Shaping the gradients driving phoretic micro-swimmers: influence of swimming speed, budget of carbonic acid and environment.

pH gradient-driven modular micro-swimmers are investigated as a model for a large variety of quasi-two-dimensional chemi-phoretic self-propelled entities. Using three-channel micro-photometry, we obtain a precise large field mapping of pH at a spatial resolution of a few microns and a pH resolution of [Formula: see text] units for swimmers of different velocities propelling on two differently charged substrates. We model our results in terms of solutions of the three-dimensional advection-diffusion equation for a 1:1 electrolyte, i.e. carbonic acid, which is produced by ion exchange and consumed by equilibration with dissolved [Formula: see text]. We demonstrate the dependence of gradient shape and steepness on swimmer speed, diffusivity of chemicals, as well as the fuel budget. Moreover, we experimentally observe a subtle, but significant feedback of the swimmer's immediate environment in terms of a substrate charge-mediated solvent convection. We discuss our findings in view of different recent results from other micro-fluidic or active matter investigations. We anticipate that they are relevant for quantitative modelling and targeted applications of diffusio-phoretic flows in general and artificial micro-swimmers in particular.

Potent Inhibition of Mandelate Racemase by Boronic Acids: Boron as a Mimic of a Carbon Acid Center.

Boronic acids have been successfully employed as inhibitors of hydrolytic enzymes. Typically, an enzymatic nucleophile catalyzing hydrolysis adds to the electrophilic boron atom forming a tetrahedral species that mimics the intermediate(s)/transition state(s) for the hydrolysis reaction. We show that para-substituted phenylboronic acids (PBAs) are potent competitive inhibitors of mandelate racemase (MR), an enzyme that catalyzes a 1,1-proton transfer rather than a hydrolysis reaction. The Ki value for PBA was 1.8 ± 0.1 µM, and p-Cl-PBA exhibited the most potent inhibition (Ki = 81 ± 4 nM), exceeding the binding affinity of the substrate by ∼4 orders of magnitude. Isothermal titration calorimetric studies with the wild-type, K166M, and H297N MR variants indicated that, of the two Brønsted acid-base catalysts Lys 166 and His 297, the former made the greater contribution to inhibitor binding. The X-ray crystal structure of the MR·PBA complex revealed the presence of multiple H-bonds between the boronic acid hydroxyl groups and the side chains of active site residues, as well as formation of a His 297 Nε2-B dative bond. The dramatic upfield change in chemical shift of 27.2 ppm in the solution-phase 11B nuclear magnetic resonance spectrum accompanying binding of PBA by MR was consistent with an sp3-hybridized boron, which was also supported by density-functional theory calculations. These unprecedented findings suggest that, beyond substituting boron at carbon centers participating in hydrolysis reactions, substitution of boron at the acidic carbon center of a substrate furnishes a new approach for generating inhibitors of enzymes catalyzing the deprotonation of carbon acid substrates.

Acid sensing by the Drosophila olfactory system.

The odour of acids has a distinct quality that is perceived as sharp, pungent and often irritating. How acidity is sensed and translated into an appropriate behavioural response is poorly understood. Here we describe a functionally segregated population of olfactory sensory neurons in the fruitfly, Drosophila melanogaster, that are highly selective for acidity. These olfactory sensory neurons express IR64a, a member of the recently identified ionotropic receptor (IR) family of putative olfactory receptors. In vivo calcium imaging showed that IR64a+ neurons projecting to the DC4 glomerulus in the antennal lobe are specifically activated by acids. Flies in which the function of IR64a+ neurons or the IR64a gene is disrupted had defects in acid-evoked physiological and behavioural responses, but their responses to non-acidic odorants remained unaffected. Furthermore, artificial stimulation of IR64a+ neurons elicited avoidance responses. Taken together, these results identify cellular and molecular substrates for acid detection in the Drosophila olfactory system and support a labelled-line mode of acidity coding at the periphery.

Chemistry of Fluorinated Carbon Acids: Synthesis, Physicochemical Properties, and Catalysis.

The bis[(trifluoromethyl)sulfonyl]methyl (Tf2CH; Tf=SO2CF3) group is known to be one of the strongest carbon acid functionalities. The acidity of such carbon acids in the gas phase is stronger than that of sulfuric acid. Our recent investigations have demonstrated that this type of carbon acids work as novel acid catalysts. In this paper, recent achievements in carbon acid chemistry by our research group, including synthesis, physicochemical properties, and catalysis, are summarized.

Effects of natural acids on surface properties of asbestos minerals and kaolinite.

Serpentine, and other asbestos minerals, are considered potential hazards to human respiratory health. It has been postulated that the surface characteristics of these substances, such as surface charge and adsorbed metals, notably Fe and other transition metals, may be the major agents responsible for their toxicity. There is a general consensus that the amphibole group of minerals possesses a greater health risk than serpentines dominated by chrysotile. There have been suggestions that natural processes can alter the surfaces of these minerals and reduce their potency. This study examined the effects of carbonic acid, oxalic acid and hydrochloric acid on the surface characteristics of two trioctahedral minerals, actinolite (amphibole) and chrysotile (serpentine), and compared the results to a non-asbestiform, dioctahedral mineral, kaolinite. Results confirm that the treatments alter the mineral surfaces by changing the zeta potential of the asbestiform minerals from positive to negative and by removing considerable amounts on non-crystalline Fe and other metals. X-ray analyses indicated that mineral structure was little affected by the treatments, and TOF-SIMS revealed that treatments did remove surface adsorbed metals and cations in octahedral coordination within the samples.

Coccolithophore community response along a natural CO2 gradient off Methana (SW Saronikos Gulf, Greece, NE Mediterranean).

A natural pH gradient caused by marine CO2 seeps off the Methana peninsula (Saronikos Gulf, eastern Peloponnese peninsula) was used as a natural laboratory to assess potential effects of ocean acidification on coccolithophores. Coccolithophore communities were therefore investigated in plankton samples collected during September 2011, September 2016 and March 2017. The recorded cell concentrations were up to ~50 x103 cells/l, with a high Shannon index of up to 2.8, along a pH gradient from 7.61 to 8.18, with values being occasionally <7. Numerous holococcolithophore species represented 60-90% of the surface water assemblages in most samples during September samplings. Emiliania huxleyi was present only in low relative abundances in September samples, but it dominated in March assemblages. Neither malformed nor corroded coccolithophores were documented. Changes in the community structure can possibly be related to increased temperatures, while the overall trend associates low pH values with high cell densities. Our preliminary results indicate that in long-termed acidified, warm and stratified conditions, the study of the total coccolithophore assemblage may prove useful to recognize the intercommunity variability, which favors the increment of lightly calcified species such as holococcolithophores.

Extracellular HCO(3)(-) dependence of electrogenic Na/HCO(3) cotransporters cloned from salamander and rat kidney.

We studied the extracellular [HCOabstract (3) (-)] dependence of two renal clones of the electrogenic Na/HCO(3) cotransporter (NBC) heterologously expressed in Xenopus oocytes. We used microelectrodes to measure the change in membrane potential (DeltaV(m)) elicited by the NBC cloned from the kidney of the salamander Ambystoma tigrinum (akNBC) and by the NBC cloned from the kidney of rat (rkNBC). We used a two-electrode voltage clamp to measure the change in current (DeltaI) elicited by rkNBC. Briefly exposing an NBC-expressing oocyte to HCOabstract (3 )(-)/CO(2) (0.33-99 mM HCOabstract (3)(-), pH(o) 7.5) elicited an immediate, DIDS (4, 4-diisothiocyanatostilbene-2,2-disulfonic acid)-sensitive and Na(+)-dependent hyperpolarization (or outward current). In DeltaV(m) experiments, the apparent K(m ) for HCOabstract (3)(-) of akNBC (10. 6 mM) and rkNBC (10.8 mM) were similar. However, under voltage-clamp conditions, the apparent K(m) for HCOabstract (3)(-) of rkNBC was less (6.5 mM). Because it has been reported that SOabstract (3)(=)/HSO abstract (3)(-) stimulates Na/HCO(3 ) cotransport in renal membrane vesicles (a result that supports the existence of a COabstract (3)(=) binding site with which SOabstract (3)(=) interacts), we examined the effect of SOabstract (3)(=)/HSO abstract (3)(-) on rkNBC. In voltage-clamp studies, we found that neither 33 mM SOabstract (4)(=) nor 33 mM SOabstract (3) (=)/HSOabstract (3)(-) substantially affects the apparent K(m) for HCO abstract (3)(-). We also used microelectrodes to monitor intracellular pH (pH(i)) while exposing rkNBC-expressing oocytes to 3.3 mM HCOabstract (3 )(-)/0.5% CO(2). We found that SO abstract (3)(=)/HSOabstract (3 )(-) did not significantly affect the DIDS-sensitive component of the pH(i) recovery from the initial CO(2 )-induced acidification. We also monitored the rkNBC current while simultaneously varying [CO(2)](o), pH(o), and [COabstract (3)(=)](o) at a fixed [HCOabstract (3)(-)](o) of 33 mM. A Michaelis-Menten equation poorly fitted the data expressed as current versus [COabstract (3)(=)](o ). However, a pH titration curve nicely fitted the data expressed as current versus pH(o). Thus, rkNBC expressed in Xenopus oocytes does not appear to interact with SOabstract (3 )(=), HSOabstract (3)(-), or COabstract (3)(=).

Carbonic acid salts at 25 or 45 degrees C to control loquat decay under shelf life conditions.

Generally recognised as save compounds (G.R.A.S) are attractive substitutes to synthetic chemicals in postharvest control diseases. They meet safety requirements, are cheap and able to be integrated with other disease control technologies. Among G.R.A.S compounds, carbonic acid salts have been investigated on carrots, bell pepper, melons, sweet cherries and their efficacy was also evaluated when combined with biological control agents. Moreover, the possibility to use sodium carbonate and sodium bicarbonate to prevent P. digitatum an P. italicum spread on Citrus fruit was studied since the begin of the 20th century. We explored the possibility to extend the use of carbonate-bicarbonate salts on loquat fruit in order to control the pathogens and to extend postharvest life. Loquat is a very perishable fruit, susceptible to decay, mechanical damage, moisture and nutritional losses during its postharvest life. We tested the combined effect of temperature and sodium or potassium carbonate-bicarbonate and ammonium carbonate. The fruit was dipped in the salt solutions at variable concentrations (0.5, 1 and 2% w/v) at 25 or 45 degrees C for two minutes and than stored under shelf life conditions (25 degrees C and 70% RH). Decay, weight loss, pH, titrable acidity and sugar content were detected after twelve days. Preliminary data show that the combined treatments were effective in decay control depending on salts. Best results were obtained with 2% potassium and sodium carbonate solution at 25 degrees C. Weight losses were related to treatment temperature and salts concentrations whereas, no differences were detected in the chemical parameters compared to the control.

Threatened Caribbean coral is able to mitigate the adverse effects of ocean acidification on calcification by increasing feeding rate.

Global climate change threatens coral growth and reef ecosystem health via ocean warming and ocean acidification (OA). Whereas the negative impacts of these stressors are increasingly well-documented, studies identifying pathways to resilience are still poorly understood. Heterotrophy has been shown to help corals experiencing decreases in growth due to either thermal or OA stress; however, the mechanism by which it mitigates these decreases remains unclear. This study tested the ability of coral heterotrophy to mitigate reductions in growth due to climate change stress in the critically endangered Caribbean coral Acropora cervicornis via changes in feeding rate and lipid content. Corals were either fed or unfed and exposed to elevated temperature (30°C), enriched pCO2 (800 ppm), or both (30°C/800 ppm) as compared to a control (26°C/390 ppm) for 8 weeks. Feeding rate and lipid content both increased in corals experiencing OA vs. present-day conditions, and were significantly correlated. Fed corals were able to maintain ambient growth rates at both elevated temperature and elevated CO2, while unfed corals experienced significant decreases in growth with respect to fed conspecifics. Our results show for the first time that a threatened coral species can buffer OA-reduced calcification by increasing feeding rates and lipid content.

Increasing platelet aggregability after venepuncture is platelet, not plasma derived.

The time course of ADP induced aggregation of human platelets was determined in aliquots of stored platelet rich plasma 3.5, 10, 30 and 100 minutes after venepuncture. The maximal rate of aggregation was found to increase throughout this entire period, even though pH (7.4), CO2 (7 volume per cent) and temperature (35 degrees C) of the samples were kept constant. The mean acceleration (+/- SEM) between 3.5 and 100 minutes was 41.7 +/- 6.9 per cent (n = 67) at an ADP-concentration of 1 mumol/l and 18.3 +/- 6.2 per cent (n = 23) at 2 mumol/l ADP. The effect did not result from changes of any platelet regulatory factors putatively present alone in the plasma. Acceleration of aggregability was only found when the platelets themselves underwent storage, but not when freshly prepared plasma was given to prestored platelets. The change in aggregability was not diminished after inhibition of platelet cyclooxygenase by oral administration of acetylsalicylic acid.

Modeling of carbonic acid pretreatment process using ASPEN-Plus.

ASPEN-Plus process modeling software is used to model carbonic acid pretreatment of biomass. ASPEN-Plus was used because of the thorough treatment of thermodynamic interactions and its status as a widely accepted process simulator. Because most of the physical property data for many of the key components used in the simulation of pretreatment processes are not available in the standard ASPEN-Plus property databases, values from an in-house database (INHSPCD) developed by the National Renewable Energy Laboratory were used. The standard non-random-two-liquid (NRTL) or renon route was used as the main property method because of the need to distill ethanol and to handle dissolved gases. The pretreatment reactor was modeled as a "black box" stoichiometric reactor owing to the unavailability of reaction kinetics. The ASPEN-Plus model was used to calculate the process equipment costs, power requirements, and heating and cooling loads. Equipment costs were derived from published modeling studies. Wall thickness calculations were used to predict construction costs for the high-pressure pretreatment reactor. Published laboratory data were used to determine a suitable severity range for the operation of the carbonic acid reactor. The results indicate that combined capital and operating costs of the carbonic acid system are slightly higher than an H2SO4-based system and highly sensitive to reactor pressure and solids concentration.

Modulation of calcium signalling by intracellular pH in exocrine acinar cells.

Cell-permeant weak acids and bases alter the rate of fluid and electrolyte secretion by a range of epithelia, including the exocrine glands. It is widely assumed that weak acids and bases exert these effects by participating in the ion transport mechanism, or by changing intracellular pH (pHi) and hence modulating electrolyte (ion) transporters. An alternative possibility is that these substances act by modifying the intracellular calcium signals which control fluid secretion. In the present study we have examined whether weak acids and bases modify intracellular free calcium ([Ca2+]i) in exocrine acinar cells. Alkalinization with weak bases and acidification with weak acids had quite different effects on [Ca2+]i in resting and agonist-stimulated cells. In unstimulated lacrimal, salivary or pancreatic acinar cells, acidifying the cytosol had no effect on [Ca2+]i, while cytosolic alkalinization caused a modest rise in [Ca2+]i. This alkalinization-induced increase in [Ca2+]i appears to result from Ca2+ release from agonist-sensitive stores, and was probably caused by a small increase in intracellular InsP3 levels. In contrast, [Ca2+]i decreased when intracellular alkalinization was induced during agonist stimulation. Conversely, acidifying the cytosol during agonist stimulation raised [Ca2+]i. This latter effect was particularly dramatic in pancreatic acinar cells, where cytosolic acidification also enhanced agonist-evoked [Ca2+]i oscillations. The effects of pHi on [Ca2+]i in stimulated cells could also be observed in Ca2+-free medium, indicating that pHi altered [Ca2+]i handling by the intracellular stores rather than plasmalemmal Ca2+ transport. The results suggest that modulation of agonist-evoked [Ca2+]i signalling by changes in pHi may constitute a novel mechanism by which weak acids and bases may modulate exocrine fluid and ion transport.

