The use of nanoparticles (NPs) in the healthcare market is growing exponentially, due to their unique physicochemical properties. Titanium dioxide nanoparticles (TiO
2
NPs) are used in the ...formulation of sunscreens, due to their photoprotective capacity, but interactions of these particles with skin cells on the nanoscale are still unexplored. In the present study we aimed to determine whether the initial nano-biological interactions, namely the formation of a nano-bio-complex (other than the protein corona), can predict rutile internalization and intracellular trafficking in primary human fibroblasts and keratinocytes. Results showed no significant effect of NPs on fibroblast and keratinocyte viability, but cell proliferation was possibly compromised due to nano-bio-interactions. The bio-complex formation is dependent upon the chemistry of the biological media and NPs' physicochemical properties, facilitating NP internalization and triggering autophagy in both cell types. For the first time, we observed that the intracellular traffic of NPs is different when comparing the two skin cell models, and we detected NPs within multivesicular bodies (MVBs) of keratinocytes. These structures grant selected input of molecules involved in the biogenesis of exosomes, responsible for cell communication and, potentially, structural equilibrium in human tissues. Nanoparticle-mediated alterations of exosome quality, quantity and function can be another major source of nanotoxicity.
TiO
2
NPs' nano-bio-interactions mediate a distinct intracellular trafficking and destiny in human skin cells.
Alternative splicing is emerging as a major mechanism for the expansion of the transcriptome and proteome diversity, particularly in human and other vertebrates. However, the proportion of ...alternative transcripts and proteins actually endowed with functional activity is currently highly debated. We present here a new release of ASPicDB which now provides a unique annotation resource of human protein variants generated by alternative splicing. A total of 256 939 protein variants from 17 191 multi-exon genes have been extensively annotated through state of the art machine learning tools providing information of the protein type (globular and transmembrane), localization, presence of PFAM domains, signal peptides, GPI-anchor propeptides, transmembrane and coiled-coil segments. Furthermore, full-length variants can be now specifically selected based on the annotation of CAGE-tags and polyA signal and/or polyA sites, marking transcription initiation and termination sites, respectively. The retrieval can be carried out at gene, transcript, exon, protein or splice site level allowing the selection of data sets fulfilling one or more features settled by the user. The retrieval interface also enables the selection of protein variants showing specific differences in the annotated features. ASPicDB is available at http://www.caspur.it/ASPicDB/.
Channeling efficiency in a target-crystal assembly Scandale, W.; Cerutti, F.; Esposito, L.S. ...
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
03/2020, Letnik:
467
Journal Article
Recenzirano
In view of possible future fixed target experiments requiring precisely steered charged particle beams, the UA9 Collaboration has undertaken experimental studies of the use of bent silicon crystals ...for this purpose. The channeling efficiency of positively charged particles inside the crystalline lattice has been investigated in detail for a setup with a tungsten target installed in front of the crystal. Due to multiple Coulomb scattering inside the target, the channeling efficiency was observed to be reduced by a factor of about 6.1 for a 180 GeV/c quasi-parallel hadron beam. The yield of nuclear interaction secondaries as an estimation of the additional machine background is also discussed.
The aims of the study were to analyze the clinical and epidemiological characteristics and treatments for patients who developed zygomycosis enrolled in italy during the european Confederation of ...medical mycology survey. This prospective multicenter study was performed between 2004 and 2007 at 49 italian Departments. 60 cases of zygomycosis were enrolled: the median age was 59.5 years (range 1-87), with a prevalence of males (70%). The majority of cases were immunocompromised patients (42 cases, 70%), mainly hematological malignancies (37). Among non-immunocompromised (18 cases, 30%), the main category was represented by patients with penetrating trauma (7/18, 39%). The most common sites of infection were sinus (35%) with/without CNS involvement, lung alone (25%), skin (20%), but in 11 cases (18%) dissemination was observed. According to EORTC criteria, the diagnosis of zygomycosis was proven in 46 patients (77%) and in most of them it was made in vivo (40/46 patients, 87%); in the remaining 14 cases (23%) the diagnosis was probable. 51 patients received antifungal therapy and in 30 of them surgical debridement was also performed. The most commonly used antifungal drug was liposomal amphotericin b (L- AmB), administered in 44 patients: 36 of these patients (82%) responded to therapy. Altogether an attributable mortality rate of 32% (19/60) was registered, which was reduced to 18% in patients treated with L-AmB (8/44). Zygomycosis is a rare and aggressive filamentous fungal infection, still associated with a high mortality rate. This study indicates an inversion of this trend, with a better prognosis and significantly lower mortality than that reported in the literature. It is possible that new extensive, aggressive diagnostic and therapeutic procedures, such as the use of L-AmB and surgery, have improved the prognosis of these patients.
