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This study investigates the fractionation of 137Cs across the geological phases of coral soils using a sequential extraction scheme. For three of the four soil samples analyzed, the largest fraction of radiocesium (70–80%) was associated with the final fraction or “acid-soluble” phase of soil, which would typically include clays and other refractory minerals that are difficult to destroy. This is common behavior for radiocesium due to its strong affinity for clays, but surprising here because these primarily calcium carbonate soils contain very minimal amounts of such minerals.

Leaf blight disease caused by Pestalotiopsismaculans lead to deleterious losses in the quality of forest container seedlings. The use of plant growth-promoting bacteria provides a promising strategy to simultaneously control diseases and enhance forest seedling production. This study investigated the biocontrol of leaf blight disease and growth promotion potential of Bacillus velezensis CE 100 in Quercus acutissima Carruth seedlings. B. velezensis CE 100 produced cell wall degrading enzymes, such as chitinase, β-l,3-glucanase, and protease, which caused cell wall lysis and hyphae deformation of P. maculans, leading to mycelial growth inhibition by 54.94%. Inoculation of B. velezensis CE 100 suppressed P. maculans infection and increased seedling survival rate by 1.6-fold and 1.3-fold compared to chemical fertilizer and control, respectively. In addition, B. velezensis CE 100 produced indole-3-acetic acid, which improved root development and nutrient uptake compared to chemical fertilizer and control. Especially, inoculation with B. velezensis CE 100 increased the total nitrogen content of Q. acutissima seedlings, improved the chlorophyll index in the leaves, and increased seedling biomass by 1.3-fold and 2.2-fold compared to chemical fertilizer and control, respectively. Thus, B. velezensis CE 100 could be applied in the eco-friendly production of high-quality forest seedlings.

Walnut anthracnose caused by Colletotrichum gloeosporioides is a deleterious disease that severely affects the production of walnut (Juglans regia L.). The aim of this study was to assess the antifungal and growth promotion activities of Bacillus velezensis CE 100 as an alternative to chemical use in walnut production. The crude enzyme from B. velezensis CE 100 exhibited chitinase, protease, and β-l,3-glucanase activity and degraded the cell wall of C. gloeosporioides, causing the inhibition of spore germination and mycelial growth by 99.3% and 33.6% at 100 µL/mL, respectively. The field application of B. velezensis CE 100 culture broth resulted in a 1.3-fold and 6.9-fold decrease in anthracnose disease severity compared to the conventional and control groups, respectively. Moreover, B. velezensis CE 100 produced indole-3-acetic acid (up to 1.4 µg/mL) and exhibited the potential for ammonium production and phosphate solubilization to enhance the availability of essential nutrients. Thus, field inoculation of B. velezensis CE 100 improved walnut root development, increased nutrient uptake, enhanced chlorophyll content, and consequently improved total biomass by 1.5-fold and 2.0-fold compared to the conventional and control groups, respectively. These results demonstrate that B. velezensis CE 100 is an effective biocontrol agent against anthracnose disease and a potential plant growth-promoting bacteria in walnut tree production.

Exercise performed in the fasted state acutely increases fatty acid availability and utilization. Furthermore, activation of energy-sensing pathways and fatty acid metabolic genes can be augmented by fasting and fasted exercise. However, whether a similar effect occurs at higher exercise intensities remains poorly understood. This study aimed to assess the effect of fed and fasted exercise upon postexercise signaling and mRNA responses during moderate- to high-intensity steady-state exercise. Eight male participants [age: 25 (SD 2) yr, V̇o2peak: 47.9 (SD 3.8) ml·kg−1·min−1] performed 1 h of cycling at 70% Wmaxin the fasted (FAST) state or 2 h following ingestion of a carbohydrate-rich mixed-macronutrient breakfast (FED). Muscle biopsies were collected pre-, immediately, and 3 h postexercise from the medial vastus lateralis, while venous blood samples were collected throughout the trial. Plasma, nonesterified fatty acid, and glycerol concentrations were elevated during FAST compared with FED, although substrate utilization during exercise was similar. AMPKThr172phosphorylation was ~2.5-fold elevated postexercise in both trials and was significantly augmented by ~30% during FAST. CREBSer133phosphorylation was elevated approximately twofold during FAST, although CREBSer133phosphorylation acutely decreased by ~50% immediately postexercise. mRNA expression of PDK4 was approximately three- to fourfold augmented by exercise and approximately twofold elevated throughout FAST, while expression of PPARGC1A mRNA was similarly activated (~10-fold) by exercise in both FED and FAST. In summary, performing moderate- to high-intensity steady-state exercise in the fasted state increases systemic lipid availability, elevates phosphorylation of AMPKThr172and CREBSer133, and augments PDK4 mRNA expression without corresponding increases in whole body fat oxidation and the mRNA expression of PPARGC1A.

Populus canadensis Moench forests established in Saemangeum-reclaimed land have been invaded by Hyphantria cunea Drury, causing defoliation and stunted growth. This study investigated the biocontrol potential of cuticle degrading chitinase and protease secreted by Lysobacter antibioticus HS124 against H. cunea larvae. In addition, L. antibioticus HS124 was examined for indole-3-acetic acid phytohormone production for plant growth promotion. To determine the larvicidal activity in the laboratory experiments, crude enzymes, bacteria culture, CY medium, and water (control) were sprayed on the larvae reared on natural diet in insect rearing dishes. Treatment with crude enzymes and bacteria culture caused 76.7% and 66.7% larvae mortality, respectively. The larvae cuticle, mainly composed of chitin and proteins, was degraded by cuticle-degrading enzymes, chitinase, and protease in both the bacteria culture and crude enzyme treatments, causing swelling and disintegration of the cuticle. Field application of the bacteria culture was achieved by vehicle-mounted sprayer. Bacterial treatment caused morphological damage on the larvae cuticles and subsequent mortality. Foliar application of the bacteria culture reduced tree defoliation by H. cunea and enhanced growth compared to the control. Especially, L. antibioticus HS124 produced auxins, and increased growth of poplar trees.

