An RxLR effector from phytophthora infestans prevents re-localisation of two plant NAC transcription factors from the endoplasmic reticulum to the nucleus

The plant immune system is activated following the perception of exposed, essential and invariant microbial molecules that are recognised as non-self. A major component of plant immunity is the transcriptional induction of genes involved in a wide array of defence responses. In turn, adapted pathogens deliver effector proteins that act either inside or outside plant cells to manipulate host processes, often through their direct action on plant protein targets. To date, few effectors have been shown to directly manipulate transcriptional regulators of plant defence. Moreover, little is known generally about the modes of action of effectors from filamentous (fungal and oomycete) plant pathogens. We describe an effector, called Pi03192, from the late blight pathogen Phytophthora infestans, which interacts with a pair of host transcription factors at the endoplasmic reticulum (ER) inside plant cells. We show that these transcription factors are released from the ER to enter the nucleus, following pathogen perception, and are important in restricting disease. Pi03192 prevents the plant transcription factors from accumulating in the host nucleus, revealing a novel means of enhancing host susceptibility

Prevention of anxiety and depression in the age group of 75 years and over: a randomised controlled trial testing the feasibility and effectiveness of a generic stepped care programme among elderly community residents at high risk of developing anxiety and depression versus usual care [ISRCTN26474556]

BACKGROUND: In frail elderly, the effects of depression and anxiety are deep encroaching. Indicated prevention studies, aimed at subjects with subthreshold disorder, have shown that well designed interventions are capable of reducing the incidence of depression and anxiety. In this randomised prevention trial for elderly, living in the community and suffering from subthreshold depression and anxiety, a stepped care programme was put together to be tested versus usual (GP) care. METHODS/DESIGN: Design: randomised controlled trial. (See figure 1: organisation chart) together with two other projects, this project is part of a national consortium that investigates the prevention of anxiety and depressive disorders in later life using a stepped care programme. The three projects have their own particular focus. This project is aimed at elderly living in the community. Inclusion: subjects with a high risk for depression and anxiety without clinical evidence of these syndromes. The participants are 75 years of age and over and have subthreshold symptoms of depression and or anxiety: they score above the cut-off point on the self-report Centre for Epidemiologic Studies Depression (CES-D) scale, but the criteria for a major depressive disorder or anxiety disorder (panic disorder, agoraphobia, social phobia, generalized anxiety disorder) according to a validated interview, the Mini International Neuropsychiatric Interview (MINI) are not fulfilled. Outcomes: primary outcome: incidence of a depressive or anxiety disorder over a period of two years (MINI); secondary outcome: a positive influence of the intervention, a stepped care programme, on symptoms of depression and anxiety and on quality of life as assessed with the CES D, the HADS A and the SF36 respectively (i.e. stabilisation or improvement of symptoms) [see table 1]. Measurements: Take place at baseline and at 3, 6, 9, 12, 18 and 24 months. Trained independent evaluators assess depression and anxiety status, the primary end point (6, 12, 18, 24 months) [see table 2]. DISCUSSION: Late-life depression and anxiety are characterised by high prevalence, unfavourable prognosis, reduced quality of life, excess mortality and substantial societal costs. No health service, however well equipped, will be able to effectively treat all elderly with depression and anxiety. Therefore, development of (cost) effective means to prevent these disorders is very important

MRI follow-up of conservatively treated meniscal knee lesions in general practice

Objective: To evaluate meniscal status change on follow-up MRI after 1 year, prognostic factors and association with clinical outcome in patients with conservatively treated knee injury. Methods: We analysed 403 meniscal horns in 101 conservatively treated patients (59 male; mean age 40 years) in general practice who underwent initial knee MRI within 5 weeks of trauma. We performed ordinal logistic regression analysis to analyse prognostic factors for meniscal change on follow-up MRI after 1 year, and we assessed the association with clinical outcome. Results: On follow-up MRI 49 meniscal horns had deteriorated and 18 had improved. Age (odds ratio [OR] 1.3/decade), body weight (OR 1.2/10 kg), total anterior cruciate ligament (ACL) rupture on initial MRI (OR 2.4), location in the posterior horn of the medial meniscus (OR 3.0) and an initial meniscal lesion (OR 0.3) were statistically significant predictors of meniscal MRI appearance change after 1 year, which was not associated with clinical outcome. Conclusion: In conservatively treated patients, meniscal deterioration on follow-up MRI 1 year after trauma is predicted by higher age and body weight, initial total ACL rupture, and location in the medial posterior horn. Change in MRI appearance is not associated with clinical outcome

