MicroRNA 497 modulates interleukin 1 signalling via the MAPK/ERK pathway

AbstractThe MAPK/ERK signalling pathway has been described to mediate IL-1 induction of target genes and is known to be regulated by microRNAs (miRNA). We describe a novel miRNA regulating the expression of the MEK1 gene and how it impacts IL-1 induced IL-6 transcription. miR-497 was predicted to target MEK1 3′UTR using bioinformatic tools. Transfection of miR-497 into HeLa cells inhibited MEK1 protein expression by 50%. In transient transfection experiments, the luciferase activity of a MEK1 3′UTR luciferase reporter construct was reduced in the presence of miR-497, and mutation of the predicted miR-497 binding site restored activity. miR-497 also decreased protein levels of RAF1 and ERK1 but not ERK2. Addition of miR-497 was further shown to inhibit IL-1 induced IL-6 gene transcription

Modeling reverberation mapping data II: dynamical modeling of the Lick AGN Monitoring Project 2008 dataset

We present dynamical modeling of the broad line region (BLR) for a sample of five Seyfert 1 galaxies using reverberation mapping data taken by the Lick AGN Monitoring Project in 2008. By modeling the AGN continuum light curve and H$\beta$ line profiles directly we are able to constrain the geometry and kinematics of the BLR and make a measurement of the black hole mass that does not depend upon the virial factor, $f$, needed in traditional reverberation mapping analysis. We find that the geometry of the BLR is generally a thick disk viewed close to face-on. While the H$\beta$ emission is found to come preferentially from the far side of the BLR, the mean size of the BLR is consistent with the lags measured with cross-correlation analysis. The BLR kinematics are found to be consistent with either inflowing motions or elliptical orbits, often with some combination of the two. We measure black hole masses of $\log_{10}(M_{\rm\,BH}/M_\odot)=6.62^{+0.10}_{-0.13}$ for Arp 151, $7.42^{+0.26}_{-0.27}$ for Mrk 1310, $7.51^{+0.23}_{-0.14}$ for NGC 5548, $6.42^{+0.24}_{-0.18}$ for NGC 6814, and $6.99^{+0.32}_{-0.25}$ for SBS 1116+583A. The $f$ factors measured individually for each AGN are found to correlate with inclination angle, although not with $M_{\rm\,BH}$, $L_{5100}$, or FWHM/$\sigma$ of the emission line profile.Comment: 21 pages, 24 figures, 3 tables, Accepted for publication in MNRAS, corrected masses for NGC 5548 and NGC 6814 in the abstrac

Providing Food Assistance in a Pandemic: Views and Lessons Learned from the Frontlines in Northwest Mississippi

The Center for Population Studies (CPS) at the University of Mississippi (UM) has partnered with the Maddox Foundation (Hernando, MS) and the Community Foundation of Northwest Mississippi (CFNM) to explore changes in communities across an 11-county region as a way to identify funding priorities designed to address challenges and build upon assets in the region. With a grant from the Maddox Foundation, the CFNM launched FEED Northwest Mississippi to provide emergency funding for area food pantries, especially ones located in rural areas (CFNM 2020). This initiative has now expanded with a host of additional contributors to the FEED Fund. Results of research involving the food pantries and similar organizations will inform additional funding priorities of Maddox and the CFNM in response to the impacts of COVID-19 on individuals, families, and their communities

Extensive Dental Caries in Patients with Oral Chronic Graft-versus-Host Disease

The oral cavity is one of the sites most frequently affected by chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (alloHCT) and can be a significant source of patient morbidity due to both mucosal and salivary gland involvement. The development of dental decay is a potentially devastating oral complication that has only rarely been reported in the transplantation literature. The purpose of this study was to comprehensively characterize a cohort of patients with cGVHD who subsequently developed extensive dental caries. A retrospective case-record review was conducted for patients who had undergone alloHCT at Dana-Farber/Brigham and Women's Cancer Center between 1990 and 2010 and developed cGVHD-associated rampant dental decay. All patients underwent dental evaluation, involving soft and hard tissue examination and dental radiography, before and after alloHCT. Any dental caries diagnosed at the pre-alloHCT evaluation were treated definitively, such that all patients were considered free of caries at the time of admission for alloHCT. A total of 21 patients were identified, with a median time of cGVHD onset of 5.4 months (range, 2.2-18.5 months) after alloHCT. All patients were diagnosed with oral cGVHD, with 90% demonstrating mucosal involvement and 95% demonstrating salivary gland involvement. Post-alloHCT dental evaluation was performed at a median of 22 months (range, 4-81) after alloHCT, when 10 patients were diagnosed with gross caries and 8 patients had 4 or more affected teeth. Cervical and interproximal patterns of dental caries were frequently diagnosed. The proportions of patients with gross caries, one surface caries, and more than one surface caries (classified as 0, 1-3, and ≥4, respectively) were significantly higher after alloHCT than before alloHCT, with at least 50% of patients experiencing an increase. Patients with oral cGVHD who were free of caries at the time of transplantation developed extensive areas of cervical decay at a median of less than 2 years after alloHCT. This is the first comprehensive characterization of this severe late complication of alloHCT and oral cGVHD. Greater awareness by transplantation oncologists and dentists, as well as more aggressive preventive measures, are needed, as are further prospective studies to better elucidate the incidence of this complication, identify risk factors, and evaluate the effectiveness of preventive interventions

Genetic association with articular damage in patients with juvenile idiopathic arthritis (JIA)

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Calcium-mediated perception and defense responses activated in plant cells by metabolite mixtures secreted by the biocontrol fungus Trichoderma atroviride

<p>Abstract</p> <p>Background</p> <p>Calcium is commonly involved as intracellular messenger in the transduction by plants of a wide range of biotic stimuli, including signals from pathogenic and symbiotic fungi. <it>Trichoderma </it>spp. are largely used in the biological control of plant diseases caused by fungal phytopathogens and are able to colonize plant roots. Early molecular events underlying their association with plants are relatively unknown.</p> <p>Results</p> <p>Here, we investigated the effects on plant cells of metabolite complexes secreted by <it>Trichoderma atroviride </it>wild type P1 and a deletion mutant of this strain on the level of cytosolic free Ca²⁺and activation of defense responses. <it>Trichoderma </it>culture filtrates were obtained by growing the fungus alone or in direct antagonism with its fungal host, the necrotrophic pathogen <it>Botrytis cinerea</it>, and then separated in two fractions (>3 and <3 kDa). When applied to aequorin-expressing soybean (<it>Glycine max </it>L.) cell suspension cultures, <it>Trichoderma </it>and <it>Botrytis </it>metabolite mixtures were distinctively perceived and activated transient intracellular Ca²⁺elevations with different kinetics, specific patterns of intracellular accumulation of reactive oxygen species and induction of cell death. Both Ca²⁺signature and cellular effects were modified by the culture medium from the knock-out mutant of <it>Trichoderma</it>, defective for the production of the secreted 42 kDa endochitinase.</p> <p>Conclusion</p> <p>New insights are provided into the mechanism of interaction between <it>Trichoderma </it>and plants, indicating that secreted fungal molecules are sensed by plant cells through intracellular Ca²⁺changes. Plant cells are able to discriminate signals originating in the single or two-fungal partner interaction and modulate defense responses.</p