Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant-pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the''Guard-Hypothesis,'' R proteins (the ``guards'') can sense modification of target molecules in the host (the ``guardees'') by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the ``guardee-effector'' interface for pathogen recognition, natural selection acts on the ``guard-guardee'' interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen

Revival of the magnetar PSR J1622-4950: observations with MeerKAT, Parkes, XMM-Newton, Swift, Chandra, and NuSTAR

New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a quiescent state since at least early 2015, reactivated between 2017 March 19 and April 5. The radio flux density, while variable, is approximately 100x larger than during its dormant state. The X-ray flux one month after reactivation was at least 800x larger than during quiescence, and has been decaying exponentially on a 111+/-19 day timescale. This high-flux state, together with a radio-derived rotational ephemeris, enabled for the first time the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV pulsed fraction is comparable to the smallest observed for magnetars. The overall pulsar geometry inferred from polarized radio emission appears to be broadly consistent with that determined 6-8 years earlier. However, rotating vector model fits suggest that we are now seeing radio emission from a different location in the magnetosphere than previously. This indicates a novel way in which radio emission from magnetars can differ from that of ordinary pulsars. The torque on the neutron star is varying rapidly and unsteadily, as is common for magnetars following outburst, having changed by a factor of 7 within six months of reactivation.Comment: Published in ApJ (2018 April 5); 13 pages, 4 figure

Hyponatremia revisited: Translating physiology to practice

The complexity of hyponatremia as a clinical problem is likely caused by the opposite scenarios that accompany this electrolyte disorder regarding pathophysiology (depletional versus dilutional hyponatremia, high versus low vasopressin levels) and therapy (rapid correction to treat cerebral edema versus slow correction to prevent osmotic demyelination, fluid restriction versus fluid resuscitation). For a balanced differentiation between these opposites, an understanding of the pathophysiology of hyponatremia is required. Therefore, in this review an attempt is made to translate the physiology of water balance regulation to strategies that improve the clinical management of hyponatremia. A physiology-based approach to the patient with hyponatremia is presented, first addressing the possibility of acute hyponatremia, and then asking if and if so why vasopressin is secreted non-osmotically. Additional diagnostic recommendations are not to rely too heavily of the assessment of the extracellular fluid volume, to regard the syndrome of inappropriate antidiuresis as a diagnosis of exclusion, and to rationally investigate the pathophysiology of hyponatremia rather than to rely on isolated laboratory values with arbitrary cutoff values. The features of the major hyponatremic disorders are discussed, including diuretic-induced hyponatremia, adrenal and pituitary insufficiency, the syndrome of inappropriate antidiuresis, cerebral salt wasting, and exercise-associated hyponatremia. The treatment of hyponatremia is reviewed from simple saline solutions to the recently introduced vasopressin receptor antagonists, including their promises and limitations. Given the persistently high rates of hospital-acquired hyponatremia, the importance of improving the management of hyponatremia seems both necessary and achievable. Copyrigh

Screen of Non-annotated Small Secreted Proteins of \u3ci\u3ePseudomonas syringae\u3c/i\u3e Reveals a Virulence Factor That Inhibits Tomato Immune Proteases

Pseudomonas syringae pv. tomato DC3000 (PtoDC3000) is an extracellular model plant pathogen, yet its potential to produce secreted effectors that manipulate the apoplast has been under investigated. Here we identified 131 candidate small, secreted, non-annotated proteins from the PtoDC3000 genome, most of which are common to Pseudomonas species and potentially expressed during apoplastic colonization. We produced 43 of these proteins through a custom-made gateway-compatible expression system for extracellular bacterial proteins, and screened them for their ability to inhibit the secreted immune protease C14 of tomato using competitive activity-based protein profiling. This screen revealed C14-inhibiting protein-1 (Cip1), which contains motifs of the chagasin-like protease inhibitors. Cip1 mutants are less virulent on tomato, demonstrating the importance of this effector in apoplastic immunity. Cip1 also inhibits immune protease Pip1, which is known to suppress PtoDC3000 infection, but has a lower affinity for its close homolog Rcr3, explaining why this protein is not recognized in tomato plants carrying the Cf-2 resistance gene, which uses Rcr3 as a co-receptor to detect pathogen-derived protease inhibitors. Thus, this approach uncovered a protease inhibitor of P. syringae, indicating that also P. syringae secretes effectors that selectively target apoplastic host proteases of tomato, similar to tomato pathogenic fungi, oomycetes and nematodes

Screen of Non-annotated Small Secreted Proteins of \u3ci\u3ePseudomonas syringae\u3c/i\u3e Reveals a Virulence Factor That Inhibits Tomato Immune Proteases

