Bedrock fracture systems facilitate weathering, allowing fresh mineral surfaces to interact with corrosive waters and biota from Earth's surface, while simultaneously promoting drainage of chemically ...equilibrated fluids. We show that topographic perturbations to regional stress fields explain bedrock fracture distributions, as revealed by seismic velocity and electrical resistivity surveys from three landscapes. The base of the fracture-rich zone mirrors surface topography where the ratio of horizontal compressive tectonic stresses to near-surface gravitational stresses is relatively large, and it parallels the surface topography where the ratio is relatively small. Three-dimensional stress calculations predict these results, suggesting that tectonic stresses interact with topography to influence bedrock disaggregation, groundwater flow, chemical weathering, and the depth of the "critical zone" in which many biogeochemical processes occur.
Quercetin is a flavonol believed to have beneficial effects on human health. Rutin, found in many plants, fruits and vegetables, is metabolized by human intestinal bacteria and converted to ...quercetin, where it is absorbed through the intestinal epithelium. This study aimed to isolate and characterize human intestinal bacteria capable of converting rutin to quercetin. A bacterium that can metabolize rutin was isolated from human faecal samples and identified by 16S rRNA gene sequencing. The whole‐cell enzymatic activities on flavonoid glycoside and the conversion profiles of the isolate were also analysed. The bacterium was identified as Enterococcus avium EFEL009 and was shown to convert rutin to isoquercetin and then to quercetin under anaerobic conditions. Microscopic analysis revealed short chains of cocci with diameters of approx. 1 μm. β‐Glucosidase was shown to be constitutively expressed in Ent. avium, while α‐rhamnosidase was expressed following induction by rutin. Both enzymes were mainly localized to the cell surface. This study is the first report on the isolation of a quercetin‐producing Ent. avium FEEL009, which could be a potential industrial starter bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: Quercetin is a member of the flavonoids family reported to have better cytoprotective abilities, stronger inhibition of lipopolysaccharide‐induced nitric oxide production, and better chemoprevention than rutin. This is the first report on the isolation and characterization of Enterococcus avium EFEL009 from the human intestine which is capable of converting rutin to quercetin.
Anti‐drug antibodies (ADAs) can form with certain biological medications, but their clinical significance is not fully understood. ADA formation in psoriasis patients treated with IL‐23 inhibitors ...was evaluated, looking at the incidence of ADAs, impact on clinical outcomes and association with adverse events. A systematic search of PubMed, Cochrane and Embase databases yielded 318 articles, which were manually reviewed. A total of 19 articles met the eligibility criteria. The incidence of ADAs with the IL‐23 inhibitors was as follows: 4.1–14.7% with guselkumab, 141–31% with risankizumab and 6.51–18% with tildrakizumab. The incidence of neutralizing antibodies ranged from 01–0.6% with guselkumab, 21–16% with risankizumab and 2.5 to 3.2% with tildrakizumab. There was no evidence of reduced efficacy of psoriasis treatment with ADA presence alone. However, some studies found a reduction in clinical response with high ADA titres or with the presence of neutralizing antibodies. A few studies reported that patients with ADAs to guselkumab and risankizumab had a higher incidence of injection site reactions (ISRs). There do not appear to be other adverse events associated with ADAs with IL‐23 inhibitors. Testing for presence of ADAs alone in this patient group does not appear to be predictive of treatment response. Clinically, it may be more productive to test for neutralizing antibodies or ADA titre values, although further investigation is required to show a definitive correlation.
Abstract Productive arbovirus infections require mechanisms to suppress or circumvent the cellular RNA interference (RNAi) pathway, a major antiviral response in mosquitoes. In this study, we ...demonstrate that two flaviviruses, Dengue virus and Kunjin virus, significantly repress siRNA-mediated RNAi in infected human cells as well as during infection of the mosquito vector Culex quinquefasciatus . Arthropod-borne flaviviruses generate a small structured non-coding RNA from the viral 3′ UTR referred to as sfRNA. Analysis of infections with a mutant Kunjin virus that is unable to generate appreciable amounts of the major sfRNA species indicated that RNAi suppression was associated with the generation of the non-coding sfRNA. Co-immunoprecipitation of sfRNA with RNAi mediators Dicer and Ago2 suggest a model for RNAi suppression. Collectively, these data help to establish a clear role for sfRNA in RNAi suppression and adds to the emerging impact of viral long non-coding RNAs in modulating aspects of anti-viral immune processes.