The present study examined how food availability interacts with age to modulate lizard adrenal steroidogenic function at the cellular level. Adult male and juvenile male and female Eastern Fence Lizards (Sceloporus undulatus) underwent a period of food deprivation with or without a shorter re-feeding period. Lizards maintained on a full feeding regimen served as the controls. Across the feeding regimens, plasma corticosterone of adult lizards was unchanged whereas that of food-deprived juvenile lizards was increased nearly 7 times and this increase was normalized by a short re-feeding period. Freshly dispersed adrenocortical cells derived from these lizards were incubated with ACTH and the production of selected steroids was measured by highly specific radioimmunoassay. Net maximal steroid rates of juvenile cells were 161% greater than those of adult cells. Adult and juvenile progesterone rates were consistently suppressed by food deprivation (by nearly 48%) and were normalized by a re-feeding period, whereas divergent effects were seen with corticosterone and aldosterone rates. Food deprivation suppressed corticosterone rates of adult cells by 43% but not those of juvenile cells. In a reciprocal manner, food deprivation had no significant effect on aldosterone rates of adult cells, but it suppressed those of juvenile cells by 52%. A short re-feeding period normalized most rates in both adult and juvenile cells and further augmented the adult aldosterone rate by 54%. The effect of the feeding regimens on ACTH sensitivity varied with life stage and with steroid. The overall sensitivity of adult cells to ACTH was nearly three times that of juvenile cells. Collectively, the data presented here and data from previous work indicate that food restriction/deprivation in Sceloporus lizard species causes a functional remodeling of the adrenocortical tissue. Furthermore, life stage adds more complexity to this remodeling.

Root rot diseases, caused by phytopathogenic oomycetes, Phytophthora spp. cause devastating losses involving forest seedlings, such as Japanese cypress (Chamaecyparis obtusa Endlicher) in Korea. Plant growth-promoting rhizobacteria (PGPR) are a promising strategy to control root rot diseases and promote growth in seedlings. In this study, the potential of Bacillus velezensis CE 100 in controlling Phytophthora root rot diseases and promoting the growth of C. obtusa seedlings was investigated. B. velezensis CE 100 produced β-1,3-glucanase and protease enzymes, which degrade the β-glucan and protein components of phytopathogenic oomycetes cell-wall, causing mycelial growth inhibition of P. boehmeriae, P. cinnamomi, P. drechsleri and P. erythoroseptica by 54.6%, 62.6%, 74.3%, and 73.7%, respectively. The inhibited phytopathogens showed abnormal growth characterized by swelling and deformation of hyphae. B. velezensis CE 100 increased the survival rate of C. obtusa seedlings 2.0-fold and 1.7-fold compared to control, and fertilizer treatment, respectively. Moreover, B. velezensis CE 100 produced indole-3-acetic acid (IAA) up to 183.7 mg/L, resulting in a significant increase in the growth of C. obtusa seedlings compared to control, or chemical fertilizer treatment, respectively. Therefore, this study demonstrates that B. velezensis CE 100 could simultaneously control Phytophthora root rot diseases and enhance growth of C. obtusa seedlings.

There is a growing interest in using biocontrol agents to control fungal diseases and increase the production of jujube fruit (Zizyphus jujua Miller var. inermis Rehder). The purpose of this study was to use Bacillus licheniformis PR2 to inhibit fungal diseases and promote fruit production in jujube orchards. B. licheniformis PR2 secreted 92.4 unit/mL of chitinase, which inhibited fungal phytopathogens through hyphal alterations with swelling and bulbous structures. B. licheniformis PR2 also inhibited mycelial growths of fruit fungal pathogens Botrytis cinerea, Colletotrichum gloeosporioides, and Phytophthora nicotianae by 81.3%, 60.1%, and 67.0%, respectively. B. licheniformis PR2 increased jujube fruit yield by 17.9 kg/tree by reducing rotting damage caused by fungal pathogens, with a yield 3.2 times higher than that achieved by the control without PR2 treatment. In addition, B. licheniformis PR2 produced auxin, which promoted cell division after flower fertilization, thus increasing fruit length and diameter by 1.2-fold compared to those of the control. These results confirmed that eco-friendly B. licheniformis PR2 could effectively control fungal diseases in jujube orchards and improve its fruit size and yield.

Accurate measurements of ozone in the upper tropical troposphere and lower stratosphere (UTLS) are challenging for most measuring systems, yet of great importance for the understanding of the chemical and dynamical processes in this region.Balloon-borne observations using Electrochemical Concentration Cell (ECC) ozone sondes are the most widely used in situ technology to measure vertical profiles of ozone in networks such as the Southern Hemisphere ADditional Ozonesondes (SHADOZ) network of tropical and subtropical ozone sonde stations.The tropical upper troposphere and the layers of near-zero ozone within the ozone hole are most sensitive to processing and preparation variations that may affect the accuracy and possibly trend estimates of ozone in low ozone regions. It is now appreciated that the complex chemistry within the ECC used to detect ozone exhibits two different time constants (τfast≈20 s, τslow≈25 min), which modify the response of the ECC during a profile. Although not well understood, the chemistry of the slow reaction is likely to represent what has conventionally been assumed a constant “background current”. The fast reaction causes some delay in the response of the ECC to changes in the vertical profile of ozone. Here we show how correcting for both improves the estimate of the lowest ozone concentration in the upper troposphere as well as the steepness of the gradient in the transition into the stratosphere. The steady state bias, which describes the contribution of the slow reaction, is the largest source of uncertainty overall; the response time of the fast reaction dominates the uncertainty in the region of the sharp gradient of ozone above the tropopause.

