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1.
Joshua D. Doyle Jennifer E. Stencel-Baerenwald Courtney A. Copeland Jillian P. Rhoads Judy J. Brown Kelli L. Boyd James B. Atkinson Terence S. Dermody 《PLoS pathogens》2015,11(3)
Reovirus is a nonenveloped mammalian virus that provides a useful model system for studies of viral infections in the young. Following internalization into host cells, the outermost capsid of reovirus virions is removed by endosomal cathepsin proteases. Determinants of capsid disassembly kinetics reside in the viral σ3 protein. However, the contribution of capsid stability to reovirus-induced disease is unknown. In this study, we found that mice inoculated intramuscularly with a serotype 3 reovirus containing σ3-Y354H, a mutation that reduces viral capsid stability, succumbed at a higher rate than those infected with wild-type virus. At early times after inoculation, σ3-Y354H virus reached higher titers than wild-type virus at several sites within the host. Animals inoculated perorally with a serotype 1 reassortant reovirus containing σ3-Y354H developed exaggerated myocarditis accompanied by elaboration of pro-inflammatory cytokines. Surprisingly, unchallenged littermates of mice infected with σ3-Y354H virus displayed higher titers in the intestine, heart, and brain than littermates of mice inoculated with wild-type virus. Together, these findings suggest that diminished capsid stability enhances reovirus replication, dissemination, lethality, and host-to-host spread, establishing a new virulence determinant for nonenveloped viruses. 相似文献
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Richard B. Pouw Mieke C. Brouwer Judy Geissler Laurens V. van Herpen Sacha S. Zeerleder Walter A. Wuillemin Diana Wouters Taco W. Kuijpers 《PloS one》2016,11(3)
The major human complement regulator in blood, complement factor H (FH), has several closely related proteins, called FH-related (FHR) proteins. As all FHRs lack relevant complement regulatory activity, their physiological role is not well understood. FHR protein 3 (FHR-3) has been suggested to compete with FH for binding to Neisseria meningitidis, thereby affecting complement-mediated clearance. Clearly, the in vivo outcome of such competition greatly depends on the FH and FHR-3 concentrations. While FH levels have been established, accurate FHR-3 levels were never unequivocally reported to date. Moreover, CFHR3 gene copy numbers commonly vary, which may impact the FHR-3 concentration. Hence, we generated five anti-FHR-3 mAbs to specifically measure FHR-3 in human healthy donors of which we determined the gene copy number variation at the CFH/CFHR locus. Finally, we examined the acute-phase response characteristics of FHR-3 in a small sepsis cohort. We determined FHR-3 levels to have a mean of 19 nM and that under normal conditions the copy number of CFHR3 correlates to a very large extent with the FHR-3 serum levels. On average, FHR-3 was 132-fold lower compared to the FH concentration in the same serum samples and FHR-3 did not behave as a major acute phase response protein. 相似文献
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Krzysztof J. Gorgolewski Dan Lurie Sebastian Urchs Judy A. Kipping R. Cameron Craddock Michael P. Milham Daniel S. Margulies Jonathan Smallwood 《PloS one》2014,9(5)
Although neural activity often reflects the processing of external inputs, intrinsic fluctuations in activity have been observed throughout the brain. These may relate to patterns of self-generated thought that can occur while not performing goal-driven tasks. To understand the relationship between self-generated mental activity and intrinsic neural fluctuations, we developed the New York Cognition Questionnaire (NYC-Q) to assess the content and form of an individual''s experiences during the acquisition of resting-state fMRI data. The data were collected as a part of the Nathan Kline Rockland Enhanced sample. We decomposed NYC-Q scores using exploratory factor analysis and found that self-reported thoughts clustered into distinct dimensions of content (future related, past related, positive, negative, and social) and form (words, images, and specificity). We used these components to perform an individual difference analysis exploring how differences in the types of self-generated thoughts relate to whole brain measures of intrinsic brain activity (fractional amplitude of low frequency fluctuations, regional