Optical Fibre Sensor For Measuring pH In Physiological Range

NASA Astrophysics Data System (ADS)

Golunski, Witold; Hypszer, Ryszard; Plucinski, Jerzy

1990-01-01

The principle of fibre optic pH sensor operation is given in this paper. PH measurement in 7.0-7.5 range is based on changing of optical property of a indicator. The indicator is sensitive to the hydrogen ion concentration in the water solution. Microspheres of the polymer XAD-2 (a styrene-divinylbenzene copolymer) containing bound phenol red were used as a indicator. Such prepared indicator was inserted in optrode. The optrode was connected with transmitter and receiver by a bundle of glass fibres (multicomponent glass). Transmitter was done by using green LED while receiver construction was based on pin photodiode.

Detecting activity-evoked pH changes in human brain

PubMed Central

Magnotta, Vincent A.; Heo, Hye-Young; Dlouhy, Brian J.; Dahdaleh, Nader S.; Follmer, Robin L.; Thedens, Daniel R.; Welsh, Michael J.; Wemmie, John A.

2012-01-01

Localized pH changes have been suggested to occur in the brain during normal function. However, the existence of such pH changes has also been questioned. Lack of methods for noninvasively measuring pH with high spatial and temporal resolution has limited insight into this issue. Here we report that a magnetic resonance imaging (MRI) strategy, T1 relaxation in the rotating frame (T1ρ), is sufficiently sensitive to detect widespread pH changes in the mouse and human brain evoked by systemically manipulating carbon dioxide or bicarbonate. Moreover, T1ρ detected a localized acidosis in the human visual cortex induced by a flashing checkerboard. Lactate measurements and pH-sensitive 31P spectroscopy at the same site also identified a localized acidosis. Consistent with the established role for pH in blood flow recruitment, T1ρ correlated with blood oxygenation level-dependent contrast commonly used in functional MRI. However, T1ρ was not directly sensitive to blood oxygen content. These observations indicate that localized pH fluctuations occur in the human brain during normal function. Furthermore, they suggest a unique functional imaging strategy based on pH that is independent of traditional functional MRI contrast mechanisms. PMID:22566645

Environmental and Hydroclimatic Sensitivities of Greenhouse Gas (GHG) Fluxes from Coastal Wetlands

NASA Astrophysics Data System (ADS)

Abdul-Aziz, O. I.; Ishtiaq, K. S.

2016-12-01

We computed the reference environmental and hydroclimatic sensitivities of the greenhouse gas (GHG) fluxes (CO2 and CH4) from coastal salt marshes. Non-linear partial least squares regression models of CO2 (net uptake) and CH4 (net emissions) fluxes were developed with a bootstrap resampling approach using the photosynthetically active radiation (PAR), air and soil temperatures, water height, soil moisture, porewater salinity, and pH as predictors. Analytical sensitivity coefficients of different predictors were then analytically derived from the estimated models. The numerical sensitivities of the dominant drivers were determined by perturbing the variables individually and simultaneously to compute their individual and combined (respectively) effects on the GHG fluxes. Four tidal wetlands of Waquoit Bay, MA — incorporating a gradient in land-use, salinity and hydrology — were considered as the case study sites. The wetlands were dominated by native Spartina Alterniflora, and characterized by high salinity and frequent flooding. Results indicated a high sensitivity of CO2 fluxes to temperature and PAR, a moderate sensitivity to soil salinity and water height, and a weak sensitivity to pH and soil moisture. In contrast, the CH4 fluxes were more sensitive to temperature and salinity, compared to that of PAR, pH, and hydrologic variables. The estimated sensitivities and mechanistic insights can aid the management of coastal carbon under a changing climate and environment. The sensitivity coefficients also indicated the most dominant drivers of GHG fluxes for the development of a parsimonious predictive model.

Ionic pH and glucose sensors fabricated using hydrothermal ZnO nanostructures

NASA Astrophysics Data System (ADS)

Wang, Jyh-Liang; Yang, Po-Yu; Hsieh, Tsang-Yen; Juan, Pi-Chun

2016-01-01

Hydrothermally synthesized aluminum-doped ZnO (AZO) nanostructures have been adopted in extended-gate field-effect transistor (EGFET) sensors to demonstrate the sensitive and stable pH and glucose sensing characteristics of AZO-nanostructured EGFET sensors. The AZO-nanostructured EGFET sensors exhibited the following superior pH sensing characteristics: a high current sensitivity of 0.96 µA1/2/pH, a high linearity of 0.9999, less distortion of output waveforms, a small hysteresis width of 4.83 mV, good long-term repeatability, and a wide sensing range from pHs 1 to 13. The glucose sensing characteristics of AZO-nanostructured biosensors exhibited the desired sensitivity of 60.5 µA·cm-2·mM-1 and a linearity of 0.9996 up to 13.9 mM. The attractive characteristics of high sensitivity, high linearity, and repeatability of using ionic AZO-nanostructured EGFET sensors indicate their potential use as electrochemical and disposable biosensors.

Functional photoacoustic microscopy of pH

NASA Astrophysics Data System (ADS)

Chatni, M. Rameez; Yao, Junjie; Danielli, Amos; Favazza, Christopher P.; Maslov, Konstantin I.; Wang, Lihong V.

2012-02-01

pH is a tightly regulated indicator of metabolic activity. In mammalian systems, imbalance of pH regulation may result from or result in serious illness. Even though the regulation system of pH is very robust, tissue pH can be altered in many diseases such as cancer, osteoporosis and diabetes mellitus. Traditional high-resolution optical imaging techniques, such as confocal microscopy, routinely image pH in cells and tissues using pH sensitive fluorescent dyes, which change their fluorescence properties with the surrounding pH. Since strong optical scattering in biological tissue blurs images at greater depths, high-resolution pH imaging is limited to penetration depths of 1mm. Here, we report photoacoustic microscopy (PAM) of commercially available pH-sensitive fluorescent dye in tissue phantoms. Using both opticalresolution photoacoustic microscopy (OR-PAM), and acoustic resolution photoacoustic microscopy (AR-PAM), we explored the possibility of recovering the pH values in tissue phantoms. In this paper, we demonstrate that PAM was capable of recovering pH values up to a depth of 2 mm, greater than possible with other forms of optical microscopy.

Sweet-sensitive protein from bovine taste buds: isolation and assay.

PubMed

Dastoli, F R; Price, S

1966-11-18

Using refractometry and ultraviolet-difference spectroscopy to indicate interaction between proteins and coinpounds of low molecular weight, we found a protein fraction in bovine tongue extracts that coinplexes sugars and saccharin. The strengths of the coinzplexes parallel the degrees of sweetness of the compounds, and the effects of pH upon formation of complexes parallel the effects of pH upon sensitivity of taste buds to sweet compounds in vivo.

Monitoring the Productivity of Coastal Systems Using PH ...

EPA Pesticide Factsheets

The impact of nutrient inputs to the eutrophication of coastal ecosystems has been one of the great themes of coastal ecology. There have been countless studies devoted to quantifying how human sources of nutrients, in particular nitrogen (N), effect coastal water bodies. These studies, which often measure in situ concentrations of nutrients, chlorophyll, and dissolved oxygen, are often spatially and/or temporally intensive and expensive. We provide evidence from experimental mesocosms, coupled with data from the water column of a well-mixed estuary, that pH can be a quick, inexpensive, and integrative measure of net ecosystem metabolism. In some cases, this approach is a more sensitive tracer of production than direct measurements of chlorophyll and carbon-14. Taken together, our data suggest that pH is a sensitive, but often overlooked, tool for monitoring estuarine production. This presentation will explore the potential utility of pH as an indicator of ecosystem productivity. Our data suggest that pH is a sensitive and potentially integrator of net ecosystem production. It should not be overlooked, that measuring pH is quick, easy, and inexpensive, further increasing its value as an analytical tool.

New fluorescent pH sensors based on covalently linkable PET rhodamines

PubMed Central

Aigner, Daniel; Borisov, Sergey M.; Orriach Fernández, Francisco J.; Fernández Sánchez, Jorge F.; Saf, Robert; Klimant, Ingo

2012-01-01

A new class of rhodamines for the application as indicator dyes in fluorescent pH sensors is presented. Their pH-sensitivity derives from photoinduced electron transfer between non-protonated amino groups and the excited chromophore which results in effective fluorescence quenching at increasing pH. The new indicator class carries a pentafluorophenyl group at the 9-position of the xanthene core where other rhodamines bear 2-carboxyphenyl substituents instead. The pentafluorophenyl group is used for covalent coupling to sensor matrices by “click” reaction with mercapto groups. Photophysical properties are similar to “classical” rhodamines carrying 2′-carboxy groups. pH sensors have been prepared with two different matrix materials, silica gel and poly(2-hydroxyethylmethacrylate). Both sensors show high luminescence brightness (absolute fluorescence quantum yield ΦF≈0.6) and high pH-sensitivity at pH 5–7 which makes them suitable for monitoring biotechnological samples. To underline practical applicability, a dually lifetime referenced sensor containing Cr(III)-doped Al2O3 as reference material is presented. PMID:22967541

A rapid, efficient and sensitive plate assay for detection and screening of l-asparaginase-producing microorganisms.

PubMed

Mahajan, Richi V; Saran, Saurabh; Saxena, Rajendra K; Srivastava, Ayush K

2013-04-01

l-Asparaginase-producing microbes are conventionally screened on phenol red l-asparagine-containing plates. However, sometimes the contrast of the zone obtained (between yellow and pink) is not very sharp and distinct. In the present investigation, an improved method for screening of the microorganisms producing extracellular l-asparaginase is reported wherein bromothymol blue (BTB) is incorporated as pH indicator in l-asparagine-containing medium instead of phenol red. Plates containing BTB at acidic pH are yellow and turn dark blue at alkaline pH. Thus, a dense dark blue zone is formed around microbial colonies producing l-asparaginase, differentiating between enzyme producers and non-producers. The present method is more sensitive and accurate than the conventional method for screening of both fungi and bacteria producing extracellular l-asparaginase. Furthermore, BTB gives a transient green colour at neutral pH (7.0) and dark blue colour at higher pH 8.0-9.0, indicating the potency of the microorganism for l-asparaginase production. © 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

External hyphae of Rhizophagus irregularis DAOM 197198 are less sensitive to low pH than roots in arbuscular mycorrhizae: evidence from axenic culture system.

PubMed

Wang, Ning; Feng, Zengwei; Zhou, Yang; Zhu, Honghui; Yao, Qing

2017-10-01

The growth of plant roots and arbuscular mycorrhizal fungi (AMF) can be inhibited by low pH; however, it is largely unknown which is more sensitive to low pH. This study aimed to compare the physiological and molecular responses of external hyphae (EH) and roots to low pH in terms of growth, development and functioning. We established AM symbiosis in a two-compartmented system (root compartment, RC; hyphal compartment, HC) using AMF and transformed hairy roots and exposed them to pH 6.5 and/or pH 4.5. The results showed that pH 4.5 significantly decreased root cell viability, while EH at pH 6.5 attenuated the effect. In either RC or HC, pH 4.5 reduced biomass, P content, colonization, ALP activity in roots, and ALP activity and polyphosphate accumulation in EH. GintPT expression in EH was inhibited by pH 4.5 in HC but not in RC. The expression of mycorrhiza-responsive LePTs was significantly reduced by the lower colonization due to decreased pH in either RC or HC, while the expression of non-mycorrhiza-responsive LePTs was not affected. Variation partitioning analysis indicated that EH was less sensitive to low pH than roots. The interactions between roots and EH under low pH stress merit further investigation. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor

PubMed Central

Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K.; Shi, Yingtang; Wagner, Paul G.; Pivaroff-Ward, Kendra; Sassic, Jessica K.; Bayliss, Douglas A.

2013-01-01

The Ether-a-go-go (EAG) superfamily of voltage-gated K+ channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K+ currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K+ channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance–voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn2+. Low pH similarly reduces Mg2+ sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca2+. Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K+ currents observed in vivo. PMID:23712551

External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor.

PubMed

Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K; Shi, Yingtang; Wagner, Paul G; Pivaroff-Ward, Kendra; Sassic, Jessica K; Bayliss, Douglas A; Jegla, Timothy

2013-06-01

The Ether-a-go-go (EAG) superfamily of voltage-gated K(+) channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K(+) currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K(+) channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance-voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn(2+). Low pH similarly reduces Mg(2+) sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca(2+). Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K(+) currents observed in vivo.

Temperature influences neuronal activity and CO2/pH sensitivity of locus coeruleus neurons in the bullfrog, Lithobates catesbeianus.

PubMed

Santin, Joseph M; Watters, Kayla C; Putnam, Robert W; Hartzler, Lynn K

2013-12-15

The locus coeruleus (LC) is a chemoreceptive brain stem region in anuran amphibians and contains neurons sensitive to physiological changes in CO2/pH. The ventilatory and central sensitivity to CO2/pH is proportional to the temperature in amphibians, i.e., sensitivity increases with increasing temperature. We hypothesized that LC neurons from bullfrogs, Lithobates catesbeianus, would increase CO2/pH sensitivity with increasing temperature and decrease CO2/pH sensitivity with decreasing temperature. Further, we hypothesized that cooling would decrease, while warming would increase, normocapnic firing rates of LC neurons. To test these hypotheses, we used whole cell patch-clamp electrophysiology to measure firing rate, membrane potential (V(m)), and input resistance (R(in)) in LC neurons in brain stem slices from adult bullfrogs over a physiological range of temperatures during normocapnia and hypercapnia. We found that cooling reduced chemosensitive responses of LC neurons as temperature decreased until elimination of CO2/pH sensitivity at 10°C. Chemosensitive responses increased at elevated temperatures. Surprisingly, chemosensitive LC neurons increased normocapnic firing rate and underwent membrane depolarization when cooled and decreased normocapnic firing rate and underwent membrane hyperpolarization when warmed. These responses to temperature were not observed in nonchemosensitive LC neurons or neurons in a brain stem slice 500 μm rostral to the LC. Our results indicate that modulation of cellular chemosensitivity within the LC during temperature changes may influence temperature-dependent respiratory drive during acid-base disturbances in amphibians. Additionally, cold-activated/warm-inhibited LC neurons introduce paradoxical temperature sensitivity in respiratory control neurons of amphibians.

Fluorescent materials for pH sensing and imaging based on novel 1,4-diketopyrrolo-[3,4-c]pyrrole dyes†Electronic supplementary information (ESI) available: NMR and MS spectra, further sensor characteristics and sensor long-time performance. See DOI: 10.1039/c3tc31130aClick here for additional data file.

PubMed

Aigner, Daniel; Ungerböck, Birgit; Mayr, Torsten; Saf, Robert; Klimant, Ingo; Borisov, Sergey M

2013-09-28

New optical pH-sensors relying on 1,4-diketopyrrolo-[3,4- c ]pyrroles (DPPs) as fluorescent pH-indicators are presented. Different polymer hydrogels are useful as immobilization matrices, achieving excellent sensitivity and good brightness in the resulting sensor. The operational pH can be tuned over a wide range (pH 5-12) by selecting the fine structure of the indicator and the matrix. A ratiometric sensor in the form of nanoparticles is also presented. It is suitable for RGB camera readout, and its practical applicability for fluorescence imaging in microfluidic systems is demonstrated. The indicators are synthesized starting from the commercially available DPP pigments by a straightforward concept employing chlorosulfonation and subsequent reaction with amines. Their sensitivity derives from two distinct mechanisms. At high pH (>9), they exhibit a remarkable alteration of both absorption and fluorescence spectra due to deprotonation of the lactam nitrogen atoms. If a phenolic group is introduced, highly effective fluorescence quenching at near-neutral pH occurs due to photoinduced electron transfer (PET) involving the phenolate form.

The gene ICS3 from the yeast Saccharomyces cerevisiae is involved in copper homeostasis dependent on extracellular pH.

PubMed

Alesso, C A; Discola, K F; Monteiro, G

2015-09-01

In the yeast Saccharomyces cerevisiae, many genes are involved in the uptake, transport, storage and detoxification of copper. Large scale studies have noted that deletion of the gene ICS3 increases sensitivity to copper, Sortin 2 and acid exposure. Here, we report a study on the Δics3 strain, in which ICS3 is related to copper homeostasis, affecting the intracellular accumulation of this metal. This strain is sensitive to hydrogen peroxide and copper exposure, but not to other tested transition metals. At pH 6.0, the Δics3 strain accumulates a larger amount of intracellular copper than the wild-type strain, explaining the sensitivity to oxidants in this condition. Unexpectedly, sensitivity to copper exposure only occurs in acidic conditions. This can be explained by the fact that the exposure of Δics3 cells to high copper concentrations at pH 4.0 results in over-accumulation of copper and iron. Moreover, the expression of ICS3 increases in acidic pH, and this is correlated with CCC2 gene expression, since both genes are regulated by Rim101 from the pH regulon. CCC2 is also upregulated in Δics3 in acidic pH. Together, these data indicate that ICS3 is involved in copper homeostasis and is dependent on extracellular pH. Copyright © 2015 Elsevier Inc. All rights reserved.

The pH sensibility of actin-bundling LIM proteins is governed by the acidic properties of their C-terminal domain.

PubMed

Moes, Danièle; Hoffmann, Céline; Dieterle, Monika; Moreau, Flora; Neumann, Katrin; Papuga, Jessica; Furtado, Angela Tavares; Steinmetz, André; Thomas, Clément

2015-08-19

Actin-bundling Arabidopsis LIM proteins are subdivided into two subfamilies differing in their pH sensitivity. Widely-expressed WLIMs are active under low and high physiologically-relevant pH conditions, whereas pollen-enriched PLIMs are inactivated by pH values above 6.8. By a domain swapping approach we identified the C-terminal (Ct) domain of PLIMs as the domain responsible for pH responsiveness. Remarkably, this domain conferred pH sensitivity to LIM proteins, when provided "in trans" (i.e., as a single, independent, peptide), indicating that it operates through the interaction with another domain. An acidic 6xc-Myc peptide functionally mimicked the Ct domain of PLIMs and efficiently inhibited LIM actin bundling activity under high pH conditions. Together, our data suggest a model where PLIMs are regulated by an intermolecular interaction between their acidic Ct domain and another, yet unidentified, domain. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Norcyanine dyes with benzo[c,d]indolium moiety: Spectral sensitivity with pH change for fluorescence pH imaging in living cells.

PubMed

Guan, Li; Liu, Qi; Zhang, Borui; Wang, Lanying

2017-01-01

Fluorescence pH imaging in living cells is a rapidly expanding research direction, however, it relies on the development of pH-sensitive fluorescent imaging agents. Here four norcyanine dyes with benzo[c,d]indolium moiety, exhibiting high spectral sensitivity with pH changes, were synthesized for fluorescence pH imaging in living cells, and characterized by 1 H NMR, 13 C NMR, IR, UV-Vis and HRMS. The investigation of their spectral properties in methanol and water showed that the absorption and emission maxima were in the region 488-618nm and 583-651nm, respectively, and four dyes exhibited high photostability. The pH spectral titrations showed that selective dye D1 had pH-dependent absorption spectral changes within the pH range of 2.4 to 9.4, and high fluorescent spectral sensitivity at pH5.0-8.0, with a pK a of 5.0. A cell association study indicated that dye D1 exhibited no or mild cytotoxicity at the application dose and duration, and could be accumulated in cells and mainly distributed in the cytoplasm, giving red fluorescence imaging. In particular, dye D1 could achieve pH-dependent fluorescence imaging in living cells with the increase of pH from 3.0 to 8.0, at excitation wavelength of 543nm and receiving wavelength of 655-755nm, which was valuable for studying the weak acidic, neutral and weak alkaline biological tissue compartments. Copyright © 2016 Elsevier B.V. All rights reserved.

New fluorescent perylene bisimide indicators--a platform for broadband pH optodes.

PubMed

Aigner, Daniel; Borisov, Sergey M; Klimant, Ingo

2011-06-01

Asymmetric perylene bisimide (PBI) dyes are prepared and are shown to be suitable for the preparation of fluorescence chemosensors for pH. They carry one amino-functional substituent which introduces pH sensitivity via photoinduced electron transfer (PET) while the other one increases solubility. The luminescence quantum yields for the new indicators exceed 75% in the protonated form. The new indicators are non-covalently entrapped in polyurethane hydrogel D4 and poly(hydroxyalkylmethacrylates). Several PET functions including aliphatic and aromatic amino groups were successfully used to tune the dynamic range of the sensor. Because of their virtually identical spectral properties, various PBIs with selected PET functions can easily be integrated into a single sensor with enlarged dynamic range (over 4 pH units). PBIs with two different substitution patterns in the bay position are investigated and possess variable spectral properties. Compared with their tetrachloro analogues, tetra-tert-butyl-substituted PBIs yield more long-wave excitable sensors which feature excellent photostability. Cross-sensitivity to ionic strength was found to be negligible. The practical applicability of the sensors may be compromised by the long response times (especially in case of tetra-tert-butyl-substituted PBIs).

pH Meter probe assembly

DOEpatents

Hale, C.J.

1983-11-15

An assembly for mounting a pH probe in a flowing solution, such as a sanitary sewer line, which prevents the sensitive glass portion of the probe from becoming coated with grease, oil, and other contaminants, whereby the probe gives reliable pH indication over an extended period of time. The pH probe assembly utilizes a special filter media and a timed back-rinse feature for flushing clear surface contaminants of the filter. The flushing liquid is of a known pH and is utilized to check performance of the probe. 1 fig.

pH Meter probe assembly

DOEpatents

Hale, Charles J.

1983-01-01

An assembly for mounting a pH probe in a flowing solution, such as a sanitary sewer line, which prevents the sensitive glass portion of the probe from becoming coated with grease, oil, and other contaminants, whereby the probe gives reliable pH indication over an extended period of time. The pH probe assembly utilizes a special filter media and a timed back-rinse feature for flushing clear surface contaminants of the filter. The flushing liquid is of a known pH and is utilized to check performance of the probe.

High Sensitive pH Sensor Based on AlInN/GaN Heterostructure Transistor.

PubMed

Dong, Yan; Son, Dong-Hyeok; Dai, Quan; Lee, Jun-Hyeok; Won, Chul-Ho; Kim, Jeong-Gil; Chen, Dunjun; Lee, Jung-Hee; Lu, Hai; Zhang, Rong; Zheng, Youdou

2018-04-24

The AlInN/GaN high-electron-mobility-transistor (HEMT) indicates better performances compared with the traditional AlGaN/GaN HEMTs. The present work investigated the pH sensor functionality of an analogous HEMT AlInN/GaN device with an open gate. It was shown that the Al 0.83 In 0.17 N/GaN device demonstrates excellent pH sense functionality in aqueous solutions, exhibiting higher sensitivity (−30.83 μA/pH for AlInN/GaN and −4.6 μA/pH for AlGaN/GaN) and a faster response time, lower degradation and good stability with respect to the AlGaN/GaN device, which is attributed to higher two-dimensional electron gas (2DEG) density and a thinner barrier layer in Al 0.83 In 0.17 N/GaN owning to lattice matching. On the other hand, the open gate geometry was found to affect the pH sensitivity obviously. Properly increasing the width and shortening the length of the open gate area could enhance the sensitivity. However, when the open gate width is too larger or too small, the pH sensitivity would be suppressed conversely. Designing an optimal ratio of the width to the length is important for achieving high sensitivity. This work suggests that the AlInN/GaN-based 2DEG carrier modulated devices would be good candidates for high-performance pH sensors and other related applications.

Analytical advantages of copolymeric microspheres for fluorimetric sensing - tuneable sensitivity sensors and titration agents.

PubMed

Stelmach, Emilia; Maksymiuk, Krzysztof; Michalska, Agata

2017-01-15

Analytical benefits related to application of copolymeric microspheres containing different number of carboxylic acid mers have been studied on example of acrylate copolymers. These structures can be used as a reagent in heterogeneous pH titration, benefiting from different number of reactive groups - i.e. different concentration of a titrant - within the series of copolymers. Thus introducing the same amount of different microspheres from a series to the sample, different amount of the titrant is introduced. Copolymeric microspheres also can be used as optical sensors - in this respect the increasing number of reactive groups in the series is useful to improve the analytical performance of microprobes - sensitivity of determination or/and response range. The increase in ion-permeability of the spheres with increasing number of reactive mers is advantageous. It is shown that for pH sensitive microspheres containing higher number of carboxyl groups the higher sensitivity for alkaline pH samples is observed for an indicator present in the beads. The significant increase of optical responses is related to enhanced ion transport within the microspheres. For zinc or potassium ions model sensors tested it was shown that by choice of pH conditions and type of microspheres from the series, the optical responses can be tuned - to enhance sensitivity for analyte concentration change as well as to change the response pattern from sigmoidal (higher sensitivity, narrow range) to linear (broader response range). For classical optode systems (e.g. microspheres containing an optical transducer - pH sensitive dye and optically silent ionophore - receptor) copolymeric microspheres containing carboxylic acid mers in their structure allow application of the sensor in alkaline pH range, which is usually inaccessible for applied optical transducer. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional photoacoustic microscopy of pH.

PubMed

Chatni, Muhammad Rameez; Yao, Junjie; Danielli, Amos; Favazza, Christopher P; Maslov, Konstantin I; Wang, Lihong V

2011-10-01

pH is a tightly regulated indicator of metabolic activity. In mammalian systems, an imbalance of pH regulation may result from or result in serious illness. In this paper, we report photoacoustic microscopy (PAM) of a commercially available pH-sensitive fluorescent dye (SNARF-5F carboxylic acid) in tissue phantoms. We demonstrated that PAM is capable of pH imaging in absolute values at tissue depths of up to 2.0 mm, greater than possible with other forms of optical microscopy.

Structural and functional analysis of the putative pH sensor in the Kir1.1 (ROMK) potassium channel.

PubMed

Rapedius, Markus; Haider, Shozeb; Browne, Katharine F; Shang, Lijun; Sansom, Mark S P; Baukrowitz, Thomas; Tucker, Stephen J

2006-06-01

The pH-sensitive renal potassium channel Kir1.1 is important for K+ homeostasis. Disruption of the pH-sensing mechanism causes type II Bartter syndrome. The pH sensor is thought to be an anomalously titrated lysine residue (K80) that interacts with two arginine residues as part of an 'RKR triad'. We show that a Kir1.1 orthologue from Fugu rubripes lacks this lysine and yet is still highly pH sensitive, indicating that K80 is not the H+ sensor. Instead, K80 functionally interacts with A177 on transmembrane domain 2 at the 'helix-bundle crossing' and controls the ability of pH-dependent conformational changes to induce pore closure. Although not required for pH inhibition, K80 is indispensable for the coupling of pH gating to the extracellular K+ concentration, explaining its conservation in most Kir1.1 orthologues. Furthermore, we demonstrate that instead of interacting with K80, the RKR arginine residues form highly conserved inter- and intra-subunit interactions that are important for Kir channel gating and influence pH sensitivity indirectly.

Biological pH sensing based on the environmentally friendly Raman technique through a polyaniline probe.

PubMed

Li, Songyang; Liu, Zhiming; Su, Chengkang; Chen, Haolin; Fei, Xixi; Guo, Zhouyi

2017-02-01

The biological pH plays an important role in various cellular processes. In this work, a novel strategy is reported for biological pH sensing by using Raman spectroscopy and polyaniline nanoparticles (PANI NPs) as the pH-sensitive Raman probe. It is found that the Raman spectrum of PANI NPs is strongly dependent on the pH value. The intensities of Raman spectral bands at 1225 and 1454 cm -1 increase obviously with pH value varying from 5.5 to 8.0, which covers the range of regular biological pH variation. The pH-dependent Raman performance of PANI NPs, as well as their robust Raman signals and sensitivities to pH, was well retained after the nanoparticles incorporated into living 4T1 breast adenocarcinoma cells. The data indicate that such PANI NPs can be used as an effective biological pH sensor. Most interestingly, the PANI spherical nanostructures can be acquired by a low-cost, metal-free, and one-pot oxidative polymerization, which gives them excellent biocompatibility for further biological applications.

Release of beryllium from mineral ores in artificial lung and skin surface fluids.

PubMed

Duling, Matthew G; Stefaniak, Aleksandr B; Lawrence, Robert B; Chipera, Steve J; Virji, M Abbas

2012-06-01

Exposure to some manufactured beryllium compounds via skin contact or inhalation can cause sensitization. A portion of sensitized persons who inhale beryllium may develop chronic beryllium disease (CBD). Little is understood about exposures to naturally occurring beryllium minerals. The purpose of this study was to assess the bioaccessibility of beryllium from bertrandite ore. Dissolution of bertrandite from two mine pits (Monitor and Blue Chalk) was evaluated for both the dermal and inhalation exposure pathways by determining bioaccessibility in artificial sweat (pH 5.3 and pH 6.5), airway lining fluid (SUF, pH 7.3), and alveolar macrophage phagolysosomal fluid (PSF, pH 4.5). Significantly more beryllium was released from Monitor pit ore than Blue Chalk pit ore in artificial sweat buffered to pH 5.3 (0.88 ± 0.01% vs. 0.36 ± 0.00%) and pH 6.5 (0.09 ± 0.00% vs. 0.03 ± 0.01%). Rates of beryllium released from the ores in artificial sweat were faster than previously measured for manufactured forms of beryllium (e.g., beryllium oxide), known to induce sensitization in mice. In SUF, levels of beryllium were below the analytical limit of detection. In PSF, beryllium dissolution was biphasic (initial rapid diffusion followed by latter slower surface reactions). During the latter phase, dissolution half-times were 1,400 to 2,000 days, and rate constants were ~7 × 10(-10) g/(cm(2)·day), indicating that bertrandite is persistent in the lung. These data indicate that it is prudent to control skin and inhalation exposures to bertrandite dusts.

pH-responsive nanoparticle assembly from peptide amphiphiles for tumor targeting drug delivery.

PubMed

Chang, Cong; Liang, Peiqing; Chen, Linlin; Liu, Junfeng; Chen, Shihong; Zheng, Guohua; Quan, Changyun

2017-09-01

In this paper, the peptide amphiphiles (PA) which consists of RGDSEEEEEEEEEEK as pH-sensitive segment and stearic acid as hydrophobic segment named RGDS-E 10 -Lys(C 18 ) was successfully synthesized. TEM images showed that uniformly dispersed nanoparticles could be formed by PA molecules in pH 7.4 medium, however, disintegrated in pH 5.0 medium. Circular dichroism (CD) spectrum indicated that polypeptide adopted a random-coil conformation in neutral medium (pH 7.4). The CD signal was significantly attenuate for decreased solubility of PA in medium with pH 5.0. As expected, the prepared RGDS-E 10 -Lys(C 18 ) assembly showed high pH-sensitive property which demonstrated a much more rapid drug release from micelles in tumor tissue (acidic environment) than in physiological environment (neutral environment). After DOX-loaded micelles incubated with tumor cells, the cytotoxicity of the micelles against Hela cells was increased obviously, indicating the great potential of micelles developed here as promising vehicle for targeted pH-responsive drug delivery.

A quantum dot-spore nanocomposite pH sensor.

PubMed

Zhang, Xingya; Li, Zheng; Zhou, Tao; Zhou, Qian; Zeng, Zhiming; Xu, Xiangdong; Hu, Yonggang

2016-04-01

A new quantum dot (QD)-based pH sensor design is investigated. The sensor is synthesized based on the self-assembly of green QDs onto treated spores to form QD@spore nanocomposites. The nanocomposites are characterized using laser scanning confocal microscopy, transmission electron microscope, and fluorescence spectroscopy, among others. Fluorescence measurements showed that these nanocomposites are sensitive to pH in a broad pH range of 5.0-10.0. The developed pH sensors have been satisfactorily applied for pH estimation of real samples and are comparable with those of the commercial assay method, indicating the potential practical application of the pH sensors. Copyright © 2015 Elsevier B.V. All rights reserved.

Nanocontainer-based corrosion sensing coating.

PubMed

Maia, F; Tedim, J; Bastos, A C; Ferreira, M G S; Zheludkevich, M L

2013-10-18

The present paper reports on the development of new sensing active coating on the basis of nanocontainers containing pH-indicating agent. The coating is able to detect active corrosion processes on different metallic substrates. The corrosion detection functionality based on the local colour change in active cathodic zones results from the interaction of hydroxide ions with phenolphthalein encapsulated in mesoporous nanocontainers which function as sensing nanoreactors. The mesoporous silica nanocontainers are synthesized and loaded with pH indicator phenolphthalein in a one-stage process. The resulting system is mesoporous, which together with bulkiness of the indicator molecules limits their leaching. At the same time, penetration of water molecules and ions inside the container is still possible, allowing encapsulated phenolphthalein to be sensitive to the pH in the surrounding environment and outperforming systems when an indicator is directly dispersed in the coating layer.The performed tests demonstrate the pH sensitivity of the developed nanocontainers being dispersed in aqueous solutions. The corrosion sensing functionality of the protective coatings with nanocontainers are proven for aluminium- and magnesium-based metallic substrates. As a result, the developed nanocontainers show high potential to be used in a new generation of active protective coatings with corrosion-sensing coatings.

In situ fluorescence imaging of localized corrosion with a pH-sensitive imaging fiber

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panova, A.A.; Pantano, P.; Walt, D.R.

1997-12-01

A fiber optic pH-sensor capable of both visualizing corrosion sites and measuring local chemical concentrations is applied to real-time corrosion monitoring. The imaging fiber`s distal face containing an immobilized pH-sensitive fluorescent dye is brought into contact with metal surfaces submerged in aqueous buffers and fluorescence images are acquired as a function of time. The observed changes in fluorescence due to increases in pH at cathodic sites and decreases in pH at anodic sites are indicative of localized corrosion rates.

