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\"The pH scale measures how acidic or basic a substance is, ranging from 0 to 14. Readers will learn how certain substances rank on the pH scale, what happens when acids and bases are mixed, and how water can make a substance either acidic or basic. These significant science concepts are discussed in clear and approachable text and supported by motivating fact boxes, charts, and images and photographs.\"-- Provided by publisher.

Lactic acid at sufficiently acidic pH is a potent microbicide, and lactic acid produced by vaginal lactobacilli may help protect against reproductive tract infections. However, previous observations likely underestimated healthy vaginal acidity and total lactate concentration since they failed to exclude women without a lactobacillus-dominated vaginal microbiota, and also did not account for the high carbon dioxide, low oxygen environment of the vagina. Fifty-six women with low (0-3) Nugent scores (indicating a lactobacillus-dominated vaginal microbiota) and no symptoms of reproductive tract disease or infection, provided a total of 64 cervicovaginal fluid samples using a collection method that avoided the need for sample dilution and rigorously minimized aerobic exposure. The pH of samples was measured by microelectrode immediately after collection and under a physiological vaginal concentration of CO2. Commercial enzymatic assays of total lactate and total acetate concentrations were validated for use in CVF, and compared to the more usual HPLC method. The average pH of the CVF samples was 3.5 ± 0.3 (mean ± SD), range 2.8-4.2, and the average total lactate was 1.0% ± 0.2% w/v; this is a five-fold higher average hydrogen ion concentration (lower pH) and a fivefold higher total lactate concentration than in the prior literature. The microbicidal form of lactic acid (protonated lactic acid) was therefore eleven-fold more concentrated, and a markedly more potent microbicide, than indicated by prior research. This suggests that when lactobacilli dominate the vaginal microbiota, women have significantly more lactic acid-mediated protection against infections than currently believed. Our results invite further evaluations of the prophylactic and therapeutic actions of vaginal lactic acid, whether provided in situ by endogenous lactobacilli, by probiotic lactobacilli, or by products that reinforce vaginal lactic acid.

The number and quality of ocean pH measurements have increased substantially over the past few decades such that trends, variability, and spatial patterns of change are now being evaluated. However, comparing pH changes across domains with different initial pH values can be misleading because a pH change reflects a relative change in the hydrogen ion concentration ([H+], expressed in mol kg−1) rather than an absolute change in [H+]. We recommend that [H+] be used in addition to pH when describing such changes and provide three examples illustrating why.

Background Lactic acid (protonated lactate) has broad antimicrobial activity. Vaginal lactobacilli produce lactic acid, and are known to confer protection against reproductive tract infections when they are predominant in the vaginal microbiota. Using novel ex vivo methods, we showed that cervicovaginal fluid (CVF) from women with a predominantly lactobacilli-morphotype microbiota contains significantly more lactic acid than previously thought, sufficient to inactivate reproductive tract pathogens. Here, we measured vaginal pH in vivo in 20 women with a predominantly lactobacilli-morphotype (low Nugent score) microbiota. We also investigated the in vitro production of protons (as hydrogen ions) and lactate by vaginal lactobacilli. Results The average vaginal pH in these women was 3.80 ± 0.20, and the average lactate concentration was 0.79% ± 0.22% w / v , with pH and lactate concentration tightly correlated for each sample. In vitro, lactobacilli cultured from these CVF samples reached an average pH of 3.92 ± 0.22, but the average lactate concentration was only 0.14% ± 0.06% w / v , approximately five-fold less than in the corresponding CVF samples. When the pH of the cultures was raised, lactate and hydrogen ion production resumed, indicating that production of lactate and hydrogen ions by vaginal lactobacilli is limited primarily by their sensitivity to hydrogen ion concentration (low pH) not lactate concentration. Conclusions Some vaginal lactobacilli cultures have a lower limiting pH than others, and limiting pHs in vitro showed good correlation with pHs measured in vivo . The limiting pH of the lactobacilli predominant in a woman’s vaginal microbiota seems critical in determining the concentration of antimicrobial lactic acid protecting her.

