Comparison of MRI properties between multimeric DOTAGA and DO3A gadolinium-dendron conjugates

The inherent lack of sensitivity of MRI needs the development of new Gd contrast agents in order to extend 20Hz,37%, the application of this technique to cellular imaging. For this purpose, two multimeric MR contrast agents obtained by peptidic coupling between an amido amine dendron and GdDOTAGA chelates (premetalation strategy, G1-4GdDOTAGA) or DO3A derivatives which then were postmetalated (G1-4GdDO-3A) have been prepared. By comparison to the monomers, an increase of longitudinal relaxivity has been observed for both structures. Especially for G1-4GdDO-3A, a marked increase is observed between 20 and 60 MHz. This structure differs from G1-4GdDOTAGA by an increased rigidity due to the aromatic linker between each chelate and the organic framework. This has the effect of limiting local rotational movements, which has a positive impact on relaxivity

<em>Tendril-less</em> regulates tendril formation in pea leaves

Tendrils are contact-sensitive, filamentous organs that permit climbing plants to tether to their taller neighbors. Tendrilled legume species are grown as field crops, where the tendrils contribute to the physical support of the crop prior to harvest. The homeotic tendril-less (tl) mutation in garden pea (Pisum sativum), identified almost a century ago, transforms tendrils into leaflets. In this study, we used a systematic marker screen of fast neutron–generated tl deletion mutants to identify Tl as a Class I homeodomain leucine zipper (HDZIP) transcription factor. We confirmed the tendril-less phenotype as loss of function by targeting induced local lesions in genomes (TILLING) in garden pea and by analysis of the tendril-less phenotype of the t mutant in sweet pea (Lathyrus odoratus). The conversion of tendrils into leaflets in both mutants demonstrates that the pea tendril is a modified leaflet, inhibited from completing laminar development by Tl. We provide evidence to show that lamina inhibition requires Unifoliata/LEAFY-mediated Tl expression in organs emerging in the distal region of the leaf primordium. Phylogenetic analyses show that Tl is an unusual Class I HDZIP protein and that tendrils evolved either once or twice in Papilionoid legumes. We suggest that tendrils arose in the Fabeae clade of Papilionoid legumes through acquisition of the Tl gene

Exploiting a fast neutron mutant genetic resource in Pisum sativum (pea) for functional genomics

A fast neutron mutagenised population was generated in Pisum sativum L. (pea) to enable the identification and isolation of genes underlying traits and processes. Studies of a number of phenotypic traits have clearly demonstrated the utility of the resource by associating gene deletions with phenotype followed by functional tests exploiting additional mutant sources, from both induced and natural variant germplasm. For forward genetic screens next generation sequencing methodologies provide an opportunity for identifying genes associated with deletions rapidly and systematically. The application of rapid reverse genetic screens of the fast neutron mutant pea population supports conclusions on the frequency of deletions based on phenotype alone. These studies further suggest that large deletions affecting one or more loci can be non-deleterious to the pea genome, yielding mutants that could not be obtained by other means. Deletion mutants affecting genes associated with seed metabolism and storage are providing unique opportunities to identify the products of complex and related gene families, and to study the downstream consequences of such deletion

The First Provenance Challenge

The first Provenance Challenge was set up in order to provide a forum for the community to help understand the capabilities of different provenance systems and the expressiveness of their provenance representations. To this end, a Functional Magnetic Resonance Imaging workflow was defined, which participants had to either simulate or run in order to produce some provenance representation, from which a set of identified queries had to be implemented and executed. Sixteen teams responded to the challenge, and submitted their inputs. In this paper, we present the challenge workflow and queries, and summarise the participants contributions

The EMSO Generic Instrument Module (EGIM): standardized and interoperable instrumentation for ocean observation

