Non-pathogenic rhizobacteria Pseudomonas spp. can reduce disease in plant tissues through induction of a defence state known as induced systemic resistance (ISR). This resistance is based on multiple ...bacterial determinants, but nothing is known about the mechanisms underlying rhizobacteria-induced resistance in grapevine. In this study, the ability of Pseudomonas fluorescens CHA0 and Pseudomonas aeruginosa 7NSK2 to induce resistance in grapevine against Botrytis cinerea is demonstrated. Both strains also triggered an oxidative burst and phytoalexin (i.e. resveratrol and viniferin) accumulation in grape cells and primed leaves for accelerated phytoalexin production upon challenge with B. cinerea. Treatment of cell cultures with crude cell extracts of bacteria strongly enhanced oxidative burst, but resulted in comparable amounts of phytoalexins and resistance to B. cinerea to those induced by living bacteria. This suggests the production of bacterial compounds serving as inducers of disease resistance. Using other strains with different characteristics, it is shown that P. fluorescens WCS417 (Pch-deficient), P. putida WCS358 (Pch- and SA-deficient) and P. fluorescens Q2-87 (a DAPG producer) were all capable of inducing resistance to an extent similar to that induced by CHA0. However, in response to WCS417 (Pch-negative) the amount of H2O2 induced is less than for the CHA0. WCS417 induced low phytoalexin levels in cells and lost the capacity to prime for phytoalexins in the leaves. This suggests that, depending on the strain, SA, pyochelin, and DAPG are potentially effective in inducing or priming defence responses. The 7NSK2 mutants, KMPCH (Pch- and Pvd-negative) and KMPCH-567 (Pch-, Pvd-, and SA-negative) induced only partial resistance to B. cinerea. However, the amount of H2O2 triggered by KMPCH and KMPCH-567 was similar to that induced by 7NSK2. Both mutants also led to a low level of phytoalexins in grapevine cells, while KMPCH slightly primed grapevine leaves for enhanced phytoalexins. This highlights the importance of SA, pyochelin, and/or pyoverdin in priming phytoalexin responses and induced grapevine resistance by 7NSK2 against B. cinerea.
Colonization of Arabidopsis thaliana roots by nonpathogenic Pseudomonas fluorescens WCS417r bacteria triggers a jasmonate/ethylene-dependent induced systemic resistance (ISR) that is effective ...against a broad range of pathogens. Microarray analysis revealed that the R2R3-MYB-like transcription factor gene MYB72 is specifically activated in the roots upon colonization by WCS417r. Here, we show that T-DNA knockout mutants myb72-1 and myb72-2 are incapable of mounting ISR against the pathogens Pseudomonas syringae pv tomato, Hyaloperonospora parasitica, Alternaria brassicicola, and Botrytis cinerea, indicating that MYB72 is essential to establish broad-spectrum ISR. Overexpression of MYB72 did not result in enhanced resistance against any of the pathogens tested, demonstrating that MYB72 is not sufficient for the expression of ISR. Yeast two-hybrid analysis revealed that MYB72 physically interacts in vitro with the ETHYLENE INSENSITIVE3 (EIN3)-LIKE3 transcription factor EIL3, linking MYB72 function to the ethylene response pathway. However, WCS417r activated MYB72 in ISR-deficient, ethylene-insensitive ein2-1 plants. Moreover, exogenous application of the ethylene precursor 1-aminocyclopropane-1-carboxylate induced wild-type levels of resistance in myb72-1, suggesting that MYB72 acts upstream of ethylene in the ISR pathway. Collectively, this study identified the transcriptional regulator MYB72 as a novel ISR signaling component that is required in the roots during early signaling steps of rhizobacteria-mediated ISR.
