Common olfactory ensheathing glial markers in the developing human olfactory system

The in situ immunocytochemical properties of olfactory ensheathing cells (OECs) have been well studied in several small to medium sized animal models including rats, mice, guinea pigs, cats and canines. However, we know very little about the antigenic characteristics of OECs in situ within the adult and developing human olfactory bulb and nerve roots. To address this gap in knowledge we undertook an immunocytochemical analysis of the 11-19 pcw human foetal olfactory system. Human foetal OECs in situ possessed important differences compared to rodents in the expression of key surface markers. P75(NTR) was not observed in OECs but was strongly expressed by human foetal Schwann cells and perineurial olfactory nerve fibroblasts surrounding OECs. We define OECs throughout the 11-19 pcw human olfactory system as S100/vimentin/SOX10+ with low expression of GFAP. Our results suggest that P75(NTR) is a robust marker that could be utilised with cell sorting techniques to generate enriched OEC cultures by first removing P75(NTR) expressing Schwann cells and fibroblasts, and subsequently to isolate OECs after P75(NTR) upregulation in vitro. O4 and PSA-NCAM were not found to be suitable surface antigens for OEC purification owing to their ambiguous and heterogeneous expression. Our results highlight the importance of corroborating cell markers when translating cell therapies from animal models to the clinic

MODELOWANIE 3D TERMICZNYCH NAPRĘŻEŃ W PŁASKIM STAŁOTLENKOWYM OGNIWIE PALIWOWYM O NOWATORSKIEJ KONSTRUKCJI

The presented modelling investigation was carried out to analyze thermal stresses and expansion in an anode supported planar Solid Oxide Fuel Cell (pSOFC). The temperature distribution was based on previously developed thermo-electrochemical model predicting fuel cell operation. The design of a single pSOFC consisted of three ceramic layers of membrane electrode assembly: anode, electrolyte, cathode and two cross-flow bipolar plates with 26 ribs. The gases flowed diagonally from one cell corner to the opposite one. The fuel and air flows were cross-wise opposed on each bipolar plate side. The study allowed to indicate the most vulnerable to thermal damage area of the fuel cell in the operating conditions. The results will be useful in further design modification and performance optimization of the SOFC.Przeprowadzone symulacje numeryczne miały na celu analizę termicznych naprężeń i ocenę stopnia wydłużenia płaskiego stałotlenkowego ogniwa paliwowego typu pSOFC (ang. planar Solid Oxide Fuel Cell). Rozkład temperatury w ogniwie wyznaczono w oparciu o wcześniej opracowany model termiczno-elektrochemiczny [11]. Nowatorskie rozwiązanie ogniwa typu pSOFC objęło ceramiczną konstrukcję, w skład której weszły porowate elektrody – anoda i katoda, elektrolit oraz dwie płytki bipolarne z 26-cioma żebrami. Przepływ paliwa i powietrza odbywał się krzyżowo i przeciwprądowo, po przekątnej ogniwa. Wyniki symulacji pozwoliły na określenie obszarów ogniwa narażonych na uszkodzenie w wyniku wysokich wartości naprężeń termicznych. Uzyskane rezultaty FEM umożliwią dalszą modyfikację konstrukcji płaskiego ogniwa  w celu optymalizacji wydajności pSOFC

Novel disease-causing variant in RDH12 presenting with autosomal dominant retinitis pigmentosa

Aim: To describe the clinical and molecular features of a novel, autosomal dominant RDH12-retinopathy. Methods: Retrospective cross-sectional study. Twelve individuals from a four-generation British pedigree underwent ophthalmic examination, genotyping using next generation sequencing, including whole genome sequencing and multimodal retinal imaging including fundus photography, optical coherence tomography (OCT), autofluorescence imaging and adaptive optics (AO) scanning light ophthalmoscopy were performed. Visual electrophysiology was performed in a subset. Results: Eight family members were confirmed as affected by genotyping heterozygous for RDH12 c.763delG. Visual acuity ranged from −0.1 to 0.2 logMAR. Affected individuals had constricted visual fields. A parafoveal and peripapillary ring of hyper-autofluorescence was seen initially, and with progression the area of perifoveal hypo-autofluorescence increased to involve the parafoveal area. Mild retinal thinning was identified on OCT imaging with reduction in both foveal total retinal and outer nuclear layer thickness. Cone densities along the temporal meridian were reduced in affected individuals compared with normative values at all temporal eccentricities studied. One individual with incomplete penetrance, was identified as clinically affected primarily on the basis of AO imaging. Full-field electroretinography demonstrated a rod-cone pattern of dysfunction and large-field pattern electroretinography identified peripheral macular dysfunction. Conclusions: This novel heterozygous variant RDH12 c.763delG is associated with a rod-cone dystrophy with variable expression. Determination of the degree of penetrance may depend on the modality employed to phenotypically characterise an individual. This rare and specific heterozygous (dominant) variant is predicted to result in a gain of function, that causes disease in a gene typically associated with biallelic (recessive) variants

Repairing Peripheral Nerves:Is there a Role for Carbon Nanotubes?