The acidification of the ocean (OA) increases the frequency and intensity of ocean acidity extreme events (OAXs), but this increase is not occurring homogeneously in time and space. Here we use daily output from a hindcast simulation with a high-resolution regional ocean model coupled to a biogeochemical ecosystem model (ROMS-BEC) to investigate this heterogeneity in the progression of OAX in the upper 250 m of the northeastern Pacific from 1984 to 2019. OAXs are defined using a relative threshold approach and using a fixed baseline. Concretely, conditions are considered extreme when the hydrogen ion concentration ([H+]) exceeds the 99th percentile of its distribution in the baseline simulation where atmospheric CO2 was held at its 1979 level. Within the 36 years of our hindcast simulation, the increase in atmospheric CO2 causes a strong increase in OAX volume, duration, and intensity throughout the upper 250 m. The increases are most accentuated near the surface, with 88 % of the surface area experiencing near-permanent extreme conditions in 2019. At the same time, a larger fraction of the OAXs become undersaturated with respect to aragonite (ΩA < 1), with some regions experiencing increases up to nearly 50 % in their subsurface. There is substantial regional heterogeneity in the progression of OAX, with the fraction of OAX volume across the top 250 m increasing in the central northeastern Pacific up to 160 times, while the deeper layers of the nearshore regions experience “only” a 4-fold increase. Throughout the upper 50 m of the northeastern Pacific, OAXs increase relatively linearly with time, but sudden rapid increases in yearly extreme days are simulated to occur in the thermocline of the far offshore regions of the central northeastern Pacific. These differences largely emerge from the spatial heterogeneity in the local [H+] variability. The limited offshore reach of offshore-propagating mesoscale eddies, which are an important driver of subsurface OAX in the northeastern Pacific, causes a sharp transition in the increase in OAX between the rather variable thermocline waters of nearshore regions and the very invariant waters of the central northeastern Pacific. The spatially and temporal heterogeneous increases in OAX, including the abrupt appearance of near-permanent extremes, likely have negative effects on the ability of marine organisms to adapt to the progression of OA and its associated extremes.

Key Points The regulation of pH in tumours involves the interplay of several proteins, including: the carbonic anhydrases (EC 4.2.1.1) CA2, CA9 and CA12; the vacuolar ATPase (V-ATPase); anion exchangers AE1, AE2 and AE3; Na + /HCO 3 − co-transporters (NBCs); electroneutral Na + -driven Cl − /HCO 3 − exchanger (NDCBE); the monocarboxylate transporters MCT1, MCT2, MCT3 and MCT4; and Na + /H + exchanger 1, among others. The concerted action of these proteins maintains a slightly alkaline intracellular pH (pH i ) and an acidic extracellular pH (pH e ) within the tumours, which favours the growth and spread of the primary tumour, leading to the formation of metastases. The inhibition of one or more of these pH regulators with specific inhibitors causes both pH i and pH e values to return to normal, with the consequent impairment of tumour growth. This property represents an antitumour mechanism that is not exploited by the classical anticancer drugs. The inhibition of CA9 and/or CA12 with sulphonamide- or coumarin-based small-molecule inhibitors reverses the effects of tumour acidification, leading to inhibition of cancer cell growth in both primary tumours and metastases. Some of these compounds are in preclinical development. This effect can also be exploited for the imaging and treatment of tumours that overexpress CA9 or CA12. The same effect has been observed with antibodies targeting CA9 (and, more recently, also CA12). Some of these antibodies (for example, cG250) are in Phase III clinical development as antitumour and diagnostic agents. Some sulphonamides also inhibit anion exchangers, whereas proton pump inhibitors of the omeprazole type show antitumour effects by inhibiting V-ATPase, thus interfering with other tumour pH regulators. Potent, specific and non-toxic compounds as well as antibodies that interfere with these proteins may represent valuable new antitumour drugs. Changes in pH i towards basic values lead to the production of splice isoforms of extracellular matrix components at the tumour site, which are ideal targets for antibody-based pharmacodelivery strategies. The ability of tumour cells to maintain a slightly alkaline intracellular pH and an acidic extracellular pH aids the growth of primary tumours and the formation of metastases. Inhibiting pH-regulating proteins in tumours represents a novel therapeutic strategy that is not exploited by the classical anticancer drugs. The high metabolic rate of tumours often leads to acidosis and hypoxia in poorly perfused regions. Tumour cells have thus evolved the ability to function in a more acidic environment than normal cells. Key pH regulators in tumour cells include: isoforms 2, 9 and 12 of carbonic anhydrase, isoforms of anion exchangers, Na + /HCO 3 − co-transporters, Na + /H + exchangers, monocarboxylate transporters and the vacuolar ATPase. Both small molecules and antibodies targeting these pH regulators are currently at various stages of clinical development. These antitumour mechanisms are not exploited by the classical cancer drugs and therefore represent a new anticancer drug discovery strategy.

