231 research outputs found
Risk of septic arthritis in patients with rheumatoid arthritis and the effect of anti-TNF therapy: results from the British Society for Rheumatology Biologics Register
Corrigendum: Modular Medical Imaging Agents Based on Azide-Alkyne Huisgen Cycloadditions:Synthesis and Pre-Clinical Evaluation of F-18-Labeled PSMA-Tracers for Prostate Cancer Imaging (vol 26, pg 10871, 2020)
Modular Medical Imaging Agents Based on Azide-Alkyne Huisgen Cycloadditions:Synthesis and Pre-Clinical Evaluation of(18)F-Labeled PSMA-Tracers for Prostate Cancer Imaging
Since the seminal contribution of Rolf Huisgen to develop the [3+2] cycloaddition of 1,3-dipolar compounds, its azideâalkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azideâalkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate-specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to pre-clinical in vivo evaluation of fluorine-18- labeled PSMA-targeting âF-PSMA-MICâ radiotracers (t1/2=109.7 min). Pre-clinical data indicate that the modular PSMA-scaffold has similar binding affinity and imaging properties to the clinically used [68Ga]PSMA-11. Furthermore, we demonstrated that targeting the arene-binding in PSMA, facilitated through the [3+2]cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA-binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents
Metabolism of multiple glycosaminoglycans by <i>Bacteroides thetaiotaomicron</i> is orchestrated by a versatile core genetic locus
The human gut microbiota (HGM), which is critical to human health, utilises complex glycans as its major carbon source. Glycosaminoglycans represent an important, high priority, nutrient source for the HGM. Pathways for the metabolism of various glycosaminoglycan substrates remain ill-defined. Here we perform a biochemical, genetic and structural dissection of the genetic loci that orchestrates glycosaminoglycan metabolism in the organism Bacteroides thetaiotaomicron. Here, we report: the discovery of two previously unknown surface glycan binding proteins which facilitate glycosaminoglycan import into the periplasm; distinct kinetic and genetic specificities of various periplasmic lyases which dictate glycosaminoglycan metabolic pathways; understanding of endo sulfatase activity questioning the paradigm of how the âsulfation problemâ is handled by the HGM; and 3D crystal structures of the polysaccharide utilisation loci encoded sulfatases. Together with comparative genomic studies, our study fills major gaps in our knowledge of glycosaminoglycan metabolism by the HGM
Thermal Stability of an MgâNd Alloy Processed by HighâPressure Torsion
The evolution of microstructure, texture and mechanical properties of an Mgâ1.43Nd (wt.%) alloy are investigated after processing by highâpressure torsion at room temperature through 5 turns and isochronal annealing for 1 h at 150, 250, 350 and 450 °C using Electron BackScatter Diffraction and Vickers microhardness. The alloy exhibits a good thermal stability up to an annealing at 250 °C, with mean grain size of â0.65 ÎŒm. The microhardness shows an initial hardening after annealing at 150 °C and then a subsequent softening. The deformation texture, a basal texture shifted 60° away from the shear direction (SD), is retained during annealing up to 250 °C. By contrast, a basal texture with symmetrical splitting towards SD is developed after annealing at 350 °C. The precipitation sequence and their pinning effect are responsible for the ageâhardening, stabilization of grain size and the texture modification. The kinetics of grain growth in the Mgâ1.43Nd alloy follows two stages depending on the temperature annealing range, with an activation energy of â26 kJ/mol in the low temperature range of 150â250 °C and ~147 kJ/mol in the high temperature range of 250â450 °C
OSS (Outer Solar System): A fundamental and planetary physics mission to Neptune, Triton and the Kuiper Belt
The present OSS mission continues a long and bright tradition by associating
the communities of fundamental physics and planetary sciences in a single
mission with ambitious goals in both domains. OSS is an M-class mission to
explore the Neptune system almost half a century after flyby of the Voyager 2
spacecraft. Several discoveries were made by Voyager 2, including the Great
Dark Spot (which has now disappeared) and Triton's geysers. Voyager 2 revealed
the dynamics of Neptune's atmosphere and found four rings and evidence of ring
arcs above Neptune. Benefiting from a greatly improved instrumentation, it will
result in a striking advance in the study of the farthest planet of the Solar
System. Furthermore, OSS will provide a unique opportunity to visit a selected
Kuiper Belt object subsequent to the passage of the Neptunian system. It will
consolidate the hypothesis of the origin of Triton as a KBO captured by
Neptune, and improve our knowledge on the formation of the Solar system. The
probe will embark instruments allowing precise tracking of the probe during
cruise. It allows to perform the best controlled experiment for testing, in
deep space, the General Relativity, on which is based all the models of Solar
system formation. OSS is proposed as an international cooperation between ESA
and NASA, giving the capability for ESA to launch an M-class mission towards
the farthest planet of the Solar system, and to a Kuiper Belt object. The
proposed mission profile would allow to deliver a 500 kg class spacecraft. The
design of the probe is mainly constrained by the deep space gravity test in
order to minimise the perturbation of the accelerometer measurement.Comment: 43 pages, 10 figures, Accepted to Experimental Astronomy, Special
Issue Cosmic Vision. Revision according to reviewers comment
Approaches in biotechnological applications of natural polymers
Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento CientfĂico e TecnolĂłgico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de NvĂel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)
- âŠ