The Impact of Extracellular Low pH on the Anti-Tumor Efficacy Against Mesothelioma

Abstract Background The low extracellular pH (pHe) of tumors resulting from glycolytic metabolism is a stress factor for the cells independent from concomitant hypoxia. The aim of the study was to analyze the impact of acidic pHe on gene expression on mRNA and protein level in two experimental tumor lines in vitro and in vivo and were compared to hypoxic conditions as well as combined acidosis+hypoxia. Methods Gene expression was analyzed in AT1 prostate and Walker-256 mammary carcinoma of the rat by Next Generation Sequencing (NGS), qPCR and Western blot. In addition, the impact of acidosis on tumor cell migration, adhesion, proliferation, cell death and mitochondrial activity was analyzed. Results NGS analyses revealed that 147 genes were uniformly regulated in both cell lines (in vitro) and 79 genes in both experimental tumors after 24 h at low pH. A subset of 25 genes was re-evaluated by qPCR and Western blot. Low pH consistently upregulated Aox1, Gls2, Gstp1, Ikbke, Per3, Pink1, Tlr5, Txnip, Ypel3 or downregulated Acat2, Brip1, Clspn, Dnajc25, Ercc6l, Mmd, Rif1, Zmpste24 whereas hypoxia alone led to a downregulation of most of the genes. Direct incubation at low pH reduced tumor cell adhesion whereas acidic pre-incubation increased the adhesive potential. In both tumor lines acidosis induced a G1-arrest (in vivo) of the cell cycle and a strong increase in necrotic cell death (but not in apoptosis). The mitochondrial O2 consumption increased gradually with decreasing pH. Conclusions These data show that acidic pHe in tumors plays an important role for gene expression independently from hypoxia. In parallel, acidosis modulates functional properties of tumors relevant for their malignant potential and which might be the result of pH-dependent gene expression.

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Stream plant chemistry as indicator of acid sulphate soils in Sweden

Agricultural and Food Science ◽

10.2137/1459606054224165 ◽

2008 ◽

Vol 14 (1) ◽

pp. 83 ◽

Cited By ~ 6

Author(s):

K. LAX

Keyword(s):

Surface Waters ◽

Stream Water ◽

Low Ph ◽

Fontinalis Antipyretica ◽

Acid Sulphate ◽

Fine Grained ◽

Acid Sulphate Soils ◽

Trace Element Chemistry ◽

Study Results ◽

The Impact

Results from the biogeochemical mapping (roots of aquatic plants and Fontinalis antipyretica) conducted by the Geological Survey of Sweden (SGU) reflects the metal load of surface waters draining acid sulphate (AS) soils in Sweden. In this study, results from the biogeochemical, soil geochemical and Quaternary mapping programmes at SGU were used to investigate the impact of fine-grained deposits hosting AS soils on stream water trace element chemistry in two separate areas. In the area around Lake Mälaren, postglacial sediments contain the highest levels of most trace elements studied. Owing to the low pH of AS soils and subsequent leaching, levels of nickel (Ni), cobalt (Co), copper (Cu), sulphur (S), yttrium (Y), uranium (U), tungsten (W), and molybdenum (Mo) were significantly elevated in aquatic roots. Levels were lower in the Skellefteå area, which may be explained by lower concentrations in source deposits. Concentrations of arsenic (As) and lead (Pb) were normal or impoverished in biogeochemical samples from postglacial, finegrained sediment areas. Maps based on ratios (Ni:Pb or Y:Pb) in biogeochemical samples can, together with results from Quaternary mapping, be used to predict areas with AS soils in Sweden.;

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Variation in brachiopod microstructure and isotope geochemistry under low pH–ocean acidification–conditions

10.5194/bg-2018-332 ◽

2018 ◽

Author(s):

Facheng Ye ◽

Hana Jurikova ◽

Lucia Angiolini ◽

Uwe Brand ◽

Gaia Crippa ◽

...