How ocean acidification will affect marine organisms depends on changes in both the long-term mean and the short-term temporal variability of carbonate chemistry1–8. Although the decadal-to-centennial response to atmospheric CO2 and climate change is constrained by observations and models1, 9, little is known about corresponding changes in seasonality10–12, particularly for pH. Here we assess the latter by analysing nine earth system models (ESMs) forced with a business-as-usual emissions scenario13. During the twenty-first century, the seasonal cycle of surface-ocean pH was attenuated by 16 ± 7%, on average, whereas that for hydrogen ion concentration [H+] was amplified by 81 ± 16%. Simultaneously, the seasonal amplitude of the aragonite saturation state (Ωarag) was attenuated except in the subtropics, where it was amplified. These contrasting changes derive from regionally varying sensitivities of these variables to atmospheric CO2 and climate change and to diverging trends in seasonal extremes in the primary controlling variables (temperature, dissolved inorganic carbon and alkalinity). Projected seasonality changes will tend to exacerbate the impacts of increasing [H+] on marine organisms during the summer and ameliorate the impacts during the winter, although the opposite holds in the high latitudes. Similarly, over most of the ocean, impacts from declining Ωarag are likely to be intensified during the summer and dampened during the winter.

In a porcine cystic fibrosis model, lack of cystic fibrosis transmembrane conductance regulator (CFTR) is shown to result in acidification of airway surface liquid (ASL), and this decrease in pH reduces the ability of ASL to kill bacteria; the findings directly link loss of the CFTR anion channel to impaired defence against bacterial infection. Lung susceptibility to bacterial infection in cystic fibrosis The discovery of a link between cystic fibrosis and mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene has stimulated two decades of extensive research. As a result, the genetic, functional and cellular aspects of CFTR are well known. But despite these advances, it has proved impossible to relate the pathogenesis of bacterial lung infection, the major cause of morbidity and mortality in the disease, to the basic physiological abnormality — the loss of CFTR anion channels. The experiments reported here show that without CFTR, when airway epithelial HCO 3 secretion is defective, the pH of the airway surface liquid falls and inhibits antimicrobial function. This impairs the killing of bacteria that enter the lungs. Reducing the pH of the airway surface layer diminished bactericidal activity in wild-type pigs, whereas increasing the pH restored antimicrobial activity in pigs lacking CFTR . These findings link CFTR mutations to defective bacterial eradication, and suggest that increasing the pH of the airway surface liquid might prevent the initial infection in patients with cystic fibrosis. Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene 1 . Although bacterial lung infection and the resulting inflammation cause most of the morbidity and mortality, how the loss of CFTR function first disrupts airway host defence has remained uncertain 2 , 3 , 4 , 5 , 6 . To investigate the abnormalities that impair elimination when a bacterium lands on the pristine surface of a newborn CF airway, we interrogated the viability of individual bacteria immobilized on solid grids and placed onto the airway surface. As a model, we studied CF pigs, which spontaneously develop hallmark features of CF lung disease 7 , 8 . At birth, their lungs lack infection and inflammation, but have a reduced ability to eradicate bacteria 8 . Here we show that in newborn wild-type pigs, the thin layer of airway surface liquid (ASL) rapidly kills bacteria in vivo , when removed from the lung and in primary epithelial cultures. Lack of CFTR reduces bacterial killing. We found that the ASL pH was more acidic in CF pigs, and reducing pH inhibited the antimicrobial activity of ASL. Reducing ASL pH diminished bacterial killing in wild-type pigs, and, conversely, increasing ASL pH rescued killing in CF pigs. These results directly link the initial host defence defect to the loss of CFTR, an anion channel that facilitates HCO 3 − transport 9 , 10 , 11 , 12 , 13 . Without CFTR, airway epithelial HCO 3 − secretion is defective, the ASL pH falls and inhibits antimicrobial function, and thereby impairs the killing of bacteria that enter the newborn lung. These findings suggest that increasing ASL pH might prevent the initial infection in patients with CF, and that assaying bacterial killing could report on the benefit of therapeutic interventions.