Genomic structural variants comprise a significant fraction of somatic mutations driving cancer onset and progression. However, such variants are not readily revealed by standard next-generation sequencing. Optical genome mapping (OGM) surpasses short-read sequencing in detecting large (&gt, 500 bp) and complex structural variants (SVs) but requires isolation of ultra-high-molecular-weight DNA from the tissue of interest. We have successfully applied a protocol involving a paramagnetic nanobind disc to a wide range of solid tumors. Using as little as 6.5 mg of input tumor tissue, we show successful extraction of high-molecular-weight genomic DNA that provides a high genomic map rate and effective coverage by optical mapping. We demonstrate the system’s utility in identifying somatic SVs affecting functional and cancer-related genes for each sample. Duplicate/triplicate analysis of select samples shows intra-sample reliability but also intra-sample heterogeneity. We also demonstrate that simply filtering SVs based on a GRCh38 human control database provides high positive and negative predictive values for true somatic variants. Our results indicate that the solid tissue DNA extraction protocol, OGM and SV analysis can be applied to a wide variety of solid tumors to capture SVs across the entire genome with functional importance in cancer prognosis and treatment.

Importance Silicone breast implants have been on the market for breast augmentation or breast reconstruction for approximately 60 years but may lead to medical complications, also called breast implant illness. Objective To evaluate the existence of silicone gel bleed and migration over a long time period, including the period in which the newer cohesive silicone gel breast implants were used. Design, setting, and participants In this single-center case series, capsule tissue and lymph node samples were collected from women who underwent removal or revision of silicone breast implants from January 1, 1986, to August 18, 2020, and data were extracted from the pathological reports and revision of the histology if data were missing. All tissues were examined using standard light microscopy, some extended with modified oil red O staining and energy-dispersive radiographic spectroscopy. A total of 365 women had capsular tissue removed, including 15 patients who also had lymph nodes removed, and 24 women had only lymph nodes removed. Data were analyzed from January to May 2021. Exposures Silicone breast implants. Main outcomes and measures The main outcome was presence or absence of silicones inside or outside the capsule. One-way analysis of variance was used to determine significance between groups. Results Among a total of 389 women with silicone breast implants (mean [SD] age, 50.5 [11.2] years), 384 women (98.8%) had silicone particles present in the tissues, indicating silicone gel bleed. In 337 women (86.6%), silicone particles were observed outside the capsule (ie, in tissues surrounding the capsule and/or lymph nodes), indicating silicone migration. In 47 women (12.1%), silicone particles were only present within the capsule. In 5 women (1.2%), no silicone particles were detected in the tissues. Patients were divided into 2 groups, with 46 women who received cohesive silicone gel breast implants and 343 women who received either an older or a newer type of breast implant. There were no differences in silicone gel bleed or migration between groups (silicone detected outside or inside capsule: 44 women [95.7%] vs 340 women [99.1%]; P = .19). Conclusions and relevance In this case series including women with noncohesive or cohesive silicone gel breast implants, silicone leakage occurred in 98.8% of women, indicating silicone gel bleed, and in 86.6% of women, migration of silicone particles outside the capsule was detected.

Synopsis Previous research has demonstrated that testosterone (T) can inhibit growth in female-larger species and stimulate growth in male-larger species, but the underlying mechanisms of this regulatory bipotentiality have not been investigated. In this study, we investigated the effects of T on the expression of hepatic insulin-like growth factor-1 (IGF-1) mRNA and circulating IGF-1 hormone in Sceloporus undulatus, a species of lizard in which females grow faster to become larger than males and in which T inhibits growth. Experiments were performed in captivity on mature female and male adults in the asymptotic phase of their growth curve and on actively growing, pre-reproductive juveniles. In adult males, the expression of hepatic IGF-1 mRNA increased following surgical castration and returned to control levels with T replacement; in intact adult females, exogenous T had no effect on IGF-1 mRNA expression. In juveniles, T significantly reduced both growth and the expression of hepatic IGF-1 mRNA to similar extents in intact females and in castrated males. The relative inhibitory effects of T on mRNA expression were greater in juveniles than in adults. Plasma IGF-1 hormone was about four times higher in juveniles than in adults, but T had no significant effect on IGF-1 hormone in either sex or in either age group. Our finding of inhibition of the expression of hepatic IGF-1 mRNA stands in contrast to the stimulatory effects of T in the published body of literature. We attribute our novel finding to our use of a species in which T inhibits rather than stimulates growth. Our findings begin to explain how T has the regulatory bipotentiality to be stimulatory in some species and inhibitory in others, requiring only an evolutionary reversal in the molecular regulation of growth-regulatory genes including IGF-1. Further comparative transcriptomic studies will be required to fully resolve the molecular mechanism of growth inhibition.

Age dating radioactive 137Cs and 90Sr sources, which are a potential concern in radiation dispersal devices, can provide evidence for attribution in a nuclear forensic investigation. Precise measurement of the 137Cs–137Ba or 90Sr–90Zr isotope ratio by ICP-MS in tandem with non-linearity and mass-bias data manipulation dramatically increases precision and decreases uncertainty, leaving inadequate chemical separation efficiencies as a major contributor—and in some cases the lead contributor—to uncertainty in age determination. To improve the separation of these isobars before ICP-MS analysis, we evaluated eluents containing EDTA and DTPA chelating agents against previously studied eluents for their ability to achieve complete removal of Sr and Ba from Eichrom Technologies’ Sr Resin. Barium separation efficiencies using 0.05 M EDTA, pH-adjusted 0.05 M EDTA, and pH-adjusted 0.05 M DTPA were found to be 100.9 ± 2.2%, 99.4 ± 0.8%, and 99.3 ± 1.2%, respectively. Strontium separation efficiencies using 0.05 M disodium EDTA and 0.05 M potassium EDTA were determined to be 100.14 ± 0.53% and 100.19 ± 0.97% respectively. These results demonstrate that eluents containing chelating agents out-perform previously studied eluent solutions at removing barium and strontium from Sr Resin.

