The Chemistry of Short-Lived α-Fluorocarbocations.
Ontology highlight
ABSTRACT:
SUBMITTER: Rozen S
PROVIDER: S-EPMC8023664 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The combination of a targeted biomolecule that specifically defines the target and a radionuclide that delivers a cytotoxic payload offers a specific way to destroy cancer cells. Targeted radionuclide therapy (TRNT) aims to deliver cytotoxic radiation to cancer cells and causes minimal toxicity to surrounding healthy tissues. Recent advances using ?-particle radiation emphasizes their potential to generate radiation in a highly localized and toxic manner because of their high level of ionization and short range in tissue.We review the importance of targeted alpha therapy (TAT) and focus on nanobodies as potential beneficial vehicles. In recent years, nanobodies have been evaluated intensively as unique antigen-specific vehicles for molecular imaging and TRNT.We expect that the efficient targeting capacity and fast clearance of nanobodies offer a high potential for TAT. More particularly, we argue that the nanobodies' pharmacokinetic properties match perfectly with the interesting decay properties of the short-lived ?-particle emitting radionuclides Astatine-211 and Bismuth-213 and offer an interesting treatment option particularly for micrometastatic cancer and residual disease.
| S-EPMC4940885 | biostudies-other
Project description:Knowledge of the mechanisms of assembly of amyloid proteins into aggregates is of central importance in building an understanding of neurodegenerative disease. Given that oligomeric intermediates formed during the aggregation reaction are believed to be the major toxic species, methods to track such intermediates are clearly needed. Here we present a method, electron paramagnetic resonance (EPR), by which the amount of intermediates can be measured over the course of the aggregation, directly in the reacting solution, without the need for separation. We use this approach to investigate the aggregation of α-synuclein (αS), a synaptic protein implicated in Parkinson's disease and find a large population of oligomeric species. Our results show that these are primary oligomers, formed directly from monomeric species, rather than oligomers formed by secondary nucleation processes, and that they are short-lived, the majority of them dissociates rather than converts to fibrils. As demonstrated here, EPR offers the means to detect such short-lived intermediate species directly in situ. As it relies only on the change in size of the detected species, it will be applicable to a wide range of self-assembling systems, making accessible the kinetics of intermediates and thus allowing the determination of their rates of formation and conversion, key processes in the self-assembly reaction.
| S-EPMC7822277 | biostudies-literature
Project description:Macrophages play a central role in tissue homeostasis and host defense. However, the properties of human macrophages in non-diseased tissues remain poorly understood. Here, we characterized human tonsil macrophages and identified three subsets with distinct phenotype, transcriptome, life cycle, and function. CD36hi macrophages were related to monocytes, while CD36lo macrophages showed features of embryonic origin and CD36int macrophages had a mixed profile. scRNA-seq on non-human primate tonsils showed that monocyte recruitment did not pre-exist an immune challenge. Functionally, CD36hi macrophages were specialized for stimulating T follicular helper cells, by producing Activin A. Combining reconstruction of ligand-receptor interactions and functional assays, we identified stromal cell-derived TNF-α as an inducer of Activin A secretion. However, only CD36hi macrophages were primed for Activin A expression, via the activity of IRF1. Our results provide insight into the heterogeneity of human lymphoid organ macrophages and show that tonsil CD36hi macrophage specialization is the result of both intrinsic features and interaction with stromal cells.
| S-EPMC10098144 | biostudies-literature
Project description:Comparison of long-lived daf-2 pathway mutants with wild type/short-lived mutants. A: age-1 fer-15; fem-1 vs. fer-15; fem-1. B: age-1 fer-15; fem-1 vs. fer-15; fem-1. C: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. D: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. E: daf-16::gfp in daf-16(mu86);daf-2(e1370) vs. daf-16(mu86);daf-2(e1370). F: daf-2(e1368); fer-15; fem-1 vs. fer-15; fem-1. G: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. H: age-1 fer-15; fem-1 vs. fer-15; fem-1. I: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. J: daf-16::gfp in daf-2(e1370); daf-16(mu86) vs. daf-2(e1370); daf-16(mu86). K: daf-2(mu150) vs. wild type. L: daf-2(e1370) vs. daf-2(e1370); daf-16(mu86). M: daf-2(e1370) vs. daf-2(e1370); daf-16(mu86). N: daf-2(e1370) vs. daf-2(e1370); daf-16(mu86).
2003-07-17 | E-MEXP-7 | biostudies-arrayexpress
Project description:Emissions reductions focused on anthropogenic climate-forcing agents with relatively short atmospheric lifetimes, such as methane (CH4) and black carbon, have been suggested as a strategy to reduce the rate of climate change over the next several decades. We find that reductions of methane and black carbon would likely have only a modest impact on near-term global climate warming. Even with maximally feasible reductions phased in from 2015 to 2035, global mean temperatures in 2050 would be reduced by 0.16 °C, with a range of 0.04-0.35 °C because of uncertainties in carbonaceous aerosol emissions and aerosol forcing per unit of emissions. The high end of this range is only possible if total historical aerosol forcing is relatively small. More realistic emission reductions would likely provide an even smaller climate benefit. We find that the climate benefit from reductions in short-lived forcing agents are smaller than previously estimated. These near-term climate benefits of targeted reductions in short-lived forcers are not substantially different in magnitude from the benefits from a comprehensive climate policy.
