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Strength is a crucial performance indicator for evaluating the durability of pervious concrete (PC). However, there are few models for estimating the remaining strength of in-service PC in sulfate and dry-wet cycle circumstances. Even though there are already direct detection methods for strength, nondestructive testing methods are still worth additional research. This paper aims to give a calculation model for the residual strength of PC under corrosion conditions based on ultrasonic methods, which is economical and convenient for engineering applications. The apparent morphological, compressive strength, and ultrasonic velocity of PC against sulfate and dry-wet cycle attack were examined. The results highlight that the primary cause of the macroscopic mechanical deterioration is the worsening in interface strength. Furthermore, the compressive strength and ultrasonic wave velocity of PC followed the same trends during sulfate and dry-wet cycles, increasing first and subsequently decreasing. Additionally, using the curve-fitting approach, an empirical model of strength deterioration based on ultrasonic velocity was developed and validated utilizing experimental data, demonstrating that the proposed model could more accurately define the strength progression. The results can provide an effective calculation method for monitoring the residual strength of PC pavement engineering in a corrosive environment. [ABSTRACT FROM AUTHOR]

Iron reduction and sulfate reduction are two of the major biogeochemical processes that occur in anoxic sediments. Microbes that catalyze these reactions are therefore some of the most abundant organisms in the subsurface, and some of the most important. Due to the variety of mechanisms that microbes employ to derive energy from these reactions, including the use of soluble electron shuttles, the dynamics between iron- and sulfate-reducing populations under changing biogeochemical conditions still elude complete characterization. Here, we amended experimental bioreactors comprised of freshwater aquifer sediment with ferric iron, sulfate, acetate, and the model electron shuttle AQDS (9,10-anthraquinone-2,6-disulfonate) and monitored both the changing redox conditions as well as changes in the microbial community over time. The addition of the electron shuttle AQDS did increase the initial rate of FeIII reduction; however, it had little effect on the composition of the microbial community. Our results show that in both AQDS- and AQDS+ systems there was an initial dominance of organisms classified as Geobacter (a genus of dissimilatory FeIII-reducing bacteria), after which sequences classified as Desulfosporosinus (a genus of dissimilatory sulfate-reducing bacteria) came to dominate both experimental systems. Furthermore, most of the ferric iron reduction occurred under this later, ostensibly "sulfate-reducing" phase of the experiment. This calls into question the usefulness of classifying subsurface sediments by the dominant microbial process alone because of their interrelated biogeochemical consequences. To better inform models of microbially-catalyzed subsurface processes, such interactions must be more thoroughly understood under a broad range of conditions. [ABSTRACT FROM AUTHOR]

Introduction: The presence of rheumatism is well recognized in primary hypothyroidism. Dehydroepiandrstenedione sulphate (DHEAS) is associated with rheumatological diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study aims to explore relationship between joint pains and DHEAS levels in primary hypothyroidism. Methods: Retrospective study of 78 subjects with subclinical hypothyroidism, with TSH within reference range. The joint pains were evaluated by European Union League against rheumatism (EULAR-CSA) score and compared with serum DHEAS, RA factor, Anti-TPO antibody, highly sensitive C-recative protein (hsCRP), vitamin D levels. Result: DHEAS levels <43.6 mcg/dl significantly predicted clinical features of pre RA as assessed by EULAR CSA criteria with acceptable specificity (82%). EULAR CSA score is fairly valid in assessing imminent RA in primary hypothyroidism. Conclusion: Lower DHEAS predicts clinical features of imminent RA in subjects with primary hypothyroidism. This is akin to low DHEAS seen in many rheumatological disease with possibly similar mechanism. Another possibility is low DHEAS alters hepato-hypothalamo pituitary adrenal axis in presense of cytokines and induces a hitherto unrecognized state of pre rheumatoid arthritis like syndrome. Future studies on primary hypothyroidism should focus on role of lower DHEAS levels in inducing symptoms of fatigue and joint pains. [ABSTRACT FROM AUTHOR]

The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3–0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD. [ABSTRACT FROM AUTHOR]

Cytotoxic and pro-inflammatory histones are present in neutrophil extracellular traps (NETs) and are elevated in blood in several inflammatory conditions, sepsis being a major example. Compounds which can attenuate activities of histones are therefore of interest, with heparin being one such material that has previously been shown to bind to histones. Heparin, a successful anticoagulant for nearly a century, has been shown experimentally to bind to histones and exhibit a protective effect in inflammatory conditions. In the present study carried out in whole blood, heparin and selectively desulfated heparin reduced histone induced inflammatory markers such as interleukin 6 (IL 6), interleukin 8 (IL 8) and tissue factor and C3a, a complement component. The selectively desulfated heparins, with reduced anticoagulant activities, retained a high degree of effectiveness as an anti-histone agent, whereas fully desulfated heparin was found to be ineffective. The results from this study indicate that the presence of sulfate and other specific structural features are required for heparin to attenuate the inflammatory action of histones in whole blood. [ABSTRACT FROM AUTHOR]

Thrips transmit one of the most devastating plant viruses worldwide–tomato spotted wilt tospovirus (TSWV). Tomato spotted wilt tospovirus is a type species in the genus Orthotospovirus and family Tospoviridae. Although there are more than 7,000 thrips species, only nine thrips species are known to transmit TSWV. In this study, we investigated the molecular factors that could affect thrips ability to transmit TSWV. We assembled transcriptomes of a vector, Frankliniella fusca [Hinds], and a non-vector, Frankliniella tritici [Fitch], and performed qualitative comparisons of contigs associated with virus reception, virus infection, and innate immunity. Annotations of F. fusca and F. tritici contigs revealed slight differences across biological process and molecular functional groups. Comparison of virus cell surface receptors revealed that homologs of integrin were present in both species. However, homologs of another receptor, heperan sulfate, were present in F. fusca alone. Contigs associated with virus replication were identified in both species, but a contig involved in inhibition of virus replication (radical s-adenosylmethionine) was only present in the non-vector, F. tritici. Additionally, some differences in immune signaling pathways were identified between vector and non-vector thrips. Detailed investigations are necessary to functionally characterize these differences between vector and non-vector thrips and assess their relevance in orthotospovirus transmission. [ABSTRACT FROM AUTHOR]

The nicotinic acetylcholine receptor (nAChR) is an excitatory pentameric ligand-gated ion channel (pLGIC), homologous to the inhibitory γ-aminobutyric acid (GABA) type A receptor targeted by pharmaceuticals and endogenous sedatives. Activation of the GABAA receptor by the neurosteroid allopregnanolone can be inhibited competitively by thyroid hormone (L-3,3’,5-triiodothyronine, or T3), but modulation of nAChR by T3 or neurosteroids has not been investigated. Here we show that allopregnanolone inhibits the nAChR from Torpedo californica at micromolar concentrations, as do T3 and the anionic neurosteroid pregnenolone sulfate (PS). We test for the role of protein and ligand charge in mediated receptor inhibition by varying pH in a narrow range around physiological pH. We find that both T3 and PS become less potent with increasing pH, with remarkably similar trends in IC50 when T3 is neutral at pH < 7.3. After deprotonation of T3 (but no additional deprotonation of PS) at pH 7.3, T3 loses potency more slowly with increasing pH than PS. We interpret this result as indicating the negative charge is not required for inhibition but does increase activity. Finally, we show that both T3 and PS affect nAChR channel desensitization, which may implicate a binding site homologous to one that was recently indicated for accelerated desensitization of the GABAA receptor by PS. [ABSTRACT FROM AUTHOR]

The impact of different bitter taste compounds on the retronasal perception of coffee aroma was investigated. A sorted napping experiment was carried out on thirteen compounds at iso-intense bitter concentrations. Differences in perceptual bitter sub-qualities among the compounds were reported by Multidimensional Scaling (MDS) and Multiple Factor Analysis (MFA) analyses. Seven exemplar compounds were further selected to investigate the impact of taste sub-qualities on cross-modal flavor interactions. In general, the different bitter compounds, when paired with a coffee aroma isolate, significantly modified the perception of the retronasal coffee aroma profile. Interestingly, the three bitter compounds endogenous to coffee had the most similar impact on the coffee aroma profile. Further sensory analysis of these sample sets indicated no significant effect of the bitter compounds on the orthonasal perception. Gas Chromatography/Mass Spectrometry (GC/MS) analysis of the volatile composition of the samples headspace also indicated negligible impact of the bitter compounds on aroma release. Altogether evidence of cross-modal interactions occurring at a higher cognitive level were demonstrated in a complex food sample, supporting the importance of multi-modal sensory integration on flavor perception. [ABSTRACT FROM AUTHOR]

