Fighting misinformation in seismology: Expert opinion on earthquake facts vs. fiction

Misinformation carries the potential for immense damage to public understanding of science and for evidence-based decision making at an individual and policy level. Our research explores the following questions within seismology: which claims can be considered misinformation, which are supported by a consensus, and which are still under scientific debate? Consensus and debate are important to quantify, because where levels of scientific consensus on an issue are high, communication of this fact may itself serve as a useful tool in combating misinformation. This is a challenge for earthquake science, where certain theories and facts in seismology are still being established. The present study collates a list of common public statements about earthquakes and provides–to the best of our knowledge–the first elicitation of the opinions of 164 earth scientists on the degree of verity of these statements. The results provide important insights for the state of knowledge in the field, helping identify those areas where consensus messaging may aid in the fight against earthquake related misinformation and areas where there is currently lack of consensus opinion. We highlight the necessity of using clear, accessible, jargon-free statements with specified parameters and precise wording when communicating with the public about earthquakes, as well as of transparency about the uncertainties around some issues in seismology

Commercial pecan insect and disease control

The Oklahoma Cooperative Extension Service periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311

Analysis of a Putative Promoter in Mycobacteriophage JacoRen57

JacoRen57 is a cluster AB mycobacteriophage that infects Mycobacterium smegmatis mc²155. We recently reported on the characterization of a putative promoter in JacoRen57 using an mCherry reporter construct. This promoter is present in a gap upstream of a gene that is present in all AB phages. In all cases, these are forward genes immediately following a long series of reverse genes. The genes are most frequently identified as a RecA-like DNA recombinases but also as RepA by bioinformatics. To further analyze this putative promoter and gene product, NWC Molecular Genetics students cloned the RecA-like DNA recombinase into an E. coli expression vector with a TVMV removable N-terminal His-tag. They expressed and we purified the tagged protein and are using it to immunize Balb/c mice. We plan to use the antiserum to confirm RecA-like DNA recombinase expression patterns when JacoRen57 infects M. smegmatis

The effect of a C298D mutation in CaHydA [FeFe]-hydrogenase: Insights into the protein-metal cluster interaction by EPR and FTIR spectroscopic investigation

AbstractA conserved cysteine located in the signature motif of the catalytic center (H-cluster) of [FeFe]-hydrogenases functions in proton transfer. This residue corresponds to C298 in Clostridium acetobutylicum CaHydA. Despite the chemical and structural difference, the mutant C298D retains fast catalytic activity, while replacement with any other amino acid causes significant activity loss. Given the proximity of C298 to the H-cluster, the effect of the C298D mutation on the catalytic center was studied by continuous wave (CW) and pulse electron paramagnetic resonance (EPR) and by Fourier transform infrared (FTIR) spectroscopies.Comparison of the C298D mutant with the wild type CaHydA by CW and pulse EPR showed that the electronic structure of the center is not altered. FTIR spectroscopy confirmed that absorption peak values observed in the mutant are virtually identical to those observed in the wild type, indicating that the H-cluster is not generally affected by the mutation. Significant differences were observed only in the inhibited state Hox–CO: the vibrational modes assigned to the COexo and Fed-CO in this state are shifted to lower values in C298D, suggesting different interaction of these ligands with the protein moiety when C298 is changed to D298. More relevant to the catalytic cycle, the redox equilibrium between the Hox and Hred states is modified by the mutation, causing a prevalence of the oxidized state.This work highlights how the interactions between the protein environment and the H-cluster, a dynamic closely interconnected system, can be engineered and studied in the perspective of designing bio-inspired catalysts and mimics

Increased insulin sensitivity and diminished pancreatic beta-cell function in DNA repair deficient Ercc1(d/-) mice

Background: Type 2 diabetes (T2DM) is an age-associated disease characterized by hyperglycemia due to insulin resistance and decreased beta-cell function. DNA damage accumulation has been associated with T2DM, but whether DNA damage plays a role in the pathogenesis of the disease is unclear. Here, we used mice deficient for the DNA excision-repair gene Ercc1 to study the impact of persistent endogenous DNA damage accumulation on energy metabolism, glucose homeostasis and beta-cell function. Methods: ERCC1-XPF is an endonuclease required for multiple DNA repair pathways and reduced expression of ERCC1-XPF causes accelerated accumulation of unrepaired endogenous DNA damage and accelerated aging in humans andmice. In this study, energy metabolism, glucose metabolism, beta-cell function and insulin sensitivity were studied in Ercc1(d/-) mice, which model a human progeroid syndrome. Results: Ercc1(d/-) mice displayed suppression of the somatotropic axis and altered energy metabolism. Insulin sensitivitywas increased, whereas, plasma insulin levelswere decreased in Ercc1(d/-) mice. Fasting induced hypoglycemia in Ercc1(d/-) mice, whichwas the result of increased glucose disposal. Ercc1(d/-) mice exhibit a significantly reduced beta-cell area, even compared to control mice of similar weight. Glucose-stimulated insulin secretion in vivo was decreased in Ercc1(d/-) mice. Islets isolated from Ercc1(d/-) mice showed increased DNA damage markers, decreased glucose-stimulated insulin secretion and increased susceptibility to apoptosis. Conclusion: Spontaneous DNA damage accumulation triggers an adaptive response resulting in improved insulin sensitivity. Loss of DNA repair, however, does negatively impacts beta-cell survival and function in Ercc1(d/-) mice. (C) 2021 The Author(s). Published by Elsevier Inc

