Single-molecule super-resolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes

Fluorescence in situ hybridization (FISH) is a powerful single-cell technique for studying nuclear structure and organization. Here we report two advances in FISH-based imaging. We first describe the in situ visualization of single-copy regions of the genome using two single-molecule super-resolution methodologies. We then introduce a robust and reliable system that harnesses single-nucleotide polymorphisms (SNPs) to visually distinguish the maternal and paternal homologous chromosomes in mammalian and insect systems. Both of these new technologies are enabled by renewable, bioinformatically designed, oligonucleotide-based Oligopaint probes, which we augment with a strategy that uses secondary oligonucleotides (oligos) to produce and enhance fluorescent signals. These advances should substantially expand the capability to query parent-of-origin-specific chromosome positioning and gene expression on a cell-by-cell basis

Improving understanding of the functional diversity of fisheries by exploring the influence of global catch reconstruction

Functional diversity is thought to enhance ecosystem resilience, driving research focused on trends in the functional composition of fisheries, most recently with new reconstructions of global catch data. However, there is currently little understanding of how accounting for unreported catches (e.g. small-scale and illegal fisheries, bycatch and discards) influences functional diversity trends in global fisheries. We explored how diversity estimates varied among reported and unreported components of catch in 2010, and found these components had distinct functional fingerprints. Incorporating unreported catches had little impact on global-scale functional diversity patterns. However, at smaller, management-relevant scales, the effects of incorporating unreported catches were large (changes in functional diversity of up to 46%). Our results suggest there is greater uncertainty about the risks to ecosystem integrity and resilience from current fishing patterns than previously recognized. We provide recommendations and suggest a research agenda to improve future assessments of functional diversity of global fisheries

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Over 675,000 lay people trained in cardiopulmonary resuscitation worldwide - The "World Restart a Heart (WRAH)" initiative 2018

Non peer reviewe

Phosphorylase activity in rat uterus after catecholamine administration

The effects of epinephrine, norepinephrine, and isoproterenol on uterine phosphorylase were studied in intact, anesthetized rats. All three agents were found to increase uterine phosphorylase a activity when administered in large doses by intraperitoneal injection. Total phosphorylase activity was unaffected. The time course for the effects of epinephrine on uterine phosphorylase activity and glycogen content was also studied. Peak phosphorylase activation occurred within 5 min after injection, and the effect had disappeared within 1 hr. Increase in phosphorylase a activity was accompanied by a decrease in uterine glycogen levels, which were still depressed at a time when phosphorylase a activity had returned to normal.Epinephrine was shown to stimulate phosphorylase a activity in the uteri of ovariectomized and estrogen-primed rats as well as in normal intact animals. Ovariectomized animals treated with estradiol had higher resting phosphorylase a activity than had normal untreated animals.The relative ability of several adrenergic blocking agents to prevent catecholamineinduced increases in uterine phosphorylase a activity was investigated, It was suggested that the catecholamines produced their effects on the uterus both directly, via [beta]-adrenergic stimulation, and indirectly, via ischemia and resultant tissue anoxia induced by activation of a-adrenergic receptors in the uterine vasculature.The ability of epinephrine to activate uterine phosphorylase when administered by intravenous infusion was also demonstrated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32054/1/0000097.pd

The Formation of the Bicoid Morphogen Gradient Requires Protein Movement from Anteriorly Localized mRNA

New quantitative data show that the Bicoid morphogen gradient is generated from a dynamic localized source and that protein gradient formation requires protein movement along the anterior-posterior axis

