149 research outputs found
Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review
Niemann-Pick disease type C (NP-C) is a neurovisceral lysosomal cholesterol trafficking and lipid storage disorder caused by mutations in one of the two genes, NPC1 or NPC2. Diagnosis has often been a difficult task, due to the wide range in age of onset of NP-C and clinical presentation of the disease, combined with the complexity of the cell biology (filipin) laboratory testing, even in combination with genetic testing. This has led to substantial delays in diagnosis, largely depending on the access to specialist centres and the level of knowledge about NP-C of the physician in the area. In recent years, advances in mass spectrometry has allowed identification of several sensitive plasma biomarkers elevated in NP-C (e.g. cholestane-3β,5α,6β-triol, lysosphingomyelin isoforms and bile acid metabolites), which, together with the concomitant progress in molecular genetic technology, have greatly impacted the strategy of laboratory testing. Specificity of the biomarkers is currently under investigation and other pathologies are being found to also result in elevations. Molecular genetic testing also has its limitations, notably with unidentified mutations and the classification of new variants. This review is intended to increase awareness on the currently available approaches to laboratory diagnosis of NP-C, to provide an up to date, comprehensive and critical evaluation of the various techniques (cell biology, biochemical biomarkers and molecular genetics), and to briefly discuss ongoing/future developments. The use of current tests in proper combination enables a rapid and correct diagnosis in a large majority of cases. However, even with recent progress, definitive diagnosis remains challenging in some patients, for whom combined genetic/biochemical/cytochemical markers do not provide a clear answer. Expertise and reference laboratories thus remain essential, and further work is still required to fulfill unmet needs
Coherent optical wavelength conversion via cavity-optomechanics
We theoretically propose and experimentally demonstrate coherent wavelength
conversion of optical photons using photon-phonon translation in a
cavity-optomechanical system. For an engineered silicon optomechanical crystal
nanocavity supporting a 4 GHz localized phonon mode, optical signals in a 1.5
MHz bandwidth are coherently converted over a 11.2 THz frequency span between
one cavity mode at wavelength 1460 nm and a second cavity mode at 1545 nm with
a 93% internal (2% external) peak efficiency. The thermal and quantum limiting
noise involved in the conversion process is also analyzed, and in terms of an
equivalent photon number signal level are found to correspond to an internal
noise level of only 6 and 4x10-3 quanta, respectively.Comment: 11 pages, 7 figures, appendi
Recommendations for the detection and diagnosis of Niemann-Pick disease type C: An update.
PURPOSE OF REVIEW:
Niemann-Pick disease type C (NP-C) is a neurovisceral disorder that may be more prevalent than earlier estimates. Diagnosis of NP-C is often delayed; a key aim for clinical practice is to reduce this delay. Recently, substantial progress has been made in the field of NP-C screening and diagnosis, justifying an update to the existing recommendations for clinical practice.
RECENT FINDINGS:
New biomarker profiling and genetic analysis technologies are included as first-line diagnostic tests for NP-C. Most diagnoses can now be confirmed by combination of biomarker and genetic analyses. Filipin staining may facilitate diagnosis in uncertain cases. Recommendations are provided for psychiatrists, neuro-ophthalmologists, and radiologists, and on screening within specific at-risk patient cohorts. The NP-C diagnostic algorithm has been updated and simplified.