Keyword(s):

Stable Isotope ◽

Ocean Acidification ◽

Isotope Geochemistry ◽

Shell Growth ◽

Low Ph ◽

Secondary Layer ◽

Ph Conditions ◽

One Year ◽

The Impact ◽

Δ13c And Δ18o

Abstract. Throughout the last few decades and in the near future CO2–induced ocean acidification is potentially a big threat to marine calcite-shelled animals (e.g., brachiopods, bivalves, corals and gastropods). Despite the great number of studies focusing on the effects of acidification on shell growth, metabolism, shell dissolution and shell repair, the consequences on biomineral formation remain poorly understood, and only few studies addressed contemporarily the impact of acidification on shell microstructure and geochemistry. In this study, a detailed microstructure and stable isotope geochemistry investigation was performed on nine adult brachiopod specimens of Magellania venosa (Dixon, 1789), grown in the natural environment as well as in controlled culturing experiments at different pH conditions (ranging 7.35 to 8.15 ± 0.05) over different time intervals (214 to 335 days). Details of shell microstructural features, such as thickness of the primary layer, density and size of endopunctae and morphology of the basic structural unit of the secondary layer were analysed using scanning electron microscopy (SEM). Stable isotope compositions (δ13C and δ18O) were tested from the secondary shell layer along shell ontogenetic increments in both dorsal and ventral valves. Based on our comprehensive dataset, we observed that, under low pH conditions, M. venosa produced a more organic-rich shell with higher density of and larger endopunctae, and smaller secondary layer fibres, when subjected to about one year of culturing. Also, increasingly negative δ13C and δ18O values are recorded by the shell produced during culturing and are related to the CO2–source in the culture setup. Both the microstructural changes and the stable isotope results are similar to observations on brachiopods from the fossil record and strongly support the value of brachiopods as robust archives of proxies for studying ocean acidification events in the geologic past.

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Cystic Fibrosis-AssociatedStenotrophomonas maltophiliaStrain-Specific Adaptations and Responses to pH

Journal of Bacteriology ◽

10.1128/jb.00478-18 ◽

2019 ◽

Vol 201 (7) ◽

Cited By ~ 2

Author(s):

Tara Gallagher ◽

Joann Phan ◽

Andrew Oliver ◽

Alexander B. Chase ◽

Whitney E. England ◽

...

Keyword(s):

Cystic Fibrosis ◽

Stenotrophomonas Maltophilia ◽

Opportunistic Infections ◽

Expression Profiles ◽

Bacterial Colonization ◽

Low Ph ◽

Lung Damage ◽

Ph Gradients ◽

Content Type ◽

The Impact

ABSTRACTThe airway fluids of cystic fibrosis (CF) patients contain local pH gradients and are more acidic than those of healthy individuals. pH is a critical factor that is often overlooked in studies seeking to recapitulate the infection microenvironment. We sought to determine the impact of pH on the physiology of a ubiqituous yet understudied microbe,Stenotrophomonas maltophilia. Phylogenomics was first used to reconstruct evolutionary relationships between 74 strains ofS. maltophilia(59 from CF patients). Neither the core genome (2,158 genes) nor the accessory genome (11,978 genes) distinguish the CF and non-CF isolates; however, strains from similar isolation sources grouped into the same subclades. We grew two human and six CFS. maltophiliaisolates from different subclades at a range of pH values and observed impaired growth and altered antibiotic tolerances at pH 5. Transcriptomes revealed increased expression of both antibiotic resistance and DNA repair genes in acidic conditions. Although the gene expression profiles ofS. maltophiliain lab cultures and CF sputum were distinct, we found that the same genes associated with low pH were also expressed during infection, and the higher pH cultures were more similar to sputum metatranscriptomes. Our findings suggest thatS. maltophiliais not well adapted to acidity and may cope with low pH by expressing stress response genes and colonizing less acidic microenvironments. As a whole, our study underlines the impact of microenvironments on bacterial colonization and adaptation in CF infections.IMPORTANCEUnderstanding bacterial responses to physiological conditions is an important priority for combating opportunistic infections. The majority of CF patients succumb to inflammation and necrosis in the airways, arising from chronic infection due to ineffective mucociliary clearance. Steep pH gradients characterize the CF airways but are not often incorporated in standard microbiology culture conditions.Stenotrophomonas maltophiliais a prevalent CF opportunistic pathogen also found in many disparate environments, yet this bacterium’s contribution to CF lung damage and its response to changing environmental factors remain largely understudied. Here, we show that pH impacts the physiology and antibiotic susceptibility ofS. maltophilia, with implications for the development of relevantin vitromodels and assessment of antibiotic sensitivity.

