Remodeling of the Tight Junction During Recovery from Exposure to Hydrogen Peroxide in Kidney Epithelial Cells

Renal ischemia-reperfusion injury results in oxidative stress-induced alterations in barrier function. Activation of the mitogen-activated protein (MAP) kinase pathway during recovery from oxidative stress may be an effector of oxidant-induced tight junction reorganization. We hypothesized that tight junction composition and barrier function would be perturbed during recovery from oxidative stress. We developed a model of short-term H2O2 exposure followed by recovery using Madin Darby canine kidney (MDCK II) cells. H2O2 perturbs barrier function without a significant cytotoxic effect except in significant doses. ERK-1/2 and p38, both enzymes of the MAP kinase pathway, were activated within minutes of exposure to H2O2. Transient exposure to H2O2 produced a biphasic response in the transepithelial electrical resistance (TER). An initial drop in TER at 6 h was followed by a significant increase at 24 h. Inhibition of ERK-1/2 activation attenuated the increase in TER observed at 24 h. Expression of occludin initially decreased, followed by partial recovery at 24 h. In contrast, claudin-1 levels decreased and failed to recover at 24 h. Claudin-2 levels were markedly decreased at 24 h; however, inhibition of ERK-1/2 activation was protective. Occludin and claudin-1 localization at the apical membrane on immunofluorescence images was fragmented at 6 h after H2O2 exposure with subsequent recovery of appropriate localization by 24 h. MDCK II cell recovery after H2O2 exposure is associated with functional and structural modifications of the tight junction that are mediated in part by activation of the MAP kinase enzymes ERK-1/2 and p38

Utility of echocardiography in predicting mortality in infants with severe bronchopulmonary dysplasia

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objective: To determine the relationship between interventricular septal position (SP) and right ventricular systolic pressure (RVSP) and mortality in infants with severe BPD (sBPD). Study design: Infants with sBPD in the Children's Hospitals Neonatal Database who had echocardiograms 34-44 weeks' postmenstrual age (PMA) were included. SP and RVSP were categorized normal, abnormal (flattened/bowed SP or RVSP > 40 mmHg) or missing. Results: Of 1157 infants, 115 infants (10%) died. Abnormal SP or RVSP increased mortality (SP 19% vs. 8% normal/missing, RVSP 20% vs. 9% normal/missing, both p < 0.01) in unadjusted and multivariable models, adjusted for significant covariates (SP OR 1.9, 95% CI 1.2-3.0; RVSP OR 2.2, 95% CI 1.1-4.7). Abnormal parameters had high specificity (SP 82%; RVSP 94%), and negative predictive value (SP 94%, NPV 91%) for mortality. Conclusions: Abnormal SP or RVSP is independently associated with mortality in sBPD infants. Negative predictive values distinguish infants most likely to survive

A Nitrile Hydratase in the Eukaryote Monosiga brevicollis

Bacterial nitrile hydratase (NHases) are important industrial catalysts and waste water remediation tools. In a global computational screening of conventional and metagenomic sequence data for NHases, we detected the two usually separated NHase subunits fused in one protein of the choanoflagellate Monosiga brevicollis, a recently sequenced unicellular model organism from the closest sister group of Metazoa. This is the first time that an NHase is found in eukaryotes and the first time it is observed as a fusion protein. The presence of an intron, subunit fusion and expressed sequence tags covering parts of the gene exclude contamination and suggest a functional gene. Phylogenetic analyses and genomic context imply a probable ancient horizontal gene transfer (HGT) from proteobacteria. The newly discovered NHase might open biotechnological routes due to its unconventional structure, its new type of host and its apparent integration into eukaryotic protein networks

Contourite depositional system after the exit of a strait: Case study from the late Miocene South Rifian Corridor, Morocco