To compare single estimations of fat-free mass (FFM) and to track FFM using single-frequency bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) compared with a ...four-compartment (4C) model in healthy elderly Americans.
Thirty-four men and thirty-eight women (Caucasian, ≥ 65 years) were included in the study. Subjects participated in either the control group or the exercise group. All testing and training took place during the 21-week investigation. Body composition assessments using nine BIA equations, DXA and a 4C model were performed during weeks 1, 12 and 24 of the study.
Single estimations for DXA and BIA produced high r values (0.79-0.95) and low standard error of estimate values (1.62-3.3 kg), producing subjective ratings of 'ideal' for men and 'excellent' for women. Both DXA and two BIA equations revealed the same significance when comparing groups and times with the 4C model. Individual accuracy for tracking changes was similar among BIA equations and DXA compared with the 4C model, with a total agreement of 25% for BIA and 27% for DXA compared with the 4C model.
The current data in combination with the reliability errors for both BIA and DXA FFM estimations suggest that individual results should be interpreted with caution if FFM changes are <5 kg. However, DXA and BIA are both valid methods that can be used interchangeably to estimate FFM at a single time point or for tracking changes in FFM in small groups (15-22) of healthy American older adults.
Summary Objective The prevalence of radiographic osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR) approaches 50%, yet the prevalence of significant knee pain is unknown. We ...applied three different models of Knee injury and Osteoarthritis Outcome Score (KOOS) thresholds for significant knee pain to an ACLR cohort to identify prevalence and risk factors. Design Multicenter Orthopaedic Outcomes Network (MOON) prospective cohort patients with a unilateral primary ACLR and normal contralateral knee were assessed at 2 and 6 years. Independent variables included patient demographics, validated Patient Reported Outcomes (PRO; Marx activity score, KOOS), and surgical characteristics. Models included: (1) KOOS criteria for a painful knee = quality of life subscale <87.5 and ≥2 of: KOOSpain <86.1, KOOSsymptoms <85.7, KOOSADL <86.8, or KOOSsports/rec <85.0; (2) KOOSpain subscale score ≤72 (≥2 standard deviations below population mean); (3) 10-point KOOSpain drop from 2 to 6 years. Proportional odds models (alpha ≤ 0.05) were used. Results 1761 patients of median age 23 years, median body mass index (BMI) 24.8 kg/m2 and 56% male met inclusion, with 87% (1530/1761) and 86% (1506/1761) follow-up at 2 and 6 years, respectively. At 6 years, n = 592 (39%), n = 131 (9%) and n = 169 (12%) met criteria for models #1 through #3, respectively. The most consistent and strongest independent risk factor at both time-points was subsequent ipsilateral knee surgery. Low 2-year Marx activity score increased the odds of a painful knee at 6 years. Conclusions Significant knee pain is prevalent after ACLR; with those who undergo subsequent ipsilateral surgery at greatest risk. The relationship between pain and structural OA warrants further study.
Adolescent marijuana use has become increasingly more problematic compared with the past; thus, understanding developmental processes that increase the liability of marijuana use is essential. Two ...developmental pathways to adolescent substance use have been proposed: an externalizing pathway that emphasizes the expression of aggressive and delinquent behavior, and an internalizing pathway that emphasizes the role of depressive symptoms and negative affect. In this study, we aimed to examine the synergistic role of impulsiveness and sensation seeking in the two risk pathways to determine whether both high and low levels of the traits are risk factors for marijuana use. Our study included 343 adolescents (52% were girls, 78% identified as Hispanic) that oversampled high-risk youth (78% had a family history of substance use disorder), assessed biannually between the ages of 13-16 years old. Moderated mediation analyses revealed that high levels of sensation seeking indirectly predicted marijuana use through higher mean levels of externalizing behavior. The positive relationship between sensation seeking and externalizing behavior was only significant at high levels of impulsiveness. Conversely, low levels of sensation seeking indirectly predicted marijuana use through higher mean levels of internalizing behavior. The negative relationship between sensation seeking and internalizing behavior was only significant at low levels of impulsiveness. Collectively, these results demonstrate that high and low levels of both impulsiveness and sensation seeking confer increased risk of marijuana use, albeit through different mechanisms.
Context.
The rotation state of small asteroids is affected by the Yarkovsky–O’Keefe–Radzievskii–Paddack (YORP) effect, which is a net torque caused by solar radiation directly reflected and thermally ...reemitted from the surface. Due to this effect, the rotation period slowly changes, which can be most easily measured in light curves because the shift in the rotation phase accumulates over time quadratically.
