A trematode parasite derived growth factor binds and exerts influences on host immune functions via host cytokine receptor complexes

The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allow- ing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF) superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL)-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory recep- tor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is depen- dent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs) in their evasion of antibody- dependent cell cytotoxicity (ADCC) by reducing the NO response of macrophages—again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for damp- ened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow for a reduced effector response targetingjuvenile parasites which we demonstrate extends to an abrogation of the ADCC response. Thus suggesting that FhTLM is a stage specific evasion molecule that utilises host cytokine receptors. These findings are the first to clearly demonstrate the interaction of a helminth cytokine with a host receptor complex resulting in immune modifications that facilitate the non-protective chronic immune response which is characteristic of F. hepatica infection

High-throughput gene discovery in the rat

The rat is an important animal model for human diseases and is widely used in physiology. In this article we present a new strategy for gene discovery based on the production of ESTs from serially subtracted and normalized cDNA libraries, and we describe its application for the development of a comprehensive nonredundant collection of rat ESTs. Our new strategy appears to yield substantially more EST clusters per ESTs sequenced than do previous approaches that did not use serial subtraction. However, multiple rounds of library subtraction resulted in high frequencies of otherwise rare internally primed cDNAs, defining the limits of this powerful approach. To date, we have generated >200,000 3′ ESTs from >100 cDNA libraries representing a wide range of tissues and developmental stages of the laboratory rat. Most importantly, we have contributed to ∼50,000 rat UniGene clusters. We have identified, arrayed, and derived 5′ ESTs from >30,000 unique rat cDNA clones. Complete information, including radiation hybrid mapping data, is also maintained locally at http://genome.uiowa.edu/clcg.html. All of the sequences described in this article have been submitted to the dbEST division of the NCBI

Paediatric acute hepatitis of unknown aetiology : a national investigation and adenoviraemia case-control study in the UK

Funding Information: This work was undertaken as part of a national enhanced incident by UK public health agencies. We thank the parents and guardians of the children who gave up their valuable time to speak to the public health investigation teams; without their support we could not have been able to undertake a thorough investigation. We are grateful to the many paediatricians and liver specialists who reported cases to us and responded to follow-up with further information. We also thank Ezra Linley and Simon Tonge of the UK Health Security Agency Seroepidemiology Unit for rapidly providing serum samples for testing. We would like to thank the Incident Management Teams of the UK nations, members of the incident cells, epidemiology, laboratory, and local Health Protection Teams who supported the investigations, in particular: Katy Sinka, Mike Gent, Suzanna Howes, Eileen Gallagher, Selene Corsini, Eleanor Clarke, Rajani Raghu, Kelsey Mowat, Iain Hayden, Matt Hibbert, Skye Firminger, Catriona Angel, Donna Haskins, Kay Ratcliffe, Hannah Emmett, Alex Elliot, Helen Hughes, Sarah Deeny, Sarah Garner, Sarah Gerver, Flora Stevens, Paula Blomquist, Gabriel Gurmail Kauffman, Kristine Cooper, Hannah Taylor, Giovanni Leonardi, Michelle Dickinson and Michelle Watson from England; Kimberly Marsh, Michael Lockhart, David Yirrell, Sandra Currie, Kate Templeton, Samantha Shepherd, Roisin Ure, Jim McMenamin, Rachel Tayler, Louisa Pollock, Antonia Ho, Chris Cunningham and Hayley Peacock from Scotland; and Katie Binley and Meg Wallace from Northern Ireland.Peer reviewe

Climate drives the geography of marine consumption by changing predator communities

Este artículo contiene 7 páginas, 3 figuras, 1 tabla.The global distribution of primary production and consumption by humans (fisheries) is well-documented, but we have no map linking the central ecological process of consumption within food webs to temperature and other ecological drivers. Using standardized assays that span 105° of latitude on four continents, we show that rates of bait consumption by generalist predators in shallow marine ecosystems are tightly linked to both temperature and the composition of consumer assemblages. Unexpectedly, rates of consumption peaked at midlatitudes (25 to 35°) in both Northern and Southern Hemispheres across both seagrass and unvegetated sediment habitats. This pattern contrasts with terrestrial systems, where biotic interactions reportedly weaken away from the equator, but it parallels an emerging pattern of a subtropical peak in marine biodiversity. The higher consumption at midlatitudes was closely related to the type of consumers present, which explained rates of consumption better than consumer density, biomass, species diversity, or habitat. Indeed, the apparent effect of temperature on consumption was mostly driven by temperature-associated turnover in consumer community composition. Our findings reinforce the key influence of climate warming on altered species composition and highlight its implications for the functioning of Earth’s ecosystems.We acknowledge funding from the Smithsonian Institution and the Tula Foundation.Peer reviewe

Are we ready to track climate-driven shifts in marine species across international boundaries? - A global survey of scientific bottom trawl data