The time-course of red blood cell intracellular pH recovery following short-circuiting in relation to venous transit times in rainbow trout, Oncorhynchus mykiss.

PubMed

Harter, Till Sebastian; May, Alexandra G; Federspiel, William J; Supuran, Claudiu T; Brauner, Colin J

2018-04-11

Accumulating evidence is highlighting the importance of a system of enhanced hemoglobin-oxygen (Hb-O 2 ) unloading for cardiovascular O 2 transport in teleosts. Adrenergically stimulated sodium-proton-exchangers (β-NHE) create H + gradients across the red blood cell (RBC) membrane that are short-circuited in the presence of plasma-accessible carbonic anhydrase (paCA) at the tissues; the result is a large arterial-venous pH shift that greatly enhances O 2 unloading from pH-sensitive Hb. However, RBC intracellular pH (pH i ) must recover during venous transit (31-90 s), to enable O 2 -loading at the gills. The halftimes (t 1/2 ) and magnitudes of RBC β-adrenergic stimulation, short-circuiting with paCA and recovery of RBC pH i , were assessed in vitro, on rainbow trout whole blood, and using changes in closed-system PO 2 as a sensitive indicator for changes in RBC pH i . In addition, the recovery rate of RBC pH i was assessed in a continuous-flow apparatus that more closely mimics RBC transit though the circulation. Results indicate that: i) the t 1/2 of CA short-circuiting is likely within the residence time of blood in the capillaries; ii) the t 1/2 of RBC pH i recovery is 17 s and within the time of RBC venous transit; and iii) after short-circuiting RBCs re-establish the initial H + gradient across the membrane and can potentially undergo repeated cycles of short-circuiting and recovery. Thus, teleosts have evolved a system that greatly enhances O 2 unloading from pH-sensitive Hb at the tissues, while protecting O 2 loading at the gills; the resulting increase in O 2 transport per unit of blood flow may enable the tremendous athletic ability of salmonids.

Real-time measurement of the intracellular pH of yeast cells during glucose metabolism using ratiometric fluorescent nanosensors.

PubMed

Elsutohy, Mohamed M; Chauhan, Veeren M; Markus, Robert; Kyyaly, Mohammed Aref; Tendler, Saul J B; Aylott, Jonathan W

2017-05-11

Intracellular pH is a key parameter that influences many biochemical and metabolic pathways that can also be used as an indirect marker to monitor metabolic and intracellular processes. Herein, we utilise ratiometric fluorescent pH-sensitive nanosensors with an extended dynamic pH range to measure the intracellular pH of yeast (Saccharomyces cerevisiae) during glucose metabolism in real-time. Ratiometric fluorescent pH-sensitive nanosensors consisting of a polyacrylamide nanoparticle matrix covalently linked to two pH-sensitive fluorophores, Oregon green (OG) and 5(6)carboxyfluorescein (FAM), and a reference pH-insensitive fluorophore, 5(6)carboxytetramethylrhodamine (TAMRA), were synthesised. Nanosensors were functionalised with acrylamidopropyltrimethyl ammonium hydrochloride (ACTA) to confer a positive charge to the nanoparticle surfaces that facilitated nanosensor delivery to yeast cells, negating the need to use stress inducing techniques. The results showed that under glucose-starved conditions the intracellular pH of yeast population (n ≈ 200) was 4.67 ± 0.15. Upon addition of d-(+)-glucose (10 mM), this pH value decreased to pH 3.86 ± 0.13 over a period of 10 minutes followed by a gradual rise to a maximal pH of 5.21 ± 0.26, 25 minutes after glucose addition. 45 minutes after the addition of glucose, the intracellular pH of yeast cells returned to that of the glucose starved conditions. This study advances our understanding of the interplay between glucose metabolism and pH regulation in yeast cells, and indicates that the intracellular pH homestasis in yeast is highly regulated and demonstrates the utility of nanosensors for real-time intracellular pH measurements.

Multianalyte biosensor based on pH-sensitive ZnO electrolyte–insulator–semiconductor structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haur Kao, Chyuan; Chun Liu, Che; Ueng, Herng-Yih

2014-05-14

Multianalyte electrolyte–insulator–semiconductor (EIS) sensors with a ZnO sensing membrane annealed on silicon substrate for use in pH sensing were fabricated. Material analyses were conducted using X-ray diffraction and atomic force microscopy to identify optimal treatment conditions. Sensing performance for various ions of Na{sup +}, K{sup +}, urea, and glucose was also tested. Results indicate that an EIS sensor with a ZnO membrane annealed at 600 °C exhibited good performance with high sensitivity and a low drift rate compared with all other reported ZnO-based pH sensors. Furthermore, based on well-established pH sensing properties, pH-ion-sensitive field-effect transistor sensors have also been developed formore » use in detecting urea and glucose ions. ZnO-based EIS sensors show promise for future industrial biosensing applications.« less

Physicochemical properties of pH-sensitive hydrogels based on hydroxyethyl cellulose-hyaluronic acid and for applications as transdermal delivery systems for skin lesions.

PubMed

Kwon, Soon Sik; Kong, Bong Ju; Park, Soo Nam

2015-05-01

We investigated the physicochemical properties of pH-sensitive hydroxyethyl cellulose (HEC)/hyaluronic acid (HA) complex hydrogels containing isoliquiritigenin (ILTG), and discussed potential applications as transdermal delivery systems for the treatment of skin lesions caused by pH imbalance. HA has skin compatibility and pH functional groups and HEC serves as scaffold to build hydrogels with varied HCE:HA mass ratio. Hydrogels were synthesized via chemical cross-linking, and three-dimensional network structures were characterized via scanning electron microscopy (SEM). The swelling properties and polymer ratios of the hydrogels were investigated at pH values in the range 1-13. HECHA13 (i.e., an HEC:HA mass ratio of 1:3) was found to have optimal rheological and adhesive properties, and was used to investigate the drug release efficiency as a function of pH; the efficiency was greater than 70% at pH 7. Antimicrobial activity assays against Propionibacterium acnes were conducted to take advantage of the pH-sensitive properties of HECHA13. At pH 7, we found that HECHA13, which contained ILTG, inhibited the growth of P. acnes. Furthermore, HECHA13 was found to exhibit excellent permeability into the skin, which penetrated mostly via the hair follicle. These results indicate that this pH-sensitive hydrogel is effective as a transdermal delivery system for antimicrobial therapeutics, with potential applications in the treatment of acne. Copyright © 2015 Elsevier B.V. All rights reserved.

New class of 19F pH indicators: fluoroanilines.

PubMed Central

Deutsch, C J; Taylor, J S

1989-01-01

The pH dependence of the 19F chemical shift has been characterized for a number of fluorine-substituted aniline derivatives. These compounds constitute a new class of 19F nuclear magnetic resonance (NMR) pH indicators, characterized by single 19F resonance lines with sensitivities ranging from 2 to 7 ppm/pH unit near the aniline pKa; total shifts between conjugate acid and base of 5-15 ppm; and pKas ranging from 1 to 7. One compound, N,N-(methyl-2-carboxyisopropyl)-4-fluoroaniline, has a pKa of 6.8 and a sensitivity of 5 ppm/pH unit. This compound displays significant broadening of its 19F resonance near the aniline pKa (6.8), due to a decreased rate of exchange between conjugate acid and base species. Our results are consistent with slow dissociation of an intramolecular hydrogen bond in the zwitterionic species that limits the exchange rate between protonated and unprotonated forms for N,N-(methyl-2-carboxyisopropyl)-4-fluoroaniline. PMID:2720073

pH-sensitive stearoyl-PEG-poly(methacryloyl sulfadimethoxine) decorated liposomes for the delivery of gemcitabine to cancer cells.

PubMed

Bersani, Sara; Vila-Caballer, Marian; Brazzale, Chiara; Barattin, Michela; Salmaso, Stefano

2014-11-01

Novel, acid-sensitive liposomes that respond to physiopathological pH for tumour targeting applications were obtained by surface decoration with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (mPEG-DSPE) and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (stearoyl-PEG-polySDM). The pH-sensitive stearoyl-PEG-polySDM copolymer contained an average of seven methacryloyl sulfadimethoxines per molecule and was found to possess an apparent pKa of 7.2. Preliminary cloud point studies showed that the hydrophilic/hydrophobic copolymer conversion occurred at pH 7.0. The copolymer was soluble above pH 7.0 and underwent aggregation at lower pH. Liposome formulations were prepared with 0.2:0.6:100, 0.5:1.5:100 and 1:3:100 mPEG-DSPE/stearoyl-PEG-polySDM/lipids molar ratios. All of the liposome formulations were stable at pH 7.4, even in the presence of foetal bovine serum, but they underwent rapid size increase at pH 6.5. TEM analysis showed that, at pH 6.5, the formulations coated with a stearoyl-PEG-polySDM/lipids molar ratio greater than 1:100 underwent aggregation. At pH 7.4, the liposomes showed negative zeta potential that significantly decreased after incubation at pH 6.5. Cell-culture studies indicated that the liposomes were not toxic up to 10mg/mL. Fluorescence spectroscopy, cytofluorimetry and confocal microscopy showed that at pH 6.5, the incubation of MCF-7 tumour cells with fluorescein-labelled 1:3:100 mPEG-DSPE/stearoyl-PEG-polySDM/lipids molar ratio liposomes resulted in time-dependent cell association, while at pH 7.4 the cell interaction was significantly lower. The same pH-responsive liposome formulation loaded with gemcitabine (98.2±4.7nmol gemcitabine/lipid μmol loading capacity) was stable at pH 7.4 for several hours, while at pH 6.5 it rapidly aggregated. At pH 6.5, these liposomes displayed higher cytotoxicity than at pH 7.4 or compared to non-responsive control liposomes at both incubation pH. Notably, treatment with free gemcitabine did not yield cytotoxic effects, indicating that the carrier can efficiently deliver the anticancer drug to the cytosolic compartment. Copyright © 2014 Elsevier B.V. All rights reserved.

Integrating In Vitro, Modeling, and In Vivo Approaches to Investigate Warfarin Bioequivalence

PubMed Central

Wen, H; Fan, J; Vince, B; Li, T; Gao, W; Kinjo, M; Brown, J; Sun, W; Jiang, W; Lionberger, R

2017-01-01

We demonstrate the use of modeling and simulation to investigate bioequivalence (BE) concerns raised about generic warfarin products. To test the hypothesis that the loss of isopropyl alcohol and slow dissolution in acidic pH has significant impact on the pharmacokinetics of warfarin sodium tablets, we conducted physiologically based pharmacokinetic absorption modeling and simulation using formulation factors or in vitro dissolution profiles as input parameters. Sensitivity analyses indicated that warfarin pharmacokinetics was not sensitive to solubility, particle size, density, or dissolution rate in pH 4.5, but was affected by dissolution rate in pH 6.8 and potency. Virtual BE studies suggested that stressed warfarin sodium tablets with slow dissolution rate in pH 4.5 but having similar dissolution rate in pH 6.8 would be bioequivalent to the unstressed warfarin sodium tablets. A four‐way, crossover, single‐dose BE study in healthy subjects was conducted to test the same hypothesis and confirmed the simulation conclusion. PMID:28379643

Miniaturized pH Sensors Based on Zinc Oxide Nanotubes/Nanorods

PubMed Central

Fulati, Alimujiang; Ali, Syed M.Usman; Riaz, Muhammad; Amin, Gul; Nur, Omer; Willander, Magnus

2009-01-01

ZnO nanotubes and nanorods grown on gold thin film were used to create pH sensor devices. The developed ZnO nanotube and nanorod pH sensors display good reproducibility, repeatability and long-term stability and exhibit a pH-dependent electrochemical potential difference versus an Ag/AgCl reference electrode over a large dynamic pH range. We found the ZnO nanotubes provide sensitivity as high as twice that of the ZnO nanorods, which can be ascribed to the fact that small dimensional ZnO nanotubes have a higher level of surface and subsurface oxygen vacancies and provide a larger effective surface area with higher surface-to-volume ratio as compared to ZnO nanorods, thus affording the ZnO nanotube pH sensor a higher sensitivity. Experimental results indicate ZnO nanotubes can be used in pH sensor applications with improved performance. Moreover, the ZnO nanotube arrays may find potential application as a novel material for measurements of intracellular biochemical species within single living cells. PMID:22291545

Functional photoacoustic microscopy of pH

PubMed Central

Chatni, Muhammad Rameez; Yao, Junjie; Danielli, Amos; Favazza, Christopher P.; Maslov, Konstantin I.; Wang, Lihong V.

2011-01-01

pH is a tightly regulated indicator of metabolic activity. In mammalian systems, an imbalance of pH regulation may result from or result in serious illness. In this paper, we report photoacoustic microscopy (PAM) of a commercially available pH-sensitive fluorescent dye (SNARF-5F carboxylic acid) in tissue phantoms. We demonstrated that PAM is capable of pH imaging in absolute values at tissue depths of up to 2.0 mm, greater than possible with other forms of optical microscopy. PMID:22029342

Hydroxylated near-infrared BODIPY fluorophores as intracellular pH sensors

PubMed Central

Salim, Mohamed M.; Owens, Eric A.; Gao, Tielong; Lee, Jeong Heon; Hyun, Hoon; Choi, Hak Soo; Henary, Maged

2015-01-01

In this study, a series of new, highly sensitive BF2-chelated tetraarylazadipyrromethane dyes are synthesized and analyzed to be suitable as on/off photo-induced electron transfer modulated fluorescent sensors for determination of intracellular pH. The ethanolic solutions of the new indicators feature absorption maxima in the range of 696–700 nm and a fluorescence emission maximum at 720 nm. Molar absorptivity and fluorescence quantum yield data were determined for the studied set of aza-BODIPY indicators. These indicators have high molar absorption coefficients of ~80 000 M−1 cm−1 and quantum yields (up to 18%). Corresponding pKa values of indicators are determined from absorbance and fluorescence measurements and range from 9.1 to 10.8, depending on the selective positioning of electron-donating functionalities. The excellent photostability of the aza-BODIPY indicators makes them particularly suitable for long duration measurements. The in vitro cellular staining of living tissues in PC3 cells based on the isosbestic point at pH 7.8 and pH 9.3 has been employed which shows an increase in fluorescence intensity at 800 nm with increase in pH for certain compounds and fluorescence intensity decreases at 700 nm. Therefore, the new indicators are suitable for exploitation and adaptation in a diverse range of analytical applications. PMID:25105177

Preparation and properties evaluation of a novel pH-sensitive liposomes based on imidazole-modified cholesterol derivatives.

PubMed

Ju, Liang; Cailin, Fang; Wenlan, Wu; Pinghua, Yu; Jiayu, Gao; Junbo, Li

2017-02-25

As a new kind of drug carries, pH-sensitive liposomes have been widely studied in tumor therapy for their advantages of target ability and sustained-release. Here, we synthesized a pH-sensitive material, N-(3-Aminopropyl)imidazole-cholesterol (IM-Chol) and prepared a novel pH-sensitive liposomes using IM-Chol and phosphatidylcholine. IM-Chol was synthesized through amidation reaction between the amino group of N-(3-Aminopropyl)imidazole and acyl chloride group of cholesteryl chloroformate in a weak base solution. Optimal conditions to prepare liposomes were obtained by the orthogonal experiment with the higher encapsulation efficiency as the evaluation indicator. The properties of liposomes, such as particle size, zeta potential, morphology, encapsulation efficiency, drug release behavior and in vitro cell toxicity were evaluated by transmission electron microscopy (TEM), dynamic light scattering (DLS) and MTT assay respectively. The results showed that the average particle size of IM-Chol liposomes was 141nm (PDI 0.323). Liposomes can assemble into uniform spheres at pH 7.4, but under the condition of pH 5.0, the spherical structure of IM-Chol liposomes was broken, exhibiting pH-sensitive property. In vitro drug releasing studies demonstrated the controlled-release behavior of the curcumin (CUR) in the IM-Chol liposomes. The cumulative release of CUR reached to 72.5% in the first 24h at pH 5.0, faster than that at pH 7.4, which confirmed that the drug carrier displayed pH-sensitive release behaviors. In addition, the MTT assay was employed to test the cytotoxicity of IM-Chol liposomes and CUR IM-Chol liposomes. All cell viabilities were greater than 80% after incubating for 24h, even up to the highest dose of 500mg/L, indicating that IM-Chol liposomes had good biocompatibility. The tumor inhibitory results towards EC109 cells of free CUR and CUR-loaded IM-Chol liposomes indicated that IM-Chol liposomes indeed enhanced the cell killing effect of CUR. These results showed that the novel IM-Chol liposomes prepared in this paper had pH-sensitive property and were expected to play a huge potential in tumor treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Design of an optically stable pH sensor based on immobilization of Giemsa on triacetylcellulose membrane.

PubMed

Khodadoust, Saeid; Kouri, Narges Cham; Talebiyanpoor, Mohammad Sharif; Deris, Jamile; Pebdani, Arezou Amiri

2015-12-01

In this work a simple, inexpensive, and sensitive optical sensor based on triacetylcellulose membrane as solid support was developed by using immobilization of Giemsa indicator for pH measurement. In this method, the influence variables on the membrane performance including pH concentration of indicator, response time, ionic strength, and reversibility were investigated. At optimum values of all variables the response of optical pH sensor is linear in the pH range of 3.0-12.0. This optical sensor was produced through simultaneous binding of the Giemsa on the activated triacetylcellulose membrane which responded to the pH changes in a broader linear range within less than 2.0 min and suitable reproducibility (RSD<5%). Stability results showed that this sensor was stable after 6 months of storage in the water/ethanol (50:50, v/v) solution without any measurable divergence in response properties (less than 5% RSD). Copyright © 2015 Elsevier B.V. All rights reserved.

Low-temperature solution processing of palladium/palladium oxide films and their pH sensing performance.

PubMed

Qin, Yiheng; Alam, Arif U; Pan, Si; Howlader, Matiar M R; Ghosh, Raja; Selvaganapathy, P Ravi; Wu, Yiliang; Deen, M Jamal

2016-01-01

Highly sensitive, easy-to-fabricate, and low-cost pH sensors with small dimensions are required to monitor human bodily fluids, drinking water quality and chemical/biological processes. In this study, a low-temperature, solution-based process is developed to prepare palladium/palladium oxide (Pd/PdO) thin films for pH sensing. A precursor solution for Pd is spin coated onto pre-cleaned glass substrates and annealed at low temperature to generate Pd and PdO. The percentages of PdO at the surface and in the bulk of the electrodes are correlated to their sensing performance, which was studied by using the X-ray photoelectron spectroscope. Large amounts of PdO introduced by prolonged annealing improve the electrode's sensitivity and long-term stability. Atomic force microscopy study showed that the low-temperature annealing results in a smooth electrode surface, which contributes to a fast response. Nano-voids at the electrode surfaces were observed by scanning electron microscope, indicating a reason for the long-term degradation of the pH sensitivity. Using the optimized annealing parameters of 200°C for 48 h, a linear pH response with sensitivity of 64.71±0.56 mV/pH is obtained for pH between 2 and 12. These electrodes show a response time shorter than 18 s, hysteresis less than 8 mV and stability over 60 days. High reproducibility in the sensing performance is achieved. This low-temperature solution-processed sensing electrode shows the potential for the development of pH sensing systems on flexible substrates over a large area at low cost without using vacuum equipment. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of critical amino acids in the proximal C-terminal of TREK-2 K+ channel for activation by acidic pHi and ATP-dependent inhibition.

PubMed

Woo, Joohan; Jun, Young Keul; Zhang, Yin-Hua; Nam, Joo Hyun; Shin, Dong Hoon; Kim, Sung Joon

2018-02-01

TWIK-related two-pore domain K + channels (TREKs) are regulated by intracellular pH (pH i ) and Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ). Previously, Glu 306 in proximal C-terminal (pCt) of mouse TREK-1 was identified as the pH i -sensing residue. The direction of PI(4,5)P 2 sensitivity is controversial, and we have recently shown that TREKs are inhibited by intracellular ATP via endogenous PI(4,5)P 2 formation. Here we investigate the anionic and cationic residues of pCt for the pH i and ATP-sensitivity in human TREK-2 (hTREK-2). In inside-out patch clamp recordings (I TREK-2,i-o ), acidic pH i -induced activation was absent in E332A and was partly attenuated in E335A. Neutralization of cationic Lys (K330A) also eliminated the acidic pH i sensitivity of I TREK-2,i-o . Unlike the inhibition of wild-type (WT) I TREK-2,i-o by intracellular ATP, neither E332A nor K330A was sensitive to ATP. Nevertheless, exogenous PI(4,5)P 2 (10 μM) abolished I TREK-2 i-o in all the above mutants as well as in WT, indicating unspecific inhibition by exogenous PI(4,5)P 2 . In whole-cell recordings of TREK-2 (I TREK-2,w-c ), K330A and E332A showed higher or fully active basal activity, showing attenuated or insignificant activation by 2-APB, arachidonic acid, or acidic pH e 6.9. I TREK-1,w-c of WT is largely suppressed by pH e 6.9, and the inhibition is slightly attenuated in K312A and E315A. The results show concerted roles of the oppositely charged Lys and Glu in pCt for the ATP-dependent low basal activity and pH i sensitivity.

Paclitaxel-Loaded pH-Sensitive Liposome: New Insights on Structural and Physicochemical Characterization.

PubMed

Monteiro, Liziane O F; Malachias, Ângelo; Pound-Lana, Gwenaelle; Magalhães-Paniago, Rogério; Mosqueira, Vanessa C F; Oliveira, Mônica C; de Barros, André Luís B; Leite, Elaine A

2018-05-22

A long-circulating and pH-sensitive liposome containing paclitaxel (SpHL-PTX) was recently developed by our group. Once in an acidic environment, for example, tumors, these liposomes undergo destabilization, releasing the encapsulated drug. In this way, the aim of this study was to evaluate the molecular and supramolecular interactions between the lipid bilayer and PTX in similar biological environment conditions. High-sensitivity analyses of SpHL-PTX structures were obtained by the small-angle X-ray scattering technique combined with other techniques such as dynamic light scattering, asymmetric flow field-flow fractionation, transmission electron microscopy, and high-performance liquid chromatography. The results showed that PTX incorporation in the liposomal bilayer clearly leads to changes in supramolecular organization of dioleoylphosphatidylethanolamine (DOPE) molecules, inducing the formation of more ordered structures. Changes in supramolecular organization were observed at lower pH, indicating that pH sensitivity was preserved even in the presence of fetal bovine serum proteins. Furthermore, morphological and physicochemical characterization of SpHL-PTX evidenced the formation of nanosized dispersion suitable for intravenous administration. In conclusion, a stable nanosized dispersion of PTX was obtained at pH 7.4 with suitable parameters for intravenous administration. At lower pH conditions, the pH sensitivity of the system was clearly evidenced by changes in the supramolecular organization of DOPE molecules, which is crucial for the delivery of PTX into the cytoplasm of the targeted cells. In this way, the results obtained by different techniques confirm the feasibility of SpHL as a promising tool to PTX delivery in acidic environments, such as tumors.

Self-assembled nanocomplexes of anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug delivery

NASA Astrophysics Data System (ADS)

Vora, Lalit; Tyagi, Monica; Patel, Ketan; Gupta, Sanjay; Vavia, Pradeep

2014-12-01

The amalgamation of chemotherapy and gene therapy is promising treatment option for cancer. In this study, novel biocompatible self-assembled nanocomplexes (NCs) between carboxylmethylated pullulan t335 (CMP) with polyallylamine (CMP-PAA NCs) were developed for plasmid DNA (pDNA) and pH-sensitive doxorubicin (DOX) delivery. DOX was conjugated to CMP (DOX-CMP) via hydrazone and confirmed by FTIR and 1H-NMR. In vitro release studies of pH-sensitive DOX-CMP conjugate showed 23 and 85 % release after 48 h at pH 7.4 (physiological pH) and pH 5 (intracellular/tumoral pH), respectively. The CMP-PAA NCs or DOX-CMP-PAA NCs self-assembled into a nanosized (<250 nm) spherical shape as confirmed by DLS and TEM. The hemolysis and cytotoxicity study indicated that the CMP-PAA NCs did not show cytotoxicity in comparison with plain polyallylamine. Gel retardation assay showed complete binding of pDNA with CMP-PAA NCs at 1:2 weight ratio. CMP-PAA NCs/pDNA showed significantly higher transfection in HEK293 cells compared to PAA/pDNA complexes. Confocal imaging demonstrated successful cellular uptake of DOX-CMP-PAA NCs in HEK293 cells. Thus, NCs hold great potential for targeted pDNA and pH-sensitive intratumoral drug delivery.

High prevalence of heartburn and low acid sensitivity in patients with idiopathic achalasia.

PubMed

Ponce, Julio; Ortiz, Vicente; Maroto, Nuria; Ponce, Marta; Bustamante, Marco; Garrigues, Vicente

2011-03-01

Heartburn is frequently reported by patients with achalasia before treatment. However, the esophageal sensitivity to acid as a possible mediator of this symptom has not been previously evaluated. To evaluate the prevalence of gastroesophageal reflux symptoms and the esophageal sensitivity to acid perfusion in patients with untreated achalasia. Forty patients with achalasia were prospectively evaluated. Forty-three patients with gastroesophageal reflux disease comprised the control group (ten of them with Barrett's esophagus). Symptoms were evaluated by a structured clinical questionnaire. Objective assessment was performed by ambulatory 24-h esophageal pH monitoring and endoscopy. Esophageal sensitivity to acid was evaluated by esophageal perfusion of ClH 0.1 N. Fifteen (37%) of the 40 patients with achalasia presented heartburn, but only four of them had esophagitis and/or abnormal esophageal pH recording. Eight patients had abnormal pH recording. Three patients had esophagitis. The esophagus was sensitive to acid in seven (17%) patients with achalasia, three of them with heartburn and one with abnormal pH recording. In the control group, 40 of 43 (93%) presented heartburn. Acid perfusion was positive in 32 (74%). Sensitivity to acid was lower in patients with achalasia than in those with gastroesophageal reflux disease with or without Barrett's esophagus. The prevalence of heartburn in patients with achalasia is high, although its association with objective indicators of gastroesophageal reflux disease is weak. Patients with achalasia have lower esophageal sensitivity to acid than patients with GERD, suggesting that heartburn is does not arise from this condition.

Synthesis and Properties of pH-, Thermo-, and Salt-Sensitive Modified Poly(aspartic acid)/Poly(vinyl alcohol) IPN Hydrogel and Its Drug Controlled Release.

PubMed

Lu, Jingqiong; Li, Yinhui; Hu, Deng; Chen, Xiaoling; Liu, Yongmei; Wang, Liping; Zhao, Yansheng

2015-01-01

Modified poly(aspartic acid)/poly(vinyl alcohol) interpenetrating polymer network (KPAsp/PVA IPN) hydrogel for drug controlled release was synthesized by a simple one-step method in aqueous system using poly(aspartic acid) grafting 3-aminopropyltriethoxysilane (KH-550) and poly(vinyl alcohol) (PVA) as materials. The hydrogel surface morphology and composition were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal stability was analyzed by thermogravimetric analysis (TGA). The swelling properties and pH, temperature, and salt sensitivities of KPAsp, KPAsp/PVA semi-interpenetrating polymer network (semi-IPN), and KPAsp/PVA IPN hydrogels were also investigated. All of the three hydrogels showed ampholytic pH-responsive properties, and swelling behavior was also extremely sensitive to the temperature, ionic strength, and cationic species. Finally, the drug controlled release properties of the three hydrogels were evaluated and results indicated that three hydrogels could control drug release by external surroundings stimuli. The drug controlled release properties of KPAsp/PVA IPN hydrogel are the most outstanding, and the correlative measured release profiles of salicylic acid at 37°C were 32.6 wt% at pH = 1.2 (simulated gastric fluid) and 62.5 wt% at pH = 7.4 (simulated intestinal fluid), respectively. These results indicated that KPAsp/PVA IPN hydrogels are a promising carrier system for controlled drug delivery.

A novel pH sensitive water soluble fluorescent nanomicellar sensor for potential biomedical applications.

PubMed

Georgiev, Nikolai I; Bryaskova, Rayna; Tzoneva, Rumiana; Ugrinova, Iva; Detrembleur, Christophe; Miloshev, Stoyan; Asiri, Abdullah M; Qusti, Abdullah H; Bojinov, Vladimir B

2013-11-01

Herein we report on the synthesis and sensor activity of a novel pH sensitive probe designed as highly water-soluble fluorescent micelles by grafting of 1,8-naphthalimide-rhodamine bichromophoric FRET system (RNI) to the PMMA block of a well-defined amphiphilic diblock copolymer-poly(methyl methacrylate)-b-poly(methacrylic acid) (PMMA48-b-PMAA27). The RNI-PMMA48-b-PMAA27 adduct is capable of self-assembling into micelles with a hydrophobic PMMA core, containing the anchored fluorescent probe, and a hydrophilic shell composed of PMAA block. Novel fluorescent micelles are able to serve as a highly sensitive pH probe in water and to internalize successfully HeLa and HEK cells. Furthermore, they showed cell specificity and significantly higher photostability than that of a pure organic dye label such as BODIPY. The valuable properties of the newly prepared fluorescent micelles indicate the high potential of the probe for future biological and biomedical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

A proteorhodopsin-based biohybrid light-powering pH sensor.

PubMed

Rao, Siyuan; Guo, Zhibin; Liang, Dawei; Chen, Deliang; Wei, Yen; Xiang, Yan

2013-10-14

The biohybrid sensor is an emerging technique for multi-functional detection that utilizes the instinctive responses or interactions of biomolecules. We develop a biohybrid pH sensor by taking advantage of the pH-dependent photoelectric characteristics of proteorhodopsin (pR). The transient absorption kinetics study indicates that the photoelectric behavior of pR is attributed to the varying lifetime of the M intermediate at different environmental pH values. This pR-based biohybrid light-powering sensor with microfluidic design can achieve real-time pH detection with quick response and high sensitivity. The results of this work would shed light on pR and its potential applications.

Sensitive and selective detection of Cu(II) ion: A new effective 1,8-naphthalimide-based fluorescence 'turn off' sensor.

PubMed

Huang, Guozhen; Li, Chuang; Han, Xintong; Aderinto, Stephen Opeyemi; Shen, Kesheng; Mao, Shanshan; Wu, Huilu

2018-06-01

The present study reports the development of a new 1,8-naphthalimide-based fluorescent sensor V for monitoring Cu(II) ions. The sensor exhibited pH independence over a wide pH range 2.52-9.58, and indicated its possible use for monitoring Cu(II) ions in a competitive pH medium. The sensor also showed high selectivity and sensitivity towards the Cu(II) ions over other competitive metal ions in DMSO-HEPES buffer (v/v, 1:1; pH 7.4) with a fluorescence 'turn off' mode of 79.79% observed. A Job plot indicated the formation of a 1:1 binding mode of the sensor with Cu(II) ions. The association constant and detection limit were 1.14 × 10 6  M -1 and 4.67 × 10 -8 M, respectively. The fluorescence spectrum of the sensor was quenched due to the powerful paramagnetic nature of the Cu(II) ions. Potential application of this sensor was also demonstrated when determining Cu(II) ion levels in two different water samples. Copyright © 2018 John Wiley & Sons, Ltd.

Microencapsulation Technologies for Corrosion Protective Coating Applications

NASA Technical Reports Server (NTRS)

Li, Wenyan; Buhrow, Jerry; Jolley, Scott; Calle, Luz; Pearman, Benjamin; Zhang, Xuejun

2015-01-01

Microencapsulation technologies for functional smart Coatings for autonomous corrosion control have been a research area of strong emphasis during the last decade. This work concerns the development of pH sensitive micro-containers (microparticles and microcapsules) for autonomous corrosion control. This paper presents an overview of the state-of-the-art in the field of microencapsulation for corrosion control applications, as well as the technical details of the pH sensitive microcontainer approach, such as selection criteria for corrosion indicators and corrosion inhibitors; the development and optimization of encapsulation methods; function evaluation before and after incorporation of the microcontainers into coatings; and further optimization to improve coating compatibility and performance.

Expression and testing in plants of ArcLight, a genetically-encoded voltage indicator used in neuroscience research.

PubMed

Matzke, Antonius J M; Matzke, Marjori

2015-10-12

It is increasingly appreciated that electrical controls acting at the cellular and supra-cellular levels influence development and initiate rapid responses to environmental cues. An emerging method for non-invasive optical imaging of electrical activity at cell membranes uses genetically-encoded voltage indicators (GEVIs). Developed by neuroscientists to chart neuronal circuits in animals, GEVIs comprise a fluorescent protein that is fused to a voltage-sensing domain. One well-known GEVI, ArcLight, undergoes strong shifts in fluorescence intensity in response to voltage changes in mammalian cells. ArcLight consists of super-ecliptic (SE) pHluorin (pH-sensitive fluorescent protein) with an A227D substitution, which confers voltage sensitivity in neurons, fused to the voltage-sensing domain of the voltage-sensing phosphatase of C iona i ntestinalis (Ci-VSD). In an ongoing effort to adapt tools of optical electrophysiology for plants, we describe here the expression and testing of ArcLight and various derivatives in different membranes of root cells in Arabidopsis thaliana. Transgenic constructs were designed to express ArcLight and various derivatives targeted to the plasma membrane and nuclear membranes of Arabidopsis root cells. In transgenic seedlings, changes in fluorescence intensity of these reporter proteins following extracellular ATP (eATP) application were monitored using a fluorescence microscope equipped with a high speed camera. Coordinate reductions in fluorescence intensity of ArcLight and Ci-VSD-containing derivatives were observed at both the plasma membrane and nuclear membranes following eATP treatments. However, similar responses were observed for derivatives lacking the Ci-VSD. The dispensability of the Ci-VSD suggests that in plants, where H(+) ions contribute substantially to electrical activities, the voltage-sensing ability of ArcLight is subordinate to the pH sensitivity of its SEpHluorin base. The transient reduction of ArcLight fluorescence triggered by eATP most likely reflects changes in pH and not membrane voltage. The pH sensitivity of ArcLight precludes its use as a direct sensor of membrane voltage in plants. Nevertheless, ArcLight and derivatives situated in the plasma membrane and nuclear membranes may offer robust, fluorescence intensity-based pH indicators for monitoring concurrent changes in pH at these discrete membrane systems. Such tools will assist analyses of pH as a signal and/or messenger at the cell surface and the nuclear periphery in living plants.

Ionophore-based optical nanosensors incorporating hydrophobic carbon dots and a pH-sensitive quencher dye for sodium detection.

PubMed

Galyean, A A; Behr, M R; Cash, K J

2018-01-21

Nanosensors present a biological monitoring method that is biocompatible, reversible, and nano-scale, and they offer many advantages over traditional organic indicators. Typical ionophore-based nanosensors incorporate nile-blue derivative pH indicators but suffer from photobleaching while quantum dot alternatives pose a potential toxicity risk. In order to address this challenge, sodium selective nanosensors containing carbon dots and a pH-sensitive quencher molecule were developed based on an ion-exchange theory and a decoupled recognition element from the pH indicator. Carbon dots were synthesized and integrated into nanosensors containing a pH-indicator, an analyte-binding ligand (ionophore), and a charge-balancing additive. These nanosensors are ion-selective against potassium (selectivity coefficient of 0.4) and lithium (selectivity coefficient of 0.9). Reversible nanosensor response to sodium is also demonstrated. The carbon dot nanosensors are resistant to changes in optical properties for at least 12 h and display stable selectivity to physiologically-relevant sodium (alpha = 0.5 of 200 mM NaCl) for a minimum of 6 days.

Measuring the Degree of Sensitization (DOS) Using an Electrochemical Technique

NASA Astrophysics Data System (ADS)

Abuzriba, Mokhtar B.; Musa, Salem M.

Sensitization can be simply defined as the susceptibility of an alloy, specifically austenitic stainless steel, to corrosion at grain boundaries. A detailed study on types 304 stainless steel has been carried out to correlate the degree of sensitization measured by electrochemical potentiokinetic reactivation test (EPR) with the susceptibility to intergranular corrosion. In this study four different heat treatments were given to alloys, i.e., solution annealed (SA) at 1020 °C for 1 h, then quenched in water; also then heat-treated in air at 620 °C for 15, 30, and 60 min. The electrolyte for the EPR tests was 1.0 N H2SO4 solution containing 0.01 M KSCN. Potentiodynamic curves from passive to active regions in deaerated solution at room temperature were obtained at a scan rate of 1.67 mV/s (6 V/h), after the passivation at 200 mV versus (SCE) for 2 min then the polarization was conducted. The criterion used to distinguish between sensitized and non-sensitized specimens is the activation charge Pa, the peak current density, Ph, in the active state, and Flade potential Ef at which the active curve breaks upward. The results indicated that the longer the sensitization time the higher the activation charge (Pa), and the higher the peak current density in the active state (Ph). The results indicated that, the EPR is more sensitive than the chemical method for measuring the degree of sensitization.

A rapid, naked-eye detection of hypochlorite and bisulfite using a robust and highly-photostable indicator dye Quinaldine Red in aqueous medium

NASA Astrophysics Data System (ADS)

Dutta, Tanoy; Chandra, Falguni; Koner, Apurba L.

2018-02-01

A ;naked-eye; detection of health hazardous bisulfite (HSO3-) and hypochlorite (ClO-) using an indicator dye (Quinaldine Red, QR) in a wide range of pH is demonstrated. The molecule contains a quinoline moiety linked to an N,N-dimethylaniline moiety with a conjugated double bond. Treatment of QR with HSO3- and ClO-, in aqueous solution at near-neutral pH, resulted in a colorless product with high selectivity and sensitivity. The detection limit was 47.8 μM and 0.2 μM for HSO3- and ClO- respectively. However, ClO- was 50 times more sensitive and with 2 times faster response compared to HSO3-. The detail characterization and related analysis demonstrate the potential of QR for a rapid, robust and highly efficient colorimetric sensor for the practical applications to detect hypochlorite in water samples.

Diversity and food web structure of nematode communities under high soil salinity and alkaline pH.

PubMed

Salamún, Peter; Kucanová, Eva; Brázová, Tímea; Miklisová, Dana; Renčo, Marek; Hanzelová, Vladimíra

2014-10-01

A long-term and intensive magnesium (Mg) ore processing in Slovenské Magnezitové Závody a.s. in Jelšava has resulted in a high Mg content and alkaline pH of the soil environment, noticeable mainly in the close vicinity of the smelter. Nematode communities strongly reacted to the contamination mostly by a decrease in abundance of the sensitive groups. Nematodes from c-p 1 group and bacterivores, tolerant to pollution played a significant role in establishing the dominance at all sites. With increasing distance from the pollution source, the nematode communities were more structured and complex, with an increase in proportion of sensitive c-p 4 and 5 nematodes, composed mainly of carnivores and omnivores. Various ecological indices (e.g. MI2-5, SI, H') indicated similar improvement of farther soil ecosystems.

Partial trypsin digestion as an indicator of mis-folding of mutant alanine:glyoxylate aminotransferase and chaperone effects of specific ligands. Study of a spectrum of missense mutants.

PubMed

Coulter-Mackie, M B; Lian, Q

2008-07-01

Alanine:glyoxylate aminotransferase (AGT) is a liver peroxisomal enzyme whose deficiency results in primary hyperoxaluria type 1 (PH1). More than 75 PH1 mutations are now documented in the AGT gene (AGXT), of which about 50% are missense. We have previously demonstrated that many such mutants expressed by transcription/translation are subject to generalized degradation by the proteasome and a specific limited trimming by an endogenous ATP-independent protease activity. Here, we report the results of partial digestion using trypsin as a mimic for the endogenous non-proteasomal protease and the use of N-terminal protein sequencing to determine the sensitive site. Partial trypsin digestion also provided an indicator of proper folding of the mutant enzyme. For selected mutations the sensitivity to trypsin could be ameliorated by addition of pyridoxal phosphate or aminooxy acetic acid as specific pharmacological chaperones.

Design and characterization of a plastic optical fiber pH sensor

NASA Astrophysics Data System (ADS)

Ferreira, Licínio; Simões, Pedro; Carvalho, Rui S.; Lopes, Paulo; Ferreira, Mário

2013-11-01

In this paper are present the design and characterization of a pH sensor using plastic optical fiber (POF) technology and a material produced by the sol-gel process with TEOS (tetraethyl orthosilicate) to immobilize universal indicator of pH (comprised of Thymol Blue, Methyl Red, Bromothymol Blue and Phenolphthalein) inside the silica matrix. This matrix is positioned between two extensions of plastic optical fiber tightly positioned at each side with both fibers aligned and sharing a common optical axis. This set will work as a pH sensor since the matrix embedded with indicator and in the presence of a solution (basic or acid solution) will change the optical transmittance properties. The optical source is a superluminescent white LED and the receiver is a photodiode having a good and linear responsivity in the visible spectrum. This pH sensitive matrix has large pores which allow the diffusion of the surrounding fluid molecules into the matrix and thus the close contact of these to the indicator molecules. This contact causes the change of color of the whole matrix allowing proper colorimetric detection by the photodiode. This variation of color associated with the detector wavelength linear response is the base of operation of the proposed device. This pH sensor presents many advantages over the standard and commercial pH meters namely, lightweight, portability and a low cost.

A novel pH optical sensor using methyl orange based on triacetylcellulose membranes as support.

PubMed

Hosseini, Mohammad; Heydari, Rouhollah; Alimoradi, Mohammad

2014-07-15

A novel pH optical sensor based on triacetylcellulose membrane as solid support was developed by using immobilization of methyl orange indicator. The prepared optical sensor was fixed into a flow cell for on-line pH monitoring. Variables affecting sensor performance, such as pH of dye bonding to triacetylcellulose membrane and dye concentration have been fully evaluated and optimized. The calibration curve showed good behavior and precision (RSD<0.4%) in the pH range of 4.0-12.0. No significant variation was observed on sensor response with increasing the ionic strength in the range of 0.0-0.5M of sodium chloride. Determination of pH by using the proposed optical sensor is on-line, quick, inexpensive, selective and sensitive in the pH range of 4.0-12.0. Copyright © 2014 Elsevier B.V. All rights reserved.

Suitability of the isolated chicken eye test for classification of extreme pH detergents and cleaning products.

PubMed

Cazelle, Elodie; Eskes, Chantra; Hermann, Martina; Jones, Penny; McNamee, Pauline; Prinsen, Menk; Taylor, Hannah; Wijnands, Marcel V W

2015-04-01

A.I.S.E. investigated the suitability of the regulatory adopted ICE in vitro test method (OECD TG 438) with or without histopathology to identify detergent and cleaning formulations having extreme pH that require classification as EU CLP/UN GHS Category 1. To this aim, 18 extreme pH detergent and cleaning formulations were tested covering both alkaline and acidic extreme pHs. The ICE standard test method following OECD Test Guideline 438 showed good concordance with in vivo classification (83%) and good and balanced specificity and sensitivity values (83%) which are in line with the performances of currently adopted in vitro test guidelines, confirming its suitability to identify Category 1 extreme pH detergent and cleaning products. In contrast to previous findings obtained with non-extreme pH formulations, the use of histopathology did not improve the sensitivity of the assay whilst it strongly decreased its specificity for the extreme pH formulations. Furthermore, use of non-testing prediction rules for classification showed poor concordance values (33% for the extreme pH rule and 61% for the EU CLP additivity approach) with high rates of over-prediction (100% for the extreme pH rule and 50% for the additivity approach), indicating that these non-testing prediction rules are not suitable to predict Category 1 hazards of extreme pH detergent and cleaning formulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

The acid test of fluoride: how pH modulates toxicity.

PubMed

Sharma, Ramaswamy; Tsuchiya, Masahiro; Skobe, Ziedonis; Tannous, Bakhos A; Bartlett, John D

2010-05-28

It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F(-)). Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of F(-). Enamel formation is initiated in a neutral pH environment (secretory stage); however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage). Low pH can facilitate entry of F(-) into cells. Here, we asked if F(-) was more toxic at low pH, as measured by increased cell stress and decreased cell function. Treatment of ameloblast-derived LS8 cells with F(-) at low pH reduced the threshold dose of F(-) required to phosphorylate stress-related proteins, PERK, eIF2alpha, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase, and secretion was quantified as a function of F(-) dose and pH. Luciferase secretion significantly decreased within 2 hr of F(-) treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm F(-) in their drinking water exhibited increased stress-mediated phosphorylation of eIF2alpha in maturation stage ameloblasts (pH<6.0) as compared to secretory stage ameloblasts (pH approximately 7.2). Intriguingly, F(-)-treated rats demonstrated a striking decrease in transcripts expressed during the maturation stage of enamel development (Klk4 and Amtn). In contrast, the expression of secretory stage genes, AmelX, Ambn, Enam and Mmp20, was unaffected. The low pH environment of maturation stage ameloblasts facilitates the uptake of F(-), causing increased cell stress that compromises ameloblast function, resulting in dental fluorosis.

The Central Role of PhEIN2 in Ethylene Responses throughout Plant Development in Petunia1

PubMed Central

Shibuya, Kenichi; Barry, Kristin G.; Ciardi, Joseph A.; Loucas, Holly M.; Underwood, Beverly A.; Nourizadeh, Saeid; Ecker, Joseph R.; Klee, Harry J.; Clark, David G.

2004-01-01

The plant hormone ethylene regulates many aspects of growth and development. Loss-of-function mutations in ETHYLENE INSENSITIVE2 (EIN2) result in ethylene insensitivity in Arabidopsis, indicating an essential role of EIN2 in ethylene signaling. However, little is known about the role of EIN2 in species other than Arabidopsis. To gain a better understanding of EIN2, a petunia (Petunia × hybrida cv Mitchell Diploid [MD]) homolog of the Arabidopsis EIN2 gene (PhEIN2) was isolated, and the role of PhEIN2 was analyzed in a wide range of plant responses to ethylene, many that do not occur in Arabidopsis. PhEIN2 mRNA was present at varying levels in tissues examined, and the PhEIN2 expression decreased after ethylene treatment in petals. These results indicate that expression of PhEIN2 mRNA is spatially and temporally regulated in petunia during plant development. Transgenic petunia plants with reduced PhEIN2 expression were compared to wild-type MD and ethylene-insensitive petunia plants expressing the Arabidopsis etr1-1 gene for several physiological processes. Both PhEIN2 and etr1-1 transgenic plants exhibited significant delays in flower senescence and fruit ripening, inhibited adventitious root and seedling root hair formation, premature death, and increased hypocotyl length in seedling ethylene response assays compared to MD. Moderate or strong levels of reduction in ethylene sensitivity were achieved with expression of both etr1-1 and PhEIN2 transgenes, as measured by downstream expression of PhEIL1. These results demonstrate that PhEIN2 mediates ethylene signals in a wide range of physiological processes and also indicate the central role of EIN2 in ethylene signal transduction. PMID:15466231

The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants.

PubMed

Nogueira, D R; Mitjans, M; Infante, M R; Vinardell, M P

2011-07-01

Surfactants are among the most versatile and widely used excipients in pharmaceuticals. This versatility, together with their pH-responsive membrane-disruptive activity and low toxicity, could also enable their potential application in drug delivery systems. Five anionic lysine-based surfactants which differ in the nature of their counterion were studied. Their capacity to disrupt the cell membrane was examined under a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model for endosomal membranes. The surfactants showed pH-sensitive hemolytic activity and improved kinetics at the endosomal pH range. Low concentrations resulted in negligible hemolysis at physiological pH and high membrane lytic activity at pH 5.4, which is in the range characteristic of late endosomes. With increasing concentration, the surfactants showed an enhanced capacity to lyse cell membranes, and also caused significant membrane disruption at physiological pH. This observation indicates that, at high concentrations, surfactant behavior is independent of pH. The mechanism of surfactant-mediated membrane destabilization was addressed, and scanning electron microscopy studies were also performed to evaluate the effects of the compounds on erythrocyte morphology as a function of pH. The in vitro cytotoxicity of the surfactants was assessed by MTT and NRU assays with the 3T3 cell line. The influence of different types of counterion on hemolytic activity and the potential applications of these surfactants in drug delivery are discussed. The possibility of using pH-sensitive surfactants for endosome disruption could hold great promise for intracellular drug delivery systems in future therapeutic applications. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Design of novel multifunctional targeting nano-carrier drug delivery system based on CD44 receptor and tumor microenvironment pH condition.

PubMed

Chen, Daquan; Lian, Shengnan; Sun, Jingfang; Liu, Zongliang; Zhao, Feng; Jiang, Yongtao; Gao, Mingming; Sun, Kaoxiang; Liu, Wanhui; Fu, Fenghua

2016-01-01

In this study, to develop a multifunctional targeting nano-carrier drug delivery system for cancer therapy, the novel pH-sensitive ketal based oligosaccharides of hyaluronan (oHA) conjugates were synthesized by chemical conjugation of hydrophobic menthone 1,2-glycerol ketal (MGK) to the backbone of oHA with the histidine as the linker of proton sponge effect. The multifunctional oHA conjugates, oHA-histidine-MGK (oHM) carried the pH-sensitive MGK as hydrophobic moieties and oHA as the target of CD44 receptor. The oHM could self-assemble to nano-sized spherical shape with the average diameters of 128.6 nm at pH 7.4 PBS conditions. The oHM nanoparticles (oHMN) could release encapsulated curcumin (Cur) with 82.6% at pH 5.0 compared with 49.3% at pH 7.4. The results of cytotoxicity assay indicated that encapsulated Cur in oHMN (Cur-oHMN) were stable and have less toxicity compared to Cur suspension. The anti-tumor efficacy in vivo suggested that Cur-oHMN suppressed tumor growth most efficiently. These results present the promising potential of oHMN as a stable and effective nano-sized pH-sensitive drug delivery system for cancer treatment.

Indications of 24-h esophageal pH monitoring, capsule pH monitoring, combined pH monitoring with multichannel impedance, esophageal manometry, radiology and scintigraphy in gastroesophageal reflux disease?

PubMed

Vardar, Rukiye; Keskin, Muharrem

2017-12-01

Ambulatory esophageal pH monitoring is an essential method in patients exhibiting signs of non-erosive reflux disease (NERD) to make an objective diagnosis. Intra-esophageal pH monitoring is important in patients who are non-responsive to medications and in those with extraesophageal symptoms, particularly in NERD, before surgical interventions. With the help of the wireless capsule pH monitoring, measurements can be made under more physiological conditions as well as longer recordings can be performed because the investigation can be better tolerated by patients. Ambulatory esophageal pH monitoring can be detected within normal limits in 17%-31.4% of the patients with endoscopic esophagitis; therefore, normal pH monitoring cannot exclude the diagnosis of gastroesophageal reflux disease (GERD). Multi-channel intraluminal impedance pH (MII-pH) technology have been developed and currently the most sensitive tool to evaluate patients with both typical and atypical reflux symptoms. The sensitivity of a pH catheter test is 58% for the detection of acid reflux compared with MII-pH monitoring; further, its sensitivity is 28% for the detection of weak acid reflux compared with MII-pH monitoring. By adding impedance to pH catheter in patients with reflux symptoms, particularly in those receiving PPIs, it has been demonstrated that higher rates of diagnoses and symptom analyses can be obtained than those using only pH catheter. Esophageal manometry is used in the evaluation of patients with functional dysphagia and unexplained noncardiac chest pain and prior to antireflux surgery. The use of esophageal manometry is suitable for the detection of esophageal motor patterns and extreme motor abnormalities (e.g., achalasia and extreme hypomotility). Esophageal manometry and ambulatory pH monitoring are often used in assessments prior to laparoscopic antireflux surgery and in patients with reflux symptoms refractory to medical treatment. Although the esophageal motility is predominantly normal in patients with non-acid reflux, ineffective esophageal motility is often monitored in patients with acid reflux. In the literature, there are contradictory and an insufficient number of studies regarding radiological methods for the diagnosis of GERD. There are inconsistent values for sensitivity and specificity among the barium studies. There are inadequate studies in the literature involving scintigraphic examinations in the diagnosis of GERD, and a majority of existing studies have been conducted in the pediatric group. The results of a few studies do not provide sufficient contribution toward the implementation in clinical practice.

Nanoparticle assembled microcapsules for application as pH and ammonia sensor.

PubMed

Amali, Arlin Jose; Awwad, Nour H; Rana, Rohit Kumar; Patra, Digambara

2011-12-05

The encapsulation of molecular probes in a suitable nanostructured matrix can be exploited to alter their optical properties and robustness for fabricating efficient chemical sensors. Despite high sensitivity, simplicity, selectivity and cost effectiveness, the photo-destruction and photo-bleaching are the serious concerns while utilizing molecular probes. Herein we demonstrate that hydroxy pyrene trisulfonate (HPTS), a pH sensitive molecular probe, when encapsulated in a microcapsule structure prepared via the assembly of silica nanoparticles mediated by poly-L-lysine and trisodium citrate, provides a robust sensing material for pH sensing under the physiological conditions. The temporal evolution under continuous irradiation indicates that the fluorophore inside the silica microcapsule is extraordinarily photostable. The fluorescence intensity alternation at dual excitation facilitates for a ratiometic sensing of the pH, however, the fluorescence lifetime is insensitive to hydrogen ion concentration. The sensing scheme is found to be robust, fast and simple for the measurement of pH in the range 5.8-8.0, and can be successfully applied for the determination of ammonia in the concentration range 0-1.2 mM, which is important for aquatic life and the environment. Copyright © 2011 Elsevier B.V. All rights reserved.

The sensitivity of particle pH to NH3: Can high NH3 cause London Fog conditions?

NASA Astrophysics Data System (ADS)

Weber, R. J.; Guo, H.; Nenes, A.

2017-12-01

High ammonia emissions from agriculture or other sources have been suggested to elevate ambient particle pH levels to near neutral acidity (pH=7), a condition that promotes rapid SO2 oxidation by NO2 to form aerosol sulfate concentration consistent with "London fog" levels. This mechanism has been used to explain pollution haze events in China. Predicted pH for locations in the US and Europe show fine particles are highly acidic with pH typically less than 2. The results are consistent with measured ammonia and nitric acid gas-particle partitioning, validating predicted pH levels. Using these data sets from representative sites around the world we conduct a thermodynamic analysis of aerosol pH and its sensitivity to ammonia levels. We find that particle pH, regardless of ammonia levels, is always acidic even for the unusually high ammonia levels found in highly polluted Asian cities, Beijing (pH=4.5) and Xi'an (pH=5), locations where sulfate production from NOx is proposed. These results indicate that sulfur dioxide oxidation through a NO2-mediated pathway is not likely in China, nor any other region of the world (e.g., US, Mediterranean) since the fine aerosol is consistently acidic. The mildly acidic conditions would, however, permit rapid oxidation of sulfur dioxide through transition metal chemistry. The limited alkalinity from the carbonate buffer in dust and seasalt can provide the only likely set of conditions where NO2-mediated oxidation of SO2 outcompetes with other well-established pathways.

pH Sensitive Microcapsules for Delivery of Corrosion Inhibitors

NASA Technical Reports Server (NTRS)

Li, Wenyan; Calle, Luz M.

2006-01-01

A considerable number of corrosion problems can be solved by coatings. However, even the best protective coatings can fail by allowing the slow diffusion of oxygen and moisture to the metal surface. Corrosion accelerates when a coating delaminates. Often, the problems start when microscopic nicks or pits on the surface develop during manufacturing or through wear and tear. This problem can be solved by the incorporation of a self-healing function into the coating. Several new concepts are currently under development to incorporate this function into a coating. Conductive polymers, nanoparticles, and microcapsules are used to release corrosion-inhibiting ions at a defect site. The objective of this investigation is to develop a smart coating for the early detection and inhibition of corrosion. The dual function of this new smart coating system is performed by pH-triggered release microcapsules. The microcapsules can be used to deliver healing agents to terminate the corrosion process at its early stage or as corrosion indicators by releasing dyes at the localized corrosion sites. The dyes can be color dyes or fluorescent dyes, with or without pH sensitivity. Microcapsules were formed through the interfacial polymerization process. The average size of the microcapsules can be adjusted from 1 to 100 micron by adjusting the emulsion formula and the microcapsule forming conditions. A typical microcapsule size is around 10 microns with a narrow size distribution. The pH sensitivity of the microcapsule can also be controlled by adjusting the emulsion formula and the polymerization reaction time. Both corrosion indicator (pH indicator) and corrosion inhibitor containing microcapsules were formed and incorporated into paint systems. Test panels of selected steels and aluminum alloys were painted using these paints. Testing of compatibility between the microcapsule system and different paint systems are in progress. Initial experiments with the microcapsule containing paint show visible color changes at induced corrosion sites and improvement of corrosion protection. Further investigation of the performance of the coating using electrochemical techniques and long term exposure are currently underway.

pH-Triggered Echogenicity and Contents Release from Liposomes

PubMed Central

2015-01-01

Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%). PMID:25271780

pH-triggered echogenicity and contents release from liposomes.

PubMed

Nahire, Rahul; Hossain, Rayat; Patel, Rupa; Paul, Shirshendu; Meghnani, Varsha; Ambre, Avinash H; Gange, Kara N; Katti, Kalpana S; Leclerc, Estelle; Srivastava, D K; Sarkar, Kausik; Mallik, Sanku

2014-11-03

Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%).

Sensitivity of sea urchin fertilization to pH varies across a natural pH mosaic.

PubMed

Kapsenberg, Lydia; Okamoto, Daniel K; Dutton, Jessica M; Hofmann, Gretchen E

2017-03-01

In the coastal ocean, temporal fluctuations in pH vary dramatically across biogeographic ranges. How such spatial differences in pH variability regimes might shape ocean acidification resistance in marine species remains unknown. We assessed the pH sensitivity of the sea urchin Strongylocentrotus purpuratus in the context of ocean pH variability. Using unique male-female pairs, originating from three sites with similar mean pH but different variability and frequency of low pH (pH T  ≤ 7.8) exposures, fertilization was tested across a range of pH (pH T 7.61-8.03) and sperm concentrations. High fertilization success was maintained at low pH via a slight right shift in the fertilization function across sperm concentration. This pH effect differed by site. Urchins from the site with the narrowest pH variability regime exhibited the greatest pH sensitivity. At this site, mechanistic fertilization dynamics models support a decrease in sperm-egg interaction rate with decreasing pH. The site differences in pH sensitivity build upon recent evidence of local pH adaptation in S. purpuratus and highlight the need to incorporate environmental variability in the study of global change biology.

A systematic study of the effect of low pH acid treatment on anti-drug antibodies specific for a domain antibody therapeutic: Impact on drug tolerance, assay sensitivity and post-validation method assessment of ADA in clinical serum samples.

PubMed

Kavita, Uma; Duo, Jia; Crawford, Sean M; Liu, Rong; Valcin, Joan; Gleason, Carol; Dong, Huijin; Gadkari, Snaehal; Dodge, Robert W; Pillutla, Renuka C; DeSilva, Binodh S

2017-09-01

We developed a homogeneous bridging anti-drug antibody (ADA) assay on an electro chemiluminescent immunoassay (ECLIA) platform to support the immunogenicity evaluation of a dimeric domain antibody (dAb) therapeutic in clinical studies. During method development we evaluated the impact of different types of acid at various pH levels on polyclonal and monoclonal ADA controls of differing affinities and on/off rates. The data shows for the first time that acids of different pH can have a differential effect on ADA of various affinities and this in turn impacts assay sensitivity and drug tolerance as defined by these surrogate controls. Acid treatment led to a reduction in signal of intermediate and low affinity ADA, but not high affinity or polyclonal ADA. We also found that acid pretreatment is a requisite for dissociation of drug bound high affinity ADA, but not for low affinity ADA-drug complexes. Although we were unable to identify an acid that would allow a 100% retrieval of ADA signal post-treatment, use of glycine pH3.0 enabled the detection of low, intermediate and high affinity antibodies (Abs) to various extents. Following optimization, the ADA assay method was validated for clinical sample analysis. Consistencies within various parameters of the clinical data such as dose dependent increases in ADA rates and titers were observed, indicating a reliable ADA method. Pre- and post-treatment ADA negative or positive clinical samples without detectable drug were reanalyzed in the absence of acid treatment or presence of added exogenous drug respectively to further assess the effectiveness of the final acid treatment procedure. The overall ADA results indicate that assay conditions developed and validated based on surrogate controls sufficed to provide a reliable clinical data set. The effect of low pH acid treatment on possible pre-existing ADA or soluble multimeric target in normal human serum was also evaluated, and preliminary data indicate that acid type and pH also affect drug-specific signal differentially in individual samples. The results presented here represent the most extensive analyses to date on acid treatment of a wide range of ADA affinities to explore sensitivity and drug tolerance issues. They have led to a refinement of our current best practices for ADA method development and provide a depth of data to interrogate low pH mediated immune complex dissociation. Copyright © 2017 Elsevier B.V. All rights reserved.

The diagnostic value of gastroesophageal reflux disease (GERD) symptoms and detection of pepsin and bile acids in bronchoalveolar lavage fluid and exhaled breath condensate for identifying lung transplantation patients with GERD-induced aspiration.

PubMed

Reder, Nicholas P; Davis, Christopher S; Kovacs, Elizabeth J; Fisichella, P Marco

2014-06-01

Gastroesophageal reflux disease (GERD) is thought to lead to aspiration and bronchiolitis obliterans syndrome after lung transplantation. Unfortunately, the identification of patients with GERD who aspirate still lacks clear diagnostic indicators. The authors hypothesized that symptoms of GERD and detection of pepsin and bile acids in the bronchoalveolar lavage fluid (BAL) and exhaled breath condensate (EBC) are effective for identifying lung transplantation patients with GERD-induced aspiration. From November 2009 to November 2010, 85 lung transplantation patients undergoing surveillance bronchoscopy were prospectively enrolled. For these patients, self-reported symptoms of GERD were correlated with levels of pepsin and bile acids in BAL and EBC and with GERD status assessed by 24-h pH monitoring. The sensitivity and specificity of pepsin and bile acids in BAL and EBC also were compared with the presence of GERD in 24-h pH monitoring. The typical symptoms of GERD (heartburn and regurgitation) had modest sensitivity and specificity for detecting GERD and aspiration. The atypical symptoms of GERD (aspiration and bronchitis) showed better identification of aspiration as measured by detection of pepsin and bile acids in BAL. The sensitivity and specificity of pepsin in BAL compared with GERD by 24-h pH monitoring were respectively 60 and 45 %, whereas the sensitivity and specificity of bile acids in BAL were 67 and 80 %. These data indicate that the measurement of pepsin and bile acids in BAL can provide additional data for identifying lung transplantation patients at risk for GERD-induced aspiration compared with symptoms or 24-h pH monitoring alone. These results support a diagnostic role for detecting markers of aspiration in BAL, but this must be validated in larger studies.

Identification of Rhizobium phaseoli Strains That Are Tolerant or Sensitive to Soil Acidity

PubMed Central

Lowendorf, Henry S.; Alexander, Martin

1983-01-01

A study was conducted to determine whether the survival of Rhizobium phaseoli in acid soils could be predicted on the basis of the tolerance of the organism to acidity in culture. Of 16 strains tested, all grew in culture at pH 4.6, but only those that grew at pH 3.8 survived in soils having pH values of 4.1 to 4.6. Strains that tolerated the lowest pH values in culture were tolerant of the highest aluminum concentrations. In one acid soil, an acid-tolerant strain was unable to survive in numbers greater than 100/g, but the poor survival was not related to the level of extractable aluminum or manganese in the soil. Reproduction of an acid-tolerant strain of R. phaseoli was enhanced in the rhizosphere of Phaseolus vulgaris in both acid and limed soils, but stimulation of an acid-sensitive strain by the plant occurred only in the limed soil. These results indicate that cultural tests can be used to predict the ability of R. phaseoli to survive in acid soil. PMID:16346239

The synthesis and application of heparin-based smart drug carrier.

PubMed

Li, Qingxuan; Gan, Lu; Tao, Hong; Wang, Qian; Ye, Lin; Zhang, Aiying; Feng, Zengguo

2016-04-20

Heparin based polymer drug which could self-assemble into sphere micelle in water was firstly prepared by grafting paclitaxel (PTX) into the hydroxyl of heparin via aconitic bond as pH sensitive spacer. Positive charged drug DOX·HCl and cationic folic acid (CFA) can be further loaded into the polymer drug via electrostatic interaction in aqueous solution so as to prepare smart drug carrier. The drug carrier was able to release more PTX and DOX at pH 4.8 than that at pH 7.4, exhibiting pH sensitivity for two drugs. Furthermore, tumor cell cytotoxicity test proved it possessed significant cytotoxicity against tumor cells MDA-MB-231 as well as its active tumor targeting ability resulting from the loading of CFA. Cellular uptake and intracellular distribution were further revealed by confocal laser scanning microscopy (CLSM). In conclusion, this paper not only provided a simple strategy but also indicated heparin is a versatile platform for the design of smart drug carrier. The as-prepared drug carrier also showed promising potential in chemotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dual functional rhodium oxide nanocorals enabled sensor for both non-enzymatic glucose and solid-state pH sensing.

PubMed

Dong, Qiuchen; Huang, Yikun; Song, Donghui; Wu, Huixiang; Cao, Fei; Lei, Yu

2018-07-30

Both pH-sensitive and glucose-responsive rhodium oxide nanocorals (Rh 2 O 3 NCs) were synthesized through electrospinning followed by high-temperature calcination. The as-prepared Rh 2 O 3 NCs were systematically characterized using various advanced techniques including scanning electron microscopy, X-ray powder diffraction and Raman spectroscopy, and then employed as a dual functional nanomaterial to fabricate a dual sensor for both non-enzymatic glucose sensing and solid-state pH monitoring. The sensing performance of the Rh 2 O 3 NCs based dual sensor toward pH and glucose was evaluated using open circuit potential, cyclic voltammetry and amperometric techniques, respectively. The results show that the as-prepared Rh 2 O 3 NCs not only maintain accurate and reversible pH sensitivity of Rh 2 O 3 , but also demonstrate a good electrocatalytic activity toward glucose oxidation in alkaline medium with a sensitivity of 11.46 μA mM -1 cm -2 , a limit of detection of 3.1 μM (S/N = 3), and a reasonable selectivity against various interferents in non-enzymatic glucose detection. Its accuracy in determining glucose in human serum samples was further demonstrated. These features indicate that the as-prepared Rh 2 O 3 NCs hold great promise as a dual-functional sensing material in the development of a high-performance sensor forManjakkal both solid-state pH and non-enzymatic glucose sensing. Copyright © 2018 Elsevier B.V. All rights reserved.

The enhanced cyan fluorescent protein: a sensitive pH sensor for fluorescence lifetime imaging.

PubMed

Poëa-Guyon, Sandrine; Pasquier, Hélène; Mérola, Fabienne; Morel, Nicolas; Erard, Marie

2013-05-01

pH is an important parameter that affects many functions of live cells, from protein structure or function to several crucial steps of their metabolism. Genetically encoded pH sensors based on pH-sensitive fluorescent proteins have been developed and used to monitor the pH of intracellular compartments. The quantitative analysis of pH variations can be performed either by ratiometric or fluorescence lifetime detection. However, most available genetically encoded pH sensors are based on green and yellow fluorescent proteins and are not compatible with multicolor approaches. Taking advantage of the strong pH sensitivity of enhanced cyan fluorescent protein (ECFP), we demonstrate here its suitability as a sensitive pH sensor using fluorescence lifetime imaging. The intracellular ECFP lifetime undergoes large changes (32 %) in the pH 5 to pH 7 range, which allows accurate pH measurements to better than 0.2 pH units. By fusion of ECFP with the granular chromogranin A, we successfully measured the pH in secretory granules of PC12 cells, and we performed a kinetic analysis of intragranular pH variations in living cells exposed to ammonium chloride.

Effect of process temperature, pH and suspended solids content upon pasteurization of a model agricultural waste during thermophilic aerobic digestion.

PubMed

Ugwuanyi, J O; Harvey, L M; McNeil, B

1999-09-01

Thermophilic aerobic digestion(TAD), or liquid composting, is a versatile new process for the treatment and stabilization of high strength wastes of liquid or, perhaps more importantly, slurry consistency. The pattern of inactivation of various pathogenic and indicator organisms was studied using batch digestions under conditions that may be expected to be found in full-scale TAD processes. Rapid inactivation of test populations occurred within the first 10 min from the start of digestion. The inactivation rate was slightly lower when digestions were conducted below 60 degrees C. In some instances, a 'tail' was apparent, possibly indicating the survival of relatively resistant sub-populations particularly in the case of Serratia marcescens and Enterococcus faecalis, or of clumping or attachment of cells to particulate materials. The effect of pH on the inactivation of the test populations depended on the temperature of digestion, but varied with the test population. At 55 degrees C Escherichia coli was more sensitive to temperature effects at pH 7 than at pH 8, but was more sensitive at pH 8, 60 degrees C. The reverse was the case at 60 degrees C for Ent. faecalis. An increase in the solid content of the digesting waste caused a progressive increase in the protection of test organisms from thermal inactivation. Challenging a TAD process with test strains allows (via estimation of D-values) a quantification of the cidal effects of such processes, with a view to manipulating process variables to enhance such effects.

Dual pH-responsive and CD44 receptor targeted multifunctional nanoparticles for anticancer intracellular delivery

NASA Astrophysics Data System (ADS)

Chen, Daquan; Sun, Jingfang; Lian, Shengnan; Liu, Zongliang; Sun, Kaoxiang; Liu, Wanhui; Wu, Zimei; Zhang, Qiang

2014-11-01

In this article, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. The polymeric mPEG-Chitosan-Ketal (PCK) carrying pH-sensitive ketal group as hydrophobic moieties and PEG group as hydrophilic moieties were synthesized. The two pH-sensitive ketal derivatives were employed to fabricate nanoparticles for anti-tumor drug delivery. The oHM-PCK nanoparticles (oHPN) can spontaneously self-assemble into mixed micellar structure with nano-sized spherical shape of 100-200 nm at pH 7.4 PBS conditions. The oHPN could release encapsulated curcumin with 92.6 % at pH 5.0 compared with 55.3 % at pH 7.4. The results of cytotoxicity assay indicated that encapsulated curcumin in oHPN (Cur-oHPN) have less toxicity compared to curcumin suspension. The anti-tumor efficacy in vivo suggested that Cur-oHPN suppressed tumor growth most efficiently. These results present the promising potential of oHPN as an effective nano-sized pH-sensitive drug delivery system for intracellular delivery.

Air pollution indications and growth of spruce and pine near a sulfite plant

Treesearch

Lars Westman

1976-01-01

A preliminary study has been made around a sulfite plant in the north of Sweden. The emission of sulfur dioxide increased considerably in 1950 as a consequence of the introduction of lye-burning. Using the pH in pine bark and two common lichen epiphytes as indicators, the resistant Parmelia physodes and the very sensitive Alectoria implexa...

Regional Monitoring of Acidic Lakes and Streams

EPA Pesticide Factsheets

This asset provides data on the acid-base status of lakes and streams. Key chemical indicators measured include: sulfate, nitrate, ammonium, chloride, Acid Neutralizing Capacity (ANC), pH, base cations, dissolved organic carbon (DOC), total aluminum. TIME and LTM are part of EPA's Environmental Monitoring and Assessment Program (EMAP). Long-term monitoring of the acid-base status (pH, ANC, SO4, NO3, NH4, DOC, base cations, Al) in lakes and streams. Monitoring is conducted in acid sensitive regions of the Eastern U.S.

Bacterially produced Pt-GFP as ratiometric dual-excitation sensor for in planta mapping of leaf apoplastic pH in intact Avena sativa and Vicia faba.

PubMed

Geilfus, Christoph-Martin; Mühling, Karl H; Kaiser, Hartmut; Plieth, Christoph

2014-01-01

Ratiometric analysis with H(+)-sensitive fluorescent sensors is a suitable approach for monitoring apoplastic pH dynamics. For the acidic range, the acidotropic dual-excitation dye Oregon Green 488 is an excellent pH sensor. Long lasting (hours) recordings of apoplastic pH in the near neutral range, however, are more problematic because suitable pH indicators that combine a good pH responsiveness at a near neutral pH with a high photostability are lacking. The fluorescent pH reporter protein from Ptilosarcus gurneyi (Pt-GFP) comprises both properties. But, as a genetically encoded indicator and expressed by the plant itself, it can be used almost exclusively in readily transformed plants. In this study we present a novel approach and use purified recombinant indicators for measuring ion concentrations in the apoplast of crop plants such as Vicia faba L. and Avena sativa L. Pt-GFP was purified using a bacterial expression system and subsequently loaded through stomata into the leaf apoplast of intact plants. Imaging verified the apoplastic localization of Pt-GFP and excluded its presence in the symplast. The pH-dependent emission signal stood out clearly from the background. PtGFP is highly photostable, allowing ratiometric measurements over hours. By using this approach, a chloride-induced alkalinizations of the apoplast was demonstrated for the first in oat. Pt-GFP appears to be an excellent sensor for the quantification of leaf apoplastic pH in the neutral range. The presented approach encourages to also use other genetically encoded biosensors for spatiotemporal mapping of apoplastic ion dynamics.

pH regulation of the kinetic stability of the lipase from Thermomyces lanuginosus.

PubMed

Wang, H; Andersen, K K; Sehgal, P; Hagedorn, J; Westh, P; Borch, K; Otzen, D E

2013-01-08

Thermomyces lanuginosus lipase (TlL) is a kinetically stable protein, resistant toward both denaturation and refolding in the presence of the ionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant decyl maltoside (DecM). We investigate the pH dependence of this kinetic stability. At pH 8, TlL remains folded and enzymatically active at multimillimolar surfactant concentrations but fails to refold from the acid urea-denatured state at submillimolar concentrations of SDS and DecM, indicating a broad concentration range of kinetic trapping or hysteresis. At pH 8, very few SDS molecules bind to TlL. The hysteresis SDS concentration range shrinks when moving to pH 4-6; in this pH range, SDS binds as micellelike clusters. Although hysteresis can be eliminated by reducing disulfide bonds, destabilizing the native state, and lowering the unfolding activation barrier, SDS sensitivity is not directly linked to intrinsic kinetic stability [its resistance to the general chemical denaturant guanidinium chloride (GdmCl)], because TlL unfolds more slowly in GdmCl at pH 6.0 than at pH 8.0. However, the estimated net charge drops from approximately -12 to approximately -5 between pH 8 and 6. SDS denatures TlL at pH 6.0 by nucleating via a critical number of bound SDS molecules on the surface of native TlL to form clusters. These results imply that SDS sensitivity is connected to the availability of appropriately charged regions on the protein. We suggest that conformational rigidity is a necessary but not sufficient feature of SDS resistance, because this has to be combined with sufficient negative electrostatic potential to avoid extensive SDS binding.

Study of the pH-sensitive mechanism of tumor-targeting liposomes.

PubMed

Fan, Yang; Chen, Cong; Huang, Yiheng; Zhang, Fang; Lin, Guimei

2017-03-01

Currently, the phosphatidylethanolamine-based, pH-sensitive, liposome drug-delivery system has been widely developed for efficient, targeted cancer therapy. However, the mechanism of pH sensitivity was unclear; it is a main obstacle in controlling the preparation of pH-sensitive liposomes (PSLs).Therefore, our research is aimed at clarifying the pH-response mechanism of the various molecules that compose liposomes. We chose the small pH-sensitive molecules oleic acid (OA), linoleic acid (LA) and cholesteryl hemisuccinate (CHEMS) and the fundamental lipids cholesterol and phosphatidylethanolamine (PE) as test molecules. The PSLs were prepared using the thin-film hydration method and characterized in detail at various pH values (pH 5.0, 6.0 and 7.4), including particle size, ζ-potential, drug encapsulation efficiency and drug loading. The surface structure was observed by transmission electron microscopy (TEM), and the electrical conductivity of the liposome dispersion was also tested. The calorimetric analysis was conducted by Nano-differential scanning calorimetry (Nano-DSC). The in vitro drug release profile showed that PSLs exhibit good pH sensitivity. At neutral pH, the particle size was approximately 150nm, and it dramatically increased at pH 5.0. The ζ-potential increased as the pH decreased. The Nano-DSC results showed that cholesterol and CHEMS can both increase the stability and phase transfer temperature of PSLs. Conductivity increased to a maximum at pH 5.0 and was rather low at pH 7.4. In conclusion, results show that the three kinds of liposomes have pH responsive release characteristics in acidic pH. The OA-PSLs have a pH sensitive point of 5. Since CHEMS has a cholesterol-like structure, it can stabilizes the phospholipid bilayer under neutral conditions as shown in the Nano-DSC data, and because it has a special steroidal rigid structure, it exhibits better pH response characteristics under acidic conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Ratiometric photoluminescence sensing based on Ti3C2 MXene quantum dots as an intracellular pH sensor.

PubMed

Chen, Xu; Sun, Xueke; Xu, Wen; Pan, Gencai; Zhou, Donglei; Zhu, Jinyang; Wang, He; Bai, Xue; Dong, Biao; Song, Hongwei

2018-01-18

Intracellular pH sensing is of importance and can be used as an indicator for monitoring the evolution of various diseases and the health of cells. Here, we developed a new class of surface-functionalized MXene quantum dots (QDs), Ti 3 C 2 , by the sonication cutting and hydrothermal approach and further explored their intracellular pH sensing. The functionalized Ti 3 C 2 QDs exhibit bright excitation-dependent blue photoluminescence (PL) originating from the size effect and surface defects. Meanwhile, Ti 3 C 2 QDs demonstrate a high PL response induced by the deprotonation of the surface defects. Furthermore, combining the highly pH sensitive Ti 3 C 2 QDs with the pH insensitive [Ru(dpp) 3 ]Cl 2 , we developed a ratiometric pH sensor to quantitatively monitor the intracellular pH values. These novel MXene quantum dots can serve as a promising platform for developing practical fluorescent nanosensors.

Evaluation of citric acid and GDL in the recovery at different pH levels of Clostridium sporogenes PA 3679 spores subjected to HTST treatment conditions.

PubMed

Silla Santos, M H; Torres Zarzo, J

1996-04-01

Spores of Clostridium sporogenes PA 3679 were treated at different temperatures (121, 126, 130 and 135 degrees C) in white asparagus purée (pH 5.8) and acidified with glucono-delta-lactone (GDL) and citric acid to pH levels of 5.5, 5.0 and 4.5. Afterwards, the spores were recovered in MPA3679 medium in various conditions: unacidified (pH 7.5), acidified with GDL (500 ppm) and acidified with citric acid (500 and 250 ppm) to pH levels of 6.5, 6.0 and 5.0. The results indicated that the pH levels, concentration and type of acid used act synergistically rather than independently. Citric acid has a stronger inhibiting effect than GDL on the recovery of C. sporogenes PA 3679 spores. At the higher heat treatments (130 and 135 degrees C) the major injury on the spores sensitize more than against the acids and low pH values.

Preparation of a novel pH optical sensor using orange (II) based on agarose membrane as support.

PubMed

Heydari, Rouhollah; Hosseini, Mohammad; Amraei, Ahmadreza; Mohammadzadeh, Ali

2016-04-01

A novel and cost effective optical pH sensor was prepared using covalent immobilization of orange (II) indicator on the agarose membrane as solid support. The fabricated optical sensor was fixed into a sample holder of a spectrophotometer instrument for pH monitoring. Variables affecting sensor performance including pH of dye bonding to agarose membrane and dye concentration were optimized. The sensor responds to the pH changes in the range of 3.0-10.0 with a response time of 2.0 min and appropriate reproducibility (RSD ≤ 0.9%). No significant variation was observed on sensor response after increasing the ionic strength in the range of 0.0-0.5M of sodium chloride. Determination of pH using the proposed optical sensor is quick, simple, inexpensive, selective and sensitive in the pH range of 3.0-10.0. Copyright © 2015 Elsevier B.V. All rights reserved.

Vulnerability of the calcifying larval stage of the Antarctic sea urchin Sterechinus neumayeri to near-future ocean acidification and warming.

PubMed

Byrne, Maria; Ho, Melanie A; Koleits, Lucas; Price, Casandra; King, Catherine K; Virtue, Patti; Tilbrook, Bronte; Lamare, Miles

2013-07-01

Stenothermal polar benthic marine invertebrates are highly sensitive to environmental perturbations but little is known about potential synergistic effects of concurrent ocean warming and acidification on development of their embryos and larvae. We examined the effects of these stressors on development to the calcifying larval stage in the Antarctic sea urchin Sterechinus neumayeri in embryos reared in present and future (2100+) ocean conditions from fertilization. Embryos were reared in 2 temperature (ambient: -1.0 °C, + 2 °C : 1.0 °C) and 3 pH (ambient: pH 8.0, -0.2-0.4 pH units: 7.8,7.6) levels. Principle coordinates analysis on five larval metrics showed a significant effect of temperature and pH on the pattern of growth. Within each temperature, larvae were separated by pH treatment, a pattern primarily influenced by larval arm and body length. Growth was accelerated by temperature with a 20-28% increase in postoral (PO) length at +2 °C across all pH levels. Growth was strongly depressed by reduced pH with a 8-19% decrease in PO length at pH 7.6-7.8 at both temperatures. The boost in growth caused by warming resulted in larvae that were larger than would be observed if acidification was examined in the absence of warming. However, there was no significant interaction between these stressors. The increase in left-right asymmetry and altered body allometry indicated that decreased pH disrupted developmental patterning and acted as a teratogen (agent causing developmental malformation). Decreased developmental success with just a 2 °C warming indicates that development in S. neumayeri is particularly sensitive to increased temperature. Increased temperature also altered larval allometry. Altered body shape impairs swimming and feeding in echinoplutei. In the absence of adaptation, it appears that the larval phase may be a bottleneck for survivorship of S. neumayeri in a changing ocean in a location where poleward migration to escape inhospitable conditions is not possible. © 2013 Blackwell Publishing Ltd.

Medial extrusion of the posterior segment of medial meniscus is a sensitive sign for posterior horn tears.

PubMed

Ohishi, Tsuyoshi; Suzuki, Daisuke; Yamamoto, Kazufumi; Banno, Tomohiro; Shimizu, Yuta; Matsuyama, Yukihiro

2014-01-01

To evaluate medial extrusion of the posterior segment of the medial meniscus in posterior horn tears. This study enrolled 72 patients without medial meniscal tears (group N), 72 patients with medial meniscal tears without posterior horn tears (group PH-), 44 patients with posterior horn tears of the medial meniscus (group PH+). All meniscal tears were confirmed by arthroscopy. Medial extrusion of the middle segment and the posterior segment was measured on coronal MRIs. Extrusions of both middle and posterior segments in groups PH- and PH+ (middle segment; 2.94±1.51 mm for group PH- and 3.75±1.69 mm for group PH+, posterior segment; 1.85±1.82 mm for group PH- and 4.59±2.74 mm for group PH+) were significantly larger than those in group N (middle segment; 2.04±1.20, posterior segment; 1.21±1.86). Both indicators of extrusion in group PH+ were larger than those in group PH-. In the early OA category, neither middle nor posterior segment in group PH- extruded more than in group N. However, only the posterior segment in group PH+ extruded significantly more than in group N. Multiple lineal regression analyses revealed that posterior segment extrusion was strongly correlated with the posterior horn tears (p<0.001) among groups PH- and PH+. The newly presented indicator for extrusion of the posterior segment of the medial meniscus is associated with posterior horn tears in comparison with the extrusion of the middle segment, especially in the early stages of osteoarthritis. Level II--Diagnostic Study. Copyright © 2013 Elsevier B.V. All rights reserved.

TASK-2 Channels Contribute to pH Sensitivity of Retrotrapezoid Nucleus Chemoreceptor Neurons

PubMed Central

Wang, Sheng; Benamer, Najate; Zanella, Sébastien; Kumar, Natasha N.; Shi, Yingtang; Bévengut, Michelle; Penton, David; Guyenet, Patrice G.; Lesage, Florian

2013-01-01

Phox2b-expressing glutamatergic neurons of the retrotrapezoid nucleus (RTN) display properties expected of central respiratory chemoreceptors; they are directly activated by CO2/H+ via an unidentified pH-sensitive background K+ channel and, in turn, facilitate brainstem networks that control breathing. Here, we used a knock-out mouse model to examine whether TASK-2 (K2P5), an alkaline-activated background K+ channel, contributes to RTN neuronal pH sensitivity. We made patch-clamp recordings in brainstem slices from RTN neurons that were identified by expression of GFP (directed by the Phox2b promoter) or β-galactosidase (from the gene trap used for TASK-2 knock-out). Whereas nearly all RTN cells from control mice were pH sensitive (95%, n = 58 of 61), only 56% of GFP-expressing RTN neurons from TASK-2−/− mice (n = 49 of 88) could be classified as pH sensitive (>30% reduction in firing rate from pH 7.0 to pH 7.8); the remaining cells were pH insensitive (44%). Moreover, none of the recorded RTN neurons from TASK-2−/− mice selected based on β-galactosidase activity (a subpopulation of GFP-expressing neurons) were pH sensitive. The alkaline-activated background K+ currents were reduced in amplitude in RTN neurons from TASK-2−/− mice that retained some pH sensitivity but were absent from pH-insensitive cells. Finally, using a working heart–brainstem preparation, we found diminished inhibition of phrenic burst amplitude by alkalization in TASK-2−/− mice, with apneic threshold shifted to higher pH levels. In conclusion, alkaline-activated TASK-2 channels contribute to pH sensitivity in RTN neurons, with effects on respiration in situ that are particularly prominent near apneic threshold. PMID:24107938

Graphene Oxide Based Nanocarrier Combined with a pH-Sensitive Tracer: A Vehicle for Concurrent pH Sensing and pH-Responsive Oligonucleotide Delivery.

PubMed

Hsieh, Chia-Jung; Chen, Yu-Cheng; Hsieh, Pei-Ying; Liu, Shi-Rong; Wu, Shu-Pao; Hsieh, You-Zung; Hsu, Hsin-Yun

2015-06-03

We chemically tuned the oxidation status of graphene oxide (GO) and constructed a GO-based nanoplatform combined with a pH-sensitive fluorescence tracer that is designed for both pH sensing and pH-responsive drug delivery. A series of GOs oxidized to distinct degrees were examined to optimize the adsorption of the model drug, poly dT30. We determined that highly oxidized GO was a superior drug-carrier candidate in vitro when compared to GOs oxidized to lesser degrees. In the cell experiment, the synthesized pH-sensitive rhodamine dye was first applied to monitor cellular pH; under acidic conditions, protonated rhodamine fluoresces at 588 nm (λex=561 nm). When the dT30-GO nanocarrier was introduced into cells, a rhodamine-triggered competition reaction occurred, and this led to the release of the oligonucleotides and the quenching of rhodamine fluorescence by GO. Our results indicate high drug loading (FAM-dT30/GO=25/50 μg/mL) and rapid cellular uptake (<0.5 h) of the nanocarrier which can potentially be used for targeted RNAi delivery to the acidic milieu of tumors.

Anionic pH-Sensitive Lipoplexes.

PubMed

Mignet, Nathalie; Scherman, Daniel

2017-01-01

To provide long circulating nanoparticles able to carry a gene to tumors, we have designed anionic pegylated lipoplexes which are pH sensitive. Anionic pegylated lipoplexes have been prepared from the combined formulation of cationic lipoplexes and pegylated anionic liposomes. The neutralization of the particle surface charge as a function of the pH was monitored by light scattering in order to determine the ratio between anionic and cationic lipids that would give pH sensitive complexes. This ratio has been optimized to form particles sensitive to pH change in the range 5.5-6.5. Compaction of DNA into these newly formed anionic complexes is checked by DNA accessibility to picogreen. The transfection efficiency and pH sensitive property of these formulations has been shown in vitro using bafilomycin, a vacuolar H + -ATPase inhibitor.

The in vivo pH of the extravascular space of the lung

PubMed Central

Effros, Richard M.; Chinard, Francis P.

1969-01-01

The partition of 5,5-dimethyloxazolidine-2,4-dione (DMO) and of 11 amines between the vascular and extravascular spaces of the lung has been determined by the multiple indicator dilution technique. Four amines (nicotine, pentylamine, quinine, and benzylamine) were found to have pH-sensitive tissue to blood concentration ratios. Of these, tritiated nicotine appears to be the nost satisfactory indicator of tissue pH and values for the pH of the pulmonary extravascular space (pHe) have been calculated from the nicotine data. At an arterial pH (pHart) between 7.38 and 7.43 pHe averaged 6.69 ±0.07. Changes in pHe usually paralleled but were consistently less than concomitant changes in pHart. Alterations in PCO2 at constant pHart regularly produced relatively small, parallel changes in extravascular hydrogen ion concentrations. Local alterations in tissue pH due to PCO2 changes are apparently buffered quite rapidly and the pHe of the lung seems more closely linked to pHart than the cellular pH of other tissues. DMO, guanidine, methylamine, morphine, and atropine were confined to the vascular volume during the first circulation and could not be used to measure tissue pH. Histamine appeared to be bound to a pH-insensitive site. The extravascular distributions of antipyrine and aniline were unresponsive to alterations in arterial pH, presumably because they are essentially uncharged at pH levels found in the lung. PMID:4898722

RuO2 pH Sensor with Super-Glue-Inspired Reference Electrode

PubMed Central

Wajrak, Magdalena; Alameh, Kamal

2017-01-01

A pH-sensitive RuO2 electrode coated in a commercial cyanoacrylate adhesive typically exhibits very low pH sensitivity, and could be paired with a RuO2 working electrode as a differential type pH sensor. However, such sensors display poor performance in real sample matrices. A pH sensor employing a RuO2 pH-sensitive working electrode and a SiO2-PVB junction-modified RuO2 reference electrode is developed as an alternative high-performance solution. This sensor exhibits a performance similar to that of a commercial glass pH sensor in some common sample matrices, particularly, an excellent pH sensitivity of 55.7 mV/pH, a hysteresis as low as 2.7 mV, and a drift below 2.2 mV/h. The developed sensor structure opens the way towards the development of a simple, cost effective, and robust pH sensor for pH analysis in various sample matrices. PMID:28878182

RuO₂ pH Sensor with Super-Glue-Inspired Reference Electrode.

PubMed

Lonsdale, Wade; Wajrak, Magdalena; Alameh, Kamal

2017-09-06

A pH-sensitive RuO₂ electrode coated in a commercial cyanoacrylate adhesive typically exhibits very low pH sensitivity, and could be paired with a RuO₂ working electrode as a differential type pH sensor. However, such sensors display poor performance in real sample matrices. A pH sensor employing a RuO₂ pH-sensitive working electrode and a SiO₂-PVB junction-modified RuO₂ reference electrode is developed as an alternative high-performance solution. This sensor exhibits a performance similar to that of a commercial glass pH sensor in some common sample matrices, particularly, an excellent pH sensitivity of 55.7 mV/pH, a hysteresis as low as 2.7 mV, and a drift below 2.2 mV/h. The developed sensor structure opens the way towards the development of a simple, cost effective, and robust pH sensor for pH analysis in various sample matrices.

Highly photostable near-infrared fluorescent pH indicators and sensors based on BF2-chelated tetraarylazadipyrromethene dyes.

PubMed

Jokic, Tijana; Borisov, Sergey M; Saf, Robert; Nielsen, Daniel A; Kühl, Michael; Klimant, Ingo

2012-08-07

In this study, a series of new BF(2)-chelated tetraarylazadipyrromethane dyes are synthesized and are shown to be suitable for the preparation of on/off photoinduced electron transfer modulated fluorescent sensors. The new indicators are noncovalently entrapped in polyurethane hydrogel D4 and feature absorption maxima in the range 660-710 nm and fluorescence emission maxima at 680-740 nm. Indicators have high molar absorption coefficients of ~80,000 M(-1) cm(-1), good quantum yields (up to 20%), excellent photostability and low cross-sensitivity to the ionic strength. pK(a) values of indicators are determined from absorbance and fluorescence measurements and range from 7 to 11, depending on the substitution pattern of electron-donating and -withdrawing functionalities. Therefore, the new indicators are suitable for exploitation and adaptation in a diverse range of analytical applications. Apparent pK(a) values in sensor films derived from fluorescence data show 0.5-1 pH units lower values in comparison with those derived from the absorption data due to Förster resonance energy transfer from protonated to deprotonated form. A dual-lifetime referenced sensor is prepared, and application for monitoring of pH in corals is demonstrated.

Brain tissue stiffness is a sensitive marker for acidosis.

PubMed

Holtzmann, Kathrin; Gautier, Hélène O B; Christ, Andreas F; Guck, Jochen; Káradóttir, Ragnhildur Thóra; Franze, Kristian

2016-09-15

Carbon dioxide overdose is frequently used to cull rodents for tissue harvesting. However, this treatment may lead to respiratory acidosis, which potentially could change the properties of the investigated tissue. Mechanical tissue properties often change in pathological conditions and may thus offer a sensitive generic readout for changes in biological tissues with clinical relevance. In this study, we performed force-indentation measurements with an atomic force microscope on acute cerebellar slices from adult rats to test if brain tissue undergoes changes following overexposure to CO2 compared to other methods of euthanasia. The pH significantly decreased in brain tissue of animals exposed to CO2. Concomitant with the drop in pH, cerebellar grey matter significantly stiffened. Tissue stiffening was reproduced by incubation of acute cerebellar slices in acidic medium. Tissue stiffness provides an early, generic indicator for pathophysiological changes in the CNS. Atomic force microscopy offers unprecedented high spatial resolution to detect such changes. Our results indicate that the stiffness particularly of grey matter strongly correlates with changes of the pH in the cerebellum. Furthermore, the method of tissue harvesting and preparation may not only change tissue stiffness but very likely also other physiologically relevant parameters, highlighting the importance of appropriate sample preparation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Post-deposition annealing temperature dependence TiO{sub 2}-based EGFET pH sensor sensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zulkefle, M. A., E-mail: alhadizulkefle@gmail.com; Rahman, R. A., E-mail: rohanieza.abdrahman@gmail.com; Yusoff, K. A., E-mail: khairul.aimi.yusof@gmail.com

EGFET pH sensor is one type of pH sensor that is used to measure and determine pH of a solution. The sensing membrane of EGFET pH sensor plays vital role in the overall performance of the sensor. This paper studies the effects of different annealing temperature of the TiO{sub 2} sensing membranes towards sensitivity of EGFET pH sensor. Sol-gel spin coating was chosen as TiO{sub 2} deposition techniques since it is cost-effective and produces thin film with uniform thickness. Deposited TiO{sub 2} thin films were then annealed at different annealing temperatures and then were connected to the gate of MOSFETmore » as a part of the EGFET pH sensor structure. The thin films now act as sensing membranes of the EGFET pH sensor and sensitivity of each sensing membrane towards pH was measured. From the results it was determined that sensing membrane annealed at 300 °C gave the highest sensitivity followed by sample annealed at 400 °C and 500 °C.« less

Abscission of flowers and floral organs is closely associated with alkalization of the cytosol in abscission zone cells

PubMed Central

Sundaresan, Srivignesh; Philosoph-Hadas, Sonia; Riov, Joseph; Belausov, Eduard; Kochanek, Betina; Tucker, Mark L.; Meir, Shimon

2015-01-01

In vivo changes in the cytosolic pH of abscission zone (AZ) cells were visualized using confocal microscopic detection of the fluorescent pH-sensitive and intracellularly trapped dye, 2’,7’-bis-(2-carboxyethyl)-5(and-6)-carboxyfluorescein (BCECF), driven by its acetoxymethyl ester. A specific and gradual increase in the cytosolic pH of AZ cells was observed during natural abscission of flower organs in Arabidopsis thaliana and wild rocket (Diplotaxis tenuifolia), and during flower pedicel abscission induced by flower removal in tomato (Solanum lycopersicum Mill). The alkalization pattern in the first two species paralleled the acceleration or inhibition of flower organ abscission induced by ethylene or its inhibitor 1-methylcyclopropene (1-MCP), respectively. Similarly, 1-MCP pre-treatment of tomato inflorescence explants abolished the pH increase in AZ cells and pedicel abscission induced by flower removal. Examination of the pH changes in the AZ cells of Arabidopsis mutants defective in both ethylene-induced (ctr1, ein2, eto4) and ethylene-independent (ida, nev7, dab5) abscission pathways confirmed these results. The data indicate that the pH changes in the AZ cells are part of both the ethylene-sensitive and -insensitive abscission pathways, and occur concomitantly with the execution of organ abscission. pH can affect enzymatic activities and/or act as a signal for gene expression. Changes in pH during abscission could occur via regulation of transporters in AZ cells, which might affect cytosolic pH. Indeed, four genes associated with pH regulation, vacuolar H+-ATPase, putative high-affinity nitrate transporter, and two GTP-binding proteins, were specifically up-regulated in tomato flower AZ following abscission induction, and 1-MCP reduced or abolished the increased expression. PMID:25504336

Large area graphene ion sensitive field effect transistors with tantalum pentoxide sensing layers for pH measurement at the Nernstian limit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fakih, Ibrahim, E-mail: ibrahim.fakih@mail.mcgill.ca; Sabri, Shadi; Szkopek, Thomas, E-mail: thomas.szkopek@mcgill.ca

2014-08-25

We have fabricated and characterized large area graphene ion sensitive field effect transistors (ISFETs) with tantalum pentoxide sensing layers and demonstrated pH sensitivities approaching the Nernstian limit. Low temperature atomic layer deposition was used to deposit tantalum pentoxide atop large area graphene ISFETs. The charge neutrality point of graphene, inferred from quantum capacitance or channel conductance, was used to monitor surface potential in the presence of an electrolyte with varying pH. Bare graphene ISFETs exhibit negligible response, while graphene ISFETs with tantalum pentoxide sensing layers show increased sensitivity reaching up to 55 mV/pH over pH 3 through pH 8. Applying themore » Bergveld model, which accounts for site binding and a Guoy-Chapman-Stern picture of the surface-electrolyte interface, the increased pH sensitivity can be attributed to an increased buffer capacity reaching up to 10{sup 14} sites/cm{sup 2}. ISFET response was found to be stable to better than 0.05 pH units over the course of two weeks.« less

Large area graphene ion sensitive field effect transistors with tantalum pentoxide sensing layers for pH measurement at the Nernstian limit

NASA Astrophysics Data System (ADS)

Fakih, Ibrahim; Sabri, Shadi; Mahvash, Farzaneh; Nannini, Matthieu; Siaj, Mohamed; Szkopek, Thomas

2014-08-01

We have fabricated and characterized large area graphene ion sensitive field effect transistors (ISFETs) with tantalum pentoxide sensing layers and demonstrated pH sensitivities approaching the Nernstian limit. Low temperature atomic layer deposition was used to deposit tantalum pentoxide atop large area graphene ISFETs. The charge neutrality point of graphene, inferred from quantum capacitance or channel conductance, was used to monitor surface potential in the presence of an electrolyte with varying pH. Bare graphene ISFETs exhibit negligible response, while graphene ISFETs with tantalum pentoxide sensing layers show increased sensitivity reaching up to 55 mV/pH over pH 3 through pH 8. Applying the Bergveld model, which accounts for site binding and a Guoy-Chapman-Stern picture of the surface-electrolyte interface, the increased pH sensitivity can be attributed to an increased buffer capacity reaching up to 1014 sites/cm2. ISFET response was found to be stable to better than 0.05 pH units over the course of two weeks.

Proton-sensing transistor systems for detecting ion leakage from plasma membranes under chemical stimuli.

PubMed

Imaizumi, Yuki; Goda, Tatsuro; Schaffhauser, Daniel F; Okada, Jun-Ichi; Matsumoto, Akira; Miyahara, Yuji

2017-03-01

The membrane integrity of live cells is routinely evaluated for cytotoxicity induced by chemical or physical stimuli. Recent progress in bioengineering means that high-quality toxicity validation is required. Here, we report a pH-sensitive transistor system developed for the continuous monitoring of ion leakage from cell membranes upon challenge by toxic compounds. Temporal changes in pH were generated with high reproducibility via periodic flushing of HepG2 cells on a gate insulator of a proton-sensitive field-effect transistor with isotonic buffer solutions with/without NH 4 Cl. The pH transients at the point of NH 4 Cl addition/withdrawal originated from the free permeation of NH 3 across the semi-permeable plasma membranes, and the proton sponge effect produced by the ammonia equilibrium. Irreversible attenuation of the pH transient was observed when the cells were subjected to a membrane-toxic reagent. Experiments and simulations proved that the decrease in the pH transient was proportional to the area of the ion-permeable pores on the damaged plasma membranes. The pH signal was correlated with the degree of hemolysis produced by the model reagents. The pH assay was sensitive to the formation of molecularly sized pores that were otherwise not measurable via detection of the leakage of hemoglobin, because the hydrodynamic radius of hemoglobin was greater than 3.1nm in the hemolysis assay. The pH transient was not disturbed by inherent ion-transporter activity. The ISFET assay was applied to a wide variety of cell types. The system presented here is fast, sensitive, practical and scalable, and will be useful for validating cytotoxins and nanomaterials. The plasma membrane toxicity and hemolysis are widely and routinely evaluated in biomaterials science and biomedical engineering. Despite the recent development of a variety of methods/materials for efficient gene/drug delivery systems to the cytosol, the methodologies for safety validation remain unchanged in many years while leaving some major issues such as sensitivity, accuracy, and fast response. The paper describes a new way of measuring the plasma membrane leakage in real time upon challenge by toxic reagents using a solid-state transistor that is sensitive to proton as the smallest indicator. Our system was reliable and was correlated to the results from hemolysis assay with advanced features in sensitivity, fast response, and wide applicability to chemical species. The downsizing and integration features of semiconductor fabrication technologies may realize cytotoxicity assays at the single-cell level in multi-parallel. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Sensitivity of endemic Snake River cutthroat trout to acidity and elevated aluminum

USGS Publications Warehouse

Woodward, D.F.; Farag, Aïda M.; Mueller, M.E.; Little, E.E.; Vertucci, F. A.

1989-01-01

Acidic episodes in waters of the western USA, do not last as long and are not as intense as those in the eastern USA, but we found that the native western cutthroat trout Oncorhynchus clarki is sensitive to even brief reductions in pH. In laboratory studies, fish were exposed to acidity (pH 4.5–6.5) alone or in the presence of aluminum during the first 7 d of the freshly fertilized egg, eyed embryo, alevin, or swim-up larva stages of development. Following exposure to acidity and aluminum, eggs and fish were held under control water quality conditions to 40 d posthatch to assess effects of the exposure on subsequent development. Reductions in pH from 6.5 to 6.0 in low-calcium water (1.4 mg/L) did not affect survival, but reduced growth offish in the early life stages. The presence of as little as 50 μg A1/L at low pH further decreased growth and reduced survival. The most sensitive indicators of stress were loss of ions (determined from whole-body sampling) and reduced swimming in alevins, reduction in the ratio of RNA:DNA, feeding inhibition, and pathology of gill tissue in swim-up larvae. A pH of 6.0 and 50 μg Al/L reduced whole-body sodium by 72% and potassium by 50% in alevins. Reductions in the RNA: DNA ratio, correlated with lower growth rates, were observed in swim-up larvae exposed to pH 5.5 and 50 μg Al/L. Exposure to 50 μg Al/L at pH 6.0 reduced swimming activity of alevins by 68% and feeding rates of swim-up larvae by 67%. In the presence of 50 μg A1/L, pathological changes in gill tissue were observed in swim-up larvae exposed to pH 6.0 or less. Although acidification is not widespread in the western USA, cutthroat trout have a narrow margin of safety between conditions that currently exist and those at which pH and aluminum reduce survival and growth.

Age-associated variation in sensory perception of iron in drinking water and the potential for overexposure in the human population.

PubMed

Mirlohi, Susan; Dietrich, Andrea M; Duncan, Susan E

2011-08-01

Humans interact with their environment through the five senses, but little is known about population variability in the ability to assess contaminants. Sensory thresholds and biochemical indicators of metallic flavor perception in humans were evaluated for ferrous (Fe(2+)) iron in drinking water; subjects aged 19-84 years participated. Metallic flavor thresholds for individuals and subpopulations based on age were determined. Oral lipid oxidation and oral pH were measured in saliva as potential biochemical indicators. Individual thresholds were 0.007-14.14 mg/L Fe(2+) and the overall population threshold was 0.17 mg/L Fe(2+) in reagent water. Average thresholds for individuals younger and older than 50 years of age (grouped by the daily recommended nutritional guidelines for iron intake) were significantly different (p = 0.013); the population thresholds for each group were 0.045 mg/L Fe(2+) and 0.498 mg/L Fe(2+), respectively. Many subjects >50 and a few subjects <50 years were insensitive to metallic flavor. There was no correlation between age, oral lipid oxidation, and oral pH. Standardized olfactory assessment found poor sensitivity for Fe(2+) corresponded with conditions of mild, moderate, and total anosmia. The findings demonstrate an age-dependent sensitivity to iron indicating as people age they are less sensitive to metallic perception.

Synergistic effect of enterocin AS-48 in combination with outer membrane permeabilizing treatments against Escherichia coli O157:H7.

PubMed

Ananou, S; Gálvez, A; Martínez-Bueno, M; Maqueda, M; Valdivia, E

2005-01-01

To determine the effects of outer membrane (OM) permeabilizing agents on the antimicrobial activity of enterocin AS-48 against Escherichia coli O157:H7 CECT 4783 strain in buffer and apple juice. We determined the influence of pH, EDTA, sodium tripolyphosphate (STPP) and heat on E. coli O157:H7 CECT 4783 sensitivity to enterocin AS-48 in buffer and in apple juice. Enterocin AS-48 was not active against intact cells of E. coli O157:H7 CECT 4783 at neutral pH. However, cells sublethally injured by OM permeabilizing agents (EDTA, STPP, pH 5, pH 8.6 and heat) became sensitive to AS-48, decreasing the amount of bacteriocin required for inhibition of E. coli O157:H7 CECT 4783. The results presented indicate that enterocin AS-48 could potentially be applied with a considerably wider range of protective agents, such as OM permeabilizing agents, with increased efficacy in inhibiting E. coli O157:H7. Results from this study support the potential use of enterocin AS-48 to control E. coli O157:H7 in combination with other hurdles.

pH sensing characteristics and biosensing application of solution-gated reduced graphene oxide field-effect transistors.

PubMed

Sohn, Il-Yung; Kim, Duck-Jin; Jung, Jin-Heak; Yoon, Ok Ja; Thanh, Tien Nguyen; Quang, Trung Tran; Lee, Nae-Eung

2013-07-15

Solution-gated reduced graphene oxide field-effect transistors (R-GO FETs) were investigated for pH sensing and biochemical sensing applications. A channel of a networked R-GO film formed by self-assembly was incorporated as a sensing layer into a solution-gated FET structure for pH sensing and the detection of acetylcholine (Ach), which is a neurotransmitter in the nerve system, through enzymatic reactions. The fabricated R-GO FET was sensitive to protons (H(+)) with a pH sensitivity of 29 mV/pH in terms of the shift of the charge neutrality point (CNP), which is attributed to changes in the surface potential caused by the interaction of protons with OH surface functional groups present on the R-GO surface. The R-GO FET immobilized with acetylcholinesterase (AchE) was used to detect Ach in the concentration range of 0.1-10mM by sensing protons generated during the enzymatic reactions. The results indicate that R-GO FETs provide the capability to detect protons, demonstrating their applicability as a biosensing device for enzymatic reactions. Copyright © 2013 Elsevier B.V. All rights reserved.

The Acid Test of Fluoride: How pH Modulates Toxicity

PubMed Central

Sharma, Ramaswamy; Tsuchiya, Masahiro; Skobe, Ziedonis; Tannous, Bakhos A.; Bartlett, John D.

2010-01-01

Background It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F−). Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of F−. Enamel formation is initiated in a neutral pH environment (secretory stage); however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage). Low pH can facilitate entry of F− into cells. Here, we asked if F− was more toxic at low pH, as measured by increased cell stress and decreased cell function. Methodology/Principal Findings Treatment of ameloblast-derived LS8 cells with F− at low pH reduced the threshold dose of F− required to phosphorylate stress-related proteins, PERK, eIF2α, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase, and secretion was quantified as a function of F− dose and pH. Luciferase secretion significantly decreased within 2 hr of F− treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm F− in their drinking water exhibited increased stress-mediated phosphorylation of eIF2α in maturation stage ameloblasts (pH<6.0) as compared to secretory stage ameloblasts (pH∼7.2). Intriguingly, F−-treated rats demonstrated a striking decrease in transcripts expressed during the maturation stage of enamel development (Klk4 and Amtn). In contrast, the expression of secretory stage genes, AmelX, Ambn, Enam and Mmp20, was unaffected. Conclusions The low pH environment of maturation stage ameloblasts facilitates the uptake of F−, causing increased cell stress that compromises ameloblast function, resulting in dental fluorosis. PMID:20531944

Intestine pH measurements using fluorescence imaging: an in-vivo preliminary study

NASA Astrophysics Data System (ADS)

Marechal, Xavier-Marie; Mordon, Serge R.; Devoisselle, Jean-Marie; Begu, Sylvie; Mathieu, D.; Buys, Bruno; Dhelin, Guy; Lesage, Jean C.; Neviere, Remi; Chopin, Claude

1999-02-01

Measurement of gastrointestinal intramucosal pH has been recognized as an important factor in the detection of hypoxia-induced dysfunctions. However, current pH measurement techniques are limited in terms of time and spatial resolution. A major advance in accurate pH measurement was the development of the ratiometric fluorescent indicator dye, 2',7'-bis(carboxyethyl)-4,5- carboxyfluorescein (BCECF). This study aimed to demonstrate the feasibility of fluorescence imaging technique to measure in vivo the pH of intestine. The intestine was inserted in an optical chamber placed under a microscope. Animals were injected i.v. with the pH-sensitive fluorescent dye BCECF. Fluorescence was visualized by illuminating the intestine alternately at 490 and 470 nm. The emitted fluorescence was directed to an intensified camera. The ratio of emitted fluorescence at excitation wavelengths of 490 and 470 nm was measured, corrected and converted to pH by constructing a calibration curve. The pH controls were performed with a pH microelectrode correlated with venous blood gas sampling. We concluded that accurate pH measurements of rat intestine can be obtained by fluorescence imaging using BCECF. This technology could be easily adapted for endoscopic pH measurement.

pH-sensitive liposomes: characterization and application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Connor, J.

1986-01-01

It has been demonstrated that liposomes composed of dioleoylphosphatidylethanolamine (DOPE) and palmitoylhomocysteine (PHC) have the ability to fuse with adjacent membranes upon exposure to mildly acid pH. The ability of liposomes to fuse is absolutely dependent on the presence of DOPE and a weakly acidic amphiphile. The acid induced fusion event is a leaky process, but the leakage can be reduced by 50%, with only a small loss of fusion ability, by the inclusion of 40 mole percent cholesterol. Using an established monoclonal antibody targeting system. pH-sensitive immunoliposomes were prepared which successfully delivered entrapped calcein to the cytoplasm of targetmore » cells. The addition of chloroquine, which raises the internal pH of cellular vacuoles, blocks the cytoplasmic delivery of the pH-sensitive immunoliposomes. pH-insensitive immunoliposomes delivered calcein only to the endosome/lysosome system and not the cytoplasm. /sup 31/P-NMR and light scattering of DOPE:OA liposomes under acidic conditions demonstrate that the effect of the protons and the divalent cations is to force the DOPE to revert to the hexagonal II configuration. In vivo experiments with DOPE:OA immunoliposomes indicate that the liposomes rapidly aggregate and release their contents upon exposure to plasma. These results indicate that pH-sensitive immunoliposomes are an effective tool for in vitro cytoplasmic delivery but are ineffective for in vivo delivery at this point in development.« less

Highly Sensitive and Reproducible SERS Sensor for Biological pH Detection Based on a Uniform Gold Nanorod Array Platform.

PubMed

Bi, Liyan; Wang, Yunqing; Yang, Ying; Li, Yuling; Mo, Shanshan; Zheng, Qingyin; Chen, Lingxin

2018-05-09

Conventional research on surface-enhanced Raman scattering (SERS)-based pH sensors often depends on nanoparticle aggregation, whereas the variability in nanoparticle aggregation gives rise to poor repeatability in the SERS signal. Herein, we fabricated a gold nanorod array platform via an efficient evaporative self-assembly method. The platform exhibits great SERS sensitivity with an enhancement factor of 5.6 × 10 7 and maintains excellent recyclability and reproducibility with relative standard deviation (RSD) values of less than 8%. On the basis of the platform, we developed a highly sensitive bovine serum albumin (BSA)-coated 4-mercaptopyridine (4-MPy)-linked (BMP) SERS-based pH sensor to report pH ranging from pH 3.0 to pH 8.0. The intensity ratio variation of 1004 and 1096 cm -1 in 4-MPy showed excellent pH sensitivity, which decreased as the surrounding pH increased. Furthermore, this BMP SERS-based pH sensor was employed to measure the pH value in C57BL/6 mouse blood. We have demonstrated that the pH sensor has great advantages such as good stability, reliability, and accuracy, which could be extended for the design of point-of-care devices.

Response of Syntrophic Propionate Degradation to pH Decrease and Microbial Community Shifts in an UASB Reactor.

PubMed

Zhang, Liguo; Ban, Qiaoying; Li, Jianzheng; Jha, Ajay Kumar

2016-08-28

The effect of pH on propionate degradation in an upflow anaerobic sludge blanket (UASB) reactor containing propionate as a sole carbon source was studied. Under influent propionate of 2,000 mg/l and 35ºC, propionate removal at pH 7.5-6.8 was above 93.6%. Propionate conversion was significantly inhibited with stepwise pH decrease from pH 6.8 to 6.5, 6.0, 5.5, 5.0, 4.5, and then to 4.0. After long-term operation, the propionate removal at pH 6.5-4.5 maintained an efficiency of 88.5%-70.1%, whereas propionate was hardly decomposed at pH 4.0. Microbial composition analysis showed that propionate-oxidizing bacteria from the genera Pelotomaculum and Smithella likely existed in this system. They were significantly reduced at pH ≤5.5. The methanogens in this UASB reactor belonged to four genera: Methanobacterium, Methanospirillum, Methanofollis, and Methanosaeta. Most detectable hydrogenotrophic methanogens were able to grow at low pH conditions (pH 6.0-4.0), but the acetotrophic methanogens were reduced as pH decreased. These results indicated that propionate-oxidizing bacteria and acetotrophic methanogens were more sensitive to low pH (5.5-4.0) than hydrogenotrophic methanogens.

Application of Anaerobic Digestion Model No. 1 for simulating anaerobic mesophilic sludge digestion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendes, Carlos, E-mail: carllosmendez@gmail.com; Esquerre, Karla, E-mail: karlaesquerre@ufba.br; Matos Queiroz, Luciano, E-mail: lmqueiroz@ufba.br

2015-01-15

Highlights: • The behavior of a anaerobic reactor was evaluated through modeling. • Parametric sensitivity analysis was used to select most sensitive of the ADM1. • The results indicate that the ADM1 was able to predict the experimental results. • Organic load rate above of 35 kg/m{sup 3} day affects the performance of the process. - Abstract: Improving anaerobic digestion of sewage sludge by monitoring common indicators such as volatile fatty acids (VFAs), gas composition and pH is a suitable solution for better sludge management. Modeling is an important tool to assess and to predict process performance. The present studymore » focuses on the application of the Anaerobic Digestion Model No. 1 (ADM1) to simulate the dynamic behavior of a reactor fed with sewage sludge under mesophilic conditions. Parametric sensitivity analysis is used to select the most sensitive ADM1 parameters for estimation using a numerical procedure while other parameters are applied without any modification to the original values presented in the ADM1 report. The results indicate that the ADM1 model after parameter estimation was able to predict the experimental results of effluent acetate, propionate, composites and biogas flows and pH with reasonable accuracy. The simulation of the effect of organic shock loading clearly showed that an organic shock loading rate above of 35 kg/m{sup 3} day affects the performance of the reactor. The results demonstrate that simulations can be helpful to support decisions on predicting the anaerobic digestion process of sewage sludge.« less

A simple reactive-transport model of calcite precipitation in soils and other porous media

NASA Astrophysics Data System (ADS)

Kirk, G. J. D.; Versteegen, A.; Ritz, K.; Milodowski, A. E.

2015-09-01

Calcite formation in soils and other porous media generally occurs around a localised source of reactants, such as a plant root or soil macro-pore, and the rate depends on the transport of reactants to and from the precipitation zone as well as the kinetics of the precipitation reaction itself. However most studies are made in well mixed systems, in which such transport limitations are largely removed. We developed a mathematical model of calcite precipitation near a source of base in soil, allowing for transport limitations and precipitation kinetics. We tested the model against experimentally-determined rates of calcite precipitation and reactant concentration-distance profiles in columns of soil in contact with a layer of HCO3--saturated exchange resin. The model parameter values were determined independently. The agreement between observed and predicted results was satisfactory given experimental limitations, indicating that the model correctly describes the important processes. A sensitivity analysis showed that all model parameters are important, indicating a simpler treatment would be inadequate. The sensitivity analysis showed that the amount of calcite precipitated and the spread of the precipitation zone were sensitive to parameters controlling rates of reactant transport (soil moisture content, salt content, pH, pH buffer power and CO2 pressure), as well as to the precipitation rate constant. We illustrate practical applications of the model with two examples: pH changes and CaCO3 precipitation in the soil around a plant root, and around a soil macro-pore containing a source of base such as urea.

Time From the Beginning of the Right Ventricle Isovolumetric Contraction to the Peak of the S Wave: A New TDI Indicator for the Non-Invasive Estimation of Pulmonary Hypertension.

PubMed

Parsaee, Mozhgan; Ghaderi, Fereshteh; Alizadehasl, Azin; Bakhshandeh, Hooman

2016-08-01

Echocardiography is a key screening tool in the diagnostic algorithm of pulmonary hypertension (PH). In addition, tissue doppler imaging (TDI) is a promising method for the noninvasive estimation of pulmonary artery pressure (PAP). The aim of this study was to validate the accuracy of measuring the time from the beginning of the right ventricular isovolumetric contraction time (RV IVRT) to the peak of the S wave in the TDI of the base of the RV free wall (time to peak or TTP), as an indicator for the non-invasive estimation of pulmonary hypertension. In this diagnostic test study, 60 consecutive patients referred for right heart catheterization (RHC) were enrolled. A pulse-wave TDI was performed before the cardiac catheterization, with a mean interval of 1 hour between the two measurements. The TDI variables, such as the RV IVRT, myocardial performance index (MPI), and the new "time to peak" parameter, were measured at the lateral basal RV free wall. The patients were divided into two sub-groups according to the RHC findings: no-PH (mean PAP < 25 mmHg) and PH (mean PAP ≥ 25 mmHg) groups. Then, we calculated the specificity and sensitivity of the TDI parameters (including the TTP) for the diagnosis of PH. In our study, the TTP showed a significant inverse relationship with the PAP. Based on our results, a TTP of less than 127 ms could be used to predict PH, with a sensitivity and specificity of about 70% (AUC = 0.746 ± 0.064). Based on the results of this study, we suggest the use of a novel "time from the beginning of isovolumetric contraction to the peak of the S wave" (TTP) parameter in the TDI of the base of the RV free wall to predict PH with acceptable accuracy in comparison with RHC.

Sensitivity of greenback cutthroat trout to acidic pH and elevated aluminum

USGS Publications Warehouse

Woodward, D.F.; Farag, Aïda M.; Little, E.E.; Steadman, B. L.; Yancik, R.

1991-01-01

The greenback cutthroat trout Oncorhynchus clarki stomias is a threatened subspecies native to the upper South Platte and Arkansas rivers between Denver and Fort Collins, Colorado, an area also susceptible to acid deposition. In laboratory studies, we exposed this subspecies to nominal pHs of 4.5–6.5 and to nominal aluminum concentrations of 0, 50, 100, and 300 μg/L; the control was pH 6.5 treatment without Al. We used soft water that contained 1.3 mg Ca/L. Exposures of 7 d each were made for four early life stages: fertilized egg, eyed embryo, alevin, and swim-up larva. Effects were measured at the end of exposure and again after a recovery period lasting until 40 d posthatch. The alevin stage was the most sensitive: at pH 5.0 with no Al, survival was reduced by 68% and swimming duration by 76%; at pH 6.0 and 50 μg Al/L, swimming duration was reduced by 62%, but survival was not affected. Reductions in whole-body concentrations of Na, K, and Ca indicated organism stress. Sodium was reduced most—about 50% in alevins exposed to pH 5.0 without Al and to pH 6.0 with 50 μg Al/L. Growth and the ratio of RNA to DNA were not affected by any exposure. All responses that were affected during exposure returned to normal by 40 d posthatch. Overall, it appeared that pH 6.0 and 50 μg Al/L might be detrimental to greenback cutthroat trout populations.

Sensitivity to acidification of subalpine ponds and lakes in north-western Colorado

USGS Publications Warehouse

Campbell, D.H.; Muths, E.; Turk, J.T.; Corn, P.S.

2004-01-01

Although acidifying deposition in western North America is lower than in many parts of the world, many high-elevation ecosystems there are extremely sensitive to acidification. Previous studies determined that the Mount Zirkel Wilderness Area (MZWA) has the most acidic snowpack and aquatic ecosystems that are among the most sensitive in the region. In this study, spatial and temporal variability of ponds and lakes in and near the MZWA were examined to determine their sensitivity to acidification and the effects of acidic deposition during and after snowmelt. Within the areas identified as sensitive to acidification based on bedrock types, there was substantial variability in acid-neutralizing capacity (ANC), which was related to differences in hydrological flowpaths that control delivery of weathering products to surface waters. Geological and topographic maps were of limited use in predicting acid sensitivity because their spatial resolution was not fine enough to capture the variability of these attributes for lakes and ponds with small catchment areas. Many of the lakes are sensitive to acidification (summer and autumn ANC < 100 µeq L−1), but none of them appeared to be threatened immediately by episodic or chronic acidification. In contrast, 22 ponds had minimum ANC < 30 µeq L−1, indicating that they are extremely sensitive to acidic deposition and could be damaged by episodic acidification, although net acidity (ANC < 0) was not measured in any of the ponds during the study. The lowest measured pH value was 5·4, and pH generally remained less than 6·0 throughout early summer in the most sensitive ponds, indicating that biological effects of acidification are possible at levels of atmospheric deposition that occurred during the study. The aquatic chemistry of lakes was dominated by atmospheric deposition and biogeochemical processes in soils and shallow ground water, whereas the aquatic chemistry of ponds was also affected by organic acids and biogeochemical processes in the water column and at the sediment–water interface. These results indicate that conceptual and mechanistic acidification models that have been developed for lakes and streams may be inadequate for predicting acidification in less-understood systems such as ponds.

Charge-transfer-based terbium MOF nanoparticles as fluorescent pH sensor for extreme acidity.

PubMed

Qi, Zewan; Chen, Yang

2017-01-15

Newly emerged metal organic frameworks (MOFs) have aroused the great interest in designing functional materials by means of its flexible structure and component. In this study, we used lanthanide Tb 3+ ions and small molecular ligands to design and assemble a kind of pH-sensitive MOF nanoparticle based on intramolecular-charge-transfer effect. This kind of made-to-order MOF nanoparticle for H + is highly specific and sensitive and could be used to fluorescently indicate pH value of strong acidic solution via preset mechanism through luminescence of Tb 3+ . The long luminescence lifetime of Tb 3+ allows eliminating concomitant non-specific fluorescence by time-revised fluorescence techniques, processing an advantage in sensing H + in biological media with strong autofluorescence. Our method showed a great potential of MOF structures in designing and constructing sensitive sensing materials for specific analytes directly via the assembly of functional ions/ligands. Copyright © 2016 Elsevier B.V. All rights reserved.

CdSe/ZnS quantum dots conjugated with a fluorescein derivative: a FRET-based pH sensor for physiological alkaline conditions.

PubMed

Kurabayashi, Tomokazu; Funaki, Nayuta; Fukuda, Takeshi; Akiyama, Shinnosuke; Suzuki, Miho

2014-01-01

Dual pH-dependent fluorescence peaks from a semiconductor quantum dot (QD) and a pH-dependent fluorescent dye can be measured by irradiating with a single wavelength light, and the pH can be estimated from the ratio of the fluorescent intensity of the two peaks. In this work, ratiometric pH sensing was achieved in an aqueous environment by a fluorescent CdSe/ZnS QD appended with a pH-sensitive organic dye, based on fluorescence resonance energy transfer (FRET). By functionalizing the CdSe/ZnS QD with 5-(and 6)-carboxynaphthofluorescein succinimidyl ester as a pH-dependent fluorescent dye, we succeeded in fabricating sensitive nanocomplexes with a linear response to a broad range of physiological pH levels (7.5-9.5) when excited at 450 nm. We found that a purification process is important for increasing the high-fluorescence intensity ratio of a ratiometric fluorescence pH-sensor, and the fluorescence intensity ratio was improved up to 1.0 at pH 8.0 after the purification process to remove unreacted CdSe/ZnS QDs even though the fluorescence of the dye could not be observed without the purification process. The fluorescence intensity ratio corresponds to the fluorescence intensity of the dye, and this fluorescent dye exhibited pH-dependent fluorescence intensity changes. These facts indicate that the fluorescence intensity ratio linearly increased with increasing pH value of the buffer solution containing the QD and the dye. The FRET efficiencies changed from 0.3 (pH 7.5) to 6.2 (pH 9.5).

Stress corrosion cracking evaluation of martensitic precipitation hardening stainless steels

NASA Technical Reports Server (NTRS)

Humphries, T. S.; Nelson, E. E.

1980-01-01

The resistance of the martensitic precipitation hardening stainless steels PH13-8Mo, 15-5PH, and 17-4PH to stress corrosion cracking was investigated. Round tensile and c-ring type specimens taken from several heats of the three alloys were stressed up to 100 percent of their yield strengths and exposed to alternate immersion in salt water, to salt spray, and to a seacoast environment. The results indicate that 15-5PH is highly resistant to stress corrosion cracking in conditions H1000 and H1050 and is moderately resistant in condition H900. The stress corrosion cracking resistance of PH13-8Mo and 17-4PH stainless steels in conditions H1000 and H1050 was sensitive to mill heats and ranged from low to high among the several heats included in the tests. Based on a comparison with data from seacoast environmental tests, it is apparent that alternate immersion in 3.5 percent salt water is not a suitable medium for accelerated stress corrosion testing of these pH stainless steels.

A single pH fluorescent probe for biosensing and imaging of extreme acidity and extreme alkalinity.

PubMed

Chao, Jian-Bin; Wang, Hui-Juan; Zhang, Yong-Bin; Li, Zhi-Qing; Liu, Yu-Hong; Huo, Fang-Jun; Yin, Cai-Xia; Shi, Ya-Wei; Wang, Juan-Juan

2017-07-04

A simple tailor-made pH fluorescent probe 2-benzothiazole (N-ethylcarbazole-3-yl) hydrazone (Probe) is facilely synthesized by the condensation reaction of 2-hydrazinobenzothiazole with N-ethylcarbazole-3-formaldehyde, which is a useful fluorescent probe for monitoring extremely acidic and alkaline pH, quantitatively. The pH titrations indicate that Probe displays a remarkable emission enhancement with a pK a of 2.73 and responds linearly to minor pH fluctuations within the extremely acidic range of 2.21-3.30. Interestingly, Probe also exhibits strong pH-dependent characteristics with pK a 11.28 and linear response to extreme-alkalinity range of 10.41-12.43. In addition, Probe shows a large Stokes shift of 84 nm under extremely acidic and alkaline conditions, high selectivity, excellent sensitivity, good water-solubility and fine stability, all of which are favorable for intracellular pH imaging. The probe is further successfully applied to image extremely acidic and alkaline pH values fluctuations in E. coli cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of high medium pH on growth, metabolism and transport in Saccharomyces cerevisiae.

PubMed

Peña, Antonio; Sánchez, Norma Silvia; Álvarez, Helber; Calahorra, Martha; Ramírez, Jorge

2015-03-01

Growth of Saccharomyces cerevisiae stopped by maintaining the pH of the medium in a pH-stat at pH 8.0 or 9.0. Studying its main physiological capacities and comparing cells after incubation at pH 6.0 vs. 8.0 or 9.0, we found that (a) fermentation was moderately decreased by high pH and respiration was similar and sensitive to the addition of an uncoupler, (b) ATP and glucose-6-phosphate levels upon glucose addition increased to similar levels and (c) proton pumping and K(+) transport were also not affected; all this indicating that energy mechanisms were preserved. Growth inhibition at high pH was also not due to a significant lower amino acid transport by the cells or incorporation into proteins. The cell cycle stopped at pH 9.0, probably due to an arrest as a result of adjustments needed by the cells to contend with the changes under these conditions, and microarray experiments showed some relevant changes to this response. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Effects of plasmalemmal V-ATPase activity on plasma membrane potential of resident alveolar macrophages.

PubMed

Heming, T A; Bidani, A

2003-01-01

The acid-base status and functional responses of alveolar macrophages (mphi) are influenced by the activity of plasmalemmal V-type H+-pump (V-ATPase), an electrogenic H+ extruder that provides a possible link between intracellular pH (pHi) and plasma membrane potential (Em). This study examined the relationships among Em, pHi, and plasmalemmal V-ATPase activity in resident alveolar mphi from rabbits. Em and pHi were measured using fluorescent probes. Em was -46 mV and pHi was 7.14 at an extracellular pH (pHo) of 7.4. The pHi declined progressively at lower pHo values. Decrements in pHo, also caused depolarization of the plasma membrane, independent of V-ATPase activity. The pH effects on Em were sensitive to external K+, and hence, probably involved pH-sensitive K+ conductance. H+ were not distributed at equilibrium across the plasma membrane. V-ATPase activity was a major determinant of the transmembrane H+ disequilibrium. Pump inhibition with bafilomycin A1 caused cytosolic acidification, due most likely to the retention of metabolically generated H+. V-ATPase inhibition also caused depolarization of the plasma membrane, but the effects were mediated indirectly via the accompanying pHi changes. V-ATPase activity was sensitive to Em. Em hyperpolarization (valinomycin-clamp) reduced V-ATPase activity, causing an acidic shift in baseline pHi under steady-state conditions and slowing pHi recovery from NH4Cl prepulse acid-loads. The findings indicate that a complex relationship exists among Em, pHi, and pHo that was partially mediated by plasmalemmal V-ATPase activity. This relationship could have important consequences for the expression of pH- and/or voltage-sensitive functions in alveolar mphi.

Recombinant antibody mediated delivery of organelle-specific DNA pH sensors along endocytic pathways

NASA Astrophysics Data System (ADS)

Modi, Souvik; Halder, Saheli; Nizak, Clément; Krishnan, Yamuna

2013-12-01

DNA has been used to build nanomachines with potential in cellulo and in vivo applications. However their different in cellulo applications are limited by the lack of generalizable strategies to deliver them to precise intracellular locations. Here we describe a new molecular design of DNA pH sensors with response times that are nearly 20 fold faster. Further, by changing the sequence of the pH sensitive domain of the DNA sensor, we have been able to tune their pH sensitive regimes and create a family of DNA sensors spanning ranges from pH 4 to 7.6. To enable a generalizable targeting methodology, this new sensor design also incorporates a `handle' domain. We have identified, using a phage display screen, a set of three recombinant antibodies (scFv) that bind sequence specifically to the handle domain. Sequence analysis of these antibodies revealed several conserved residues that mediate specific interactions with the cognate DNA duplex. We also found that all three scFvs clustered into different branches indicating that their specificity arises from mutations in key residues. When one of these scFvs is fused to a membrane protein (furin) that traffics via the cell surface, the scFv-furin chimera binds the `handle' and ferries a family of DNA pH sensors along the furin endocytic pathway. Post endocytosis, all DNA nanodevices retain their functionality in cellulo and provide spatiotemporal pH maps of retrogradely trafficking furin inside living cells. This new molecular technology of DNA-scFv-protein chimeras can be used to site-specifically complex DNA nanostructures for bioanalytical applications.DNA has been used to build nanomachines with potential in cellulo and in vivo applications. However their different in cellulo applications are limited by the lack of generalizable strategies to deliver them to precise intracellular locations. Here we describe a new molecular design of DNA pH sensors with response times that are nearly 20 fold faster. Further, by changing the sequence of the pH sensitive domain of the DNA sensor, we have been able to tune their pH sensitive regimes and create a family of DNA sensors spanning ranges from pH 4 to 7.6. To enable a generalizable targeting methodology, this new sensor design also incorporates a `handle' domain. We have identified, using a phage display screen, a set of three recombinant antibodies (scFv) that bind sequence specifically to the handle domain. Sequence analysis of these antibodies revealed several conserved residues that mediate specific interactions with the cognate DNA duplex. We also found that all three scFvs clustered into different branches indicating that their specificity arises from mutations in key residues. When one of these scFvs is fused to a membrane protein (furin) that traffics via the cell surface, the scFv-furin chimera binds the `handle' and ferries a family of DNA pH sensors along the furin endocytic pathway. Post endocytosis, all DNA nanodevices retain their functionality in cellulo and provide spatiotemporal pH maps of retrogradely trafficking furin inside living cells. This new molecular technology of DNA-scFv-protein chimeras can be used to site-specifically complex DNA nanostructures for bioanalytical applications. Electronic supplementary information (ESI) available: Detailed description of all oligonucleotide sequences used in this study; list of figures that support claims from the main text. Mainly these show sensor sequences, phage display results, scFv purification and binding data, cell images clamped at different pH and co-localization studies with endocytic tracers. See DOI: 10.1039/c3nr03769j

[Influence of simulated acid rain on nitrogen and phosphorus contents and their stoichiome-tric ratios of tea organs in a red soil region, China].

