In vivo stem cell tracking using scintigraphy in a canine model of DMD

One of the main challenges in cell therapy for muscle diseases is to efficiently target the muscle. To address this issue and achieve better understanding of in vivo cell fate, we evaluated the relevance of a non-invasive cell tracking method in the Golden Retriever Muscular Dystrophy (GRMD) model, a well-recognised model of Duchenne Muscular Dystrophy (DMD). Mesoangioblasts were directly labelled with 111In-oxine, and injected through one of the femoral arteries. The scintigraphy images obtained provided the first quantitative mapping of the immediate biodistribution of mesoangioblasts in a large animal model of DMD. The results revealed that cells were trapped by the first capillary filters: the injected limb and the lung. During the days following injection, radioactivity was redistributed to the liver. In vitro studies, performed with the same cells prepared for injecting the animal, revealed prominent cell death and 111In release. In vivo, cell death resulted in 111In release into the vasculature that was taken up by the liver, resulting in a non-specific and non-cell-bound radioactive signal. Indirect labelling methods would be an attractive alternative to track cells on the mid- and long-term

Alteration of Cardiac Progenitor Cell Potency in GRMD Dogs

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PHIL photoinjector test line

LAL is now equiped with its own platform for photoinjectors tests and Research and Developement, named PHIL (PHotoInjectors at LAL). This facility has two main purposes: push the limits of the photoinjectors performances working on both the design and the associated technology and provide a low energy (MeV) short pulses (ps) electron beam for the interested users. Another very important goal of this machine will be to provide an opportunity to form accelerator physics students, working in a high technology environment. To achieve this goal a test line was realised equipped with an RF source, magnets and beam diagnostics. In this article we will desrcibe the PHIL beamline and its characteristics together with the description of the first two photoinjector realised in LAL and tested: the ALPHAX and the PHIN RF Guns

Oral and pharyngeal cancer in South Asians and non-South Asians in relation to socioeconomic deprivation in South East England.

From UK Thames Cancer Registry data, after controlling for socioeconomic deprivation of area of residence, South Asian males showed a higher relative risk of oral (1.36; 95% CI: 1.11, 1.67), but not of pharyngeal cancer than non-South Asian males, whereas South Asian females had much higher risks of these cancers (3.67; 95% CI: 2.97, 4.53 and 2.06; 95% CI: 1.44, 2.93), respectively, than non-South Asians

International nursing advanced competency-based training for intensive care: a europe-wide survey.

This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published (Open Access

HACD1, a regulator of membrane composition and fluidity, promotes myoblast fusion and skeletal muscle growth

The reduced diameter of skeletal myofibres is a hallmark of several congenital myopathies, yet the underlying cellular and molecular mechanisms remain elusive. In this study, we investigate the role of HACD1/PTPLA, which is involved in the elongation of the very long chain fatty acids, in muscle fibre formation. In humans and dogs, HACD1 deficiency leads to a congenital myopathy with fibre size disproportion associated with a generalized muscle weakness. Through analysis of HACD1-deficient Labradors, Hacd1-knockout mice, and Hacd1-deficient myoblasts, we provide evidence that HACD1 promotes myoblast fusion during muscle development and regeneration. We further demonstrate that in normal differentiating myoblasts, expression of the catalytically active HACD1 isoform, which is encoded by a muscle-enriched splice variant, yields decreased lysophosphatidylcholine content, a potent inhibitor of myoblast fusion, and increased concentrations of ≥C18 and monounsaturated fatty acids of phospholipids. These lipid modifications correlate with a reduction in plasma membrane rigidity. In conclusion, we propose that fusion impairment constitutes a novel, non-exclusive pathological mechanism operating in congenital myopathies and reveal that HACD1 is a key regulator of a lipid-dependent muscle fibre growth mechanism

Leveraging population admixture to characterize the heritability of complex traits.

Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2)

Combined sensitivity to the neutrino mass ordering with JUNO, the IceCube Upgrade, and PINGU

The ordering of the neutrino mass eigenstates is one of the fundamental open questions in neutrino physics. While current-generation neutrino oscillation experiments are able to produce moderate indications on this ordering, upcoming experiments of the next generation aim to provide conclusive evidence. In this paper we study the combined performance of the two future multi-purpose neutrino oscillation experiments JUNO and the IceCube Upgrade, which employ two very distinct and complementary routes toward the neutrino mass ordering. The approach pursued by the 20 kt medium-baseline reactor neutrino experiment JUNO consists of a careful investigation of the energy spectrum of oscillated νe produced by ten nuclear reactor cores. The IceCube Upgrade, on the other hand, which consists of seven additional densely instrumented strings deployed in the center of IceCube DeepCore, will observe large numbers of atmospheric neutrinos that have undergone oscillations affected by Earth matter. In a joint fit with both approaches, tension occurs between their preferred mass-squared differences Δm312=m32-m12 within the wrong mass ordering. In the case of JUNO and the IceCube Upgrade, this allows to exclude the wrong ordering at >5σ on a timescale of 3-7 years - even under circumstances that are unfavorable to the experiments' individual sensitivities. For PINGU, a 26-string detector array designed as a potential low-energy extension to IceCube, the inverted ordering could be excluded within 1.5 years (3 years for the normal ordering) in a joint analysis

Design and performance of the first IceAct demonstrator at the South Pole

In this paper we describe the first results of IceAct, a compact imaging air-Cherenkov telescope operating in coincidence with the IceCube Neutrino Observatory (IceCube) at the geographic South Pole. An array of IceAct telescopes (referred to as the IceAct project) is under consideration as part of the IceCube-Gen2 extension to IceCube. Surface detectors in general will be a powerful tool in IceCube-Gen2 for distinguishing astrophysical neutrinos from the dominant backgrounds of cosmic-ray induced atmospheric muons and neutrinos: the IceTop array is already in place as part of IceCube, but has a high energy threshold. Although the duty cycle will be lower for the IceAct telescopes than the present IceTop tanks, the IceAct telescopes may prove to be more effective at lowering the detection threshold for air showers. Additionally, small imaging air-Cherenkov telescopes in combination with IceTop, the deep IceCube detector or other future detector systems might improve measurements of the composition of the cosmic ray energy spectrum. In this paper we present measurements of a first 7-pixel imaging air Cherenkov telescope demonstrator, proving the capability of this technology to measure air showers at the South Pole in coincidence with IceTop and the deep IceCube detector