HHV-6A infection induces amyloid-beta expression and activation of microglial cells.

BACKGROUND: The control of viral infections in the brain involves the activation of microglial cells, the macrophages of the brain that are constantly surveying the central nervous system, and the production of amyloid-beta (Aβ) as an anti-microbial molecule. Recent findings suggest a possible implication of HHV-6A in AD. We evaluated the effect of HHV-6A infection on microglial cell expression Aβ and the activation status, determined by TREM2, ApoE, cytokines, and tau expression. METHODS: We have infected microglial cells (HMC3, ATCC®CRL-3304), in monolayer and human peripheral blood monocyte-derived microglia (PBM-microglia) spheroid 3D model, with HHV-6A (strain U1102) cell-free virus inocula with 100 genome equivalents per 1 cell. We collected the cells 1, 3, 7, and 14 days post-infection (d.p.i.) and analyzed them for viral DNA and RNA, ApoE, Aβ (1-40, 1-42), tau, and phospho-tau (Threonine 181) by real-time immunofluorescence and cytokines by immunoenzymatic assay. RESULTS: We observed a productive infection by HHV-6A. The expression of Aβ 1-42 increased from 3 d.p.i., while no significant induction was observed for Aβ 1-40. The HHV-6A infection induced the activation (TREM2, IL-1beta, ApoE) and migration of microglial cells. The secretion of tau started from 7 d.p.i., with an increasing percentage of the phosphorylated form. CONCLUSIONS: In conclusion, microglial cells are permissive to HHV-6A infection that induces the expression of Aβ and an activation status. Meanwhile, we hypothesize a paracrine effect of HHV-6A infection that activates and induces microglia migration to the site of infection

Validation of TiAlN functional coatings through cryo-tribological characterization using a pin-on-disk experiment

Abstract The purpose of this study has been to investigate the effects of TiAlN functional coatings in cryo-tribological pin-on-disk experiments. Nowadays, the introduction of new machining technologies for chip removal, both at high speed and in cryogenic conditions, is posing new challenges and opening new horizons to research. As a matter of fact, that in this technology needs to focus on the choice of workpiece materials to be machining and tools coatings used. For the latter, the wear phenomenon has been studied employing pins-on-disk (made by nickel-based alloys) under a liquid nitrogen jet flows simulating cryogenic machining. The coatings used have been of two different types: the coating C1 is a ZrTiAlN quaternary, while the coating C2 is a TiAlN/ZrN. The films were deposited with processes developed by the ENEA Brindisi laboratory using a dual magnetron sputtering and HiPPMS physical deposition technique. The wear measures were acquired employing a full factorial design with two factors: i.e., the test conditions (DRY or CRYO) and the pin coatings (not coated NC, coating C1 or C2). The number of tests was 12 since 2 were the replications. Based on preliminary experimental results, it can be stated that there is a type of coating, i.e., TiAlN/ZrN, that allows for high processing speed, high material removal, and a considerable increase in tool life

Residual Stress and Tribological Performance of ZrN Coatings Produced by Reactive Bipolar Pulsed Magnetron Sputtering

In the past few decades, ZrN thin films have been identified as wear resistant coatings for tribological applications. The mechanical and tribological properties of ZrN thin layers depend on internal stress induced by the adopted deposition techniques and deposition parameters such as pressure, temperature, and growth rate. In sputtering deposition processes, the selected target voltage waveform and the plasma characteristics also play a crucial influence on physical properties of produced coatings. In present work, ZrN thin films, obtained setting different values of duty cycle in a reactive bipolar pulsed dual magnetron sputtering plant, were investigated to evaluate their residual stress through the substrate curvature method. A considerable progressive increase of residual stress values was measured at decreasing duty cycle, attesting the significant role of voltage waveform in stress development. An evident correlation was also highlighted between the values of the duty cycle and those of wear factor. The performed analysis attested an advantageous effect of internal stress, having the samples with high compressive stress, higher wear resistance. A downward trend for wear rate with the increase of internal residual stress was observed. The choice of suitable values of duty cycle allowed to produce ceramic coatings with improved tribological performance

Residual stress and tribological performance of ZrN coatings produced by reactive bipolar magnetron sputtering

