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991.
Boyle CD Vice SF Campion J Chackalamannil S Lankin CM McCombie SW Billard W Binch H Crosby G Williams MC Coffin VL Cox KA Grotz DE Duffy RA Ruperto V Lachowicz JE 《Bioorganic & medicinal chemistry letters》2002,12(23):3479-3482
We previously reported the initial discovery of a novel class of stabilized benzylidene ketal M(2) receptor antagonists. This paper discusses new analogues consisting of benzamide modifications which not only improved M(2) receptor affinity and selectivity, but also enhanced the pharmacokinetic properties of the series. These changes led to the discovery of a highly potent and selective M(2) antagonist, which demonstrated in vivo efficacy and had good bioavailability in multiple species. 相似文献
992.
Spatial organisation of the genome within the nucleus can play a role in maintaining the expressed or silent state of some genes [1]. There are distinct addresses for specific chromosomes, which have different functional characteristics, within the nuclei of dividing populations of human cells [2]. Here, we demonstrate that this level of nuclear architecture is altered in cells that have become either quiescent or senescent. Upon cell cycle exit, a gene-poor human chromosome moves from a location at the nuclear periphery to a more internal site in the nucleus, and changes its associations with nuclear substructures. The chromosome moves back toward the edge of the nucleus at a distinctive time after re-entry into the cell cycle. There is a 2-4 hour period at the beginning of G1 when the spatial organisation of these human chromosomes is established. Lastly, these experiments provide evidence that temporal control of DNA replication can be independent of spatial chromosome organisation. We conclude that the sub-nuclear organisation of chromosomes in quiescent or senescent mammalian somatic cells is fundamentally different from that in proliferating cells and that the spatial organisation of the genome is plastic. 相似文献
993.
Sheliza Halani Panashe E. Tombindo Ryan OReilly Rafael N. Miranda Laura K. Erdman Clare Whitehead Joanna M. Bielecki Lauren Ramsay Raphael Ximenes Justin Boyle Carsten Krueger Shannon Willmott Shaun K. Morris Kellie E. Murphy Beate Sander 《PLoS neglected tropical diseases》2021,15(7)
BackgroundZika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally.MethodsThis review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools.FindingsWe identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS.ConclusionsThe ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae. 相似文献
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Although the sound production mechanisms of male and female Ophidion rochei (Ophidiidae) differ significantly, temperature affects them in the same manner. In both sexes, temperature correlated negatively with pulse period and positively with sound frequencies but had no, or weak effects on other sound characteristics. 相似文献
998.
Seleem M Ali M Al-Azeem MW Boyle SM Sriranganathan N 《Applied microbiology and biotechnology》2007,75(6):1385-1392
The creation of a double His-tag fusion that forms a RNA stem loop in the mRNA encoding the N-terminus of the target protein
is a novel approach for the enhancement of expression, purification, and detection of a recombinant protein. Compared to a
single His-tag fusion, a tandem His-tag fusion RNA stem loop, located downstream of the constitutive groE and Ch promoters, enhanced heterologous gene expression in Brucella, Salmonella, and Escherichia. We demonstrated one-step detection and purification of recombinant green fluorescence protein (GFP) directly from Brucella spp. without using Escherichia coli as an expression host. The amount of purified GFP using the tandem His-tag RNA stem loop increased more than threefold; moreover,
the sensitivity of detection increased more than fourfold in comparison to the single His-tag fusion form. This method has
the potential to significantly improve heterologous gene expression and high-throughput protein synthesis and purification. 相似文献
999.
Kondrachuk AV Sirenko SP Boyle R 《Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology》2007,14(1):P73-P74
The function of semicircular canals (SC) is based on the precise equality of densities of the cupula and endolymph. Otherwise the information provided by SC would depend on the orientation of both the gravity vector relative to canal plane and the axis of rotation. It would also depend on the distance between the axis of rotation and the center of the SC. We believe that the equality of densities is approximate and expect that due to the high sensitivity of the SC, even the small differences of densities (approximately 10(-4) g/cm3) can influence the SC dynamics, and this influence depends on the conditions of canal stimulation. The work aims to examine this hypothesis and analyze the parameters of the SC and mechanical stimulation under which the effect of the difference of densities on the SC functioning could be observed. 相似文献
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