Golden alga Prymnesium parvum Carter is a euryhaline, ichthyotoxic haptophyte (Chromista). Because of its presumed coastal/marine origin where SO42- levels are high, the relatively high SO42- concentration of its brackish inland habitats, and the sensitivity of marine chromists to sulfur deficiency, this study examined whether golden alga growth is sensitive to SO42- concentration. Fluoride is a ubiquitous ion that has been reported at higher levels in golden alga habitat; thus, the influence of F- on growth also was examined. In low-salinity (5 psu) artificial seawater medium, overall growth was SO42—dependent up to 1000 mg l-1 using MgSO4 or Na2SO4 as source; the influence on growth rate, however, was more evident with MgSO4. Transfer from 5 to 30 psu inhibited growth when salinity was raised with NaCl but in the presence of seawater levels of SO42-, these effects were fully reversed with MgSO4 as source and only partially reversed with Na2SO4. Growth inhibition was not observed after acute transfer to 30 psu in a commercial sea salt mixture. In 5-psu medium, F- inhibited growth at all concentrations tested. These observations support the hypothesis that spatial differences in SO42- –but not F-–concentration help drive the inland distribution and growth of golden alga and also provide physiological relevance to reports of relatively high Mg2+ concentrations in golden alga habitat. At high salinity, however, the ability of sulfate to maintain growth under osmotic stress was weak and overshadowed by the importance of Mg2+. A mechanistic understanding of growth responses of golden alga to SO42-, Mg2+ and other ions at environmentally relevant levels and under different salinity scenarios will be necessary to clarify their ecophysiological and evolutionary relevance. [ABSTRACT FROM AUTHOR]

Objective: Local antibiotic delivery systems with differing chemical and mechanical properties have been developed to assist in the management of osteomyelitis. We investigated the bone conductive and resorptive capabilities of a calcium phosphate-calcium sulfate (CaP/CaS) composite compared with commercially available polymethylmethacrylate (PMMA). In addition, we compared the in vivo preventative and treatment efficacies of both biomaterials in a proven osteomyelitis model. Methods: Sixty-four, male Sprague-Dawley rats were inoculated with 10 μl of 1.5 x 108 CFU/ml of Staphylococcus aureus in a surgically drilled defect in the right proximal tibia. Infected animals were randomly allocated into prevention and treatment groups with 32 rats each. In the prevention group, the defect was filled with a plug containing either PMMA or CaP/CaS immediately after the inoculation. In the treatment group, the infected defects were irrigated, debrided, and filled with either a PMMA or CaP/CaS plug. Both CaP/CaS and PMMA were impregnated with 10% weight of vancomycin. Rats were sacrificed 6 weeks after cement insertion. Infection was detected by bacterial culture and histological analysis. Bone formation in the defect was assessed with micro-computed tomography and histology. Results: No bacteria were detected in any group. Both the prevention and treatment groups using CaP/CaS had significantly more bone volume fraction, bone area, and cartilage area than the PMMA groups. Conclusions: When loaded with 10% of vancomycin, CaP/CaS and PMMA have the same efficacy for treatment and prevention of osteomyelitis. CaP/CaS enhances bone defect healing through improved bone remodeling in our osteomyelitis rat model. [ABSTRACT FROM AUTHOR]

Despite the importance of microbial activity in mobilizing arsenic in groundwater aquifers, the phylogenetic distribution of contributing microbial metabolisms is understudied. Groundwater samples from Ohio aquifers were analyzed using metagenomic sequencing to identify functional potential that could drive arsenic cycling, and revealed mechanisms for direct (i.e., Ars system) and indirect (i.e., iron reduction) arsenic mobilization in all samples, despite differing geochemical conditions. Analyses of 194 metagenome-assembled genomes (MAGs) revealed widespread functionality related to arsenic mobilization throughout the bacterial tree of life. While arsB and arsC genes (components of an arsenic resistance system) were found in diverse lineages with no apparent phylogenetic bias, putative aioA genes (aerobic arsenite oxidase) were predominantly identified in Methylocystaceae MAGs. Both previously described and undescribed respiratory arsenate reduction potential via arrA was detected in Betaproteobacteria, Deltaproteobacteria, and Nitrospirae MAGs, whereas sulfate reduction potential was primarily limited to members of the Deltaproteobacteria and Nitrospirae. Lastly, iron reduction potential was detected in the Ignavibacteria, Deltaproteobacteria, and Nitrospirae. These results expand the phylogenetic distribution of taxa that may play roles in arsenic mobilization in subsurface systems. Specifically, the Nitrospirae are a much more functionally diverse group than previously assumed and may play key biogeochemical roles in arsenic-contaminated ecosystems. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the specific gross and radiographic anatomy of the digestive tract of inland bearded dragons (Pogona vitticeps). Eleven bearded dragon cadavers of both sexes (6 females, 5 males) were dissected to examine, measure, and document the specific gross anatomy of the alimentary canal. Measurements collected from the cadavers included snout-vent length, total length of the alimentary canal, and the lengths of the individual sections of the gastrointestinal tract, including the esophagus, stomach, small intestine, ampulla coli, isthmus coli, rectum, and the distance from the coprodeum to the vent opening. Twenty-two healthy adult bearded dragons (13 females, 9 males) maintained under standardized husbandry conditions underwent a physical examination, blood collection, and whole-body dorsoventral and lateral survey radiographs; these animals were used to provide the radiographic images of the complete digestive tract. For the subsequent contrast passage studies, two different contrast media, barium sulfate (BaSO4, Barilux suspension) and an iodinated ionic radiocontrast agent (Sodium meglumine amidotrizoate [SMAT], Gastrografin), were used. Water-diluted Barilux suspension (dose 9 ml/kg) was administered orally to 5 bearded dragons, while Gastrografin (dose 5ml/kg) was administered orally to 21 bearded dragons. Four animals were used for both contrast media studies, but received a break of four weeks in between. Dorsoventral and laterolateral radiographs were collected at 0 (baseline), 15, 30, and 45 minutes and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, and 36 hours after each contrast medium was administered. Both contrast media were found to illustrate the alimentary tracts in the adult bearded dragons. Transit time was substantially faster with SMAT, and SMAT illustrated the entire gastrointestinal tract within 36 hours; BaSO4 did not fully illustrate the gastrointestinal tract in 36 hours. These results might serve as a guideline for the interpretation of subsequent contrast studies in this lizard species. [ABSTRACT FROM AUTHOR]

Objective: Ischaemia/reperfusion-injury degrades endothelial glycocalyx. Graft glycocalyx degradation was studied in human liver transplantation. Methods: To assess changes within the graft, blood was drawn from portal and hepatic veins in addition to systemic samples in 10 patients. Plasma syndecan-1, heparan sulfate and chondroitin sulfate, were measured with enzyme-linked immunosorbent assay. Results: During reperfusion, syndecan-1 levels were higher in graft caval effluent [3118 (934–6141) ng/ml, P = 0.005] than in portal venous blood [101 (75–121) ng/ml], indicating syndecan-1 release from the graft. Concomitantly, heparan sulfate levels were lower in graft caval effluent [96 (32–129) ng/ml, P = 0.037] than in portal venous blood [112 (98–128) ng/ml], indicating heparan sulfate uptake within the graft. Chondroitin sulfate levels were equal in portal and hepatic venous blood. After reperfusion arterial syndecan-1 levels increased 17-fold (P < 0.001) and heparan sulfate decreased to a third (P < 0.001) towards the end of surgery. Conclusion: Syndecan-1 washout from the liver indicates extensive glycocalyx degradation within the graft during reperfusion. Surprisingly, heparan sulfate was taken up by the graft during reperfusion. Corroborating previous experimental reports, this suggests that endogenous heparan sulfate might be utilized within the graft in the repair of damaged glycocalyx. [ABSTRACT FROM AUTHOR]

Clear-cuts of forests severely affect soil structure and thus soil organic matter (SOM) and nutrient cycling dynamics therein, though with yet unknown consequences for SOM composition as well as phosphorus (P) and sulfur (S) chemical form within the soil microaggregate size fraction. To determine the effects of conventional clear-cutting on soil chemistry in a Cambisol of the Wüstebach Forest (northwestern Germany), we sampled the mineral A- and B-horizons prior to clear-cut as well as 10 and 24 month thereafter. We measured the SOM composition of soil microaggregates using pyrolysis field ionization mass spectrometry (Py-FIMS), as well as P and S chemical form and speciation using wet-chemical extractions and X-ray absorption near edge structure (XANES) spectroscopy. We found that clear-cut led to an increase of the microaggregate size fraction up to 6% due to break-down of macroaggregates and initially significantly increased total elemental concentrations (C, N, P, S) due to the introduction of slash-residues. The SOM of slash-residues consisted to a substantial amount of sterols and was generally found to be of low thermal stability and probably did not contribute to aggregate stability. Deterioration of the aggregate structure probably led to an exposure of originally inaccessible sites within aggregates to the attack by soil microorganisms and thus to an increased P and S turnover as reflected in a significantly reduction of available P proportions (4 to 7%) and a reduction of the most reduced S forms (5%). A probable increased microbial activity and contribution to SOM after clear-cut is also reflected in the significantly increasing hexose:pentose ratio by 0.25 between 10 and 24 month after clear-cut, significantly increasing the general thermal stability of SOM in the microaggregate size fraction and believed to contribute to aggregate stability. This indicated that a first deterioration of the aggregate structure after clear-cut might in the long-term be remediated with time. [ABSTRACT FROM AUTHOR]