Synthesis, pharmacologic and toxicologic study of carbonic and carbamic acid esters.

The results of the pharmacologic study of some synthesized derivatives of carbamic and carbonic acids show that the compounds are biologically active. They are less toxic than imipramine, and exert a marked excitation effect on the central nervous system. Some of the compounds (including PS-1, P-8-Y and PS-4) possess greater antidepressive action than imipramine.

[Synthesis of 3-cyano-6-methyl-4-pyridyl-2(1H)-pyridinethiones as well as 2-substituted 6-methyl-4-pyridyl-pyridine-3-carbonitriles and 3-carbonic acid amides, respectively, and testing their cardiovascular activity]. / Synthese von 3-Cyan-6-methyl-4-pyridyl-2(1H)-pyridinthionen sowie neuer in 2-Stellung substituierter 6-Methyl-4-pyridyl-pyridin-3-carbonitrile bzw. -3-carbonsäureamide und deren Prüfung auf kardiovaskuläre Wirksamkeit.

By the base catalyzed reaction of our previously described 3-cyano-6-methyl-4-pyridyl-2(1H)-pyridinethiones 1 and 2, respectively, with branched and unbranched, respectively, alkyl, aralkyl-, alkinyl-, hydroxyalkyl-, ethoxycarbonyl- and carbamoylalkylhalides the new in 2-position substituted 6-methyl-4-pyridyl-pyridine-3-carbonitriles 15-30 were formed. By means of oxidation of the 2-methylthio-substituted pyridine-3-carbonitriles 3 and 4 with potassium periodate and potassium permanganate in diluted acetic acid, respectively, the sulfinyl compounds 5 and 6, respectively, and the sulfonyl compounds 7 and 8, respectively, were prepared. By heating of 3 and 4, respectively, with concentrated sulphuric acid the 2-methylthio-pyridine-3-carboxamides 9 and 10 were obtained. The oxidation of these compounds with potassium periodate and potassium permanganate, respectively, had yield the pyridines 11 and 12, respectively, as well as 13 and 14, respectively.

[Effect of different levels of carbonic acid on glutamate dehydrogenase activity]. / Vliianie razlichnykh urovnei uglekisloty na aktivnost' glutamatdegidrogenazy.

The initial rate of direct and reverse reactions catalyzed by crystalline NAD(P)+-dependent glutamate dehydrogenase from bovine liver as well as Km, V and some other kinetic parameters were studied as affected by carbonic acid in different concentrations (0, 10, 20, 40, 60 mM) at p Hof the incubation media 6.4-9.1. It is shown that the dependence of the initial rate on pH both of the direct and reverse reactions varies with the carbonic acid concentration. In the pH alkaline range the glutamate dehydrogenase activity is inhibited in the presence of a mixture of HCO3 and pCO2 (soluble carbonic acid) and in the acid range pH it has a tendency to increase. The pKb value lowers by an order and the pKa value remains practically unchanged. The interaction of pCO2 with E-amino group of the lysin residue in the enzyme molecule accompanied by formation of carbamate is supposed to be possible. The bicarbonate ion may also affect the enzyme.

[Effect of carbonic acid on glutamate dehydrogenase interaction with NADH]. / Vliianie uglekisloty na vzaimodeistvie glutamatdegidrogenazy s NADH.

The method of fluorescent titration was used to study the effect of carbonic acid on the process of NADH binding with the purified preparation of glutamate dehydrogenase as well as on fluorescent properties of the above mentioned coenzyme. It is shown that in bicarbonate buffer at the alkaline values of pH there is a decrease in the maximal capacity of the binding sites of the enzyme with low affinity to co-enzyme. The capacity of high-affinity binding sites in this case is unchanged. It is found that pCO2, HCO3- and H+ exert an effect on the dissociation constants of the NADH-glutamate dehydrogenase complex as well as on fluorescent properties of bound NADH. It is supposed that the effects observed are a result of the interaction of dissolved carbon dioxide with free amino groups of protein molecule.

[Analysis of the mechanism of action of carbonic acid on tissue chemoreceptors]. / Analiz mekhanizma deistviia uglekisloty na tkanevye khemoretseptory.

Perfusion of the small intestine of anesthetized cats with a solution imitating metabolic acidosis (pH = 7.3; [HCO-3] = =20.2 mM; PCO2 = 38 mm Hg) produced a threshold reflex increase in the blood pressure. The subsequent decrease of [HCO-3] to 3.2 mM and pH to 6.5 evoked a gradual raise of the blood pressure followed by a sharp increase of pressor reflexes amplitude within the range of pH 6.5--6.3. Solutions imitating metabolic acidosis (pH = 7.1; [HCO-3] = 12.7 mM) were found to increase the concentration of H+ ions in the outflow perfusate and blood pressure to larger extent than solutions imitating respiratory acidosis (pH = 7.1; PCO2 = 75 mm Hg). If the solution pH was held constantly at 7.4 by simultaneous decreasing PCO2 and [HCO-3] by a factor of two, a reflex increase in the blood pressure and decrease of perfusate pH had no effect either on blood pressure or perfusate pH. The data obtained suggest that one of the primary determinants of different responses of the tissue chemoreceptors to CO2 is the interstitial pH.

[Effect of carbonic acid of different concentrations of the glycolysis processes and tricarboxylic acid cycle in rat liver tissues]. / Vliianie razlichnykh kontsentratsii uglekisloty na protsessy glikoliza i tsikl trikarbonovykh kislot v tkani pecheni krys.

A rise in the carbonic acid and pH level in rat blood determines an increase in oxidative properties of the liver cell cytoplasm. Simultaneously the content of alpha-ketoglutarate, isocitrate, glutamate, alpha-glycerophosphate, dihydroxyacetone phosphate, pyruvate, lactate, malate increases and the level of glucose, glutamine and ammonia decreases. The in vitro experiments showed that the rise in the level of carbonic acid in the incubation medium from 10 up to 40 mM under all the studied values of pH (7.2, 7.4, 7.6) stimulates formation of dihydroxyacetone phosphate, malate, pyruvate, alpha-ketoglutarate (by 1.5-2.0 times). The same regularity is observed for lactate and glutamate at pH 7.4 and 7.6. The increase in the level of carbonic acid under the all studied values of pH produces a 1.5-fold decrease in the ammonia concentration.

[Sanitary interest of carbonic, carbogaseous or acidulated waters]. / Interés sanitario de las aguas carbónicas, carbogaseosas o acídulas.

The intention of this Communication is to highlight the main characteristics of the carbonic, carbogaseoses or acidulated waters of the Spanish legislation, as therapeutics agent as well as bottled drinking waters. These waters stimulate the secretion and motility of the digestive apparatus and if they are given by oral way in a correct amount, they have diuretic effects. In balneation they also introduce a vasodilatation, effect due to the penetration of the gas carbonic into the skin and its contact with the vascular walls, but this practice is not common in Spain.