The migratory pathways of the cells that form the endocardium, dorsal aortae, and head vasculature in the mouse embryo

BACKGROUND: Vasculogenesis in amniotes is often viewed as two spatially and temporally distinct processes, occurring in the yolk sac and in the embryo. However, the spatial origins of the cells that form the primary intra-embryonic vasculature remain uncertain. In particular, do they obtain their haemato-endothelial cell fate in situ, or do they migrate from elsewhere? Recently developed imaging techniques, together with new Tal1 and existing Flk1 reporter mouse lines, have allowed us to investigate this question directly, by visualising cell trajectories live and in three dimensions. RESULTS: We describe the pathways that cells follow to form the primary embryonic circulatory system in the mouse embryo. In particular, we show that Tal1-positive cells migrate from within the yolk sac, at its distal border, to contribute to the endocardium, dorsal aortae and head vasculature. Other Tal1 positive cells, similarly activated within the yolk sac, contribute to the yolk sac vasculature. Using single-cell transcriptomics and our imaging, we identify VEGF and Apela as potential chemo-attractants that may regulate the migration into the embryo. The dorsal aortae and head vasculature are known sites of secondary haematopoiesis; given the common origins that we observe, we investigate whether this is also the case for the endocardium. We discover cells budding from the wall of the endocardium with high Tal1 expression and diminished Flk1 expression, indicative of an endothelial to haematopoietic transition. CONCLUSIONS: In contrast to the view that the yolk sac and embryonic circulatory systems form by two separate processes, our results indicate that Tal1-positive cells from the yolk sac contribute to both vascular systems. It may be that initial Tal1 activation in these cells is through a common mechanism

Growth, strain, and spin-orbit torques in epitaxial Ni-Mn-Sb films sputtered on GaAs

We report current-induced spin torques in epitaxial NiMnSb films on a commercially available epiready GaAs substrate. The NiMnSb was grown by cosputtering from three targets using optimized parameters. The films were processed into microscale bars to perform current-induced spin-torque measurements. Magnetic dynamics were excited by microwave currents, and electric voltages along the bars were measured to analyze the symmetry of the current-induced torques. We found that the extracted symmetry of the spin torques matches those expected from spin-orbit interaction in a tetragonally distorted half-Heusler crystal. Both fieldlike and dampinglike torques are observed in all the samples characterized, and the efficiency of the current-induced torques is comparable to that of ferromagnetic metal/heavy-metal bilayers

Fuzzy Fibers: Uncertainty in dMRI Tractography

Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI) allows for noninvasive reconstruction of fiber bundles in the human brain. In this chapter, we discuss sources of error and uncertainty in this technique, and review strategies that afford a more reliable interpretation of the results. This includes methods for computing and rendering probabilistic tractograms, which estimate precision in the face of measurement noise and artifacts. However, we also address aspects that have received less attention so far, such as model selection, partial voluming, and the impact of parameters, both in preprocessing and in fiber tracking itself. We conclude by giving impulses for future research

Defining Meyer's loop-temporal lobe resections, visual field deficits and diffusion tensor tractography

Anterior temporal lobe resection is often complicated by superior quadrantic visual field deficits (VFDs). In some cases this can be severe enough to prohibit driving, even if a patient is free of seizures. These deficits are caused by damage to Meyer's loop of the optic radiation, which shows considerable heterogeneity in its anterior extent. This structure cannot be distinguished using clinical magnetic resonance imaging sequences. Diffusion tensor tractography is an advanced magnetic resonance imaging technique that enables the parcellation of white matter. Using seed voxels antero-lateral to the lateral geniculate nucleus, we applied this technique to 20 control subjects, and 21 postoperative patients. All patients had visual fields assessed with Goldmann perimetry at least three months after surgery. We measured the distance from the tip of Meyer's loop to the temporal pole and horn in all subjects. In addition, we measured the size of temporal lobe resection using postoperative T1-weighted images, and quantified VFDs. Nine patients suffered VFDs ranging from 22% to 87% of the contralateral superior quadrant. In patients, the range of distance from the tip of Meyer's loop to the temporal pole was 24–43 mm (mean 34 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was –15 to +9 mm (mean 0 mm). In controls the range of distance from the tip of Meyer's loop to the temporal pole was 24–47 mm (mean 35 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was –11 to +9 mm (mean 0 mm). Both quantitative and qualitative results were in accord with recent dissections of cadaveric brains, and analysis of postoperative VFDs and resection volumes. By applying a linear regression analysis we showed that both distance from the tip of Meyer's loop to the temporal pole and the size of resection were significant predictors of the postoperative VFDs. We conclude that there is considerable variation in the anterior extent of Meyer's loop. In view of this, diffusion tensor tractography of the optic radiation is a potentially useful method to assess an individual patient's risk of postoperative VFDs following anterior temporal lobe resection

A comprehensive assessment of cerebellar damage in multiple sclerosis using diffusion tractography and volumetric analysis

Background: White matter (WM) and grey matter (GM) brain damage in multiple sclerosis (MS) is widespread, but the extent of cerebellar involvement and impact on disability needs to be clarified

