A high-throughput chemically induced inflammation assay in zebrafish

Artículo de publicación ISIBackground: Studies on innate immunity have benefited from the introduction of zebrafish as a model system. Transgenic fish expressing fluorescent proteins in leukocyte populations allow direct, quantitative visualization of an inflammatory response in vivo. It has been proposed that this animal model can be used for high-throughput screens aimed at the identification of novel immunomodulatory lead compounds. However, current assays require invasive manipulation of fish individually, thus preventing high-content screening. Results: Here we show that specific, noninvasive damage to lateral line neuromast cells can induce a robust acute inflammatory response. Exposure of fish larvae to sublethal concentrations of copper sulfate selectively damages the sensory hair cell population inducing infiltration of leukocytes to neuromasts within 20 minutes. Inflammation can be assayed in real time using transgenic fish expressing fluorescent proteins in leukocytes or by histochemical assays in fixed larvae. We demonstrate the usefulness of this method for chemical and genetic screens to detect the effect of immunomodulatory compounds and mutations affecting the leukocyte response. Moreover, we transformed the assay into a high-throughput screening method by using a customized automated imaging and processing system that quantifies the magnitude of the inflammatory reaction. Conclusions: This approach allows rapid screening of thousands of compounds or mutagenized zebrafish for effects on inflammation and enables the identification of novel players in the regulation of innate immunity and potential lead compounds toward new immunomodulatory therapies. We have called this method the chemically induced inflammation assay, or ChIn assay.This work was supported by grants to MA from Fondecyt (1070867), FONDAP (15090007), ICM (P06-039F), CORFO-Innova (09MCSS-6705), DFG-Conicyt 075-2009; to CD from UNAB (DI- 01-09/1) and Fondecyt (24090004); to UL from Dopaminet (EU FP7 223744); and to CG by a Marie Curie International Reintegration Grant (EU FP7; PIRG07-GA-2010-267552)

Observation of giant and tunable thermal diffusivity of a Dirac fluid at room temperature

Conducting materials typically exhibit either diffusive or ballistic charge transport. When electron–electron interactions dominate, a hydrodynamic regime with viscous charge flow emerges. More stringent conditions eventually yield a quantum-critical Dirac-fluid regime, where electronic heat can flow more efficiently than charge. However, observing and controlling the flow of electronic heat in the hydrodynamic regime at room temperature has so far remained elusive. Here we observe heat transport in graphene in the diffusive and hydrodynamic regimes, and report a controllable transition to the Dirac-fluid regime at room temperature, using carrier temperature and carrier density as control knobs. We introduce the technique of spatiotemporal thermoelectric microscopy with femtosecond temporal and nanometre spatial resolution, which allows for tracking electronic heat spreading. In the diffusive regime, we find a thermal diffusivity of roughly 2,000 cm s, consistent with charge transport. Moreover, within the hydrodynamic time window before momentum relaxation, we observe heat spreading corresponding to a giant diffusivity up to 70,000 cm s, indicative of a Dirac fluid. Our results offer the possibility of further exploration of these interesting physical phenomena and their potential applications in nanoscale thermal management.We thank M. Polini and P. Piskunow for fruitful discussions, and H. Agarwal and K. Soundarapandian for help with sample fabrication. We acknowledge the following funding sources: European Union’s Horizon 2020 research and innovation programme under grant nos. 804349 (K.-J.T.), 873028 (A.P.), 785219 (F.H.L.K. and S.R.), 881603 (F.H.L.K. and S.R.) and 670949 (N.F.v.H.); Spanish MCIU/AEI under grant nos. RYC-2017-22330 (K.-J.T.), PID2019-111673GB-I00 (K.-J.T.), BES-2016-078727 (M.L.), RTI2018-099957-J-I00 (M.L.) and PGC2018-096875-B-I00 (M.L. and N.F.v.H.); the Government of Catalonia under grant nos. SGR1656 (F.H.L.K.) and 2017SGR1369 (N.F.v.H.) and the CERCA program (ICN2 and ICFO); Spanish MINECO under grant nos. SEV-2017-0706 (ICN2) and CEX-2019-000910-S (ICFO); the International PhD fellowship program ‘la Caixa’ (A.B.); Leverhulme Trust grant no. RPG-2019-363 (A.P.); the Elemental Strategy Initiative conducted by the MEXT, Japan, grant no. JPMXP0112101001 (K.W. and T.T.), JSPS KAKENHI grant no. JP20H00354 (K.W. and T.T.) and the CREST (grant no. JPMJCR15F3) and JST (K.W. and T.T.); Fundació Privada Cellex (ICFO) and Fundació Mir-Puig (ICFO)

neXtProt: a knowledge platform for human proteins

neXtProt (http://www.nextprot.org/) is a new human protein-centric knowledge platform. Developed at the Swiss Institute of Bioinformatics (SIB), it aims to help researchers answer questions relevant to human proteins. To achieve this goal, neXtProt is built on a corpus containing both curated knowledge originating from the UniProtKB/Swiss-Prot knowledgebase and carefully selected and filtered high-throughput data pertinent to human proteins. This article presents an overview of the database and the data integration process. We also lay out the key future directions of neXtProt that we consider the necessary steps to make neXtProt the one-stop-shop for all research projects focusing on human proteins

