On field effect studies and superconductor-insulator transition in high-Tc cuprates

We summarize previous field effect studies in high-T c cuprates and then discuss our method to smoothly tune the carrier concentration of a cuprate film over a wide range using an applied electric field. We synthesized epitaxial one-unit-cell thick films of La2−x Sr x CuO4 and from them fabricated electric double layer transistor devices utilizing various gate electrolytes. We were able to vary the carrier density by about 0.08 carriers per Cu atom, with the resulting change in T c of 30 K. The superconductor-insulator transition occurred at the critical resistance very close to the quantum resistance for pairs, R Q = h/(2e)2 = 6.5 kΩ. This is suggestive of a quantum phase transition, possibly driven by quantum phase fluctuations, between a "Bose insulator” and a high-T c superconductor stat

HDLs protect the MIN6 insulinoma cell line against tunicamycin-induced apoptosis without inhibiting ER stress and without restoring ER functionality.

HDLs protect pancreatic beta cells against apoptosis induced by several endoplasmic reticulum (ER) stressors, including thapsigargin, cyclopiazonic acid, palmitate and insulin over-expression. This protection is mediated by the capacity of HDLs to maintain proper ER morphology and ER functions such as protein folding and trafficking. Here, we identified a distinct mode of protection exerted by HDLs in beta cells challenged with tunicamycin (TM), a protein glycosylation inhibitor inducing ER stress. HDLs were found to inhibit apoptosis induced by TM in the MIN6 insulinoma cell line and this correlated with the maintenance of a normal ER morphology. Surprisingly however, this protective response was neither associated with a significant ER stress reduction, nor with restoration of protein folding and trafficking in the ER. These data indicate that HDLs can use at least two mechanisms to protect beta cells against ER stressors. One that relies on the maintenance of ER function and one that operates independently of ER function modulation. The capacity of HDLs to activate several anti-apoptotic pathways in beta cells may explain their ability to efficiently protect these cells against a variety of insults

Outbreak among drug users caused by a clonal strain of group A streptococcus.

We describe an outbreak among drug users of severe soft-tissue infections caused by a clonal strain of group A streptococcus of M-type 25. Cases (n = 19) in drug users were defined as infections (mainly needle abscesses) due to the outbreak strain. Comparison with controls showed that infected drug users bought drugs more often at a specific place. Drug purchase and use habits may have contributed to this outbreak

CRISPR/Cas9 genome-wide screening identifies KEAP1 as a sorafenib, lenvatinib, and regorafenib sensitivity gene in hepatocellular carcinoma.

Sorafenib is the first-line drug used for patients with advanced hepatocellular carcinoma (HCC). However, acquired sorafenib resistance in cancer patients limits its efficacy. Here, we performed the first genome-wide CRISPR/Cas9-based screening on sorafenib-treated HCC cells to identify essential genes for non-mutational mechanisms related to acquired sorafenib resistance and/or sensitivity in HCC cells. KEAP1 was identified as the top candidate gene by Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK). KEAP1 disrupted HCC cells were less sensitive than wild-type cells in short- and long-term sorafenib treatments. Compared to wild-type cells, KEAP1-disrupted cells showed lower basal and sorafenib-induced reactive oxygen species (ROS) levels and were more resistant to oxidative stress-induced cell death. The absence of KEAP1 led to increased activity of Nrf2, a key transcription factor controlling antioxidant responses, as further evidenced by increased expression of Nrf2-controlled genes including NQO1, GPX2 and TXNRD1, which were positively associated with chemoresistance. In addition, KEAP1 disruption counteracted the reduction of cell viability and the elevation of ROS caused by lenvatinib, a drug that recently showed clinical efficacy as a first-line treatment for unresectable HCC. Finally, Keap1 disruption also increased the resistance of cells to regorafenib, a recently approved drug to treat HCC as a second line therapy. Taken together, our data indicate that deregulation of the KEAP1/Nrf2 pathway following KEAP1 inactivation contributes to sorafenib, lenvatinib, and regorafenib resistance in human HCC cells through up-regulation of Nrf2 downstream genes and decreased ROS levels

Revisiting a pollen-transmitted ilarvirus previously associated with angular mosaic of grapevine

We report the characterization of a novel tri-segmented RNA virus infecting Mercurialis annua, a common crop weed and model species in plant science. The virus, named "Mercurialis latent virus" (MeLaV) was first identified in a mixed infection with the recently described Mercurialis orthotospovirus 1 (MerV1) on symptomatic plants grown in glasshouses in Lausanne (Switzerland). Both viruses were found to be transmitted by Thrips tabaci, which presumably help the inoculation of infected pollen in the case of MeLaV. Complete genome sequencing of the latter revealed a typical ilarviral architecture and close phylogenetic relationship with members of the Ilarvirus subgroup 1. Surprisingly, a short portion of MeLaV replicase was found to be identical to the partial sequence of grapevine angular mosaic virus (GAMV) reported in Greece in the early 1990s. However, we have compiled data that challenge the involvement of GAMV in angular mosaic of grapevine, and we propose alternative causal agents for this disorder. In parallel, three highly-conserved MeLaV isolates were identified in symptomatic leaf samples in The Netherlands, including a herbarium sample collected in 1991. The virus was also traced in diverse RNA sequencing datasets from 2013-2020, corresponding to transcriptomic analyses of M. annua and other plant species from five European countries, as well as metaviromics analyses of bees in Belgium. Additional hosts are thus expected for MeLaV, yet we argue that infected pollen grains have likely contaminated several sequencing datasets and may have caused the initial characterization of MeLaV as GAMV

