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51.
52.
Schedlich LJ Graham LD O'Han MK Muthukaruppan A Yan X Firth SM Baxter RC 《Archives of biochemistry and biophysics》2007,465(2):359-369
IGFBP-3 interacts with the retinoid X receptor-alpha (RXRalpha) and retinoic acid receptor-alpha (RARalpha) and thereby interferes with the formation of RXR:RAR heterodimers. Here we identify the domains in RXRalpha and IGFBP-3 that participate in this interaction. When different regions of RXRalpha were expressed independently, we found that only the DNA-binding domain (C-domain) bound IGFBP-3. Residues in the second Zn-finger loop (Gln49, Arg52), which contribute to C-domain dimerization on DR1 response elements, proved essential to IGFBP-3 binding. In complementary studies, we found that residues within the N-terminal domain of IGFBP-3 (Thr58, Arg60) and motifs in its C-terminal domain ((220)LysLysLys, (228)LysGlyArgLysArg) were required for interaction with RXRalpha and RARalpha. Unlike wild-type IGFBP-3, the non-retinoid receptor-binding mutants of IGFBP-3 were unable to attenuate all-trans-retinoic acid-induced transactivation of the RAR response element by RXR:RAR heterodimers. We conclude that residues in both the N- and C-terminal domains of IGFBP-3 are involved in binding the retinoid receptors, and that this interaction is essential to the modulation of RAR-signaling by IGFBP-3. 相似文献
53.
This study of the morphology, histology, histochemistry, and ultrastructure of the Harderian gland in Geckos (Squamata, Gekkota) revealed previously unreported variation. The gecko Harderian gland is unlike that of other squamates in that each cell of the secretory epithelium has both lipid and protein secretory granules. Lipid secretion has not been reported previously for the squamate Harderian gland. The structure of the protein granules resembles that described for a scincomorph lizard (Podarcis, Lacertidae). Differences between representatives of the subfamilies Gekkoninae and Diplodactylinae suggest possible phylogenetic constraints in the structure or function of Harderian glands within gekkotan lineages. The structural relationship between the Harderian gland and the lacrimal duct supports previous suggestions of a possible functional link between the Harderian gland and the vomeronasal organ. J Morphol 231:253–259, 1997. © 1997 Wiley-Liss, Inc. 相似文献
54.
Anna C. Peterson Bruno M. Ghersi Fernando Alda Cadhla Firth Matthew J. Frye Ying Bai Lynn M. Osikowicz Claudia Riegel W. Ian Lipkin Michael Y. Kosoy Michael J. Blum 《EcoHealth》2017,14(4):771-782
It is becoming increasingly likely that rodents will drive future disease epidemics with the continued expansion of cities worldwide. Though transmission risk is a growing concern, relatively little is known about pathogens carried by urban rats. Here, we assess whether the diversity and prevalence of Bartonella bacteria differ according to the (co)occurrence of rat hosts across New Orleans, LA (NO), where both Norway (Rattus norvegicus) and roof rats (Rattus rattus) are found, relative to New York City (NYC) which only harbors Norway rats. We detected human pathogenic Bartonella species in both NYC and New Orleans rodents. We found that Norway rats in New Orleans harbored a more diverse assemblage of Bartonella than Norway rats in NYC and that Norway rats harbored a more diverse and distinct assemblage of Bartonella compared to roof rats in New Orleans. Additionally, Norway rats were more likely to be infected with Bartonella than roof rats in New Orleans. Flea infestation appears to be an important predictor of Bartonella infection in Norway rats across both cities. These findings illustrate that pathogen infections can be heterogeneous in urban rodents and indicate that further study of host species interactions could clarify variation in spillover risk across cities. 相似文献
55.
Ada Hamosh Joanna S. Amberger Carol A. Bocchini Joann Bodurtha Carol J. Bult Christopher G. Chute Garry R. Cutting Harry C. Dietz Helen V. Firth Richard A. Gibbs Wayne W. Grody Melissa A. Haendel James R. Lupski Jennifer E. Posey Peter N. Robinson Lynn M. Schriml Alan F. Scott Nara L. Sobreira David Valle Nan Wu Sonja A. Rasmussen 《American journal of human genetics》2021,108(9):1807
56.
Top‐down control of species distributions: feral cats driving the regional extinction of a threatened rodent in northern Australia
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57.
John Torous Sandra Bucci Imogen H. Bell Lars V. Kessing Maria FaurholtJepsen Pauline Whelan Andre F. Carvalho Matcheri Keshavan Jake Linardon Joseph Firth 《World psychiatry》2021,20(3):318
As the COVID‐19 pandemic has largely increased the utilization of telehealth, mobile mental health technologies – such as smartphone apps, virtual reality, chatbots, and social media – have also gained attention. These digital health technologies offer the potential of accessible and scalable interventions that can augment traditional care. In this paper, we provide a comprehensive update on the overall field of digital psychiatry, covering three areas. First, we outline the relevance of recent technological advances to mental health research and care, by detailing how smartphones, social media, artificial intelligence and virtual reality present new opportunities for “digital phenotyping” and remote intervention. Second, we review the current evidence for the use of these new technological approaches across different mental health contexts, covering their emerging efficacy in self‐management of psychological well‐being and early intervention, along with more nascent research supporting their use in clinical management of long‐term psychiatric conditions – including major depression; anxiety, bipolar and psychotic disorders; and eating and substance use disorders – as well as in child and adolescent mental health care. Third, we discuss the most pressing challenges and opportunities towards real‐world implementation, using the Integrated Promoting Action on Research Implementation in Health Services (i‐PARIHS) framework to explain how the innovations themselves, the recipients of these innovations, and the context surrounding innovations all must be considered to facilitate their adoption and use in mental health care systems. We conclude that the new technological capabilities of smartphones, artificial intelligence, social media and virtual reality are already changing mental health care in unforeseen and exciting ways, each accompanied by an early but promising evidence base. We point out that further efforts towards strengthening implementation are needed, and detail the key issues at the patient, provider and policy levels which must now be addressed for digital health technologies to truly improve mental health research and treatment in the future. 相似文献
58.
