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91.
We have recently shown that overexpression of dominant-negative AtSKD1 versions under control of the trichome and non-root-hair-cell specific GL2 promoter (GL2pro) blocks trafficking of soluble cargo to the vacuole, resulting in its fragmentation and ultimately cell death. GL2pro is also active in the Arabidopsis seeds. When we inspected seeds of the dominant-negative AtSKD1 variants we found two phenotypes. The seeds display a transparent testa phenotype caused by a lack of proanthocyanidin (PA) and do not possess seed coat mucilage. Both phenotypes could be connected by cell death induced by the overexpression of dominant-negative AtSKD1.Key words: VPS4, ESCRT, plant, Arabidopsis, SKD1, ATPase, MVB, proanthocyanidin, transparent testa, mucilage, tannin, seed coat, AtSKD1AAA ATPases are important regulators of a plethora of cellular functions such as peroxisome biogenesis, vesicle-mediated transport, control of cell divisions and gene expression. This variety is based on a common mechanism, the energy dependent unfolding, remodeling and disassembly of proteins and protein complexes.1Mammalian SKD1 and its yeast homolog VPS4 are AAA ATPases involved in the sorting of monoubiquitylated trans-membrane cargo to the lysosome/vacuole by dismantling the members of the endosomal sorting complex required for transport (ESCRT) complexes from the endosomal membrane.2 The Arabidopsis SKD1 homolog, AtSKD1, has been characterized recently and has been shown to be an ortholog of SKD1/Vps4.3,4 Mutations for all three ATPases are known that alone or in combination render them dominant-negative.3–6 Overexpression of dominant-negative AtSKD1 is, however, lethal for Arabidopsis plants. Therefore, we have used the trichome and non-root-hair-cell-specific GL2pro promoter to address the function of AtSKD1 in planta. Cells that express the dominant-negative versions show multiple nuclei, fragmented vacuoles and ultimately die. These phenotypes are most likely due to a block in vacuolar trafficking of soluble cargo that is instead secreted.4GL2pro is also active in the coat of developing Arabidopsis seeds. We therefore inspected seeds of lines overexpressing dominant-negative and wild-type AtSKD1. 相似文献
92.
Nelson PA Khodadoust M Prodhomme T Spencer C Patarroyo JC Varrin-Doyer M Ho JD Stroud RM Zamvil SS 《PloS one》2010,5(11):e15050
Autoantibodies that target the water channel aquaporin-4 (AQP4) in neuromyelitis optica (NMO) are IgG1, a T cell-dependent Ig subclass. However, a role for AQP4-specific T cells in this CNS inflammatory disease is not known. To evaluate their potential role in CNS autoimmunity, we have identified and characterized T cells that respond to AQP4 in C57BL/6 and SJL/J mice, two strains that are commonly studied in models of CNS inflammatory diseases. Mice were immunized with either overlapping peptides or intact hAQP4 protein encompassing the entire 323 amino acid sequence. T cell determinants identified from examination of the AQP4 peptide (p) library were located within AQP4 p21-40, p91-110, p101-120, p166-180, p231-250 and p261-280 in C57BL/6 mice, and within p11-30, p21-40, p101-120, p126-140 and p261-280 in SJL/J mice. AQP4-specific T cells were CD4+ and MHC II-restricted. In recall responses to immunization with intact AQP4, T cells responded primarily to p21-40, indicating this region contains the immunodominant T cell epitope(s) for both strains. AQP4 p21-40-primed T cells secreted both IFN-γ and IL-17. The core immunodominant AQP4 21-40 T cell determinant was mapped to residues 24-35 in C57BL/6 mice and 23-35 in SJL/J mice. Our identification of the AQP4 T cell determinants and characterization of its immunodominant determinant should permit investigators to evaluate the role of AQP4-specific T cells in vivo and to develop AQP4-targeted murine NMO models. 相似文献
93.
