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Sulfur (S) is an essential macronutrient for plants and its availability in soils is an important determinant for growth and development. Current regulatory policies aimed at reducing industrial S emissions together with changes in agronomical practices have led to a decline in S contents in soils worldwide. Deficiency of sulfate—the primary form of S accessible to plants in soil—has adverse effects on both crop yield and nutritional quality. Hence, recent research has increasingly focused on unraveling the molecular mechanisms through which plants detect and adapt to a limiting supply of sulfate. A significant part of these studies involves the use of omics technologies and has generated comprehensive catalogs of sulfate deficiency-responsive genes and processes, principally in Arabidopsis together with a few studies centering on crop species such as wheat, rice, or members of the Brassica genus. Although we know that sulfate deficiency elicits an important reprogramming of the transcriptome, the transcriptional regulators orchestrating this response are not yet well understood. In this review, we summarize our current knowledge of gene expression responses to sulfate deficiency and recent efforts towards the identification of the transcription factors that are involved in controlling these responses. We further compare the transcriptional response and putative regulators between Arabidopsis and two important crop species, rice and tomato, to gain insights into common mechanisms of the response to sulfate deficiency. [ABSTRACT FROM AUTHOR]

Sulfur (S) is an essential macronutrient for plant growth and metabolism. SULTR2;1 is a low-affinity sulfate transporter facilitating the long-distance transport of sulfate in Arabidopsis. The physiological function of SULTR2;1 in the plant life cycle still needs to be determined. Therefore, we analyzed the sulfate transport, S-containing metabolite accumulation and plant growth using Arabidopsis SULTR2;1 disruption lines, sultr2;1–1 and sultr2;1–2 , from seedling to mature growth stages to clarify the metabolic and physiological roles of SULTR2;1. We observed that sulfate distribution to the stems was affected in sultr2;1 mutants, resulting in decreased levels of sulfate, cysteine, glutathione (GSH) and total S in the stems, flowers and siliques; however, the GSH levels increased in the rosette leaves. This suggested the essential role of SULTR2;1 in sulfate transport from rosette leaves to the primary stem. In addition, sultr2;1 mutants unexpectedly bolted earlier than the wild-type without affecting the plant biomass. Correlation between GSH levels in rosette leaves and the bolting timing suggested that the rosette leaf GSH levels or limited sulfate transport to the early stem can trigger bolting. Overall, this study demonstrated the critical roles of SULTR2;1 in maintaining the S metabolite levels in the aerial part and transitioning from the vegetative to the reproductive growth phase. [ABSTRACT FROM AUTHOR]

The roles of keratan sulfate (KS) as a proton detection glycosaminoglycan in neurosensory processes in the central and peripheral nervous systems is reviewed. The functional properties of the KS-proteoglycans aggrecan, phosphacan, podocalyxcin as components of perineuronal nets in neurosensory processes in neuronal plasticity, cognitive learning and memory are also discussed. KS-glycoconjugate neurosensory gels used in electrolocation in elasmobranch fish species and KS substituted mucin like conjugates in some tissue contexts in mammals need to be considered in sensory signalling. Parallels are drawn between KS's roles in elasmobranch fish neurosensory processes and its roles in mammalian electro mechanical transduction of acoustic liquid displacement signals in the cochlea by the tectorial membrane and stereocilia of sensory inner and outer hair cells into neural signals for sound interpretation. The sophisticated structural and functional proteins which maintain the unique high precision physical properties of stereocilia in the detection, transmittance and interpretation of acoustic signals in the hearing process are important. The maintenance of the material properties of stereocilia are essential in sound transmission processes. Specific, emerging roles for low sulfation KS in sensory bioregulation are contrasted with the properties of high charge density KS isoforms. Some speculations are made on how the molecular and electrical properties of KS may be of potential application in futuristic nanoelectronic, memristor technology in advanced ultrafast computing devices with low energy requirements in nanomachines, nanobots or molecular switches which could be potentially useful in artificial synapse development. Application of KS in such innovative areas in bioregulation are eagerly awaited. [ABSTRACT FROM AUTHOR]

