Active Immunization with Extracellular Vesicles Derived from Staphylococcus aureus Effectively Protects against Staphylococcal Lung Infections, Mainly via Th1 Cell-Mediated Immunity

Staphylococcus aureus is an important pathogenic bacterium that causes various infectious diseases. Extracellular vesicles (EVs) released from S. aureus contain bacterial proteins, nucleic acids, and lipids. These EVs can induce immune responses leading to similar symptoms as during staphylococcal infection condition and have the potential as vaccination agent. Here, we show that active immunization (vaccination) with S. aureus-derived EVs induce adaptive immunity of antibody and T cell responses. In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells. Moreover, vaccination with S. aureus EVs conferred protection against lethality induced by airway challenge with lethal dose of S. aureus and also pneumonia induced by the administration of sub-lethal dose of S. aureus. These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice. Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17. Together, the study herein suggests that S. aureus EVs are a novel vaccine candidate against S. aureus infections, mainly via Th1 cellular response.111814Ysciescopu

Superconductivity below 20 K in heavily electron-doped surface layer of FeSe bulk crystal

A superconducting transition temperature (T-c) as high as 100 K was recently discovered in one monolayer FeSe grown on SrTiO3. The discovery ignited efforts to identify the mechanism for the markedly enhanced T-c from its bulk value of 8 K. There are two main views about the origin of the T-c enhancement: interfacial effects and/or excess electrons with strong electron correlation. Here, we report the observation of superconductivity below 20 K in surface electron-doped bulk FeSe. The doped surface layer possesses all the key spectroscopic aspects of the monolayer FeSe on SrTiO3. Without interfacial effects, the surface layer state has a moderate T-c of 20 K with a smaller gap opening of 4.2 meV. Our results show that excess electrons with strong correlation cannot induce the maximum T-c, which in turn reveals the need for interfacial effects to achieve the highest T-c in one monolayer FeSe on SrTiO3.1116Ysciescopu

Oral immunization of haemaggulutinin H5 expressed in plant endoplasmic reticulum with adjuvant saponin protects mice against highly pathogenic avian influenza A virus infection

Pandemics in poultry caused by the highly pathogenic avian influenza (HPAI) A virus occur too frequently globally, and there is growing concern about the HPAI A virus due to the possibility of a pandemic among humans. Thus, it is important to develop a vaccine against HPAI suitable for both humans and animals. Various approaches are underway to develop such vaccines. In particular, an edible vaccine would be a convenient way to vaccinate poultry because of the behaviour of the animals. However, an edible vaccine is still not available. In this study, we developed a strategy of effective vaccination of mice by the oral administration of transgenic Arabidopsis plants (HA-TG) expressing haemagglutinin (HA) in the endoplasmic reticulum (ER). Expression of HA in the ER resulted in its high-level accumulation, N-glycosylation, protection from proteolytic degradation and long-term stability. Oral administration of HA-TG with saponin elicited high levels of HA-specific systemic IgG and mucosal IgA responses in mice, which resulted in protection against a lethal influenza virus infection with attenuated inflammatory symptoms. Based on these results, we propose that oral administration of freeze-dried leaf powders from transgenic plants expressing HA in the ER together with saponin is an attractive strategy for vaccination against influenza A virus.X111411Ysciescopu

Clinical significance of amyloid β positivity in patients with probable cerebral amyloid angiopathy markers

Purpose: We investigated the frequency and clinical significance of amyloid β (Aβ) positivity on PET in patients with cerebral amyloid angiopathy (CAA). / Methods: We recruited 65 patients who met the modified Boston criteria for probable CAA. All underwent amyloid PET, MRI, APOE genotyping and neuropsychological testing, and we obtained information on MRI markers of CAA and ischemic cerebral small-vessel disease (CSVD). We investigated the CAA/ischemic CSVD burden and APOE genotypes in relation to Aβ positivity and investigated the effect of Aβ positivity on longitudinal cognitive decline. / Results: Among the 65 CAA patients, 43 (66.2%) showed Aβ PET positivity (Aβ+). Patients with Aβ+ CAA had more lobar microbleeds (median 9, interquartile range 2–41, vs. 3, 2–8; P = 0.045) and a higher frequency of cortical superficial siderosis (34.9% vs. 9.1%; P = 0.025), while patients with Aβ− CAA had more lacunes (1, 0–2, vs. 0, 0–1; P = 0.029) and a higher frequency of severe white matter hyperintensities (45.5% vs. 20.9%; P = 0.040). The frequency of ε4 carriers was higher in Aβ+ patients (57.1%) than in Aβ− patients (18.2%; P = 0.003), while the frequency of ε2 carriers did not differ between the two groups. Finally, Aβ positivity was associated with faster decline in multiple cognitive domains including language (P < 0.001), visuospatial function (P < 0.001), and verbal memory (P < 0.001) in linear mixed effects models. / Conclusion: Our findings suggest that a significant proportion of patients with probable CAA in a memory clinic are Aβ− on PET. Aβ positivity in CAA patients is associated with a distinct pattern of CSVD biomarker expression, and a worse cognitive trajectory. Aβ positivity has clinical relevance in CAA and might represent either advanced CAA or additional Alzheimer’s disease neuropathological changes

SREBP-2/PNPLA8 axis improves non-alcoholic fatty liver disease through activation of autophagy

