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Fishing for G-quadruplexes in solution with a perylene diimide derivative labeled with biotins
2018
A new fluorescent, non‐cytotoxic perylene diimide derivative with two biotins at the peri position, PDI2B, has been synthesized. This molecule is able to interact selectively with G‐quadruplexes with scarce or no affinity towards single‐ or double‐stranded DNA. These features have made it possible to design a simple, effective, safe, cheap, and selective method for fishing G‐quadruplex structures in solution by use of PDI2B and streptavidin coated magnetic beads. The new cyclic method reported leads to the recovery of more than 80 % of G‐quadruplex structures from solution, even in the presence of an excess of single‐stranded or duplex DNA as competitors. Moreover, PDI2B is a G4 ligand that…
Comparison Study of Two Differently Clicked 18F-Folates—Lipophilicity Plays a Key Role
2018
Within the last decade, several folate-based radiopharmaceuticals for Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) have been evaluated; however, there is still a lack of suitable 18F-folates for clinical PET imaging. Herein, we report the synthesis and evaluation of two novel 18F-folates employing strain-promoted and copper-catalyzed click chemistry. Furthermore, the influence of both click-methods on lipophilicity and pharmacokinetics of the 18F-folates was investigated. 18F-Ala-folate and 18F-DBCO-folate were both stable in human serum albumin. In vitro studies proved their high affinity to the folate receptor (FR). The lipophilic character of …
Bioelectrical Coupling of Single-Cell States in Multicellular Systems.
2020
The spatiotemporal distributions of signaling ions and molecules that modulate biochemical pathways in nonexcitable cells are influenced by multicellular electric potentials. These potentials act as distributed controllers encoding instructive spatial patterns in development and regeneration. We review experimental facts and discuss recent bioelectrical models that provide new physical insights and complement biochemical approaches. Single-cell states are modulated at the multicellular level because of the coupling between neighboring cells, thus allowing memories and multicellular patterns. The model is based on (i) two generic voltage-gated ion channels that promote the polarized and depo…
Single nucleotide polymorphisms in A4GALT spur extra products of the human Gb3/CD77 synthase and underlie the P1PK blood group system.
2018
Contrary to the mainstream blood group systems, P1PK continues to puzzle and generate controversies over its molecular background. The P1PK system comprises three glycosphingolipid antigens: Pk, P1 and NOR, all synthesised by a glycosyltransferase called Gb3/CD77 synthase. The Pk antigen is present in most individuals, whereas P1 frequency is lesser and varies regionally, thus underlying two common phenotypes: P1, if the P1 antigen is present, and P2, when P1 is absent. Null and NOR phenotypes are extremely rare. To date, several single nucleotide polymorphisms (SNPs) have been proposed to predict the P1/P2 status, but it has not been clear how important they are in general and in relation …
Characterisation of microsatellite and SNP markers from Miseq and genotyping-by-sequencing data among parapatric Urophora cardui (Tephritidae) popula…
2017
Phylogeographic analyses of the gall flyUrophora carduihave in earlier studies based on allozymes and mtDNA identified small-scale, parapatrically diverged populations within an expanding Western Palearctic population. However, the low polymorphism of these markers prohibited an accurate delimitation of the evolutionary origin of the parapatric divergence.Urophora carduifrom the Western Palearctic have been introduced into Canada as biological control agents of the host plantCirsium arvense. Here, we characterise 12 microsatellite loci with hexa-, penta- and tetra-nucleotide repeat motifs and report a genotyping-by-sequencing SNP protocol. We test the markers for genetic variation among thr…
Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients.
2016
Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, lin…
Direct Visualization of the Conformational Dynamics of Single Influenza Hemagglutinin Trimers
2018
Influenza hemagglutinin (HA) is the canonical type I viral envelope glycoprotein and provides a template for the membrane-fusion mechanisms of numerous viruses. The current model of HA-mediated membrane fusion describes a static "spring-loaded" fusion domain (HA2) at neutral pH. Acidic pH triggers a singular irreversible conformational rearrangement in HA2 that fuses viral and cellular membranes. Here, using single-molecule Förster resonance energy transfer (smFRET)-imaging, we directly visualized pH-triggered conformational changes of HA trimers on the viral surface. Our analyses reveal reversible exchange between the pre-fusion and two intermediate conformations of HA2. Acidification of p…
Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying effects of the TCF7L2-rs7903146 polymorphism
2019
Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid rat…
Endogenous β-neurexins on axons and within synapses show regulated dynamic behavior
2021
Summary: Neurexins are key organizer molecules that regulate synaptic function and are implicated in autism and schizophrenia. β-neurexins interact with numerous cell adhesion and receptor molecules, but their neuronal localization remains elusive. Using single-molecule tracking and high-resolution microscopy to detect neurexin1β and neurexin3β in primary hippocampal neurons from knockin mice, we demonstrate that endogenous β-neurexins are present in fewer than half of excitatory and inhibitory synapses. Moreover, we observe a large extrasynaptic pool of β-neurexins on axons and show that axonal β-neurexins diffuse with higher surface mobility than those transiently confined within synapses…
Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2
2021
12 páginas, 2 figuras, 1 tabla.