Keratan sulfate glycosaminoglycan is composed of repeating N -acetyllactosamine (LacNAc) disaccharide units consisting of galactose (Gal) and N -acetylglucosamine (GlcNAc), both often 6- O -sulfated. Sulfate contents of keratan sulfate are heterogeneous depending upon the origins. In this study, keratan sulfate is classified as either highly sulfated (in which both GlcNAc and Gal residues are 6- O -sulfated) or low-sulfated (in which only GlcNAc residues are 6- O -sulfated). It is reported that highly sulfated keratan sulfate detected by the 5D4 monoclonal antibody is preferentially expressed in normal epithelial cells lining the female genital tract and in their neoplastic counterparts; however, expression of low-sulfated keratan sulfate in either has not been characterized. In the present study, we generated the 294-1B1 monoclonal antibody, which selectively recognizes low-sulfated keratan sulfate, and performed precise glycan analysis of sulfated glycans expressed on human serous ovarian carcinoma OVCAR-3 cells. We found that OVCAR-3 cells do not express highly sulfated keratan sulfate but rather express low-sulfated form, which was heterogeneous in 294-1B1 reactivity. Comparison of mass spectrometry spectra of sulfated glycans in 294-1B1-positive versus -negative OVCAR-3 cells indicated that the 294-1B1 epitope is likely at least 2, and possibly 3 or more, tandem GlcNAc-6- O -sulfated LacNAc units. Then, using the 294-1B1 antibody, we performed quantitative immunohistochemical analysis of 40 specimens from patients with ovarian cancer, consisting of 10 each of serous, endometrioid, clear cell, and mucinous carcinomas, and found that among them low-sulfated keratan sulfate was widely expressed in all but mucinous ovarian carcinoma. [ABSTRACT FROM AUTHOR]

Sulfate/sulfite-reducing microorganisms (SRM) are ubiquitous in nature, driving the global sulfur cycle. A hallmark of SRM is the dissimilatory sulfite reductase encoded by the genes dsrAB. Based on analysis of 950 mainly metagenome-derived dsrAB -carrying genomes, we redefine the global diversity of microorganisms with the potential for dissimilatory sulfate/sulfite reduction and uncover genetic repertoires that challenge earlier generalizations regarding their mode of energy metabolism. We show: (i) 19 out of 23 bacterial and 2 out of 4 archaeal phyla harbor uncharacterized SRM, (ii) four phyla including the Desulfobacterota harbor microorganisms with the genetic potential to switch between sulfate/sulfite reduction and sulfur oxidation, and (iii) the combination as well as presence/absence of different dsrAB- types , dsrL -types and dsrD provides guidance on the inferred direction of dissimilatory sulfur metabolism. We further provide an updated dsrAB database including > 60% taxonomically resolved, uncultured family-level lineages and recommendations on existing dsrAB -targeted primers for environmental surveys. Our work summarizes insights into the inferred ecophysiology of newly discovered SRM, puts SRM diversity into context of the major recent changes in bacterial and archaeal taxonomy, and provides an up-to-date framework to study SRM in a global context. [ABSTRACT FROM AUTHOR]

Under conditions of sulfur deprivation, O -acetylserine (OAS) accumulates, which leads to the induction of a common set of six genes, called OAS cluster genes. These genes are induced not only under sulfur deprivation, but also under other conditions where OAS accumulates, such as shift to darkness and stress conditions leading to reactive oxygen species (ROS) or methyl-jasmonate accumulation. Using the OAS cluster genes as a query in ATTED-II, a co-expression network is derived stably spanning several hundred conditions. This allowed us not only to describe the downstream function of the OAS cluster genes but also to score for functions of the members of the co-regulated co-expression network and hence the effects of the OAS signal on the sulfate assimilation pathway and co-regulated pathways. Further, we summarized existing knowledge on the regulation of the OAS cluster and the co-expressed genes. We revealed that the known sulfate deprivation-related transcription factor EIL3/SLIM1 exhibits a prominent role, as most genes are subject to regulation by this transcription factor. The role of other transcription factors in response to OAS awaits further investigation. [ABSTRACT FROM AUTHOR]

High-performance liquid chromatographic method was developed, validated and applied for miconazole, mometasone and gentamicin in Momenta® cream. Physical separation was applied using two extraction procedures due to different solubility of the three components. First, a methanolic extract of the cream contained miconazole and mometasone was chromatographed on ODS-3 Inertsil C18 column (150 × 4.6, 5 μm) using acetonitrile: water (80:20, v/v) as a mobile phase, flow rate 1.5 mL·min−1, scanned at 230 nm, showing tR 2.817 and 6.808 min for mometasone and miconazole, respectively. Second, an aqueous extract of the cream containing gentamicin was derivatized with o-phthalaldehyde in order to enhance the gentamicin UV detection and subjected to ion pairing chromatography on Inertsil ODS-3 C18 column (150 × 4.6, 5 μm), using methanol: 0.025 M heptane sulphonic acid: glacial acetic acid (75:20:5, by volume) as a mobile phase, flow rate 0.8 mL·min−1, scanned at 330 nm where the three active gentamicin isomers were separated at tR 11.7, 15.6 and 18.3 min. Suitability of this method for quantitative estimation of the drugs was proved by validation according to ICH guidelines. The method was selective, precise and accurate so could be used for analysis of cream formulation in QC labs. [ABSTRACT FROM AUTHOR]