In the past few decades, ZrN thin films have been identified as wear resistant coatings for tribological applications. The mechanical and tribological properties of ZrN thin layers depend on internal stress induced by the adopted deposition techniques and deposition parameters such as pressure, temperature, and growth rate. In sputtering deposition processes, the selected target voltage waveform and the plasma characteristics also play a crucial influence on physical properties of produced coatings. In present work, ZrN thin films, obtained setting different values of duty cycle in a reactive bipolar pulsed dual magnetron sputtering plant, were investigated to evaluate their residual stress through the substrate curvature method. A considerable progressive increase of residual stress values was measured at decreasing duty cycle, attesting the significant role of voltage waveform in stress development. An evident correlation was also highlighted between the values of the duty cycle and those of wear factor. The performed analysis attested an advantageous effect of internal stress, having the samples with high compressive stress, higher wear resistance. A downward trend for wear rate with the increase of internal residual stress was observed. The choice of suitable values of duty cycle allowed to produce ceramic coatings with improved tribological performance

Dandy-Walker malformation: is the "tail sign" the key sign?

OBJECTIVE.To demonstrate the value of the "tail sign" in the assessment of Dandy-Walker Malformation (DWM). METHODS: A total of 31fetal MRI, performed before 24 weeks of gestation after second-line US examination between May 2013 and September 2014, were examined retrospectively. All MRI examinations were performed using a 1.5 Tesla magnet without maternal sedation. RESULTS: MRI diagnosed 15/31 cases of Dandy-Walker Malformation, 6/31 cases of vermian partial caudal agenesis, 2/31 of vermian hypoplasia, 4/31 of vermian malrotation, 2/31 of Walker-Warburg Syndrome, 1/31 of Blake pouch cyst, 1/31 of rhombencephalosynapsis. All data were compared with fetopsy results, Fetal MR after the 30th week or postnatal MRI; the follow up depended on the maternal decision to terminate or continue pregnancy. In our review study we found the presence of the "tail sign"; this sign was visible only in Dandy-Walker Malformation and Walker-Warburg Syndrome. CONCLUSION: The "tail sign" could be helpful in the difficult differential diagnosis between Dandy Walker, vermian malrotation, vermian hypoplasia and vermian partial agenesis

Separase prevents genomic instability by controlling replication fork speed

Proper chromosome segregation is crucial for preserving genomic integrity, and errors in this process cause chromosome mis-segregation, which may contribute to cancer development. Sister chromatid separation is triggered by Separase, an evolutionary conserved protease that cleaves the cohesin complex, allowing the dissolution of sister chromatid cohesion. Here we provide evidence that Separase participates in genomic stability maintenance by controlling replication fork speed. We found that Separase interacted with the replication licensing factors MCM2-7, and genome-wide data showed that Separase co-localized with MCM complex and cohesin. Unexpectedly, the depletion of Separase increased the fork velocity about 1.5-fold and caused a strong acetylation of cohesin's SMC3 subunit and altered checkpoint response. Notably, Separase silencing triggered genomic instability in both HeLa and human primary fibroblast cells. Our results show a novel mechanism for fork progression mediated by Separase and thus the basis for genomic instability associated with tumorigenesis

Separase prevents genomic instability by controlling replication fork speed

Proper chromosome segregation is crucial for preserving genomic integrity, and errors in this process cause chromosome mis-segregation, which may contribute to cancer development. Sister chromatid separation is triggered by Separase, an evolutionary conserved protease that cleaves the cohesin complex, allowing the dissolution of sister chromatid cohesion. Here we provide evidence that Separase participates in genomic stability maintenance by controlling replication fork speed. We found that Separase interacted with the replication licensing factors MCM2-7, and genome-wide data showed that Separase co-localized with MCM complex and cohesin. Unexpectedly, the depletion of Separase increased the fork velocity about 1.5-fold and caused a strong acetylation of cohesin's SMC3 subunit and altered checkpoint response. Notably, Separase silencing triggered genomic instability in both HeLa and human primary fibroblast cells. Our results show a novel mechanism for fork progression mediated by Separase and thus the basis for genomic instability associated with tumorigenesis

MOD derived pyrochlore films as buffer layer for all-chemical YBCO coated conductors