Idealized facies of bottom current deposits (contourites) have been established for fine-grained contourite drifts in modern deep-marine sedimentary environments. Their equivalent facies in the ancient record however are only scarcely recognized due to the weathered nature of most fine-grained deposits in outcrop. Facies related to the erosional elements (i.e. contourite channels) of contourite depositional systems have not yet been properly established and related deposits in outcrop appear non-existent. To better understand the sedimentary facies and facies sequences of contourites, the upper Miocene contourite depositional systems of the South Rifian Corridor (Morocco) is investigated. This contourite depositional system formed by the dense palaeo-Mediterranean Outflow Water. Foraminifera assemblages were used for age-constraints (7.51 to 7.35 Ma) and to determine the continental slope depositional domains. Nine sedimentary facies have been recognized based on lithology, grain-size, sedimentary structures and biogenic structures. These facies were subsequently grouped into five facies associations related to the main interpreted depositional processes (hemipelagic settling, contour currents and gravity flows). The vertical sedimentary facies succession records the tectonically induced, southward migration of the contourite depositional systems and the intermittent behaviour of the palaeo-Mediterranean Outflow Water, which is mainly driven by precession and millennial-scale climate variations. Tides substantially modulated the palaeo-Mediterranean Outflow Water on a sub-annual scale. This work shows exceptional examples of muddy and sandy contourite deposits in outcrop by which a facies distribution model from the proximal continental slope, the contourite channel to its adjacent contourite drift, is proposed. This model serves as a reference for contourite recognition both in modern environments and the ancient record. Furthermore, by establishing the hydrodynamics of overflow behaviour a framework is provided that improves process-based interpretation of deep-water bottom current deposits

Utilization of chlorobenzoates by microbial populations in sewage.

Microorganisms in sewage decomposed 3.4-dichlorobenzoate and m-, p-, and o-chlorobenzoates. As the substrate disappeared, populations capable of growing on these compounds proliferated. Neither 2,4-dichlorobenzoate nor 2,3,6-trichlorobenzoate was destroyed by the sewage microflora. The addition of glucose or benzoate and m-chlorobenzoate to the sewage did not promote degradation of 2,4-di- or 2,3,6-trichlorobenzoates. The populations responsible for the biodegradation of the chlorinated compounds were initially less than 100 cells/ml. During the metabolism of m-chlorobenzoate, 5-chlorosalicylate and 4-chlorocatechol were formed

Can a Risk Factor Based Approach Safely Reduce Screening for Retinopathy of Prematurity?

Objective. Current American retinopathy of prematurity (ROP) screening guidelines is imprecise for infants ≥ 30 weeks with birth weights between 1500 and 2000 g. Our objective was to evaluate a risk factor based approach for screening premature infants at low risk for severe ROP. Study Design. We performed a 13-year review from Intermountain Health Care (IHC) data. All neonates born at ≤32 weeks were reviewed to determine ROP screening and/or development of severe ROP. Severe ROP was defined by stage ≥ 3 or need for laser therapy. Regression analysis was used to identify significant risk factors for severe ROP. Results. We identified 4607 neonates ≤ 32 weeks gestation. Following exclusion for death, with no retinal exam or incomplete data, 2791 (61%) were included in the study. Overall, severe ROP occurred in 260 (9.3%), but only 11/1601 ≥ 29 weeks (0.7%). All infants with severe ROP ≥ 29 weeks had at least 2 identified ROP risk factors. Implementation of this risk based screening strategy to the IHC population over the timeline of this study would have eliminated screening in 21% (343/1601) of the screened population. Conclusions. Limiting ROP screening for infants ≥ 29 and ≤ 32 weeks to only those with clinical risk factors could significantly reduce screening exams while identifying all infants with severe ROP

Assessment of Blood Lead, Zinc, and Mercury Concentrations and Cholinesterase Activity in Captive-reared Alligator Snapping Turtles ( Macrochelys temminckii) in Louisiana, USA

The alligator snapping turtle ( Macrochelys temminckii) is a freshwater apex predator that has experienced severe population declines throughout its range due to historical overharvesting and habitat degradation. Because of its long lifespan, high trophic level, and limited home range, it is a suitable sentinel species for monitoring environmental contaminants. In Louisiana, US a pilot program aims to augment free-ranging populations by releasing captive-reared individuals. Baseline values of potential environmental contaminants were determined as part of an overall health assessment to evaluate captive-reared alligator snapping turtles for release. Blood samples from 3-yr-old ( n=23) and 4-yr-old ( n=11) captive-reared alligator snapping turtles were tested for lead (Pb), mercury (Hg), and zinc (Zn) levels by atomic absorption spectrophotometry and cholinesterase (ChE) activity (as a biomarker for organophosphate and carbamate exposure) by the modified Ellman method. Reference intervals were determined for Zn (34 to 295 μg/dL), Hg (0 to 4.8 μg/dL), and ChE (0.17 to 1.65 μmole acetylthiocholine/mL per minute). Elevations of Pb, Zn, or Hg, or decreases in ChE activity levels of this cohort during recapture sampling may indicate point-source intoxications or bioaccumulation, both ultimately attributable to environmental contamination. The released animals may serve as sentinels for biomonitoring of their new habitat for the evaluated toxicants