Sulfate assimilation is an essential pathway of plant primary metabolism, regulated by the demand for reduced sulfur (S). The S-containing tripeptide glutathione (GSH) is the key signal for such regulation in Arabidopsis, but little is known about the conservation of these regulatory mechanisms beyond this model species. Using two model monocot species, C3 rice (Oryza sativa) and C4 Setaria viridis , and feeding of cysteine or GSH, we aimed to find out how conserved are the regulatory mechanisms described for Arabidopsis in these species. We showed that while in principle the regulation is similar, there are many species-specific differences. For example, thiols supplied by the roots are translocated to the shoots in rice but remain in the roots of Setaria. Cysteine and GSH concentrations are highly correlated in Setaria , but not in rice. In both rice and Setaria , GSH seems to be the signal for demand-driven regulation of sulfate assimilation. Unexpectedly, we observed cysteine oxidation to sulfate in both species, a reaction that does not occur in Arabidopsis. This reaction is dependent on sulfite oxidase, but the enzyme(s) releasing sulfite from cysteine still need to be identified. Altogether our data reveal a number of unique features in the regulation of S metabolism in the monocot species and indicate the need for using multiple taxonomically distinct models to better understand the control of nutrient homeostasis, which is important for generating low-input crop varieties. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of breed on voluntary preferential intake of two sources of Cu, Mn, and Zn when added to white salt-based trace mineral supplement (days 0 to 55; experiment 1) and protein supplement (days 56 to 112; experiment 2). On day 0, Nelore and ½ Angus × ½ Nelore heifers (n  = 20/breed) were stratified by breed, body weight (BW = 347 ± 82 kg), and age (12 to 30 mo), and randomly allocated into 1 of the 40 drylot pens (1 heifer/pen). Both experiments were divided into washout (days 0 to 27 in experiment 1 and days 56 to 83 in experiment 2) and preferential intake periods (days 28 to 55 in experiment 1 and days 84 to 112 in experiment 2). During the respective preferential intake period, heifers were provided simultaneous free-choice access to sulfate (SUL) and hydroxychloride (HYD) sources of Cu, Mn, and Zn mixed into salt-based trace mineral supplements from days 28 to 55 (experiment 1) and then protein supplements from days 84 to 112 (experiment 2). Heifers were provided free-choice access to Tifton 85 (Cynodon sp.) hay from days 0 to 112. Effects of breed × source × day of the study were detected (P  ≤ 0.05) for daily trace mineral intake from days 28 to 56 and days 84 to 112. Angus × Nelore heifers consumed a greater amount of SUL vs. HYD supplements on days 31 to 33 (P  = 0.02) and HYD vs. SUL supplements on days 37 to 42 (P  ≤ 0.02), whereas Nelore heifers consumed more HYD vs. SUL supplements on days 31 to 33 and 43 to 51 (P  ≤ 0.05). Both breeds consumed (P  ≤ 0.05) a greater amount of protein supplement containing HYD vs. SUL from days 84 to 112, but the differences in protein supplement intake increased (P  ≤ 0.04) in greater magnitude for Nelore vs. Angus × Nelore heifers. Supplement intake coefficient of variation (CV) from days 28 to 41 and days 84 to 97 tended (P  = 0.06) to be greater for Nelore vs. Angus × Nelore heifers. Effects of breed × source were detected (P  = 0.02) for supplement intake CV from days 84 to 112. Intake CV of supplements added with HYD did not differ (P  ≥ 0.40) between Nelore vs. Angus × Nelore heifers but was greater (P  < 0.01) for Nelore vs. Angus × Nelore heifers fed SUL supplements. Overall, Nelore heifers had greater preferential intake for mineral and protein supplements containing hydroxychloride vs. sulfate sources compared to Angus × Nelore heifers. Hydroxychloride sources encouraged voluntary intake and reduced variation in supplement consumption compared to SUL sources of the same metals. [ABSTRACT FROM AUTHOR]

