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1.
Nat Commun ; 15(1): 3339, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688961

RESUMO

Social networks are a mathematical representation of interactions among individuals which are prevalent across various animal species. Studies of human populations have shown the breadth of what can spread throughout a social network: obesity, smoking cessation, happiness, drug use and divorce. 'Betweenness centrality' is a key property of social networks that indicates an individual's importance in facilitating communication and cohesion within the network. Heritability of betweenness centrality has been suggested in several species, however the genetic regulation of this property remains enigmatic. Here, we demonstrate that the gene CG14109, referred to as degrees of kevin bacon (dokb), influences betweenness centrality in Drosophila melanogaster. We identify strain-specific alleles of dokb with distinct amino acid sequences and when the dokb allele is exchanged between strains, flies exhibit the betweenness centrality pattern dictated by the donor allele. By inserting a GAL4 reporter into the dokb locus, we confirm that dokb is expressed in the central nervous system. These findings define a novel genetic entry point to study social network structure and thereby establish gene-to-social structure relationships. While dokb sequence homology is exclusive to Diptera, we anticipate that dokb-associated molecular pathways could unveil convergent neural mechanisms of social behaviour that apply in diverse animal species.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Drosophila melanogaster/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Alelos , Masculino , Feminino , Comportamento Animal , Comportamento Social , Rede Social
2.
Eur J Nucl Med Mol Imaging ; 49(11): 3761-3771, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35732972

RESUMO

PURPOSE: Non-invasive imaging is a key clinical tool for detection and treatment monitoring of infections. Existing clinical imaging techniques are frequently unable to distinguish infection from tumors or sterile inflammation. This challenge is well-illustrated by prosthetic joint infections that often complicate joint replacements. D-methyl-11C-methionine (D-11C-Met) is a new bacteria-specific PET radiotracer, based on an amino acid D-enantiomer, that is rapidly incorporated into the bacterial cell wall. In this manuscript, we describe the biodistribution, radiation dosimetry, and initial human experience using D-11C-Met in patients with suspected prosthetic joint infections. METHODS: 614.5 ± 100.2 MBq of D-11C-Met was synthesized using an automated in-loop radiosynthesis method and administered to six healthy volunteers and five patients with suspected prosthetic joint infection, who were studied by PET/MRI. Time-activity curves were used to calculate residence times for each source organ. Absorbed doses to each organ and body effective doses were calculated using OLINDA/EXM 1.1 with both ICRP 60 and ICRP 103 tissue weighting factors. SUVmax and SUVpeak were calculated for volumes of interest (VOIs) in joints with suspected infection, the unaffected contralateral joint, blood pool, and soft tissue background. A two-tissue compartment model was used for kinetic modeling. RESULTS: D-11C-Met was well tolerated in all subjects. The tracer showed clearance from both urinary (rapid) and hepatobiliary (slow) pathways as well as low effective doses. Moreover, minimal background was observed in both organs with resident micro-flora and target organs, such as the spine and musculoskeletal system. Additionally, D-11C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUVmax and SUVpeak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P < 0.01). Furthermore, higher distribution volume and binding potential were observed in suspected infections compared to the unaffected joints. CONCLUSION: D-11C-Met has a favorable radiation profile, minimal background uptake, and fast urinary extraction. Furthermore, D-11C-Met showed increased uptake in areas of suspected infection, making this a promising approach. Validation in larger clinical trials with a rigorous gold standard is still required.


Assuntos
Metionina , Tomografia por Emissão de Pósitrons , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons/métodos , Radiometria , Distribuição Tecidual
3.
Pharm Pat Anal ; 5(1): 17-47, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26670619

RESUMO

The most commonly utilized PET radionuclide is fluorine-18 ((18)F) because of its convenient half-life and excellent imaging properties. In this review, we present the first analysis of patents issued for radiotracers labeled with fluorine-18 (between 2009 and 2015), and provide perspective on current trends and future directions in PET radiotracer development.


Assuntos
Radioisótopos de Flúor , Compostos Radiofarmacêuticos , Animais , Cardiopatias/diagnóstico por imagem , Humanos , Neoplasias/diagnóstico por imagem , Doenças do Sistema Nervoso/diagnóstico por imagem , Neuroimagem , Patentes como Assunto , Cintilografia
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