PubMed

Zhang, Yu Fei; Fang, Xiang Min; Chen, Fu Sheng; Zong, Ying Ying; Gu, Han Jiao; Hu, Xiao Fei

2017-04-18

A 25-year-old tea plantation in a typical red soil region was selected for an in situ simulated acid rain experiment treated by pH 4.5, 3.5, 2.5 and water (control, CK). Roots with different functions, leaves and twigs with different ages were collected to measure nitrogen (N) and phosphorus (P) contents in the third year after simulated acid rain treatment. The N/P and acid rain sensitivity coefficient of tea plant organs were also calculated. The results indicated that with the increase of acid rain intensity, the soil pH, NO 3 - -N and available P decreased, while the absorption root N content increased. Compared with the control, the N content in absorption root was increased by 32.9% under the treatment of pH 2.5. The P content in storage root significantly decreased with enhanced acid rain intensity, and the acid rain treatment significantly enhanced N/P of absorption root. Young and mature leaf N, P contents were not sensitive to different intensities of acid rain, but the mature leaf N/P was significantly increased under pH 3.5 treatment compared with the control. The effects of acid rain treatments differed with tea twig ages. Compared with the control, low intensity acid treatment (pH 4.5) significantly increased young twig N content and N/P, while no signi-ficant differences in old twig N content and N/P were observed among four acid rain treatments. Acid rain sensitivity coefficients of absorption root, young leaf and twig N contents were higher than that of storage root, old leaf and twig, respectively. And the storage root and leaf P had higher acid rain sensitivity coefficient than other tea organs. In sum, tea organs N content was sensitive to acid rain treatment, and moderate acid rain could increase young organ N content and N/P, and change the cycle and balance of N and P in tea plantation.

Optimization of pH sensing using silicon nanowire field effect transistors with HfO2 as the sensing surface.

PubMed

Zafar, Sufi; D'Emic, Christopher; Afzali, Ali; Fletcher, Benjamin; Zhu, Y; Ning, Tak

2011-10-07

Silicon nanowire field effect transistor sensors with SiO(2)/HfO(2) as the gate dielectric sensing surface are fabricated using a top down approach. These sensors are optimized for pH sensing with two key characteristics. First, the pH sensitivity is shown to be independent of buffer concentration. Second, the observed pH sensitivity is enhanced and is equal to the Nernst maximum sensitivity limit of 59 mV/pH with a corresponding subthreshold drain current change of ∼ 650%/pH. These two enhanced pH sensing characteristics are attributed to the use of HfO(2) as the sensing surface and an optimized fabrication process compatible with silicon processing technology.

Modulating Transmembrane α-Helix Interactions through pH-Sensitive Boundary Residues.

PubMed

Ng, Derek P; Deber, Charles M

2016-08-09

Changes in pH can alter the structure and activity of proteins and may be used by the cell to control molecular function. This coupling can also be used in non-native applications through the design of pH-sensitive biomolecules. For example, the pH (low) insertion peptide (pHLIP) can spontaneously insert into a lipid bilayer when the pH decreases. We have previously shown that the α-helicity and helix-helix interactions of the TM2 α-helix of the proteolipid protein (PLP) are sensitive to the local hydrophobicity at its C-terminus. Given that there is an ionizable residue (Glu-88) at the C-terminus of this transmembrane (TM) segment, we hypothesized that changing the ionization state of this residue through pH may alter the local hydrophobicity of the peptide enough to affect both its secondary structure and helix-helix interactions. To examine this phenomenon, we synthesized peptide analogues of the PLP TM2 α-helix (wild-type sequence (66)AFQYVIYGTASFFFLYGALLLAEGF(90)). Using circular dichroism and Förster resonance energy transfer in the membrane-mimetic detergent sodium dodecyl sulfate, we found that a decrease in pH increases both peptide α-helicity and the extent of self-association. This pH-dependent effect is due specifically to the presence of Glu-88 at the C-terminus. Additional experiments in which Phe-90 was mutated to residues of varying hydrophobicities indicated that the strength of this effect is dependent on the local hydrophobicity near Glu-88. Our results have implications for the design of TM peptide switches and improve our understanding of how membrane protein structure and activity can be regulated through local molecular environmental changes.

Genipin-crosslinked O-carboxymethyl chitosan-gum Arabic coacervate as a pH-sensitive delivery system and microstructure characterization.

PubMed

Huang, Guo-Qing; Cheng, Ling-Yun; Xiao, Jun-Xia; Wang, Shi-Qing; Han, Xiao-Na

2016-08-01

The possibility of genipin-crosslinked O-carboxymethyl chitosan-gum Arabic coacervate as a pH-sensitive delivery vehicle was investigated. O-carboxymethyl chitosan-gum Arabic coacervates separated in pH 3.0, 4.5, and 6.0 were crosslinked by genipin for different durations and the crosslinked products were subjected to crosslinking degree, swelling behavior, bovine serum albumin release profile, and microstructure characterization. Genipin-crosslinking greatly improved the stability of the coacervates against the simulated gastric solution and created certain pH-sensitivity. The coacervates displayed higher swelling ratios in the simulated gastric solution than in the simulated intestine and colon solutions; meanwhile, the coacervates prepared in pH 4.5 and 6.0 swelled more severely than the complex separated in pH 3.0. Nevertheless, the bovine serum albumin release in the simulated gastric solution from the microcapsules prepared in pH 6.0 was much lower than those prepared in pH 4.5 and 3.0, whose cumulative release percentages in the three simulated solutions were 17.14%, 55.23%, and 79.79%, respectively, in crosslinking duration 2 h. X-ray diffraction, scanning electron microscopy, and transmission electron microscopy analysis revealed that genipin-crosslinking improved the regularity and compactness of coacervate structure, whereas confocal laser scanning microscopy observation indicated that O-carboxymethyl chitosan content was possibly the major reason for the different swelling and bovine serum albumin release behavior of the coacervates. It was concluded that the genipin-crosslinked O-carboxymethyl chitosan-gum Arabic coacervate was a potential intestine-targeted delivery system and its delivery performance could be tailored by varying the crosslinking degree and coacervation acidity. © The Author(s) 2016.

A novel method to visually determine the intracellular pH of xenografted tumor in vivo by utilizing fluorescent protein as an indicator.

PubMed

Tanaka, Shotaro; Harada, Hiroshi; Hiraoka, Masahiro

2015-09-04

The alkalization of intracellular pH (pHin) advances together with enhancement of aerobic glycolysis within tumor cells (the Warburg effect), and that is responsible for the progression of tumor malignancy together with hypoxia and angiogenesis. But how they correlate each other during tumor growth is poorly understood, partly due to the lack of suitable imaging methods. In present study, we propose a novel method to visually determine the pHin of tumor xenograft model from fluorescent image ratios. We utilized tandemly-linked two fluorescent proteins as a pH indicator; yellow fluorescent protein (YFP, pH sensitive) as an indicator, and red fluorescent protein (RFP, pH insensitive) as a reference. This method can eliminate the influence of optical factors from tissue as well as of the diverse expression level of pH indicator in the grafted cells. In addition, that can be operated by filter-based fluorescent imagers that are generally used in small animal study. The efficacy of the pH indicator, RFP-YFP, was confirmed by studies using recombinant protein in vitro and HeLa cells expressing RFP-YFP in vivo. Furthermore, we prepared nude mice subcutaneously xenografted HeLa cells expressing RFP-YFP cells as tumor model. The image ratios (YFP/RFP) of the tumor at the day 5 after surgery clearly showed the heterogeneous distribution of diverse pHin cells in the tumor tissue. Concomitantly acquired angiography using near-infrared fluorescence (680 nm for emission) also indicated that the relative alkaline pHin cells located in the region far from tumor vessels in which tumor aerobic glycolysis would be facilitated by progression of hypoxia and nutrient starvation. Applying the present method for a multi-wavelength imaging concerning pO2 and/or nutrient starvation states in addition to pHin and angiogenesis would provide valuable information about complicated alteration of tumoral cell states during tumorigenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Isolation and characterization of acid-sensitive mutants of Pediococcus acidilactici.

PubMed

Kurdi, Peter; Smitinont, Thitapha; Valyasevi, Ruud

2009-02-01

Acid-sensitive mutants of Pediococcus acidilactici BCC 9545, a starter culture of the Thai fermented pork sausage nham, were isolated as spontaneous neomycin resistant mutants. The mutants generally produced less acid and acidified the culture media less than the parent strain in a 72 h culturing period. Interestingly, the ATPase activities of the mutants did not differ considerably from that of the parent strain in acidic conditions. It was also found that the internal pH values of the mutant strains were somewhat lower in neutral environment, while at pH 5.0 their internal pHs were significantly lower compared to the parent's. Inhibiting the H(+)-ATPase activities in energized cells by N,N'-dicyclohexyl carbodiimide also revealed that protons were leaking from the mutants at neutral pH, which increased under acidic conditions. In contrast, the parent strain exhibited a smaller proton leak and only under acidic conditions. The membrane fatty acid analysis of the mutants indicated that under acidic conditions the mutants had a significantly smaller major unsaturated/saturated fatty acids ratio ((C(18:1)+C(18:3n6))/(C(16:0)+C(18:0))) compared to the parent strain's membrane. Taken together, these observations suggest there is a reasonable possibility that the membrane fatty acid profile differences in the mutants resulted in their acid-sensitivity.

BSA-coated nanoparticles for improved SERS-based intracellular pH sensing.

PubMed

Zheng, Xiao-Shan; Hu, Pei; Cui, Yan; Zong, Cheng; Feng, Jia-Min; Wang, Xin; Ren, Bin

2014-12-16

Local microenvironment pH sensing is one of the key parameters for the understanding of many biological processes. As a noninvasive and high sensitive technique, surface-enhanced Raman spectroscopy (SERS) has attracted considerable interest in the detection of the local pH of live cells. We herein develop a facile way to prepare Au-(4-MPy)-BSA (AMB) pH nanosensor. The 4-MPy (4-mercaptopyridine) was used as the pH sensing molecule. The modification of the nanoparticles with BSA not only provides a high sensitive response to pH changes ranging from pH 4.0 to 9.0 but also exhibits a high sensitivity and good biocompatibility, stability, and reliability in various solutions (including the solutions of high ionic strength or with complex composition such as the cell culture medium), both in the aggregation state or after long-term storage. The AMB pH nanosensor shows great advantages for reliable intracellular pH analysis and has been successfully used to monitor the pH distribution of live cells and can address the grand challenges in SERS-based pH sensing for practical biological applications.

Development of a radiation-sensitive indicator

NASA Astrophysics Data System (ADS)

Abdel-Fattah, A. A.; El-Kelany, M.; Abdel-Rehim, F.

1996-10-01

A poly(vinyl alcohol) (PVA) film containing acid-sensitive dye (bromophenol red, BPR) and water soluble chlorine-containing substance [CCl 3COONa or chloral hydrate (CCl 3CH(OH) 2, 2,2,2-trichloroethan-1,1-diol)] may be useful as a radiation-sensitive indicator. The acid-sensitive dye in the film changes its color from violet to pale yellow by irradiation due to the consequent lowering of the pH of the film caused by the HCl generated from the radiolysis of the Cl-containing substance. This film can be used as a dosimeter in a relatively low dose range up to 5 kGy. This response range makes this film useful in some food irradiation, pasteurization and water purification applications. The effects of temperature and relative humidity during irradiation and post-irradiation storage on the response of the film are discussed. It is inexpensive, does not require toxic solvents in preparation and easy to prepare in a laboratory.

m-Cresol purple functionalized surface enhanced Raman scattering paper chips for highly sensitive detection of pH in the neutral pH range.

PubMed

Zou, Xinxin; Wang, Yunqing; Liu, Wanhui; Chen, Lingxin

2017-06-26

Herein, a pH sensitive paper SERS chip was prepared by selecting m-cresol purple, a molecule with halochromic properties in the neutral pH range as a Raman reporter. The adsorbed m-cresol purple underwent a reversible change in its electronic configuration from a non-resonant species to a resonant species, which resulted in a significant Raman signal intensity variation due to the transformation of the sensing mode from SERS to surface-enhanced resonance Raman scattering (SERRS). The chips have a sensitive pH range of 6.0 to 8.0 and exhibited good performance for the detection of natural water samples with detection precision of approximately 0.03 pH units, suggesting great potential for environmental pH monitoring applications.

Evaluation of vaginal pH for detection of bacterial vaginosis

PubMed Central

Hemalatha, R.; Ramalaxmi, Baru Anantha; Swetha, Eluru; Balakrishna, N.; Mastromarino, Paola

2013-01-01

Background & objectives: Bacterial vaginosis (BV) is highly prevalent among women in reproductive age group. Little information exists on routine vaginal pH measurement in women with BV. We undertook this study to assess the utility of vaginal pH determination for initial evaluation of bacterial vaginosis. Methods: In this cross-sectional study vaginal swabs were collected from women with complaints of white discharge, back ache and pain abdomen attending a government hospital and a community health clinic, and subjected to vaginal pH determination, Gram stain, wet mount and whiff test. Nugent score and Amsel criteria were used for BV confirmation. Results: Of the 270 women included in the analysis, 154 had BV based on Nugents’ score. The mean vaginal pH in women with BV measured by pH strips and pH glove was 5 and 4.9, respectively. The vaginal pH was significantly higher in women with BV. Vaginal discharge was prevalent in 84.8 per cent women, however, only 56.8 per cent of these actually had BV by Nugent score (NS). Presence of clue cells and positive whiff test were significant for BV. Vaginal pH >4.5 by pH strips and pH Glove had a sensitivity of 72 and 79 per cent and specificity of 60 and 53 per cent, respectively to detect BV. Among the combination criteria, clue cells and glove pH >4.5 had highest sensitivity and specificity to detect BV. Interpretation & conclusions: Vaginal pH determination is relatively sensitive, but less specific in detecting women with BV. Inclusion of whiff test along with pH test reduced the sensitivity, but improved specificity. Both, the pH strip and pH glove are equally suitable for screening women with BV on outpatient basis. PMID:24135180

Herceptin conjugated PLGA-PHis-PEG pH sensitive nanoparticles for targeted and controlled drug delivery.

PubMed

Zhou, Zilan; Badkas, Apurva; Stevenson, Max; Lee, Joo-Youp; Leung, Yuet-Kin

2015-06-20

A dual functional nano-scaled drug carrier, comprising of a targeting ligand and pH sensitivity, has been made in order to increase the specificity and efficacy of the drug delivery system. The nanoparticles are made of a tri-block copolymer, poly(d,l lactide-co-glycolide) (PLGA)-b-poly(l-histidine) (PHis)-b-polyethylene glycol (PEG), via nano-precipitation. To provide the nanoparticle feature of endolysosomal escape and pH sensitivity, poly(l-histidine) was chosen as a proton sponge polymer. Herceptin, which specifically binds to HER2 antigen, was conjugated to the nanoparticles through click chemistry. The nanoparticles were characterized via dynamic light scattering (DLS) and transmission electron microscopy (TEM). Both methods showed the sizes of about 100nm with a uniform size distribution. The pH sensitivity was assessed by drug releases and size changes at different pH conditions. As pH decreased from 7.4 to 5.2, the drug release rate accelerated and the size significantly increased. During in vitro tests against human breast cancer cell lines, MCF-7 and SK-BR-3 showed significantly increased uptake for Herceptin-conjugated nanoparticles, as compared to non-targeted nanoparticles. Herceptin-conjugated pH-sensitive nanoparticles showed the highest therapeutic effect, and thus validated the efficacy of a combined approach of pH sensitivity and active targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

Inactivation of Renibacterium salmoninarum by free chlorine

USGS Publications Warehouse

Pascho, Ronald J.; Landolt, Marsha L.; Ongerth, Jerry E.

1995-01-01

Salmonid fishes contract bacterial kidney disease by vertical or horizontal transmission of the pathogenic bacterium, Renibacterium salmoninarum. Procedures to reduce vertical transmission are under evaluation, but methods are still needed to eliminate sources of waterborne R. salmoninarum. We examined the efficacy of chlorine to inactivate R. salmoninarum. The bacterium was exposed to various levels of chlorine at pH 6, 7, or 8, and at 7.5 °C or 15 °C. At pH 7 and 15 °C, 99% inactivation occurred within 18 s, even at free chlorine concentrations as low as 0.05 mg/l. Chlorine was most effective at neutral or acidic pH, and 15 °C. The inactivation curves for 7.5 °C and pH 7, or 15 °C and pH 8, deviated from first-order kinetics by exhibiting shoulders or a tailing-off effect, suggesting that chlorine and the bacterial cells were not the sole reactants. A plot of the concentration-time (Ct) products for free chlorine at pH 7 and 15 °C produced a line with a slope less than 1, indicating that the duration of exposure was more important than the concentration of free chlorine. These data indicate that R. salmoninarum is very sensitive to chlorine, and that this disinfectant may be appropriate for use in fish hatcheries rearing salmonids affected by bacterial kidney disease.

Highly Photostable Near-Infrared Fluorescent pH Indicators and Sensors Based on BF2-Chelated Tetraarylazadipyrromethene Dyes

PubMed Central

2012-01-01

In this study, a series of new BF2-chelated tetraarylazadipyrromethane dyes are synthesized and are shown to be suitable for the preparation of on/off photoinduced electron transfer modulated fluorescent sensors. The new indicators are noncovalently entrapped in polyurethane hydrogel D4 and feature absorption maxima in the range 660–710 nm and fluorescence emission maxima at 680–740 nm. Indicators have high molar absorption coefficients of ∼80 000 M–1 cm–1, good quantum yields (up to 20%), excellent photostability and low cross-sensitivity to the ionic strength. pKa values of indicators are determined from absorbance and fluorescence measurements and range from 7 to 11, depending on the substitution pattern of electron-donating and -withdrawing functionalities. Therefore, the new indicators are suitable for exploitation and adaptation in a diverse range of analytical applications. Apparent pKa values in sensor films derived from fluorescence data show 0.5–1 pH units lower values in comparison with those derived from the absorption data due to Förster resonance energy transfer from protonated to deprotonated form. A dual-lifetime referenced sensor is prepared, and application for monitoring of pH in corals is demonstrated. PMID:22738322

Development of pH Sensitive Nanoparticles for Intestinal Drug Delivery Using Chemically Modified Guar Gum Co-Polymer.

PubMed

Varma, Vegesna Naga Sravan Kumar; Shivakumar, Hosakote Gurumalappa; Balamuralidhara, Veerna; Navya, Manne; Hani, Umme

2016-01-01

The aim of the research work was to chemically modify guargum (GG) as a pH sensitive co-polymer and formulating intestinal targeting ESO nanoparticles (NPs) using the synthesized co-polymer. Poly acrylamide-grafted-guar gum (PAAm-g-GG) co-polymer was synthesized by free radical polymerization. Chemical modification of PAAm-g-GG by alkaline hydrolysis results in formation of a pH-sensitive co-polymer. The effect of GG and acryl amide (AAm) on grafting was studied. Esomeprazole magnesium (ESO) loaded pH sensitive NPs were prepared by nano-emulsification polymer crosslinking method and characterized. Sixteen formulations were prepared and the concentration of process variables wasvaried to obtain nanoparticles of 200-600 nm. The NPs were found to be homogenous in size distribution. The encapsulation efficiency and drug loading ranged from 33.2% to 50.1% and 12.2% to 17.2% respectively. Particle size, encapsulation efficiency and drug loading increasedalong with co-polymer concentration. In-vitro release studies at pH 1.2 for 2 h, followed by pH 6.8 showed that environment pH significantly affected the drug release. SEM has shown that NPsare spherical with smooth surface. The pH sensitive PAAm-g-GGNPs resisted the initial release of the drug from the drug loaded NPs in acidic pH and delayed the release process to a longer period in alkaline environment.

Development of pH Sensitive Nanoparticles for Intestinal Drug Delivery Using Chemically Modified Guar Gum Co-Polymer

PubMed Central

Varma, Vegesna Naga Sravan Kumar; Shivakumar, Hosakote Gurumalappa; Balamuralidhara, Veerna; Navya, Manne; Hani, Umme

2016-01-01

The aim of the research work was to chemically modify guargum (GG) as a pH sensitive co-polymer and formulating intestinal targeting ESO nanoparticles (NPs) using the synthesized co-polymer. Poly acrylamide-grafted-guar gum (PAAm-g-GG) co-polymer was synthesized by free radical polymerization. Chemical modification of PAAm-g-GG by alkaline hydrolysis results in formation of a pH-sensitive co-polymer. The effect of GG and acryl amide (AAm) on grafting was studied. Esomeprazole magnesium (ESO) loaded pH sensitive NPs were prepared by nano-emulsification polymer crosslinking method and characterized. Sixteen formulations were prepared and the concentration of process variables wasvaried to obtain nanoparticles of 200-600 nm. The NPs were found to be homogenous in size distribution. The encapsulation efficiency and drug loading ranged from 33.2% to 50.1% and 12.2% to 17.2% respectively. Particle size, encapsulation efficiency and drug loading increasedalong with co-polymer concentration. In-vitro release studies at pH 1.2 for 2 h, followed by pH 6.8 showed that environment pH significantly affected the drug release. SEM has shown that NPsare spherical with smooth surface. The pH sensitive PAAm-g-GGNPs resisted the initial release of the drug from the drug loaded NPs in acidic pH and delayed the release process to a longer period in alkaline environment. PMID:27610149

pH- and ion-sensitive polymers for drug delivery

PubMed Central

Yoshida, Takayuki; Lai, Tsz Chung; Kwon, Glen S; Sako, Kazuhiro

2013-01-01

Introduction Drug delivery systems (DDSs) are important for effective, safe, and convenient administration of drugs. pH- and ion-responsive polymers have been widely employed in DDS for site-specific drug release due to their abilities to exploit specific pH- or ion-gradients in the human body. Areas covered Having pH-sensitivity, cationic polymers can mask the taste of drugs and release drugs in the stomach by responding to gastric low pH. Anionic polymers responsive to intestinal high pH are used for preventing gastric degradation of drug, colon drug delivery and achieving high bioavailability of weak basic drugs. Tumor-targeted DDSs have been developed based on polymers with imidazole groups or poly(β-amino ester) responsive to tumoral low pH. Polymers with pH-sensitive chemical linkages, such as hydrazone, acetal, ortho ester and vinyl ester, pH-sensitive cell-penetrating peptides and cationic polymers undergoing pH-dependent protonation have been studied to utilize the pH gradient along the endocytic pathway for intracellular drug delivery. As ion-sensitive polymers, ion-exchange resins are frequently used for taste-masking, counterion-responsive drug release and sustained drug release. Polymers responding to ions in the saliva and gastrointestinal fluids are also used for controlled drug release in oral drug formulations. Expert opinion Stimuli-responsive DDSs are important for achieving site-specific and controlled drug release; however, intraindividual, interindividual and intercellular variations of pH should be considered when designing DDSs or drug products. Combination of polymers and other components, and deeper understanding of human physiology are important for development of pH- and ion-sensitive polymeric DDS products for patients. PMID:23930949

Process-based modelling of NH3 exchange with grazed grasslands

NASA Astrophysics Data System (ADS)

Móring, Andrea; Vieno, Massimo; Doherty, Ruth M.; Milford, Celia; Nemitz, Eiko; Twigg, Marsailidh M.; Horváth, László; Sutton, Mark A.

2017-09-01

In this study the GAG model, a process-based ammonia (NH3) emission model for urine patches, was extended and applied for the field scale. The new model (GAG_field) was tested over two modelling periods, for which micrometeorological NH3 flux data were available. Acknowledging uncertainties in the measurements, the model was able to simulate the main features of the observed fluxes. The temporal evolution of the simulated NH3 exchange flux was found to be dominated by NH3 emission from the urine patches, offset by simultaneous NH3 deposition to areas of the field not affected by urine. The simulations show how NH3 fluxes over a grazed field in a given day can be affected by urine patches deposited several days earlier, linked to the interaction of volatilization processes with soil pH dynamics. Sensitivity analysis showed that GAG_field was more sensitive to soil buffering capacity (β), field capacity (θfc) and permanent wilting point (θpwp) than the patch-scale model. The reason for these different sensitivities is dual. Firstly, the difference originates from the different scales. Secondly, the difference can be explained by the different initial soil pH and physical properties, which determine the maximum volume of urine that can be stored in the NH3 source layer. It was found that in the case of urine patches with a higher initial soil pH and higher initial soil water content, the sensitivity of NH3 exchange to β was stronger. Also, in the case of a higher initial soil water content, NH3 exchange was more sensitive to the changes in θfc and θpwp. The sensitivity analysis showed that the nitrogen content of urine (cN) is associated with high uncertainty in the simulated fluxes. However, model experiments based on cN values randomized from an estimated statistical distribution indicated that this uncertainty is considerably smaller in practice. Finally, GAG_field was tested with a constant soil pH of 7.5. The variation of NH3 fluxes simulated in this way showed a good agreement with those from the simulations with the original approach, accounting for a dynamically changing soil pH. These results suggest a way for model simplification when GAG_field is applied later at regional scale.

Critical loads of acidity for 90,000 lakes in northern Saskatchewan: A novel approach for mapping regional sensitivity to acidic deposition

NASA Astrophysics Data System (ADS)

Cathcart, H.; Aherne, J.; Jeffries, D. S.; Scott, K. A.

2016-12-01

Atmospheric emissions of sulphur dioxide (SO2) from large point sources are the primary concern for acidic deposition in western Canada, particularly in the Athabasca Oil Sands Region (AOSR) where prevailing winds may potentially carry SO2 over acid-sensitive lakes in northern Saskatchewan. A novel catchment-scale regression kriging approach was used to assess regional sensitivity and critical loads of acidity for the total lake population of northern Saskatchewan (89,947 lakes). Lake catchments were delineated using Thiessen polygons, and surface water chemistry was predicted for sensitivity indicators (calcium, pH, alkalinity, and acid neutralizing capacity). Critical loads were calculated with the steady state water chemistry model using regression-kriged base cations, sulphate, and dissolved organic carbon concentrations modelled from surface water observations (n > 800) and digital landscape-scale characteristics, e.g., climate, soil, vegetation, landcover, and geology maps. A large region (>13,726 km2) of two or more indicators of acid sensitivity (pH < 6 and acid neutralizing capacity, alkalinity, calcium < 50 μeq L-1) and low critical loads < 5 meq m-2 yr-1 were predicted on the Athabasca Basin. Exceedance of critical loads under 2006 modelled total sulphate deposition was predicted for 12% of the lakes (covering an area of 3742 km2), primarily located on the Athabasca Basin, within 100 km of the AOSR. There have been conflicting scientific reports of impacts from atmospheric emissions from the AOSR; the results of this study suggest that catchments in the Athabasca Basin within 100 km of the AOSR have received acidic deposition in excess of their critical loads and many of them may be at risk of ecosystem damage owing to their sensitivity.

Poly(styrene-co-maleic acid)-based pH-sensitive liposomes mediate cytosolic delivery of drugs for enhanced cancer chemotherapy.

PubMed

Banerjee, Shubhadeep; Sen, Kacoli; Pal, Tapan K; Guha, Sujoy K

2012-10-15

pH-responsive polymers render liposomes pH-sensitive and facilitate the intracellular release of encapsulated payload by fusing with endovascular membranes under mildly acidic conditions found inside cellular endosomes. The present study reports the use of high-molecular weight poly(styrene-co-maleic acid) (SMA), which exhibits conformational transition from a charged extended structure to an uncharged globule below its pK(1) value, to confer pH-sensitive property to liposomes. The changes in the co-polymer chain conformation resulted in destabilization of the liposomes at mildly acidic pH due to vesicle fusion and/or channel formation within the membrane bilayer, and ultimately led to the release of the encapsulated cargo. The vesicles preserved their pH-sensitivity and stability in serum unlike other polymer-based liposomes and exhibited no hemolytic activity at physiological pH. The lysis of RBCs at endosomal pH due to SMA-based liposome-induced alterations in the bilayer organization leading to spherocyte formation indicated the potential of these vesicles to mediate cytosolic delivery of bio-active molecules through endosome destabilization. The SMA-loaded liposomes exhibiting excellent cytocompatibility, efficiently delivered chemotherapeutic agent 5-Fluorouracil (5-FU) within colon cancer cells HT-29 in comparison to neat liposomes. This caused increased cellular-availability of the drug, which resulted in enhanced apoptosis and highlighted the clinical potential of SMA-based vesicles. Copyright © 2012 Elsevier B.V. All rights reserved.

Genetically Targeted Ratiometric and Activated pH Indicator Complexes (TRApHIC) for Receptor Trafficking.

PubMed

Perkins, Lydia A; Yan, Qi; Schmidt, Brigitte F; Kolodieznyi, Dmytro; Saurabh, Saumya; Larsen, Mads Breum; Watkins, Simon C; Kremer, Laura; Bruchez, Marcel P

2018-02-06

Fluorescent protein-based pH sensors are useful tools for measuring protein trafficking through pH changes associated with endo- and exocytosis. However, commonly used pH-sensing probes are ubiquitously expressed with their protein of interest throughout the cell, hindering our ability to focus on specific trafficking pools of proteins. We developed a family of excitation ratiometric, activatable pH responsive tandem dyes, consisting of a pH sensitive Cy3 donor linked to a fluorogenic malachite green acceptor. These cell-excluded dyes are targeted and activated upon binding to a genetically expressed fluorogen-activating protein and are suitable for selective labeling of surface proteins for analysis of endocytosis and recycling in live cells using both confocal and superresolution microscopy. Quantitative profiling of the endocytosis and recycling of tagged β2-adrenergic receptor (B2AR) at a single-vesicle level revealed differences among B2AR agonists, consistent with more detailed pharmacological profiling.

Application of arteether-loaded polyurethane nanomicelles to induce immune response in breast cancer model.

PubMed

Jabbarzadegan, Mona; Rajayi, Hajar; Mofazzal Jahromi, Mirza Ali; Yeganeh, Hamid; Yousefi, Mehdi; Muhammad Hassan, Zuhair; Majidi, Jafar

2017-06-01

To concentrate a potent anticancer drug (Arteether) in tumor microenvironment, we encapsulated it in biodegradable and pH sensitive polyurethane (PU) nanomicelles (NMs). The nanocomplex was characterized by Fourier transform infrared (FTIR), dynamic light scattering (DLS). The loading capacity and release profile in pH of 5.4 and 7.4 were considered. The cytotoxicity effect was evaluated in vitro and in vivo settings. The level of IFN-γ and IL-4 cytokines of mice splenocytes were assessed by enzyme-linked immunosorbent assay (ELISA). The nanocomplex showed negative zeta charge of -26.2 mV, size of 42.30 nm and high loading capacity (92%). Release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4. It indicated significant inhibitory effect on the growth of 4T1 cell line and increased IFN-γ level.

The pH of commonly available soaps, liquid cleansers, detergents and alcohol gels.

PubMed

Boonchai, Waranya; Iamtharachai, Pacharee

2010-01-01

The hydrogen ion concentration (pH) of a cleanser certainly has an impact on skin condition. Dermatologists always need to recommend a cleanser to patients with hand dermatitis or sensitive skin; particularly during the outbreak of swine (AH1N1 virus) influenza, frequent hand washing and alcohol gel cleansing were greatly recommended. The purpose of this study was to evaluate the pH of various commonly available cleansers and alcohol gels on the market to assess patient comfort in using such products and to make good recommendations to our patients. Multiple brands of liquid cleansers, dishwashing liquids, soaps, laundry detergents, and alcohol gels commonly available on the market were assessed for pH by using a pH meter and pH-indicator strips. The pH assessment imitated real-life conditions by diluting each cleanser with tap water and then comparing the changed pH. The pH levels of liquid cleansers, dishwashing liquids, a beauty bar, and alcohol gels were acidic to neutral and compatible with normal skin pH. Most bar soaps, baby soaps, and powdered laundry detergents had a pH in the alkali range. The pH of concentrated cleansers was slightly different from that of their dissolved forms. Regarding the antiseptic property and pH of the cleansers, alcohol gels with moisturizers appeared to be the best hand cleansers to recommend to our patients.

Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules.

PubMed

Hundshammer, Christian; Düwel, Stephan; Ruseckas, David; Topping, Geoffrey; Dzien, Piotr; Müller, Christoph; Feuerecker, Benedikt; Hövener, Jan B; Haase, Axel; Schwaiger, Markus; Glaser, Steffen J; Schilling, Franz

2018-02-15

pH is a tightly regulated physiological parameter that is often altered in diseased states like cancer. The development of biosensors that can be used to non-invasively image pH with hyperpolarized (HP) magnetic resonance spectroscopic imaging has therefore recently gained tremendous interest. However, most of the known HP-sensors have only individually and not comprehensively been analyzed for their biocompatibility, their pH sensitivity under physiological conditions, and the effects of chemical derivatization on their logarithmic acid dissociation constant (p K a ). Proteinogenic amino acids are biocompatible, can be hyperpolarized and have at least two pH sensitive moieties. However, they do not exhibit a pH sensitivity in the physiologically relevant pH range. Here, we developed a systematic approach to tailor the p K a of molecules using modifications of carbon chain length and derivatization rendering these molecules interesting for pH biosensing. Notably, we identified several derivatives such as [1- 13 C]serine amide and [1- 13 C]-2,3-diaminopropionic acid as novel pH sensors. They bear several spin-1/2 nuclei ( 13 C, 15 N, 31 P) with high sensitivity up to 4.8 ppm/pH and we show that 13 C spins can be hyperpolarized with dissolution dynamic polarization (DNP). Our findings elucidate the molecular mechanisms of chemical shift pH sensors that might help to design tailored probes for specific pH in vivo imaging applications.