Plants develop an enhanced defensive capacity against a broad spectrum of plant pathogens after colonization of the roots by selected strains of nonpathogenic, fluorescent Pseudomonas spp. In ...Arabidopsis thaliana, this rhizobacteria-induced systemic resistance (ISR) functions independently of salicylic acid but requires responsiveness to the plant hormones jasmonic acid and ethylene. In contrast to pathogen-induced systemic acquired resistance, rhizobacteria-mediated ISR is not associated with changes in the expression of genes encoding pathogenesis-related proteins. To identify ISR-related genes, we surveyed the transcriptional response of over 8,000 Arabidopsis genes during rhizobacteria-mediated ISR. Locally in the roots, ISR-inducing Pseudomonas fluorescens WCS417r bacteria elicited a substantial change in the expression of 97 genes. However, systemically in the leaves, none of the approximately 8,000 genes tested showed a consistent change in expression in response to effective colonization of the roots by WCS417r, indicating that the onset of ISR in the leaves is not associated with detectable changes in gene expression. After challenge inoculation of WCS417r-induced plants with the bacterial leaf pathogen P. syringae pv. tomato DC3000, 81 genes showed an augmented expression pattern in ISR-expressing leaves, suggesting that these genes were primed to respond faster or more strongly upon pathogen attack. The majority of the primed genes was predicted to be regulated by jasmonic acid or ethylene signaling. Priming of pathogen-induced genes allows the plant to react more effectively to the invader encountered, which might explain the broad-spectrum action of rhizobacteria-mediated ISR.
To postpone cognitive decline and dementia in old age, primary prevention is required earlier in life during middle age. Dietary components may be modifiable determinants of mental performance. In ...the present study, habitual fruit and vegetable intake was studied in association with cognitive function and cognitive decline during middle age. In the Doetinchem Cohort Study, 2613 men and women aged 43–70 years at baseline (1995–2002) were examined for cognitive function twice, with a 5-year time interval. Global cognitive function and the domains memory, information processing speed and cognitive flexibility were assessed. Dietary intake was assessed with a semi-quantitative FFQ. In multivariate linear regression analyses, habitual fruit and vegetable intake was studied in association with baseline and change in cognitive function. Higher reported vegetable intake was associated with lower information processing speed (P = 0·02) and worse cognitive flexibility (P = 0·03) at baseline, but with smaller decline in information processing speed (P < 0·01) and global cognitive function (P = 0·02) at follow-up. Total intakes of fruits, legumes and juices were not associated with baseline or change in cognitive function. High intakes of some subgroups of fruits and vegetables (i.e. nuts, cabbage and root vegetables) were associated with better cognitive function at baseline and/or smaller decline in cognitive domains. In conclusion, total intake of fruits and vegetables was not or inconsistently associated with cognitive function and cognitive decline. A high habitual consumption of some specific fruits and vegetables may diminish age-related cognitive decline in middle-aged individuals. Further research is needed to verify these findings before recommendations can be made.
Plants of which the roots are colonized by selected strains of non-pathogenic, fluorescent Pseudomonas spp. develop an enhanced defensive capacity against a broad spectrum of foliar pathogens. In ...Arabidopsis thaliana, this rhizobacteria-induced systemic resistance (ISR) functions independently of salicylic acid but requires responsiveness to jasmonic acid and ethylene. In contrast to pathogen-induced systemic acquired resistance (SAR), ISR is not associated with systemic changes in the expression of genes encoding pathogenesis-related (PR) proteins. To identify genes that are specifically expressed in response to colonization of the roots by ISR-inducing Pseudomonas fluorescens WCS417r bacteria, we screened a collection of Arabidopsis enhancer trap and gene trap lines containing a transposable element of the Ac/Ds system and the GUS reporter gene. We identified an enhancer trap line (WET121) that specifically showed GUS activity in the root vascular bundle upon colonization of the roots by WCS417r. Fluorescent Pseudomonas spp. strains P. fluorescens WCS374r and P. putida WCS358r triggered a similar expression pattern, whereas ISR-non-inducing Escherichia coli bacteria did not. Exogenous application of the ethylene precursor 1-aminocyclopropane-1-carboxylate (ACC) mimicked the rhizobacteria-induced GUS expression pattern in the root vascular bundle, whereas methyl jasmonic acid and salicylic acid did not, indicating that the Ds element in WET121 is inserted in the vicinity of an ethylene-responsive gene. Analysis of the expression of the genes in the close vicinity of the Ds element revealed AtTLP1 as the gene responsible for the in cis activation of the GUS reporter gene in the root vascular bundle. AtTLP1 encodes a thaumatin-like protein that belongs to the PR-5 family of PR proteins, some of which possess antimicrobial properties. AtTLP1 knockout mutant plants showed normal levels of WCS417r-mediated ISR against the bacterial leaf pathogen Pseudomonas syringae pv. tomato DC3000, suggesting that expression of AtTLP1 in the roots is not required for systemic expression of ISR in the leaves. Together, these results indicate that induction of AtTLP1 is a local response of Arabidopsis roots to colonization by non-pathogenic fluorescent Pseudomonas spp. and is unlikely to play a role in systemic resistance.
