all intracellular compartments, of which 72 are novel. We measured the binding kinetics of 74 targets with calmodulin using a high throughput surface plasmon resonance assay. Most of the novel calmodulin-target complexes identified have low dissociation rates (koff = 10(3) s(-1)) and high affinity (K(D) = 1 muM), consistent with the design of the screen. Many of the identified proteins are known to assemble in neural tissue, forming assemblies such as the spectrin scaffold and the postsynaptic density. We have developed a microarray of the identified target proteins with which we can characterise the biochemistry of calmodulin for all targets in parallel. Four novel targets were verified in neural cells by co-immunoprecipitation, and four were selected for exploration of the calmodulin-binding regions. Using synthetic peptides and isothermal titration calorimetry, calmodulin binding motifs were identified in the potassium voltage gated channel Kv6.1, (residues 474-493), CaM kinase-like vesicle-associated protein (302-316), EF-hand domain family member A2 (202-216) and phosphatidylinositol-4-phosphate 5-kinase, type I, gamma (400-415).
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| 1139. |
- Olsen, Jeanine L, et al.
(författare)
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The genome of the seagrass Zostera marina reveals angiosperm adaptation to the sea.
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 530:7590, s. 331-5
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Tidskriftsartikel (refereegranskat)abstract
- Seagrasses colonized the sea on at least three independent occasions to form the basis of one of the most productive and widespread coastal ecosystems on the planet. Here we report the genome of Zostera marina (L.), the first, to our knowledge, marine angiosperm to be fully sequenced. This reveals unique insights into the genomic losses and gains involved in achieving the structural and physiological adaptations required for its marine lifestyle, arguably the most severe habitat shift ever accomplished by flowering plants. Key angiosperm innovations that were lost include the entire repertoire of stomatal genes, genes involved in the synthesis of terpenoids and ethylene signalling, and genes for ultraviolet protection and phytochromes for far-red sensing. Seagrasses have also regained functions enabling them to adjust to full salinity. Their cell walls contain all of the polysaccharides typical of land plants, but also contain polyanionic, low-methylated pectins and sulfated galactans, a feature shared with the cell walls of all macroalgae and that is important for ion homoeostasis, nutrient uptake and O2/CO2 exchange through leaf epidermal cells. The Z. marina genome resource will markedly advance a wide range of functional ecological studies from adaptation of marine ecosystems under climate warming, to unravelling the mechanisms of osmoregulation under high salinities that may further inform our understanding of the evolution of salt tolerance in crop plants.
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| 1140. |
- Ortmanns, Lara Celine, 1990, et al.
(författare)
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Magnon dispersion in bilayers of two-dimensional ferromagnets
- 2021
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Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 103:15
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Tidskriftsartikel (refereegranskat)abstract
- We determine magnon spectra of an atomic bilayer magnet with ferromagnetic intra- and both ferro- and antiferromagnetic interlayer coupling. Analytic expressions for the full magnon band of the latter case reveal that both exchange interactions govern the fundamental magnon gap. The inter- and intralayer magnetic ordering are not independent: a stronger ferromagnetic intralayer coupling effectively strengthens the antiferromagnetic interlayer coupling as we see from comparison of two bilayer systems. The trivial topology of these exchange-anisotropy spin models without spin-orbit interaction excludes a magnon thermal Hall effect.
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