Microbial surface properties are important for interactions with the environment in which cells reside. Surface properties of lactic acid bacteria significantly vary and some strains can form strong emulsions when mixed with a hydrocarbon. Lactococcus lactis NCDO712 forms oil-in-water emulsions upon mixing of a cell suspension with petroleum. In the emulsion the bacteria locate at the oil-water interphase which is consistent with Pickering stabilization. Cells of strain NCDO712 mixed with sunflower seed oil did not stabilize the oil droplets. This study shows that the addition of either ethanol or ammonium sulfate led to cell aggregation, which subsequently allowed stabilizing oil-in-water emulsions. From this, we conclude that bacterial cell aggregation is important for emulsion droplet stabilization. To determine how bacterial emulsification influences the microbial transcriptome RNAseq analysis was performed on lactococci taken from the oil-water interphase. In comparison to cells in suspension 72 genes were significantly differentially expressed with a more than 4-fold difference. The majority of these genes encode proteins involved in transport processes and the metabolism of amino acids, carbohydrates and ions. Especially the proportion of genes belonging to the CodY regulon was high. Our results also point out that in a complex environment such as food fermentations a heterogeneous response of microbes might be caused by microbe-matrix interactions. In addition, microdroplet technologies are increasingly used in research. The understanding of interactions between bacterial cells and oil-water interphases is of importance for conducting and interpreting such experiments. [ABSTRACT FROM AUTHOR]

The adverse consequences of herbicide drift towards sensitive crops have been extensively reported in the literature. However, little to no information is available on the consequences of herbicide drift onto weed species inhabiting boundaries of agricultural fields. Exposure to herbicide drift could be detrimental to long-term weed management as several weed species have evolved herbicide-resistance after recurrent selection with sublethal herbicide rates This study investigated the deposition of glyphosate, 2,4-D, and dicamba spray particle drift from applications with two different nozzles in a low speed wind tunnel, and their impact on growth and development of Amaranthus spp. Herbicide drift resulted in biomass reduction or complete plant mortality. Inflection points (distance to 50% biomass reduction) for Amaranthus tuberculatus were 7.7, 4.0, and 4.1 m downwind distance for glyphosate, 2,4-D, and dicamba applications with the flat-fan nozzle, respectively, whereas these values corresponded to 2.8, 2.5, and 1.9 m for applications with the air-inclusion nozzle. Inflection points for Amaranthus palmeri biomass reduction were 16.3, 10.9, and 11.5 m for glyphosate, 2,4-D, and dicamba applications with the flat-fan nozzle, respectively, whereas these values corresponded to 7.6, 5.4, and 5.4 m for applications with the air-inclusion nozzle. Plants were more sensitive to glyphosate at higher exposure rates than other herbicides, whereas plants were more sensitive to 2,4-D and dicamba at lower exposure rates compared to glyphosate. Applications with the flat-fan nozzle resulted in 32.3 and 11.5% drift of the applied rate at 1.0 and 3.0 m downwind, respectively, whereas the air-inclusion nozzle decreased the dose exposure in the same distances (11.4 and 2.7%, respectively). Herbicide drift towards field boundaries was influenced by nozzle design and exposed weeds to herbicide rates previously reported to select for herbicide-resistant biotypes. [ABSTRACT FROM AUTHOR]

The objective of this clinical trial was to evaluate the effectiveness of zinc supplementation on diarrhea and average daily weight gain (ADG) in pre-weaned dairy calves. A total of 1,482 healthy Holstein heifer and bull calves from a large California dairy were enrolled at 24 to 48 hours of age until hutch exit at approximately 90 days of age. Calves were block-randomized by time to one of three treatments: 1) placebo, 2) zinc methionine (ZM), or 3) zinc sulfate (ZS) administered in milk once daily for 14 days. Serum total protein at enrollment and body weight at birth, treatment end, and hutch exit were measured. Fecal consistency was assessed daily for 28 days post-enrollment. For a random sample of 127 calves, serum zinc concentrations before and after treatment and a fecal antigen ELISA at diarrhea start and resolution for Escherichia coli K99, rotavirus, coronavirus, and Cryptosporidium parvum were performed. Linear regression showed that ZM-treated bull calves had 22 g increased ADG compared to placebo-treated bulls (P = 0.042). ZM-treated heifers had 9 g decreased ADG compared to placebo-treated heifers (P = 0.037), after adjusting for average birth weight. Sex-stratified models showed that high birth weight heifers treated with ZM gained more than placebo-treated heifers of the same birth weight, which suggests a dose-response effect rather than a true sex-specific effect of ZM on ADG. Cox regression showed that ZM and ZS-treated calves had a 14.7% (P = 0.015) and 13.9% (P = 0.022) reduced hazard of diarrhea, respectively, compared to placebo-treated calves. Calves supplemented for at least the first five days of diarrhea with ZM and ZS had a 21.4% (P = 0.027) and 13.0% (P = 0.040) increased hazard of cure from diarrhea, respectively, compared to placebo-treated calves. Logistic regression showed that the odds of microbiological cure at diarrhea resolution for rotavirus, C. parvum, or any single fecal pathogen was not different between treatment groups. Zinc supplementation delayed diarrhea and expedited diarrhea recovery in pre-weaned calves. Additionally, zinc improved weight gain differentially in bulls compared to heifers, indicating a research need for sex-specific dosing. [ABSTRACT FROM AUTHOR]

Geobacillus thermoglucosidans DSM2542 is an industrially important microbe, however the complex nutritional requirements of Geobacilli confound metabolic engineering efforts. Previous studies have utilised semi-defined media recipes that contain complex, undefined, biologically derived nutrients which have unknown ingredients that cannot be quantified during metabolic profiling. This study used design of experiments to investigate how individual nutrients and interactions between these nutrients contribute to growth. A mathematically derived defined medium has been formulated that has been shown to robustly support growth of G. thermoglucosidans in two different environmental conditions (96-well plate and shake flask) and with a variety of lignocellulose-based carbohydrates. This enabled the catabolism of industrially relevant carbohydrates to be investigated. [ABSTRACT FROM AUTHOR]

Objectives: To determine the influence of local spread of clonal strains and testing of follow-up isolates on categorical (CA) and essential agreement rates (EA) of common colistin (COL) drug susceptibility testing methods with the broth microdilution (BMD) reference method. Methods: COL MICs were determined for 178 bacterial isolates (Enterobacteriaceae, n = 97; Pseudomonas aeruginosa, n = 81) collected within one year from 64 patients by BMD according to ISO standard 20776–1 (reference method), the SensiTest BMD panel (ST), agar dilution (AD), the VITEK 2 instrument, and gradient diffusion (GD) using antibiotic strips of two and Muller-Hinton agar plates of three manufacturers. CA and EA with BMD were calculated for all isolates and compared to the subset of 68 unique isolates. Results: CA ranges were 79.4% to 94.1% for the unique isolateq panel and 89.9% to 96.1% for all tested isolates. EA ranges were 64.7% to 86.8% and 67.4% to 91.0%, respectively. In both panels, EA for all GD assays was lower than 90%. Both lower and higher EA values ranging from—18.3% (MTS on BD agar) to + 6.3% (AD, Vitek 2) were observed in the full one-year sample. Acquisition of colistin resistance under therapy was observed for 3 patients. Conclusions: i) Repeat testing and local spread of clonal strains can positively or negatively affect CA and EA, ii) CA is more robust towards local influences than EA, iii) EA of GD and AD methods for COL with the reference BMD method is insufficient. [ABSTRACT FROM AUTHOR]

Background and aim: Various drugs have been developed for inflammatory bowel disease (IBD), but still there are limitations in the treatment due to the insufficient responses and significant adverse effects of immunosuppressant. Apocynin is an NADPH-oxidase inhibitor with established safety profiles. We aimed to investigate the protective efficacy of apocynin in IBD using chemical-induced mouse colitis model. Method: We induced experimental colitis by administrating 5% dextran sulfate sodium (DSS) to 8-week old BALB/c mouse for 11 days. Apocynin (400 mg/kg) or sulfasalazine (150 mg/kg) were administeredduring7 days. We monitored bodyweight daily and harvested colon and spleen at day 11 to check weight and length. We also examined histopathologic change and pro-, anti-inflammatory cytokines and enzymes from harvested colons (iNOS, COX-2, TNF-α, MCP-1, p-NrF2, and HO-1). Result: Apocynin significantly alleviated weight reduction induced by DSS treatment (21.64 ± 0.55 for Apocynin group vs. 20.33 ± 0.90 for DSS group, p = 0.005). Anti-inflammatory efficacy of apocynin was also shown by the recovery of colon weight and length. Histopathologic examination revealed significantly reduced inflammatory foci and erosions by apocynin treatment. Colonic expression of iNOS, COX-2, TNF-α, and MCP-1 was decreased significantly in the apocynin treated group. Anti-inflammatory mediators Nrf2 and HO-1 were activated significantly in apocynin treated mouse. Conclusion: Apocynin showed significant anti-inflammatory efficacy against chemically induced colonic inflammation. This study also revealed the unique action of apocynin compared to the currently prescribed drug, sulfasalazine. Given its excellent safety profile and potent efficacy with novel action mechanism, apocynin can be a new therapeutic molecule for the IBD treatment, which can be added to the currently available drugs. [ABSTRACT FROM AUTHOR]