Insulator to metal transition in WO3 induced by electrolyte gating

Tungsten oxide and its associated bronzes (compounds of tungsten oxide and an alkali metal) are well known for their interesting optical and electrical characteristics. We have modified the transport properties of thin WO3 films by electrolyte gating using both ionic liquids and polymer electrolytes. We are able to tune the resistivity of the gated film by more than five orders of magnitude, and a clear insulator-to-metal transition is observed. To clarify the doping mechanism, we have performed a series of incisive operando experiments, ruling out both a purely electronic effect (charge accumulation near the interface) and oxygen-related mechanisms. We propose instead that hydrogen intercalation is responsible for doping WO3 into a highly conductive ground state and provide evidence that it can be described as a dense polaronic gas

Risks management and cobots. Identifying critical variables

Trabajo presentado en: 29th European Safety and Reliability Conference (ESREL), 22–26 September 2019, HannoverA collaborative robot or a "Cobot" is the name of a robot that can share a workspace with operators in the absence of a protective fence or with only partial protection. They represent a new and expanding sector of industrial robotics. This investigation draws from the latest international rules and safety parameters related to work with collaborative robots. Its detailed research is motivated by the design of a collaborative industrial robot system, hazard elimination, risk reduction, and different collaborative operations, such as power and force limiting, collaborative operation design, and end-effector safety requirements, among others. The purpose of our study is to analyze the most important variables that must be controlled in accordance with the desired use of the Cobot, according to ISO / TS 15066, ISO / TR 20218-1and some other generic safety regulations on machines and industrial robots. A series of observations and appreciations on the use of the Cobot will also be presented

TLR4 activation induces IL-1ss release via an IPAF dependent but caspase 1/11/8 independent pathway in the lung

Background: The IL-1 family of cytokines is known to play an important role in inflammation therefore understanding the mechanism by which they are produced is paramount. Despite the recent plethora of publications dedicated to the study of these cytokines, the mechanism by which they are produced in the airway following endotoxin, Lipopolysaccharide (LPS), exposure is currently unclear. The aim was to determine the mechanism by which the IL-1 cytokines are produced after LPS inhaled challenge. Methods:Mice were challenged with aerosolised LPS, and lung tissue and bronchiolar lavage fluid (BALF) collected. Targets were measured at the mRNA and protein level; caspase activity was determined using specific assays. Results: BALF IL-1b/IL-18, but not IL-1a, was dependent on Ice Protease-Activating Factor (IPAF), and to a lesser extent Apoptosis-associated Speck-like protein containing a CARD (ASC). Interestingly, although we measured an increase in mRNA expression for caspase 1 and 11, we could not detect an increase in lung enzyme activity or a role for them in IL-1a/b production. Further investigations showed that whilst we could detect an increase in caspase 8 activity at later points in the time course (during resolution of inflammation), it appeared to play no role in the production of IL-1 cytokines in this model system. Conclusions: TLR4 activation increases levels of BALF IL-1b/IL-18 via an IPAF dependent and caspase 1/11/8 independent pathway. Furthermore, it would appear that the presence of IL-1a in the BALF is independent of these pathways. This novel data sheds light on innate signalling pathways in the lung that control the production of these key inflammatory cytokines

Tiotropium modulates transient receptor potential V1 (TRPV1) in airway sensory nerves: A beneficial off-target effect?⋆

BackgroundRecent studies have suggested that the long-acting muscarinic receptor antagonist tiotropium, a drug widely prescribed for its bronchodilator activity in patients with chronic obstructive pulmonary disease and asthma, improves symptoms and attenuates cough in preclinical and clinical tussive agent challenge studies. The mechanism by which tiotropium modifies tussive responses is not clear, but an inhibition of vagal tone and a consequent reduction in mucus production from submucosal glands and bronchodilation have been proposed.ObjectiveThe aim of this study was to investigate whether tiotropium can directly modulate airway sensory nerve activity and thereby the cough reflex.MethodsWe used a conscious cough model in guinea pigs, isolated vagal sensory nerve and isolated airway neuron tissue– and cell-based assays, and in vivo single-fiber recording electrophysiologic techniques.ResultsInhaled tiotropium blocked cough and single C-fiber firing in the guinea pig to the transient receptor potential (TRP) V1 agonist capsaicin, a clinically relevant tussive stimulant. Tiotropium and ipratropium, a structurally similar muscarinic antagonist, inhibited capsaicin responses in isolated guinea pig vagal tissue, but glycopyrrolate and atropine did not. Tiotropium failed to modulate other TRP channel–mediated responses. Complementary data were generated in airway-specific primary ganglion neurons, demonstrating that tiotropium inhibited capsaicin-induced, but not TRPA1-induced, calcium movement and voltage changes.ConclusionFor the first time, we have shown that tiotropium inhibits neuronal TRPV1-mediated effects through a mechanism unrelated to its anticholinergic activity. We speculate that some of the clinical benefit associated with taking tiotropium (eg, in symptom control) could be explained through this proposed mechanism of action