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121.
Francesca Rosini Pamela Federighi Elena Pretegiani Pietro Piu R. John Leigh Alessandro Serra Antonio Federico Alessandra Rufa 《PloS one》2013,8(7)
Fixation instability due to saccadic intrusions is a feature of autosomal recessive spinocerebellar ataxias, and includes square wave intrusions (SWI) and macrosaccadic oscillations (MSO). A recent report suggested that the non-competitive antagonist of NMDA receptors, memantine, could decrease MSO and improve fixation in patients with spinocerebellar ataxia with saccadic intrusions (SCASI). We similarly tested two sisters, respectively of 58 and 60 years, with an unrecognized form of recessive, adult-onset cerebellar ataxia, peripheral neuropathy and slow saccades, who showed prominent SWI and also complained with difficulty in reading. We tested horizontal visually guided saccades (10°–18°) and three minutes of steady fixation in each patient and in thirty healthy controls. Both patients showed a significant reduction of peak and mean velocity compared with control subjects. Large SWI interrupting steady fixation were prominent during steady fixation and especially following visually guided saccades. Eye movements were recorded before and during the treatment with memantine, 20 mg/daily for 6 months. The treatment with memantine reduced both the magnitude and frequency of SWI (the former significantly), but did not modified neurological conditions or saccade parameters. Thus, our report suggests that memantine may have some general suppressive effect on saccadic intrusions, including both SWI and MSO, thereby restoring the capacity of reading and visual attention in these and in other recessive forms of ataxia, including Friedreich’s, in which saccadic intrusions are prominent. 相似文献
122.
Xunjun Xiao Michael R. Ferguson Kelsey E. Magee Pamela D. Hale Yan Wang Mark E. Lowe 《Journal of lipid research》2013,54(2):514-521
Colipase is essential for efficient fat digestion. An arginine-to-cysteine polymorphism at
position 92 of colipase (Arg92Cys) associates with an increased risk for developing type-2 diabetes
through an undefined mechanism. To test our hypothesis that the extra cysteine increases colipase
misfolding, thereby altering its intracellular trafficking and function, we expressed Cys92 colipase
in HEK293T cells. Less Cys92 colipase is secreted and more is retained intracellularly in an
insoluble form compared with Arg92 colipase. Nonreducing gel electrophoresis suggests the folding of
secreted Cys92 colipase differs from Arg92 colipase. Cys92 colipase misfolding does not trigger the
unfolded protein response (UPR) or endoplasmic reticulum (ER) stress. The ability of secreted Cys92
colipase to stimulate pancreatic triglyceride lipase (PTL) is reduced with all substrates tested,
particularly long-chain triglycerides. The reaction of Cys92 colipase with triolein and Intralipid
has a much longer lag time, reflecting decreased ability to anchor PTL on those substrates. Our data
predicts that humans with the Arg92Cys substitution will secrete less functional colipase into the
duodenum and have less efficient fat digestion. Whether inefficient fat digestion or another
property of colipase contributes to the risk for developing diabetes remains to be clarified. 相似文献
123.
124.
Daniel J. Howard Pamela G. Gregory Jiming Chu Michael L. Cain 《Evolution; international journal of organic evolution》1998,52(2):511-516
Conspecific sperm precedence is widespread in animals, appears to evolve rapidly, and is thought to have the potential to prevent hybridization between closely related species. However, to date no study has tested the isolating potential of such a barrier in mixed populations of two taxa under conditions in which other potential barriers to gene flow are controlled for or are prevented from operating. We tested the isolating potential of conspecific sperm precedence in the ground crickets Allonemobius fasciatus and A. socius in population cage experiments in which the frequency of the two species was varied. Despite the observation of abundant interspecific matings, the proportions of hybrid progeny were low and differed statistically from the proportions expected in the absence of conspecific sperm precedence. The results demonstrate that conspecific sperm precedence can severely limit gene flow between closely related species, even when one species is less abundant than the other. 相似文献
125.
Senescence-induced RNases in tomato 总被引:18,自引:0,他引:18
126.
Gaurav Bhatti Lakshmi Jayanthi Pamela VandeVord Yeshitila Gebremichael 《Journal of molecular modeling》2013,19(2):779-792
The unique conformation of the active site in calpains along with the implication of their role in several diseases has prompted widespread research interest in the scientific community. Structural studies devoted to m- and μ-calpains have proposed a two-stage calcium-dependent activation mechanism for calpains. In this work, we performed conventional and targeted molecular dynamics simulations to investigate global and local changes in the structure of the protease core of m-calpain upon calcium binding. Simulations were performed on the protease core of calcium free (pdbid: 1kfu) and calcium bound (pdbid: 3df0) m-calpain with and without the presence of calcium ions. Our results indicate that the inactive, open conformation of the protease core does not transform into the active, closed conformation simply upon removal of constraints from the neighbor domains. The role of other factors, including calcium binding and the subsequent formation of an Arg94–Glu305 inter-domain salt bridge and the change in the orientation of Trp288 side chain, in the activation of the protease core is elicited. 相似文献
127.
