Ectopic A-lattice seams destabilize microtubules

Natural microtubules typically include one A-lattice seam within an otherwise helically symmetric B-lattice tube. It is currently unclear how A-lattice seams influence microtubule dynamic instability. Here we find that including extra A-lattice seams in GMPCPP microtubules, structural analogues of the GTP caps of dynamic microtubules, destabilizes them, enhancing their median shrinkage rate by >20-fold. Dynamic microtubules nucleated by seeds containing extra A-lattice seams have growth rates similar to microtubules nucleated by B-lattice seeds, yet have increased catastrophe frequencies at both ends. Furthermore, binding B-lattice GDP microtubules to a rigor kinesin surface stabilizes them against shrinkage, whereas microtubules with extra A-lattice seams are stabilized only slightly. Our data suggest that introducing extra A-lattice seams into dynamic microtubules destabilizes them by destabilizing their GTP caps. On this basis, we propose that the single A-lattice seam of natural B-lattice MTs may act as a trigger point, and potentially a regulation point, for catastrophe

Synaesthesia: a distinct entity that is an emergent feature of adaptive neurocognitive differences

In this article, I argue that synaesthesia is not on a continuum with neurotypical cognition. Synaesthesia is special: its phenomenology is different; it has distinct causal mechanisms; and is likely to be associated with a distinct neurocognitive profile. However, not all synaesthetes are the same, and there are quantifiable differences between them. In particular, the number of types of synaesthesia that a person possesses is a hitherto underappreciated variable that predicts cognitive differences along a number of dimensions (mental imagery, sensory sensitivity, attention to detail). Together with enhanced memory, this may constitute a common core of abilities that may go some way to explaining why synaesthesia might have evolved. I argue that the direct benefits of synaesthesia are generally limited (i.e. the synaesthetic associations do not convey novel information about the world) but, nevertheless, synaesthesia may develop due to other adaptive functions (e.g. perceptual ability, memory) that necessitate changes to design features of the brain. The article concludes by suggesting that synaesthesia forces us to reconsider what we mean by a ‘normal’ mind/brain. There may be multiple ‘normal’ neurodevelopmental trajectories that can sculpt very different ways of experiencing the world, of which synaesthesia is but one. This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’

Liquefaction hazard of the Groningen region of the Netherlands due to induced seismicity

The operator of the Groningen gas field is leading an effort to quantify the seismic hazard and riskof the region due to induced earthquakes, includingoverseeing one of the most comprehensive liquefaction hazard studies performedgloballyto date. Due tothe unique characteristics of the seismic hazard and the geologic deposits in Groningen, efforts first focused on developing relationships for a Groningen-specific liquefaction triggering model. The liquefaction hazard was then assessedusing a Monte Carlo method, wherein a range of credibleevent scenarios were considered in computingliquefaction damage-potentialhazard curves. Thiseffort entailed the use of a regional stochastic seismic source model,ground motion prediction equation,site response model,and geologic model that were developed as part of the broader regional seismic hazardassessment.“No-to-Minor Surficial Liquefaction Manifestations”arepredicted for mostsites across the study areafor a 75-year return period. The only sites where “Moderate Surficial Liquefaction Manifestations” are predicted are in the town of Zandeweer, with only some of the sites in the townbeing predicted to experience this severityof liquefactionfor thisreturn period

Spectra of supernovae in the nebular phase

When supernovae enter the nebular phase after a few months, they reveal spectral fingerprints of their deep interiors, glowing by radioactivity produced in the explosion. We are given a unique opportunity to see what an exploded star looks like inside. The line profiles and luminosities encode information about physical conditions, explosive and hydrostatic nucleosynthesis, and ejecta morphology, which link to the progenitor properties and the explosion mechanism. Here, the fundamental properties of spectral formation of supernovae in the nebular phase are reviewed. The formalism between ejecta morphology and line profile shapes is derived, including effects of scattering and absorption. Line luminosity expressions are derived in various physical limits, with examples of applications from the literature. The physical processes at work in the supernova ejecta, including gamma-ray deposition, non-thermal electron degradation, ionization and excitation, and radiative transfer are described and linked to the computation and application of advanced spectral models. Some of the results derived so far from nebular-phase supernova analysis are discussed.Comment: Book chapter for 'Handbook of Supernovae,' edited by Alsabti and Murdin, Springer. 51 pages, 14 figure

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner

Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages

This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments

Ventriculo-atrial gradient due to first degree atrio-ventricular block: a case report

BACKGROUND: Isolated, asymptomatic first degree AV block with narrow QRS has not prognostic significance and is not usually treated with pacemaker implantation. In some cases, yet, loss of AV synchrony because of a marked prolongation of the PR interval may cause important hemodynamic alterations, with subsequent symptoms of heart failure. Indeed, AV synchrony is crucial when atrial systole, the "atrial kick", contributes in a major way to left ventricular filling, as in case of reduced left ventricular compliance because of aging or concomitant structural heart disease. CASE PRESENTATION: We performed a trans-septal left atrium catheterization aimed at evaluating the entity of a mitral valve stenosis in a 72-year-old woman with a marked first-degree AV block, a known moderate aortic stenosis and NYHA class III symptoms of functional deterioration. We occurred in a deep alteration in cardiac hemodynamics consisting in an end-diastolic ventriculo-atrial gradient without any evidence of mitral stenosis. The patient had a substantial improvement in echocardiographic parameters and in her symptoms of heart failure after permanent pacemaker implantation with physiological AV delay. CONCLUSION: We conclude that if a marked first degree AV block is associated to instrumental signs or symptoms of heart failure, the restoration of an optimal AV synchrony, achieved with dual-chamber pacing, may represent a reasonable therapeutic option leading to a consequent clinical improvement