Enhanced biological carbon consumption in a high CO2 ocean

The oceans have absorbed nearly half of the fossil-fuel carbon dioxide (CO2) emitted into the atmosphere since pre-industrial times1, causing a measurable reduction in seawater pH and carbonate saturation2. If CO2 emissions continue to rise at current rates, upper-ocean pH will decrease to levels lower than have existed for tens of millions of years and, critically, at a rate of change 100 times greater than at any time over this period3. Recent studies have shown effects of ocean acidification on a variety of marine life forms, in particular calcifying organisms4, 5, 6. Consequences at the community to ecosystem level, in contrast, are largely unknown. Here we show that dissolved inorganic carbon consumption of a natural plankton community maintained in mesocosm enclosures at initial CO2 partial pressures of 350, 700 and 1,050 μatm increases with rising CO2. The community consumed up to 39% more dissolved inorganic carbon at increased CO2 partial pressures compared to present levels, whereas nutrient uptake remained the same. The stoichiometry of carbon to nitrogen drawdown increased from 6.0 at low CO2 to 8.0 at high CO2, thus exceeding the Redfield carbon:nitrogen ratio of 6.6 in today’s ocean7. This excess carbon consumption was associated with higher loss of organic carbon from the upper layer of the stratified mesocosms. If applicable to the natural environment, the observed responses have implications for a variety of marine biological and biogeochemical processes, and underscore the importance of biologically driven feedbacks in the ocean to global change

Ultra-diffuse hydrothermal venting supports Fe-oxidizing bacteria and massive umber deposition at 5000 m off Hawaii

© International Society for Microbial Ecology, 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in The ISME Journal 5 (2011): 1748–1758, doi:10.1038/ismej.2011.48.A novel hydrothermal field has been discovered at the base of Lōihi Seamount, Hawaii, at 5000 mbsl. Geochemical analyses demonstrate that ‘FeMO Deep’, while only 0.2 °C above ambient seawater temperature, derives from a distal, ultra-diffuse hydrothermal source. FeMO Deep is expressed as regional seafloor seepage of gelatinous iron- and silica-rich deposits, pooling between and over basalt pillows, in places over a meter thick. The system is capped by mm to cm thick hydrothermally derived iron-oxyhydroxide- and manganese-oxide-layered crusts. We use molecular analyses (16S rDNA-based) of extant communities combined with fluorescent in situ hybridizations to demonstrate that FeMO Deep deposits contain living iron-oxidizing Zetaproteobacteria related to the recently isolated strain Mariprofundus ferroxydans. Bioenergetic calculations, based on in-situ electrochemical measurements and cell counts, indicate that reactions between iron and oxygen are important in supporting chemosynthesis in the mats, which we infer forms a trophic base of the mat ecosystem. We suggest that the biogenic FeMO Deep hydrothermal deposit represents a modern analog for one class of geological iron deposits known as ‘umbers’ (for example, Troodos ophilolites, Cyprus) because of striking similarities in size, setting and internal structures.Funding has been provided by the NSF Microbial Observatories Program (KJE, DE, BT, HS and CM), by the Gordon and Betty Moore Foundation (KJE), the College of Letters, Arts, and Sciences at the University of Southern California (KJE) and by the NASA Astrobiology Institute (KJE, DE)

A quantitative mass spectrometry-based approach to monitor the dynamics of endogenous chromatin-associated protein complexes.

