HSV-2 Infection of Human Genital Epithelial Cells Upregulates TLR9 Expression Through the SP1/JNK Signaling Pathway

It is known that herpes simplex virus type 2 (HSV-2) triggers the activation of Toll-like receptor (TLR) 9 signaling pathway and the consequent production of antiviral cytokines in dendritic cells. However, the impact of HSV-2 infection on TLR9 expression and signaling in genital epithelial cells, the primary HSV-2 targets, has yet to be determined. In the current study, by using both human genital epithelial cell lines and primary genital epithelial cells as models, we found that HSV-2 infection enhances TLR9 expression at both mRNA and protein levels. Such enhancement is virus replication-dependent and CpG-independent, while the HSV-2-mediated upregulation of TLR9 does not activate TLR9 signaling pathway. Mechanistically, a SP1 binding site on TLR9 promoter appears to be essential for HSV-2-induced TLR9 transactivation. Upon HSV-2 infection, SP1 translocates from the cytoplasm to the nucleus, and consequently binds to TLR9 promoter. By using specific inhibitors, the JNK signaling pathway is shown to be involved in the HSV-2-induced TLR9 transactivation, while HSV-2 infection increases the phosphorylation but not the total level of JNK. In agreement, antagonism of JNK signaling pathway inhibits the HSV-2-induced SP1 nuclear translocation. Taken together, our study demonstrates that HSV-2 infection of human genital epithelial cells promotes TLR9 expression through SP1/JNK signaling pathway. Findings in this study provide insights into HSV-2-host interactions and potential targets for immune intervention

Bis[μ-3-(2-hy­droxy­phen­yl)propenoato]bis­{aqua­(4,4′-bipyridine)­bis­[3-(2-hydroxy­phen­yl)propenoato]yttrium(III)} 4,4′-bipyridine disolvate

The title compound, [Y2(C9H7O3)6(C10H8N2)2(H2O)2]·2C10H8N2, contains two eight-coordinated YIII ions, which are linked by two carboxyl­ate groups from two 2-hy­droxy­cinnamate anions, leading to a centrosymmetric dinuclear structure surrounded by solvent 4,4′-bipyridine mol­ecules. It forms a three-dimensional framework connected by extensive O—H⋯O and O—H⋯N hydrogen-bonding inter­actions

Multiscale Mechanistic Insights of Shaped Catalyst Body Formulations and Their Impact on Catalytic Properties

International audienceZeolite-based catalysts are globally employed in many industrial processes, such as in crude-oil refining and in the production of bulk chemicals. However, to be implemented in industrial reactors efficiently, zeolite powders are required to be shaped in catalyst bodies. Scale-up of zeolite catalysts into such forms comes with side effects to its overall physicochem-ical properties and to those of its constituting components. Although fundamental research into "technical" solid catalysts is scarce, binder effects have been reported to significantly impact their catalytic properties and lifetime. Given the large number of additional (in)organic components added in the formulation, it is somehow surprising to see that there is a distinct lack of research into the unintentional impact organic additives can have on the properties of the zeolite and the catalyst bodies in general. Here, we systematically prepared a series of alumina-bound zeolite ZSM-5-based catalyst bodies, with organic additives such as peptizing, plasticizing, and lubricating agents, to rationalize their impacts on the physicochemical properties of the shaped catalyst bodies. By utilizing a carefully selected arsenal of bulk and high-spatial resolution multiscale characterization techniques, as well as specifically sized bioinspired fluorescent nanoprobes to study pore accessibility, we clearly show that, although the organic additives achieve their primary function of a mechanically robust material, uncontrolled processes are taking place in parallel. We reveal that the extrusion process can lead to zeolite dealumination (from acid peptizing treatment, and localized steaming upon calcination); meso-and macropore structural rearrangement (via burning-out of organic plasticizing and lubricating agents upon calcination); and abating of known alumina binder effects (via scavenging of Al species via chelating lubricating agents), which significantly impact catalytic performance. Understanding the mechanisms behind such effects in industrial-grade catalyst formulations can lead to enhanced design of these important materials, which can improve process efficiency in a vast range of industrial catalytic reactions