Dysregulated autophagy is associated with steatosis and non-alcoholic fatty liver disease (NAFLD), however the mechanisms connecting them remain poorly understand. Here, we show that co-administration of lovastatin and ezetimibe (L/E) significantly reverses hepatic triglyceride accumulation concomitant with an increase in SREBP-2 driven autophagy in mice fed a high-fat diet (HFD). We further show that the statin mediated increase in SREBP-2 directly activates expression of patatin-like phospholipase domain-containing enzyme 8 (PNPLA8) gene, and PNPLA8 associates with autophagosomes and is associated with a decrease in cellular triglyceride. Moreover, we show that over-expression of PNPLA8 dramatically decreases hepatic steatosis through increased autophagy in hepatocytes of HFD-fed mice. Live-cell imaging analyses also reveal that PNPLA8 dynamically interacts with LC3 and we suggest that the SREBP-2/PNPLA8 axis represents a novel regulatory mechanism for lipid homeostasis. These data provide a possible mechanism for the reported beneficial effects of statins for decreasing hepatic triglyceride levels in NAFLD patients.ope

Attention deficit hyperactivity symptoms predict problematic mobile phone use

Attention-deficit-hyperactivity disorder (ADHD) is the most commonly diagnosed childhood disorder characterised by inattention, hyperactivity/impulsivity, or both. Some of the key traits of ADHD have previously been linked to addictive and problematic behaviours. The aim of the present study was to examine the relationship between problematic mobile phone use, smartphone addiction risk and ADHD symptoms in an adult population. A sample of 273 healthy adult volunteers completed the Adult ADHD Self-Report Scale (ASRS), the Mobile Phone Problem Usage Scale (MPPUS), and the Smartphone Addiction Scale (SAS). A significant positive correlation was found between the ASRS and both scales. More specifically, inattention symptoms and age predicted smartphone addiction risk and problematic mobile phone use. Our results suggest that there is a positive relationship between ADHD traits and problematic mobile phone use. In particular, younger adults with higher level of inattention symptoms could be at higher risk of developing smartphone addiction. The implication of our findings for theoretical frameworks of problematic mobile phone use and clinical practice are discussed

Consistent LDA'+DMFT approach to electronic structure of transition metal oxides: charge transfer insulators and correlated metals

We discuss the recently proposed LDA'+DMFT approach providing consistent parameter free treatment of the so called double counting problem arising within the LDA+DMFT hybrid computational method for realistic strongly correlated materials. In this approach the local exchange-correlation portion of electron-electron interaction is excluded from self consistent LDA calculations for strongly correlated electronic shells, e.g. d-states of transition metal compounds. Then the corresponding double counting term in LDA+DMFT Hamiltonian is consistently set in the local Hartree (fully localized limit - FLL) form of the Hubbard model interaction term. We present the results of extensive LDA'+DMFT calculations of densities of states, spectral densities and optical conductivity for most typical representatives of two wide classes of strongly correlated systems in paramagnetic phase: charge transfer insulators (MnO, CoO and NiO) and strongly correlated metals (SrVO3 and Sr2RuO4). It is shown that for NiO and CoO systems LDA'+DMFT qualitatively improves the conventional LDA+DMFT results with FLL type of double counting, where CoO and NiO were obtained to be metals. We also include in our calculations transition metal 4s-states located near the Fermi level missed in previous LDA+DMFT studies of these monooxides. General agreement with optical and X-ray experiments is obtained. For strongly correlated metals LDA$^\prime$+DMFT results agree well with earlier LDA+DMFT calculations and existing experiments. However, in general LDA'+DMFT results give better quantitative agreement with experimental data for band gap sizes and oxygen states positions, as compared to the conventional LDA+DMFT.Comment: 13 pages, 11 figures, 1 table. In v2 there some additional clarifications are include

Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and proinflammatory dysregulation

Pigs are evidently more resistant to avian than swine influenza A viruses, mediated in part through frontline epithelial cells and alveolar macrophages (AM). Although porcine AM (PAM) are crucial in influenza virus control, their mode of control is unclear. To gain insight into the possible role of PAM in the mediation of avian influenza virus resistance, we compared the host effects and replication of two avian (H2N3 and H6N1) and three mammalian (swine H1N1, human H1N1 and pandemic H1N1) influenza viruses in PAM. We found that PAM were readily susceptible to initial infection with all five avian and mammalian influenza viruses but only avian viruses caused early and extensive apoptosis (by 6 h of infection) resulting in reduced virus progeny and moderated pro- inflammation. Full length viral PB1-F2 present only in avian influenza viruses is a virulence factor that targets AM for mitochondrial associated apoptotic cell death. With the use of reverse genetics on an avian H5N1 virus, we found that full length PB1-F2 contributed to increased apoptosis and pro-inflammation but not to reduced virus replication. Taken together, we propose that early apoptosis of PAM limits the spread of avian influenza viruses and that PB1-F2 could play a contributory role in the process

F-18-AV-1451 PET Imaging in Three Patients with Probable Cerebral Amyloid Angiopathy

Cerebrovascular deposition of amyloid-β, known as cerebral amyloid angiopathy (CAA), is associated with MRI findings of lobar hemorrhage, cerebral microbleeds, and cortical superficial siderosis. Although pathological studies suggest that tau may co-localize with vascular amyloid, this has not yet been investigated in CAA in vivo. Three patients with probable CAA underwent 11C-Pittsburgh Compound B (PiB) PET or 18F-florbetaben PET to evaluate amyloid burden, and 18F-AV-1451 PET to evaluate paired helical filament tau burden. Regions that had cerebral microbleeds or cortical superficial siderosis largely overlapped with those showing increased 18F-AV-1451. Our preliminary study raised the possibility that lobar cerebral microbleeds, and cortical superficial siderosis, which are characteristic markers of vascular amyloid, may be associated with local production of paired helical filament tau

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined