A fundamental question that applies to all organisms is how barrier epithelia efficiently manage continuous contact with microorganisms. Here, we show that in
Drosophila an extracellular ...immune-regulated catalase (IRC) mediates a key host defense system that is needed during host-microbe interaction in the gastrointestinal tract. Strikingly, adult flies with severely reduced IRC expression show high mortality rates even after simple ingestion of microbe-contaminated foods. However, despite the central role that the NF-κB pathway plays in eliciting antimicrobial responses, NF-κB pathway mutant flies are totally resistant to such infections. These results imply that homeostasis of redox balance by IRC is one of the most critical factors affecting host survival during continuous host-microbe interaction in the gastrointestinal tract.
Objectives
Dietary fiber intake is associated with a lower risk of diabetes, cardiovascular disease, and cancer. However, it is unknown whether dietary fiber has a beneficial effect on preventing the ...development of chronic kidney disease (CKD).
Design, Setting, Participants and Measurements
Using the UK Biobank prospective cohort, 110,412 participants who completed at least one dietary questionnaire and had an estimated glomerular filtration rate ≥60 mL/min/1.73 m
2
, urinary albumin-to-creatinine ratio <30 mg/g, and no history of CKD were included. The primary exposure was total dietary fiber density, calculated by dividing the absolute amount of daily total fiber intake by total energy intake (g/1,000 kcal). We separately examined soluble and insoluble fiber densities as additional predictors. The primary outcome was incident CKD based on diagnosis codes.
Results
A total of 3,507 (3.2%) participants developed incident CKD during a median follow-up of 9.9 years. In a multivariable cause-specific model, the adjusted hazard ratios (aHRs; 95% confidence intervals CIs) for incident CKD were 0.85 (0.77–0.94), 0.78 (0.70–0.86), and 0.76 (0.68–0.86), respectively, for the second, third, and highest quartiles of dietary fiber density (reference: lowest quartile). In a continuous model, the aHR for each +Δ1.0g/1,000 kcal increase in dietary fiber density was 0.97 (95% CI, 0.95–0.99). This pattern of associations was similar for both soluble and insoluble fiber densities and did not differ across subgroups of sex, age, body mass index, hypertension, diabetes, smoking, and inflammation.
Conclusion
Increased fiber intake was associated with a lower risk of CKD in this large well-characterized cohort.
The two endonucleases, Rad27 (yeast Fen1) and Dna2, jointly participate in the processing of Okazaki fragments in yeasts. Mus81-Mms4 is a structure-specific endonuclease that can resolve stalled ...replication forks as well as toxic recombination intermediates. In this study, we show that Mus81-Mms4 can suppress dna2 mutational defects by virtue of its functional and physical interaction with Rad27. Mus81-Mms4 stimulated Rad27 activity significantly, accounting for its ability to restore the growth defects caused by the dna2 mutation. Interestingly, Rad27 stimulated the rate of Mus81-Mms4 catalyzed cleavage of various substrates, including regressed replication fork substrates. The ability of Rad27 to stimulate Mus81-Mms4 did not depend on the catalytic activity of Rad27, but required the C-terminal 64 amino acid fragment of Rad27. This indicates that the stimulation was mediated by a specific protein-protein interaction between the two proteins. Our in vitro data indicate that Mus81-Mms4 and Rad27 act together during DNA replication and resolve various structures that can impede normal DNA replication. This conclusion was further strengthened by the fact that rad27 mus81 or rad27 mms4 double mutants were synergistically lethal. We discuss the significance of the interactions between Rad27, Dna2 and Mus81-Mms4 in context of DNA replication.
South Korea has one of the highest suicide rates in the world, and the most alarming suicide rate is among its elders. This study aims to understand the social, historical, and cultural context of ...the Korean older adults and examine suicide trends based on that understanding. The results show that the suicide risk increases with age, the male suicide rate outweighs that of females, and the suicide rate decreases with educational attainment. In addition, several suggestions for reducing elderly suicide rate are addressed, including differentiating the existing social services for elders by age and expanding suicide prevention programs beyond schools to communities so that all people in need can access them.
Aim
We aimed to isolate and propagate internal and external anal sphincter progenitor cells from the human anal sphincter, with or without radiotherapy, for tailored cell therapy of faecal ...incontinence.
Methods
Sphincter progenitor cells were isolated from normal internal and external anal sphincters collected from 10 patients with rectal cancer who had undergone abdominoperineal resection with (n = 6) or without (n = 4) preoperative chemoradiotherapy. The isolated cells and differentiated muscle fibres were identified using immunofluorescence assay, western blotting and reverse transcription polymerase chain reaction (RT‐PCR). The proliferation of progenitor cells with and without radiotherapy was compared by quantitative 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay.