Clinical impact of FDG PET-CT on management decisions for patients with primary biliary tumours

Objectives: To assess the impact on clinical management of introducing 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)-computed tomography (CT) in to the work-up of patients with primary and recurrent biliary malignancy. Methods: Consecutive patients with primary biliary tumours undergoing FDG PET-CT at a single large tertiary referral centre between November 2007 and September 2010 were retrospectively analysed. Findings on FDG PET-CT compared with CT/magnetic resonance imaging (MRI) and impact on subsequent patient management were evaluated. Impact was divided into: (1) major—detection of occult disease or characterisation of indeterminate lesion(s) on CT/MRI; (2) minor—confirmation of suspected metastases seen on CT/MRI; (3) no impact. Results: One hundred and eleven patients underwent 118 FDG PET-CT scans, including 30 with suspected gallbladder carcinoma and 81 with cholangiocarcinoma. Eighty-nine scans were performed for initial staging, five for restaging following neoadjuvant chemotherapy and 24 for suspected disease recurrence. In 33 cases (28 %), FDG PET-CT had a major impact on subsequent patient management (39 % gallbladder carcinoma, 26 % intrahepatic cholangiocarcinoma and 21 % extrahepatic cholangiocarcinoma). FDG PET-CT had a minor impact in 20 cases (17 %) and no impact in 65 cases (55 %). Conclusions: By detecting occult metastatic disease and characterising indeterminate lesions, FDG PET-CT can have a major influence on clinical decision-making in primary and recurrent biliary malignancy

Strategically Equivalent Contests

Using a two-player Tullock-type contest, we show that intuitively and structurally different contests can be strategically equivalent. Strategically equivalent contests generate the same best response functions and, as a result, the same equilibrium efforts. However, strategically equivalent contests may yield different equilibrium payoffs. We propose a simple two-step procedure to identify strategically equivalent contests. Using this procedure, we identify contests that are strategically equivalent to the original Tullock contest, and provide new examples of strategically equivalent contests. Finally, we discuss possible contest design applications and avenues for future theoretical and empirical research

Clinical impact and diagnostic accuracy of 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (PET/CT) brain imaging in patients with cognitive impairment: a tertiary centre experience in the UK

Aim To evaluate the clinical impact of combined 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) brain imaging performed in selected patients with cognitive impairment at a tertiary referral centre in the UK, and to assess the accuracy of FDG PET/CT to correctly establish the diagnosis of Alzheimer's dementia (AD) in “real-world” clinical practice. Methods and materials Using an institutional radiology database, 136 patients were identified for inclusion in the study. FDG PET/CT was performed using a standard technique and interpreted by dual-trained radiologists and nuclear medicine physicians. Standardised questionnaires were sent to the referring clinicians to establish the final clinical diagnosis and to obtain information about the clinical impact of FDG PET/CT. Results There was a 72% questionnaire return (98/136), with mean patient follow-up of 471 (standard deviation 205) days. FDG PET/CT had an impact on patient management in 81%, adding confidence to the pre-test diagnosis in 43%, changing the pre-test diagnosis in 35%, reducing the need for further investigations in 42%, and resulting in a change in therapy in 32%. There was substantial correlation between the PET/CT diagnosis and final clinical diagnosis with a correlation (k) coefficient of 0.78 (p<0.0001). The accuracy of FDG PET/CT in diagnosis of AD was 94% (95% confidence interval [CI]: 87–99), with a sensitivity of 87% (95% CI: 75–92) and a specificity of 97% (95% CI: 87–99). Conclusion FDG PET/CT brain imaging has a significant clinical impact when performed selectively in patients with cognitive impairment and shows high accuracy in the diagnosis of AD in “real-world” clinical practice

RNA editing of hepatitis B virus transcripts by activation-induced cytidine deaminase.