Multivalent proteins or protein dendrimers are useful for clinical and biotechnological applications. However, assembly of chemically defined protein dendrimers is a challenging endeavor. In the past, majority of protein dendrimers have been developed on branched lysine scaffolds and are usually limited to a valency of two to four. The naturally occurring cyclodextrin (CD) scaffold composed of 6–8 glucose units offers the possibility of expanding the valency. Here we have adapted a chemoenzymatic-click strategy for displaying heptavalent peptides and large proteins on the β-cyclodextrin (β-CD) scaffold. We demonstrate that recombinant proteins (engineered with a LPXTG pentapeptide motif at the carboxy terminus), labeled with an alkyne moiety by sortase-mediated ligation, can be easily clicked on to the azide-derivatized β-cyclodextrin through the Huisgen cycloaddition reaction yielding a well-defined heptavalent display of proteins. [ABSTRACT FROM AUTHOR]

The role of glutathione (GSH) in eukaryotic cells is well known. The biosynthesis of this γ-glutamine tripeptide is well studied. However, other γ-glutamyl peptides were found in various sources, and the pathways of their formation were not always clear. The aim of the present study was to determine whether Saccharomyces cerevisiae can produce γ-glutamyl tripeptides other than GSH and to identify the pathways associated with the formation of these peptides. The tripeptide γ-Glu-Val-Gly (γ-EVG) was used as a model. Wild-type yeast cells were shown to produce this peptide during cultivation in minimal synthetic medium. Two different biosynthetic pathways for this peptide were identified. The first pathway consisted of two steps. In the first step, γ-Glu-Val (γ-EV) was produced from glutamate and valine by the glutamate-cysteine ligase (GCL) Gsh1p or by the transfer of the γ-glutamyl group from GSH to valine by the γ-glutamyltransferase (GGT) Ecm38p or by the (Dug2p-Dug3p)2 complex. In the next step, γ-EV was combined with glycine by the glutathione synthetase (GS) Gsh2p. The second pathway consisted of transfer of the γ-glutamyl residue from GSH to the dipeptide Val-Gly (VG). This reaction was carried out mainly by the (Dug2p-Dug3p)2 complex, whereas the GGT Ecm38p did not participate in this reaction. The contribution of each of these two pathways to the intracellular pool of γ-EVG was dependent on cultivation conditions. In this work, we also found that Dug1p, previously identified as a Cys-Gly dipeptidase, played an essential role in the hydrolysis of the dipeptide VG in yeast cells. It was also demonstrated that γ-EV and γ-EVG could be effectively imported from the medium and that γ-EVG was imported by Opt1p, known to be a GSH importer. Our results demonstrated that γ-glutamyl peptides, particularly γ-EVG, are produced in yeast as products of several physiologically important reactions and are therefore natural components of yeast cells. [ABSTRACT FROM AUTHOR]

Introduction: Glucosamine dietary supplements are commonly used for the management of osteoarthritis (OA). However, clinical trials have reported varying outcomes with regard to joint function and disease progression. One of the possible reasons for variability in observed effects of glucosamine could be that, unlike prescription drugs, the quality of manufactured dietary supplements is not closely monitored in many countries. Therefore, there is the possibility that the actual amount of glucosamine present in a dietary supplement is different from that claimed on the label. The quality control of glucosamine supplements is further complicated by the unavailability of a simple and effective analytical method for the analysis of glucosamine. Therefore, the aim of this study was to develop a simple analytical method that could be easily adapted by the pharmaceutical industry for routine analysis of glucosamine. Aims: To develop a novel high-performance liquid chromatography (HPLC) method for the quantification of glucosamine, and determine the amount of glucosamine present in a sample of dietary supplements commercially available in Australia and India. Methods: Chromatographic separation of glucosamine was achieved using a zwitter-ionic hydrophilic interaction liquid chromatography column with a mobile phase consisting of 60% acetonitrile and 40% of 85 mM ammonium acetate, at a flow rate of 0.3 mL/min and column temperature 40°C. The developed method was validated for intra- and inter-day linearity, accuracy, precision, and reproducibility. The newly-developed method was subsequently used to analyse 12 glucosamine supplements. Results: The developed method was selective for glucosamine, which had a retention time of 5.9 min. The standard curve was linear with a correlation coefficient (r2) exceeding 0.99, over the range of 10–200 μg/mL for glucosamine. The relative standard deviations for intra- and inter-day accuracy, precision and reproducibility were all less than 4%. The amount of glucosamine determined in six Australian and six Indian glucosamine supplements ranged between 98.7–101.7% and 85.9–101.8% of the labelled values, respectively. Discussion: Unlike previous HPLC methods, this newly-developed HPLC technique does not require pre-derivatisation and can separate glucosamine from both hydrochloride and sulphate salts, and from other amino sugars, such as chondroitin sulphate present in dietary supplements. This simple and effective technique can be employed by analytical laboratories for the quality control of glucosamine dietary supplements. Conclusion: The current study has developed a new analytical technique using HPLC-Corona CAD, which can analyse underivatised glucosamine hydrochloride and sulphate within 6 minutes. Using the novel assay, we confirmed that unlike the tested Australian dietary supplements, only half of the tested Indian products had a glucosamine content within ±10% of what was claimed on the label. [ABSTRACT FROM AUTHOR]

Persulfate (PSF) is a strong oxidant that has been used extensively in the In-Situ Chemical Oxidation (ISCO) technology. The geoenvironmental impact of PSF treatment is barely investigated. This situation should be carefully considered as it may affect the reutilization of contaminated soil as engineering materials. This paper studied the removal of bisphenol A (BPA) by PSF with Nano Zero-Valent Iron (nZVI) and percarbonate (SPC) activated/enhanced and their subsequent impacts on the engineering properties of soil. The physicochemical and geotechnical properties of soils before and after treatment were evaluated using batch experiments. The results indicate that the introduced pristine PSF can be activated by some naturally occurring matters and subsequently lead to the mineralization of BPA. Both non-activated PSF and activated/enhanced PSF treatment led to the soil improvement in the undrained shear strength at different degrees. The primary mechanism of soil improvement is ascribed to the heterogeneous sulfate and/or carbonate precipitation. Meanwhile, Ca2+ in the pore fluid played a significant role in the enhancement of the soil strength. A conclusion was drawn that the treatment of both non-activated PSF, nZVI- and SPC-activated PSF treatment can achieve removal of BPA and soil improvement in the short-term simultaneously. This study can improve the PSF-involved remediation of brownfields and dredged sediments for a sustainable and low-carbon society. [ABSTRACT FROM AUTHOR]

A potentiometric whole cell biosensor based on immobilized marine bacterium, Pseudomonas carrageenovora producing κ-carrageenase and glycosulfatase enzymes for specific and direct determination of κ-carrageenan, is described. The bacterial cells were immobilized on the self-plasticized hydrogen ion (H+)-selective acrylic membrane electrode surface to form a catalytic layer. Hydrogen ionophore I was incorporated in the poly(n-butyl acrylate) [poly(nBA)] as a pH ionophore. Catalytic decomposition of κ-carrageenan by the bienzymatic cascade reaction produced neoagarobiose, an inorganic sulfate ion and a proton. The latter was detectable by H+ ion transducer for indirect potentiometric quantification of κ-carrageenan concentration. The use of a disposable screen-printed Ag/AgCl electrode (SPE) provided no cleaning requirement and enabled κ-carrageenan detection to be carried out conveniently without cross contamination in a complex food sample. The SPE-based microbial biosensor response was found to be reproducible with high reproducibility and relative standard deviation (RSD) at 2.6% (n = 3). The whole cell biosensor demonstrated a broad dynamic linear response range to κ-carrageenan from 0.2–100 ppm in 20 mM phosphate buffer saline (PBS) at pH 7.5 with a detection limit at 0.05 ppm and a Nernstian sensitivity of 58.78±0.87 mV/decade (R2 = 0.995). The biosensor showed excellent selectivity towards κ-carrageenan compared to other types of carrageenans tested e.g. ι-carrageenan and λ-carrageenan. No pretreatment to the food sample was necessary when the developed whole cell biosensor was employed for direct assay of κ-carrageenan in dairy product. [ABSTRACT FROM AUTHOR]