It is still a huge challenge for bone regenerative biomaterial to balance its mechanical, biological and biodegradable properties. In the present study, a new composite material including treated dentin matrix (TDM) and α-calcium sulphate hemihydrate (α-CSH) was prepared. The optimal composition ratio between TDM and α-CSH was explored. The results indicate that both components were physically mixed and structurally stable. Its compressive strength reaches up to 5.027 ± 0.035 MPa for 50%TDM/α-CSH group, similar to human cancellous bone tissues. Biological experiments results show that TDM/α-CSH composite exhibits excellent biocompatibility and the expression of osteogenic related genes and proteins (ALP, RUNX2, OPN) is significantly increased. In vivo experiments suggest that the addition of TDM for each group (10%, 30%, 50%) effectively promotes cell proliferation and osteomalacia. In addition, 50% of the TDM/α-CSH combination displays optimal osteoconductivity. The novel TDM/α-CSH composite is a good candidate for certain applications in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Background Chronic kidney disease (CKD) is a major public health issue associated with increased cardiovascular, infectious and all-cause mortality. The neutrophil:lymphocyte ratio (NLR) is a predictive marker of the risk of death and cardiovascular events. Uremic toxins, notably indoxyl sulfate (IS), are involved in immune deficiency and cardiovascular complications associated with CKD. The aim of this study was to assess whether the NLR was related to uremic toxins and could predict clinical outcome in hemodialysis (HD) patients. Methods We conducted a prospective cohort study of 183 patients on chronic HD. The main objective was to study the correlation between the NLR and uremic toxin serum levels. The secondary objective was to test if the NLR can predict the incidence of mortality, cardiovascular events and infectious events. Results Patients were separated into two groups according to the NLR median value (3.49). The NLR at inclusion was correlated with the NLR at the 6-month (r  = 0.55, P < 0.0001) and 12-month (r  = 0.62, P < 0.0001) follow-up. Among uremic toxins, IS levels were higher in the group with high NLR (104 µmol/L versus 81 µmol/L; P = 0.004). In multivariate analysis, the NLR remained correlated with IS (P = 0.03). The incidence of death, cardiovascular events and severe infectious events was higher in the group with high NLR [respectively, 38% versus 18% (P = 0.004), 45% versus 26% (P = 0.01) and 33% versus 21% (P = 0.02)] than in the low NLR group. Multivariate analysis showed an independent association of the NLR with mortality (P = 0.02) and cardiovascular events (P = 0.03) but not with severe infectious events. Conclusions In HD patients, the NLR predicted mortality and cardiovascular events but not severe infections and correlated positively with the level of the uremic toxin IS. The NLR could be an interesting marker for monitoring the risk of clinical events in CKD patients. [ABSTRACT FROM AUTHOR]

Introduction: It is established that higher prediagnostic circulating androgen and estrogen levels are associated with increased breast cancer risk in premenopausal and postmenopausal women. Pooled analyses in postmenopausal women report higher androgen and estrogen levels in current heavy cigarette smokers compared to nonsmokers. However, evidence among premenopausal women has been inconsistent.Aims and Methods: We conducted a systematic review and meta-analysis to estimate differences in standardized mean hormone levels among current premenopausal smokers compared to nonsmokers. We reviewed and collated publications with sex hormone levels by smoking status among healthy, premenopausal women who were nonusers of exogenous hormones, including oral contraceptives, using PubMed through December 2019. A random effects meta-analysis was conducted to combine the standardized mean differences (SMD) and 95% confidence intervals (CIs) for estradiol, progesterone, testosterone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and sex hormone-binding globulin by smoking status. Findings were summarized by menstrual cycle phase and overall.Results: Nineteen published peer-reviewed articles were included. Significantly increased testosterone levels among smokers compared to nonsmokers were identified from cross-sectional studies with varied menstrual phase timing (SMD 0.14; 95% CI 0.0005, 0.29) and significantly increased dehydroepiandrosterone-sulfate levels were found over all phases (SMD 0.12; 95% CI 0.01, 0.22). However, substantial heterogeneity existed in these studies.Conclusions: This meta-analysis suggests that smoking may increase blood androgen levels in healthy premenopausal women which may increase breast cancer risk; however, the differences were modest. Larger and covariate-adjusted studies with standardized collection over the menstrual cycle are needed to better understand this relationship and to reduce heterogeneity.Implications: Existing research has described associations between high prediagnostic estradiol and androgen levels with breast cancer risk among premenopausal women and has established active smoking as a breast cancer risk factor. However, the smoking and circulating sex hormone associations among premenopausal women remain inadequately studied. In this meta-analysis, we identified an association between smoking and higher mean testosterone and dehydroepiandrosterone-sulfate levels with consideration of menstrual phase, providing additional information on smoking's potential pathway to premenopausal breast cancer. [ABSTRACT FROM AUTHOR]

Background Beryllium and its compounds are carcinogenicity, but the mechanisms through which this occurs have yet to be clarified. Accumulating evidence exists that long noncoding RNAs (lncRNAs) play an important role in occurrence and development of cancer. Aims and Methods To explore the carcinogenic mechanism of beryllium, human bronchial epithelial cells (16HBE) were treated with 50 μM beryllium sulfate (BeSO4) for 45 passages (~23 weeks). The expression levels of lncRNA SNHG7, SNHG11, SNHG15, MIR22HG, GMPS, and SIK1 were detected at passage 0 (P0), 15 (P15), 25 (P25), 35 (P35), and 45 (P45). Results The results indicated that enhanced cell proliferation, extensive clones in soft agar, protein expressions of up-regulated matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 2 (MMP2), proliferating cell nuclear antigen (PCNA), cyclin D1, and down-regulated p53 were all observed at the 45th passage in 16HBE cells. Thus, BeSO4-transformed 16HBE cells (T-16HBE) were established. Meanwhile, the study found that the expression of lncRNA SNHG11 was elevated during malignant transformation. Knockdown of SNHG11 in T-16HBE cells blocked cell proliferation, invasion, and migration, and decreased the protein levels of MMP9, MMP2, PCNA, cyclin D1, but increased p53. Conclusions The studies revealed that SNHG11 acts as an oncogene in the malignant transformation of 16HBE cells induced by BeSO4, which signifies progress in the study of the carcinogenic mechanism of beryllium. [ABSTRACT FROM AUTHOR]

