Recent insights into the molecular mechanisms of the NLRP3 inflammasome activation

Inflammasomes are high-molecular-weight protein complexes that are formed in the cytosolic compartment in response to danger- or pathogen-associated molecular patterns. These complexes enable activation of an inflammatory protease caspase-1, leading to a cell death process called pyroptosis and to proteolytic cleavage and release of pro-inflammatory cytokines interleukin (IL)-1beta and IL-18. Along with caspase-1, inflammasome components include an adaptor protein, ASC, and a sensor protein, which triggers the inflammasome assembly in response to a danger signal. The inflammasome sensor proteins are pattern recognition receptors belonging either to the NOD-like receptor (NLR) or to the AIM2-like receptor family. While the molecular agonists that induce inflammasome formation by AIM2 and by several other NLRs have been identified, it is not well understood how the NLR family member NLRP3 is activated. Given that NLRP3 activation is relevant to a range of human pathological conditions, significant attempts are being made to elucidate the molecular mechanism of this process. In this review, we summarize the current knowledge on the molecular events that lead to activation of the NLRP3 inflammasome in response to a range of K (+) efflux-inducing danger signals. We also comment on the reported involvement of cytosolic Ca (2+) fluxes on NLRP3 activation. We outline the recent advances in research on the physiological and pharmacological mechanisms of regulation of NLRP3 responses, and we point to several open questions regarding the current model of NLRP3 activation

A molecular analysis to assess codling moth \u3ci\u3eCydia pomonella\u3c/i\u3e L. (Lepidoptera: Tortricidae) predation by orchard birds

The codling moth Cydia pomonella L. (Lepidoptera: Tortricidae) is a major economic pest in organic apple orchards. Observational methods, prey removal experiments and correlative experiments with exclosures or nest boxes have demonstrated that birds contribute to the removal of this insect pest. However, the majority of research conducted in the last several decades has taken place outside of the United States and methods for studying biological pest control have advanced dramatically and now include molecular techniques. We conducted a proof-of-concept study to test a DNA-based approach to detect C. pomonella prey in the diets of birds occupying organic apple orchards. We tested published Tortricidae primers, polymerase chain reaction (PCR) and sequencing for detection of C. pomonella in avian feces. We also tested the quality of DNA isolated and purified from fecal samples using two DNA extraction kits. Finally, we field-tested this tool to identify the presence or absence of C. pomonella in the laboratory and from field samples. C. pomonella DNA was amplified in less than 1% of field samples and was successfully sequenced in 0.5%. A single species, the brown-headed cowbird Molothrus ater (Boddaert), had fecal samples positive for C. pomonella DNA. While our results do not provide evidence that birds play a strong role in the control of C. pomonella in western Colorado organic apple orchards, the approach we present is a new tool for understanding bird-mediated ecosystem services, avian feeding ecology, and supporting management decisions for sustainable agricultural practices and farmland biodiversity

Change: A Leader’s Perspective

Change: A Leader\u27s Perspective represents the culmination of the Change Leadership course taught at Winona State University in the fall term of 2017. Leadership is a broad category with many facets. This book explores the subject and offers students of leadership and aspiring leaders current perspectives on leadership theories, the omnipresence of change, and personal reflections on the course material. Additional thoughts which resonate throughout this text are that leaders influence outcomes and that leadership manifests itself in change, whether by cause or effect.https://openriver.winona.edu/leadershipeducationbooks/1000/thumbnail.jp

The TLR signalling adaptor TRIF/TICAM-1 has an N-terminal helical domain with structural similarity to IFIT proteins

