Maintenance Of pH Research Articles

PH control of an upflow pyrite-oxidizing denitrifying bioreactor via electrohydrogenesis

Maintenance of stable pH during pyrite-oxidizing denitrification process is important. Here, we demonstrated effective pH control (7.80 ± 0.20–8.40 ± 0.30) in an electrochemical-H2 and pyrite-oxidizing denitrifying bioreactor (HPR) through in situ electrohydrogenesis. HPR achieved a higher nitrate removal activity (maximum:19.66 ± 0.63 mg NO3−-N/(L·h)) with excellent resistance to high nitrate loading (up to 400 mg/L NO3−-N) compared to that of the control groups. Nitrate removal rate of HPR fitted the Michaelis-Menten kinetic model (R2 = 0.98, p < 0.01) well, and the denitrification followed the zero-order rate law. The results of the biofilm community analyses suggested that Thauera was the dominant bacteria in the cathode biofilm of HPR and may prefer hydrogen as an electron donor for autotrophic denitrification, while the relative abundance of Pseudomonas were similar in the cathode biofilm and pyrite biofilm. This study provides a new alternative for effective pH control in denitrifying bioreactors with pyrite as a packing material.

Acid-Induced Downregulation of ASS1 Contributes to the Maintenance of Intracellular pH in Cancer.

Downregulation of the urea cycle enzyme argininosuccinate synthase (ASS1) by either promoter methylation or by HIF1α is associated with increased metastasis and poor prognosis in multiple cancers. We have previously shown that in normoxic conditions, ASS1 downregulation facilitates cancer cell proliferation by increasing aspartate availability for pyrimidine synthesis by the enzyme complex CAD. Here we report that in hypoxia, ASS1 expression in cancerous cells is downregulated further by HIF1α-mediated induction of miR-224-5p, making the cells more invasive and dependent on upstream substrates of ASS1 for survival. ASS1 was downregulated under acidic conditions, and ASS1-depleted cancer cells maintained a higher intracellular pH (pHi), depended less on extracellular glutamine, and displayed higher glutathione levels. Depletion of substrates of urea cycle enzymes in ASS1-deficient cancers decreased cancer cell survival. Thus, ASS1 levels in cancer are differentially regulated in various environmental conditions to metabolically benefit cancer progression. Understanding these alterations may help uncover specific context-dependent cancer vulnerabilities that may be targeted for therapeutic purposes. SIGNIFICANCE: Cancer cells in an acidic or hypoxic environment downregulate the expression of the urea cycle enzyme ASS1, which provides them with a redox and pH advantage, resulting in better survival.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/3/518/F1.large.jpg.

Neurovascular Coupling Remains Intact During Incremental Ascent to High Altitude (4240 m) in Acclimatized Healthy Volunteers.

Neurovascular coupling (NVC) is the temporal link between neuronal metabolic activity and regional cerebral blood flow (CBF), supporting adequate delivery of nutrients. Exposure to high altitude (HA) imposes several stressors, including hypoxia and hypocapnia, which modulate cerebrovascular tone in an antagonistic fashion. Whether these contrasting stressors and subsequent adaptations affect NVC during incremental ascent to HA is unclear. The aim of this study was to assess whether incremental ascent to HA influences the NVC response. Given that CBF is sensitive to changes in arterial blood gasses, in particular PaCO2, we hypothesized that the vasoconstrictive effect of hypocapnia during ascent would decrease the NVC response. 10 healthy study participants (21.7 ± 1.3 years, 23.57 ± 2.00 kg/m2, mean ± SD) were recruited as part of a research expedition to HA in the Nepal Himalaya. Resting posterior cerebral artery velocity (PCAv), arterial blood gasses (PaO2, SaO2, PaCO2, [HCO3-], base excess and arterial blood pH) and NVC response of the PCA were measured at four pre-determined locations: Calgary/Kathmandu (1045/1400 m, control), Namche (3440 m), Deboche (3820 m) and Pheriche (4240 m). PCAv was measured using transcranial Doppler ultrasound. Arterial blood draws were taken from the radial artery and analyzed using a portable blood gas/electrolyte analyzer. NVC was determined in response to visual stimulation (VS; Strobe light; 6 Hz; 30 s on/off × 3 trials). The NVC response was averaged across three VS trials at each location. PaO2, SaO2, and PaCO2 were each significantly decreased at 3440, 3820, and 4240 m. No significant differences were found for pH at HA (P > 0.05) due to significant reductions in [HCO3-] (P < 0.043). As expected, incremental ascent to HA induced a state of hypoxic hypocapnia, whereas normal arterial pH was maintained due to renal compensation. NVC was quantified as the delta (Δ) PCAv from baseline for mean PCAv, peak PCAv and total area under the curve (ΔPCAv tAUC) during VS. No significant differences were found for Δmean, Δpeak or ΔPCAv tAUC between locations (P > 0.05). NVC remains remarkably intact during incremental ascent to HA in healthy acclimatized individuals. Despite the array of superimposed stressors associated with ascent to HA, CBF and NVC regulation may be preserved coincident with arterial pH maintenance during acclimatization.

Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High-Risk Livers Using Normothermic Machine Perfusion.

Increased use of high‐risk allografts is critical to meet the demand for liver transplantation. We aimed to identify criteria predicting viability of organs, currently declined for clinical transplantation, using functional assessment during normothermic machine perfusion (NMP). Twelve discarded human livers were subjected to NMP following static cold storage. Livers were perfused with a packed red cell–based fluid at 37°C for 6 hours. Multilevel statistical models for repeated measures were employed to investigate the trend of perfusate blood gas profiles and vascular flow characteristics over time and the effect of lactate‐clearing (LC) and non‐lactate‐clearing (non‐LC) ability of the livers. The relationship of lactate clearance capability with bile production and histological and molecular findings were also examined. After 2 hours of perfusion, median lactate concentrations were 3.0 and 14.6 mmol/L in the LC and non‐LC groups, respectively. LC livers produced more bile and maintained a stable perfusate pH and vascular flow >150 and 500 mL/minute through the hepatic artery and portal vein, respectively. Histology revealed discrepancies between subjectively discarded livers compared with objective findings. There were minimal morphological changes in the LC group, whereas non‐LC livers often showed hepatocellular injury and reduced glycogen deposition. Adenosine triphosphate levels in the LC group increased compared with the non‐LC livers. We propose composite viability criteria consisting of lactate clearance, pH maintenance, bile production, vascular flow patterns, and liver macroscopic appearance. These have been tested successfully in clinical transplantation. In conclusion, NMP allows an objective assessment of liver function that may reduce the risk and permit use of currently unused high‐risk livers.

Hydrogen battery using neutralization energy

Low-cost, non-toxic and environment-friendly electrochemistry is highly needed for clean energy storage technologies. Here we propose a most simple rechargeable pH differential hydrogen battery using neutralization energy as an efficient energy storage system to utilize renewable energy and waste acid/base. The overall battery reaction can be simplified as follow: 2 H+ + 2OH-←charge→discharge 2H2O. This proposed hydrogen battery can deliver a theoretical specific energy of up to 250 Wh kg−1 and a maximum energy density of up to 355 Wh L−1, very high values among aqueous battery systems. We show adding excessive amount of NaClO4 can lead to effective pH maintenance, higher coulombic efficiency, higher power and more stable cyclic performance at 9 mA cm−2. This work offers new opportunities to develop clean and high-energy battery technologies.

Exploring the autoinhibitory domain of the electrogenic Na+ /HCO3- transporter NBCe1-B, from residues 28 to 62.