Abrikosov vortex nucleation and its detrimental effect on superconducting spin pumping in Pt/Nb/Ni80Fe20/Nb/Pt proximity structures

We report Abrikosov vortex nucleation in Pt / Nb / Ni 80 Fe 20 / Nb / Pt proximity-coupled structures under oblique ferromagnetic resonance that turns out to be detrimental to superconducting spin pumping. By measuring an out-of-plane field-angle θ H dependence and comparing with Pt-absent control samples, we show that as θ H increases, the degree of enhancement (suppression) of spin pumping efficiency in the superconducting state for the Pt-present (Pt-absent) sample diminishes and it reverts to the normal state value at θ H = 90 ∘ . This can be explained in terms of a substantial out-of-plane component of the resonance field for the Ni 80 Fe 20 layer (with in-plane magnetization anisotropy and high aspect ratio) that approaches the upper critical field of the Nb, turning a large fraction of the singlet superconductor volume into the normal state

A thirty year clinical and MRI observational study of multiple sclerosis and clinically isolated syndromes

OBJECTIVE: Clinical outcomes in multiple sclerosis (MS) are highly variable. We aim to determine the long-term clinical outcomes in MS, and to identify early prognostic features of these outcomes. METHODS: 132 people presenting with a clinically isolated syndrome (CIS) were prospectively recruited between 1984-87, and followed up clinically and radiologically 1, 5, 10, 14, 20 and now 30 years later. All available notes and magnetic resonance imaging (MRI) scans were reviewed, and MS was defined according to the 2010 McDonald criteria. RESULTS: Clinical outcome data was obtained in 120 participants at 30 years. Eighty were known to have developed MS by 30 years. Expanded disability status scale (EDSS) scores were available in 107 participants, of whom 77 had MS: thirty-two (42%) remained fully ambulatory (EDSS ≤3.5) all of whom had relapsing-remitting MS (RRMS), three (4%) had RRMS and EDSS >3.5, 26 (34%) had secondary progressive MS (all had EDSS >3.5), and MS contributed to death in 16 (20%). Of those with MS, 11 have been treated with a DMT. The strongest early predictors (within 5 years of presentation) of secondary progressive MS (SPMS) at 30 years were presence of baseline infratentorial lesions and deep white matter lesions at one year. INTERPRETATION: Thirty years after onset, in a largely untreated cohort, there was a divergence of MS outcomes; some people accrued substantial disability early on, while others ran a more favourable long-term course. These outcomes could, in part, be predicted by radiological findings from within a year of first presentation

Dispersively detected Pauli Spin-Blockade in a Silicon Nanowire Field-Effect Transistor

We report the dispersive readout of the spin state of a double quantum dot formed at the corner states of a silicon nanowire field-effect transistor. Two face-to-face top-gate electrodes allow us to independently tune the charge occupation of the quantum dot system down to the few-electron limit. We measure the charge stability of the double quantum dot in DC transport as well as dispersively via in-situ gate-based radio frequency reflectometry, where one top-gate electrode is connected to a resonator. The latter removes the need for external charge sensors in quantum computing architectures and provides a compact way to readout the dispersive shift caused by changes in the quantum capacitance during interdot charge transitions. Here, we observe Pauli spin-blockade in the high-frequency response of the circuit at finite magnetic fields between singlet and triplet states. The blockade is lifted at higher magnetic fields when intra-dot triplet states become the ground state configuration. A lineshape analysis of the dispersive phase shift reveals furthermore an intradot valley-orbit splitting $\Delta_{vo}$ of 145 $\mu$eV. Our results open up the possibility to operate compact CMOS technology as a singlet-triplet qubit and make split-gate silicon nanowire architectures an ideal candidate for the study of spin dynamics

ImmunoCluster provides a computational framework for the non-specialist to profile high- dimensional cytometry data

High dimensional cytometry is an innovative tool for immune monitoring in health and disease, it has provided novel insight into the underlying biology as well as biomarkers for a variety of diseases. However, the analysis of large multiparametric datasets usually requires specialist computational knowledge. Here we describe ImmunoCluster (https://github.com/kordastilab/ImmunoCluster) an R package for immune profiling cellular heterogeneity in high dimensional liquid and imaging mass cytometry, and flow cytometry data, designed to facilitate computational analysis by a non-specialist. The analysis framework implemented within ImmunoCluster is readily scalable to millions of cells and provides a variety of visualization and analytical approaches, as well as a rich array of plotting tools that can be tailored to users' needs. The protocol consists of three core computational stages: 1, data import and quality control; 2, dimensionality reduction and unsupervised clustering; and 3, annotation and differential testing, all contained within an R-based open-source framework

Neurocognitive function in HIV infected patients on antiretroviral therapy

OBJECTIVE To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. DESIGN We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. MAIN OUTCOME MEASURE NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. RESULTS Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). CONCLUSIONS In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. TRIAL REGISTRY ClinicalTrials.gov, NCT01230580