Peripheral nerve injury continues to be a major global health problem that can result in debilitating neurological deficits and neuropathic pain. Current state-of-the-art treatment involves reforming the damaged nerve pathway using a nerve autograft. Engineered nerve repair conduits can provide an alternative to the nerve autograft avoiding the inevitable tissue damage caused at the graft donor site. Commercially available nerve repair conduits are currently only considered suitable for repairing small nerve lesions; the design and performance of engineered conduits requires significant improvements to enable their use for repairing larger nerve defects

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Multi-disciplinary team directed analysis of whole genome sequencing reveals pathogenic non-coding variants in molecularly undiagnosed inherited retinal dystrophies

PURPOSE: To identify, using genome sequencing (GS), likely pathogenic non-coding variants in inherited retinal dystrophy (IRD) genes Methods: Patients with IRD were recruited to the study and underwent comprehensive ophthalmological evaluation and GS. The results of GS were investigated through virtual gene panel analysis and plausible pathogenic variants and clinical phenotype evaluated by multi-disciplinary team (MDT) discussion. For unsolved patients in whom a specific gene was suspected to harbour a missed pathogenic variant, targeted re-analysis of non-coding regions was performed on GS data. Candidate variants were functionally tested including by mRNA analysis, minigene and luciferase reporter assays. RESULTS: Previously unreported, likely pathogenic, non-coding variants, in 7 genes (PRPF31, NDP, IFT140, CRB1, USH2A, BBS10, and GUCY2D), were identified in 11 patients. These were shown to lead to mis-splicing (PRPF31, IFT140, CRB1, USH2A) or altered transcription levels (BBS10, GUCY2D). CONCLUSION: MDT-led, phenotype driven, non-coding variant re-analysis of GS is effective in identifying missing causative alleles

Mixing performance of viscoelastic fluids in a kenics km in-line static mixer

AbstractThe mixing of ideal viscoelastic (Boger) fluids within a Kenics KM static mixer has been assessed by the analysis of images obtained by Planar Laser Induced Fluorescence (PLIF). The effect of fluid elasticity and fluid superficial velocity has been investigated, with mixing performance quantified using the traditional measure of coefficient of variance CoV alongside the areal method developed by Alberini et al. (2013). As previously reported for non-Newtonian shear thinning fluids, trends in the coefficient of variance follow no set pattern, whilst areal analysis has shown that the >90% mixed fraction (i.e. portion of the flow that is within ±10% of the perfectly mixed concentration) decreases as fluid elasticity increases. Further, the >90% mixed fraction does not collapse onto a single curve with traditional dimensionless parameters such as Reynolds number Re and Weissenberg number Wi, and thus a generalised Reynolds number Reg=Re/(1+2Wi) has been implemented with data showing a good correlation to this parameter

Nanotechnology in peripheral nerve repair and reconstruction

The recent progress in biomaterials science and development of tubular conduits (TCs) still fails in solving the current challenges in the treatment of peripheral nerve injuries (PNIs), in particular when disease-related and long-gap defects need to be addressed. Nanotechnology-based therapies that seemed unreachable in the past are now being considered for the repair and reconstruction of PNIs, having the power to deliver bioactive molecules in a controlled manner, to tune cellular behavior, and ultimately guide tissue regeneration in an effective manner. It also offers opportunities in the imaging field, with a degree of precision never achieved before, which is useful for diagnosis, surgery and in the patientâ s follow-up. Nanotechnology approaches applied in PNI regeneration and theranostics, emphasizing the ones that are moving from the lab bench to the clinics, are herein overviewed.The authors acknowledge the Portuguese Foundation for Science and Technology (FCT) for the financial support provided to Joaquim M. Oliveira (IF/01285/2015) and Joana Silva-Correia (IF/00115/2015) under the program “Investigador FCT”.info:eu-repo/semantics/publishedVersio

Criteria for numerical modeling of low-tempe- rature non-thermal plasma

W pracy omówiono krytyczne parametry niezbędne do właściwego zdefiniowania problemu obliczeniowego z udziałem niskotemperaturowej plazmy nietermicznej w reaktorze typu DBD. Dobór tych parametrów jest zagadnieniem złożonym z uwagi na nieliniowy charakter zjawisk, przebiegających podczas wyładowań elektrycznych. Pomocne w tym zakresie są kody obliczeniowe numerycznej mechaniki płynów, które umożliwiają ilościowy opis nieliniowych relacji pomiędzy zmiennymi w czasie parametrami.Critical parameters necessary to properly define a computational problem involving a low-temperature non-thermal plasma reactor of DBD type are discussed in the paper. A choice of these parameters is a complex issue due to nonlinear nature of the phenomena which take place during the electrical discharge. The codes of computational fluid dynamics are helpful in this issue. They enable the quantitative description of non-linear relationships between the time-dependent parameters