The oceans are a fundamental source for climate balance, sustainability of resources and life on Earth, therefore society has a strong and pressing interest in maintaining and, where possible, restoring the health of the marine ecosystems. Effective, integrated ocean observation is key to suggesting actions to reduce anthropogenic impact from coastal to deep-sea environments and address the main challenges of the 21st century, which are summarized in the UN Sustainable Development Goals and Blue Growth strategies. The European Multidisciplinary Seafloor and water column Observatory (EMSO), is a European Research Infrastructure Consortium (ERIC), with the aim of providing long-term observations via fixed-point ocean observatories in key environmental locations across European seas from the Arctic to the Black Sea. These may be supported by ship-based observations and autonomous systems such as gliders. In this paper, we present the EMSO Generic Instrument Module (EGIM), a deployment ready multi-sensor instrumentation module, designed to measure physical, biogeochemical, biological and ecosystem variables consistently, in a range of marine environments, over long periods of time. Here, we describe the system, features, configuration, operation and data management. We demonstrate, through a series of coastal and oceanic pilot experiments that the EGIM is a valuable standard ocean observation module, which can significantly improve the capacity of existing ocean observatories and provides the basis for new observatories. The diverse examples of use included the monitoring of fish activity response upon oceanographic variability, hydrothermal vent fluids and particle dispersion, passive acoustic monitoring of marine mammals and time series of environmental variation in the water column. With the EGIM available to all the EMSO Regional Facilities, EMSO will be reaching a milestone in standardization and interoperability, marking a key capability advancement in addressing issues of sustainability in resource and habitat management of the oceans.This work was funded by the project EMSODEV (Grant agreement No 676555) supported by DG Research and Innovation of the European Commission under the Research Infrastructures Programme of the H2020. EMSO-link EC project (Grant agreement No 731036) provided additional funding. Other projects which supported the work include Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020, project BITER-LANDER PID2020- 114732RB-C32, iFADO (Innovation in the Framework of the Atlantic Deep Ocean, 2017–2021) EAPA_165/2016. The Spanish Government contributed through the “Severo Ochoa Centre Excellence” accreditation to ICM-CSIC (CEX2019-000928-S) and the Research Unit Tecnoterra (ICM-CSIC/UPC). UK colleagues were supported by Climate Linked Atlantic Sector Science (CLASS) project supported by NERC National Capability funding (NE/R015953/1).Peer ReviewedArticle signat per 33 autors/es: Nadine Lantéri; Henry A. Ruh; Andrew Gates; Enoc Martínez; Joaquin del Rio Fernandez; Jacopo Aguzzi; Mathilde Cannat; Eric Delory; Davide Embriaco; Robert Huber; Marjolaine Matabos;George Petihakis; Kieran Reilly; Jean-François Rolin; Mike van der Schaar; Michel André; Jérôme Blandin; Andrés Cianca; Marco Francescangeli; Oscar Garcia; Susan Hartman; Jean-Romain Lagadec; Julien Legrand; Paris Pagonis; Jaume Piera; Xabier Remirez; Daniel M. Toma; Giuditta Marinaro; Bertrand Moreau; Raul Santana; Hannah Wright; Juan José Dañobeitia; Paolo FavaliPostprint (published version

The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish models.

BACKGROUND: Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process. RESULTS: To decipher the genetics of these melanomas, we sequence the protein coding exons of 53 primary melanomas generated from several BRAF(V600E) or NRAS(Q61K) driven transgenic zebrafish lines. We find that engineered zebrafish melanomas show an overall low mutation burden, which has a strong, inverse association with the number of initiating germline drivers. Although tumors reveal distinct mutation spectrums, they show mostly C > T transitions without UV light exposure, and enrichment of mutations in melanogenesis, p53 and MAPK signaling. Importantly, a recurrent amplification occurring with pre-configured drivers BRAF(V600E) and p53-/- suggests a novel path of BRAF cooperativity through the protein kinase A pathway. CONCLUSION: This is the first analysis of a melanoma mutational landscape in the absence of UV light, where tumors manifest with remarkably low mutation burden and high heterogeneity. Genotype specific amplification of protein kinase A in cooperation with BRAF and p53 mutation suggests the involvement of melanogenesis in these tumors. This work is important for defining the spectrum of events in BRAF or NRAS driven melanoma in the absence of UV light, and for informed exploitation of models such as transgenic zebrafish to better understand mechanisms leading to human melanoma formation

Australian chiropractic sports medicine: half way there or living on a prayer?

Sports chiropractic within Australia has a chequered historical background of unorthodox individualistic displays of egocentric treatment approaches that emphasise specific technique preference and individual prowess rather than standardised evidence based management. This situation has changed in recent years with the acceptance of many within sports chiropractic to operate under an evidence informed banner and to embrace a research culture. Despite recent developments within the sports chiropractic movement, the profession is still plagued by a minority of practitioners continuing to espouse certain marginal and outlandish technique systems that beleaguer the mainstream core of sports chiropractic as a cohesive and homogeneous group. Modern chiropractic management is frequently multimodal in nature and incorporates components of passive and active care. Such management typically incorporates spinal and peripheral manipulation, mobilisation, soft tissue techniques, rehabilitation and therapeutic exercises. Externally, sports chiropractic has faced hurdles too, with a lack of recognition and acceptance by organized and orthodox sports medical groups. Whilst some arguments against the inclusion of chiropractic may be legitimate due to its historical baggage, much of the argument appears to be anti-competitive, insecure and driven by a closed-shop mentality.sequently, chiropractic as a profession still remains a pariah to the organised sports medicine world. Add to this an uncertain continuing education system, a lack of protection for the title 'sports chiropractor', a lack of a recognized specialist status and a lack of support from traditional chiropractic, the challenges for the growth and acceptance of the sports chiropractor are considerable. This article outlines the historical and current challenges, both internal and external, faced by sports chiropractic within Australia and proposes positive changes that will assist in recognition and inclusion of sports chiropractic in both chiropractic and multi-disciplinary sports medicine alike