Background Blastomyces spp, the etiologic agents of blastomycosis, are endemic dimorphic fungi that require prolonged antifungal therapy, which can be complicated by adverse drug effects. Isavuconazonium sulphate (ISA) is a triazole with in vitro and in vivo activity against Blastomyces spp, but there is a paucity of clinical data supporting its use for treatment of blastomycosis. Methods This retrospective case series identified 14 patients with blastomycosis at least partially treated with ISA at the University of Wisconsin between 2015 and 2019. Treatment duration and outcomes were documented. In addition, 29 clinical isolates of Blastomyces spp between 2004 and 2017 were tested for minimum inhibitory concentrations against ISA and other antifungals. Results Fourteen patients were treated with a median of 255 days of ISA accounting for 68% of total therapy. Half (7 of 14) of the patients were immunocompromised, 11 of 14 (79%) were proven cases of blastomycosis, 7 of 14 (50%) had central nervous system (CNS) involvement, and 11 of 14 (79%) were cured. Antifungal susceptibility testing showed a consistently low minimum inhibitory concentration to ISA ≤ 0.015 mcg/mL. Conclusions This case series supports the efficacy and safety for ISA in the treatment of blastomycosis with or without CNS disseminated, especially when alternative triazoles cannot be used. [ABSTRACT FROM AUTHOR]

Effective tumor immunotherapy requires physical contact of T cells with cancer cells. However, tumors often constitute a specialized microenvironment that excludes T cells from the vicinity of cancer cells, and its underlying mechanisms are still poorly understood. DOCK2 is a Rac activator critical for migration and activation of lymphocytes. We herein show that cancer-derived cholesterol sulfate (CS), a lipid product of the sulfotransferase SULT2B1b, acts as a DOCK2 inhibitor and prevents tumor infiltration by effector T cells. Using clinical samples, we found that CS was abundantly produced in certain types of human cancers such as colon cancers. Functionally, CS-producing cancer cells exhibited resistance to cancer-specific T-cell transfer and immune checkpoint blockade. Although SULT2B1b is known to sulfate oxysterols and inactivate their tumor-promoting activity, the expression levels of cholesterol hydroxylases, which mediate oxysterol production, are low in SULT2B1b-expressing cancers. Therefore, SULT2B1b inhibition could be a therapeutic strategy to disrupt tumor immune evasion in oxysterol-non-producing cancers. Thus, our findings define a previously unknown mechanism for tumor immune evasion and provide a novel insight into the development of effective immunotherapies. [ABSTRACT FROM AUTHOR]

A sensitive and selective gas chromatography–tandem mass spectrometry method was developed for the identification and quantification of five potential genotoxic impurities (PGIs), i.e. chloromethane, 2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate, in abiraterone acetate. The method was validated according to the International Council for Harmonisation (ICH) guidelines. The linearity was established for the concentration range of 30–480 ng/mL (2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate) and 90–1440 ng/mL (chloromethane). The correlation coefficient of each PGIs was >0.995. The extraction recoveries ranged from 90.49 to 106.79% for the five PGIs. The quantitation limit, detection limit, accuracy, precision, repeatability and stability of the method demonstrated that the method was an adequate quality control tool for quantitation and identification of chloromethane, 2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate at trace levels in drug substances and drug products. [ABSTRACT FROM AUTHOR]

Steroid sulfate esters are important metabolites for anti-doping efforts in sports, pathology and research. Analysis of these metabolites is facilitated by hydrolysis using either acid or enzymatic catalysis. Although enzymatic hydrolysis is preferred for operating at neutral pH, no known enzyme is capable of hydrolyzing all steroid sulfate metabolites. Pseudomonas aeruginosa arylsulfatase (PaS) is ideal for the hydrolysis of β-configured steroid sulfates but like other known class I sulfatases it is inefficient at hydrolyzing α-configured steroid sulfates. We have used directed evolution with liquid chromatography mass spectrometry screening to find variants capable of hydrolyzing a α-configured steroid sulfate: etiocholanolone sulfate (ECS). After targeting two regions of PaS, four residues were identified and optimized to yield a final variant with a total of seven mutations (DRN-PaS) capable of hydrolyzing ECS ~80 times faster than the best PaS variant previously available. This DRN-PaS also shows improved activity for other α-configured steroid sulfates. Simultaneous mutagenesis was essential to obtain DRN-PaS due to complementarity between targeted residues. [ABSTRACT FROM AUTHOR]