Formate induces a metabolic switch in nucleotide and energy metabolism

Formate is a precursor for the de novo synthesis of purine and deoxythymidine nucleotides. Formate also interacts with energy metabolism by promoting the synthesis of adenine nucleotides. Here we use theoretical modelling together with metabolomics analysis to investigate the link between formate, nucleotide and energy metabolism. We uncover that endogenous or exogenous formate induces a metabolic switch from low to high adenine nucleotide levels, increasing the rate of glycolysis and repressing the AMPK activity. Formate also induces an increase in the pyrimidine precursor orotate and the urea cycle intermediate argininosuccinate, in agreement with the ATP-dependent activities of carbamoyl-phosphate and argininosuccinate synthetase. In vivo data for mouse and human cancers confirms the association between increased formate production, nucleotide and energy metabolism. Finally, the in vitro observations are recapitulated in mice following and intraperitoneal injection of formate. We conclude that formate is a potent regulator of purine, pyrimidine and energy metabolism

Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer

Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown. Here we report a novel method for digital quantitative analyses of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC). Initial analyses identified marker-defined subsets of PC, including cells expressing PDGFR-beta or alpha-SMA or both markers. PC subsets were largely independently expressed in a manner unrelated to vessel density and size. Association studies implied specific oncogenic mutations in malignant cells as determinants of PC status. Semi-quantitative and digital-image-analyses-based scoring of the NORDIC-VII cohort identified significant associations between low expression of perivascular PDGFR-alpha and -beta and shorter overall survival. Analyses of the SPCRC cohort confirmed these findings. Perivascular PDGFR-alpha and -beta remained independent factors for survival in multivariate analyses. Overall, our study identified host vasculature and oncogenic status as determinants of tumor perivascular features. Perivascular PDGFR-alpha and -beta were identified as novel independent markers predicting survival in mCRC. The novel methodology should be suitable for similar analyses in other tumor collections

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio

Intensity standardization methods in magnetic resonance imaging of head and neck cancer

BACKGROUND AND PURPOSE: Conventional magnetic resonance imaging (MRI) poses challenges in quantitative analysis because voxel intensity values lack physical meaning. While intensity standardization methods exist, their effects on head and neck MRI have not been investigated. We developed a workflow based on healthy tissue region of interest (ROI) analysis to determine intensity consistency within a patient cohort. Through this workflow, we systematically evaluated intensity standardization methods for MRI of head and neck cancer (HNC) patients.MATERIALS AND METHODS: Two HNC cohorts (30 patients total) were retrospectively analyzed. One cohort was imaged with heterogenous acquisition parameters (HET cohort), whereas the other was imaged with homogenous acquisition parameters (HOM cohort). The standard deviation of cohort-level normalized mean intensity (SD NMI c), a metric of intensity consistency, was calculated across ROIs to determine the effect of five intensity standardization methods on T2-weighted images. For each cohort, a Friedman test followed by a post-hoc Bonferroni-corrected Wilcoxon signed-rank test was conducted to compare SD NMI c among methods. RESULTS: Consistency (SD NMI c across ROIs) between unstandardized images was substantially more impaired in the HET cohort (0.29 ± 0.08) than in the HOM cohort (0.15 ± 0.03). Consequently, corrected p-values for intensity standardization methods with lower SD NMI c compared to unstandardized images were significant in the HET cohort (p &lt; 0.05) but not significant in the HOM cohort (p &gt; 0.05). In both cohorts, differences between methods were often minimal and nonsignificant. CONCLUSIONS: Our findings stress the importance of intensity standardization, either through the utilization of uniform acquisition parameters or specific intensity standardization methods, and the need for testing intensity consistency before performing quantitative analysis of HNC MRI.</p

Colorectal tumors require NUAK1 for protection from oxidative stress

The authors wish to thank the staff of the CRUK Beatson Institute Biological Services Unit for animal husbandry and assistance with in vivo experiments; the staff of the CRUK BI Histology core facility and William Clark of the NGS core facility; David McGarry, Rene Jackstadt, Jiska Van der Reest, Justin Bower and Heather McKinnon for many helpful discussions, and countless colleagues at the CRUK BI and Glasgow Institute of Cancer Sciences for support; Prem Premsrirut & Mirimus Inc. for design and generation of dox-inducible Nuak1 shRNA expressing mice Nathanael Gray for initial provision of NUAK1 inhibitors. Funding was provided by the University of Glasgow and the CRUK Beaton Institute. J.P. was supported by European Commission Marie Curie actions C.I.G. 618448 “SERPLUC” to D.J.M.; N.M. was supported through Worldwide Cancer (formerly AICR) grant 15-0279 to O.J.S. & D.J.M.; B.K. was funded through EC Marie Curie actions mobility award 705190 “NuSiCC”; T.M. was funded through British Lung Foundation grant APHD13-5. The laboratories of S.R.Z. (A12935), O.J.S. (A21139) and M.D. (A17096) are funded by Cancer Research UK. O.J.S. was additionally supported by European Research Council grant 311301 “ColoCan”.Peer reviewedPostprin