The tear film protects the terrestrial animal's ocular surface and the lacrimal gland provides important aqueous secretions necessary for its maintenance. Despite the importance of the lacrimal gland ...in ocular health, molecular aspects of its development remain poorly understood. We have identified a noncoding RNA (miR-205) as an important gene for lacrimal gland development. Mice lacking miR-205 fail to properly develop lacrimal glands, establishing this noncoding RNA as a key regulator of lacrimal gland development. Specifically, more than half of knockout lacrimal glands never initiated, suggesting a critical role of miR-205 at the earliest stages of lacrimal gland development. RNA-seq analysis uncovered several up-regulated miR-205 targets that may interfere with signaling to impair lacrimal gland initiation. Supporting this data, combinatorial epistatic deletion of Fgf10, the driver of lacrimal gland initiation, and miR-205 in mice exacerbates the lacrimal gland phenotype. We develop a molecular rheostat model where miR-205 modulates signaling pathways related to Fgf10 in order to regulate glandular development. These data show that a single microRNA is a key regulator for early lacrimal gland development in mice and highlights the important role of microRNAs during organogenesis.
Alpha spectrometry applications with mass separated samples Dion, M.P.; Eiden, Gregory C.; III, Orville T. Farmer ...
Applied radiation and isotopes,
January 2016, 2016-01-00, 20160101, 2016-01-01, Letnik:
107, Številka:
C
Journal Article
Recenzirano
Odprti dostop
241Am has been deposited using a novel technique that employs a commercial inductively coupled plasma mass spectrometer. This work presents results of high-resolution alpha spectrometry on the 241Am ...samples using a small area passivated implanted planar silicon detector. We have also investigated the mass-based separation capability by developing a 238Pu sample, present as a minor constituent in a 244Pu standard, and performed subsequent radiometric counting. With this new sample development method, the 241Am samples achieved the intrinsic energy resolution of the detector used for these measurements. There was no detectable trace of any other isotopes contained in the 238Pu implant demonstrating the mass-based separation (or enhancement) attainable with this technique.
•High resolution alpha samples created using a commercial ICP-MS.•Mass-based isolation of a plutonium isotope (238Pu) from a mixed plutonium standard.•Fit technique with alpha spectroscopy quantifies the enhancement of 238Pu signature.
The use of naturally occurring antimicrobial peptides provides a promising route to selectively target pathogenic agents and to shape microbiome structure. Lantibiotics, such as duramycin, are one ...class of bacterially produced peptidic natural products that can selectively inhibit the growth of other bacteria. However, despite longstanding characterization efforts, the microbial selectivity and mode of action of duramycin are still obscure. We describe here a suite of biological, chemical, and physical characterizations that shed new light on the selective and mechanistic aspects of duramycin activity. Bacterial screening assays have been performed using duramycin and
-derived bacterial isolates to determine species selectivity. Lipidomic profiles of selected resistant and sensitive strains show that the sensitivity of Gram-positive bacteria depends on the presence of phosphatidylethanolamine (PE) in the cell membrane. Further the surface and interface morphology were studied by high resolution atomic force microscopy and showed a progression of cellular changes in the cell envelope after treatment with duramycin for the susceptible bacterial strains. Together, these molecular and cellular level analyses provide insight into duramycin's mode of action and a better understanding of its selectivity.
The use of urea as a nitrogenous fertilizer has increased over the past two decades, with urea itself being readily detected at high concentrations in many lakes. Urea has been linked to ...cyanobacterial blooms as it is a readily assimilated nitrogen (N) - source for cyanobacteria that possess the enzyme urease. We tested the hypothesis that urea may also act as a carbon (C) source to supplemental growth requirements during the alkaline conditions created by dense cyanobacterial blooms, when concentrations of dissolved CO
2
are vanishingly low. High rates of photosynthesis markedly reduce dissolved CO
2
concentrations and drive up pH. This was observed in Lake Erie during the largest bloom on record (2015) over long periods (months) and short periods (days) of time, suggesting blooms experience periods of CO
2
-limitation on a seasonal and daily basis. We used
13
C-urea to demonstrate that axenic cultures of the model toxic cyanobacterium,
Microcystis aeruginosa
NIES843, assimilated C at varying environmentally relevant pH conditions directly into a spectrum of metabolic pools during urea hydrolysis. Primarily,
13
C from urea was assimilated into central C metabolism and amino acid biosynthesis pathways, including those important for the production of the hepatotoxin, microcystin, and incorporation into these pathways was at a higher percentage during growth at higher pH. This corresponded to increased growth rates on urea as the sole N source with increasing pH. We propose this ability to incorporate C from urea represents yet another competitive advantage for this cyanobacterium during dense algal blooms.