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Nutrient Addition to Low pH Base Wines (L. cv. Riesling) during Yeast Acclimatization for Sparkling Wine: Its Influence on Yeast Cell Growth, Sugar Consumption and Nitrogen Usage

Beverages ◽

10.3390/beverages6010010 ◽

2020 ◽

Vol 6 (1) ◽

pp. 10

Author(s):

Belinda Kemp ◽

Jessy Plante ◽

Debra L. Inglis

Keyword(s):

Alcoholic Fermentation ◽

Low Ph ◽

Nutrient Concentrations ◽

Sparkling Wine ◽

Sugar Consumption ◽

Wine Production ◽

Nutrient Sources ◽

Time Required ◽

The Impact ◽

Kinetics Of

In traditional method sparkling wine production, to carry out a successful second alcoholic fermentation, yeast are acclimatized to stressful base wine conditions. Base wines typically have low pH, low nutrient concentrations, high acid concentrations, contain sulfur dioxide (SO2), and high ethanol concentrations. Supplementing yeast during the acclimatization stages prior to second alcoholic fermentation with different nutrient sources was assessed to determine the impact on yeast growth, sugar consumption and nitrogen usage. Four treatments were tested with Saccharomyces cerevisiae strain EC1118: the control (T1) with no additives; addition of diammonium phosphate (DAP) during acclimatization, (T2); Go-Ferm® inclusion during yeast rehydration (GF), (T3); and DAP + GF (T4). Results (n = 4) indicated that supplementing with DAP, GF or DAP + GF increased both the rate of sugar consumption and the concentration of viable cells during the yeast acclimatization phase in comparison to the control. Treatments supplemented with DAP + GF or DAP alone resulted in yeast consuming 228 and 220 mg N/L during the acclimatization phase, respectively. Yeast treated only with GF consumed 94 mg N/L in comparison to the control, which consumed 23 mg N/L. The time required to reach the target specific gravity (1.010) during acclimatization was significantly reduced to 57 h for yeast treated with DAP and GF, 69 h for yeast treated with DAP only and 81 h for yeast rehydrated with GF in comparison to 105 h for the control. Our results suggest that nutrients used during yeast acclimatization could have an important impact on the kinetics of second alcoholic fermentation.

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Acidosis downregulates platelet haemostatic functions and promotes neutrophil proinflammatory responses mediated by platelets

Thrombosis and Haemostasis ◽

10.1160/th11-06-0443 ◽

2012 ◽

Vol 107 (01) ◽

pp. 99-110 ◽

Cited By ~ 39

Author(s):

Julia Etulain ◽

Soledad Negrotto ◽

Agostina Carestia ◽

Roberto Pozner ◽

María Romaniuk ◽

...

Keyword(s):

Tissue Injury ◽

Atp Release ◽

Low Ph ◽

Significant Inhibition ◽

Dependent Manner ◽

Clot Retraction ◽

Extracellular Acidosis ◽

Proinflammatory Responses ◽

Microparticle Formation ◽

The Impact

SummaryAcidosis is one of the hallmarks of tissue injury such as trauma, infection, inflammation, and tumour growth. Although platelets participate in the pathophysiology of all these processes, the impact of acidosis on platelet biology has not been studied outside of the quality control of laboratory aggregation assays or platelet transfusion optimization. Herein, we evaluate the effect of physiologically relevant changes in extracellular acidosis on the biological function of platelets, placing particular emphasis on haemostatic and secretory functions. Platelet haemostatic responses such as adhesion, spreading, activation of αIIbβ3 integrin, ATP release, aggregation, thromboxane B2 generation, clot retraction and procoagulant activity including phosphatidilserine exposure and microparticle formation, showed a statistically significant inhibition of thrombin-induced changes at pH of 7.0 and 6.5 compared to the physiological pH (7.4). The release of alpha granule content was differentially regulated by acidosis. At low pH, thrombin or collagen-induced secretion of vascular endothelial growth factor and endostatin were dramatically reduced. The release of von Willebrand factor and stromal derived factor-1α followed a similar, albeit less dramatic pattern. In contrast, the induction of CD40L was not changed by low pH, and P-selectin exposure was significantly increased. While the generation of mixed platelet-leukocyte aggregates and the increased chemotaxis of neutrophils mediated by platelets were further augmented under acidic conditions in a P-selectin dependent manner, the increased neutrophil survival was independent of P-selectin expression. In conclusion, our results indicate that extracellular acidosis downregulates most of the haemostatic platelet functions, and promotes those involved in amplifying the neutrophil-mediated inflammatory response.

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The impact of ocean acidification and warming on the skeletal mechanical properties of the sea urchin Paracentrotus lividus from laboratory and field observations

ICES Journal of Marine Science ◽

10.1093/icesjms/fsv018 ◽

2015 ◽

Vol 73 (3) ◽

pp. 727-738 ◽

Cited By ~ 27

Author(s):

Marie Collard ◽

Samuel P. S. Rastrick ◽

Piero Calosi ◽

Yoann Demolder ◽

Jean Dille ◽

...