Pseudomonas syringae pv. tomato DC3000 (PtoDC3000) is an extracellular model plant pathogen, yet its potential to produce secreted effectors that manipulate the apoplast has been under investigated. Here we identified 131 candidate small, secreted, non-annotated proteins from the PtoDC3000 genome, most of which are common to Pseudomonas species and potentially expressed during apoplastic colonization. We produced 43 of these proteins through a custom-made gateway-compatible expression system for extracellular bacterial proteins, and screened them for their ability to inhibit the secreted immune protease C14 of tomato using competitive activity-based protein profiling. This screen revealed C14-inhibiting protein-1 (Cip1), which contains motifs of the chagasin-like protease inhibitors. Cip1 mutants are less virulent on tomato, demonstrating the importance of this effector in apoplastic immunity. Cip1 also inhibits immune protease Pip1, which is known to suppress PtoDC3000 infection, but has a lower affinity for its close homolog Rcr3, explaining why this protein is not recognized in tomato plants carrying the Cf-2 resistance gene, which uses Rcr3 as a co-receptor to detect pathogen-derived protease inhibitors. Thus, this approach uncovered a protease inhibitor of P. syringae, indicating that also P. syringae secretes effectors that selectively target apoplastic host proteases of tomato, similar to tomato pathogenic fungi, oomycetes and nematodes

Trans-Amazon Drilling Project (TADP): origins and evolution of the forests, climate, and hydrology of the South American tropics

This article presents the scientific rationale for an ambitious ICDP drilling project to continuously sample Late Cretaceous to modern sediment in four different sedimentary basins that transect the equatorial Amazon of Brazil, from the Andean foreland to the Atlantic Ocean. The goals of this project are to document the evolution of plant biodiversity in the Amazon forests and to relate biotic diversification to changes in the physical environment, including climate, tectonism, and the surface landscape. These goals require long sedimentary records from each of the major sedimentary basins across the heart of the Brazilian Amazon, which can only be obtained by drilling because of the scarcity of Cenozoic outcrops. The proposed drilling will provide the first long, nearly continuous regional records of the Cenozoic history of the forests, their plant diversity, and the associated changes in climate and environment. It also will address fundamental questions about landscape evolution, including the history of Andean uplift and erosion as recorded in Andean foreland basins and the development of west-to-east hydrologic continuity between the Andes, the Amazon lowlands, and the equatorial Atlantic. Because many modern rivers of the Amazon basin flow along the major axes of the old sedimentary basins, we plan to locate drill sites on the margin of large rivers and to access the targeted drill sites by navigation along these rivers

Influence of firm size on the competencies required to management engineers in the Jordanian telecommunications sector

This is an Accepted Manuscript of an article published by Taylor & Francis in European Journal of Engineering Education on [13 jun 2016], available online:http://www.tandfonline.com/ doi/abs/10.1080/03043797.2016.1197890.[EN] The objective of this study is to identify the competencies required to achieve success in the transition from higher education to the labour market based on the perceptions of employers. This paper analyses the assessments made by a group of engineering company employers. An item-battery of 20 competencies was grouped into 3 dimensions by using factor analysis. Subsequently, respondents scores were also clustered into three groups and characterised through contingency tables. The competencies demanded by employers were grouped into business and finance, problem-solving and strategic planning. Significant differences were found between responses from employers working in medium and small companies, who placed more importance on competencies related to problem-solving and strategic planning, and employers in big companies, who were more concerned about the difficulties of finding well-trained graduates. The findings from this paper have important implications for research in the areas of higher education and organisations that usually employ graduate engineers.The authors would like to thank the Education, Audiovisual and Culture Executive Agency (EACEA) [Tempus program. Project number 511074] of the European Commission for providing funding for conducting this study. This publication reflects the views only of the authors, and the Commission cannot be held responsible for any use which may be made of the information contained therein.Conchado Peiró, A.; Bas Cerdá, MDC.; Gharaibeh, KM.; Kaylani, H. (2016). 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Pentalogy of Cantrell: two patients and a review to determine prognostic factors for optimal approach

Two patients with incomplete pentalogy of Cantrell are described. The first was a girl with a large omphalocele with evisceration of the heart, liver and intestines with an intact sternum. Echocardiography showed profound intracardiac defects. The girl died 33 h after birth. The second patient was a female fetus with ectopia cordis (EC) without intracardiac anomalies; a large omphalocele with evisceration of the heart, stomach, spleen and liver; a hypoplastic sternum and rib cage; and a scoliosis. The pregnancy was terminated. A review of patients described in the literature is presented with the intention of finding prognostic factors for an optimal approach to patients with the pentalogy of Cantrell. In conclusion the prognosis seems to be poorer in patients with the complete form of pentalogy of Cantrell, EC, and patients with associated anomalies. Intracardial defects do not seem to be a prognostic factor

Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone

Background Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with RAS and BRAF wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location. Methods Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively. Results When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75, P = 0.003 and HR 0.12, 95% CI 0.04–0.36, P < 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04–0.71, P = 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36–0.96, P = 0.034). Conclusions The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy