BACKGROUND: Several studies explored the interdependence between Paco2 and bicarbonate during respiratory acid-base derangements. The authors aimed to reframe the bicarbonate adaptation to respiratory disorders according to the physical-chemical approach, hypothesizing that (1) bicarbonate concentration during respiratory derangements is associated with strong ion difference; and (2) during acute respiratory disorders, strong ion difference changes are not associated with standard base excess. METHODS: This is an individual participant data meta-analysis from multiple canine and human experiments published up to April 29, 2021. Studies testing the effect of acute or chronic respiratory derangements and reporting the variations of Paco2, bicarbonate, and electrolytes were analyzed. Strong ion difference and standard base excess were calculated. RESULTS: Eleven studies were included. Paco2 ranged between 21 and 142 mmHg, while bicarbonate and strong ion difference ranged between 12.3 and 43.8 mM, and 32.6 and 60.0 mEq/l, respectively. Bicarbonate changes were linearly associated with the strong ion difference variation in acute and chronic respiratory derangement (β-coefficient, 1.2; 95% CI, 1.2 to 1.3; P < 0.001). In the acute setting, sodium variations justified approximately 80% of strong ion difference change, while a similar percentage of chloride variation was responsible for chronic adaptations. In the acute setting, strong ion difference variation was not associated with standard base excess changes (β-coefficient, -0.02; 95% CI, -0.11 to 0.07; P = 0.719), while a positive linear association was present in chronic studies (β-coefficient, 1.04; 95% CI, 0.84 to 1.24; P < 0.001). CONCLUSIONS: The bicarbonate adaptation that follows primary respiratory alterations is associated with variations of strong ion difference. In the acute phase, the variation in strong ion difference is mainly due to sodium variations and is not paralleled by modifications of standard base excess. In the chronic setting, strong ion difference changes are due to chloride variations and are mirrored by standard base excess.
- MeSH
- acidobazická rovnováha * MeSH
- chloridy farmakologie MeSH
- hydrogenuhličitany * MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- psi MeSH
- sodík farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- Názvy látek
- chloridy MeSH
- hydrogenuhličitany * MeSH
- sodík MeSH
A new method for modifying the structure of tetracyclic quinobenzothiazinium derivatives has been developed, allowing introduction of various substituents at different positions of the benzene ring. The method consists of reacting appropriate aniline derivatives with 5,12-(dimethyl)thioquinantrenediinium bis-chloride. A series of new quinobenzothiazine derivatives was obtained with propyl, allyl, propargyl and benzyl substituents in 9, 10 and 11 positions, respectively. The structure of the obtained compounds was analyzed by 1H and 13C NMR (HSQC, HMBC) and X-ray analysis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212, and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). In addition, all the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. 9-Benzyloxy-5-methyl-12H-quino [3,4-b][1,4]benzothiazinium chloride (6j), 9-propoxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6a) and 9-allyloxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6d) demonstrated high activity against the entire tested microbial spectrum. The activities of the compounds were comparable with oxacillin, tetracycline and ciprofloxacinagainst staphylococcal strains and with rifampicin against both mycobacterial strains. Compound 6j had a significant effect on the inhibition of bacterial respiration as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity, but also bactericidal activity. Preliminary in vitro cytotoxicity screening of the compounds performed using normal human dermal fibroblasts (NHDF) proved that the tested compounds showed an insignificant cytotoxic effect on human cells (IC50 > 37 µM), making these compounds interesting for further investigation. Moreover, the intermolecular similarity of novel compounds was analyzed in the multidimensional space (mDS) of the structure/property-related in silico descriptors by means of principal component analysis (PCA) and hierarchical clustering analysis (HCA), respectively. The distance-oriented structure/property distribution was related with the experimental lipophilic data.