Dural stimulation in rats causes BDNF-dependent priming to subthreshold stimuli including a migraine trigger

PubMed Central

Burgos-Vega, Carolina C.; Quigley, Lilyana D.; Avona, Amanda; Price, Theodore; Dussor, Gregory

2016-01-01

Migraine is one of the most common and most disabling disorders. Between attacks, migraine patients are otherwise normal but are sensitized to non-noxious events known as triggers. The purpose of these studies was to investigate whether a headache-like event causes sensitization, or priming, to subsequent subthreshold events. Interleukin-6 (IL-6) was applied to the rat cranial dura mater which produced cutaneous facial and hindpaw allodynia that lasted 24 hours. At 72-hours, IL-6 treated rats developed allodynia in response to dural stimulation with either a pH 6.8 or pH 7.0 solution and to a systemic nitric oxide (NO) donor, a well-known migraine trigger. Vehicle-treated rats did not respond to either pH stimulus nor to the NO donor, demonstrating that IL-6 exposure primes rats to subthreshold stimuli. Inhibitors of brain-derived neurotrophic factor (BDNF) signaling given either systemically or intracisternally 24-hours after IL-6 eliminated responses to dural pH stimulation at 72 hours. Additionally, intracisternal administration of BDNF without prior dural stimulation produced allodynia and once resolved, animals were primed to dural pH 6.8/pH 7.0 and a systemic NO donor. Finally, hindpaw IL-6 produced paw allodynia but not priming to paw injection of pH 7.0 at 72 hours demonstrating differences in priming depending on location. These data indicate that afferent input from the meninges produces BDNF-dependent priming of the dural nociceptive system. This primed state mimics the interictal period of migraine where attacks can be triggered by normally non-noxious events and suggests that BDNF-dependent plasticity may contribute to migraine. PMID:27841839

Ethylene regulates phosphorus remobilization and expression of a phosphate transporter (PhPT1) during petunia corolla senescence

PubMed Central

Chapin, Laura J.; Jones, Michelle L.

2009-01-01

The programmed degradation of macromolecules during petal senescence allows the plant to remobilize nutrients from dying to developing tissues. Ethylene is involved in regulating the timing of nucleic acid degradation in petunia, but it is not clear if ethylene has a role in the remobilization of phosphorus during petal senescence. To investigate ethylene's role in nutrient remobilization, the P content of petals (collectively called the corolla) during early development and senescence was compared in ethylene-sensitive wild type Petunia×hybrida ‘Mitchell Diploid’ (MD) and transgenic petunias with reduced sensitivity to ethylene (35S::etr1-1). When compared to the total P content of corollas on the day of flower opening (the early non-senescing stage), P in MD corollas had decreased 74% by the late stage of senescence (advanced wilting). By contrast, P levels were only reduced by an average of 32% during etr1-1 corolla (lines 44568 and Z00-35-10) senescence. A high-affinity phosphate transporter, PhPT1 (PhPht1;1), was cloned from senescing petunia corollas by RT-PCR. PhPT1 expression was up-regulated during MD corolla senescence and a much smaller increase was detected during the senescence of etr1-1 petunia corollas. PhPT1 mRNA levels showed a rapid increase in detached corollas (treated at 1 d after flower opening) following treatment with low levels of ethylene (0.1 μl l-1). Transcripts accumulated in the presence of the protein synthesis inhibitor, cycloheximide, indicating that PhPT1 is a primary ethylene response gene. PhPT1 is a putative phosphate transporter that may function in Pi translocation during senescence. PMID:19380421

Sensitivity of greenback cutthroat trout to acidic pH and elevated aluminum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woodward, D.F.; Farag, A.M.; Little E.E.

1991-01-01

The greenback cutthroat trout Oncorhynchus clarki stomias is a threatened subspecies native to the upper South Platte and Arkansas rivers between Denver and Fort Collins, Colorado, an area also susceptible to acid deposition. In laboratory studies, the authors exposed this subspecies to nominal pHs of 4.5-6.5 and to nominal aluminum concentrations of 0, 50, 100, and 300 {mu}g/L; the control was pH 6.5 treatment without Al. The authors used soft water that contained 1.3 mg Ca/L. Exposures of 7 days each were made for four early life stages: fertilized egg, eyed embryo, alevin, and swim-up larva. Effects were measured atmore » the end of exposure and again after a recovery period lasting until 40 days posthatch. The alevin stage was the most sensitive: at pH 5.0 with no Al, survival was reduced by 68% and swimming duration by 76%, at pH 6.0 and 50 {mu}g Al/L, swimming duration was reduced by 62%, but survival was not affected. Reductions in whole-body concentrations of Na, K, and Ca indicated organism stress. Sodium was reduced most-about 50% in alevins exposed to pH 5.0 without Al and to pH 6.0 with 50 {mu}g Al/L. Growth and the ratio of RNA to DNA were not affected by any exposure. All responses that were affected during exposure returned to normal by 40 days posthatch. Overall, it appeared that pH 6.0 and 50 {mu}g Al/L might be detrimental to greenback cutthroat trout populations.« less

Acute and chronic toxicity of aluminum to a unionid mussel (Lampsilis siliquoidea) and an amphipod (Hyalella azteca) in water‐only exposures

USGS Publications Warehouse

Wang, Ning; Ivey, Chris D.; Brunson, Eric L.; Cleveland, Danielle; Ingersoll, Christopher G.; Stubblefield, William A.; Cardwell, Allison S.

2018-01-01

The US Environmental Protection Agency (USEPA) is reviewing the protectiveness of the national ambient water quality criteria (WQC) for aluminum (Al) and compiling a toxicity data set to update the WQC. Freshwater mussels are one of the most imperiled groups of animals in the world, but little is known about their sensitivity to Al. The objective of the present study was to evaluate acute 96‐h and chronic 28‐d toxicity of Al to a unionid mussel (Lampsilis siliquoidea) and a commonly tested amphipod (Hyalella azteca) at a pH of 6 and water hardness of 100 mg/L as CaCO3. The acute 50% effect concentration (EC50) for survival of both species was >6200 μg total Al/L. The EC50 was greater than all acute values in the USEPA acute Al data set for freshwater species at a pH range of 5.0 to <6.5 and hardness normalized to 100 mg/L, indicating that the mussel and amphipod were insensitive to Al in acute exposures. The chronic 20% effect concentration (EC20) based on dry weight was 163 μg total Al/L for the mussel and 409 μg total Al/L for the amphipod. Addition of the EC20s to the USEPA chronic Al data set for pH 5.0 to <6.5 would rank the mussel (L. siliquoidea) as the fourth most sensitive species and the amphipod (H. azteca) as the fifth most sensitive species, indicating the 2 species were sensitive to Al in chronic exposures. The USEPA‐proposed acute and chronic WQC for Al would adequately protect the mussel and amphipod tested; however, inclusion of the chronic data from the present study and recalculation of the chronic criterion would likely lower the proposed chronic criterion. 

Variability in larval gut pH regulation defines sensitivity to ocean acidification in six species of the Ambulacraria superphylum.

PubMed

Hu, Marian; Tseng, Yung-Che; Su, Yi-Hsien; Lein, Etienne; Lee, Hae-Gyeong; Lee, Jay-Ron; Dupont, Sam; Stumpp, Meike

2017-10-11

The unusual rate and extent of environmental changes due to human activities may exceed the capacity of marine organisms to deal with this phenomenon. The identification of physiological systems that set the tolerance limits and their potential for phenotypic buffering in the most vulnerable ontogenetic stages become increasingly important to make large-scale projections. Here, we demonstrate that the differential sensitivity of non-calcifying Ambulacraria (echinoderms and hemichordates) larvae towards simulated ocean acidification is dictated by the physiology of their digestive systems. Gastric pH regulation upon experimental ocean acidification was compared in six species of the superphylum Ambulacraria. We observed a strong correlation between sensitivity to ocean acidification and the ability to regulate gut pH. Surprisingly, species with tightly regulated gastric pH were more sensitive to ocean acidification. This study provides evidence that strict maintenance of highly alkaline conditions in the larval gut of Ambulacraria early life stages may dictate their sensitivity to decreases in seawater pH. These findings highlight the importance of identifying and understanding pH regulatory systems in marine larval stages that may contribute to substantial energetic challenges under near-future ocean acidification scenarios. © 2017 The Author(s).

ISFET pH Sensitivity: Counter-Ions Play a Key Role.

PubMed

Parizi, Kokab B; Xu, Xiaoqing; Pal, Ashish; Hu, Xiaolin; Wong, H S Philip

2017-02-02

The Field Effect sensors are broadly used for detecting various target analytes in chemical and biological solutions. We report the conditions under which the pH sensitivity of an Ion Sensitive Field Effect transistor (ISFET) sensor can be significantly enhanced. Our theory and simulations show that by using pH buffer solutions containing counter-ions that are beyond a specific size, the sensor shows significantly higher sensitivity which can exceed the Nernst limit. We validate the theory by measuring the pH response of an extended gate ISFET pH sensor. The consistency and reproducibility of the measurement results have been recorded in hysteresis free and stable operations. Different conditions have been tested to confirm the accuracy and validity of our experiment results such as using different solutions, various oxide dielectrics as the sensing layer and off-the-shelf versus IC fabricated transistors as the basis of the ISFET sensor.

ISFET pH Sensitivity: Counter-Ions Play a Key Role

PubMed Central

Parizi, Kokab B.; Xu, Xiaoqing; Pal, Ashish; Hu, Xiaolin; Wong, H. S. Philip

2017-01-01

The Field Effect sensors are broadly used for detecting various target analytes in chemical and biological solutions. We report the conditions under which the pH sensitivity of an Ion Sensitive Field Effect transistor (ISFET) sensor can be significantly enhanced. Our theory and simulations show that by using pH buffer solutions containing counter-ions that are beyond a specific size, the sensor shows significantly higher sensitivity which can exceed the Nernst limit. We validate the theory by measuring the pH response of an extended gate ISFET pH sensor. The consistency and reproducibility of the measurement results have been recorded in hysteresis free and stable operations. Different conditions have been tested to confirm the accuracy and validity of our experiment results such as using different solutions, various oxide dielectrics as the sensing layer and off-the-shelf versus IC fabricated transistors as the basis of the ISFET sensor. PMID:28150700

Expression of pH-sensitive green fluorescent protein in Arabidopsis thaliana

NASA Technical Reports Server (NTRS)

Moseyko, N.; Feldman, L. J.

2001-01-01

This is the first report on using green fluorescent protein (GFP) as a pH reporter in plants. Proton fluxes and pH regulation play important roles in plant cellular activity and therefore, it would be extremely helpful to have a plant gene reporter system for rapid, non-invasive visualization of intracellular pH changes. In order to develop such a system, we constructed three vectors for transient and stable transformation of plant cells with a pH-sensitive derivative of green fluorescent protein. Using these vectors, transgenic Arabidopsis thaliana and tobacco plants were produced. Here the application of pH-sensitive GFP technology in plants is described and, for the first time, the visualization of pH gradients between different developmental compartments in intact whole-root tissues of A. thaliana is reported. The utility of pH-sensitive GFP in revealing rapid, environmentally induced changes in cytoplasmic pH in roots is also demonstrated.

Characterization of Polyelectrolyte Complex Formation Between Anionic and Cationic Poly(amino acids) and Their Potential Applications in pH-Dependent Drug Delivery.

PubMed

Folchman-Wagner, Zoë; Zaro, Jennica; Shen, Wei-Chiang

2017-06-30

Polyelectrolyte complexes (PECs) are self-assembling nano-sized constructs that offer several advantages over traditional nanoparticle carriers including controllable size, biodegradability, biocompatibility, and lack of toxicity, making them particularly appealing as tools for drug delivery. Here, we discuss potential application of PECs for drug delivery to the slightly acidic tumor microenvironment, a pH in the range of 6.5-7.0. Poly(l-glutamic acid) (E n ), poly(l-lysine) (K n ), and a copolymer composed of histidine-glutamic acid repeats ((HE) n ) were studied for their ability to form PECs, which were analyzed for size, polydispersity, and pH sensitivity. PECs showed concentration dependent size variation at residue lengths of E 51 /K 55 and E 135 /K 127 , however, no complexes were observed when E 22 or K 21 were used, even in combination with the longer chains. (HE) 20 /K 55 PECs could encapsulate daunomycin, were stable from pH 7.4-6.5, and dissociated completely between pH 6.5-6.0. Conversely, the E 51-dauno /K 55 PEC dissociated between pH 4.0 and 3.0. These values for pH-dependent particle dissociation are consistent with the p K a 's of the ionizable groups in each formulation and indicate that the specific pH-sensitivity of (HE) 20-dauno /K 55 PECs is mediated by incorporation of histidine. This response within a pH range that is physiologically relevant to the acidic tumors suggests a potential application of these PECs in pH-dependent drug delivery.

2D ratiometric fluorescent pH sensor for tracking of cells proliferation and metabolism.

PubMed

Ma, Jun; Ding, Changqin; Zhou, Jie; Tian, Yang

2015-08-15

Extracellular pH plays a vital role no matter in physiological or pathological studies. In this work, a hydrogel, CD@Nile-FITC@Gel (Gel sensor), entrapping the ratiometric fluorescent probe CD@Nile-FITC was developed. The Gel sensor was successfully used for real-time extracellular pH monitoring. In the case of CD@Nile-FITC, pH-sensitive fluorescent dye fluorescein isothiocyanate (FITC) was chosen as the response signal for H(+) and Nile blue chloride (Nile) as the reference signal. The developed fluorescent probe exhibited high selectivity for pH over other metal ions and amino acids. Meanwhile, the carbon-dots-based inorganic-organic probe demonstrated excellent photostability against long-term light illumination. In order to study the extracellular pH change in processes of cell proliferation and metabolism, CD@Nile-FITC probe was entrapped in sodium alginate gel and consequently formed CD@Nile-FITC@Gel. The MTT assay showed low cytotoxicity of the Gel and the pH titration indicated that it could monitor the pH fluctuations linearly and rapidly within the pH range of 6.0-9.0, which is valuable for physiological pH determination. As expected, the real-time bioimaging of the probe was successfully achieved. Copyright © 2015 Elsevier B.V. All rights reserved.

Effective and efficient detection of pH fluctuations based on ratiometric metallic-ciprofloxacin architectures

NASA Astrophysics Data System (ADS)

Wang, Zhuosen; Gao, Jinwei; Zhang, Kaibo; Mai, Zhihong; Wang, Qianming

2018-07-01

The availability of lanthanide ciprofloxacin complexes and the exploration of efficient new ways to the target species have made fluorescent signals as essential tools for chemical sensing. Both terbium (III) and europium (III) compounds possess easily distinguished, line-like emission bands occurring in the green and red region respectively. Based on the steps of ionizations and the coordination structure changes, the two molecular probes give rise to unique pH-sensitivities at different conditions. The photoluminescence properties of the mixture for the two complexes are demonstrated. At pH from 3 to 6, the Eu(III) emission is found to be less affected and the solution emits blue light in acidic environment (pH = 3). The terbium (III) characteristic luminescence exhibited off-on changes within a narrow pH range (pH = 5-6). Further spectroscopic pH titrations (pH from 6 to 10) are performed and the Eu (III) red emission has been significantly improved. The molecular-based probes have excellent water solubility, negligible cytotoxicity and enough permeability to across cell membrane. Such pH-responsive performance has been carried out for the investigation of intracellular pH measurement and these novel pH indicators were considered to be suitable for detecting bio-medical samples.

The Fab1/PIKfyve phosphoinositide phosphate kinase is not necessary to maintain the pH of lysosomes and of the yeast vacuole.

PubMed

Ho, Cheuk Y; Choy, Christopher H; Wattson, Christina A; Johnson, Danielle E; Botelho, Roberto J

2015-04-10

Lysosomes and the yeast vacuole are degradative and acidic organelles. Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a master architect of endolysosome and vacuole identity, is thought to be necessary for vacuolar acidification in yeast. There is also evidence that PtdIns(3,5)P2 may play a role in lysosomal acidification in higher eukaryotes. Nevertheless, these conclusions rely on qualitative assays of lysosome/vacuole pH. For example, quinacrine, an acidotropic fluorescent base, does not accumulate in the vacuoles of fab1Δ yeast. Fab1, along with its mammalian ortholog PIKfyve, is the lipid kinase responsible for synthesizing PtdIns(3,5)P2. In this study, we employed several assays that quantitatively assessed the lysosomal and vacuolar pH in PtdIns(3,5)P2-depleted cells. Using ratiometric imaging, we conclude that lysosomes retain a pH < 5 in PIKfyve-inhibited mammalian cells. In addition, quantitative fluorescence microscopy of vacuole-targeted pHluorin, a pH-sensitive GFP variant, indicates that fab1Δ vacuoles are as acidic as wild-type yeast. Importantly, we also employed fluorimetry of vacuoles loaded with cDCFDA, a pH-sensitive dye, to show that both wild-type and fab1Δ vacuoles have a pH < 5.0. In comparison, the vacuolar pH of the V-ATPase mutant vph1Δ or vph1Δ fab1Δ double mutant was 6.1. Although the steady-state vacuolar pH is not affected by PtdIns(3,5)P2 depletion, it may have a role in stabilizing the vacuolar pH during salt shock. Overall, we propose a model in which PtdIns(3,5)P2 does not govern the steady-state pH of vacuoles or lysosomes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The Fab1/PIKfyve Phosphoinositide Phosphate Kinase Is Not Necessary to Maintain the pH of Lysosomes and of the Yeast Vacuole*

PubMed Central

Ho, Cheuk Y.; Choy, Christopher H.; Wattson, Christina A.; Johnson, Danielle E.; Botelho, Roberto J.

2015-01-01

Lysosomes and the yeast vacuole are degradative and acidic organelles. Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a master architect of endolysosome and vacuole identity, is thought to be necessary for vacuolar acidification in yeast. There is also evidence that PtdIns(3,5)P2 may play a role in lysosomal acidification in higher eukaryotes. Nevertheless, these conclusions rely on qualitative assays of lysosome/vacuole pH. For example, quinacrine, an acidotropic fluorescent base, does not accumulate in the vacuoles of fab1Δ yeast. Fab1, along with its mammalian ortholog PIKfyve, is the lipid kinase responsible for synthesizing PtdIns(3,5)P2. In this study, we employed several assays that quantitatively assessed the lysosomal and vacuolar pH in PtdIns(3,5)P2-depleted cells. Using ratiometric imaging, we conclude that lysosomes retain a pH < 5 in PIKfyve-inhibited mammalian cells. In addition, quantitative fluorescence microscopy of vacuole-targeted pHluorin, a pH-sensitive GFP variant, indicates that fab1Δ vacuoles are as acidic as wild-type yeast. Importantly, we also employed fluorimetry of vacuoles loaded with cDCFDA, a pH-sensitive dye, to show that both wild-type and fab1Δ vacuoles have a pH < 5.0. In comparison, the vacuolar pH of the V-ATPase mutant vph1Δ or vph1Δ fab1Δ double mutant was 6.1. Although the steady-state vacuolar pH is not affected by PtdIns(3,5)P2 depletion, it may have a role in stabilizing the vacuolar pH during salt shock. Overall, we propose a model in which PtdIns(3,5)P2 does not govern the steady-state pH of vacuoles or lysosomes. PMID:25713145

Abscission of flowers and floral organs is closely associated with alkalization of the cytosol in abscission zone cells.

PubMed

Sundaresan, Srivignesh; Philosoph-Hadas, Sonia; Riov, Joseph; Belausov, Eduard; Kochanek, Betina; Tucker, Mark L; Meir, Shimon

2015-03-01

In vivo changes in the cytosolic pH of abscission zone (AZ) cells were visualized using confocal microscopic detection of the fluorescent pH-sensitive and intracellularly trapped dye, 2',7'-bis-(2-carboxyethyl)-5(and-6)-carboxyfluorescein (BCECF), driven by its acetoxymethyl ester. A specific and gradual increase in the cytosolic pH of AZ cells was observed during natural abscission of flower organs in Arabidopsis thaliana and wild rocket (Diplotaxis tenuifolia), and during flower pedicel abscission induced by flower removal in tomato (Solanum lycopersicum Mill). The alkalization pattern in the first two species paralleled the acceleration or inhibition of flower organ abscission induced by ethylene or its inhibitor 1-methylcyclopropene (1-MCP), respectively. Similarly, 1-MCP pre-treatment of tomato inflorescence explants abolished the pH increase in AZ cells and pedicel abscission induced by flower removal. Examination of the pH changes in the AZ cells of Arabidopsis mutants defective in both ethylene-induced (ctr1, ein2, eto4) and ethylene-independent (ida, nev7, dab5) abscission pathways confirmed these results. The data indicate that the pH changes in the AZ cells are part of both the ethylene-sensitive and -insensitive abscission pathways, and occur concomitantly with the execution of organ abscission. pH can affect enzymatic activities and/or act as a signal for gene expression. Changes in pH during abscission could occur via regulation of transporters in AZ cells, which might affect cytosolic pH. Indeed, four genes associated with pH regulation, vacuolar H(+)-ATPase, putative high-affinity nitrate transporter, and two GTP-binding proteins, were specifically up-regulated in tomato flower AZ following abscission induction, and 1-MCP reduced or abolished the increased expression. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Measurement of the Extracellular pH of Adherently Growing Mammalian Cells with High Spatial Resolution Using a Voltammetric pH Microsensor.

PubMed

Munteanu, Raluca-Elena; Stǎnicǎ, Luciana; Gheorghiu, Mihaela; Gáspár, Szilveszter

2018-05-15

There are only a few tools suitable for measuring the extracellular pH of adherently growing mammalian cells with high spatial resolution, and none of them is widely used in laboratories around the world. Cell biologists very often limit themselves to measuring the intracellular pH with commercially available fluorescent probes. Therefore, we built a voltammetric pH microsensor and investigated its suitability for monitoring the extracellular pH of adherently growing mammalian cells. The voltammetric pH microsensor consisted of a 37 μm diameter carbon fiber microelectrode modified with reduced graphene oxide and syringaldazine. While graphene oxide was used to increase the electrochemically active surface area of our sensor, syringaldazine facilitated pH sensing through its pH-dependent electrochemical oxidation and reduction. The good sensitivity (60 ± 2.5 mV/pH unit), reproducibility (coefficient of variation ≤3% for the same pH measured with 5 different microsensors), and stability (pH drift around 0.05 units in 3 h) of the built voltammetric pH sensors were successfully used to investigate the acidification of the extracellular space of both cancer cells and normal cells. The results indicate that the developed pH microsensor and the perfected experimental protocol based on scanning electrochemical microscopy can reveal details of the pH regulation of cells not attainable with pH sensors lacking spatial resolution or which cannot be reproducibly positioned in the extracellular space.

Pyrene functionalized molecular beacon with pH-sensitive i-motif in a loop.

PubMed

Dembska, Anna; Juskowiak, Bernard

2015-01-01

In this work, we present a spectral characterization of pH-sensitive system, which combines the i-motif properties with the spatially sensitive fluorescence signal of pyrene molecules attached to hairpin ends. The excimer production (fluorescence max. ∼480 nm) by pyrene labels at the ends of the molecular beacon is driven by pH-dependent i-motif formation in the loop. To illustrate the performance and reversible work of our systems, we performed the experiments with repeatedly pH cycling between pH values of 7.5±0.3 and 6.5±0.3. The sensor gives analytical response in excimer-monomer switching mode in narrow pH range (1.5 pH units) and exhibits high pH resolution (0.1 pH unit). Copyright © 2015 Elsevier B.V. All rights reserved.

Role of deposition and annealing of the top gate dielectric in a-IGZO TFT-based dual-gate ion-sensitive field-effect transistors

NASA Astrophysics Data System (ADS)

Kumar, Narendra; Sutradhar, Moitri; Kumar, Jitendra; Panda, Siddhartha

2017-03-01

The deposition of the top gate dielectric in thin film transistor (TFT)-based dual-gate ion-sensitive field-effect transistors (DG ISFETs) is critical, and expected not to affect the bottom gate TFT characteristics, while providing a higher pH sensitive surface and efficient capacitive coupling between the gates. Amorphous Ta2O5, in addition to having good sensing properties, possesses a high dielectric constant of ˜25 making it well suited as the top gate dielectric in a DG ISFET by providing higher capacitive coupling (ratio of C top/C bottom) leading to higher amplification. To avoid damage of the a-IGZO channel reported to be caused by plasma exposure, deposition of Ta2O5 by e-beam evaporation followed by annealing was investigated in this work to obtain sensitivity over the Nernst limit. The deteriorated bottom gate TFT characteristics, indicated by an increase in the channel conductance, confirmed that plasma exposure is not the sole contributor to the changes. Oxygen vacancies at the Ta2O5/a-IGZO interface, which emerged during processing, increased the channel conductivity, became filled by optimum annealing in oxygen at 400 °C for 1 h, which was confirmed by an x-ray photoelectron spectroscopy depth profiling analysis. The obtained pH sensitivity of the TFT-based DG ISFET was 402 mV pH-1, which is about 6.8 times the Nernst limit (59 mV pH-1). The concept of capacitive coupling was also demonstrated by simulating an a-IGZO-based DG TFT structure. Here, the exposure of the top gate dielectric to the electrolyte without applying any top gate bias led to changes in the measured threshold voltage of the bottom gate TFT, and this obviated the requirement of a reference electrode needed in conventional ISFETs and other reported DG ISFETs. These devices, with high sensitivities and requiring low volumes (˜2 μl) of analyte solution, could be potential candidates for utilization as chemical sensors and biosensors.

Growth and survival of cowpea rhizobia in acid, aluminum-rich soils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartel, P.G.; Alexander, M.

1983-01-01

A study was undertaken to determine whether Al-sensitive cowpea Rhizobium survives in acid, Al-rich soils. The lower pH limit for growth of 20 strains in a defined liquid medium varied from pH 4.2 to less than pH 3.6. The mean lower limit for growth was pH 3.9. Several of the strains clumped in this medium at pH 4.5. Of 11 strains that were tested for tolerance to high levels of Al in a defined liquid medium at pH 4.5, nine tolerated 75 ..mu..M Al, and the other two were sensitive to levels above 15 ..mu..M. Three strains, one Al-tolerant, onemore » Al-sensitive, and one Al-tolerant or Al-sensitive depending on the presence of vitamins in the medium, were selected for studies in Al-rich sterile and nonsterile soils. These rhizobia did not survive in soils of less than pH 4.7 sterilized by /sup 60/Co irradiation. When inoculated into sterile soil at pH 4.7, the consistently sensitive strain initially failed to proliferate and then grew slowly, but populations of the other two rhizobia increased rapidly. No consistent relationship was found between the Al tolerance of these three rhizobia and their growth and survival in four acid, Al-rich soils. The data suggest that Al is of minor importance to growth and survival of cowpea Rhizobium strains in acid soils. 16 references, 4 figures, 1 table.« less

pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1.

PubMed

Varma, Manthena V; Rotter, Charles J; Chupka, Jonathan; Whalen, Kevin M; Duignan, David B; Feng, Bo; Litchfield, John; Goosen, Theunis C; El-Kattan, Ayman F

2011-08-01

The human organic anion transporting polypeptide 2B1 (OATP2B1, SLCO2B1) is ubiquitously expressed and may play an important role in the disposition of xenobiotics. The present study aimed to examine the role of OATP2B1 in the intestinal absorption and tissue uptake of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitors (statins). We first investigated the functional affinity of statins to the transporter as a function of extracellular pH, using OATP2B1-transfeced HEK293 cells. The results indicate that OATP2B1-mediated transport is significant for rosuvastatin, fluvastatin and atorvastatin, at neutral pH. However, OATP2B1 showed broader substrate specificity as well as enhanced transporter activity at acidic pH. Furthermore, uptake at acidic pH was diminished in the presence of proton ionophore, suggesting proton gradient as the driving force for OATP2B1 activity. Notably, passive transport rates are predominant or comparable to active transport rates for statins, except for rosuvastatin and fluvastatin. Second, we studied the effect of OATP modulators on statin uptake. At pH 6.0, OATP2B1-mediated transport of atorvastatin and cerivastatin was not inhibitable, while rosuvastatin transport was inhibited by E-3-S, rifamycin SV and cyclosporine with IC(50) values of 19.7 ± 3.3 μM, 0.53 ± 0.2 μM and 2.2 ± 0.4 μM, respectively. Rifamycin SV inhibited OATP2B1-mediated transport of E-3-S and rosuvastatin with similar IC(50) values at pH 6.0 and 7.4, suggesting that the inhibitor affinity is not pH-dependent. Finally, we noted that OATP2B1-mediated transport of E-3-S, but not rosuvastatin, is pH sensitive in intestinal epithelial (Caco-2) cells. However, uptake of E-3-S and rosuvastatin by Caco-2 cells was diminished in the presence of proton ionophore. The present results indicate that OATP2B1 may be involved in the tissue uptake of rosuvastatin and fluvastatin, while OATP2B1 may play a significant role in the intestinal absorption of several statins due to their transporter affinity at acidic pH.

A simple and highly sensitive colorimetric detection method for gaseous formaldehyde.

PubMed

Feng, Liang; Musto, Christopher J; Suslick, Kenneth S

2010-03-31

A colorimetric detection method using amine-functionalized polymer films doped with a pH indicator has been developed for the rapid, sensitive, and quantitative detection of gaseous formaldehyde at concentrations well below the immediately dangerous to life or health (IDLH) limit. In 1 min, visible color changes are easily observed, even down to the permissible exposure limit (PEL) at 750 ppb. The limit of detection is below 50 ppb (7% of the PEL) after 10 min of exposure. This sensor is essentially unaffected by changes in humidity or temperature (4 to 50 degrees C) and is not sensitive to common interferents.

Adsorption of Polycyclic aromatic hydrocarbons (fluoranthene and anthracenemethanol) by functional graphene oxide and removal by pH and temperature-sensitive coagulation.

PubMed

Zhang, Caili; Wu, Lin; Cai, Dongqing; Zhang, Caiyun; Wang, Ning; Zhang, Jing; Wu, Zhengyan

2013-06-12

A new kind of functional graphene oxide with fine stability in water was fabricated by mixing graphene oxide (GO) and brilliant blue (BB) with a certain weight ratio. The adsorption performance of this mixture of BB and GO (BBGO) to polycyclic aromatic hydrocarbons (anthracenemethanol (AC) and fluoranthene (FL)) was investigated, and the results indicated BBGO possessed adsorption capacity of 1.676 mmol/g and removal efficiency of 72.7% as to AC and adsorption capacity of 2.212 mmol/g and removal efficiency of 93.2% as to FL. After adsorption, pH and temperature-sensitive coagulation (PTC) method was used to remove the AC/BBGO or FL/BBGO complex and proved to be an effective approach to flocculate the AC/BBGO or FL/BBGO complex into large flocs, which tended to be removed from the aqueous solution.

Preparation of pH-sensitive poly(glycidol) derivatives with varying hydrophobicities: their ability to sensitize stable liposomes to pH.

PubMed

Sakaguchi, Naoki; Kojima, Chie; Harada, Atsushi; Kono, Kenji

2008-05-01

We have previously shown that modification with succinylated poly(glycidol) (SucPG) provides stable egg yolk phosphatidylcholine (EYPC) liposomes with pH-sensitive fusogenic property. Toward production of efficient pH-sensitive liposomes, in this study, we newly prepared three carboxylated poly(glycidol) derivatives with varying hydrophobicities by reacting poly(glycidol) with glutaric anhydride, 3-methylglutaric anhydride, and 1,2-cyclohexanedicarboxylic anhydride, respectively, designated as GluPG, MGluPG, and CHexPG. Correlation between side-chain structures of these polymers and their respective abilities to sensitize stable liposomes to pH was investigated. These polymers are soluble in water at neutral pH but became water-insoluble in weakly acidic conditions. The pH at which the polymer precipitated was higher in the order SucPG < GluPG < MGluPG < CHexPG, which is consistent with the number of carbon atoms of these polymers' side chains. Although CHexPG destabilized EYPC liposomes even at neutral pH, attachment of other polymers provided pH-sensitive properties to the liposomes. The liposomes bearing polymers with higher hydrophobicity exhibited more intense responses, such as content release and membrane fusion, at mildly acidic pH and achieved more efficient cytoplasmic delivery of membrane-impermeable dye molecules. As a result, modification with appropriate hydrophobicity, MGluPG, produced highly potent pH-sensitive liposomes, which might be useful for efficient cytoplasmic delivery of bioactive molecules, such as proteins and genes.

Imaging Lysosomal pH Alteration in Stressed Cells with a Sensitive Ratiometric Fluorescence Sensor.