Despite hostile environmental conditions, microbial communities have been found in µL-sized water droplets enclosed in heavy oil of the Pitch Lake, Trinidad. Some droplets showed high sulfate concentrations and surprisingly low relative abundances of sulfate-reducing bacteria in a previous study. Hence, we investigated here whether sulfate reduction might be inhibited naturally. Ion chromatography revealed very high formate concentrations around 2.37 mM in 21 out of 43 examined droplets. Since these concentrations were unexpectedly high, we performed growth experiments with the three sulfate-reducing type strains Desulfovibrio vulgaris , Desulfobacter curvatus , and Desulfococcus multivorans , and tested the effects of 2.5, 8, or 10 mM formate on sulfate reduction. Experiments demonstrated that 8 or 10 mM formate slowed down the growth rate of D. vulgaris and D. curvatus and the sulfate reduction rate of D. curvatus and D. multivorans. Increasing formate concentrations delayed the onsets of growth and sulfate reduction of D. multivorans , which were even inhibited completely while formate was added constantly. Contrary to previous studies, D. multivorans was the only organism capable of formate consumption. Our study suggests that formate accumulates in the natural environment of the water droplets dispersed in oil and that such levels are very likely inhibiting sulfate-reducing microorganisms. [ABSTRACT FROM AUTHOR]

Context: The adrenal cortex produces specific steroid hormones including steroid sulfates such as dehydroepiandrosterone sulfate (DHEAS), the most abundant steroid hormone in the human circulation. Steroid sulfation involves a multistep enzyme machinery that may be impaired by inborn errors of steroid metabolism. Emerging data suggest a role of steroid sulfates in the pathophysiology of adrenal tumors and as potential biomarkers.Evidence Acquisition: Selective literature search using "steroid," "sulfat*," "adrenal," "transport," "mass spectrometry" and related terms in different combinations.Evidence Synthesis: A recent study highlighted the tissue abundance of estrogen sulfates to be of prognostic impact in adrenocortical carcinoma tissue samples using matrix-assisted laser desorption ionization mass spectrometry imaging. General mechanisms of sulfate uptake, activation, and transfer to substrate steroids are reasonably well understood. Key aspects of this pathway, however, have not been investigated in detail in the adrenal; these include the regulation of substrate specificity and the secretion of sulfated steroids. Both for the adrenal and targeted peripheral tissues, steroid sulfates may have relevant biological actions beyond their cognate nuclear receptors after desulfation. Impaired steroid sulfation such as low DHEAS in Cushing adenomas is of diagnostic utility, but more comprehensive studies are lacking. In bioanalytics, the requirement of deconjugation for gas-chromatography/mass-spectrometry has precluded the study of steroid sulfates for a long time. This limitation may be overcome by liquid chromatography/tandem mass spectrometry.Conclusions: A role of steroid sulfation in the pathophysiology of adrenal tumors has been suggested and a diagnostic utility of steroid sulfates as biomarkers is likely. Recent analytical developments may target sulfated steroids specifically. [ABSTRACT FROM AUTHOR]

Peatlands are responsible for over half of wetland methane emissions, yet major uncertainties remain regarding carbon flow, especially when increased availability of electron acceptors stimulates competing physiologies. We used microcosm incubations to study the effects of sulfate on microorganisms in two temperate peatlands, one bog and one fen. Three different electron donor treatments were used (13C-acetate, 13C-formate and a mixture of 12C short-chain fatty acids) to elucidate the responses of sulfate-reducing bacteria (SRB) and methanogens to sulfate stimulation. Methane production was measured and metagenomic sequencing was performed, with only the heavy DNA fraction sequenced from treatments receiving 13C electron donors. Our data demonstrate stimulation of dissimilatory sulfate reduction in both sites, with contrasting community responses. In McLean Bog (MB), hydrogenotrophic Deltaproteobacteria and acetotrophic Peptococcaceae lineages of SRB were stimulated, as were lineages with unclassified dissimilatory sulfite reductases. In Michigan Hollow Fen (MHF), there was little stimulation of Peptococcaceae populations, and a small stimulation of Deltaproteobacteria SRB populations only in the presence of formate as electron donor. Sulfate stimulated an increase in relative abundance of reads for both oxidative and reductive sulfite reductases, suggesting stimulation of an internal sulfur cycle. Together, these data indicate a stimulation of SRB activity in response to sulfate in both sites, with a stronger growth response in MB than MHF. This study provides valuable insights into microbial community responses to sulfate in temperate peatlands and is an important first step to understanding how SRB and methanogens compete to regulate carbon flow in these systems. [ABSTRACT FROM AUTHOR]