Production of steroid hormones is complex and dependent upon steroidogenic enzymes, cofactors, receptors, and transporters expressed within a tissue. Collectively, these factors create an environment for tissue-specific steroid hormone profiles and potentially tissue-specific responses to drug administration. Our objective was to assess steroid production, including sulfated steroid metabolites in the boar testis, prostate, and liver following inhibition of aromatase, the enzyme that converts androgen precursors to estrogens. Boars were treated with the aromatase inhibitor, letrozole from 11 to 16 weeks of age and littermate boars received the canola oil vehicle. Steroid profiles were evaluated in testes, prostate, and livers of 16, 20, and 40 week old boars using liquid chromatography/mass spectrometry. Testis, prostate, and liver had unique steroid profiles in vehicle-treated animals. Only C18 steroid hormones were altered by treatment with the aromatase inhibitor, letrozole; no significant differences were detected in any of the C19 or C21 steroids evaluated. Testis was the only tissue with significantly decreased free estrogens following treatment with the aromatase inhibitor; estrone and estradiol concentrations were lower (p < 0.05) in testes from 16, 20, and 40 week letrozole-treated boars. However, concentrations of the sulfated conjugates, estrone-sulfate and estradiol-sulfate, were significantly decreased (p<0.05) in 16 and 20 week boar testes, prostates, and livers from letrozole-treated boars. Hence, the distribution of estrogens between the free and conjugated forms was altered in a tissue-specific manner following inhibition of aromatase. The results suggest sulfated testicular estrogens are important estrogen precursors for the prostate, potentially enabling peripheral target tissues to synthesize free estrogens in the male pig. [ABSTRACT FROM AUTHOR]

Eleven biconical vessels from the Copper Age sites Pietrele and Blejeşti (Romania) have been investigated using p-XRF. In most cases, traces of lead could be measured on their surfaces. Samples of slag-like material from two vessels and the clay of one vessel were investigated using laboratory methods, namely SEM, XRD, LIA and optical microscopy. The vessels were obviously used as a kind of crucible in which slag-like remains and galena ore were detected. It still remains unclear as to what final product was gained by smelting galena in this way. The amount of these such vessels in the Pietrele settlement, their appearance as grave goods in Pietrele and Vărăști (Romania), and their supposed occurrence in a number of other Copper Age settlements in Romania and Bulgaria show the significance of this phenomenon. It must have been a widespread and more or less well known practice, an important part of cultural habit during a particular period in the Lower Danube region and likely even farther afield. For the first time, extensive experimentation with lead ore can be shown in a clear chronological horizon, ca. 4400–4300 BCE in southeastern Europe. [ABSTRACT FROM AUTHOR]

We describe methods to improve the efficiency with which HIV-1 Envelope glycoprotein SOSIP trimer immunogens can be produced by transient transfection of ExpiCHO-S cells and then affinity purified using the trimer-specific human monoclonal antibody PGT145. The specificity of PGT145 for properly folded trimers allows for the facile, one-step, isolation of these immunogens in research laboratories. PGT145 columns are also valuable as a component of more complex purification processes in current Good Manufacturing Practice programs. However, we found that PGT145 purification was highly variable and markedly inefficient when used to process supernatants from transiently transfected ExpiCHO-S cells expressing the BG505 SOSIP.664 and other trimeric Env proteins. In contrast, no such problems arose when the same Env proteins derived from a stable CHO cell line were processed on the same PGT145 columns, or with transient transfection supernatants from 293F cells. An investigation of the ExpiCHO-S transfection system identified the presence of polyanions, including but perhaps not limited to dextran sulfate, in the Enhancer component of the transfection system. We hypothesized that these polyanions bound to the cationic PGT145 epitope on the trimers and impeded their ability to bind to the PGT145 affinity column. We found that replacing the Enhancer component with alternative culture medium supplements substantially increased the yield of PGT145-purifiable trimers, and we also confirmed that both dextran sulfate and the Enhancer component were indeed inhibitors of PGT145 binding to BG505 SOSIP.664 trimers in immunoassays. The presence of polyanions, including but not limited to nucleic acids, should be considered in other circumstances where PGT145 columns are less efficient than expected at purifying native-like trimers. [ABSTRACT FROM AUTHOR]

Antimicrobial biopolymers provide a biodegradable, sustainable, safe, and cheap approach to drug delivery and wound dressing to control bacterial infection and improve wound healing respectively. Here, we report a one-step method of making antimicrobial alginate polymer from sodium alginate and aqueous extract of Wakame using antibiotic aminoglycosides. Thin layer chromatography of commercially available sodium alginate and Wakame extract showed similar oligosaccharide profiles. Screening of six aminoglycosides showed that kanamycin disulfate and neomycin sulfate produces the highest amount of biopolymer; however, kanamycin disulfate produces the most malleable and form fitting biopolymer. Image texture analysis of biopolymers showed similar quantification parameters for all the six aminoglycosides. Weight of alginate polymer as a function of aminoglycoside concentration follows a growth model of prion protein, consistent with the aggregating nature of both processes. Slow release of antibiotics and the resulting zone of inhibition against E. coli DH5α were observed by agar well diffusion assay. Inexpensive method of production and slow release of antibiotics will enable diverse applications of antimicrobial alginate biopolymer reported in this paper. [ABSTRACT FROM AUTHOR]

Fe(III)-rich deposits referred to as “iron mounds” develop when Fe(II)-rich acid mine drainage (AMD) emerges at the terrestrial surface, and aeration of the fluids induces oxidation of Fe(II), with subsequent precipitation of Fe(III) phases. As Fe(III) phases accumulate in these systems, O2 gradients may develop in the sediments and influence the distributions and extents of aerobic and anaerobic microbiological Fe metabolism, and in turn the solubility of Fe. To determine how intrusion of O2 into iron mound sediments influences microbial community composition and Fe metabolism, we incubated samples of these sediments in a column format. O2 was only supplied through the top of the columns, and microbiological, geochemical, and electrochemical changes at discrete depths were determined with time. Despite the development of dramatic gradients in dissolved Fe(II) concentrations, indicating Fe(II) oxidation in shallower portions and Fe(III) reduction in the deeper portions, microbial communities varied little with depth, suggesting the metabolic versatility of organisms in the sediments with respect to Fe metabolism. Additionally, the availability of O2 in shallow portions of the sediments influenced Fe metabolism in deeper, O2-free sediments. Total potential (EH + self-potential) measurements at discrete depths in the columns indicated that Fe transformations and electron transfer processes were occurring through the sediments and could explain the impact of O2 on Fe metabolism past where it penetrates into the sediments. This work shows that O2 availability (or lack of it) minimally influences microbial communities, but influences microbial activities beyond its penetration depth in AMD-derived Fe(III) rich sediments. Our results indicate that O2 can modulate Fe redox state and solubility in larger volumes of iron mound sediments than only those directly exposed to O2. [ABSTRACT FROM AUTHOR]

Introduction: Nigeria has one of the highest maternal mortality ratios in the world. The nurses and midwives being the first point of contact play a central role in addressing these problems. This study was conducted to assess the knowledge and utilization of the technologies (misoprostol, anti-shock garment and magnesium sulphate) in the reduction of maternal mortality amongst the Primary Health Care (PHC) nurses and midwives in Lagos State, Nigeria. In addition, the availability of the technologies in the flagship Primary Health Centres (PHCs) was assessed. Methods: This was a cross-sectional study among all the nurses and midwives at the flagship PHCs in Lagos state and a total of 230 were eventually studied. Data was collected using a self-administered, structured questionnaire and a checklist. Descriptive and inferential statistics were applied. Level of significance was set at 5% (p<0.05). Results: All the respondents were aware of the technologies but most (73.9%) had poor knowledge of them. Majority (74.8%) of the respondents had good knowledge of maternal mortality and its major causes. Most, 81.3% of the respondents have administered misoprostol, 37.0% magnesium sulphate while 52.2% have administered anti shock garment. Out of the 57 flagship PHCs, 27 (47.4%) had magnesium sulphate, 42 (73.7%) had misoprostol and 52 (91.2%) had anti-shock garments in their facilities. Respondents who were double qualified (nurse/midwife) had significantly better knowledge of maternal mortality and its major causes (p = 0.009) than the other cadres. Longer years of experience (p = 0.019), training in the use of misoprostol (p = 0.020) and training in the use of magnesium sulphate (p = 0.001) significantly improved knowledge of the technologies. Conclusion: Respondents had good knowledge of maternal mortality and its major causes and poor knowledge of the technologies for maternal mortality reduction, despite the trainings attended. Of the three technologies considered, misoprostol was the most commonly used. Periodic refresher courses for the training and retraining of PHC nurses and midwives on the technologies for maternal mortality reduction is recommended. [ABSTRACT FROM AUTHOR]

Primary cilia of renal epithelial cells express several members of the transient receptor potential (TRP) class of cation-conducting channel, including TRPC1, TRPM3, TRPM4, TRPP2, and TRPV4. Some cases of autosomal dominant polycystic kidney disease (ADPKD) are caused by defects in TRPP2 (also called polycystin-2, PC2, or PKD2). A large-conductance, TRPP2-dependent channel in renal cilia has been well described, but it is not known whether this channel includes any other protein subunits. To study this question, we investigated the pharmacology of the TRPP2-dependent channel through electrical recordings from the cilia of mIMCD-3 cells, a murine cell line of renal epithelial origin. The pharmacology was found to match that of TRPM3 channels. The ciliary TRPP2-dependent channel is known to be activated by depolarization and by increasing cytoplasmic Ca2+. This activation was greatly enhanced by external pregnenolone sulfate, an agonist of TRPM3 channels. Pregnenolone sulfate did not change the single-channel current-voltage relation. The channels were effectively blocked by isosakuranetin, a specific inhibitor of TRPM3 channels. Both pregnenolone sulfate and isosakuranetin were effective at concentrations as low as 1 μM. Knocking out TRPM3 by CRISPR/Cas9 genome editing eliminated the ciliary channel. Thus the channel is both TRPM3-dependent and TRPP2-dependent, suggesting that it may include both types of subunit. Knocking out TRPM3 did not change the level of TRPP2 protein in the cilia, so it is unlikely that the absence of functional ciliary channels results from a failure of trafficking. [ABSTRACT FROM AUTHOR]