Slc4a4 (mouse) encodes at least five variants of the electrogenic sodium/bicarbonate transporter NBCe1. The initial 41 cytosolic amino acids of NBCe1-A and -D are unique; NBCe1-A has high activity. The initial 85 amino acids of NBCe1-B, -C and -E are unique; NBCe1-B and -C have low activity. Previous work showed that deleting residues 1-85 or 40-62 of NBCe1-B, or 1-87 of NBCe1-C, eliminates autoinhibition. These regions also include binding determinants for IRBIT (inositol trisphosphate (IP3 )-receptor binding protein released with IP3 ), which relieves autoinhibition. Here, systematically replacing/deleting residues 28-62, we find that only the nine amino acid cationic cluster (residues 40-48) of NBCe1-B is essential for autoinhibition. IRBIT stimulates all but one low-activity construct. We suggest that electrostatic interactions - which IRBIT presumably interrupts - between the cationic cluster and the membrane or other domains of NBCe1 play a central role in tempering the activity of NBCe1-B in the pancreas, brain and other organs. Variant B of the electrogenic Na+ /HCO3- cotransporter (NBCe1-B) contributes to the vectorial transport of HCO3- in epithelia (e.g. pancreatic ducts) and to the maintenance of intracellular pH in the central nervous systems (e.g. astrocytes). NBCe1-B has very low basal activity due to an autoinhibitory domain (AID) located, at least in part, in the unique portion (residues 1-85) of the cytosolic NH2 -terminus. Previous work has shown that removing 23 amino acids (residues 40-62) stimulates NBCe1-B. Here, we test the hypothesis that a cationic cluster of nine consecutive positively charged amino acids (residues 40-48) is a necessary part of the AID. Using two-electrode voltage clamping of Xenopus oocytes, we assess the activity of human NBCe1-B constructs in which we systematically replace or delete residues 28-62, which includes the cationic cluster. We find that replacing or deleting all residues within the cationic cluster markedly increases NBCe1-B activity (i.e. eliminates autoinhibition). On the background of a cationic clusterless construct, systematically restoring Arg residues restores autoinhibition in two distinct quanta, with one to three Arg residues restoring ∼50%, and four or more Arg residues restoring virtually all autoinhibition. Systematically deleting residues before the cluster reduces autoinhibition by, at most, a small amount. Replacing or deleting residues after the cluster has no effect. For constructs with low NBCe1 activity (but good surface expression, as assessed by biotinylation), co-expression with super-IRBIT (lacking PP1-binding site) restores full activity (i.e. relieves autoinhibition). In summary, the cationic cluster is a necessary component of the AID of NBCe1-B.

Water bicarbonate modulates the response of the shore crab Carcinus maenas to ocean acidification.

Ocean acidification causes an accumulation of CO2 in marine organisms and leads to shifts in acid-base parameters. Acid-base regulation in gill breathers involves a net increase of internal bicarbonate levels through transmembrane ion exchange with the surrounding water. Successful maintenance of body fluid pH depends on the functional capacity of ion-exchange mechanisms and associated energy budget. For a detailed understanding of the dependence of acid-base regulation on water parameters, we investigated the physiological responses of the shore crab Carcinus maenas to 4weeks of ocean acidification [OA, P(CO2)w = 1800µatm], at variable water bicarbonate levels, paralleled by changes in water pH. Cardiovascular performance was determined together with extra-(pHe) and intracellular pH (pHi), oxygen consumption, haemolymph CO2 parameters, and ion composition. High water P(CO2) caused haemolymph P(CO2) to rise, but pHe and pHi remained constant due to increased haemolymph and cellular [HCO3-]. This process was effective even under reduced seawater pH and bicarbonate concentrations. While extracellular cation concentrations increased throughout, anion levels remained constant or decreased. Despite similar levels of haemolymph pH and ion concentrations under OA, metabolic rates, and haemolymph flow were significantly depressed by 40 and 30%, respectively, when OA was combined with reduced seawater [HCO3-] and pH. Our findings suggest an influence of water bicarbonate levels on metabolic rates as well as on correlations between blood flow and pHe. This previously unknown phenomenon should direct attention to pathways of acid-base regulation and their potential feedback on whole-animal energy demand, in relation with changing seawater carbonate parameters.

The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification

SummaryMacrophages represent the first line of immune defense against pathogens, and phagosome acidification is a necessary step in pathogen clearance. Here, we identified the bicarbonate transporter SLC4A7, which is strongly induced upon macrophage differentiation, as critical for phagosome acidification. Loss of SLC4A7 reduced acidification of phagocytosed beads or bacteria and impaired the intracellular microbicidal capacity in human macrophage cell lines. The phenotype was rescued by wild-type SLC4A7, but not by SLC4A7 mutants, affecting transport capacity or cell surface localization. Loss of SLC4A7 resulted in increased cytoplasmic acidification during phagocytosis, suggesting that SLC4A7-mediated, bicarbonate-driven maintenance of cytoplasmic pH is necessary for phagosome acidification. Altogether, we identify SLC4A7 and bicarbonate-driven cytoplasmic pH homeostasis as an important element of phagocytosis and the associated microbicidal functions in macrophages.