The Glutathione S-transferases (GSTs) protects cellular DNA against oxidative damage. The role of GSTP1 polymorphism (A313G; Ile105Val) as a susceptibility factor in oral cancer was evaluated in a hospital-based case-control study in North-East India, because the habit of chewing raw areca-nut (RAN) with/without tobacco is common in this region. Genetic polymorphism was investigated by genotyping 445 cases and 444 controls. Individuals with the GSTP1 AA-genotype showed association with the oral cancer (OR = 3.1, 95% CI = 2.4–4.2, p = 0.0002). Even after adjusting for age, sex and habit the AA-genotype is found to be significantly associated with oral cancer (OR = 2.4, 95% CI = 1.7–3.2, p = 0.0001). A protein-protein docking analysis demonstrated that in the GG-genotype the binding geometry between c-Jun Kinase and GSTP1 was disrupted. It was validated by immunohistochemistry in human samples, showing lower c-Jun-phosphorylation and down-regulation of pro-apoptotic genes in normal oral epithelial cells with the AA-genotype. In silico docking revealed that AA-genotype weakly detoxifies the RAN/tobacco metabolites. In addition, experiments revealed a higher level of 8-Oxo-2′-deoxyguanosine induction in tumor samples with the AA-genotype. Thus, habit of using RAN/tobacco and GSTP1 AA-genotype together play a significant role in predisposition to oral cancer risk by showing higher DNA-lesions and lower c-Jun phosphorylation that may inhibit apoptosis.

The Electrochemical Concentration Cell (ECC) ozonesonde has been the main instrument for in situ profiling of ozone worldwide; yet, some details of its operation, which contribute to the ozone uncertainty budget, are not well understood. Here, we investigate the time response of the chemical reactions inside the ECC and how corrections can be used to remove some systematic biases. The analysis is based on the understanding that two reaction pathways involving ozone occur inside the ECC that generate electrical currents on two very different time scales. A slow reaction pathway involving the buffer with a time constant of about 25 min can be interpreted as what has conventionally been considered the “background current”. This contribution can be calculated and removed from the measured current instead of the “background current”. The remaining fast reaction pathway with a time constant of about 20 s is due the conversion of iodide to molecular iodine and the generation of two free electrons per ozone molecule. Here we provide an algorithm to calculate and remove the contribution of the slow reaction pathway and to correct for the time lag of the faster reaction pathway. This processing algorithm has been applied to ozonesonde profiles at Costa Rica and during the Central Equatorial Pacific Experiment (CEPEX) and to laboratory experiments evaluating the performance of ECC ozonesondes. At Costa Rica, where a 1 % KI, 1/10th buffer solution is used, there is no change in the derived total ozone column; however, in the upper troposphere and lower stratosphere, average reported ozone concentrations increase by up to 7 % and above 30 km decrease by up to 7 %. During CEPEX, where a 1 % KI, full buffer solution was used, ozone concentrations are increased mostly in the upper troposphere with no change near to the top of the profile. In the laboratory measurements, the processing algorithms have been applied to measurements using all current sensing solutions and using only the stronger pump efficiency correction reported by Johnson et al. (2002), which improves the time response of the ECCs and removes some biases relative to the reference instruments. In the surface layer, the correction algorithm shows that ECC ozonesonde measurements are influenced by the operational procedures prior to launch and that typical gradients above the surface layer may be steeper than originally reported.

Tropospheric ozone damages ecosystems and causes human health problems. The high spatial and temporal variability of ozone concentrations in the troposphere challenges global observing systems to monitor ozone at all relevant scales. TROPOMI is a nadir-viewing UV-Vis-NIR-SWIR sensor that combines a high spatial resolution, a large swath width and the spectral measurement characteristics required to deliver trace gas data records at unprecedented detail. The first tropospheric data product was publicly released in Fall 2018, a year after launch on the Sentinel-5p platform (S5p). It is based on the convective-cloud differential technique (CCD) to infer 0.5°x1° resolved daily maps of 3-day moving mean values of the tropospheric ozone column (surface to 270 hPa) between 20°S and 20°N in clear-sky conditions. This makes it the highest resolved tropospheric ozone data set currently available for the tropical belt. About two years of data have been collected since the end of the commissioning phase in April 2018.We present an assessment of the quality of the Sentinel-5p TROPOMI convective-cloud differential tropospheric ozone column data products (O3_TCL OFFL v01.01.05-01.01.07), carried out within the context of ESA’s Sentinel-5p Mission Performance Center (MPC) and the S5PVT AO project CHEOPS-5p. Our assessment of the first two years of TROPOMI data is based on comparisons with (a) quality-assured co-located in-situ measurements by the SHADOZ ozonesonde network, and, (b) satellite data by the GOME-2 and OMI sensors. These well-characterized observational data records serve as references to evaluate the bias and the dispersion of S5p data, and their dependence on influence quantities. Additional visual inspections of the S5p tropospheric ozone maps unveiled non-geophysical structures introduced by the sampling pattern of sensor and clouds. We conclude by assessing the compliance of S5p tropospheric ozone data with respect to mission and user requirements for key data applications.

The geometrical deviations from planar to folded or from linear to bent structures observed in multiply bonded heavy main group element analogues of ethylene and acetylene are treated from a second-order Jahn–Teller (SOJT) perspective. The structural distortions can be regarded as a consequence of a mixing of the filled highest occupied molecular orbital (HOMO) and an unoccupied orbital (LUMO+1). This mixing stabilizes the HOMO and destabilizes the unoccupied LUMO+1 orbital and produces nonbonding electron density, which causes the geometrical distortion through interelectronic repulsion. This occurs more readily in the heavier species because of their generally weaker bonds, which permit a closer approach and hence greater interaction of the molecular levels. Predicting which geometrical distortion enables the HOMO/LUMO+1 mixing requires knowledge of the symmetries of these frontier orbitals and the symmetry of the distortion. For the undistorted structures the product of the symmetries of the interactin...

