Temperature increase inside LED-based illuminators for in vitro aPDT photodamage studies

Abstract Antimicrobial PhotoDynamic Therapy (aPDT) is an emerging strategy aimed at the eradication of bacterial infections, with a special focus on antibiotic-resistant bacteria. This method is easy to apply, not expensive and particularly interesting in case of bacteria that spontaneously produce the required photosensitizers. In the framework of a project aimed at the development of an ingestible pill for the application of aPDT to gastric infections by Helicobacter pylori, a LED-based illuminating prototype (LED-BIP) was purposely designed in order to evaluate the photodamage induced by light of different wavelengths on porphyrin-producing bacteria. This short paper reports about temperature tests performed to assess the maximum exposure time and light dose that can be administered to bacterial cultures inside LED-BIP without reaching temperatures exceeding the physiological range

Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP

Stop codon mutations in the gene encoding the prion protein (PRNP) are very rare and have thus far only been described in two patients with prion protein cerebral amyloid angiopathy (PrP-CAA). In this report, we describe the clinical, histopathological and pathological prion protein (PrPSc) characteristics of two Dutch patients carrying novel adjacent stop codon mutations in the C-terminal part of PRNP, resulting in either case in hereditary prion protein amyloidoses, but with strikingly different clinicopathological phenotypes. The patient with the shortest disease duration (27 months) carried a Y226X mutation and showed PrP-CAA without any neurofibrillary lesions, whereas the patient with the longest disease duration (72 months) had a Q227X mutation and showed an unusual Gerstmann-Sträussler-Scheinker disease phenotype with numerous cerebral multicentric amyloid plaques and severe neurofibrillary lesions without PrP-CAA. Western blot analysis in the patient with the Q227X mutation demonstrated the presence of a 7 kDa unglycosylated PrPSc fragment truncated at both the N- and C-terminal ends. Our observations expand the spectrum of clinicopathological phenotypes associated with PRNP mutations and show that a single tyrosine residue difference in the PrP C-terminus may significantly affect the site of amyloid deposition and the overall phenotypic expression of the prion disease. Furthermore, it confirms that the absence of the glycosylphosphatidylinositol anchor in PrP predisposes to amyloid plaque formation

Quantum-Statistical Correlations and Single Particle Distributions for Slowly Expanding Systems with Temperature Profile

Competition among particle evaporation, temperature gradient and flow is investigated in a phenomenological manner, based on a simultaneous analysis of quantum statistical correlations and momentum distributions for a non-relativistic, spherically symmetric, three-dimensionally expanding, finite source. The parameters of the model emission function are constrained by fits to neutron and proton momentum distributions and correlation functions in intermediate energy heavy-ion collisions. The temperature gradient is related to the momentum dependence of the radius parameters of the two-particle correlation function, as well as to the momentum-dependent temperature parameter of the single particle spectrum, while a long duration of particle evaporation is found to be responsible for the low relative momentum behavior of the two-particle correlations.Comment: 20 pages + 5 ps figures, ReVTeX, uses psfig.sty, the description is extended to include final state interactions, phenomenological evaporation and to fit intermediate energy heavy ion proton and neutron spectrum and correlation dat

Muon `Depth -- Intensity' Relation Measured by LVD Underground Experiment and Cosmic-Ray Muon Spectrum at Sea Level

We present the analysis of the muon events with all muon multiplicities collected during 21804 hours of operation of the first LVD tower. The measured angular distribution of muon intensity has been converted to the `depth -- vertical intensity' relation in the depth range from 3 to 12 km w.e.. The analysis of this relation allowed to derive the power index, $\gamma$, of the primary all-nucleon spectrum: $\gamma=2.78 \pm 0.05$. The `depth -- vertical intensity' relation has been converted to standard rock and the comparison with the data of other experiments has been done. We present also the derived vertical muon spectrum at sea level.Comment: 7 pages, 3 figures, to be published on Phys. Rev.

Upper Limit on the Prompt Muon Flux Derived from the LVD Underground Experiment

We present the analysis of the muon events with all muon multiplicities collected during 21804 hours of operation of the first LVD tower. The measured depth-angular distribution of muon intensities has been used to obtain the normalization factor, A, the power index, gamma, of the primary all-nucleon spectrum and the ratio, R_c, of prompt muon flux to that of pi-mesons - the main parameters which determine the spectrum of cosmic ray muons at the sea level. The value of gamma = 2.77 +/- 0.05 (68% C.L.) and R_c < 2.0 x 10^-3 (95% C.L.) have been obtained. The upper limit to the prompt muon flux favours the models of charm production based on QGSM and the dual parton model.Comment: 10 pages, 4 figures, RevTex. To appear in Phys. Rev.