The fate of hematopoietic stem cells (HSCs) can be directed by microenvironmental factors including extracellular calcium ion concentration ([Ca 2+ ] e ), but the local [Ca 2+ ] e around individual HSCs in vivo remains unknown. Here we develop intravital ratiometric analyses to quantify the absolute pH and [Ca 2+ ] e in the mouse calvarial bone marrow, taking into account the pH sensitivity of the calcium probe and the wavelength-dependent optical loss through bone. Unexpectedly, the mean [Ca 2+ ] e in the bone marrow (1.0 ± 0.54 mM) is not significantly different from the blood serum, but the HSCs are found in locations with elevated local [Ca 2+ ] e (1.5 ± 0.57 mM). With aging, a significant increase in [Ca 2+ ] e is found in M-type cavities that exclusively support clonal expansion of activated HSCs. This work thus establishes a tool to investigate [Ca 2+ ] e and pH in the HSC niche with high spatial resolution and can be broadly applied to other tissue types. The fate of hematopoietic stem cells can be controlled by factors such as calcium ion concentration. Here the authors report an intravital ratiometric analysis method to measure extracellular calcium ion concentrations and absolute pH in mouse bone marrow.

Adsorption capacity and percentage removal efficiency of Cu(II) and Ni(II) ions were studied and compared between raw kaolinite and acid-activated kaolinite. Acid-activated kaolin was prepared by refluxing raw kaolinite with concentrated sulphuric acid followed by calcination to enhance its surface properties and adsorption ability. Both raw and acid-activated kaolinite samples were characterized by Fourier transform infrared spectroscopy, energy dispersive X-ray, scanning electron micrograph and zeta potential analysis. Upon acid treatment, acid-activated kaolinite was discovered to have altered chemical composition and larger BET surface area as compared with raw kaolinite. The batch adsorption studies on aqueous solution were performed under different factors such as contact time, pH condition, adsorbent dosage, initial metal ion concentration and temperature. The optimum condition was selected for each factor including a contact time of 60 min, pH of 7.0, adsorbent dosage of 0.1 g, initial metal ion concentration of 100 mg/L and temperature of 25 °C. Then, the adsorption studies on wastewater samples were carried out at the selected optimum conditions. Acid-activated kaolinite always had better adsorption capacity and percentage removal efficiency than raw kaolinite due to the increasing amount of negative charges on the adsorbent surface and the number of metal ion binding sites upon acid treatment. The adsorption kinetic obtained was well described by the pseudo-second-order model, whereas the adsorption isotherms obtained were well described by either the Freundlich or the Langmuir adsorption model. The results showed that acid-activated kaolinite adsorbent is a better option as a favourable and feasible commercial low-cost adsorbent for wastewater treatment.