TRIF/TICAM-1 (TIR domain-containing adaptor inducing interferon-beta/TIR domain-containing adaptor molecule 1) is the adaptor protein in the Toll-like receptor (TLR) 3 and 4 signalling pathway that leads to the production of type 1 interferons and cytokines. The signalling involves TIR (Toll/interleukin-1 receptor) domain-dependent TRIF oligomerization. A protease-resistant N-terminal region is believed to be involved in self-regulation of TRIF by interacting with its TIR domain. Here, the structural and functional characterization of the N-terminal domain of TRIF (TRIF-NTD) comprising residues 1-153 is reported. The 2.22 angstrom resolution crystal structure was solved by single-wavelength anomalous diffraction (SAD) using selenomethionine-labelled crystals of TRIF-NTD containing two additional introduced Met residues (TRIF-NTDA66M/L113M). The structure consists of eight antiparallel helices that can be divided into two subdomains, and the overall fold shares similarity to the interferon-induced protein with tetratricopeptide repeats (IFIT) family of proteins, which are involved in both the recognition of viral RNA and modulation of innate immune signalling. Analysis of TRIF-NTD surface features and the mapping of sequence conservation onto the structure suggest several possible binding sites involved in either TRIF auto-regulation or interaction with other signalling molecules or ligands. TRIF-NTD suppresses TRIF-mediated activation of the interferon-beta promoter, as well as NF-kappa B-dependent reporter-gene activity. These findings thus identify opportunities for the selective targeting of TLR3- and TLR4-mediated inflammation

Is facet joint distraction a cause of postoperative axial neck pain after ACDF surgery?

Introduction: Intervertebral distraction in anterior cervical discectomy and fusion (ACDF) has been postulated to injure the degenerative facet joints posteriorly and increase postoperative pain and disability. This study aims to determine if there is a correlation between the amount of facet distraction and postoperative patient reported outcomes. Methods: A retrospective cohort analysis of patients undergoing ACDF for degenerative pathologies was performed. Each patient received lateral cervical spine x-rays at the immediate postoperative time point and were split into groups based on the amount of facet distraction measured on these films: Group A: \u3c 1.5 mm; Group B: 1.5-2.0 mm; and Group C: \u3e 2.0 mm. Patients reported outcome measures were obtained preoperatively and at 1-year postoperatively. Univariate and multivariate analyses were performed to compare outcomes between groups. Results: A total of 229 patients were included with an average follow-up of 19.8 [19.0, 20.7] months with a mean facet joint distraction of 1.7mm. There were 87 patients in Group A, 76 patients in Group B, and 66 patients in Group C. Patients significantly improved across all outcome measures from baseline to postoperatively (p \u3c 0.05). There was no difference between groups at any time point with respect to outcome scores (p \u3e 0.05). Multiple regression analysis did not identify increasing distraction as a predictor of patient outcomes. Conclusions: There were no significant differences between patient outcomes and the amount of facet distraction after ACDF surgery. Multivariate analysis did not find a correlation between facet distraction and overall HRQOL outcome

Still no convincing evidence for cognitive map use by honeybees

Cheeseman et al. (1) claim that an ability of honey bees to travel home through a landscape with conflicting information from a celestial compass proves the bees' use of a cognitive map. Their claim involves a curious assumption about the visual information that can be extracted from the terrain: that there is sufficient information for a bee to identify where it is, but insufficient to guide its path without resorting to a cognitive map. We contend that the authors’ claims are unfounded

Lateral Approach to the Lumbar Spine: The Utility of an Access Surgeon

BACKGROUND: Lateral lumbar interbody fusions (LLIFs) utilize a retroperitoneal approach that avoids the intraperitoneal organs and manipulation of the anterior vasculature encountered in anterior approaches to the lumbar spine. The approach was championed by spinal surgeons; however, general/vasculature surgeons may be more comfortable with the approach. OBJECTIVE: The objective of this study was to compare short-term outcomes following LLIF procedures based on whether a spine surgeon or access surgeon performed the approach. MATERIALS AND METHODS: We retrospectively identified all one- to two-level LLIFs at a tertiary care center from 2011 to 2021 for degenerative spine disease. Patients were divided into groups based on whether a spine surgeon or general surgeon performed the surgical approach. The electronic medical record was reviewed for hospital readmissions and complication rates. RESULTS: We identified 239 patients; of which 177 had approaches performed by spine surgeons and 62 by general surgeons. The spine surgeon group had fewer levels with posterior instrumentation (1.40 vs. 2.00; CONCLUSION: Similar outcomes may be seen regardless of whether a spine or access surgeon performs the approach for an LLIF