Background Glomerular filtration rate (GFR) is a measure of kidney function, commonly estimated using equations that adjust serum creatinine concentration for age, race, and sex. The Modification of ...Diet in Renal Disease (MDRD) Study equation is widely used, but underestimates GFR at higher levels. The serum creatinine–based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPIcr ) equation generally provides more accurate estimation at GFR >60 mL/min/1.73 m2 . Newer equations have been reported using cystatin C concentration either alone (CKD-EPIcys ) or in combination with creatinine concentration (CKD-EPIcr-cys ). None of these equations has been well validated in older people. We tested the accuracy of these equations in people 74 years or older compared with GFR measured by a reference method. Study Design Diagnostic test evaluation in a prospective cohort. Setting & Participants Participants (n = 394; median age, 80 range, 74-97 years) recruited from nephrology clinics and the community. Index Test GFR estimated using the MDRD Study, CKD-EPIcr , CKD-EPIcys and CKD-EPIcr-cys equations. Reference Test GFR measured using an iohexol clearance method. Results Median measured GFR was 53.4 (range, 7.2-100.9) mL/min/1.73 m2 . MDRD Study–, CKD-EPIcr –, and CKD-EPIcr-cys –estimated GFRs overestimated GFR (median differences of 3.5 P < 0.001, 1.7 P < 0.001, and 0.8 P = 0.02 mL/min/1.73 m2 , respectively); the CKD-EPIcys equation was unbiased. Accuracy (percentage of estimates within 30% of measured GFR P30 ) was 81%, 83%, 86%, and 86% for the MDRD Study, CKD-EPIcr , CKD-EPIcys , and CKD-EPIcr-cys equations, respectively. Accuracy of the MDRD Study equation was inferior ( P = 0.004) to the CKD-EPIcr equation at GFR >60 mL/min/1.73 m2. Limitations Those of non-European ancestry were not included. For practical reasons, only a 4-hour sampling protocol was used for iohexol clearance. Conclusions The CKD-EPIcr equation appeared less biased and was more accurate than the MDRD Study equation. No equation achieved an ideal P30 in the overall population. Our data suggest that GFR estimation is as satisfactory in older people of European ancestry as it has been reported to be in younger individuals.
AIMS: The aim of this study was to isolate novel antibiofilm compounds produced by environmental bacteria. METHODS AND RESULTS: Cell‐free extracts were prepared from lawns of bacteria cultured on ...agar. A total of 126 bacteria isolated from soil, cave and river habitats were employed. Extracts were tested for their ability to inhibit Staphylococcus aureus biofilm in a 96‐well microtitre plate assay. A total of 55/126 extracts (44%) significantly inhibited Staph. aureus biofilm. Seven extracts were selected for further analysis. The antibiofilm activities in all seven extracts exhibited unique patterns of molecular mass, chemical polarity, heat stability and spectrum of activity against Staph. aureus, Staphylococcus epidermidis and Pseudomonas fluorescens, suggesting that these seven antibiofilm activities were mediated by unique chemical compounds with different mechanisms of action. CONCLUSIONS: Environmental bacteria produce abundant and diverse antibiofilm compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: Screening cell‐free extracts is a useful method for identifying secreted compounds that regulate biofilm formation. Such compounds may represent a novel source of antibiofilm agents for technological development.