The solubility of 7Be particles was measured in vitro as part of an evaluation of the exposure of workers who inhaled particles released from a damaged source. Initial in vivo measurements performed with one worker revealed that a significant fraction of 7Be particles were rapidly removed from the respiratory tract with a half-life of approximately 0.4 days. Since rapid clearance of 7Be was not supported by conventional biokinetic models, a study of the solubility of the particles in vitro was launched. A representative sample of the 7Be particles was collected from the damaged source and exposed to a surrogate lung fluid solution for increasing periods of time. Over 98% of the material was dissolved at the end of the dissolution period. The effective half-time for solubility of the majority of 7Be particles was found to be ≅ 0.4 days and is wholly consistent with results of in vivo measurements.

Targeted alpha therapy has the properties of direct ionization, oxygen independency, high linear energy transfer, a short half-life, and minimal depth of penetration, which are advantageous in cancer treatment. This modified, inexpensive, high-resolution, autoradiographic study of 232Th decay in a tissue specimen, to both locate and quantify individual alpha-particle origins, track lengths, and dose rates, utilized conventional Ilford Pan F Plus, 135–36, Black and White, 35 mm, ISO 50 film. Dose rates measured 0.14 cGy d−1 in the liver, 0.03 cGy d−1 in the right kidney, and 0.003 cGy d−1 in the heart, leading to a dosimetric concern of where the final alpha-particle deposition occurs.

Oxidopyrylium-alkene [5 + 2] cycloaddition conjugate addition cascade (C3) sequences are described. Intramolecular cycloadditions involving terminal alkenes, enals, and enones were investigated. Substrates with tethers of varying lengths delivered five- and six-membered carbocycles and heterocycles thus demonstrating the scope and limitation of the cycloaddition–conjugate addition cascade. Several experiments and theoretical calculations provide evidence for the proposed mechanistic pathway.

Our previous work with adrenocortical cells from several Sceloporus lizard species suggests that gonadal hormones influence the steroidogenic capacity and the sensitivity to ACTH. However, there are discrepancies in these cellular response parameters suggesting that the effects of gonadal hormones on adrenocortical function vary with species, sex, age, season, and environmental/experimental conditions. To gain further insight into these complex interactions, here we report studies on Coleonyx elegans , Eublepharidae (Yucatan Banded Gecko), which is only distantly related to Sceloporus lizards via a basal common ancestor and in captivity, reproduces throughout the year. We hypothesized that a more constant reproductive pattern would result in less variable effects of gonadal hormones on adrenocortical function. Reproductively mature male geckos were orchiectomized with and without replacement of testosterone (300 μg) via an implanted Silastic® tube. Reproductively mature intact female geckos received implants with and without testosterone. After 11 weeks, adrenocortical cells were isolated from these lizards and incubated with corticotropin (ACTH) for 3 h at 28 °C. Three adrenocortical steroids, progesterone, corticosterone and aldosterone, were measured by highly specific radioimmunoassays. The production rate of each steroid was statistically analyzed using established software and net maximal rate (by subtracting the basal rate) in response to ACTH was determined. In general, corticosterone predominated and comprised ∼83% of the total net maximal rate, followed by progesterone (∼14%) and aldosterone (∼3%). Compared to the functional responses of adrenocortical cells derived from other lizards thus far, adrenocortical cells from C. elegans exhibited a depressed steroid response to ACTH and this depressed response was more pronounced in male cells. In addition, other sex differences in cellular response were apparent. In female cells, the net maximal rates of progesterone, corticosterone and aldosterone were, respectively, 161, 122 and 900% greater than those in intact-male cells. In contrast, cellular sensitivity to ACTH, as determined by the half-maximally effective steroidogenic concentration (EC 50 ) of ACTH, did not differ between intact-male and intact-female adrenocortical cells. Treatment effects were most striking for corticosterone, the putative, major glucocorticoid in lizards. Orchiectomy caused an increase in the net maximal corticosterone rate equivalent to that of intact-female cells. Testosterone maintenance in orchiectomized lizards completely suppressed the stimulatory effect of orchiectomy. However, orchiectomy with or without testosterone maintenance did not alter cellular sensitivity to ACTH. The effect of testosterone supplementation in intact females, although suppressive, was notably different from its effect in orchiectomized males. Its effect on the net maximal corticosterone rate was relatively modest and did not completely “masculinize” the greater rate seen in intact-female cells. However, testosterone supplementation dramatically suppressed the basal corticosterone rate (by 82%) and enhanced the overall cellular sensitivity to ACTH by 150%, two effects not seen in cells derived from testosterone-treated orchiectomized lizards. Collectively, these findings clearly indicating that the gonad directly or indirectly regulates lizard adrenocortical cell function. Whereas other gonadal or extra-gonadal factors may play a role, testosterone appears to be an essential determinant of the observed sex differences in adrenocortical function.