Trans-life cycle acclimation to experimental ocean acidification affects gastric pH homeostasis and larval recruitment in the sea star Asterias rubens.

Experimental simulation of near-future ocean acidification (OA) has been demonstrated to affect growth and development of echinoderm larval stages through energy allocation towards ion and pH compensatory processes. To date, it remains largely unknown how major pH regulatory systems and their energetics are affected by trans-generational exposure to near-future acidification levels. Here, we used the common sea star Asterias rubens in a reciprocal transplant experiment comprising different combinations of OA scenarios, to study trans-generational plasticity using morphological and physiological endpoints. Acclimation of adults to pHT 7.2 (pCO2 3500μatm) led to reductions in feeding rates, gonad weight and fecundity. No effects were evident at moderate acidification levels (pHT 7.4; pCO2 2000μatm). Parental pre-acclimation to pHT 7.2 for 85days reduced developmental rates even when larvae were raised under moderate and high pH conditions, whereas pre-acclimation to pHT 7.4 did not alter offspring performance. Microelectrode measurements and pharmacological inhibitor studies carried out on larval stages demonstrated that maintenance of alkaline gastric pH represents a substantial energy sink under acidified conditions that may contribute up to 30% to the total energy budget. Parental pre-acclimation to acidification levels that are beyond the pH that is encountered by this population in its natural habitat (eg, pHT 7.2) negatively affected larval size and development, potentially through reduced energy transfer. Maintenance of alkaline gastric pH and reductions in maternal energy reserves probably constitute the main factors for a reduced juvenile recruitment of this marine keystone species under simulated OA.

In situ base release for pH maintenance can allow shake flasks to better mimic bioreactor performance for CHO cell culture

AbstractBACKGROUNDShake flasks are widely used for evaluating mammalian cells in suspension. Lack of pH control can contribute to differences in culture performance between them and bioreactors. This study evaluates whether a previously reported in situ base releasing hydrogel (pHmH) to counter pH decrease can enable shake flask cultures to better mimic bioreactor cultures.RESULTSCompared with bioreactor culture, fed‐batch cultures of a recombinant Chinese hamster ovary (CHO) cell‐line in shake flasks without pHmH showed a decrease in pH to 6.6, accompanied by 40, 60 and 22% lower peak cell density, lactate accumulation, and immunoglobulin G (IgG) titer, respectively. Use of pHmH allowed shake flasks to maintain pH above 6.8 and reduced this difference to 20, 30, and 15%, respectively, thus enabling culture performance in shake flasks to better mimic the bioreactor. IgG glycosylation profiles were similar in identically fed cultures across all three platforms. Application of pHmH hydrogel during clone screening was evaluated by comparing correlation between titers for five recombinant CHO clones in bioreactors and shake flasks with and without pHmH; a higher correlation was found in shake flasks with pHmH than without.CONCLUSIONIn situ base release through hydrogel can allow identically fed fed‐batch cultures in shake flasks to better mimic cell growth, lactate accumulation and IgG titers in bioreactors, without additional infrastructure. © 2018 Society of Chemical Industry

Versatile effects of magnesium hydroxide nanoparticles in PLGA scaffold–mediated chondrogenesis

Artificial scaffolds made up of various synthetic biodegradable polymers have been reported to have many advantages including cheap manufacturing, easy scale up, high mechanical strength, convenient manipulation, and molding into an unlimited variety of shapes. However, the synthetic biodegradable polymers still have the insufficiency for cartilage regeneration owing to their acidic degradation products. To reduce acidification by degradation of synthetic polymers, we incorporated magnesium hydroxide (MH) nanoparticles into porous polymer scaffold not only to effectively neutralize the acidic hydrolysate but also to minimize the structural disturbance of scaffolds. The neutralization effect of poly(D,L-lactic-co-glycolic acid; PLGA)/MH scaffold was confirmed with the maintenance of neutral pH, contrary to a PLGA scaffold with low pH. Further, the scaffolds were applied to evaluate the chondrogenic differentiation of the human bone marrow mesenchymal stem cells. In in vitro study, the PLGA/MH scaffold enhanced the chondrogenesis markers and reduced the calcification, compared to the PLGA scaffold. Additionally, the PLGA/MH scaffold reduced the release of inflammatory cytokines, compared to the PLGA scaffold, as the cell death decreased. Moreover, the addition of MH reduced necrotic cell death at the early stage of chondrogenic differentiation. Further, the necrotic cell death by the PLGA scaffold was mediated by cleavage of caspase-1, the so-called interleukin 1-converting enzyme, and MH alleviated it as well as nuclear factor kappa B expression. Furthermore, the PLGA/MH scaffold highly supported chondrogenic healing of rat osteochondral defect sites in in vivo study. Therefore, it was suggested that a synthetic polymer scaffold containing MH could be a novel healing tool to support cartilage regeneration and further treatment of orthopedic patients. Statement of SignificanceSynthetic polymer scaffolds have been widely utilized for tissue regeneration. However, they have a disadvantage of releasing acidic products through degradation. This paper demonstrated a novel type of synthetic polymer scaffold with pH-neutralizing ceramic nanoparticles composed of magnesium hydroxide for cartilage regeneration. This polymer showed pH-neutralization property during polymer degradation and significant enhancement of chondrogenic differentiation of mesenchymal stem cells. It reduced not only chondrogenic calcification but also release of proinflammatory cytokines. Moreover, it has an inhibitory effect on necrotic cell death, particularly caspase-1-mediated necrotic cell death (pyroptosis). In in vivo study, it showed higher healing rate of the damaged cartilage in a rat osteochondral defect model. We expected that this novel type of scaffold can be effectively applied to support cartilage regeneration and further treatment of orthopedic patients.

The Neurovascular Coupling Response Remains Intact During Incremental Ascent to High Altitude (4370m) in Acclimatized Healthy Volunteers

Neurovascular coupling (NVC) is the link between neuronal metabolic activity and regional cerebral blood flow. NVC is responsible for ensuring adequate delivery of nutrients (O2 and glucose) during periods of increased neuronal metabolic demand. Exposure to high‐altitude (HA) elicits ventilatory and acid‐base adjustments for maintaining blood pH. Acute exposure to HA causes hypoxic vasodilation. Hypoxia also drives a ventilatory response, inducing hypocapnia, a potent vasoconstrictor. Whether these dynamic and conflicting responses affect NVC during incremental ascent to HA is unclear.The aim of this project was to assess whether changes in arterial blood gases (ABGs) associated with ascent to HA influences the NVC response. Given that CBF is particularly sensitive to changes in PaCO2, we hypothesized that hypocapnic vasoconstriction during ascent would decrease the NVC response with ascent.10 healthy study participants (21.7±1.3 yrs, 70.46±13.65kg, mean±SD) were recruited as part of a research expedition to Everest base camp, Nepal. Resting posterior cerebral artery velocity (PCAv), ABGs (PaO2, PaCO2), SaO2, arterial blood pH and bicarbonate [HCO3−] were measured at four locations: Calgary (1045m; baseline; BL), Namche (3440m), Deboche (3820m) and Pheriche (4370m). Resting PCAv was measured using transcranial Doppler ultrasound. Arterial blood draws were taken from the radial artery and analysed using a portable blood gas/electrolyte analyser used to monitor changes in ABGs (PaCO2, PaO2, SaO2), pH and [HCO3−] during ascent. NVC was tested via visual stimulation (VS; Strobe light; 6Hz; 30sec on/off ×3). The NVC response was averaged across three VS trials at each location. NVC was quantified as the change (delta) in mean and peak PCAv from baseline, during VS.A one‐factor‐repeated measures analysis of variance (ANOVA) was used to assess for differences in baseline PCAv, NVC, ABGs, blood pH and [HCO3−] between locations. PaO2, PaCO2 and SaO2 were significantly decreased from BL at each altitude (P&lt;0.001, P&lt;0.016 and P&lt;0.013, respectively). No significant differences were found for pH at any location compared to BL (P&gt;0.05) due to reductions in arterial [HCO3−] (P&lt;0.043). No significant differences were found in baseline PCAv between locations (P&gt;0.05) or for mean or peak NVC responses (P&gt;0.085 and P&gt;0.08 respectively).As expected, incremental ascent to HA induced a state of hypoxic hypocapnia, as demonstrated by significant reductions in PaO2, SaO2 and PaCO2, whereas arterial pH was maintained via reductions in [HCO3−]. Our data suggests that NVC remains remarkably intact during incremental ascent to HA in healthy acclimatized individuals. Despite the array of superimposed stressors associated with ascent to HA, CBF and NVC regulation may be a unique function of arterial pH maintenance.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