Chronic kidney disease and life expectancy STEVENS, Paul E; FARMER, Christopher K. T
Nephrology, dialysis, transplantation,
08/2012, Letnik:
27, Številka:
8
Journal Article
Experiments were performed to assess the significance of water ingression cooling in the quenching of molten corium. Water ingression is a mechanism by which water penetrates into cracks and pores of ...solidified corium to enhance cooling that would otherwise be severely limited by the low thermal conductivity of the material. Quench tests were conducted with 2100
°C melts weighing ∼75
kg composed of UO
2, ZrO
2 and chemical constituents of concrete. The amount of concrete in the melts was varied between 4% and 23%. The melts were quenched with an overlying water layer; three tests were conducted at a system pressure of 1
bar and four tests at 4
bar. The measured cooling rates were found to decrease with increasing concrete content and, contrary to expectations, are essentially independent of system pressure. For the lower concrete content melts, cooling rates exceeded the conduction-limited rate with the difference being attributed to the water ingression mechanism. Measurements of the permeability of the corium “ingots” produced by the quench tests were used to obtain a second, independent set of dryout heat flux data, which exhibits the same trend as the quench test data. The data was used to validate an existing dryout heat flux model based on corium permeability associated with thermally induced cracking. The model uses the thermal and mechanical properties of the corium and coolant, and it reproduces the very particular data trend found for the dryout heat flux as a function of concrete content. The model predicts that water ingression cooling would be most effective for concrete-free corium mixtures such as in-vessel type melts. For such a melt the model predicts a dryout heat flux of ∼400
kW/m
2 at a pressure of 1
bar. The results of this study provide an experimental basis for a water ingression model that can be incorporated into computer codes used to assess accident management strategies.
► Experiments tested two engineered corium cooling systems. ► The systems passively inject water into corium from below. ► These systems cool corium much faster than top flooding.
The coolability of ...ex-vessel core debris continues to be an issue of concern in the realm of light water reactor safety. Extensive research into corium/concrete interaction phenomena has been unable to establish the certainty of melt quench and stabilization within the containment boundary for all credible cases of cooling restricted to top flooding. As a result, there has been continuing interest in engineered systems that can augment cooling. This paper describes the testing of two passive cooling concepts that inject water into corium from below via nozzles embedded within the basemat: one with porous concrete nozzles and the other with a type of composite nozzle. The latter supplements water injection with noncondensable gas to stabilize flow and suppress vapor explosions. Each test involved a 136
kg melt composed of 56/23/14
wt% UO
2/ZrO
2/siliceous concrete at an initial depth of 30
cm. The setup with the porous concrete nozzles successfully injected water into the melt at heads as low as 2.3
m. The composite nozzle test was partially successful, with three nozzles delivering coolant while a fourth was damaged by the melt and failed to inject water. The melts cooled twice as fast as similar ones tested in a top flooding configuration. These experiments confirmed earlier work at Forschungszentrum Karlsruhe and elsewhere indicating that cooling via bottom water injection is a particularly effective method for quenching ex-vessel corium melts.
Lower head failure and corium-concrete interaction were predicted to occur at Fukushima Daiichi Unit 1 (1F1) by several different system-level code analyses, including MELCOR v2.1 and MAAP5. Although ...these codes capture a wide range of accident phenomena, they do not contain detailed models for ex-vessel core melt behavior. However, specialized codes exist for the analysis of ex-vessel melt spreading (e.g., MELTSPREAD) and long-term debris coolability (e.g., CORQUENCH). On this basis, an analysis was carried out to further evaluate ex-vessel behavior for 1F1 using MELTSPREAD and CORQUENCH. Best-estimate melt pour conditions predicted by MELCOR v2.1 and MAAP5 were used as input. MELTSPREAD was then used to predict the spatially dependent melt conditions and extent of spreading during relocation from the vessel. The results of the MELTSPREAD analysis are reported in a companion paper. This information was used as input for the long-term debris coolability analysis with CORQUENCH. For the MELCOR-based melt pour scenario, CORQUENCH predicted the melt would readily cool within 2.5 h after the pour, and the sumps would experience limited ablation (approximately 18 cm) under water-flooded conditions. For the MAAP-based melt pour scenarios, CORQUENCH predicted that the melt would cool in approximately 22.5 h, and the sumps would experience approximately 65 cm of concrete ablation under water-flooded conditions.
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