Summary In Alzheimer’s disease, soluble oligomers of the amyloid-β peptide (Aβo) trigger a cascade of events that includes abnormal hyperphosphorylation of the protein tau, which is essential for pathogenesis. However, the mechanistic link between these two key pathological proteins remains unclear. Using hippocampal slices, we show here that an Aβo-mediated increase in glutamate release probability causes enhancement of synaptically evoked N-methyl-d-aspartate subtype glutamate receptor (NMDAR)-dependent long-term depression (LTD). We also find that elevated glutamate release probability is required for Aβo-induced pathological hyperphosphorylation of tau, which is likewise NMDAR dependent. Finally, we show that chronic, repeated chemical or optogenetic induction of NMDAR-dependent LTD alone is sufficient to cause tau hyperphosphorylation without Aβo. Together, these results support a possible causal chain in which Aβo increases glutamate release probability, thus leading to enhanced LTD induction, which in turn drives hyperphosphorylation of tau. Our data identify a mechanistic pathway linking the two critical pathogenic proteins of AD., Graphical abstract, Highlights • Amyloid-β oligomers mediate increased neuronal glutamate release probability (Pr) • Increased Pr enhances the magnitude of hippocampal long-term depression (LTD) • Enhanced LTD drives the accumulation of pathologically hyperphosphorylated tau • This mechanism links the two key pathogenic proteins of Alzheimer’s disease, How amyloid-β triggers the recruitment and hyperphosphorylation of tau in Alzheimer’s disease remains unclear. Taylor et al. show that an oligomeric amyloid-β-mediated increase in glutamate release probability enhances the magnitude of Hebbian long-term depression (LTD) in the hippocampus, which in turn drives the accumulation of pathologically hyperphosphorylated tau.

The electrochemical concentration cell (ECC) ozonesonde has been the main instrument for in situ profiling of ozone worldwide; yet, some details of its operation, which contribute to the ozone uncertainty budget, are not well understood. Here, we investigate the time response of the chemical reactions inside the ECC and how corrections can be used to remove some systematic biases. The analysis is based on the understanding that two reaction pathways involving ozone occur inside the ECC that generate electrical currents on two very different timescales. The main fast-reaction pathway with a time constant of about 20 s is due the conversion of iodide to molecular iodine and the generation of two free electrons per ozone molecule. A secondary slow-reaction pathway involving the buffer generates an excess current of about 2 %–10 % with a time constant of about 25 min. This excess current can be interpreted as what has conventionally been considered the “background current”. This contribution can be calculated and removed from the measured current instead of the background current. Here we provide an algorithm to calculate and remove the contribution of the slow-reaction pathway and to correct for the time lag of the fast-reaction pathway. This processing algorithm has been applied to ozonesonde profiles at Costa Rica and during the Central Equatorial Pacific Experiment (CEPEX) as well as to laboratory experiments evaluating the performance of ECC ozonesondes. At Costa Rica, where a 1 % KI, 1/10th buffer solution is used, there is no change in the derived total ozone column; however, in the upper troposphere and lower stratosphere, average reported ozone concentrations increase by up to 7 % and above 30 km decrease by up to 7 %. During CEPEX, where a 1 % KI, full-buffer solution was used, ozone concentrations are increased mostly in the upper troposphere, with no change near the top of the profile. In the laboratory measurements, the processing algorithms have been applied to measurements using the majority of current sensing solutions and using only the stronger pump efficiency correction reported by Johnson et al. (2002). This improves the accuracy of the ECC sonde ozone profiles, especially for low ozone concentrations or large ozone gradients and removes systematic biases relative to the reference instruments. In the surface layer, operational procedures prior to launch, in particular the use of filters, influence how typical gradients above the surface are detected. The correction algorithm may report gradients that are steeper than originally reported, but their uncertainty is strongly influenced by the prelaunch procedures.

Amyloid-β (Aβ)-dependent dysfunction and eventual loss of glutamatergic synapses is central to Alzheimer’s disease (AD) pathogenesis. However, the underlying mechanisms remain poorly understood, hindering the development of effective therapeutics. Here, we report that pathogenic Aβ causes a rapid, sustained enhancement of evoked glutamate release probability due to a specific functional potentiation of presynaptic Cav2.1 voltage-gated Ca2+ channels. Mechanistically, this is dependent on a signaling pathway initiated by membrane insertion of the Na+ leak channel ENaC at presynaptic terminals. Pharmacological Cav2.1 inhibition normalizes neurotransmitter release, thereby rescuing amyloid-β-induced loss of dendritic spines and synaptic long-term potentiation (LTP). Likewise, genetic Cav2.1 haploinsufficiency robustly prevents spine loss, memory deficits and premature mortality in AD model mice. Our findings reveal a previously unknown disease mechanism wherein enhanced neurotransmitter release drives AD pathogenesis, and suggest that partial suppression of Cav2.1 function can delay or prevent disease progression.

Purpose Exertional heat stress adversely distrupts (GI) barrier integrity and, through subsequent microbial translocation (MT), negativly impacts health. Despite widespread application, the temporal reliability of popular GI barrier integity and MT biomarkers is poorly characterised. Method Fourteen males completed two 80‐min exertional heat stress tests (EHST) separated by 7–14 days. Venous blood was drawn pre, immediately‐ and 1‐hr post both EHSTs. GI barrier integrity was assessed using the serum Dual‐Sugar Absorption Test (DSAT), Intestinal Fatty‐Acid‐Binding Protein (I‐FABP) and Claudin‐3 (CLDN‐3). MT was assessed using plasma Lipopolysaccharide Binding Protein (LBP), total 16S bacterial DNA and Bacteroides DNA. Results No GI barrier integrity or MT biomarker, except absolute Bacteroides DNA, displayed systematic trial order bias (p ≥ .05). I‐FABP (trial 1 = Δ 0.834 ± 0.445 ng ml−1; trial 2 = Δ 0.776 ± 0.489 ng ml−1) and CLDN‐3 (trial 1 = Δ 0.317 ± 0.586 ng ml−1; trial 2 = Δ 0.371 ± 0.508 ng ml−1) were increased post‐EHST (p ≤ .01). All MT biomarkers were unchanged post‐EHST. Coefficient of variation and typical error of measurement post‐EHST were: 11.5% and 0.004 (ratio) for the DSAT 90‐min postprobe ingestion; 12.2% and 0.004 (ratio) at 150‐min postprobe ingestion; 12.1% and 0.376 ng ml−1 for I‐FABP; 4.9% and 0.342 ng ml−1 for CLDN‐3; 9.2% and 0.420 µg ml−1 for LBP; 9.5% and 0.15 pg µl−1 for total 16S DNA; and 54.7% and 0.032 for Bacteroides/total 16S DNA ratio. Conclusion Each GI barrier integrity and MT translocation biomarker, except Bacteroides/total 16S ratio, had acceptable reliability at rest and postexertional heat stress., The aim of this study was to assess the reliability of gastrointestinal barrier integrity and microbial translocation biomarkers both at rest and in response to exertional heat stress. Fourteen healthy male participants undertook two identical exertional heat stress tests interspersed by 7–14 days. Acceptable and defined levels of reliability are presented for the serum Dual‐Sugar Absorption (lactulose/L‐rhamnose) Test, Intestinal Fatty‐Acid Binding Protein, Claudin‐3, Lipopolysaccharide Binding Protein, total 16s DNA, but not the Bacteroides/total 16s DNA ratio at both measurement points.