Comparative effects of cytokines and cytokine combinations on complement component C3 secretion by HepG2 cells 总被引:4,自引:0,他引:4
The mechanisms that control complement protein synthesis are incompletely understood. Recent evidence suggests that cytokines are involved in the regulation of hepatic synthesis of circulating complement components. Therefore, we compared the effects of human recombinant IL-1alpha, IL-1beta, IL-6, IFN-gamma, and TNF-alpha individually or in combination, on HepG2 secretion of complement component C3, the major opsonic protein of the complement system. HepG2 cells were incubated with each cytokine alone and with various combinations of the cytokines. At 24, 48, 72, and 96 h of incubation, the C3 and albumin secreted by the HepG2 cells were quantified by a sandwich ELISA. IL-1alpha and IFN-gamma significantly enhanced C3 secretion by the cells (P<0.02 vs. control cells). IL-1beta when combined with either IL-6 or IFN-gamma also increased C3 secretion (P<0.03 vs. control cells). The stimulatory effect on HepG2 cells by the IL-1beta/IL-6 combination was synergistic. With the exception of IL-1alpha, which increased albumin secretion, HepG2 secretion of albumin was not affected by incubation with individual cytokines or the cytokine combinations. Therefore, IL-1alpha, IFN-gamma, and the combination of IL-1beta with IL-6 or IFN-gamma specifically enhanced C3 secretion by HepG2 cells. The greatest magnitude of C3 secretion was induced by the combination of IL-1beta and IL-6. 相似文献
128.
Thomas C. Darton Christoph J. Blohmke Eleni Giannoulatou Claire S. Waddington Claire Jones Pamela Sturges Craig Webster Hal Drakesmith Andrew J. Pollard Andrew E. Armitage 《PLoS neglected tropical diseases》2015,9(9)
BackgroundIron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge.Conclusions/SignificanceWe demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S. Typhi. 相似文献
129.
Top 10 plant pathogenic bacteria in molecular plant pathology 总被引:7,自引:0,他引:7
Mansfield J Genin S Magori S Citovsky V Sriariyanum M Ronald P Dow M Verdier V Beer SV Machado MA Toth I Salmond G Foster GD 《Molecular Plant Pathology》2012,13(6):614-629
Many plant bacteriologists, if not all, feel that their particular microbe should appear in any list of the most important bacterial plant pathogens. However, to our knowledge, no such list exists. The aim of this review was to survey all bacterial pathologists with an association with the journal Molecular Plant Pathology and ask them to nominate the bacterial pathogens they would place in a 'Top 10' based on scientific/economic importance. The survey generated 458 votes from the international community, and allowed the construction of a Top 10 bacterial plant pathogen list. The list includes, in rank order: (1) Pseudomonas syringae pathovars; (2) Ralstonia solanacearum; (3) Agrobacterium tumefaciens; (4) Xanthomonas oryzae pv. oryzae; (5) Xanthomonas campestris pathovars; (6) Xanthomonas axonopodis pathovars; (7) Erwinia amylovora; (8) Xylella fastidiosa; (9) Dickeya (dadantii and solani); (10) Pectobacterium carotovorum (and Pectobacterium atrosepticum). Bacteria garnering honourable mentions for just missing out on the Top 10 include Clavibacter michiganensis (michiganensis and sepedonicus), Pseudomonas savastanoi and Candidatus Liberibacter asiaticus. This review article presents a short section on each bacterium in the Top 10 list and its importance, with the intention of initiating discussion and debate amongst the plant bacteriology community, as well as laying down a benchmark. It will be interesting to see, in future years, how perceptions change and which bacterial pathogens enter and leave the Top 10. 相似文献
130.
Leigh A. Johnson Douglas E. Soltis Pamela S. Soltis 《Plant Systematics and Evolution》1999,214(1-4):65-89
Cladistic analyses of chloroplast DNA disagree with current classifications by placingPolemoniaceae near sympetalous families with two staminal whorls, includingFouquieriaceae andDiapensiaceae, rather than near sympetalous families with a single staminal whorl, such asHydrophyllaceae andConvolvulaceae. To explore further the affinities ofPolemoniaceae, we sequenced 18S ribosomal DNA for eight genera ofPolemoniaceae and 31 families representing a broadly definedAsteridae. The distribution of variation in these sequences suggest some sites are hypervariable and multiple hits at these sites have obscured much of the hierarchical structure present in the data. Nevertheless, parsimony, least-squares minimum evolution, and maximum likelihood methods all support a monophyleticPolemoniaceae that is placed nearFouquieriaceae, Diapensiaceae and related ericalean families. 相似文献