- Klíčová slova
- antibacterial activity, azaphenothiazines, cytotoxicity, descriptor-based similarity analysis, phenothiazine,
- MeSH
- antibakteriální látky chemie MeSH
- chloridy farmakologie MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus * MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- chloridy MeSH
OBJECTIVES: To evaluate the effect of smear layer deproteinization using hypochlorous acid (HOCl) with/without metal chlorides (SrCl2 and ZnCl2) on the microtensile bond strength (µTBS) of two simplified adhesives to dentin. METHODS: Human dentin surfaces with a standardized smear layer were pretreated using a 105 ppm HOCl solution with/without SrCl2 (0.05 M, 0.1 M, 0.2 M, 0.4 M) or ZnCl2 (0.05 M, 0.1 M, 0.2 M) for 5 s, 15 s, or 30 s. After the deproteinizing solution was washed out with water for 5 s, 15 s, or 30 s, pretreated surfaces were bonded with one-step self-etch adhesive Bond Force II or universal adhesive Clearfil Universal Bond Quick, and µTBS was measured after 24 h. Additionally, the deproteinizing effects of HOCl solutions with/without the metal chlorides were compared by measuring changes in the amide:phosphate ratio using attenuated total reflection Fourier transform infrared spectroscopy. Statistical analysis was performed using multifactor ANOVA, Tukey's post hoc tests and t-tests (p < 0.05). RESULTS: Pretreatment with pure HOCl for 15 s and 30 s significantly decreased the amide:phosphate ratio (p < 0.05), indicating effective deproteinization, but the µTBS of both adhesives increased significantly only if HOCl was washed out for 30 s (p < 0.05). Increasing the concentrations of metal chlorides enabled shortening of the wash-out time down to 5 s while maintaining the improved µTBS (p < 0.05). The deproteinizing effect of HOCl was not significantly altered by the addition of metal chlorides (p > 0.05). SIGNIFICANCE: The effectiveness of smear layer deproteinization using HOCl can be improved by the addition of metal chlorides, as their increasing concentration allowed to shorten the wash-out time from 30 s down to 5 s.
- Klíčová slova
- Adhesion, FTIR, Hypochlorous acid, Microtensile bond strength, Pretreatment, Smear layer deproteinization, Strontium chloride, Zinc chloride,
- MeSH
- amidy analýza farmakologie MeSH
- chloridy analýza farmakologie MeSH
- dentin chemie MeSH
- dentinová adheziva chemie MeSH
- fosfáty farmakologie MeSH
- kyselina chlorná analýza farmakologie MeSH
- lidé MeSH
- pevnost v tahu MeSH
- pryskyřičné cementy chemie MeSH
- smear layer * MeSH
- testování materiálů MeSH
- vazba zubní * MeSH
- zubní cementy farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amidy MeSH
- chloridy MeSH
- dentinová adheziva MeSH
- fosfáty MeSH
- kyselina chlorná MeSH
- pryskyřičné cementy MeSH
- zubní cementy MeSH
The ability of endogenous neurosteroids (NSs) with pregnane skeleton modified at positions C-3 and C-5 to modulate the functional activity of inhibitory glycine receptors (GlyR) and ionotropic ɣ-aminobutyric acid receptors (GABAA R) was estimated. The glycine and GABA-induced chloride current (IGly and IGABA ) were measured in isolated pyramidal neurons of the rat hippocampus and in isolated rat cerebellar Purkinje cells, respectively. Our experiments demonstrated that pregnane NSs affected IGABA and IGly in a different manner. At low concentrations (up to 5 μM), tested pregnane NSs increased or did not change the peak amplitude of the IGABA , but reduced the IGly by decreasing the peak amplitude and/or accelerating desensitization. Namely, allopregnanolone (ALLO), epipregnanolone (EPI), pregnanolone (PA), pregnanolone sulfate (PAS) and 5β-dihydroprogesterone (5β-DHP) enhanced the IGABA in Purkinje cells. Dose-response curves plotted in the concentration range from 1 nM to 100 μM were smooth for EPI and 5β-DHP, but bell-shaped for ALLO, PA and PAS. The peak amplitude of the IGly was reduced by PA, PAS, and 5α- and 5β-DHP. In contrast, ALLO, ISO and EPI did not modulate it. Dose-response curves for the inhibition of the IGly peak amplitude were smooth for all active compounds. All NSs accelerated desensitization of the IGly . The dose-response relationship for this effect was smooth for ALLO, PA, PAS and 5β-DHP, but it was U-shaped for EPI, 5α-DHP and ISO. These results, together with our previous results on NSs with androstane skeleton, offer comprehensive overview for understanding the mechanisms of effects of NSs on IGly and IGABA .
- Klíčová slova
- GABAA receptor, glycine receptor, neurosteroid, pregnane, structure-activity relationship study,
- MeSH
- 5alfa-dihydroprogesteron farmakologie MeSH
- chloridy farmakologie MeSH
- GABA MeSH
- glycin farmakologie MeSH
- krysa rodu Rattus MeSH
- neurony fyziologie MeSH
- neurosteroidy * MeSH
- potkani Wistar MeSH
- pregnanolon * farmakologie MeSH
- pregnany farmakologie MeSH
- receptory GABA-A fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 5alfa-dihydroprogesteron MeSH
- chloridy MeSH
- GABA MeSH
- glycin MeSH
- neurosteroidy * MeSH
- pregnanolon * MeSH
- pregnany MeSH
- receptory GABA-A MeSH
Sperm capacitation, the ultimate maturation event preparing mammalian spermatozoa for fertilization, was first described in 1951, yet its regulatory mechanisms remain poorly understood. The capacitation process encompasses an influx of bicarbonate and calcium ions, removal of decapacitating factors, changes of pH and sperm proteasomal activities, and the increased protein tyrosine phosphorylation. Here, we document a novel biological phenomenon of a unique zinc (Zn2+) ion redistribution associated with mammalian sperm in vitro capacitation (IVC). Using image-based flow cytometry (IBFC), we identified four distinct types of sperm zinc ion distribution patterns (further zinc signature) and their changes during IVC. The zinc signature was altered after sperm capacitation, reduced by proteasomal inhibitors, removed by zinc chelators, and maintained with addition of external ZnCl2. These findings represent a fundamental shift in the understanding of mammalian fertilization, paving the way for improved semen analysis, in vitro fertilization (IVF), and artificial insemination (AI).
- MeSH
- analýza spermatu MeSH
- chelátory farmakologie MeSH
- chloridy farmakologie MeSH
- kapacitace spermií účinky léků fyziologie MeSH
- kationty dvojmocné metabolismus MeSH
- prasata MeSH
- průtoková cytometrie metody MeSH
- sloučeniny zinku farmakologie MeSH
- spermie metabolismus MeSH
- zinek metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- chelátory MeSH
- chloridy MeSH
- kationty dvojmocné MeSH
- sloučeniny zinku MeSH
- zinc chloride MeSH Prohlížeč
- zinek MeSH
The uptake of stable cesium (133Cs) by Calla palustris was evaluated from four different substrates: water, soil, keramzit (a clay granule) and water with the addition of a potassium compound, after an eight days exposure to a solution of 0.5mM cesium chloride. Stable cesium was used because it is commonly supposed that its uptake by plants is the same of that of radiocesium (137Cs). The plants were differentiated in their parts (roots, healthy leaves, dead leaves and flowers) and analyzed with ICP-MS. The lowest average concentration of absorbed Cs was found in plants exposed in soil (0.7mg/kg, S.D.=96.8), while the highest in plants exposed in water (147mg/kg, S.D.=51.7). During the experiment the water planted plants removed 31.6% of provided Cs while those planted in soil removed only 0.06%. The addition of potassium to water was tested because of the competition effect that arises between these two elements: this effect was confirmed with the result that the average uptake in the presence of potassium was lower (41mg/kg in exposed plants, S.D.=76.1). The uptake was also lower in the solid-based substrates (soil and keramzit), because of the known tendency of Cs to bind with soil particles, thus becoming less available to plants. There was no evidence that the different parts of the plant showed different uptake effectiveness, or that the health of the plant (evaluated with a qualitative method) had any effect on the uptake of Cs.
- Klíčová slova
- (133)Cs, Calla palustris, Phytoremediation, Radiocesium, Stable cesium, Uptake,
- MeSH
- biodegradace MeSH
- Calla (rostlina) metabolismus MeSH
- cesium metabolismus farmakologie MeSH
- chloridy farmakologie MeSH
- draslík metabolismus farmakologie MeSH
- kořeny rostlin metabolismus MeSH
- látky znečišťující životní prostředí metabolismus MeSH
- minerály MeSH
- nadzemní části rostlin metabolismus MeSH
- půda MeSH
- voda MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cesium chloride MeSH Prohlížeč
- cesium MeSH
- chloridy MeSH
- draslík MeSH
- keramzit MeSH Prohlížeč
- látky znečišťující životní prostředí MeSH
- minerály MeSH
- půda MeSH
- voda MeSH