Epiphyton, Renalcis, and Girvanella are ubiquitous genera of calcified cyanobacteria/algae from Early Paleozoic shallow-marine limestones. One genus, Epiphyton, is characterized by a particular dendritic outline, and extensive research has revealed the morphology of calcified remains although little information on cellular structure is known. The mass occurrence of calcified Epiphyton in microbialites from Cambrian Miaolingian, the Mianchi area of North China is preserved as black clots within thrombolites and have dendritic and spherical outlines when viewed with a petrographic microscope. These remains, visible under scanning electron microscope (SEM), also comprise spherical or rectangle capsules. These capsules are made up from external envelopes and internal calcite with numerous pits, which closely resemble modern benthic coccoid cyanobacteria. These pits are between 2 μm and 4 μm in diameter and are interpreted here to represent the remnants of degraded coccoid cells, while the calcite that surrounds these pits is interpreted as calcified thin extracellular polymeric substances (EPS). In contrast, associated capsular envelopes represent thick EPS mineralized by calcium carbonate with an admixture of Al-Mg-Fe silicates. Dendritic ‘thalli’ are typically stacked apically because of the repeated growth and calcification of these capsules. Carbon and oxygen isotope results are interpreted to indicate that both photosynthesis and heterotrophic bacterial metabolism (especially sulfate reducing bacteria) contributed to carbonate precipitation by elevated alkalinity. Epiphyton are therefore here interpreted as colonies of calcified coccoid cyanobacteria, and the carbonate-oversaturated seawater during the Cambrian was conducive to their mineralization. [ABSTRACT FROM AUTHOR]

Proton conductivity is important in many natural phenomena including oxidative phosphorylation in mitochondria and archaea, uncoupling membrane potentials by the antibiotic Gramicidin, and proton actuated bioluminescence in dinoflagellate. In all of these phenomena, the conduction of protons occurs along chains of hydrogen bonds between water and hydrophilic residues. These chains of hydrogen bonds are also present in many hydrated biopolymers and macromolecule including collagen, keratin, chitosan, and various proteins such as reflectin. All of these materials are also proton conductors. Recently, our group has discovered that the jelly found in the Ampullae of Lorenzini- shark’s electro-sensing organs- is the highest naturally occurring proton conducting substance. The jelly has a complex composition, but we proposed that the conductivity is due to the glycosaminoglycan keratan sulfate (KS). Here we measure the proton conductivity of hydrated keratan sulfate purified from Bovine Cornea. PdHx contacts at 0.50 ± 0.11 mS cm -1, which is consistent to that of Ampullae of Lorenzini jelly at 2 ± 1 mS cm -1. Proton conductivity, albeit with lower values, is also shared by other glycosaminoglycans with similar chemical structures including dermatan sulfate, chondroitin sulfate A, heparan sulfate, and hyaluronic acid. This observation supports the relationship between proton conductivity and the chemical structure of biopolymers. [ABSTRACT FROM AUTHOR]

Familial members of urolithiasis have high risk for stone development. We observed the low sulfated glycosaminoglycan (GAG) excretion in urolithiasis patients and their descendants. In this study, we investigated urinary excretion of sulfated GAG, chondroitin sulfate (CS), heparan sulfate (HS) and hyaluronic acid (HA) in urolithiasis and their children, and explored the effect of CS and HA supplement in urolithic hyperoxaluric rats. The 24-hour urines were collected from urolithiasis patients (28) and their children (40), as well as healthy controls (45) and their children (33) to measure urinary sulfated GAG, CS, HS and HA excretion rate. Our result showed that urinary sulfated GAG and CS were diminished in both urolithiasis patients and their children, while decreased HS and increased HA were observed only in urolithiasis patients. Percentage of HS per sulfated GAG increased in both urolithiasis patients and their children. In hyperoxaluric rats induced by ethylene glycol and vitamin D, we found that CS supplement could prevent stone formation, while HA supplement had no effect on stone formation. Our study revealed that decreased urinary GAG and CS excretion are common in familial members of urolithiasis patients, and CS supplement might be beneficial in calcium oxalate urolithiasis prophylaxis for hyperoxaluric patients. [ABSTRACT FROM AUTHOR]

Sulphate attack is one of the most important factors that limit the lifetime of pure concrete constructions. Harsh environmental conditions have a large impact on the operational costs of concrete columns or piles dipped into soil. The results are non-deterministic; therefore, reliability analysis is often used. The strength characteristics of the substrate around the construction were modelled as one-dimensional prismatic beams related with random p-y curves. Sulphate deterioration is defined as a set of random variables jointed with two dimensional mechanical systems at acceptable levels. Fick’s second law describes the penetration of sulphate ingress into pure concrete with explicit numerical solutions for boundary conditions and an increase in the transition factor under the progress of sulphate ingress. This process was partially solved via analytical methods for sulphate ion transport and numerically for a random field. This solves the mechanical task and determines the system reliability. A numerical example is provided to illustrate the proposed method to prevent unexpected structural failures during column service life. The proposed methodology can assist designers and can help to make decisions on existing foundations to ensure the safety of geotechnical construction. [ABSTRACT FROM AUTHOR]

Both iron- and sulfur- reducing bacteria strongly impact the mineralogy of iron, but their activity has long been thought to be spatially and temporally segregated based on the higher thermodynamic yields of iron over sulfate reduction. However, recent evidence suggests that sulfur cycling can predominate even under ferruginous conditions. In this study, we investigated the potential for bacterial iron and sulfur metabolisms in the iron-rich (1.2 mM dissolved Fe2+), sulfate-poor (< 20 μM) Lake Pavin which is expected to host large populations of iron-reducing and iron-oxidizing microorganisms influencing the mineralogy of iron precipitates in its permanently anoxic bottom waters and sediments. 16S rRNA gene amplicon libraries from at and below the oxycline revealed that highly diverse populations of sulfur/sulfate-reducing (SRB) and sulfur/sulfide-oxidizing bacteria represented up to 10% and 5% of the total recovered sequences in situ, respectively, which together was roughly equivalent to the fraction of putative iron cycling bacteria. In enrichment cultures amended with key iron phases identified in situ (ferric iron phosphate, ferrihydrite) or with soluble iron (Fe2+), SRB were the most competitive microorganisms, both in the presence and absence of added sulfate. The large fraction of Sulfurospirillum, which are known to reduce thiosulfate and sulfur but not sulfate, present in all cultures was likely supported by Fe(III)-driven sulfide oxidation. These results support the hypothesis that an active cryptic sulfur cycle interacts with iron cycling in the lake. Analyses of mineral phases showed that ferric phosphate in cultures dominated by SRB was transformed to vivianite with concomitant precipitation of iron sulfides. As colloidal FeS and vivianite have been reported in the monimolimnion, we suggest that SRB along with iron-reducing bacteria strongly influence iron mineralogy in the water column and sediments of Lake Pavin. [ABSTRACT FROM AUTHOR]

Bone mineral density (BMD) and lipid levels are two of the most extensively studied risk factors for common diseases of aging, such as cardiovascular disease (CVD) and osteoporosis (OP). These two risk factors are also correlated with each other, but little is known about the molecular mechanisms behind this correlation. Recent studies revealed that circulating levels of several metabolites involved in the biosynthesis of androsterone correlate significantly with BMD and have the capacity to affect cholesterol and lipids levels. A main aim of the present study was to investigate the hypothesis that androsterone-related metabolites could provide a link between CVD and OP, as a common cause of lipid levels and BMD. The present study employed data from the NIHR BRC TwinsUK BioResource, comprising 1909 and 1994 monozygotic and dizygotic twin pairs, respectively, to address the causal relationships among BMD and lipids, and their associated metabolites, using reciprocal causation twin modelling, as well as Mendelian randomization (MR) using large publicly-available GWAS datasets on lipids and BMD, in conjunction with TwinsUK metabolite data. While results involving the twin modelling and MR analyses with metabolites were unable to establish a causal link between metabolite levels and either lipids or BMD, MR analyses of BMD and lipids suggest that lipid levels have a causal impact on BMD, which is consistent with findings from clinical trials of lipid-lowering drugs, which have also increased BMD. [ABSTRACT FROM AUTHOR]