Introduction: The rate of sport-related concussion (SRC) has increased steadily over the past two decades in the pediatric population. Docosahexaenoic acid (DHA), an Omega-3 fatty acid important for brain development in children, may aid in recovery following SRC. The purpose of this study was to determine the feasibility, outcomes, and safety of DHA as early treatment for SRC in pediatrics. Methods: A double-blind, randomized, placebo-controlled feasibility trial was conducted. Inclusion criteria were ages 14-18 and SRC within 4 days of enrollment. Exclusion criteria included taking DHA, radiographic evidence of TBI, participation in motorized sports, or previous concussion within past 6 months. Following diagnosis of concussion and initiation of standard treatment, subjects were randomized in a 1:1 fashion to DHA or a placebo and were instructed to take 2 capsules twice daily for 12 weeks. DHA capsules contained a total of 2000 mg of DHA/day and PLACEBO capsules contained corn and soy oil. Both were flavored with masking agents. Subjects were followed prospectively. Standard clinical assessments, SCAT-3 symptoms, ImPACT scores, BESS scores, adverse effects, and drug compliance was collected at enrollment, 1-week, 2-weeks, 4-weeks and 12-weeks. Demographics, day of injury symptoms, injury characteristics, and sport played were also collected. Subjects who demonstrated normal neurocognitive testing, complete symptom resolution and were cleared to begin a return to play (RTP) progression prior to the 4-week follow-up visit were permitted to forgo additional study visits, but requested to return for the 12-week visit. Groups were compared using Mann-Whitney tests for continuous variables and chi-square tests for categorical variables. Results: 40 subjects were enrolled; 20 in the DHA group (mean age: 16.02 years; 65% male) and 20 in the PLACEBO group (mean age: 15.97 years; 70% male). No significant differences in demographics, sport, symptoms, ImPACT scores, or BESS scores at enrollment were noted between groups. 25 (62.5%) subjects completed the 12-week visit. Overall drug compliance was 61.57% in the DHA group compared to 66.34% in the PLACEBO group (p=0.727). Subjects in the DHA group were symptom-free 4 days earlier than the PLACEBO group (16.1 vs. 20.9 days, p=0.082), demonstrated normal ImPACT neurocognitive testing (12.2 vs. 16.8 days, p=0.382), and were cleared to begin a RTP progression (21.4 vs. 23.4 days, p=0.115) sooner than those in the PLACEBO group. Two adverse effects were noted in the DHA group. One event was determined to be unrelated to the study. The second event was drug-related eructation and considered minor. No adverse effects were reported in the PLACEBO group. Conclusion: This study demonstrated that use of high-dose DHA for treatment of SRC in pediatrics is feasible and safe. DHA may allow for a faster symptom-free state and for an earlier return to play, but a large-scale trial is needed.

OBJECTIVES To analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs). METHODS Patients in 18 HIV reference centres in France were prospectively included in the Dat'AIDS cohort. Data were collected from all patients starting an INSTI-containing regimen between 1 January 2006 and 31 December 2016. All causes of INSTI-containing regimen discontinuations were analysed, and patients' characteristics related to discontinuation due to NPAEs were sought. RESULTS INSTIs were prescribed to 21315 patients: 6274 received dolutegravir, 3421 received elvitegravir boosted by cobicistat, and 11620 received raltegravir. Discontinuation was observed in 12.5%, 20.2% and 50.9% of the dolutegravir-, elvitegravir- and raltegravir-treated patients, respectively (P

Density functional theory (DFT) calculations are used to probe the validity of mechanistic proposals for the conversion of isozizanoic acid to 12-norisoziza-5-ene, a reaction that occurs during steam distillation of vetiver oil. While this conversion corresponds overall to a simple decarboxylation, a multistep mechanism involving carbocation intermediates is supported by the computational results.