BACKGROUND: Next Generation Sequencing (NGS) technologies provide exciting possibilities for whole genome sequencing of a plethora of organisms including bacterial strains and phages, with many possible applications in research and diagnostics. No Streptomyces flavovirens phages have been sequenced to date; there is therefore a lack in available information about S. flavovirens phage genomics. We report biological and physiochemical features and use NGS to provide the complete annotated genomes for two new strains (Sf1 and Sf3) of the virulent phage Streptomyces flavovirens, isolated from Egyptian soil samples. RESULTS: The S. flavovirens phages (Sf1 and Sf3) examined in this study show higher adsorption rates (82 and 85%, respectively) than other actinophages, indicating a strong specificity to their host, and latent periods (15 and 30 min.), followed by rise periods of 45 and 30 min. As expected for actinophages, their burst sizes were 1.95 and 2.49 virions per mL. Both phages were stable and, as reported in previous experiments, showed a significant increase in their activity after sodium chloride (NaCl) and magnesium chloride (MgCl2.6H2O) treatments, whereas after zinc chloride (ZnCl2) application both phages showed a significant decrease in infection. The sequenced phage genomes are parts of a singleton cluster with sizes of 43,150 bp and 60,934 bp, respectively. Bioinformatics analyses and functional characterizations enabled the assignment of possible functions to 19 and 28 putative identified ORFs, which included phage structural proteins, lysis components and metabolic proteins. Thirty phams were identified in both phages, 10 (33.3%) of them with known function, which can be used in cluster prediction. Comparative genomic analysis revealed significant homology between the two phages, showing the highest hits among Sf1, Sf3 and the closest Streptomyces phage (VWB phages) in a specific 13Kb region. However, the phylogenetic analysis using the Major Capsid Protein (MCP) sequences highlighted that the isolated phages belong to the BG Streptomyces phage group but are clearly separated, representing a novel sub-cluster. CONCLUSION: The results of this study provide the first physiological and genomic information for S. flavovirens phages and will be useful for pharmaceutical industries based on S. flavovirens and future phage evolution studies.
- Klíčová slova
- Bacteriophage, Biological stability, Comparative genomics, NGS, Whole genome sequence,
- MeSH
- bakteriofágy genetika izolace a purifikace patogenita fyziologie MeSH
- biologická evoluce MeSH
- chlorid hořečnatý farmakologie MeSH
- chlorid sodný farmakologie MeSH
- chloridy farmakologie MeSH
- DNA virů izolace a purifikace MeSH
- fylogeneze MeSH
- genom virový genetika fyziologie MeSH
- genomika MeSH
- hostitelská specificita MeSH
- otevřené čtecí rámce genetika MeSH
- půda MeSH
- půdní mikrobiologie MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- sekvenční homologie nukleových kyselin MeSH
- sloučeniny zinku farmakologie MeSH
- Streptomyces virologie MeSH
- virion MeSH
- virové geny MeSH
- virové plášťové proteiny genetika MeSH
- virové proteiny genetika MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Egypt MeSH
- Názvy látek
- chlorid hořečnatý MeSH
- chlorid sodný MeSH
- chloridy MeSH
- DNA virů MeSH
- půda MeSH
- sloučeniny zinku MeSH
- virové plášťové proteiny MeSH
- virové proteiny MeSH
- zinc chloride MeSH Prohlížeč
In this study, a series of twenty-five ring-substituted 4-arylamino-7-chloroquinolinium chlorides were prepared and characterized. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts and also primary in vitro screening of the synthesized compounds was performed against mycobacterial species. 4-[(2-Bromophenyl)amino]-7-chloroquinolinium chloride showed high biological activity against M. marinum, M. kansasii, M. smegmatis and 7-chloro-4-[(2-methylphenyl)amino]quinolinium chloride demonstrated noteworthy biological activity against M. smegmatis and M. avium subsp. paratuberculosis. The most effective compounds demonstrated quite low toxicity (LD₅₀ > 20 μmol/L) against the human monocytic leukemia THP-1 cell line within preliminary in vitro cytotoxicity screening. The tested compounds were found to inhibit PET in photosystem II. The PET-inhibiting activity expressed by IC₅₀ value of the most active compound 7-chloro-4-[(3-trifluoromethylphenyl)amino]quinolinium chloride was 27 μmol/L and PET-inhibiting activity of ortho-substituted compounds was significantly lower than this of meta- and para-substituted ones. The structure-activity relationships are discussed for all compounds.