Activation-induced cytidine deaminase (AID) is essential for the somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes. The mechanism by which AID triggers SHM and CSR has been explained by two distinct models. In the DNA deamination model, AID converts cytidine bases in DNA into uridine. The uridine is recognized by the DNA repair system, which produces DNA strand breakages and point mutations. In the alternative model, RNA edited by AID is responsible for triggering CSR and SHM. However, RNA deamination by AID has not been demonstrated. Here we found that C-to-T and G-to-A mutations accumulated in hepatitis B virus (HBV) nucleocapsid DNA when AID was expressed in HBV-replicating hepatic cell lines. AID expression caused C-to-T mutations in the nucleocapsid DNA of RNase H-defective HBV, which does not produce plus-strand viral DNA. Furthermore, the RT-PCR products of nucleocapsid viral RNA from AID-expressing cells exhibited significant C-to-T mutations, whereas viral RNAs outside the nucleocapsid did not accumulate C-to-U mutations. Moreover, AID was packaged within the nucleocapsid by forming a ribonucleoprotein complex with HBV RNA and the HBV polymerase protein. The encapsidation of the AID protein with viral RNA and DNA provides an efficient environment for evaluating AID's RNA and DNA deamination activities. A bona fide RNA-editing enzyme, apolipoprotein B mRNA editing catalytic polypeptide 1, induced a similar level of C-to-U mutations in nucleocapsid RNA as AID. Taken together, the results indicate that AID can deaminate the nucleocapsid RNA of HBV

Transport poverty meets the digital divide : accessibility and connectivity in rural communities

Peer reviewedPublisher PD

Continuous Mott transition in semiconductor moir\'e superlattices

The evolution of a Landau Fermi liquid into a nonmagnetic Mott insulator with increasing electronic interactions is one of the most puzzling quantum phase transitions in physics. The vicinity of the transition is believed to host exotic states of matter such as quantum spin liquids, exciton condensates and unconventional superconductivity. Semiconductor moir\'e materials realize a highly controllable Hubbard model simulator on a triangular lattice, providing a unique opportunity to drive a metal-insulator transition (MIT) via continuous tuning of the electronic interactions. Here, by electrically tuning the effective interaction strength in MoTe2/WSe2 moir\'e superlattices, we observe a continuous MIT at a fixed filling of one electron per unit cell. The existence of quantum criticality is supported by the scaling behavior of the resistance, a continuously vanishing charge-gap as the critical point is approached from the insulating side, and a diverging quasiparticle effective mass from the metallic side. We also observe a smooth evolution of the low-temperature magnetic susceptibility across the MIT and find no evidence of long-range magnetic order down to ~ 5% of the Curie-Weiss temperature. The results signal an abundance of low-energy spinful excitations on the insulating side that is further corroborated by the presence of the Pomeranchuk effect on the metallic side. Our results are consistent with the universal critical theory of a continuous MIT from a Landau Fermi liquid to a nonmagnetic Mott insulator in two dimensions

Physics-Informed Data Denoising for Real-Life Sensing Systems

Sensors measuring real-life physical processes are ubiquitous in today's interconnected world. These sensors inherently bear noise that often adversely affects performance and reliability of the systems they support. Classic filtering-based approaches introduce strong assumptions on the time or frequency characteristics of sensory measurements, while learning-based denoising approaches typically rely on using ground truth clean data to train a denoising model, which is often challenging or prohibitive to obtain for many real-world applications. We observe that in many scenarios, the relationships between different sensor measurements (e.g., location and acceleration) are analytically described by laws of physics (e.g., second-order differential equation). By incorporating such physics constraints, we can guide the denoising process to improve even in the absence of ground truth data. In light of this, we design a physics-informed denoising model that leverages the inherent algebraic relationships between different measurements governed by the underlying physics. By obviating the need for ground truth clean data, our method offers a practical denoising solution for real-world applications. We conducted experiments in various domains, including inertial navigation, CO2 monitoring, and HVAC control, and achieved state-of-the-art performance compared with existing denoising methods. Our method can denoise data in real time (4ms for a sequence of 1s) for low-cost noisy sensors and produces results that closely align with those from high-precision, high-cost alternatives, leading to an efficient, cost-effective approach for more accurate sensor-based systems.Comment: SenSys 202