Evidence of an Antigen Presenting Cell Phenotype in Granular Cell Tumours

Granular Cell Tumours (GCTs) are rare subepithelial lesions that are believed to develop from Schwann cells and are characterized by large polygonal cells with abundant lysosomes. Pilot studies from our laboratory showing unexpected HLA-DR immunoreactivity in GCTs lead us to hypothesize that GCTs have an antigen presenting cell (APC) phenotype. To test our hypothesis, we assessed immunoreactivity of GCT lesions to APC phenotype markers, including CD68, HLA-DR, CD163, CD40 and CD11c. In addition, we assessed markers of neural crest cell (NCC) origin S100, SOX10, NSE and GAP43. Samples subjected to these studies included 23 cases of GCTs and 10 cases of Schwannomas, used as comparators. To confirm the key findings, we detected transcript levels of select genes using quantitative polymerase chain reaction. We identified a new NCC marker for GCTs, GAP43. We also provide evidence of an APC phenotype of GCTs, as determined from CD68 and HLA-DR immunoreactivity. Due to the limited nucleic acid yield from paraffin-embedded GCT sections, we were unable to draw conclusions from transcript assessment

Human Activity Differentially Redistributes Large Mammals in the Canadian Rockies National Parks

National parks are important for conservation of species such as wolves (Canis lupus) and elk (Cervus canadensis). However, topography, vegetation conditions, and anthropogenic infrastructure within parks may limit available habitat. Human activity on trails and roads may lead to indirect habitat loss, further limiting available habitat. Predators and prey may respond differentially to human activity, potentially disrupting ecological processes. However, research on such impacts to wildlife is incomplete, especially at fine spatial and temporal scales. Our research investigated the relationship between wolf and elk distribution and human activity using fine-scale Global Positioning System (GPS) wildlife telemetry locations and hourly human activity measures on trails and roads in Banff, Kootenay, and Yoho National Parks, Canada. We observed a complex interaction between the distance animals were located from trails and human activity level resulting in species adopting both mutual avoidance and differential response behaviors. In areas \u3c 50 m from trails human activity led to a mutual avoidance response by both wolves and elk. In areas 50 - 400 m from trails low levels of human activity led to differential responses; wolves avoided these areas, whereas elk appeared to use these areas as a predation refugia. These differential impacts on elk and wolves may have important implications for trophic dynamics. As human activity increased above two people/hour, areas 50 - 400 m from trails were mutually avoided by both species, resulting in the indirect loss of important montane habitat. If park managers are concerned with human impacts on wolves and elk, or on these species\u27 trophic interactions with other species, they can monitor locations near trails and roads and consider hourly changes of human activity levels in areas important to wildlife

Gas-Driven Fracturing of Saturated Granular Media

Multiphase flows in deformable porous materials are important in numerous geological and geotechnical applications, however the complex flow behaviour make subsurface transport processes difficult to control or even characterise. Here we study gas-driven (pneumatic) fracturing of a wet unconsolidated granular packing confined in a Hele-Shaw cell, and present an in-depth analysis of both pore-scale phenomena and large-scale pattern formation. The process is governed by a complex interplay between pressure, capillary, frictional and viscous forces. At low gas injection rate, fractures grow in a stick-slip fashion and branch out to form a simply connected network. We observe the emergence of a characteristic length-scale -- the separation distance between fracture branches -- creating an apparent uniform spatial fracture density. We conclude that the well defined separation distance is the result of local compaction fronts surrounding fractures, keeping them apart. A scaling argument is presented that predicts fracture density as a function of granular friction, grain size, and capillary interactions. We study the influence of gas injection rate, and find that the system undergoes a fluidisation transition above a critical injection rate, resulting in directional growth of fractures, and a fracture density that increases with increasing rate. A dimensionless Fluidisation number F is defined as the ratio of viscous to frictional forces, and our experiments reveal a frictional regime for F1) characterized by continuous growth in several fracture branches simultaneously

Probing the Solution Structure of IκB Kinase (IKK) Subunit γ and Its Interaction with Kaposi Sarcoma-associated Herpes Virus Flice-interacting Protein and IKK Subunit β by EPR Spectroscopy.

Viral flice-interacting protein (vFLIP), encoded by the oncogenic Kaposi sarcoma-associated herpes virus (KSHV), constitutively activates the canonical nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) pathway. This is achieved through subversion of the IκB kinase (IKK) complex (or signalosome), which involves a physical interaction between vFLIP and the modulatory subunit IKKγ. Although this interaction has been examined both in vivo and in vitro, the mechanism by which vFLIP activates the kinase remains to be determined. Because IKKγ functions as a scaffold, recruiting both vFLIP and the IKKα/β subunits, it has been proposed that binding of vFLIP could trigger a structural rearrangement in IKKγ conducive to activation. To investigate this hypothesis we engineered a series of mutants along the length of the IKKγ molecule that could be individually modified with nitroxide spin labels. Subsequent distance measurements using electron paramagnetic resonance spectroscopy combined with molecular modeling and molecular dynamics simulations revealed that IKKγ is a parallel coiled-coil whose response to binding of vFLIP or IKKβ is localized twisting/stiffening and not large-scale rearrangements. The coiled-coil comprises N- and C-terminal regions with distinct registers accommodated by a twist: this structural motif is exploited by vFLIP, allowing it to bind and subsequently activate the NF-κB pathway. In vivo assays confirm that NF-κB activation by vFLIP only requires the N-terminal region up to the transition between the registers, which is located directly C-terminal of the vFLIP binding site

Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic: An EAACI statement

The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a “cytokine storm” and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded

Clinical and genetic heterogeneity in familial focal segmental glomerulosclerosis

Clinical and genetic heterogeneity in familial focal segmental glomerulosclerosis.BackgroundFamilial forms of focal segmental glomerulosclerosis (FFSGS) that exhibit autosomal dominant or recessive patterns of inheritance have been described. The genetic basis of these hereditary forms of FSGS is unknown. One recent study of a kindred from Oklahoma with an autosomal dominant form of FSGS linked this disease to a region of chromosome 19q. In addition, polymorphisms in a gene in this region on chromosome 19q13 have been linked to congenital nephrotic syndrome of the Finnish type. We have ascertained and characterized a large family with autosomal dominant FFSGS (Duke 6530).MethodsFamilies were compared for clinical and genetic heterogeneity. To test for linkage of our family to this portion of chromosome 19, genomic DNA was isolated from 102 family members, and polymerase chain reaction was performed using eight microsatellite markers that spanned the area of interest on chromosome 19. Data were evaluated using two-point linkage analysis, multipoint analysis, and an admixture test.ResultsLinkage was excluded at a distance of ±5 to 10cm for all markers tested with two-point log10 of the odds of linkage (LOD) scores and from an approximate 60cm interval in this area of chromosome 19q via multipoint analysis.ConclusionFSGS has been called the “final common pathway” of glomerular injury, as it is a frequent pathological manifestation with diverse etiologies. This diversity likely correlates with the genetic heterogeneity that we have established. Thus, our data demonstrate that there are at least two genes responsible for this disease, and there is genetic as well as clinical heterogeneity in autosomal dominant FSGS

Growth rates and the prevalence and progression of scoliosis in short-statured children on Australian growth hormone treatment programmes

STUDY DESIGN AND AIM: This was a longitudinal chart review of a diverse group (cohort) of patients undergoing HGH (Human Growth Hormone) treatment. Clinical and radiological examinations were performed with the aim to identify the presence and progression of scoliosis. METHODS AND COHORT: 185 patients were recruited and a database incorporating the age at commencement, dose and frequency of growth hormone treatment and growth charts was compiled from their Medical Records. The presence of any known syndrome and the clinical presence of scoliosis were included for analysis. Subsequently, skeletally immature patients identified with scoliosis were followed up over a period of a minimum four years and the radiologic type, progression and severity (Cobb angle) of scoliosis were recorded. RESULTS: Four (3.6%) of the 109 with idiopathic short stature or hormone deficiency had idiopathic scoliosis (within normal limits for a control population) and scoliosis progression was not prospectively observed. 13 (28.8%) of 45 with Turner syndrome had scoliosis radiologically similar to idiopathic scoliosis. 11 (48%) of 23 with varying syndromes, had scoliosis. In the entire cohort, the growth rates of those with and without scoliosis were not statistically different and HGH treatment was not ceased because of progression of scoliosis. CONCLUSION: In this study, there was no evidence of HGH treatment being responsible for progression of scoliosis in a small number of non-syndromic patients (four). An incidental finding was that scoliosis, similar to the idiopathic type, appears to be more prevalent in Turner syndrome than previously believed

Graphene on quartz modified with rhenium oxide as a semitransparent electrode for organic electronic

Our research shows that commercially available graphene on quartz modified with rhenium oxide meets the requirements for its use as a conductive and transparent anode in optoelectronic devices. The cluster growth of rhenium oxide enables an increase in the work function of graphene by 1.3 eV up to 5.2 eV, which guarantees an appropriate adjustment to the energy levels of the organic semiconductors used in OLED devices.Comment: 8 pages, 3 figure

EEG-neurofeedback and executive function enhancement in healthy adults: a systematic-review

EEG-neurofeedback training (EEG-NFT) is a promising technique that supports individuals in learning to modulate their brain activity to obtain cognitive and behavioural improvements. EEG-NFT is gaining increasing attention for its potential \u201cpeak performance\u201d applications on healthy individuals. However, evidence for clear cognitive performance enhancements with healthy adults is still lacking. In particular, whether EEG-NFT represents an effective technique for enhancing healthy adults\u2019 executive functions is still controversial. Therefore, the main objective of this systematic-review is to assess whether the existing EEG-NFT studies targeting executive functions have provided reliable evidence for NFT effectiveness. To this end, we conducted a qualitative analysis of the literature since the limited number of retrieved studies did not allow us meta-analytical comparisons. Moreover, a second aim was to identify optimal frequencies as NFT targets for specifically improving executive functions. Overall, our systematic review provides promising evidence for NFT effectiveness in boosting healthy adults\u2019 executive functions. However, more rigorous NFT studies are required in order to overcome the methodological weaknesses that we encountered in our qualitative analysis