The Relationship between Sport-Related Concussion and Sensation-Seeking

Sensation-seeking, or the need for novel and exciting experiences, is thought to play a role in sport-related concussion (SRC), yet much remains unknown regarding these relationships and, more importantly, how sensation-seeking influences SRC risk. The current study assessed sensation-seeking, sport contact level, and SRC history and incidence in a large sample of NCAA collegiate athletes. Data included a full study sample of 22,374 baseline evaluations and a sub-sample of 2037 incident SRC. Independent samples t-test, analysis of covariance, and hierarchical logistic regression were constructed to address study hypotheses. Results showed that (1) among participants without SRC, sensation-seeking scores were higher in athletes playing contact sports compared to those playing limited- or non-contact sports (p < 0.001, R2 = 0.007, η2p = 0.003); (2) in the full study sample, a one-point increase in sensation-seeking scores resulted in a 21% greater risk of prior SRC (OR = 1.212; 95% CI: 1.154–1.272), and in the incident SRC sub-sample, a 28% greater risk of prior SRC (OR = 1.278; 95% CI: 1.104–1.480); (3) a one-point increase in sensation-seeking scores resulted in a 12% greater risk of incident SRC among the full study sample; and (4) sensation-seeking did not vary as a function of incident SRC (p = 0.281, η2p = 0.000). Our findings demonstrate the potential usefulness of considering sensation-seeking in SRC management

Look Who’s Talking:Using creative, playful arts-based methods in research with young children

Young children are often ignored or marginalised in the drive to address children’s participation and their wider set of rights. This is the case generally in social research, as well as within the field of Arts-Based Education Research. This article contributes to the growing literature on young children’s involvement in arts-based research, by providing a reflective account of our learning and playful engagement with children using creative methods. This small pilot project forms part of a larger international project titled Look Who’s Talking: Eliciting the Voices of Children from Birth to Seven, led by Professor Kate Wall at the University of Strathclyde. Visiting one nursery in Scotland, we worked with approximately 30 children from 3 to 5 years old. Seeking to connect with their play-based nursery experiences, we invited children to participate in a range of arts-based activities including drawing, craft-making, sculpting, a themed ‘play basket’ with various props, puppetry and videography. In this article, we develop reflective, analytical stories of our successes and dilemmas in the project. We were keen to establish ways of working with children that centred their own creativity and play, shaped by the materials we provided but not directed by us. However, we struggled to balance our own agenda with the more open-ended methods we had used. We argue that an intergenerational approach to eliciting voice with young children – in which adults are not afraid to shape the agenda, but do so in responsive, gradual and sensitive ways – creates the potential for a more inclusive experience for children that also meets researcher needs

Automatic Robust Neurite Detection and Morphological Analysis of Neuronal Cell Cultures in High-content Screening

Cell-based high content screening (HCS) is becoming an important and increasingly favored approach in therapeutic drug discovery and functional genomics. In HCS, changes in cellular morphology and biomarker distributions provide an information-rich profile of cellular responses to experimental treatments such as small molecules or gene knockdown probes. One obstacle that currently exists with such cell-based assays is the availability of image processing algorithms that are capable of reliably and automatically analyzing large HCS image sets. HCS images of primary neuronal cell cultures are particularly challenging to analyze due to complex cellular morphology. Here we present a robust method for quantifying and statistically analyzing the morphology of neuronal cells in HCS images. The major advantages of our method over existing software lie in its capability to correct non-uniform illumination using the contrast-limited adaptive histogram equalization method; segment neuromeres using Gabor-wavelet texture analysis; and detect faint neurites by a novel phase-based neurite extraction algorithm that is invariant to changes in illumination and contrast and can accurately localize neurites. Our method was successfully applied to analyze a large HCS image set generated in a morphology screen for polyglutaminemediated neuronal toxicity using primary neuronal cell cultures derived from embryos of a Drosophila Huntington’s Disease (HD) model.National Institutes of Health (U.S.) (Grant