Results
The immunofluorescence assay before differentiation confirmed that the internal anal sphincter progenitor cells expressed CD34 and neural‐glial antigen 2 (NG2), whereas the external anal sphincter progenitor cells expressed CD34 and PAX7. After differentiation, the internal anal sphincter progenitor cells expressed desmin, calponin and α‐smooth muscle actin, whereas the external anal sphincter progenitor cells expressed desmin, myogenic factor 4 and myosin heavy chain. The differential expression profiles of both cell types were confirmed by western blotting and RT‐PCR. MTT assays showed that the viability of internal and external anal sphincter progenitor cells was significantly lower in the radiotherapy group than that in the nonradiotherapy group.
Conclusions
This study describes the differential harvest internal and external sphincter muscle progenitor cells from human anal sphincters. We confirm that radiotherapy decreases the viability of internal and external anal sphincter progenitor cells.
ABSTRACT We describe directed searches for continuous gravitational waves (GWs) in data from the sixth Laser Interferometer Gravitational-wave Observatory (LIGO) science data run. The targets were ...nine young supernova remnants not associated with pulsars; eight of the remnants are associated with non-pulsing suspected neutron stars. One target's parameters are uncertain enough to warrant two searches, for a total of 10. Each search covered a broad band of frequencies and first and second frequency derivatives for a fixed sky direction. The searches coherently integrated data from the two LIGO interferometers over time spans from 5.3-25.3 days using the matched-filtering -statistic. We found no evidence of GW signals. We set 95% confidence upper limits as strong (low) as 4 × 10−25 on intrinsic strain, 2 × 10−7 on fiducial ellipticity, and 4 × 10−5 on r-mode amplitude. These beat the indirect limits from energy conservation and are within the range of theoretical predictions for neutron-star ellipticities and r-mode amplitudes.
The objective of this study was to assess the lake sediment budget of land use changes using the Universal Soil Loss Equation (USLE), sediment delivery ratio (SDR), and trap efficiency (TE). The ...geographic information system was combined with the USLE to estimate the soil erosion of the Lake Asan watershed. Spatial data for each of the USLE factors were obtained from the land use, soil, and 1/25,000 scale digital contour maps. Landsat-5 TM images were selected for analyzing soil erosion changes due to land use changes. The sediment yield to Lake Asan was estimated using the SDR and TE. The estimated sediment budget was compared with observed data from the Lake Asan watershed between 1974 and 2003. The total estimated annual mean sediment budgets from Lake Asan in 1986, 1992, and 2000 were 0.267, 0.301, and 0.339 × 10⁶ ton, respectively, with an average of 0.302 × 10⁶ ton. The average measured sediment budget was 3.15 × 10⁶ ton year⁻¹. The average estimated value shows reasonable agreement with the observed sediment balance. The average estimated and measured sediment budgets contain uncertainties due to both the methods and the approach used by the observers. The simulated results indicated that soil erosion in the Lake Asan watershed increased at a rate of approximately 2 % per year from 1986 to 2000 due to land use change. This study may be useful for managers to identify reservoir rehabilitation management methods for stable irrigation water supply.
Background. Previous studies have demonstrated that AST-120 (Kremezin®), a well-known oral adsorbent, inhibits the progression of diabetic (DM) and non-DM chronic kidney disease along with a decrease ...in oxidative stress. This study was undertaken to investigate whether AST-120 could reduce oxidative stress and ameliorate the development of nephropathy in experimental DM rats with normal renal function. Methods. Rats were injected with diluent (C, n = 16) or 65 mg/kg streptozotocin intraperitoneally (DM, n = 16), and eight rats from each group were treated with chow containing 5% AST-120. After 3 months, plasma advanced oxidation protein products (AOPP) and total malondialdehyde (MDA) levels, 24-h urinary albumin excretion, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) excretion were determined by ELISA. Glomerular endothelial nitric oxide synthase (eNOS), subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91phox, p47phox and p22phox), and fibronectin (FN) mRNA and protein expressions were determined by real-time PCR and western blot, respectively. In addition, dichlorodihydrofluorescein diacetate (DCF-DA) staining was performed to detect glomerular reactive oxygen species (ROS) production. Results. Compared to the C group, 24-h urinary albumin excretion was significantly higher in the DM group (P < 0.01), and AST-120 treatment significantly reduced albuminuria in DM rats (P < 0.05). Glomerular eNOS, gp91phox, p47phox and FN expression were significantly increased in DM rats compared to C rats, and these increases in DM glomeruli were significantly abrogated by AST-120 treatment (P < 0.05). The increases in plasma AOPP and MDA levels as well as renal oxidative stress in DM rats, assessed by DCF-DA staining and urinary 8-OHdG excretion rates, were also significantly attenuated by AST-120 treatment (P < 0.05). Conclusion. In conclusion, the renoprotective effects of AST-120 in DM nephropathy seem to be associated with the amelioration of enhanced oxidative stress and FN expression under diabetic conditions.
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