Understanding the dynamics of endogenous protein-protein interactions in complex networks is pivotal in deciphering disease mechanisms. To enable the in-depth analysis of protein interactions in chromatin-associated protein complexes, we have previously developed a method termed RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins). Here, we present a quantitative multiplexed method (qPLEX-RIME), which integrates RIME with isobaric labelling and tribrid mass spectrometry for the study of protein interactome dynamics in a quantitative fashion with increased sensitivity. Using the qPLEX-RIME method, we delineate the temporal changes of the Estrogen Receptor alpha (ERα) interactome in breast cancer cells treated with 4-hydroxytamoxifen. Furthermore, we identify endogenous ERα-associated proteins in human Patient-Derived Xenograft tumours and in primary human breast cancer clinical tissue. Our results demonstrate that the combination of RIME with isobaric labelling offers a powerful tool for the in-depth and quantitative characterisation of protein interactome dynamics, which is applicable to clinical samples

Promotion of a healthy lifestyle among 5-year-old overweight children: Health behavior outcomes of the 'Be active, eat right' study

Background: This study evaluates the effects of an intervention performed by youth health care professionals on child health behaviors. The intervention consisted of offering healthy lifestyle counseling to parents of overweight (not obese) 5-year-old children. Effects of the intervention on the child having breakfast, drinking sweet beverages, watching television and playing outside were evaluated. Methods. Data were collected with the 'Be active, eat right' study, a cluster randomized controlled trial among nine youth health care centers in the Netherlands. Parents of overweight children received lifestyle counseling according to the intervention protocol in the intervention condition (n = 349) and usual care in the control condition (n = 288). Parents completed questionnaires regarding demographic characteristics, health behaviors and the home environment at baseline and at 2-year follow-up. Cluster adjusted regression models were applied; interaction terms were explored. Results: The population for analysis consisted of 38.1% boys; mean age 5.8 [sd 0.4] years; mean BMI SDS 1.9 [sd 0.4]. There were no significant differences in the number of minutes of outside play or television viewing a day between children in the intervention and the control condition. Also, the odds ratio for having breakfast daily or drinking two or less glasses of sweet beverages a day showed no significant differences between the two conditions. Additional analyses showed that the odds ratio for drinking less than two glasses of sweet beverages at follow-up compared with baseline was significantly higher for children in both the intervention (p < 0.001) and the control condition (p = 0.029). Conclusions: Comparison of the children in the two conditions showed that the intervention does not contribute to a change in health behaviors. Further studies are needed to investigate opportunities to adjust the intervention protocol, such as integration of elements in the regular well-child visit. The intervention protocol for youth health care may become part of a broader approach to tackle childhood overweight and obesity. Trial registration. Current Controlled Trials ISRCTN04965410

Presence of celiac disease epitopes in modern and old hexaploid wheat varieties: wheat breeding may have contributed to increased prevalence of celiac disease

Gluten proteins from wheat can induce celiac disease (CD) in genetically susceptible individuals. Specific gluten peptides can be presented by antigen presenting cells to gluten-sensitive T-cell lymphocytes leading to CD. During the last decades, a significant increase has been observed in the prevalence of CD. This may partly be attributed to an increase in awareness and to improved diagnostic techniques, but increased wheat and gluten consumption is also considered a major cause. To analyze whether wheat breeding contributed to the increase of the prevalence of CD, we have compared the genetic diversity of gluten proteins for the presence of two CD epitopes (Glia-α9 and Glia-α20) in 36 modern European wheat varieties and in 50 landraces representing the wheat varieties grown up to around a century ago. Glia-α9 is a major (immunodominant) epitope that is recognized by the majority of CD patients. The minor Glia-α20 was included as a technical reference. Overall, the presence of the Glia-α9 epitope was higher in the modern varieties, whereas the presence of the Glia-α20 epitope was lower, as compared to the landraces. This suggests that modern wheat breeding practices may have led to an increased exposure to CD epitopes. On the other hand, some modern varieties and landraces have been identified that have relatively low contents of both epitopes. Such selected lines may serve as a start to breed wheat for the introduction of ‘low CD toxic’ as a new breeding trait. Large-scale culture and consumption of such varieties would considerably aid in decreasing the prevalence of CD