Development of a short and an ultra-brief version of the Saving Inventory-revised (SI-R) for assessing hoarding severity: The SI-R9 and the SI-R3.

Hoarding Disorder (HD) is marked by the inability to discard possessions, and often excessive acquiring, which results in cluttered living spaces that substantially disrupt daily life. While the Saving Inventory-Revised (SI-R) serves as a reliable and valid tool for assessing hoarding severity, its length may preclude routine use. We aimed to develop a valid shorter version of the scale using Item Response Theory and Confirmatory Factor Analysis in a non-selected sample of 2890 individuals and a clinical HD sample of 200 participants, which were divided into test and confirmatory samples in a 2:1 ratio.

Murine norovirus infection of macrophages induces intrinsic apoptosis as the major form of programmed cell death.

Human norovirus is the leading cause of acute gastroenteritis worldwide, however despite the significance of this pathogen, we have a limited understanding of how noroviruses cause disease, and modulate the innate immune response. Programmed cell death (PCD) is an important part of the innate response to invading pathogens, but little is known about how specific PCD pathways contribute to norovirus replication. Here, we reveal that murine norovirus (MNV) virus-induced PCD in macrophages correlates with the release of infectious virus.

Nlrp3 inflammasome activation and Gasdermin D-driven pyroptosis are immunopathogenic upon gastrointestinal norovirus infection.

Norovirus infection is the leading cause of food-borne gastroenteritis worldwide, being responsible for over 200,000 deaths annually. Studies with murine norovirus (MNV) showed that protective STAT1 signaling controls viral replication and pathogenesis, but the immune mechanisms that noroviruses exploit to induce pathology are elusive. Here, we show that gastrointestinal MNV infection leads to widespread IL-1β maturation in MNV-susceptible STAT1-deficient mice.

The role of the NLRP3 inflammasome in regulation of antiviral responses to influenza A virus infection.

The innate immune system provides the host with both a dynamic barrier to prevent infection and a means to which rapid anti-microbial responses can be mounted. The inflammasome pathway is a critical host early response mechanism that enables detection of pathogens and initiates production of inflammatory cytokines, inducing recruitment of effector cells to the site of infection. The complete mechanism of inflammasome activation requires two signals: an initial priming step upon detection of pathogen, followed by activation of intracellular pattern recognition receptors critical to the formation of the inflammasome complex.

The Norovirus NS3 Protein Is a Dynamic Lipid- and Microtubule-Associated Protein Involved in Viral RNA Replication.

Unlabelled: Norovirus (NoV) infections are a significant health burden to society, yet the lack of reliable tissue culture systems has hampered the development of appropriate antiviral therapies. Here we show that the NoV NS3 protein, derived from murine NoV (MNV), is intimately associated with the MNV replication complex and the viral replication intermediate double-stranded RNA (dsRNA). We observed that when expressed individually, MNV NS3 and NS3 encoded by human Norwalk virus (NV) induced the formation of distinct vesicle-like structures that did not colocalize with any particular protein markers to cellular organelles but localized to cellular membranes, in particular those with a high cholesterol content.

Norovirus Infection: Replication, Manipulation of Host, and Interaction with the Host Immune Response.

Noroviruses (NoVs) belong to the Caliciviridae family of viruses and are responsible for causing the majority of gastroenteritis outbreaks worldwide. In the past decade, research on NoV biology has intensified because of the discovery of murine NoV and subsequently the first cell culture system and small animal model for NoV replication and pathogenesis. In this review, we discuss the current literature on NoV biology, focusing particularly on NoV replication and the interaction between NoV and the host immune response.

The acetyltransferase HAT1 moderates the NF-κB response by regulating the transcription factor PLZF.

To date, the activities of protein kinases have formed the core of our understanding of cell signal transduction. Comprehension of the extent of protein acetylation has raised expectations that this alternate post-transcriptional modification will be shown to rival phosphorylation in its importance in mediating cellular responses. However, limited instances have been identified.

Sequence-dependent off-target inhibition of TLR7/8 sensing by synthetic microRNA inhibitors.

Anti-microRNA (miRNA) oligonucleotides (AMOs) with 2'-O-Methyl (2'OMe) residues are commonly used to study miRNA function and can achieve high potency, with low cytotoxicity. Not withstanding this, we demonstrate the sequence-dependent capacity of 2'OMe AMOs to inhibit Toll-like receptor (TLR) 7 and 8 sensing of immunostimulatory RNA, independent of their miRNA-targeting function. Through a screen of 29 AMOs targeting common miRNAs, we found a subset of sequences highly inhibitory to TLR7 sensing in mouse macrophages.

Integrin-linked kinase modulates lipopolysaccharide- and Helicobacter pylori-induced nuclear factor κB-activated tumor necrosis factor-α production via regulation of p65 serine 536 phosphorylation.

Integrin-linked kinase (ILK) is a ubiquitously expressed and highly conserved serine-threonine protein kinase that regulates cellular responses to a wide variety of extracellular stimuli. ILK is involved in cell-matrix interactions, cytoskeletal organization, and cell signaling. ILK signaling has also been implicated in oncogenesis and progression of cancers.

Inosine-mediated modulation of RNA sensing by Toll-like receptor 7 (TLR7) and TLR8.

RNA-specific adenosine deaminase (ADAR)-mediated adenosine-to-inosine (A-to-I) editing is a critical arm of the antiviral response. However, mechanistic insights into how A-to-I RNA editing affects viral infection are lacking. We posited that inosine incorporation into RNA facilitates sensing of nonself RNA by innate immune sensors and accordingly investigated the impact of inosine-modified RNA on Toll-like receptor 7 and 8 (TLR7/8) sensing.

Human Toll-like receptor 8 can be cool too: implications for foreign RNA sensing.

Recent advances in our understanding of foreign nucleic acid sensing indicate an important role for the human Toll-like receptor (TLR) 8 in the initiation of immune responses to certain pathogens. However, TLR8, far too often grouped together with TLR7 for its common ability to detect RNA, has a function on its own in the initiation of specific proinflammatory responses to viruses and bacteria. Here, we present an overview of what is currently known of human TLR8 biology, from genetic regulation to its function in innate immunity, and discuss how TLR8 could present novel therapeutic opportunities in viral and cancer diseases.

A miR-19 regulon that controls NF-κB signaling.

Fine-tuning of inflammatory responses by microRNAs (miRNAs) is complex, as they can both enhance and repress expression of pro-inflammatory mediators. In this study, we investigate inflammatory responses following global miRNA depletion, to better define the overall contribution of miRNAs to inflammation. We demonstrate that miRNAs positively regulate Toll-like receptor signaling using inducible Dicer1 deletion and global miRNA depletion.