Introduction: The Malawian government recently introduced cost-covering consultation fees for self-referral patients in tertiary public hospitals. Previously, patients received medicines free of charge in government-owned health facilities, but must pay elsewhere. Before the government implements a payment policy in other areas of health care, it is important to investigate the prices, affordability and availability of essential medicines in Malawi. Methods: Data on availability and prices of 50 essential medicines were collected in 44 health facilities in two major cities and two districts. These included 12 public facilities, 11 facilities of the Christian Health Association of Malawi (CHAM), nine retail pharmacies, eight wholesalers and four private clinics/hospitals. Price, availability and affordability were assessed based on the methodology developed by the World Health Organization and Health Action International, which compares local prices to international reference prices. Results and discussion: The overall availability of medicines was 48.5% in public facilities, 71.1% in retail pharmacies, 62.9% in CHAM facilities and 57.5% in private clinics. The availability of essential medicines varied from 0% for ethosuximide to 100% for amoxicillin and cotrimoxazole tablets. Antibiotic formulations for adults were widely available, in contrast to the low availability of pediatric formulations. Several medicines for non-communicable diseases like sodium valproate, phenytoin, paraldehyde, captopril and simvastatin showed poor availability and affordability. The overall median price ratio compared to the international reference price was 1.11 for wholesalers, 2.54 in CHAM facilities, 2.70 in retail pharmacies, and 4.01 in private clinics, which is low compared to other countries. But nevertheless, for 18 out of 32 medicines assessed, the cost of one course exceeded the statutory minimum daily wage, making them unaffordable to a majority of the population. Therefore, continued provision of free public health care is still of critical importance for the foreseeable future until other financing mechanisms have been explored. [ABSTRACT FROM AUTHOR]

Seepage of methane (CH4) on land and in the sea may significantly affect Earth’s biogeochemical cycles. However processes of CH4 generation and consumption, both abiotic and microbial, are not always clear. We provide new geochemical and isotope data to evaluate if a recently discovered CH4 seepage from the shallow seafloor close to the Island of Elba (Tuscany) and two small islands nearby are derived from abiogenic or biogenic sources and whether carbonate encrusted vents are the result of microbial or abiotic processes. Emission of gas bubbles (predominantly CH4) from unlithified sands was observed at seven spots in an area of 100 m2 at Pomonte (Island of Elba), with a total rate of 234 ml m-2 d-1. The measured carbon isotope values of CH4 of around -18‰ (VPDB) in combination with the measured δ2H value of -120‰ (VSMOW) and the inverse correlation of δ13C-value with carbon number of hydrocarbon gases are characteristic for sites of CH4 formation through abiogenic processes, specifically abiogenic formation of CH4 via reduction of CO2 by H2. The H2 for methanogenesis likely derives from ophiolitic host rock within the Ligurian accretionary prism. The lack of hydrothermal activity allows CH4 gas to become decoupled from the stagnant aqueous phase. Hence no hyperalkaline fluid is currently released at the vent sites. Within the seep area a decrease in porewater sulphate concentrations by ca. 5 mmol/l relative to seawater and a concomitant increase in sulphide and dissolved inorganic carbon (DIC) indicate substantial activity of sulphate-dependent anaerobic oxidation of methane (AOM). In absence of any other dissimilatory pathway, the δ13C-values between -17 and -5‰ in dissolved inorganic carbon and aragonite cements suggest that the inorganic carbon is largely derived from CH4. The formation of seep carbonates is thus microbially induced via anaerobic oxidation of abiotic CH4. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunistic pathogen that causes severe infections, such as pneumonia and bacteremia. Several studies demonstrated that flagellar motility is an important virulence factor for P. aeruginosa infection. In this study, we determined whether sulfated vizantin affects P. aeruginosa flagellar motility in the absence of direct antimicrobial activity. We found that 100 μM sulfated vizantin suppressed P. aeruginosa PAO1 from penetrating through an artificial mucin layer by affecting flagellar motility, although it did not influence growth nor bacterial protease activity. To further clarify the mechanism in which sulfated vizantin suppresses the flagellar motility of P. aeruginosa PAO1, we examined the effects of sulfated vizantin on the composition of the flagellar filament and mRNA expression of several flagella-related genes, finding that sulfated vizantin did not influence the composition of the flagellar complex (fliC, motA, and motB) in P. aeruginosa PAO1, but significantly decreased mRNA expression of the chemotaxis-related genes cheR1, cheW, and cheZ. These results indicated that sulfated vizantin is an effective inhibitor of flagellar motility in P. aeruginosa. [ABSTRACT FROM AUTHOR]

In the present study, a comprehensive approach to the biosorption process was proposed. Biosorption of Cr(III), Mn(II) and Mg(II) ions by a freshwater macroalga Cladophora glomerata was examined using several advanced techniques including FTIR (Fourier Transform Infrared Spectroscopy), ICP-OES (Inductively Coupled Plasma–Optical Emission Spectrometry) and SEM-EDX (Scanning Electron Microscopy with Energy Dispersive X-Ray Spectroscopy). The enriched biomass can become a valuable, bioactive feed additive for different breeds of animals. Additionally, the collected algal biomass was soaked in water in order to reduce the content of carbohydrate, what is especially important for animals with metabolic disorders. The content of starch was reduced by 22% but additionally some elements–mainly Si, K and P were removed from the biomass. It was shown that the natural macroalga had better biosorption properties than soaked. Cr(III) ions were sorbed by the biomass in the highest extent, then Mn(II) and finally Mg(II) ions. The content of chromium in the enriched algal biomass increased almost ~200 000 times, manganese ~75 times and magnesium ~4.5 times (both for Mg(II) ions used from magnesium sulphate, as well as from magnesium chloride) when compared to the natural Cladophora glomerata. In the case of the soaked biomass the increase of the content of elements in the enriched biomass was as follows ~17 165 times for Cr, ~25 times for Mn and for Mg ~3.5 times for chloride and 3.8 times for sulphate. The type of magnesium salt (chloride or sulphate) had no significant effect on the algal sorption capacity. The proposed mechanism of the biosorption is ion exchange in which mainly potassium participated. The applied FTIR analysis enabled the identification of the functional groups that participated in the biosorption process–mainly carboxyl and hydroxyl. The main changes in the appearance of the spectra were observed for the following wavenumbers– 3300–3400; 2900; 1700; 1400–1500 and 1200–1300 cm-1. The application of SEM-EDX proved that the metal ions were sorbed on the surface of both tested algae. [ABSTRACT FROM AUTHOR]

Recent studies have shown that HDAC inhibitors act synergistically with camptothecin derivatives in combination therapies. To exploit this synergy, new hybrid molecules targeting simultaneously topoisomerase I and HDAC were designed. In particular, a selected multivalent agent containing a camptothecin and a SAHA-like template showed a broad spectrum of antiproliferative activity, with IC50 values in the nanomolar range. Preliminary in vivo results indicated a strong antitumor activity on human mesothelioma primary cell line MM473 orthotopically xenografted in CD-1 nude mice and very high tolerability. [ABSTRACT FROM AUTHOR]

An influenza epidemic is still a problem despite the development of vaccines and anti-influenza drugs. Preventive measures such as handwashing are fundamental and important for counteracting influenza virus infection. In this study, we clarified the anti-influenza virus effects of surfactants, which are the main components of hand soaps for hand washing: potassium oleate (C18:1), sodium laureth sulfate (LES) and sodium lauryl sulfate (SDS). For a human influenza virus strain (H3N2), C18:1 reduced the infectivity by 4 logs or more, whereas LES and SDS reduced the infectivity by 1 log or less. Similar results were obtained when an avian influenza virus strain (H5N3) was used. The interaction between the surfactant and virus was then investigated by isothermal titration calorimetry. The LES-virus system showed a positive value of enthalpy changes (ΔH), meaning an exothermic interaction that indicated a hydrophobic interaction. In contrast, both the C18:1-virus system and the SDS-virus system showed negative values of ΔH, meaning an endothermic interaction that indicated an electrical interaction. The ΔH value of the C18:1-virus system was much higher than that of the SDS-virus system. A mixture of C18:1 and HA proteins similarly showed negative values of ΔH. These results indicate that influenza virus inactivation by a hydrophobic interaction of a surfactant with the viral envelope is insufficient to prevent infection, whereas inactivation by an electrical interaction of a surfactant with HA proteins is sufficient to prevent influenza virus infection. [ABSTRACT FROM AUTHOR]

Introduction: Proliferative glomerulonephritis manifests in a range of renal diseases and is characterized by the influx of inflammatory cells into the glomerulus. Heparan sulfate (HS) is an important (co-)receptor for binding of chemokines, cytokines and leukocytes to the endothelial glycocalyx, a thick glycan layer that covers the inside of blood vessels. During glomerulonephritis, HS in the glomerular endothelial glycocalyx plays a central role in chemokine presentation and oligomerization, and in binding of selectins and integrins expressed by leukocytes. We hypothesize that distinct endothelial HS domains determine the binding of different chemokines. In this study we evaluated the interaction of three pro-inflammatory chemokines (CXCL1, CXCL2 and CCL2) with mouse glomerular endothelial cells (mGEnC-1) in ELISA in competition with different HS preparations and anti-HS single chain variable fragment (scFv) antibodies specific for distinct HS domains. Results: HS appeared to be the primary ligand mediating chemokine binding to the glomerular endothelial glycocalyx in vitro. We found differential affinities of CXCL1, CXCL2 and CCL2 for HS in isolated mGEnC-1 glycocalyx, heparan sulfate from bovine kidney or low molecular weight heparin in competition ELISAs using mGEnC-1 as a substrate, indicating that chemokine binding is affected by the domain structure of the different HS preparations. Blocking of specific HS domains with anti-HS scFv antibodies revealed a domain-specific interaction of the tested chemokines to HS on mGEnC-1. Furthermore, chemokines did not compete for the same binding sites on mGEnC-1. Conclusion: CXCL1, CXCL2 and CCL2 binding to the glomerular endothelial glycocalyx appears differentially mediated by specific HS domains. Our findings may therefore contribute to the development of HS-based treatments for renal and possibly other inflammatory diseases specifically targeting chemokine-endothelial cell interactions. [ABSTRACT FROM AUTHOR]