We report a detailed study performed on La2Zr2O7 (LZO) pyrochlore material grown by Metal-Organic Decomposition (MOD) method as buffer layers for YBa2Cu3O7-x (YBCO) coated conductors. High quality epitaxial LZO thin films have been obtained on single crystal (SC) and Ni-5%at.W substrates. In order to evaluate structural and morphological properties, films have been characterized by means of X-ray diffraction analyses (XRD), atomic force microscope (AFM) and scanning electron microscope (SEM). Precursors solutions and heat treatments have been studied by thermogravimetric analyses (TG-DTA-DTG) and infrared spectra (FT-IR) with the aim of optimizing the annealing process. Thin films of YBCO have been deposited by pulsed laser ablation (PLD) on this buffer layers. The best results obtained on SC showed YBCO films with critical temperature values above 90 K, high self field critical current density values (Jc > 1 MA/cm2) and high irreversibility field values (8.3 T) at 77 K together with a rather high depinning frequency vp (0.5 T, 77 K)>44 GHz as determined at microwaves. The best results on Ni-5%at.W has been obtained introducing in the heat treatment a pyrolysis process at low temperature in air in order to remove the residual organic part of the precursor solution

Obesity and Breast Cancer: Molecular Interconnections and Potential Clinical Applications

Obesity is an important risk factor for breast cancer (BC) in postmenopausal women; interlinked molecular mechanisms might be involved in the pathogenesis. Increased levels of estrogens due to aromatization of the adipose tissue, inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and prostaglandin E2, insulin resistance and hyperactivation of insulin-like growth factors pathways, adipokines, and oxidative stress are all abnormally regulated in obese women and contribute to cancerogenesis. These molecular factors interfere with intracellular signaling in the mitogen-activated protein kinase and phosphatydilinositol-3-phosphate/mammalian target of rapamycin (mTOR) pathways, which regulate the progression of the cell cycle, apoptosis, and protein synthesis. In this context, structural defects of typical genes related to both BC and obesity, such as leptin, leptin receptor, serum paraoxonase/arylesterase 1, the fat mass and obesity-associated gene and melanocortin receptor 4, have been associated with a high or low risk of BC development. The early detection of these gene alterations might be useful as risk predictors in obese women, and targeting these pathways involved in the BC pathogenesis in obese women is a potential therapeutic tool. In particular, mTOR pathway deregulation concurs in both obesity and BC, and inhibition of this might disrupt the molecular interlinks in a similar manner to that of metformin, which exerts definite anticancer activity and is currently used as an antidiabetic drug with a weight-reducing property. The identification of both genetic and pharmacological implications on the prevention and management of BC is the ultimate aim of these studies

Audiologic profile of OSAS and simple snoring patients: the effect of chronic nocturnal intermittent hypoxia on auditory function

The objective of this work was to study the effect of nocturnal intermittent hypoxia on auditory function of simple snoring patients and subjects affected by OSAS; we compared the audiologic profile with the severity of OSAS to detect early signs of cochlear damage. One hundred-sixty patients underwent overnight polysomnography, micro-otoscopy, multi-frequency audiometry, acufenometry, TEOAE recording and d-ROMs test. All subjects were divided in four groups, based on presence/absence of AHI (simple snoring without OSAS, mild OSAS, moderate OSAS, severe OSAS). Sixty (37.5 %) patients were not affected by OSAS, 58 (36.25 %) presented a mild OSAS, 18 (11.25 %) a moderate OSAS and 24 (15 %) a severe OSAS; the 57.14 % of moderate to severe OSAS suffered from tinnitus with respect to the 31.03 % of mild OSAS (P = 0.024). A higher percentage (41.66 %) of hearing loss was found among individuals with moderate to severe degree of OSAS (P < 0.0001). All groups were characterized by a mean hearing threshold <25 dB HL for 0.25–3 kHz frequencies and a progressive decrease in hearing sensitivity, particularly for 6–16 kHz frequencies (P < 0.05). The analysis of otoacoustic emissions SNR mean values evidenced a significant difference between simple snoring and severe OSAS individuals for 3 and 4 kHz frequencies (P < 0.05). d-ROM levels resulted higher in patients with severe OSAS with respect to simple snoring subjects (P = 0.004). Our data underline the key role of chronic nocturnal intermittent hypoxia in the development of an early cochlear damage and a more marked high-frequency hearing loss in case of severe OSAS (P < 0.05)