Keyword(s):

Mechanical Properties ◽

Laboratory Experiment ◽

Young’S Modulus ◽

Sea Urchin ◽

Sea Urchins ◽

Young's Modulus ◽

Paracentrotus Lividus ◽

Low Ph ◽

Fracture Force ◽

The Impact

Abstract Increased atmospheric CO2 concentration is leading to changes in the carbonate chemistry and the temperature of the ocean. The impact of these processes on marine organisms will depend on their ability to cope with those changes, particularly the maintenance of calcium carbonate structures. Both a laboratory experiment (long-term exposure to decreased pH and increased temperature) and collections of individuals from natural environments characterized by low pH levels (individuals from intertidal pools and around a CO2 seep) were here coupled to comprehensively study the impact of near-future conditions of pH and temperature on the mechanical properties of the skeleton of the euechinoid sea urchin Paracentrotus lividus. To assess skeletal mechanical properties, we characterized the fracture force, Young's modulus, second moment of area, material nanohardness, and specific Young's modulus of sea urchin test plates. None of these parameters were significantly affected by low pH and/or increased temperature in the laboratory experiment and by low pH only in the individuals chronically exposed to lowered pH from the CO2 seeps. In tidal pools, the fracture force was higher and the Young's modulus lower in ambital plates of individuals from the rock pool characterized by the largest pH variations but also a dominance of calcifying algae, which might explain some of the variation. Thus, decreases of pH to levels expected for 2100 did not directly alter the mechanical properties of the test of P. lividus. Since the maintenance of test integrity is a question of survival for sea urchins and since weakened tests would increase the sea urchins' risk of predation, our findings indicate that the decreasing seawater pH and increasing seawater temperature expected for the end of the century should not represent an immediate threat to sea urchins vulnerability.

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Antagonistic interplay between pH and food resources affects copepod traits and performance in a year-round upwelling system

Scientific Reports ◽

10.1038/s41598-019-56621-6 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Victor M. Aguilera ◽

Cristian A. Vargas ◽

Hans G. Dam

Keyword(s):

Ocean Acidification ◽

Egg Production ◽

Egg Size ◽

Ingestion Rate ◽

Food Resources ◽

Low Ph ◽

Phenotypic Traits ◽

Upwelling System ◽

And Performance ◽

The Impact

AbstractLinking pH/pCO2 natural variation to phenotypic traits and performance of foundational species provides essential information for assessing and predicting the impact of ocean acidification (OA) on marine ecosystems. Yet, evidence of such linkage for copepods, the most abundant metazoans in the oceans, remains scarce, particularly for naturally corrosive Eastern Boundary Upwelling systems (EBUs). This study assessed the relationship between pH levels and traits (body and egg size) and performance (ingestion rate (IR) and egg reproduction rate (EPR)) of the numerically dominant neritic copepod Acartia tonsa, in a year-round upwelling system of the northern (23° S) Humboldt EBUs. The study revealed decreases in chlorophyll (Chl) ingestion rate, egg production rate and egg size with decreasing pH as well as egg production efficiency, but the opposite for copepod body size. Further, ingestion rate increased hyperbolically with Chl, and saturated at ~1 µg Chl. L−1. Food resources categorized as high (H, >1 µg L−1) and low (L, <1 µg L−1) levels, and pH-values categorized as equivalent to present day (≤400 µatm pCO2, pH > 7.89) and future (>400 µatm pCO2, pH < 7.89) were used to compare our observations to values globally employed to experimentally test copepod sensitivity to OA. A comparison (PERMANOVA) test with Chl/pH (2*2) design showed that partially overlapping OA levels expected for the year 2100 in other ocean regions, low-pH conditions in this system negatively impacted traits and performance associated with copepod fitness. However, interacting antagonistically with pH, food resource (Chl) maintained copepod production in spite of low pH levels. Thus, the deleterious effects of ocean acidification are modulated by resource availability in this system.