"Do-It-Yourself" reliable pH-stat device by using open-source software, inexpensive hardware and available laboratory equipment.

In this paper, we present the construction of a reliable and inexpensive pH stat device, by using open-source “OpenPhControl” software, inexpensive hardware (a peristaltic and a syringe pump, Arduino, a step motor…), readily available laboratory devices: a pH meter, a computer, a webcam, and some 3D printed parts. We provide a methodology for the design, development and test results of each part of the device, as well as of the entire system. In addition to dosing reagents by means of a low-cost peristaltic pump, we also present carefully controlled dosing of reagents by an open-source syringe pump. The upgrading of the basic open-source syringe pump is given in terms of pump control and application of a larger syringe. In addition to the basic functions of pH stat, i.e. pH value measurement and maintenance, an improvement allowing the device to be used for potentiometric titration has been made as well. We have demonstrated the device’s utility when applied for cellulose fibers oxidation with 2,2,6,6-tetramethylpiperidine-1-oxyl radical, i.e. for TEMPO-mediated oxidation. In support of this, we present the results obtained for the oxidation kinetics, the consumption of added reagent and experimental repeatability. Considering that the open-source scientific tools are available to everyone, and that researchers can construct and adjust the device according to their needs, as well as, that the total cost of the open-source pH stat device, excluding the existing laboratory equipment (pH meter, computer and glossary) was less than 150 EUR, we believe that, at a small fraction of the cost of available commercial offers, our open-source pH stat can significantly improve experimental work where the use of pH stat is necessary.

Investigation of Metabolomic Changes in Sunitinib-Resistant Human Renal Carcinoma 786-O Cells by Capillary Electrophoresis-Time of Flight Mass Spectrometry.

Acquired resistance to sunitinib is a challenge in the treatment of renal cell carcinoma (RCC). The dysregulation of cellular metabolism is prevalent during resistance acquisition. It is known that in sunitinib-resistant RCC 786-O (786-O Res) cells sunitinib is mainly sequestered in the intracellular lysosomes. However, the relevance between sunitinib resistance and cellular metabolism has not been examined. In this study, we examined the metabolic changes in 786-O Res by using capillary electrophoresis-time of flight mass spectrometry. The cell line 786-O Res was established via persistent treatment with sunitinib, where increase in intracellular sunitinib, and sizes of lysosomes and nuclei were enhanced as compared with those in the parental 786-O (786-O Par) cells. Metabolic analyses revealed that out of the 110 metabolites examined, 13 were up-regulated and 4 were down-regulated in the 786-O Res cells. The glycolysis, tricarboxylic acid cycle and pentose phosphate pathway (PPP) were identified as being altered in the sunitinib-resistant cells, which resulted in the enhanced metabolisms of energy, nucleic acids, and glutathione redox cycle. As sunitinib was sequestered in the enlarged lysosomes in 786-O Res, the enriched energy metabolism might contribute to the maintenance of luminal pH in lysosomes via the H+ ATPase. The changes in the PPP could contribute to nuclei enlargement through up-regulation of nucleic acid biosynthesis and protect 786-O Res from cytotoxicity induced by sunitinib through up-regulation of reduced glutathione. Though the direct link between sunitinib resistance and metabolic alternation remains to be elucidated, this metabolomics study provides fundamental insights into acquisition of sunitinib resistance.

PH and Microbial Infections.

Maintenance of an acidic stratum corneum pH is a major component of the skin's protective system and creates a hostile environment for colonization with pathogenic microorganisms. This barrier can however be overcome on healthy and in particular on compromised skin. Mycosis, diaper/incontinence dermatitis and wound healing are examples of cases where microbial infection is promoted by the altered skin conditions or environment. Fungi have a complex system that senses ambient pH that leads to metabolic responses allowing adhesion, growth and invasion, as microbial metabolites further increase skin pH resulting in a clinically manifest infection (mycosis). Diabetic patients with a higher pH in intertriginous areas are particularly vulnerable to candidiasis. In diaper and incontinence dermatitis, the increase in skin pH and damage to the skin barrier function is triggered by the contact with urine and faeces with or without occlusion and maintained by host and microbial enzymes and metabolites. This leads to the reduction of the protective resident microflora and fungal overgrowth, mostly with Candida albicans. Skin care with slightly acidic products may help to prevent and treat this kind of dermatitis. Wound healing is a complex sequence of biologic events correlated with ambient pH, which influences the different phases of the healing process. The pH determines the appropriate activity of immune cells and key enzymes as well as biofilm formation. Chronic wounds emerging from the disruption of the healing process are characterized by a neutral to slightly alkaline pH and may benefit from wound pH monitoring and therapeutic acidification.

The combined effects of acidification and hypoxia on pH and aragonite saturation in the coastal waters of the California current ecosystem and the northern Gulf of Mexico

Inorganic carbon chemistry data from the surface and subsurface waters of the West Coast of North America have been compared with similar data from the northern Gulf of Mexico to demonstrate how future changes in CO2 emissions will affect chemical changes in coastal waters affected by respiration-induced hypoxia ([O2] ≤ ~ 60µmolkg−1). In surface waters, the percentage change in the carbon parameters due to increasing CO2 emissions are very similar for both regions even though the absolute decrease in aragonite saturation is much higher in the warmer waters of the Gulf of Mexico. However, in subsurface waters the changes are enhanced due to differences in the initial oxygen concentration and the changes in the buffer capacity (i.e., increasing Revelle Factor) with increasing respiration from the oxidation of organic matter, with the largest impacts on pH and CO2 partial pressure (pCO2) occurring in the colder West Coast waters. As anthropogenic CO2 concentrations begin to build up in subsurface waters, increased atmospheric CO2 will expose organisms to hypercapnic conditions (pCO2 >1000 µatm) within subsurface depths. Since the maintenance of the extracellular pH appears as the first line of defense against external stresses, many biological response studies have been focused on pCO2-induced hypercapnia. The extent of subsurface exposure will occur sooner and be more widespread in colder waters due to their capacity to hold more dissolved oxygen and the accompanying weaker acid-base buffer capacity. Under present conditions, organisms in the West Coast are exposed to hypercapnic conditions when oxygen concentrations are near 100µmolkg−1 but will experience hypercapnia at oxygen concentrations of 260µmolkg−1 by year 2100 under the highest elevated-CO2 conditions. Hypercapnia does not occur at present in the Gulf of Mexico but will occur at oxygen concentrations of 170µmolkg−1 by the end of the century under similar conditions. The aragonite saturation horizon is currently above the hypoxic zone in the West Coast. With increasing atmospheric CO2, it is expected to shoal up close to surface waters under the IPCC Representative Concentration Pathway (RCP) 8.5 in West Coast waters, while aragonite saturation state will exhibit steeper gradients in the Gulf of Mexico. This study demonstrates how different biological thresholds (e.g., hypoxia, CaCO3 undersaturation, hypercapnia) will vary asymmetrically because of local initial conditions that are affected differently with increasing atmospheric CO2. The direction of change in amplitude of hypercapnia will be similar in both ecosystems, exposing both biological communities from the West Coast and Gulf of Mexico to intensification of stressful conditions. However, the region of lower Revelle factors (i.e., the Gulf of Mexico), currently provides an adequate refuge habitat that might no longer be the case under the most severe RCP scenarios.

The Role of the Plasma Membrane H+-ATPase in Plant Responses to Aluminum Toxicity.