Marine biota are redistributing at a rapid pace in response to climate change and shifting seascapes. While changes in fish populations and community structure threaten the sustainability of fisheries, our capacity to adapt by tracking and projecting marine species remains a challenge due to data discontinuities in biological observations, lack of data availability, and mismatch between data and real species distributions. To assess the extent of this challenge, we review the global status and accessibility of ongoing scientific bottom trawl surveys. In total, we gathered metadata for 283,925 samples from 95 surveys conducted regularly from 2001 to 2019. We identified that 59% of the metadata collected are not publicly available, highlighting that the availability of data is the most important challenge to assess species redistributions under global climate change. Given that the primary purpose of surveys is to provide independent data to inform stock assessment of commercially important populations, we further highlight that single surveys do not cover the full range of the main commercial demersal fish species. An average of 18 surveys is needed to cover at least 50% of species ranges, demonstrating the importance of combining multiple surveys to evaluate species range shifts. We assess the potential for combining surveys to track transboundary species redistributions and show that differences in sampling schemes and inconsistency in sampling can be overcome with spatio-temporal modeling to follow species density redistributions. In light of our global assessment, we establish a framework for improving the management and conservation of transboundary and migrating marine demersal species. We provide directions to improve data availability and encourage countries to share survey data, to assess species vulnerabilities, and to support management adaptation in a time of climate-driven ocean changes.En prensa6,86

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

An index to assess the health and benefits of the global ocean

The ocean plays a critical role in supporting human well-being, from providing food, livelihoods and recreational opportunities to regulating the global climate. Sustainable management aimed at maintaining the flow of a broad range of benefits from the ocean requires a comprehensive and quantitative method to measure and monitor the health of coupled human–ocean systems. We created an index comprising ten diverse public goals for a healthy coupled human–ocean system and calculated the index for every coastal country. Globally, the overall index score was 60 out of 100 (range 36–86), with developed countries generally performing better than developing countries, but with notable exceptions. Only 5% of countries scored higher than 70, whereas 32% scored lower than 50. The index provides a powerful tool to raise public awareness, direct resource management, improve policy and prioritize scientific research.This is the publisher’s final pdf. The published article is copyrighted by the Nature Publishing Group and can be found at: http://www.nature.com/nature/index.htm

The effects of single bouts of aerobic exercise, videogame play, and exergaming on cognitive control

The effects of single bouts of aerobic exercise, action videogame playing, and exergaming on event-related brain potentials and task performance indices of cognitive control were studied. Thirty-six young adults performed a modified flanker task during four separate, counterbalanced sessions, using a within-subjects design. Participants were trained on the flanker and gaming tasks prior to completing the experimental conditions, and then completed a cardiorespiratory fitness assessment. Each session consisted of 20 minutes of activity followed by cognitive testing once heart rate (HR) returned to within 10% of pre-exercise levels. The experimental activities consisted of seated rest, seated videogame play, treadmill-based aerobic exercise, and exergame-based aerobic exercise; the latter two conditions occurring at an intensity of 60% of maximum HR. Task performance indicated decreased reaction time interference following treadmill exercise relative to seated rest and videogame play. Further, P3 amplitude replicated previous research as it was larger following treadmill exercise compared to rest, suggesting an increased allocation of attentional resources during the cognitive control task. The seated videogame and exergame did not differ from any other condition. These findings indicate that single bouts of treadmill exercise may improve cognitive control through an increase in the allocation of attentional resources and greater interference control during cognitively demanding tasks. However, similar benefits may not occur following single sessions of aerobic exergaming or seated videogame participation

Improving hospital care and collaborative communications for the 21st century : key recommendations for general internal medicine

BACKGROUND: Communication and collaboration failures can have negative impacts on the efficiency of both individual clinicians and health care system delivery as well as on the quality of patient care. Recognizing the problems associated with clinical and collaboration communication, health care professionals and organizations alike have begun to look at alternative communication technologies to address some of these inefficiencies and to improve interprofessional collaboration. OBJECTIVE: To develop recommendations that assist health care organizations in improving communication and collaboration in order to develop effective methods for evaluation. METHODS: An interprofessional meeting was held in a large urban city in Canada with 19 nationally and internationally renowned experts to discuss suitable recommendations for an ideal communication and collaboration system as well as a research framework for general internal medicine (GIM) environments. RESULTS: In designing an ideal GIM communication and collaboration system, attendees believed that the new system should possess attributes that aim to: a) improve workflow through prioritization of information and detection of individuals' contextual situations; b) promote stronger interprofessional relationships with adequate exchange of information; c) enhance patient-centered care by allowing greater patient autonomy over their health care information; d) enable interoperability and scalability between and within institutions; and e) function across different platforms. In terms of evaluating the effects of technology in GIM settings, participants championed the use of rigorous scientific methods that span multiple perspectives and disciplines. Specifically, participants recommended that consistent measures and definitions need to be established so that these impacts can be examined across individual, group, and organizational levels. CONCLUSIONS: Discussions from our meeting demonstrated the complexities of technological implementations in GIM settings. Recommendations on the design principles and research paradigms for an improved communication system are described