Background: Many hormones display distinct circadian rhythms, driven by ce ntral regulators, hormonal bioavailability, and half-life. A set of 11-oxygenated C19 steroids (11-oxyandrogens) and pregnenolone sulfate (PregS) ar e elevated in congenital adrenal hyperplasia and other disorders, but their c ircadian patterns have not been characterized. Participants and methods: Peripheral blood was collected every 2 h over 24 h from health y volunteer men (10 young, 18-30 years, and 10 older, 60-80 years). We used mas s spectrometry to quantify 15 steroids, including androstenedione (A4), testosterone (T), 11ß-hydroxy- and 11-ketotestosterone (11OHT, 11KT),11ß-hydroxy- and 11-ketoandrostenedione (11OHA4, 11KA4), and 4 Δ5-steroid sulfates. Diurnal models including mesor (rhythm adjus ted median), peak, and nadir concentrations, acrophase, and amplitu de were computed. Results: 11OHA4 followed a rhythm similar to cortisol: acrophase 8:00 h, nadir 21:00 h and were similar in young and old men. 11KT had similar diurnal patterns, but the peak was lo wer in older than in young men, as was the case for A4. All four steroid sulfates were higher in young vs older men. Pr egS and 17-hydroxypregnenolone sulfate (17OHPregS) showed sustained elevations between 8:00 and 18:00 h, and nadir s around midnight, while DHEAS and AdiolS displayed minimal diurnal variations. All 4 11-oxyandrogens cor related tightly with cortisol (r from 0.54 for 11OHT to 0.81 for 11OHA4, P < 0.0001 for all), but very weakly with T, supporting their adre nal origin and ACTH governance. Conclusions: 11-Oxyandrogens, PregS, and 17OHPregS display distinct circadi an and age variations, which should be accounted for when used as clinical biomarkers. [ABSTRACT FROM AUTHOR]

This study evaluated the impact of naturally occurring water with a high-sulfate concentration on dry matter intake (DMI), water intake, growth, and trace mineral status of yearling beef heifers. Angusbased heifers (n = 48; 398.4 ± 22.1 kg) were randomly assigned to 1 of 12 pens (4 heifers/pen) and fed for 100 d arranged into 25 d periods. Heifers were provided water containing 350 (CON); 2,300 (MEDS); or 4,300 mg/L (HIGHS) sulfate. Concentrated water (71,482 mg/L sulfate) from natural source was collected and blended to achieve the treatments. All data were analyzed using the fixed effects of treatment, period (d 1-25, 26-50, 51-75, and 76-100), and the treatment × period interaction, with period as a repeated measure. Average daily gain, and gain-to-feed were not affected (P>0.29). Provision of HIGHS decreased (interaction, P< 0.01) DMI from d 1-25, 26-50 and 51-75, with no effect from d 76-100 compared with CON. Heifers drinking CON and MEDS during d 26-50 had greater (interaction, P< 0.01) water intake than HIGHS with no differences among treatments otherwise. Total sulfate intake (g/d) was greater for HIGHS, followed by MEDS and CON with a greater difference between treatments during d 26-50 (interaction, P< 0.01). Heifers provided MEDS and HIGHS had a greater (interaction, P< 0.01) reduction in serum copper compared with CON. Liver copper concentration did not differ at the start of the study but was 74% and 62% of CON for MEDS and HIGHS, respectively at the end of the study (interaction, P< 0.01). Serum selenium was greater for MEDS and HIGHS than CON; while liver selenium was least for HIGHS heifers at the end of the study (interaction, P< 0.01). These data highlight that beef heifers were able to tolerate 213 g/d of sulfate intake with no negative impact on growth performance; however, MEDS and HIGHS decreased liver copper and liver selenium concentrations. [ABSTRACT FROM AUTHOR]