Communities in high definition : Spatial and environmental factors shape the micro-distribution of aquatic invertebrates

According to metacommunity theories, the structure of natural communities is the result of both environmental filtering and spatial processes, with their relative importance depending on factors including local habitat characteristics, functional features of organisms, and the spatial scale considered. However, few studies have explored environmental and spatial processes in riverine systems at local scales, explicitly incorporating spatial coordinates into multi-taxa distribution models. To address this gap, we conducted a small-scale study to discriminate between abiotic and biotic factors affecting the distribution of aquatic macroinvertebrates, applying metacommunity concepts. We studied a mountain section in each of three perennial streams within the Po River Basin (northern Italy). We sampled macroinvertebrates both in summer and winter, using specific in situ 50-point random sampling grids. Environmental factors, including benthic organic matter (BOM), flow velocity, water depth, and substrate were recorded together with spatial coordinates for each sampling point. The relationships between community metrics (taxon richness, abundance, biomass, biomass-abundance ratio, and functional feeding groups) and explanatory variables (environmental and spatial) were assessed using generalised additive models. The influence of the explanatory variables on community structure was analysed with joint species distribution models. Environmental variables-primarily BOM-were the main drivers affecting community metrics, whereas the effects of spatial variables varied among metrics, streams, and seasons. During summer, community structure was strongly affected by BOM and spatial position within the riverbed, the latter probably being a proxy for mass effects mediated by biotic and stochastic processes. In contrast, community structure was mainly shaped by hydraulic variables in winter. Using macroinvertebrate communities as a model group, our results demonstrate that metacommunity concepts can explain small-scale variability in community structure. We found that both environmental filtering and biotic processes shape local communities, with the strength of these drivers depending on the season. These insights provide baseline knowledge that informs our understanding of ecological responses to environmental variability in contexts including restoration ecology, habitat suitability modelling, and biomonitoring.Peer reviewe

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): study protocol for a pilot randomized controlled trial.

BACKGROUND: Trauma is the leading cause of morbidity and mortality in children in the United States. The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage, however, the drug has not been evaluated in a clinical trial in severely injured children. We designed the Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC) trial to evaluate the feasibility of conducting a confirmatory clinical trial that evaluates the effects of TXA in children with severe trauma and hemorrhagic injuries. METHODS: Children with severe trauma and evidence of hemorrhagic torso or brain injuries will be randomized to one of three arms: (1) TXA dose A (15 mg/kg bolus dose over 20 min, followed by 2 mg/kg/hr infusion over 8 h), (2) TXA dose B (30 mg/kg bolus dose over 20 min, followed by 4 mg/kg/hr infusion over 8 h), or (3) placebo. We will use permuted-block randomization by injury type: hemorrhagic brain injury, hemorrhagic torso injury, and combined hemorrhagic brain and torso injury. The trial will be conducted at four pediatric Level I trauma centers. We will collect the following outcome measures: global functioning as measured by the Pediatric Quality of Life (PedsQL) and Pediatric Glasgow Outcome Scale Extended (GOS-E Peds), working memory (digit span test), total amount of blood products transfused in the initial 48 h, intracranial hemorrhage progression at 24 h, coagulation biomarkers, and adverse events (specifically thromboembolic events and seizures). DISCUSSION: This multicenter trial will provide important preliminary data and assess the feasibility of conducting a confirmatory clinical trial that evaluates the benefits of TXA in children with severe trauma and hemorrhagic injuries to the torso and/or brain. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT02840097 . Registered on 14 July 2016

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Tau, prions and Aβ: the triad of neurodegeneration

This article highlights the features that connect prion diseases with other cerebral amyloidoses and how these relate to neurodegeneration, with focus on tau phosphorylation. It also discusses similarities between prion disease and Alzheimer’s disease: mechanisms of amyloid formation, neurotoxicity, pathways involved in triggering tau phosphorylation, links to cell cycle pathways and neuronal apoptosis. We review previous evidence of prion diseases triggering hyperphosphorylation of tau, and complement these findings with cases from our collection of genetic, sporadic and transmitted forms of prion diseases. This includes the novel finding that tau phosphorylation consistently occurs in sporadic CJD, in the absence of amyloid plaques