Ordookhani A Padyab M Goldasteh A Mirmiran P Richter J Azizi F 《Chronobiology international》2010,27(9-10):1854-1869
Seasonal aggregation and the monthly rate of neonatal transient hyperthyrotropinemia (THT) were assessed. From November 1998 to April 2005, neonates of gestational age ≥37 wks, birth weight 2500-4000?g, birth length 45-55 cm, and 1st min Apgar score >3, who had thyrotropin (TSH) ≥20 mU/L in their cord dried-blood specimen, but without congenital hypothyroidism, were enrolled in the study. The recall rate equals the rate of THT occurrence in this study. Of 47,945 neonates, 555 had THT (recall rate: 1.2%). The aggregated seasonal recall rate (recall for further assessment to rule out congenital hypothyroidism) was significantly higher in winter (January, February, and March) than the other seasons (p < .0001). Winter had higher recall rate in each year as compared to other seasons, but the overall rate of recalls decreased in 2001 and 2002. Excluding the first 6 months (due to erratic variations), the remaining 72 months revealed a relatively sinusoidal pattern in monthly recall rates; indeed, there was an initial 11-month high recall rates (1.7%), followed by a 33-month decrease (0.7%), a 19-month increase (1.9%), and a final 9-month decrease (0.8%). The recall rate of each of these time intervals was significantly different from that of the next time interval (p < .0001). The monthly recall rates were best fitted to cubic curve estimation and then autoregressive integrated moving average (ARIMA) (0, 1, 1) models. THT occurs significantly more in winter than in other seasons, and this suggests a possible role for time-varying factor(s) contributing to its seasonal preponderance. 相似文献
94.
Jafari-Azad Aida Hosseini Leila Rajabi Mojgan Høilund-Carlsen Poul Flemming Vafaee Manouchehr Seyedi Feyzizadeh Saeid Badalzadeh Reza 《Molecular biology reports》2021,48(4):3089-3096
Molecular Biology Reports - It has been documented that aging increases the risk of cardiovascular disease including myocardial ischemia/reperfusion (IR) injury and acute myocardial infarction. In... 相似文献
95.
Objective
Idiopathic trigeminal neuralgia (TN) is characterized by paroxysms of severe facial pain but without the major sensory loss that commonly accompanies neuropathic pain. Since neurovascular compression of the trigeminal nerve root entry zone does not fully explain the pathogenesis of TN, we determined whether there were brain gray matter abnormalities in a cohort of idiopathic TN patients. We used structural MRI to test the hypothesis that TN is associated with altered gray matter (GM) in brain areas involved in the sensory and affective aspects of pain, pain modulation, and motor function. We further determined the contribution of long-term TN on GM plasticity.Methods
Cortical thickness and subcortical GM volume were measured from high-resolution 3T T1-weighted MRI scans in 24 patients with right-sided TN and 24 healthy control participants.Results
TN patients had increased GM volume in the sensory thalamus, amygdala, periaqueductal gray, and basal ganglia (putamen, caudate, nucleus accumbens) compared to healthy controls. The patients also had greater cortical thickness in the contralateral primary somatosensory cortex and frontal pole compared to controls. In contrast, patients had thinner cortex in the pregenual anterior cingulate cortex, the insula and the orbitofrontal cortex. No relationship was observed between GM abnormalities and TN pain duration.Conclusions
TN is associated with GM abnormalities in areas involved in pain perception, pain modulation and motor function. These findings may reflect increased nociceptive input to the brain, an impaired descending modulation system that does not adequately inhibit pain, and increased motor output to control facial movements to limit pain attacks. 相似文献96.
Mojgan Masoodi Daniel S. Pearl Michael Eiden Janis K. Shute James F. Brown Philip C. Calder Timothy M. Trebble 《PloS one》2013,8(10)
Objectives
Ulcerative colitis (UC) is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA)) are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX) inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids) within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC.Design
Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically.Results
Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems.Conclusions
Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile. 相似文献97.
Tsivkovskii R Sabet M Tarazi Z Griffith DC Lomovskaya O Dudley MN 《FEMS immunology and medical microbiology》2011,61(2):141-146
Inflammation resulting from chronic bacterial infection in the lung contributes to long-term pulmonary complications in chronic pulmonary infections such as cystic fibrosis. Aerosol administration of levofloxacin as in the form of the investigational formulation MP-376 results in higher concentrations in lung tissues that are higher than those that can be attained with oral or intravenous dosing of levofloxacin. The objective of this study was to evaluate the effect of high concentrations of levofloxacin achieved with aerosol administration of MP-376 on proinflammatory cytokine secretion by immortalized human bronchial epithelia cells in vitro. Additionally, we investigated the potential mechanisms of the immunomodulatory effect of levofloxacin. In vitro studies in human lung epithelial cell lines showed that levofloxacin led to a dose-related reduction in IL-6 and IL-8 concentrations, with 300 μg mL(-1) resulting in the reduction of levels of IL-6 by fourfold and IL-8 by twofold (P<0.05); in contrast, tobramycin increased IL-6 levels by 50%, but had no effect on IL-8. Levofloxacin treatment did not affect the cytokine mRNA level and nuclear factor-κB-dependent promoter activity. These findings suggest that high concentrations of levofloxacin obtained in pulmonary tissues following the administration of aerosol MP-376 may provide additional benefits in patients with chronic pulmonary infections that are independent of its antibacterial properties. 相似文献
98.