Eosinophils are effector cells that have an important role in the pathogenesis of allergic disease. Defective removal of these cells likely leads to chronic inflammatory diseases such as asthma. ...Thus, there is great interest in understanding the mechanisms responsible for the elimination of eosinophils from inflammatory sites. Previous studies have demonstrated a role for certain mediators and molecular pathways responsible for the survival and death of leukocytes at sites of inflammation. Reactive oxygen species have been described as proinflammatory mediators but their role in the resolution phase of inflammation is poorly understood. The aim of this study was to investigate the effect of reactive oxygen species in the resolution of allergic inflammatory responses. An eosinophilic cell line (Eol-1) was treated with hydrogen peroxide and apoptosis was measured. Allergic inflammation was induced in ovalbumin sensitized and challenged mouse models and reactive oxygen species were administered at the peak of inflammatory cell infiltrate. Inflammatory cell numbers, cytokine and chemokine levels, mucus production, inflammatory cell apoptosis and peribronchiolar matrix deposition was quantified in the lungs. Resistance and elastance were measured at baseline and after aerosolized methacholine. Hydrogen peroxide accelerates resolution of airway inflammation by induction of caspase-dependent apoptosis of eosinophils and decrease remodeling, mucus deposition, inflammatory cytokine production and airway hyperreactivity. Moreover, the inhibition of reactive oxygen species production by apocynin or in gp91(phox-/-) mice prolonged the inflammatory response. Hydrogen peroxide induces Eol-1 apoptosis in vitro and enhances the resolution of inflammation and improves lung function in vivo by inducing caspase-dependent apoptosis of eosinophils.
We report the outcome of liver transplantation (LT) in the only surviving patient with lathosterolosis, a defect of cholesterol biosynthesis characterized by high lathosterol levels associated with ...progressive cholestasis, multiple congenital anomalies and mental retardation. From her diagnosis at age 2 she had shown autistic behavior, was unable to walk unaided and her sight was impaired by cataracts. By age 7 she developed end‐stage liver disease. After a soul‐searching discussion within the transplantation team, she was treated with LT as this represented her only lifesaving option. At 1‐year follow‐up, her lathosterol levels had returned to normal (0.61 mg/dL from 13.04 ± 2.65) and her nutrition improved. She began exploring her environment and walking by holding onto an adult's hand and then independently. Her brain magnetic resonance imaging (MRI) had shown a normal picture at age 1, whereas a volume reduction of white matter with ex vacuo ventricular dilatation and defective myelinization were observed before transplant. At 5‐year follow‐up, a complete biochemical recovery, an arrest of mental deterioration and a stable MRI picture were achieved, with a return to her every day life albeit with limitations. Timely liver transplant in defects of cholesterol biosynthesis might arrest the progression of neurological damage.
Liver transplantation corrects the metabolic unbalance in a child with lathosterolosis (OMIM #607330) and favors amelioration of her neurodevelopmental delay.
We aimed to assess the association between decreasing estimated glomerular filtration rate (eGFR) or abnormal albuminuria and the risk of certain cardiac conduction defects in patients with type 2 ...diabetes mellitus (T2DM).
We examined a hospital-based sample of 923 patients with T2DM discharged from our Division of Endocrinology over the years 2007–2014. Standard electrocardiograms (ECGs) were performed in all patients. eGFR was estimated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, whilst albuminuria was measured by an immuno-nephelometric method on morning spot urine samples.
A total of 253 (27.4%) patients had some type of cardiac conduction defects on standard ECGs (defined as at least one heart block among first-degree atrioventricular block, second-degree block, third-degree block, left bundle branch block, right bundle branch block, left anterior hemi-block or left posterior hemi-block). Prevalence of patients with eGFRCKD-EPI < 30 mL/min/1.73 m2, eGFRCKD-EPI 59–30 mL/min/1.73 m2 or abnormal albuminuria (i.e. urinary albumin-to-creatinine ratio ≥ 30 mg/g) were 7.0%, 29.4% and 41.3%, respectively. After adjustment for known cardiovascular risk factors, diabetes-related variables and potential confounders, there was a significant, graded association between decreasing eGFR values and risk of any cardiac conduction defects adjusted-odds ratios of 2.05 (95% CI: 1.2–3.5), 2.85 (95% CI: 1.6–5.1) and 3.62 (95% CI: 1.6–8.1) for eGFRCKD-EPI 89–60, eGFRCKD-EPI 59–30 and eGFRCKD-EPI < 30 mL/min/1.73 m2, respectively. Conversely, abnormal albuminuria was not independently associated with an increased risk of any conduction defects (adjusted-odds ratio: 1.09, 95% CI: 0.7–1.6).
Decreasing eGFR is independently associated with an increased risk of cardiac conduction defects in hospitalized patients with T2DM.
Deflection of 400 GeV/c protons by a short bent silicon crystal was studied at the CERN SPS. It was shown that the dechanneling probability increases while the dechanneling length decreases with an ...increase of incident angles of particles relative to the crystal planes. The observation of the dechanneling length reduction provides evidence of the particle population increase at the top levels of transverse energies in the potential well of the planar channels.
During the shutdown of the CERN Large Hadron Collider in 2013-2014, an additional pixel layer was installed between the existing Pixel detector of the ATLAS experiment and a new, smaller radius beam ...pipe. The motivation for this new pixel layer, the Insertable B-Layer (IBL), was to maintain or improve the robustness and performance of the ATLAS tracking system, given the higher instantaneous and integrated luminosities realised following the shutdown. Because of the extreme radiation and collision rate environment, several new radiation-tolerant sensor and electronic technologies were utilised for this layer. This paper reports on the IBL construction and integration prior to its operation in the ATLAS detector.
At large accelerators, bent crystals are employed to deflect weakly divergent proton beams at the stages of extraction and collimation. We demonstrate that a divergent particle beam may be ...efficiently deflected using a crystal with a focusing entry face. A 180 GeV/c pion beam with divergence near 0.060 mrad, which exceeds the Lindhard angle by a factor of 4, has been experimentally deflected by 0.25 mrad with efficiency near 22%. The proposed focusing crystal may serve as an element of a novel particle optics for secondary-particle beams in the TeV energy region.
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