- MeSH
- antituberkulotika chemická syntéza farmakologie MeSH
- buněčné linie MeSH
- chinolinové sloučeniny chemická syntéza farmakologie MeSH
- chloridy chemická syntéza farmakologie MeSH
- chloroplasty účinky léků metabolismus MeSH
- fotosyntéza účinky léků MeSH
- inhibiční koncentrace 50 MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium účinky léků MeSH
- preklinické hodnocení léčiv MeSH
- rozpustnost MeSH
- Spinacia oleracea účinky léků metabolismus MeSH
- transport elektronů účinky léků MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antituberkulotika MeSH
- chinolinové sloučeniny MeSH
- chloridy MeSH
The GTPases Arl1 and Ypt6 are involved in the intracellular transport of vesicles and their fusion with the trans-Golgi network. This work is focused on comparing the roles of these GTPases in the tolerance of Saccharomyces cerevisiae cells to an increased concentration of alkali metal cations and other stress factors. We studied the phenotypes of arl1 or ypt6 deletions in combination with the deletions of genes encoding alkali-metal-cation transporters (ena1-4, nha1, nhx1, and kha1). Salt sensitivity of the arl1 and ypt6 mutants was shown to be independent of the tested cation transporters and electrochemical membrane potential. Phenotype manifestations of ypt6 deletion were usually more prominent than those of arl1 (cells were more sensitive to KCl, NaCl, LiCl, hygromycin B, increased temperature, and increased pH). At suboptimal temperature, the growth inhibition of arl1 and ypt6 mutants was approximately the same, and low pH was the only condition where arl1 mutants grew even worse than ypt6 mutants. Overexpression of the ARL1 gene suppressed the phenotypes of ypt6 deletion; however, this did not work vice versa (additional copies of YPT6 could not replace ARL1). Our results suggest partially overlapping functions of the GTPases in resistance to various stress factors, with Ypt6 being more efficient under physiological conditions and Arl1 more versatile when overexpressed.
- MeSH
- chloridy farmakologie MeSH
- delece genu MeSH
- hygromycin B farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- monomerní proteiny vázající GTP genetika metabolismus MeSH
- proteiny přenášející kationty genetika metabolismus MeSH
- reakce na tepelný šok * MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae účinky léků genetika růst a vývoj metabolismus MeSH
- teplota MeSH
- vezikulární transportní proteiny genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- ARL1 protein, S cerevisiae MeSH Prohlížeč
- chloridy MeSH
- hygromycin B MeSH
- monomerní proteiny vázající GTP MeSH
- proteiny přenášející kationty MeSH
- Saccharomyces cerevisiae - proteiny MeSH
- vezikulární transportní proteiny MeSH
- YPT6 protein, S cerevisiae MeSH Prohlížeč
The physiological role of Candida albicans Cnh1, a member of the Na+/H+ antiporter family, was characterized. Though CaCnh1p had broad substrate specificity and mediated efflux of at least four alkali metal cations upon heterologous expression in Saccharomyces cerevisiae, its presence in C. albicans cells was important especially for potassium homeostasis. In C. albicans, CaCnh1p tagged with GFP was localized in the plasma membrane of cells growing as both yeasts and hyphae. Deletion of CNH1 alleles did not affect tolerance to NaCl, LiCl or CsCl, but resulted in increased sensitivity to high external concentrations of KCl and RbCl. The potassium and rubidium tolerance of a cnh1 homozygous mutant was fully restored by reintegration of CNH1 into the genome. The higher sensitivity of the cnh1/cnh1 mutant to external KCl was caused by a lower K+ efflux from these cells. Together, the functional characterization of the CaCnh1 antiporter in C. albicans revealed that this antiporter plays a significant role in C. albicans physiology. It ensures potassium and rubidium tolerance and participates in the regulation of intracellular potassium content of C. albicans cells.
- MeSH
- antibakteriální látky farmakologie MeSH
- buněčná membrána chemie MeSH
- Candida albicans metabolismus MeSH
- cesium farmakologie MeSH
- chlorid draselný farmakologie MeSH
- chlorid lithný farmakologie MeSH
- chlorid sodný farmakologie MeSH
- chloridy farmakologie MeSH
- delece genu MeSH
- draslík metabolismus MeSH
- exprese genu MeSH
- fungální léková rezistence MeSH
- fungální proteiny analýza genetika metabolismus MeSH
- homeostáza MeSH
- hyfy chemie MeSH
- klonování DNA MeSH
- kvasinky chemie MeSH
- Na(+)-H(+) antiport analýza genetika metabolismus MeSH
- rubidium farmakologie MeSH
- Saccharomyces cerevisiae genetika metabolismus MeSH
- substrátová specifita MeSH
- testy genetické komplementace MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antibakteriální látky MeSH
- cesium chloride MeSH Prohlížeč
- cesium MeSH
- chlorid draselný MeSH
- chlorid lithný MeSH
- chlorid sodný MeSH
- chloridy MeSH
- CNH1 protein, Candida albicans MeSH Prohlížeč
- draslík MeSH
- fungální proteiny MeSH
- Na(+)-H(+) antiport MeSH
- rubidium chloride MeSH Prohlížeč
- rubidium MeSH