Aminnejad M Diaz M Arabatzis M Castañeda E Lazera M Velegraki A Marriott D Sorrell TC Meyer W 《Mycopathologia》2012,173(5-6):337-346
Cryptococcus neoformans and Cryptococcus gattii are pathogenic yeasts causing meningoencephalitis in immunocompromised and immunocompetent hosts. The fungus is typically haploid, and sexual reproduction occurs normally between individuals with opposite mating types, α and a. C. neoformans var. grubii (serotype A) is comprised of molecular types VNI, VNII, and VNB, and C. neoformans var. neoformans (serotype D) contains the molecular type VNIV. Additionally, diploid or aneuploid AD hybrids (VNIII) have been reported. C. gattii contains the molecular types VGI, VGII, VGIII, and VGIV, which encompass both serotypes B and C. To identify possible hybrid strains, URA5-RFLP analysis was performed on 350 globally obtained clinical, environmental, and veterinary isolates. Four clinical isolates from cerebrospinal fluid showed combination patterns of C. neoformans var. grubii and C. gattii: Brazil (n = 2), Colombia (n = 1), and India (n = 1). These strains were monokaryotic and diploid or aneuploid. M13 PCR fingerprinting showed that they contained fragments of both proposed parental groups. Luminex IGS genotyping identified these isolates as hybrids with two different molecular type combinations: three VNI/VGII and one VNI/VGI. Blue color development on CGB agar was delayed in three isolates and absent in one. C. gattii-specific PCR confirmed the presence of C. gattii in the hybrids. CAP59 allele-specific PCR revealed that all the hybrids contained both serotype A and B alleles. Determination of mating-type allelic patterns by PCR revealed that the isolates were αA aB. This is the first study discovering novel natural hybrids between C. neoformans molecular type VNI and C. gattii molecular type VGII. 相似文献
99.
Kouyos RD Leventhal GE Hinkley T Haddad M Whitcomb JM Petropoulos CJ Bonhoeffer S 《PLoS genetics》2012,8(3):e1002551
Although fitness landscapes are central to evolutionary theory, so far no biologically realistic examples for large-scale fitness landscapes have been described. Most currently available biological examples are restricted to very few loci or alleles and therefore do not capture the high dimensionality characteristic of real fitness landscapes. Here we analyze large-scale fitness landscapes that are based on predictive models for in vitro replicative fitness of HIV-1. We find that these landscapes are characterized by large correlation lengths, considerable neutrality, and high ruggedness and that these properties depend only weakly on whether fitness is measured in the absence or presence of different antiretrovirals. Accordingly, adaptive processes on these landscapes depend sensitively on the initial conditions. While the relative extent to which mutations affect fitness on their own (main effects) or in combination with other mutations (epistasis) is a strong determinant of these properties, the fitness landscape of HIV-1 is considerably less rugged, less neutral, and more correlated than expected from the distribution of main effects and epistatic interactions alone. Overall this study confirms theoretical conjectures about the complexity of biological fitness landscapes and the importance of the high dimensionality of the genetic space in which adaptation takes place. 相似文献
100.
Mojgan Rabiey Shyamali R. Roy Dominique Holtappels Linda Franceschetti Billy J. Quilty Ryan Creeth George W. Sundin Jeroen Wagemans Rob Lavigne Robert W. Jackson 《Microbial biotechnology》2020,13(5):1428-1445
Bacterial canker is a major disease of Prunus species, such as cherry (Prunus avium). It is caused by Pseudomonas syringae pathovars, including P. syringae pv. syringae (Pss) and P. syringae pv. morsprunorum race 1 (Psm1) and race 2 (Psm2). Concerns over the environmental impact of, and the development of bacterial resistance to, traditional copper controls calls for new approaches to disease management. Bacteriophage-based biocontrol could provide a sustainable and natural alternative approach to combat bacterial pathogens. Therefore, seventy phages were isolated from soil, leaf and bark of cherry trees in six locations in the south east of England. Subsequently, their host range was assessed against strains of Pss, Psm1 and Psm2. While these phages lysed different Pss, Psm and some other P. syringae pathovar isolates, they did not infect beneficial bacteria such as Pseudomonas fluorescens. A subset of thirteen phages were further characterized by genome sequencing, revealing five distinct clades in which the phages could be clustered. No known toxins or lysogeny-associated genes could be identified. Using bioassays, selected phages could effectively reduce disease progression in vivo, both individually and in cocktails, reinforcing their potential as biocontrol agents in agriculture. 相似文献