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The Impact of pH on Clostridioides difficile Sporulation and Physiology

Applied and Environmental Microbiology ◽

10.1128/aem.02706-19 ◽

2019 ◽

Vol 86 (4) ◽

Cited By ~ 1

Author(s):

Daniela Wetzel ◽

Shonna M. McBride

Keyword(s):

Phenotypic Diversity ◽

Toxin Production ◽

Low Ph ◽

Spore Morphology ◽

Content Type ◽

Clostridioides Difficile ◽

Alkaline Environments ◽

Acidic Conditions ◽

Ph Conditions ◽

The Impact

ABSTRACT Clostridioides difficile is a pathogenic bacterium that infects the human colon to cause diarrheal disease. Growth of the bacterium is known to be dependent on certain bile acids, oxygen levels, and nutrient availability in the intestine, but how the environmental pH can influence C. difficile is mostly unknown. Previous studies indicated that C. difficile modulates the intestinal pH, and prospective cohort studies have found a strong association between a more alkaline fecal pH and C. difficile infection. Based on these data, we hypothesized that C. difficile physiology can be affected by various pH conditions. In this study, we investigated the impact of a range of pH conditions on C. difficile to assess potential effects on growth, sporulation, motility, and toxin production in the strains 630Δerm and R20291. We observed pH-dependent differences in sporulation rate, spore morphology, and viability. Sporulation frequency was lowest under acidic conditions, and differences in cell morphology were apparent at low pH. In alkaline environments, C. difficile sporulation was greater for strain 630Δerm, whereas R20291 produced relatively high levels of spores in a broad range of pH conditions. Rapid changes in pH during exponential growth impacted sporulation similarly among the strains. Furthermore, we observed an increase in C. difficile motility with increases in pH, and strain-dependent differences in toxin production under acidic conditions. The data demonstrate that pH is an important parameter that affects C. difficile physiology and may reveal relevant insights into the growth and dissemination of this pathogen. IMPORTANCE Clostridioides difficile is an anaerobic bacterium that causes gastrointestinal disease. C. difficile forms dormant spores which can survive harsh environmental conditions, allowing their spread to new hosts. In this study, we determine how intestinally relevant pH conditions impact C. difficile physiology in the two divergent strains, 630Δerm and R20291. Our data demonstrate that low pH conditions reduce C. difficile growth, sporulation, and motility. However, toxin production and spore morphology were differentially impacted in the two strains at low pH. In addition, we observed that alkaline environments reduce C. difficile growth, but increase cell motility. When pH was adjusted rapidly during growth, we observed similar impacts on both strains. This study provides new insights into the phenotypic diversity of C. difficile grown under diverse pH conditions present in the intestinal tract, and demonstrates similarities and differences in the pH responses of different C. difficile isolates.

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Peroxidase activity against guaiacol, NADH, chlorogenic acid, ferulic acid and coniferyl alcohol in root tips of Lotus japonicus and L. corniculatus grown under low pH and aluminium stress

Biologia ◽

10.2478/s11756-010-0029-3 ◽

2010 ◽

Vol 65 (2) ◽

Cited By ~ 3

Author(s):

Veronika Zelinová ◽

Igor Mistrík ◽

Peter Paľove-Balang ◽

Ladislav Tamás

Keyword(s):

Ferulic Acid ◽

Chlorogenic Acid ◽

Lotus Japonicus ◽

Lotus Corniculatus ◽

Low Ph ◽

Coniferyl Alcohol ◽

Defence Response ◽

Root Tip ◽

H2o2 Production ◽

The Impact

AbstractThe purpose of this study was to examine the impact of low pH and Al stress on the apoplastic production of H2O2 and POD activity against guaiacol, ferulic acid, coniferyl alcohol, NADH and chlorogenic acid in the root tip (RT) of two cultivars of Lotus corniculatus and the model Lotus japonicus Gifu, with the goal to determine the possible role of POD activity in proton and Al tolerance. Our results suggest that Lotus corniculatus cv. UFRGS is more tolerant to low pH and Al than cv. Draco due to the high POD activities involved in CW strengthening. The enzymatic response of Lotus japonicus Gifu is similar rather to the sensitive cultivar. On the other hand, in cvs Draco and Gifu low pH induced the activation of CW-modifying PODs, which is probably a component of the defence response of roots to the presence of toxic protons. Aluminium did not activate further these activities suggesting that defence response and acclimation to low pH confers also effective defence against Al toxicity in Lotus species. The activity of NADH-POD and CGA-POD were not affected significantly by exposure to low pH or Al. Al and pH induced drop in H2O2 production, which was more relevant in cv. Gifu and Draco than in cv. UFRGS is probably associated with enhanced activity of peroxidases involved in secondary CW metabolism utilizing H2O2 as an electron acceptor.

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