INDIGO-DataCloud: a Platform to Facilitate Seamless Access to E-Infrastructures

[EN] This paper describes the achievements of the H2020 project INDIGO-DataCloud. The project has provided e-infrastructures with tools, applications and cloud framework enhancements to manage the demanding requirements of scientific communities, either locally or through enhanced interfaces. The middleware developed allows to federate hybrid resources, to easily write, port and run scientific applications to the cloud. In particular, we have extended existing PaaS (Platform as a Service) solutions, allowing public and private e-infrastructures, including those provided by EGI, EUDAT, and Helix Nebula, to integrate their existing services and make them available through AAI services compliant with GEANT interfederation policies, thus guaranteeing transparency and trust in the provisioning of such services. Our middleware facilitates the execution of applications using containers on Cloud and Grid based infrastructures, as well as on HPC clusters. Our developments are freely downloadable as open source components, and are already being integrated into many scientific applications.INDIGO-Datacloud has been funded by the European Commision H2020 research and innovation program under grant agreement RIA 653549.Salomoni, D.; Campos, I.; Gaido, L.; Marco, J.; Solagna, P.; Gomes, J.; Matyska, L.... (2018). INDIGO-DataCloud: a Platform to Facilitate Seamless Access to E-Infrastructures. Journal of Grid Computing. 16(3):381-408. https://doi.org/10.1007/s10723-018-9453-3S381408163García, A.L., Castillo, E.F.-d., Puel, M.: Identity federation with VOMS in cloud infrastructures. In: 2013 IEEE 5Th International Conference on Cloud Computing Technology and Science, pp 42–48 (2013)Chadwick, D.W., Siu, K., Lee, C., Fouillat, Y., Germonville, D.: Adding federated identity management to OpenStack. Journal of Grid Computing 12(1), 3–27 (2014)Craig, A.L.: A design space review for general federation management using keystone. 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Integrin β3 Crosstalk with VEGFR Accommodating Tyrosine Phosphorylation as a Regulatory Switch

Integrins mediate cell adhesion, migration, and survival by connecting intracellular machinery with the surrounding extracellular matrix. Previous studies demonstrated the importance of the interaction between β3 integrin and VEGF type 2 receptor (VEGFR2) in VEGF-induced angiogenesis. Here we present in vitro evidence of the direct association between the cytoplasmic tails (CTs) of β3 and VEGFR2. Specifically, the membrane-proximal motif around 801YLSI in VEGFR2 mediates its binding to non-phosphorylated β3CT, accommodating an α-helical turn in integrin bound conformation. We also show that Y747 phosphorylation of β3 enhances the above interaction. To demonstrate the importance of β3 phosphorylation in endothelial cell functions, we synthesized β3CT-mimicking Y747 phosphorylated and unphosphorylated membrane permeable peptides. We show that a peptide containing phospho-Y747 but not F747 significantly inhibits VEGF-induced signaling and angiogenesis. Moreover, phospho-Y747 peptide exhibits inhibitory effect only in WT but not in β3 integrin knock-out or β3 integrin knock-in cells expressing β3 with two tyrosines substituted for phenylalanines, demonstrating its specificity. Importantly, these peptides have no effect on fibroblast growth factor receptor signaling. Collectively these data provide novel mechanistic insights into phosphorylation dependent cross-talk between integrin and VEGFR2

The Impact of Social Disparity on Prefrontal Function in Childhood

The prefrontal cortex (PFC) develops from birth through late adolescence. This extended developmental trajectory provides many opportunities for experience to shape the structure and function of the PFC. To date, a few studies have reported links between parental socioeconomic status (SES) and prefrontal function in childhood, raising the possibility that aspects of environment associated with SES impact prefrontal function. Considering that behavioral measures of prefrontal function are associated with learning across multiple domains, this is an important area of investigation. In this study, we used fMRI to replicate previous findings, demonstrating an association between parental SES and PFC function during childhood. In addition, we present two hypothetical mechanisms by which SES could come to affect PFC function of this association: language environment and stress reactivity. We measured language use in the home environment and change in salivary cortisol before and after fMRI scanning. Complexity of family language, but not the child's own language use, was associated with both parental SES and PFC activation. Change in salivary cortisol was also associated with both SES and PFC activation. These observed associations emphasize the importance of both enrichment and adversity-reduction interventions in creating good developmental environments for all children