Extracellular signals responsible for spatially regulated proliferation in the differentiating Drosophila eye 总被引:3,自引:0,他引:3
Spatially and temporally choreographed cell cycles accompany the differentiation of the Drosophila retina. The extracellular signals that control these patterns have been identified through mosaic analysis of mutations in signal transduction pathways. All cells arrest in G1 prior to the start of neurogenesis. Arrest depends on Dpp and Hh, acting redundantly. Most cells then go through a synchronous round of cell division before fate specification and terminal cell cycle exit. Cell cycle entry is induced by Notch signaling and opposed in subsets of cells by EGF receptor activity. Unusually, Cyclin E levels are not limiting for retinal cell cycles. Rbf/E2F and the Cyclin E antagonist Dacapo are important, however. All retinal cells, including the postmitotic photoreceptor neurons, continue dividing when rbf and dacapo are mutated simultaneously. These studies identify the specific extracellular signals that pattern the retinal cell cycles and show how differentiation can be uncoupled from cell cycle exit. 相似文献
59.
Eike Steinig Sebastin Duchêne Izzard Aglua Andrew Greenhill Rebecca Ford Mition Yoannes Jan Jaworski Jimmy Drekore Bohu Urakoko Harry Poka Clive Wurr Eri Ebos David Nangen Laurens Manning Moses Laman Cadhla Firth Simon Smith William Pomat Steven Y C Tong Lachlan Coin Emma McBryde Paul Horwood 《Molecular biology and evolution》2022,39(3)
Nanopore sequencing and phylodynamic modeling have been used to reconstruct the transmission dynamics of viral epidemics, but their application to bacterial pathogens has remained challenging. Cost-effective bacterial genome sequencing and variant calling on nanopore platforms would greatly enhance surveillance and outbreak response in communities without access to sequencing infrastructure. Here, we adapt random forest models for single nucleotide polymorphism (SNP) polishing developed by Sanderson and colleagues (2020. High precision Neisseria gonorrhoeae variant and antimicrobial resistance calling from metagenomic nanopore sequencing. Genome Res. 30(9):1354–1363) to estimate divergence and effective reproduction numbers (Re) of two methicillin-resistant Staphylococcus aureus (MRSA) outbreaks from remote communities in Far North Queensland and Papua New Guinea (PNG; n = 159). Successive barcoded panels of S. aureus isolates (2 × 12 per MinION) sequenced at low coverage (>5× to 10×) provided sufficient data to accurately infer genotypes with high recall when compared with Illumina references. Random forest models achieved high resolution on ST93 outbreak sequence types (>90% accuracy and precision) and enabled phylodynamic inference of epidemiological parameters using birth–death skyline models. Our method reproduced phylogenetic topology, origin of the outbreaks, and indications of epidemic growth (Re > 1). Nextflow pipelines implement SNP polisher training, evaluation, and outbreak alignments, enabling reconstruction of within-lineage transmission dynamics for infection control of bacterial disease outbreaks on portable nanopore platforms. Our study shows that nanopore technology can be used for bacterial outbreak reconstruction at competitive costs, providing opportunities for infection control in hospitals and communities without access to sequencing infrastructure, such as in remote northern Australia and PNG. 相似文献
60.
Early studies on the evolutionary dynamics of plant RNA viruses suggested that they may evolve more slowly than their animal
counterparts, sometimes dramatically so. However, these estimates were often based on an assumption of virus–host codivergence
over time-scales of many millions of years that is difficult to verify. An important example are viruses of the genus Tobamovirus, where the assumption of host–virus codivergence over 100 million years has led to rate estimates in the range of ~1 × 10−8 nucleotide substitutions per site, per year. Such a low evolutionary rate is in apparent contradiction with the ability of
some tobamoviruses to quickly overcome inbred genetic resistance. To resolve how rapidly molecular evolution proceeds in the
tobomaviruses, we estimated rates of nucleotide substitution, times to common ancestry, and the extent of congruence between
virus and host phylogenies. Using Bayesian coalescent methods applied to time-stamped sequences, we estimated mean evolutionary
rates at the nucleotide and amino acid levels of between 1 × 10−5 and 1.3 × 10−3 substitutions per site, per year, and hence similar to those seen in a broad range of animal and plant RNA viruses. Under
these rates, a conservative estimate for the time of origin of the sampled tobamoviruses is within the last 100,000 years,
and hence a far more recently than proposed assuming codivergence. This is supported by our cophylogeny analysis which revealed
significantly discordant evolutionary histories between the tobamoviruses and the plant families they infect. 相似文献