This study evaluated in vivo effects of increasing sulfate concentrations of drinking water on dry matter intake (DMI), water intake, ruminal fermentation, and apparent total-tract digestibility, and in vitro effects of water sulfate and bismuth subsalicylate (BSS) dose. Eight ruminal-cannulated beef heifers (382 ± 45 kg) were stratified into two complete and one incomplete 3×3 Latin squares with 28 d periods. Water contained 341 ± 29 (LS), 2,785 ± 71 (MS), or 4,948 ± 163 mg/L (HS) sulfate. Feed and water intake, ruminal fermentation, and nutrient digestibility were evaluated. Ruminal gas samples were collected every 4 h on d 27 to analyze hydrogen sulfide (H2S) concentration. At the end of each period, digesta collected from heifers in the complete Latin squares were used for in vitro incubation to evaluate water sulfate and BSS dose (0.0, 0.2, 0.4, and 0.6% dry matter). Water intake was 7 L/d greater (P < 0.01) for HS than LS, while MS did not differ. Water sulfate did not affect DMI, but total sulfur intake increased with increasing water sulfate concentration (P < 0.01). Heifers drinking MS and HS had greater ruminal H2S for 10.5 h after water provision and HS continued to be greater for another 4 h relative to LS (sulfate hour, P < 0.01). Ruminal SCFA concentration, molar proportions of major acids, and nutrient digestibility were not affected (P≥0.19). There were no interactions between water sulfate and BSS in vitro. In vitro H2S production (μg/48 h) increased with increasing sulfate concentration (P < 0.01) and was reduced (P=0.05) by BSS inclusion. Neutral detergent fiber digestibility was not affected by sulfate or BSS. Increasing water sulfate concentrations did not negatively affect water or feed intake but did increase H2S concentration and production in vivo and in vitro, respectively. Bismuth subsalicylate may be a potential strategy to reduce H2S production. [ABSTRACT FROM AUTHOR]

Boar taint is an off-odour or off-flavour that develops in heated pork products from entire male pigs, which is caused by the accumulation of androstenone, a sex pheromone, in the fat. However, we have previously demonstrated that a significant amount of androstenone undergoes sulfoconjugation upon synthesis in the Leydig cells and circulates in the plasma primarily as a polar steroid sulfate. Therefore, the purpose of this study was to determine if androstenone sulfate can be deconjugated within the adipose tissue by the sulfatase enzyme to return free androstenone and indirectly contribute to the development of boar taint. Backfat was obtained from 6-month-old terminal cross [Duroc x (Landrace x Yorkshire)] boars that had high (n=4) or low (n=4) sulfatase expression as determined by RT-PCR. Sulfatase activity in the fat was measured by quantifying the conversion of androstenone sulfate to free androstenone. Backfat was homogenized and the supernatant was incubated with [3H]-androstenone sulfate for 24-hours. Androstenone was extracted from the incubation using ether and steroid conversion was quantified using high-performance liquid chromatography (HPLC). Additionally, fat androstenone concentrations were quantified using an established HPLC procedure. Statistical analysis was conducted using a Student's t-test. There was a significant difference (p=0.04) in the expression of sulfatase between the high (2.99 ± 0.67) and low (1.21 ± 0.19) sulfatase boars and the percentage of androstenone sulfate that was converted to free androstenone was proportional to the expression of sulfatase. Interestingly, the expression of sulfatase was positively related to the concentration of androstenone in the fat in boars with high sulfatase expression; however, this relation was not as strong in animals with low sulfatase expression. These preliminary results suggest that the development of boar taint may occur indirectly through the deconjugation of androstenone sulfate in boars with high expression of sulfatase in the fat. [ABSTRACT FROM AUTHOR]

A randomized complete block design was used to evaluate the effects of bismuth subsalicylate (BSS) on in vitro ruminal fermentation with differing concentrations of sulfate. In vitro fermentation consisted of 50 mL of a 4:1 buffer:ruminal fluid inoculum and 0.7 g (pre-dehydrated) of substrate [WW-B Dahl bluestem hay (Bothriochloa bladhii)] incubated for 48 h (39oC). Treatments were arranged as a 3 × 4 factorial with concentration of sulfate (0.2, 2.9, or 5.6 g sulfate/L buffer) and BSS (0.0, 0.165, 0.330, or 0.495% substrate DM) as the main factors. In vitro organic matter digestibility (IVOMD), and CH4, H2S, and total gas production (TGP) were measured. Data were analyzed using the MIXED procedure of SAS with the fixed effects of BSS, sulfate, and their interaction. Incubation day (block) was considered a random effect. The average of 2 bottles within day was considered experimental unit. A BSS × sulfate interaction was observed for TGP (P = 0.040) and H2S production (P < 0.001), where BSS had a larger negative impact on TGP and production of H2S with greater concentrations of sulfate. A linear effect (P < 0.001) of sulfate was observed for CH4 production per gram of incubated OM, where CH4 was decreased as sulfate concentration increased. A quadratic effect of sulfate was observed for IVOMD (P = 0.010) and pH (P = 0.009). Production of H2S linearly decreased (P = 0.001) as BSS concentration increased. The addition of BSS to in vitro incubations did not affect (P > 0.10) any other variables measured. Bismuth subsalicylate does not appear to have negative effects on in vitro fermentation parameters while decreasing H2S production; however, elevated concentrations of sulfate in the buffer appears to have negative impacts on fermentation. Further in vivo research is warranted to support BSS supplementation to cattle with high dietary sulfate. [ABSTRACT FROM AUTHOR]