homogeneity, and degree centrality). We found patterns of self-generated thoughts related to changes that were distributed across a wide range of cortical areas. For example, individuals who reported greater imagery exhibited greater low frequency fluctuations in a region of perigenual cingulate cortex, a region that is known to participate in the so-called default-mode network. We also found certain forms of thought were associated with other areas, such as primary visual cortex, the insula, and the cerebellum. For example, individuals who reported greater future thought exhibited less homogeneous neural fluctuations in a region of lateral occipital cortex, a result that is consistent with the claim that particular types of self-generated thought depend on processes that are decoupled from sensory processes. These data provide evidence that self-generated thought is a heterogeneous category of experience and that studying its content can be helpful in understanding brain dynamics. 相似文献
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Judy L. Stone 《Oecologia》1996,107(4):504-512
In this paper I report components of effectiveness for pollinators of a tropical distylous shrub, Psychotria suerrensis (Rubiaceae), which is visited by a variety of bees, wasps, and butterflies, and by two species of hummingbirds. In the field, I measured the following components of effectiveness: frequency of visits, evenness of visits across plants, and diurnal pattern of visits. I also used flight-cage experiments to compare pollentransfer abilities of euglossine bees and heliconiid butterflies. Euglossine bees visited more frequently, visited earlier in the day, and visited a higher proportion of plants in the population than did other taxa. In flight cage experiments, bees and butterflies transferred similar amounts of pollen overall, but bees transferred significantly more inter-morph (compatible) pollen. For each component measured, euglossine bees appeared to be the most effective pollinators. 相似文献
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Isolation and expression of an anther-specific gene from tomato 总被引:31,自引:0,他引:31
David Twell Rod Wing Judy Yamaguchi Sheila McCormick 《Molecular & general genetics : MGG》1989,217(2-3):240-245
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Direct evidence for a role of intramitochondrial Ca2+ in the regulation of oxidative phosphorylation in the stimulated rat heart. Studies using 31P n.m.r. and ruthenium red. 总被引:2,自引:1,他引:1 下载免费PDF全文
J F Unitt J G McCormack D Reid L K MacLachlan P J England 《The Biochemical journal》1989,262(1):293-301
1. The concentrations of free ATP, phosphocreatine (PCr), Pi, H+ and ADP (calculated) were monitored in perfused rat hearts by 31P n.m.r. before and during positive inotropic stimulation. Data were accumulated in 20 s blocks. 2. Administration of 0.1 microM-(-)-isoprenaline resulted in no significant changes in ATP, transient decreases in PCr, and transient increases in ADP and Pi. However, the concentrations of all of these metabolites returned to pre-stimulated values within 1 min, whereas cardiac work and O2 uptake remained elevated. 3. In contrast, in hearts perfused continuously with Ruthenium Red (2.5 micrograms/ml), a potent inhibitor of mitochondrial Ca2+ uptake, administration of isoprenaline caused significant decreases in ATP, and also much larger and more prolonged changes in the concentrations of ADP, PCr and Pi. In this instance values did not fully return to pre-stimulated concentrations. Administration of Ruthenium Red alone to unstimulated hearts had minor effects. 4. It is proposed that, in the absence of Ruthenium Red, the transmission of changes in cytoplasmic Ca2+ across the mitochondrial inner membrane is able to maintain the phosphorylation potential of the heart during positive inotropic stimulation, through activation of the Ca2+-sensitive intramitochondrial dehydrogenases (pyruvate, NAD+-isocitrate and 2-oxoglutarate dehydrogenases) leading to enhanced NADH production. 5. This mechanism is unavailable in the presence of Ruthenium Red, and oxidative phosphorylation must be stimulated primarily by a fall in phosphorylation potential, in accordance with the classical concept of respiratory control. However, the full oxidative response of the heart to stimulation may not be achievable under such circumstances. 相似文献
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