Objective: This study evaluates molecular, nutritional and biochemical alterations in human intervertebral discs between middle and old age. Methods: Twenty-eight human lumbar intervertebral discs from donors were evaluated and separated into two groups: Middle-aged (35–50 years old, relatively non-degenerate discs of Pfirrmann grades 1–3, n = 15) and Old-aged (≥80 years old, all degenerate Pfirrmann grade 4 or 5, n = 13). Parameters which might be expected to to be related to nutrient supply and so the health of disc cells (eg the porosity of the vertebral endplate, cell viability and cell density) and to disc extracellular composition (ie quantification of glycosaminoglycan disaccharides and hyaluronic acid molecular weight) and collagen organization, were analyzed. Three regions of the intervertebral disc (anterior annulus fibrosus, nucleus pulposus, and posterior annulus fibrosus) were examined. Results: The old-aged group showed a decrease in content of sulphated and non-sulphated glycosaminoglycans relative to middle-aged and there were also alterations in the proportion of GAG disaccharides and a decrease of collagen fiber size. Hyaluronic acid molecular weight was around 200 kDa in all regions and ages studied. The anterior annulus differed from the posterior annulus particularly in relation to cell density and GAG content. Additionally, there were changes in the bony endplate, with fewer openings observed in the caudal than cranial endplates of all discs in both groups. Conclusions: Results show the cranial vertebral endplate is the main vascular source for the intervertebral discs. Hylauronic acid molecular weight is the same through the intervertebral disc after age of 50 years. [ABSTRACT FROM AUTHOR]

Bloodstream infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are associated with treatment failure and increased mortality. Detection of CPE from blood cultures (BC) by standard methods takes 16–72 hours, which can delay the initiation of appropriate antimicrobial therapy and compromise patient outcome. In the present study, we developed and evaluated a new method for the rapid detection of carbapenemases directly from positive BC using a new multiplex immunochromatographic test (ICT). The new ICT was assessed using 170 molecularly characterized Enterobacteriaceae clinical isolates including 126 CPE (OXA-48-like (N = 79), KPC (N = 18) and NDM (N = 29)). After spiking with bacteria and incubation in a BC system, blood from positive BC bottles was hemolyzed, bacteria concentrated by centrifugation and lysed. The lysate was transferred to the RESIST-3 O.K.N. ICT (Coris BioConcept, Gembloux, Belgium), which detects OXA-48-like, KPC and NDM carbapenemases. The final results of the ICT were read when they became positive, at the latest after 15 min. All CPE isolates (126/126) were correctly detected with the new protocol (100% sensitivity, 100% specificity). There was perfect concordance between ICT results and molecular characterization. Total time to result was 20–45 min. Conclusions: This proof-of-principle study demonstrates that with the newly developed method, OXA-48-like, KPC and NDM carbapenemases can be reliably detected directly from positive BC bottles. The new method is more rapid than other currently available assays and can be performed in any routine microbiology laboratory. This can help to rapidly identify patients with CPE BSI and optimize the management of patients with these difficult-to-treat infections. Further studies are needed to assess the performance of the ICT in routine diagnostics. [ABSTRACT FROM AUTHOR]

In pest eradication programs, traps can directly reduce pest populations; however, their application to gastropod programs remains relatively unexplored. The South Florida Giant African Snail, Liassachatina fulica (Pulmonata: Achatinidae), eradication program allowed a realistic evaluation of their utility. Field studies were conducted to determine the best bait, barrier and trap for use during the eradication program. Immature and adult snails were attracted to banana fruit and a commercially produced bait but only the commercially produced bait did not attract non-target and pest mammals. Four commercially produced traps and 4 barriers were field evaluated for snail retention efficacy. Snails escaped all traps and trap/barrier combinations but the rate of escape ranged from 10–100% after 24 hrs. Laboratory studies confirmed that snails can survive crossing a 5 cm barrier of copper tape, salt, insect stickem or antifouling paint. In the laboratory study snails did not cross copper sulfate but they crossed the barrier in the field. Adding salt to traps as a means to retain snails reduced the number of snails trapped. Laboratory studies confirmed that dry salt decreased the number of snails entering traps and snails did not enter traps when the salt was dissolved in water. Two trap types and the commercial bait were selected for a large-scale program test. For three months, trapping along with hand collection and pesticide application were conducted on 114 properties in five locations. Traps caught snails when surveys and regular pesticide applications on the same properties did not detect them. On 21 occasions snails were only found in traps, and both immature and adult snails were caught. This study showed that traps could be effectively deployed in an eradication program and they could capture snails that may have escaped other control measures. [ABSTRACT FROM AUTHOR]

The long-term use of proton pump inhibitors (PPIs) has been shown to increase the risk of cardiovascular mortality, however the molecular mechanisms are unknown. Superoxide has been implicated in the regulation of nerve growth factor (NGF), a mediator of sympathetic innervation. The purpose of this study was to determine whether PPIs increase ventricular arrhythmias through magnesium-mediated superoxide production in infarcted rats. Male Wistar rats were randomly assigned to receive vehicle, omeprazole, omeprazole + magnesium sulfate, or famotidine treatment for 4 weeks starting 24 hours after the induction of myocardial infarction by ligating the coronary artery. Increased myocardial superoxide and nitrotyrosine levels were noted post-infarction, in addition to a significant upregulation of NGF expression on mRNA and protein levels. Sympathetic hyperinnervation after infarction was confirmed by measuring myocardial norepinephrine and immunofluorescent analysis. Compared with the vehicle, omeprazole-treated infarcted rats had significantly reduced myocardial magnesium content, increased oxidant production, and increased sympathetic innervation, which in turn increased ventricular arrhythmias. These effects were prevented by the coadministration of magnesium sulfate. In an in vivo study, an omeprazole-induced increase in NGF was associated with a superoxide pathway, which was further confirmed by an ex vivo study showing the attenuation of NGF levels after coadministration of the superoxide scavenger Tiron. Magnesium sulfate did not further attenuate NGF levels compared with omeprazole + Tiron. Our results indicate that the long-term administration of PPIs was associated with reduced tissue magnesium content and increased myocardial superoxide production, which exacerbated ventricular arrhythmias after infarction. Magnesium may be a potential target for PPI-related arrhythmias after infarction. [ABSTRACT FROM AUTHOR]

It is suggested that most cases of low back pain are related to degeneration of intervertebral discs. Disc degeneration is a chronic and progressive disease and the search for effective medical treatments continues. Neurotropin is widely used in Japan and China to treat low back pain and neck–shoulder–arm syndrome. The present study aimed to investigate the effect of Neurotropin on glycosaminoglycan synthesis in nucleus pulposus cells. Cultured human nucleus pulposus cells were treated with Neurotropin every second day for two weeks. Production of glycosaminoglycan was assessed using a dimethyl-methylene blue assay and PicoGreen was used to measure DNA content. Microarray analysis, real-time PCR, and western blotting were performed to assess the biological processes related to Neurotropin-stimulated glycosaminoglycan synthesis. The results showed that the level of glycosaminoglycan normalized to DNA content was significantly upregulated by the addition of Neurotropin. Gene expression profiling showed over two-fold upregulation of 697 genes in response to Neurotropin treatment. Among these genes, ontological analysis suggested significant implication of phosphatidylinositol 3-kinase signaling, and analysis focused on this pathway demonstrated marked upregulation of angiopoietin 1 and insulin-like growth factor 1. Activation of phosphorylation of the signal transducer protein AKT was detected by western blotting. Of the genes related to sulfated glycosaminoglycan synthesis, the greatest increase in mRNA levels was observed for chondroitin sulfate N-acetylgalactosaminyltransferase 1, an enzyme initiating synthesis of chondroitin sulfate side chains attached to a core protein of aggrecan, which is a predominant disc matrix component. These findings suggest that Neurotropin may activate the phosphatidylinositol 3-kinase–AKT pathway and stimulate glycosaminoglycan synthesis through upregulation of expression of mRNA for chondroitin sulfate N-acetylgalactosaminyltransferase 1. Because there was no cytotoxic cellular growth inhibition, Neurotropin treatment might offer an accessible therapeutic strategy for intervertebral disc degeneration. [ABSTRACT FROM AUTHOR]