Herpes simplex viruses (HSVs) are unusual in that unlike most enveloped viruses, they require at least four entry glycoproteins, gB, gD, gH, and gL, for entry into target cells in addition to a cellular receptor for gD. The dissection of the herpes simplex virus 1 (HSV-1) entry mechanism is complicated by the presence of more than a dozen proteins on the viral envelope. To investigate HSV-1 entry requirements in a simplified system, we generated vesicular stomatitis virus (VSV) virions pseudotyped with HSV-1 essential entry glycoproteins gB, gD, gH, and gL but lacking the native VSV fusogen G. These virions, referred to here as VSVΔG-BHLD virions, infected a cell line expressing a gD receptor, demonstrating for the first time that the four essential entry glycoproteins of HSV-1 are not only required but also sufficient for cell entry. To our knowledge, this is the first time the VSV pseudotyping system has been successfully extended beyond two proteins. Entry of pseudotyped virions required a gD receptor and was inhibited by HSV-1 specific anti-gB or anti-gH/gL neutralizing antibodies, which suggests that membrane fusion during the entry of the pseudotyped virions shares common requirements with the membrane fusion involved in HSV-1 entry and HSV-1-mediated syncytium formation. The HSV pseudotyping system established in this study presents a novel tool for systematic exploration of the HSV entry and membrane fusion mechanisms. IMPORTANCE Herpes simplex viruses (HSVs) are human pathogens that can cause cold sores, genital herpes, and blindness. No vaccines or preventatives are available. HSV entry into cells—a prerequisite for a successful infection—is a complex process that involves multiple viral and host proteins and occurs by different routes. Detailed mechanistic knowledge of the HSV entry is important for understanding its pathogenesis and would benefit antiviral and vaccine development, yet the presence of more than a dozen proteins on the viral envelope complicates the dissection of the HSV entry mechanisms. In this study, we generated heterologous virions displaying the four essential entry proteins of HSV-1 and showed that they are capable of cell entry and, like HSV-1, require all four entry glycoproteins along with a gD receptor. This HSV pseudotyping system pioneered in this work opens doors for future systematic exploration of the herpesvirus entry mechanisms.

In this paper, we describe the construction of the Stratospheric Water and Ozone Satellite Homogenized (SWOOSH) database, which includes vertically resolved ozone and water vapor data from a subset of the limb profiling satellite instruments operating since the 1980s. The primary SWOOSH products are zonal-mean monthly-mean time series of water vapor and ozone mixing ratio on pressure levels (12 levels per decade from 316 to 1 hPa). The SWOOSH pressure level products are provided on several independent zonal-mean grids (2.5, 5, and 10°), and additional products include two coarse 3-D griddings (30° long × 10° lat, 20° × 5°) as well as a zonal-mean isentropic product. SWOOSH includes both individual satellite source data as well as a merged data product. A key aspect of the merged product is that the source records are homogenized to account for inter-satellite biases and to minimize artificial jumps in the record. We describe the SWOOSH homogenization process, which involves adjusting the satellite data records to a “reference” satellite using coincident observations during time periods of instrument overlap. The reference satellite is chosen based on the best agreement with independent balloon-based sounding measurements, with the goal of producing a long-term data record that is both homogeneous (i.e., with minimal artificial jumps in time) and accurate (i.e., unbiased). This paper details the choice of reference measurements, homogenization, and gridding process involved in the construction of the combined SWOOSH product and also presents the ancillary information stored in SWOOSH that can be used in future studies of water vapor and ozone variability. Furthermore, a discussion of uncertainties in the combined SWOOSH record is presented, and examples of the SWOOSH record are provided to illustrate its use for studies of ozone and water vapor variability on interannual to decadal timescales. The version 2.5 SWOOSH data are publicly available at doi:10.7289/V5TD9VBX.

In this study, a multi-tracer approach was applied to a complex, methane-impacted site in Southern California to (1) distinguish between natural gas and landfill gas (LFG)-derived methane impacts at site perimeter gas probes, (2) estimate the relative age of the LFG at these probes, and (3) document natural attenuation trends during a 3-year monitoring period. Relationships between methane and ethane values suggest that at the majority of probes, methane is from LFG and not from natural gas and that the relative contribution of LFG methane at these probes has increased over the monitoring period. To evaluate whether LFG is attenuating in the subsurface, the relative age of LFG was estimated by comparing readily degraded VOCs that are major constituents in LFG (toluene in this case) with those resistant to degradation (Freons). Time-series data trends are consistent with several probes being impacted by fresh LFG from recent releases that occurred after the update of the local LFG collection and control system (LFGCCS). Data further indicate some probes to be only affected by legacy LFG from a past release that occurred prior to the LFGCCS update and that, because of a lack of oxygen in the subsurface, had not been fully degraded. The outlined attenuation evaluation methodology is potentially applicable to other sites or even groundwater contaminants; however, the assessment is limited by the degree of homogeneity of the LFG source composition and non-LFG-derived toluene inputs to the analyzed samples.

l-Glutamine (GLN) is a conditionally essential amino acid which supports gastrointestinal (GI) and immune function prior to catabolic stress (e.g., strenuous exercise). Despite potential dose-dependent benefits, GI tolerance of acute high dose oral GLN supplementation is poorly characterised. Fourteen healthy males (25 &plusmn, 5 years, 1.79 &plusmn, 0.07 cm, 77.7 &plusmn, 9.8 kg, 14.8 &plusmn, 4.6% body fat) ingested 0.3 (LOW), 0.6 (MED) or 0.9 (HIGH) g&middot, kg&middot, FFM&minus, 1 GLN beverages, in a randomised, double-blind, counter-balanced, cross-over trial. Individual and accumulated GI symptoms were recorded using a visual analogue scale at regular intervals up to 24-h post ingestion. GLN beverages were characterised by tonicity measurement and microscopic observations. 24-h accumulated upper- and lower- and total-GI symptoms were all greater in the HIGH, compared to LOW and MED trials (p &lt, 0.05). Specific GI symptoms (discomfort, nausea, belching, upper GI pain) were all more pronounced on the HIGH versus LOW GLN trial (p &lt, 0.05). Nevertheless, most symptoms were still rated as mild. In comparison, the remaining GI symptoms were either comparable (flatulence, urge to regurgitate, bloating, lower GI pain) or absent (heart burn, vomiting, urge to defecate, abnormal stools, stitch, dizziness) between trials (p &gt, 0.05). All beverages were isotonic and contained a dose-dependent number of GLN crystals. Acute oral GLN ingestion in dosages up to 0.9 g&middot, 1 are generally well-tolerated. However, the severity of mild GI symptoms appeared dose-dependent during the first two hours post prandial and may be due to high-concentrations of GLN crystals.