To determine the proportion of participants of a running program for novice runners that discontinued running and investigate the main reasons to discontinue and characteristics associated with ...discontinuation.
Prospective cohort study.
The study included 774 participants of Start to Run, a 6-week running program for novice runners. Before the start of the program, participants filled-in a baseline questionnaire to collect information on demographics, physical activity and perceived health. The 26-weeks follow-up questionnaire was used to obtain information on the continuation of running (yes/no) and main reasons for discontinuation. To determine predictors for discontinuation of running, multivariable logistic regression was performed.
Within 26 weeks after the start of the 6-week running program, 29.5% of the novice runners (n=225) had stopped running. The main reason for discontinuation was a running-related injury (n=108, 48%). Being female (OR 1.74; 95% CI 1.13–2.68), being unsure about the continuation of running after the program (OR 2.06; 95% CI 1.31–3.24) and (almost) no alcohol use (OR 1.62; 95%CI 1.11–2.37) were associated with a higher chance of discontinuation of running. Previous running experience less than one year previously (OR 0.46; 95% CI 0.26–0.83) and a higher score on the RAND-36 subscale physical functioning (OR 0.98; 95% CI 0.96–0.99) were associated with a lower chance of discontinuation.
In this group of novice runners, almost one-third stopped running within six months. A running-related injury was the main reason to stop running. Women with a low perceived physical functioning and without running experience were prone to discontinue running.
The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in ...the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods/access. Trail registration: https://www.trialregister.nl/trial/7955.
The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined ...mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains.
As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters.
The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.
OBJECTIVE This study aimed to determine the prognostic value of MRI variables to predict outcome in patients with herniated disc-related sciatica, and whether MRI could facilitate the decision making ...between early surgery and prolonged conservative care in these patients. METHODS A prospective observational evaluation of patients enrolled in a randomized trial with 1-year follow-up was completed. A total of 283 patients with sciatica who had a radiologically confirmed disc herniation were randomized either to surgery or to prolonged conservative care with surgery if needed. Outcome measures were recovery and leg pain severity. Recovery was registered on a 7-point Likert scale. Complete/near complete recovery was considered a satisfactory outcome. Leg pain severity was measured on a 0- to 100-mm visual analog scale. Multiple MRI characteristics of the degenerated disc herniation were independently scored by 3 spine experts. Cox models were used to study the influence of MRI variables on rate of recovery, and linear mixed models were used to determine the predictive value of MRI variables for leg pain severity during follow-up. The interaction of each MRI predictor with treatment allocation was tested. There were no study-specific conflicts of interest. RESULTS Baseline MRI variables associated with less leg pain severity were the reader's assessment of presence of nerve root compression (p < 0.001), and assessment of extrusion compared with protrusion of the disc herniation (p = 0.006). Both variables tended to be associated, but not significantly, with satisfactory outcome during follow-up (HR 1.45, 95% CI 0.93-2.24, and HR 1.24, 95% CI 0.96-1.61, respectively). The size of disc herniation at baseline was not associated with outcome. There was no significant change in the effects between treatment groups. CONCLUSIONS MRI assessment of the presence of nerve root compression and extrusion of a herniated disc at baseline was associated with less leg pain during 1-year follow-up, irrespective of a surgical or conservative treatment. MRI findings seem not to be helpful in determining which patients might fare better with early surgery compared with a strategy of prolonged conservative care. Clinical trial registration no.: ISRCTN26872154 ( controlled-trials.com ).
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