Aluminum (Al) toxicity is a key factor limiting plant growth and crop production on acid soils. Increasing the plant Al-detoxification capacity and/or breeding Al-resistant cultivars are a cost-effective strategy to support crop growth on acidic soils. The plasma membrane H+-ATPase plays a central role in all plant physiological processes. Changes in the activity of the plasma membrane H+-ATPase through regulating the expression and phosphorylation of this enzyme are also involved in many plant responses to Al toxicity. The plasma membrane H+-ATPase mediated H+ influx may be associated with the maintenance of cytosolic pH and the plasma membrane gradients as well as Al-induced citrate efflux mediated by a H+-ATPase-coupled MATE co-transport system. In particular, modulating the activity of plasma membrane H+-ATPase through application of its activators (e.g., magnesium or IAA) or using transgenics has effectively enhanced plant resistance to Al stress in several species. In this review, we critically assess the available knowledge on the role of the plasma membrane H+-ATPase in plant responses to Al stress, incorporating physiological and molecular aspects.

Phosphorus dissolution from dewatered anaerobic sludge: Effect of pHs, microorganisms, and sequential extraction

Phosphorus (P) and iron mass balance from Limassol Wastewater Treatment Plant showed that the major removal and accumulation occurred at the aerobic secondary stage and at Dewatered Anaerobic Sludge (DWAS), respectively. The purpose of this study was to examine various parameters that effect the P dissolution under low pH from DWAS. The parameters that significantly contribute to P extraction were the exposure to pH 2.5, the anaerobic conditions and the sequential extraction. The addition of chemolithotrophic acidophilic bacteria has negatively influenced P dissolution, whereas the addition of acidophilic Heterotrophic Iron Reducing (HIR) bacteria has slightly increased P dissolution but they contributed to pH maintenance at lower levels compared to no addition of HIR. P fractionation of the residual sludge after sequential extraction pointed out that the organically bound P was hardly dissoluted from DWAS. The residual DWAS after acid treatment generated around 45% less methane compared to the initial DWAS.

PH Change in Electroosmotic Flow Hysteresis.

Electroosmotic flow (EOF) or electro-osmosis has been shown to exhibit a hysteresis effect under displacement flow involving two solutions with different concentrations, i.e. the flow velocity for a high-concentration solution displacing a low-concentration solution is faster than the flow velocity in the reverse direction involving the same solution pair. On the basis of our recent numerical analysis, a pH change initiated at the interface between the two solutions has been hypothesized as the cause for the observed anomalies. We report the first experimental evidence of EOF hysteresis induced by a pH change in the bulk solution. pH-sensitive dye was employed to quantify the pH changes in the microchannel during EOF. The electric-field gradient across the boundary of two solutions generates an accumulation or depletion of a minority of pH-governing ions such as hydronium (H3O+) ions, thus inducing pH variations across the microchannel. When a high-concentration solution displaced a lower-concentration solution, a pH increase was observed, while the flow in the reverse direction induced a decrease in pH. This effect causes significant changes to the zeta potential and flow velocity. The experimental results show good quantitative agreement with numerical simulations. This work presents the experimental proof which validates the hypothesis of a pH change during electroomostic flow hysteresis as predicted by numerical analysis. The understanding of pH changes during EOF is crucial for accurate flow manipulation in microfluidic devices and maintenance of constant pH in biological and chemical systems under an electric field.

Cycles of vascular plexus formation within the nephrogenic zone of the developing mouse kidney

The renal vasculature is required for blood filtration, blood pressure regulation, and pH maintenance, as well as other specialised kidney functions. Yet, despite its importance, many aspects of its development are poorly understood. To provide a detailed spatiotemporal analysis of kidney vascularisation, we collected images of embryonic mouse kidneys at various developmental time-points. Here we describe the first stages of kidney vascularisation and demonstrate that polygonal networks of vessels (endothelial plexuses) form in cycles at the periphery of the kidney. We show that kidney vascularisation initiates at E11, when vessels connected to the embryonic circulation form a ring around the ureteric bud. From E13.5, endothelial plexuses organise around populations of cap mesenchymal and ureteric bud cells in a cyclical, predictable manner. Specifically, as the ureteric bud bifurcates, endothelia form across the bifurcation site as the cap mesenchyme splits. The plexuses are vascular, carry erythrocytes, are enclosed within a basement membrane, and can always be traced back to the renal artery. Our results are a major step towards understanding how the global architecture of the renal vasculature is achieved.