Aims.
By new photometric observations of selected near-Earth asteroids, we want to enlarge the sample of asteroids with a detected YORP effect.
Methods.
We collected archived light curves and carried out new photometric observations for asteroids (10115) 1992 SK, (1620) Geographos, and (1685) Toro. We applied the method of light curve inversion to fit observations with a convex shape model. The YORP effect was modeled as a linear change of the rotation frequency
υ
≡ d
ω
∕d
t
and optimized together with other spin and shape parameters.
Results.
We detected the acceleration
υ
= (8.3 ± 0.6) × 10
−8
rad d
−2
of the rotation for asteroid (10115) 1992 SK. This observed value agrees well with the theoretical value of YORP-induced spin-up computed for our shape and spin model. For (1685) Toro, we obtained
υ
= (3.3 ± 0.3) × 10
−9
rad d
−2
, which confirms an earlier tentative YORP detection. For (1620) Geographos, we confirmed the previously detected YORP acceleration and derived an updated value of
υ
with a smaller uncertainty. We also included the effect of solar precession into our inversion algorithm, and we show that there are hints of this effect in Geographos’ data.
Conclusions.
The detected change of the spin rate of (10115) 1992 SK has increased the total number of asteroids with YORP detection to ten. In all ten cases, the d
ω
∕d
t
value is positive, so the rotation of these asteroids is accelerated. It is unlikely to be just a statistical fluke, but it is probably a real feature that needs to be explained.
Several studies have shown physiological functions of interleukin (IL)-32, a novel cytokine. However, the role of IL-32 in cancer development has not been reported. In this study, we showed that ...IL-32γ inhibited tumor growth in IL-32γ-overexpressing transgenic mice inoculated with melanoma as well as colon tumor growth in xenograft nude mice inoculated with IL-32γ-transfected colon cancer cells (SW620). The inhibitory effect of IL-32γ on tumor growth was associated with the inhibition of constitutive activated nuclear transcription factor-κB (NF-κB) and of signal transducer and activator of transcription 3 (STAT3). The expression of antiapoptotic, cell proliferation and tumor-promoting genes (bcl-2, X-chromosome inhibitor of apoptosis protein (IAP), cellular IAP and cellular FADD-like IL-1β-converting enzyme-inhibitory protein, cyclin D), cyclin-dependent kinase 4, cycolooxygenase-2 and inducible nitric oxide synthase was decreased, whereas the expression of apoptotic target genes (caspase-3 and -9, bax) increased. In tumor, spleen and blood, the number of cytotoxic CD8(+) T cells and CD57(+) natural killer cells and the levels of IL-10 increased, but that of tumor necrosis factor-α (TNF-α), IL-1β and IL-6 decreased. We also found that forced overexpression of IL-32γ inhibited colon cancer cell (SW620 and HCT116) growth accompanied with the inhibition of activated NF-κB and STAT3 in vitro. In addition, when IL-32γ was knocked down by small interfering RNA (siRNA) or neutralized with an anti-IL-32γ antibody, IL-32γ-induced colon cancer cell growth inhibition, the IL-32γ-induced decrease of TNF-α, IL-1 and IL-6 production, and the increase of IL-10 production were abolished. However, siRNA of NF-κB and STAT3 augmented IL-32γ-induced colon cancer cell growth inhibition. These findings indicate significant pathophysiological roles of IL-32γ in cancer development.
We demonstrate that both Hepatitis C virus (HCV) and Bovine Viral Diarrhea virus (BVDV) contain regions in their 5' UTRs that stall and repress the enzymatic activity of the cellular 5'-3' ...exoribonuclease XRN1, resulting in dramatic changes in the stability of cellular mRNAs. We used biochemical assays, virus infections, and transfection of the HCV and BVDV 5' untranslated regions in the absence of other viral gene products to directly demonstrate the existence and mechanism of this novel host-virus interaction. In the context of HCV infection, we observed globally increased stability of mRNAs resulting in significant increases in abundance of normally short-lived mRNAs encoding a variety of relevant oncogenes and angiogenesis factors. These findings suggest that non-coding regions from multiple genera of the Flaviviridae interfere with XRN1 and impact post-transcriptional processes, causing global dysregulation of cellular gene expression which may promote cell growth and pathogenesis.
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