| S-EPMC3761570 | biostudies-literature
Project description:Almost all epidemic models make the assumption that infection is driven by the interaction between pairs of individuals, one of whom is infectious and the other of whom is susceptible. However, in society individuals mix in groups of varying sizes, at varying times, allowing one or more infectives to be in close contact with one or more susceptible individuals at a given point in time. In this paper we study the effect of mixing groups beyond pairs on the transmission of an infectious disease in an SIR (susceptible [Formula: see text] infective [Formula: see text] recovered) model, both through a branching process approximation for the initial stages of an epidemic with few initial infectives and a functional central limit theorem for the trajectories of the numbers of infectives and susceptibles over time for epidemics with many initial infectives. We also derive central limit theorems for the final size of (i) an epidemic with many initial infectives and (ii) a major outbreak triggered by few initial infectives. We show that, for a given basic reproduction number [Formula: see text], the distribution of the size of mixing groups has a significant impact on the probability and final size of a major epidemic outbreak. Moreover, the standard pair-based homogeneously mixing epidemic model is shown to represent the worst case scenario, with both the highest probability and the largest final size of a major epidemic.
| S-EPMC9622612 | biostudies-literature
Project description:The plant growth hormone indoleacetic acid (IAA) transcriptionally activates gene expression in plants. Some of the genes whose expression is induced by IAA encode a family of proteins in pea (PS-IAA4 and PS-IAA6) and Arabidopsis (IAA1 and IAA2) that contain putative nuclear localization signals that direct a beta-glucuronidase reporter protein into the nucleus. Pulse-chase and immunoprecipitation experiments have defined the t1/2 of the PS-IAA4 and PS-IAA6 proteins to be 8 and 6 min, respectively. Their most prominent feature is the presence of a beta alpha alpha motif similar to the beta-sheet DNA-binding domain found in prokaryotic repressors of the Arc family. Based on these data, we suggest that plant tissues express short-lived nuclear proteins as a primary response to IAA. We propose that these proteins act as activators or repressors of genes responsible for mediating the various auxin responses.
| S-EPMC42940 | biostudies-other
Project description:We developed a generalized technique to characterize polymer-nanopore interactions via single channel ionic current measurements. Physical interactions between analytes, such as DNA, proteins, or synthetic polymers, and a nanopore cause multiple discrete states in the current. We modeled the transitions of the current to individual states with an equivalent electrical circuit, which allowed us to describe the system response. This enabled the estimation of short-lived states that are presently not characterized by existing analysis techniques. Our approach considerably improves the range and resolution of single-molecule characterization with nanopores. For example, we characterized the residence times of synthetic polymers that are three times shorter than those estimated with existing algorithms. Because the molecule's residence time follows an exponential distribution, we recover nearly 20-fold more events per unit time that can be used for analysis. Furthermore, the measurement range was extended from 11 monomers to as few as 8. Finally, we applied this technique to recover a known sequence of single-stranded DNA from previously published ion channel recordings, identifying discrete current states with subpicoampere resolution.
| S-EPMC3943493 | biostudies-other
Project description:Bats are the longest-lived mammals given their body size with majority of species exhibiting exceptional longevity. However, there are some short-lived species that do not exhibit extended lifespans. Here we conducted a comparative genomic and transcriptomic study on long-lived Myotis myotis (maximum lifespan = 37.1 years) and short-lived Molossus molossus (maximum lifespan = 5.6 years) to ascertain the genetic difference underlying their divergent longevities. Genome-wide selection tests on 12,467 single-copy genes between M. myotis and M. molossus revealed only three genes (CCDC175, FATE1 and MLKL) that exhibited significant positive selection. Although 97.96% of 12,467 genes underwent purifying selection, we observed a significant heterogeneity in their expression patterns. Using a linear mixed model, we obtained expression of 2,086 genes that may truly represent the genetic difference between M. myotis and M. molossus. Expression analysis indicated that long-lived M. myotis exhibited a transcriptomic profile of enhanced DNA repair and autophagy pathways, compared to M. molossus. Further investigation of the longevity-associated genes suggested that long-lived M. myotis have naturally evolved a diminished anti-longevity transcriptomic profile. Together with observations from other long-lived species, our results suggest that heightened DNA repair and autophagy activity may represent a universal mechanism to achieve longevity in long-lived mammals.
| S-EPMC7485743 | biostudies-literature
Project description:CD8 effector T cells with a CD127hi KLRG1- phenotype are considered precursors to the long-lived memory pool, while KLRG1+ CD127low cells are viewed as short-lived effectors. Nevertheless, we and others have shown that a KLRG1+ CD127low population persists into the memory phase and that these T cells (termed long-lived effector cells or LLEC) display robust protective function during acute re-challenge with bacteria or viruses. Whether these T cells represent a true memory population or are instead a remnant effector cell population that failed to undergo initial contraction has remained unclear. Here, we show that LLEC from mice express a distinct phenotypic and transcriptional signature that shares characteristics of both early effectors and long-lived memory cells. Furthermore, we find that LLEC are exclusively derived from day 12 KLRG1+ effector cells. Our work challenges the concept that the KLRG1+ CD127low population is dominated by short-lived cells and shows that KLRG1 downregulation is not a prerequisite to become a long-lived protective memory T cell.
2020-08-26 | GSE152841 | GEO