SUMMARY: This publication provides expert recommendations for clinicians who may see patients presenting with the signs and symptoms of NP-C, including general practitioners, pediatricians, neurologists, and psychiatrists
Nonlinear dynamics and chaos in an optomechanical beam
[EN] Optical nonlinearities, such as thermo-optic mechanisms and free-carrier dispersion, are often considered unwelcome effects in silicon-based resonators and, more specifically, optomechanical cavities, since they affect, for instance, the relative detuning between an optical resonance and the excitation laser. Here, we exploit these nonlinearities and their intercoupling with the mechanical degrees of freedom of a silicon optomechanical nanobeam to unveil a rich set of fundamentally different complex dynamics. By smoothly changing the parameters of the excitation laser we demonstrate accurate control to activate two-and four-dimensional limit cycles, a period-doubling route and a six-dimensional chaos. In addition, by scanning the laser parameters in opposite senses we demonstrate bistability and hysteresis between two-and four-dimensional limit cycles, between different coherent mechanical states and between four-dimensional limit cycles and chaos. Our findings open new routes towards exploiting silicon-based optomechanical photonic crystals as a versatile building block to be used in neurocomputational networks and for chaos-based applications.This work was supported by the European Comission project PHENOMEN (H2020-EU-713450), the Spanish Severo Ochoa Excellence program and the MINECO project PHENTOM (FIS2015-70862-P). DNU, PDG and MFC gratefully acknowledge the support of a Ramon y Cajal postdoctoral fellowship (RYC-2014-15392), a Beatriu de Pinos postdoctoral fellowship (BP-DGR 2015 (B) and a Severo Ochoa studentship, respectively. We would like to acknowledge Jose C. Sabina de Lis, J.M. Plata Suarez, A. Trifonova and C. Masoller for fruitful discussions.Navarro-Urrios, D.; Capuj, NE.; Colombano, MF.; GarcĂa, PD.; Sledzinska, M.; Alzina, F.; Griol Barres, A.... (2017). Nonlinear dynamics and chaos in an optomechanical beam. Nature Communications. 8. https://doi.org/10.1038/ncomms14965S8Strogatz, S. H. 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FADS2 Function Loss at the Cancer Hotspot 11q13 Locus Diverts Lipid Signaling Precursor Synthesis to Unusual Eicosanoid Fatty Acids
Background: Genes coding for the fatty acid desaturases (FADS1, 2, 3) localized at the cancer genomic hotspot 11q13 locus are required for the biosynthesis of 20 carbon polyunsaturated fatty acids (PUFA) that are direct eicosanoid precursors. In several cancer cell lines, FADS2 encoded D6 and D8 desaturation is not functional. Methodology/Principal Findings: Analyzing MCF7 cell fatty acids with detailed structural mass spectrometry, we show that in the absence of FADS2 activity, the FADS1 product D5-desaturase operates to produce 5,11,14–20:3 and 5,11,14,17–20:4. These PUFA are missing the 8–9 double bond of the eicosanoid signaling precursors arachidonic acid (5,8,11,14–20:4) and eicosapentaenoic acid (5,8,11,14,17–20:5). Heterologous expression of FADS2 restores D6 and D8-desaturase activity and normal eicosanoid precursor synthesis. Conclusions/Significance: The loss of FADS2-encoded activities in cancer cells shuts down normal PUFA biosynthesis, deleting the endogenous supply of eicosanoid and downstream docosanoid precursors, and replacing them with unusual butylene-interrupted fatty acids. If recapitulated in vivo, the normal eicosanoid and docosanoid cell signaling milieu would be depleted and altered due to reduction and substitution of normal substrates with unusual substrates, with unpredictable consequences for cellular communication
Adjuvant enoxaparin therapy may decrease the incidence of postoperative thrombotic events though does not increase the incidence of postoperative intracranial hemorrhage in patients with meningiomas
TDP-43-Mediated Neuron Loss In Vivo Requires RNA-Binding Activity
Alteration and/or mutations of the ribonucleoprotein TDP-43 have been firmly linked to human neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The relative impacts of TDP-43 alteration, mutation, or inherent protein function on neural integrity, however, remain less clear—a situation confounded by conflicting reports based on transient and/or random-insertion transgenic expression. We therefore performed a stringent comparative investigation of impacts of these TDP-43 modifications on neural integrity in vivo. To achieve this, we systematically screened ALS/FTLD-associated and synthetic TDP-43 isoforms via same-site gene insertion and neural expression in Drosophila; followed by transposon-based motor neuron-specific transgenesis in a chick vertebrate system. Using this bi-systemic approach we uncovered a requirement of inherent TDP-43 RNA-binding function—but not ALS/FTLD-linked mutation, mislocalization, or truncation—for TDP-43-mediated neurotoxicity in vivo
Strong vacuum squeezing from bichromatically driven Kerrlike cavities: from optomechanics to superconducting circuits
Squeezed light, displaying less fluctuation than vacuum in some observable, is key in the flourishing field of quantum technologies. Optical or microwave cavities containing a Kerr nonlinearity are known to potentially yield large levels of squeezing, which have been recently observed in optomechanics and nonlinear superconducting circuit platforms. Such Kerr-cavity squeezing however suffers from two fundamental drawbacks. First, optimal squeezing requires working close to turning points of a bistable cycle, which are highly unstable against noise thus rendering optimal squeezing inaccessible. Second, the light field has a macroscopic coherent component corresponding to the pump, making it less versatile than the so-called squeezed vacuum, characterised by a null mean field. Here we prove analytically and numerically that the bichromatic pumping of optomechanical and superconducting circuit cavities removes both limitations. This finding should boost the development of a new generation of robust vacuum squeezers in the microwave and optical domains with current technology
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