PubMed

Xue, Zhongwei; Zhao, Hu; Liu, Jian; Han, Jiahuai; Han, Shoufa

2017-03-24

The organelle-specific pH is crucial for cell homeostasis. Aberrant pH of lysosomes has been manifested in myriad diseases. To probe lysosome responses to cell stress, we herein report the detection of lysosomal pH changes with a dual colored probe (CM-ROX), featuring a coumarin domain with "always-on" blue fluorescence and a rhodamine-lactam domain activatable to lysosomal acidity to give red fluorescence. With sensitive ratiometric signals upon subtle pH changes, CM-ROX enables discernment of lysosomal pH changes in cells undergoing autophagy, cell death, and viral infection.

PH-sensitive dispersion of carbon nanotubes by myoglobin

NASA Astrophysics Data System (ADS)

Nie, Haiyu; Shen, Ganni; Sun, Junlin; Zhang, Tao

2017-03-01

A facile and effective method of dispersion of double-walled carbon nanotubes (DWNTs) was developed. At appropriate pH value and sonication, myoglobin helps the solubilization of DWNTs. The product is a pH-sensitive dispersion, which remains in a highly dispersed state at pH<3.0 and pH>10.0. This approach can be used to disperse DWNTs in scale. A reversible conversion of the highly dispersed state to the aggregated state could be observed by changing the pH value. This feature holds great promise for the development of pH sensors.

The interplay between pH sensitivity and label-free protein detection in immunologically modified nano-scaled field-effect transistor.

PubMed

Shalev, Gil; Rosenwaks, Yossi; Levy, Ilan

2012-01-15

We present experimental results in order to establish a correlation between pH sensitivity of immunologically modified nano-scaled field-effect transistor (NS-ImmunoFET) with their sensing capacity for label-free detection. The NS-ImmunoFETs are fabricated from silicon-on-insulator (SOI) wafers and are fully-depleted with thickness of ~20 nm. The data shows that higher sensitivity to pH entails enhanced sensitivity to analyte detection. This suggests that the mechanism of analyte detection as pure electrostatic perturbation induced by antibody-analyte interaction is over simplified. The fundamental assumption, in existing models for field-effect sensing mechanism assumes that the analyte molecules do not directly interact with the surface but rather stand 'deep' in the solution and away from the dielectric surface. Recent studies clearly provide contradicting evidence demonstrating that antibodies lie down flat on the surface. These observations led us to propose that the proteins that cover the gate area intimately interact with active sites on the surface thus forming a network of interacting sites. Since sensitivity to pH is directly correlated with the amount of amphoteric sites, we witness a direct correlation between sensitivity to pH and analyte detection. The highest and lowest threshold voltage shift for a label-free and specific detection of 6.5 nM IgG were 40 mV and 2.3 mV for NS-ImmunoFETs with pH sensitivity of 35 mV/decade and 15 mV/decade, respectively. Finally, physical modeling of the NS-ImmunoFET is presented and charge of a single IgG protein at pH 6 is calculated. The obtained value is consistent with charge of IgG protein cited in literature. Copyright © 2011 Elsevier B.V. All rights reserved.

A novel "modularized" optical sensor for pH monitoring in biological matrixes.

PubMed

Liu, Xun; Zhang, Shang-Qing; Wei, Xing; Yang, Ting; Chen, Ming-Li; Wang, Jian-Hua

2018-06-30

A novel core-shell structure optical pH sensor is developed with upconversion nanoparticles (UCNPs) serving as the core and silica as the shell, followed by grafting bovineserumalbumin (BSA) as another shell via glutaraldehyde cross-linking. The obtained core-shell-shell structure is shortly termed as UCNPs@SiO 2 @BSA, and its surface provides a platform for loading various pH sensitive dyes, which are alike "modules" to make it feasible for measuring pHs within different pH ranges by simply regulating the type of dyes. Generally, a single pH sensitive dye is adopted to respond within a certain pH range. This study employs bromothymol blue (BTB) and rhodamine B (RhB) to facilitate their responses to pH variations within two ranges, i.e., pH 5.99-8.09 and pH 4.98-6.40, respectively, with detection by ratio-fluorescence protocol. The core-shell-shell structure offers superior sensitivity, which is tens of times more sensitive than those achieved by ratio-fluorescence approaches based on various nanostructures, and favorable stability is achieved in high ionic strength medium. In addition, this sensor exhibits superior photostability under continuous excitation at 980 nm. Thanks to the near infrared excitation in the core-shell-shell structure, it effectively avoids the self-fluorescence from biological samples and thus facilitates accurate sensing of pH in various biological sample matrixes. Copyright © 2018 Elsevier B.V. All rights reserved.

A ph sensor based on a flexible substrate

NASA Astrophysics Data System (ADS)

Huang, Wen-Ding

pH sensor is an essential component used in many chemical, food, and bio-material industries. Conventional glass electrodes have been used to construct pH sensors, however, have some disadvantages. Glass electrodes are easily affected by alkaline or HF solution, they require a high input impedance pH meter, they often exhibit a sluggish response. In some specific applications, it is also difficult to use glass electrodes for in vivo biomedical or food monitoring applications due to the difficulty of size miniaturization, planarization and polymerization based on current manufacturing technologies. In this work, we have demonstrated a novel flexible pH sensor based on low-cost sol-gel fabrication process of iridium oxide (IrOx) sensing film (IROF). A pair of flexible miniature IrOx/AgCl electrode generated the action potential from the solution by electrochemical mechanism to obtain the pH level of the reagent. The fabrication process including sol-gel, thermal oxidation, and the electro-plating process of the silver chloride (AgCl) reference electrode were reported in the work. The IrOx film was verified and characterized using electron dispersive analysis (EDAX), scanning electron microscope (SEM), and x-ray diffraction (XRD). The flexible pH sensor's performance and characterization have been investigated with different testing parameters such as sensitivity, response time, stability, reversibility, repeatability, selectivity and temperature dependence. The flexible IrOx pH sensors exhibited promising sensing performance with a near-Nernstian response of sensitivity which is between --51.1mV/pH and --51.7mV/pH in different pH levels ranging from 1.5 to 12 at 25°C. Two applications including gastroesophageal reflux disease (GERD) diagnosis and food freshness wireless monitoring using our micro-flexible IrOx pH sensors were demonstrated. For the GERD diagnosing system, we embedded the micro flexible pH sensor on a 1.2cmx3.8cm of the capsule size of wireless sensor implanted inside the esophagus. Our pH electrode can monitor the pH changes of gastric juice in real time when the reflux happening in the esophagus. Our micro flexible pH sensor performed clear responses in each distinct pH reflux episode quickly and accurately comparing with the other commercial pH monitoring system. For the food freshness monitoring applications, we used the flexible pH sensor as a freshness indicator to monitor the pH changing profile during the food spoilage procedure. The sensor was then embedded with radio frequency identification (RFID) based passive telemetry enabling remote monitoring of food freshness. In the result, our pH-wireless RFID system presented 633Hz/pH of the sensitivity in the frequency calibration. The calibration of stability and dynamical response of the RFID system were also demonstrated before the test on food freshness monitoring. Finally, a white fish meat for long term spoilage procedure monitoring was applied and tested by using our wireless IrOx pH sensing system. Our RFID pH sensing module is able to monitor, collect and transmit the pH information continuously for 18 hours during the food spoilage procedure. In this dissertation, a micro size of IrOx/AgCl pH sensor was fabricated on a flexible substrate. The physical properties of the IrO x thin film was verified in the work. The different sensing capability such as the sensitivity, stability, reversibility, response time, repeatability, selectivity, and temperature dependence was then demonstrated in this work. After the different in-vitro tests, the pH sensor were embedded with our passive RFID circuitry for the in-vivo GERD diagnosis and food freshness monitoring application. Our wireless pH sensing system was able to deliver the accurate and quick pH sensing data wirelessly. In conclusion, our deformable IrOx pH electrodes have been demonstrated with the advantages of accommodating and conforming sensors in small spaces or curved surfaces. This miniature IrOx pH sensor can respond to distinct potentials of the various pH levels as traditional glass electrodes, however, the miniature, bio-compatible and flexible substrate and the ability to be integrated in batterryless telemetry enable the pH sensor to be applied on many new medical, bio-chemical and biological field.

Measuring Synaptic Vesicle Endocytosis in Cultured Hippocampal Neurons.

PubMed

Villarreal, Seth; Lee, Sung Hoon; Wu, Ling-Gang

2017-09-04

During endocytosis, fused synaptic vesicles are retrieved at nerve terminals, allowing for vesicle recycling and thus the maintenance of synaptic transmission during repetitive nerve firing. Impaired endocytosis in pathological conditions leads to decreases in synaptic strength and brain functions. Here, we describe methods used to measure synaptic vesicle endocytosis at the mammalian hippocampal synapse in neuronal culture. We monitored synaptic vesicle protein endocytosis by fusing a synaptic vesicular membrane protein, including synaptophysin and VAMP2/synaptobrevin, at the vesicular lumenal side, with pHluorin, a pH-sensitive green fluorescent protein that increases its fluorescence intensity as the pH increases. During exocytosis, vesicular lumen pH increases, whereas during endocytosis vesicular lumen pH is re-acidified. Thus, an increase of pHluorin fluorescence intensity indicates fusion, whereas a decrease indicates endocytosis of the labelled synaptic vesicle protein. In addition to using the pHluorin imaging method to record endocytosis, we monitored vesicular membrane endocytosis by electron microscopy (EM) measurements of Horseradish peroxidase (HRP) uptake by vesicles. Finally, we monitored the formation of nerve terminal membrane pits at various times after high potassium-induced depolarization. The time course of HRP uptake and membrane pit formation indicates the time course of endocytosis.

Fiber optic SERS-based plasmonics nanobiosensing in single living cells

NASA Astrophysics Data System (ADS)

Scaffidi, Jonathan P.; Gregas, Molly K.; Seewaldt, Victoria; Vo-Dinh, Tuan

2009-05-01

We describe the development of small molecule-sensitive plasmonics-active fiber-optic nanoprobes suitable for intracellular bioanalysis in single living human cells using surface-enhanced Raman scattering (SERS) detection. The practical utility of SERS-based fiber-optic nanoprobes is illustrated by measurements of intracellular pH in HMEC- 15/hTERT immortalized "normal" human mammary epithelial cells and PC-3 human prostate cancer cells. The results indicate that fiber-optic nanoprobe insertion and interrogation provide a sensitive and selective means to monitor biologically-relevant small molecules at the single cell level.

pH-Sensitive nanoparticles as smart carriers for selective intracellular drug delivery to tumor.

PubMed

Li, Xin-Xin; Chen, Jing; Shen, Jian-Min; Zhuang, Ran; Zhang, Shi-Qi; Zhu, Zi-Yun; Ma, Jing-Bo

2018-05-05

Herein, a smart pH-sensitive nanoparticle (DGL-PEG-Tat-KK-DMA-DOX) was prepared to achieve the selective intracellular drug delivery. In this nanoparticle, a PEG-grafted cell penetrating peptide (PEG-Tat-KK) was designed and acted as the cell penetrating segment. By introducing the pH-sensitive amide bonds between the peptide and blocking agent (2,3-dimethylmaleic anhydride, DMA), the controllable moiety (PEG-Tat-KK-DMA) endowed the nanoparticle with a charge-switchable shell and temporarily blocked penetrating function, thus improving the specific internalization. Besides, dendrigraft poly-L-lysine (DGL) used as the skeleton can greatly improve the drug loading because of the highly dendritic framework. Under the stimuli of acidic pH, this nanoparticle exhibited a remarkable charge-switchable property. The drug release showed an expected behavior with little release in the neutral pH media but relatively fast release in the acidic media. The in vitro experiments revealed that the cellular uptake and cytotoxicity were significantly enhanced after the pH was decreased. In vivo biodistribution and antitumor research indicated that the nanoparticle had noteworthy specificity and antitumor efficacy with a tumor inhibition rate of 79.7%. These results verified this nanoparticle could efficiently improve the selective intracellular delivery and possessed a great potential in tumor treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Flexible Sensory Platform Based on Oxide-based Neuromorphic Transistors

NASA Astrophysics Data System (ADS)

Liu, Ning; Zhu, Li Qiang; Feng, Ping; Wan, Chang Jin; Liu, Yang Hui; Shi, Yi; Wan, Qing

2015-12-01

Inspired by the dendritic integration and spiking operation of a biological neuron, flexible oxide-based neuromorphic transistors with multiple input gates are fabricated on flexible plastic substrates for pH sensor applications. When such device is operated in a quasi-static dual-gate synergic sensing mode, it shows a high pH sensitivity of ~105 mV/pH. Our results also demonstrate that single-spike dynamic mode can remarkably improve pH sensitivity and reduce response/recover time and power consumption. Moreover, we find that an appropriate negative bias applied on the sensing gate electrode can further enhance the pH sensitivity and reduce the power consumption. Our flexible neuromorphic transistors provide a new-concept sensory platform for biochemical detection with high sensitivity, rapid response and ultralow power consumption.

Flexible Sensory Platform Based on Oxide-based Neuromorphic Transistors

PubMed Central

Liu, Ning; Zhu, Li Qiang; Feng, Ping; Wan, Chang Jin; Liu, Yang Hui; Shi, Yi; Wan, Qing

2015-01-01

Inspired by the dendritic integration and spiking operation of a biological neuron, flexible oxide-based neuromorphic transistors with multiple input gates are fabricated on flexible plastic substrates for pH sensor applications. When such device is operated in a quasi-static dual-gate synergic sensing mode, it shows a high pH sensitivity of ~105 mV/pH. Our results also demonstrate that single-spike dynamic mode can remarkably improve pH sensitivity and reduce response/recover time and power consumption. Moreover, we find that an appropriate negative bias applied on the sensing gate electrode can further enhance the pH sensitivity and reduce the power consumption. Our flexible neuromorphic transistors provide a new-concept sensory platform for biochemical detection with high sensitivity, rapid response and ultralow power consumption. PMID:26656113

Block of nicotinic acetylcholine receptors by philanthotoxins is strongly dependent on their subunit composition

PubMed Central

Kachel, Hamid S.; Patel, Rohit N.; Franzyk, Henrik; Mellor, Ian R.

2016-01-01

Philanthotoxin-433 (PhTX-433) is an active component of the venom from the Egyptian digger wasp, Philanthus triangulum. PhTX-433 inhibits several excitatory ligand-gated ion channels, and to improve selectivity two synthetic analogues, PhTX-343 and PhTX-12, were developed. Previous work showed a 22-fold selectivity of PhTX-12 over PhTX-343 for embryonic muscle-type nicotinic acetylcholine receptors (nAChRs) in TE671 cells. We investigated their inhibition of different neuronal nAChR subunit combinations as well as of embryonic muscle receptors expressed in Xenopus oocytes. Whole-cell currents in response to application of acetylcholine alone or co-applied with PhTX analogue were studied by using two-electrode voltage-clamp. α3β4 nAChRs were most sensitive to PhTX-343 (IC50 = 12 nM at −80 mV) with α4β4, α4β2, α3β2, α7 and α1β1γδ being 5, 26, 114, 422 and 992 times less sensitive. In contrast α1β1γδ was most sensitive to PhTX-12 along with α3β4 (IC50 values of 100 nM) with α4β4, α4β2, α3β2 and α7 being 3, 3, 26 and 49 times less sensitive. PhTX-343 inhibition was strongly voltage-dependent for all subunit combinations except α7, whereas this was not the case for PhTX-12 for which weak voltage dependence was observed. We conclude that PhTX-343 mainly acts as an open-channel blocker of nAChRs with strong subtype selectivity. PMID:27901080

[The construction of cell-penetrating peptide R8 and pH sensitive cleavable polyethylene glycols co-modified liposomes].

PubMed

Zhang, Li; Wang, Yang; Gao, Hui-le; He, Qin

2015-06-01

The purpose of the study is to construct R8 peptide (RRRRRRRR) and pH sensitive polyethylene glycols (PEG) co-modified liposomes (Cl-Lip) and utilize them in breast cancer treatment. The co-modified liposomes were prepared with soybean phospholipid, cholesterol, DSPE-PEG2K-R8 and PEG5K-Hz-PE (pH sensitive PEG). The size and zeta potential of Cl-Lip were also characterized. The in vitro experiment demonstrated that the Cl-Lip had high serum stability in 50% fetal bovine serum. The cellular uptake of Cl-Lip under different pre-incubated conditions was evaluated on 4T1 cells. And the endocytosis pathway, lysosome escape ability and tumor spheroid penetration ability were also evaluated. The results showed the particle size of the Cl-Lip was (110.4 ± 5.2) nm, PDI of the Cl-Lip was 0.207 ± 0.039 and zeta potential of the Cl-Lip was (-3.46 ± 0.05) mV. The cellular uptake of Cl-Lip on 4T1 cells was pH sensitive, as the cellular uptake of Cl-Lip pre-incubated in pH 6.0 was higher than that of pH 7.4 under each time point. The main endocytosis pathways of Cl-Lip under pH 6.0 were micropinocytosis and energy-dependent pathway. At the same time, the Cl-Lip with pre-incubation in pH 6.0 had high lysosome escape ability and high tumor spheroid penetration ability. All the above results demonstrated that the Cl-Lip we constructed had high pH sensitivity and is a promising drug delivery system.

Novel CD44 receptor targeting multifunctional "nano-eggs" based on double pH-sensitive nanoparticles for co-delivery of curcumin and paclitaxel to cancer cells and cancer stem cells

NASA Astrophysics Data System (ADS)

Chen, Daquan; Wang, Guohua; Song, Weiguo; Zhang, Qiang

2015-10-01

Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the "nano-eggs." The formed nano-eggs had a smaller size (120.6 ± 4.5 nm) than oHM micelles (158.6 ± 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the "nano-eggs" were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug delivery to both cancer cells and cancer stem cells.

Electrostatics Control Actin Filament Nucleation and Elongation Kinetics*

PubMed Central

Crevenna, Alvaro H.; Naredi-Rainer, Nikolaus; Schönichen, André; Dzubiella, Joachim; Barber, Diane L.; Lamb, Don C.; Wedlich-Söldner, Roland

2013-01-01

The actin cytoskeleton is a central mediator of cellular morphogenesis, and rapid actin reorganization drives essential processes such as cell migration and cell division. Whereas several actin-binding proteins are known to be regulated by changes in intracellular pH, detailed information regarding the effect of pH on the actin dynamics itself is still lacking. Here, we combine bulk assays, total internal reflection fluorescence microscopy, fluorescence fluctuation spectroscopy techniques, and theory to comprehensively characterize the effect of pH on actin polymerization. We show that both nucleation and elongation are strongly enhanced at acidic pH, with a maximum close to the pI of actin. Monomer association rates are similarly affected by pH at both ends, although dissociation rates are differentially affected. This indicates that electrostatics control the diffusional encounter but not the dissociation rate, which is critical for the establishment of actin filament asymmetry. A generic model of protein-protein interaction, including electrostatics, explains the observed pH sensitivity as a consequence of charge repulsion. The observed pH effect on actin in vitro agrees with measurements of Listeria propulsion in pH-controlled cells. pH regulation should therefore be considered as a modulator of actin dynamics in a cellular environment. PMID:23486468

Genetically encoded pH-indicators reveal activity-dependent cytosolic acidification of Drosophila motor nerve termini in vivo

PubMed Central

Rossano, Adam J; Chouhan, Amit K; Macleod, Gregory T

2013-01-01

All biochemical processes, including those underlying synaptic function and plasticity, are pH sensitive. Cytosolic pH (pHcyto) shifts are known to accompany nerve activity in situ, but technological limitations have prevented characterization of such shifts in vivo. Genetically encoded pH-indicators (GEpHIs) allow for tissue-specific in vivo measurement of pH. We expressed three different GEpHIs in the cytosol of Drosophila larval motor neurons and observed substantial presynaptic acidification in nerve termini during nerve stimulation in situ. SuperEcliptic pHluorin was the most useful GEpHI for studying pHcyto shifts in this model system. We determined the resting pH of the nerve terminal cytosol to be 7.30 ± 0.02, and observed a decrease of 0.16 ± 0.01 pH units when the axon was stimulated at 40 Hz for 4 s. Realkalinization occurred upon cessation of stimulation with a time course of 20.54 ± 1.05 s (τ). The chemical pH-indicator 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein corroborated these changes in pHcyto. Bicarbonate-derived buffering did not contribute to buffering of acid loads from short (≤4 s) trains of action potentials but did buffer slow (∼60 s) acid loads. The magnitude of cytosolic acid transients correlated with cytosolic Ca2+ increase upon stimulation, and partial inhibition of the plasma membrane Ca2+-ATPase, a Ca2+/H+ exchanger, attenuated pHcyto shifts. Repeated stimulus trains mimicking motor patterns generated greater cytosolic acidification (∼0.30 pH units). Imaging through the cuticle of intact larvae revealed spontaneous pHcyto shifts in presynaptic termini in vivo, similar to those seen in situ during fictive locomotion, indicating that presynaptic pHcyto shifts cannot be dismissed as artifacts of ex vivo preparations. PMID:23401611

pH-sensitive micelles self-assembled from polymer brush (PAE-g-cholesterol)-b-PEG-b-(PAE-g-cholesterol) for anticancer drug delivery and controlled release

PubMed Central

Huang, Xiangxuan; Liao, Wenbo; Zhang, Gang; Kang, Shimin; Zhang, Can Yang

2017-01-01

A novel amphiphilic pH-sensitive triblock polymer brush (poly(β-amino esters)-g-cholesterol)-b-poly(ethylene glycol)-b-(poly(β-amino esters)-g-cholesterol) ((PAE-g-Chol)-b-PEG-b-(PAE-g-Chol)) was designed and synthesized successfully through a three-step reaction, and their self-assembled polymeric micelles were used as hydrophobic anticancer drug delivery carriers to realize effectively controlled release. The critical micelle concentrations were 6.8 μg/mL, 12.6 μg/mL, 17.4 μg/mL, and 26.6 μg/mL at pH values of 7.4, 6.5, 6.0, and 5.0, respectively. The trend of critical micelle concentrations indicated that the polymer had high stability that could prolong the circulation time in the body. The hydrodynamic diameter and zeta potential of the polymeric micelles were influenced significantly by the pH values. As pH decreased from 7.4 to 5.0, the particle size and zeta potential increased from 205.4 nm to 285.7 nm and from +12.7 mV to +47.0 mV, respectively. The pKb of the polymer was confirmed to be approximately 6.5 by the acid–base titration method. The results showed that the polymer had sharp pH-sensitivity because of the protonation of the amino groups, resulting in transformation of the PAE segment from hydrophobic to hydrophilic. Doxorubicin-loaded polymeric micelles were prepared with a high loading content (20%) and entrapment efficiency (60%) using the dialysis method. The in vitro results demonstrated that drug release rate and cumulative release were obviously dependent on pH values. Furthermore, the drug release mechanism was also controlled by the pH values. The polymer had barely any cytotoxicity, whereas the doxorubicin-loaded system showed high toxicity for HepG2 cells as free drugs. All the results proved that the pH-sensitive triblock polymer brush and its self-assembled micelle might be a potential delivery carrier for anticancer drugs with sustained release. PMID:28356738

pH-sensitive micelles self-assembled from polymer brush (PAE-g-cholesterol)-b-PEG-b-(PAE-g-cholesterol) for anticancer drug delivery and controlled release.

PubMed

Huang, Xiangxuan; Liao, Wenbo; Zhang, Gang; Kang, Shimin; Zhang, Can Yang

2017-01-01

A novel amphiphilic pH-sensitive triblock polymer brush (poly(β-amino esters)- g -cholesterol)- b -poly(ethylene glycol)- b -(poly(β-amino esters)- g -cholesterol) ((PAE- g -Chol)- b -PEG- b -(PAE- g -Chol)) was designed and synthesized successfully through a three-step reaction, and their self-assembled polymeric micelles were used as hydrophobic anticancer drug delivery carriers to realize effectively controlled release. The critical micelle concentrations were 6.8 μg/mL, 12.6 μg/mL, 17.4 μg/mL, and 26.6 μg/mL at pH values of 7.4, 6.5, 6.0, and 5.0, respectively. The trend of critical micelle concentrations indicated that the polymer had high stability that could prolong the circulation time in the body. The hydrodynamic diameter and zeta potential of the polymeric micelles were influenced significantly by the pH values. As pH decreased from 7.4 to 5.0, the particle size and zeta potential increased from 205.4 nm to 285.7 nm and from +12.7 mV to +47.0 mV, respectively. The p K b of the polymer was confirmed to be approximately 6.5 by the acid-base titration method. The results showed that the polymer had sharp pH-sensitivity because of the protonation of the amino groups, resulting in transformation of the PAE segment from hydrophobic to hydrophilic. Doxorubicin-loaded polymeric micelles were prepared with a high loading content (20%) and entrapment efficiency (60%) using the dialysis method. The in vitro results demonstrated that drug release rate and cumulative release were obviously dependent on pH values. Furthermore, the drug release mechanism was also controlled by the pH values. The polymer had barely any cytotoxicity, whereas the doxorubicin-loaded system showed high toxicity for HepG2 cells as free drugs. All the results proved that the pH-sensitive triblock polymer brush and its self-assembled micelle might be a potential delivery carrier for anticancer drugs with sustained release.

Rumen Bacteria Communities and Performances of Fattening Lambs with a Lower or Greater Subacute Ruminal Acidosis Risk

PubMed Central

Li, Fei; Wang, Zhilan; Dong, Chunxiao; Li, Fadi; Wang, Weimin; Yuan, Zehu; Mo, Futao; Weng, Xiuxiu

2017-01-01

Several ruminal cellulolytic bacteria species are sensitive to pH and could therefore be used as biomarkers to determine the risk of sub-acute ruminal acidosis (SARA) in finishing lambs. This study compared a 2–4 h post feeding ruminal pH measurement to abundances of the ruminal pH-sensitive bacteria to evaluate the risk of SARA in a herd of 120 finishing lambs. The lambs were reared in individual units for 50 days. Ruminal fluid was collected by use of an orogastric tube on day 51 2-4 h after feeding. Although the lambs were fed an identical diet, they responded differently in the abundances of four ruminal pH sensitive cellulolytic bacteria (Ruminococcus albus, Ruminococcus flavefaciens and Fibrobacter succinogenes and Butyrivibrio fibrisolvens). Lambs with the most or the least cellulolytic bacteria were then classified as either lower SARA risk (LSR, n = 10) or higher SARA risk group (HSR, n = 10), respectively. Data showed that the ruminal pH and VFA profiles were uncorrelated with the number of cellulolytic bacteria (P > 0.050). Lambs with the HSR showed lower ruminal pH (P = 0.013) and acetate to propionate ratio (P = 0.018), higher concentrations of lactate (P = 0.035) and proportion of propionate (P = 0.033) compared to those with the LSR. The DMI and ADG did not differ in LSR and HSR lambs (P > 0.050). A diversity analysis revealed significantly lower diversity in HSR lambs than in LSR (Simpson index, P = 0.004). The relative abundances of the phyla Bacteroidetes, Fibrobacteres, Verruomicrobia, and Proteobacteria were higher in LSR lambs than in HSR (P < 0.050). The abundances of several phyla including Firmicutes, Tenericutes and Actinobacteria were higher in the HSR than in the LSR group (P < 0.050). The bacterial communities of the LSR and HSR clustered separately in rumen based on the Unifrac distances, indicating distinct bacteria communities at OTU level between the LSR and HSR lambs. Overall, there was no correlation between 2 and 4 h post-feeding ruminal pH and the abundance of pH-sensitive bacteria and the amount of these bacteria could be used as a potential biomarker of SARA in lamb herd. PMID:29312208

pH optrode

DOEpatents

Northrup, M. Allen; Langry, Kevin C.

1993-01-01

A process is provided for forming a long-lasting, stable, pH-sensitive dye-acrylamide copolymer useful as a pH-sensitive material for use in an optrode or other device sensitive to pH. An optrode may be made by mechanically attaching the copolymer to a sensing device such as an optical fiber.

Development of a novel colorimetric sensor based on alginate beads for monitoring rainbow trout spoilage.

PubMed

Majdinasab, Marjan; Hosseini, Seyed Mohammad Hashem; Sepidname, Marziyeh; Negahdarifar, Manizheh; Li, Peiwu

2018-05-01

Alginate is a non-toxic, renewable, and linear copolymer obtained from the brown algae Laminaria digitata that can be easily shaped into beads. Its good gel forming properties have made it useful for entrapping food and pharmaceutical ingredients. In this study, alginate beads were used in a novel application as a colorimetric sensor in food intelligent packaging. Colorimetric sensor was developed through entrapping red cabbage extract as a pH indicator in alginate beads. The pH indicator beads were used in rainbow trout packaging for monitoring fillets spoilage. Color change of beads during fish storage was measured using the CIELab method. The alginate bead colorimetric sensor is validated by measuring total volatile basic nitrogen (TVB-N) levels and microbial populations in fish samples. Moreover, peroxide value (PV) and thiobarbituric acid reactive substances (TBARS) were evaluated during storage. Results indicated that increasing the bacterial population during storage and production of proteolytic enzymes resulted in protein degradation, accumulation of volatile amine compounds, increase in the pH and finally color change of alginate beads. The values of TVB-N, pH, PV and TBARS increased with time of storage. The results of TVB-N and microbial growth were in accordance with color change of beads and CIELab data. Therefore, the proposed system enjoys a high sensitivity to pH variations and is capable of monitoring the spoilage of fish or other protein-rich products through its wide range of color changes. The alginate beads containing the red cabbage extract can, thus, be used as a low-cost colorimetric sensor for intelligent packaging applications.

Water Transport Properties of Roots and Root Cortical Cells in Proton- and Al-Stressed Maize Varieties.

PubMed Central

Gunse, B.; Poschenrieder, C.; Barcelo, J.

1997-01-01

Root and root cell pressure-probe techniques were used to investigate the possible relationship between Al- or H+-induced alterations of the hydraulic conductivity of root cells (LPc) and whole-root water conductivity (LPr) in maize (Zea mays L.) plants. To distinguish between H+ and Al effects two varieties that differ in H+ and Al tolerance were assayed. Based on root elongation rates after 24 h in nutrient solution of pH 6.0, pH 4.5, or pH 4.5 plus 50 [mu]M Al, the variety Adour 250 was found to be H+-sensitive and Al-tolerant, whereas the variety BR 201 F was found to be H+-tolerant but Al-sensitive. No Al-induced decrease of root pressure and root cell turgor was observed in Al-sensitive BR 201 F, indicating that Al toxicity did not cause a general breakdown of membrane integrity and that ion pumping to the stele was maintained. Al reduced LPc more than LPr in Al-sensitive BR 201 F. Proton toxicity in Adour 250 affected LPr more than LPc. In this Al-tolerant variety LPc was increased by Al. Nevertheless, this positive effect on LPc did not render higher LPr values. In conclusion, there were no direct relationships between Al- or H+-induced decreases of LPr and the effects on LPc. To our knowledge, this is the first time that the influence of H+ and Al on root and root cell water relations has been directly measured by pressure-probe techniques. PMID:12223628

A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities.

PubMed

Geng, Yanyan; Ferreira, Juan J; Dzikunu, Victor; Butler, Alice; Lybaert, Pascale; Yuan, Peng; Magleby, Karl L; Salkoff, Lawrence; Santi, Celia M

2017-05-26

To fertilize an oocyte, sperm must first undergo capacitation in which the sperm plasma membrane becomes hyperpolarized via activation of potassium (K + ) channels and resultant K + efflux. Sperm-specific SLO3 K + channels are responsible for these membrane potential changes critical for fertilization in mouse sperm, and they are only sensitive to pH i However, in human sperm, the major K + conductance is both Ca 2+ - and pH i -sensitive. It has been debated whether Ca 2+ -sensitive SLO1 channels substitute for human SLO3 (hSLO3) in human sperm or whether human SLO3 channels have acquired Ca 2+ sensitivity. Here we show that hSLO3 is rapidly evolving and reveal a natural structural variant with enhanced apparent Ca 2+ and pH sensitivities. This variant allele (C382R) alters an amino acid side chain at a principal interface between the intramembrane-gated pore and the cytoplasmic gating ring of the channel. Because the gating ring contains sensors to intracellular factors such as pH and Ca 2+ , the effectiveness of transduction between the gating ring and the pore domain appears to be enhanced. Our results suggest that sperm-specific genes can evolve rapidly and that natural genetic variation may have led to a SLO3 variant that differs from wild type in both pH and intracellular Ca 2+ sensitivities. Whether this physiological variation confers differences in fertility among males remains to be established. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Preparation of dual-stimuli-responsive liposomes using methacrylate-based copolymers with pH and temperature sensitivities for precisely controlled release.

PubMed

Sugimoto, Takumi; Yamazaki, Naoko; Hayashi, Takaaki; Yuba, Eiji; Harada, Atsushi; Kotaka, Aki; Shinde, Chiharu; Kumei, Takayuki; Sumida, Yasushi; Fukushima, Mitsuhiro; Munekata, Yuki; Maruyama, Keiichi; Kono, Kenji

2017-07-01

Dual-signal-sensitive copolymers were synthesized by copolymerization of methoxy diethylene glycol methacrylate, methacrylic acid, and lauroxy tetraethylene glycol methacrylate, which respectively provide temperature sensitivity, pH sensitivity, and anchoring to liposome surfaces. These novel copolymers, with water solubility that differs depending on temperature and pH, are soluble in water under neutral pH and low-temperature conditions, but they become water-insoluble and form aggregates under acidic pH and high-temperature conditions. Liposomes modified with these copolymers exhibited enhanced content release at weakly acidic pH with increasing temperature, although no temperature-dependent content release was observed in neutral conditions. Interaction between the copolymers and the lipid monolayer at the air-water interface revealed that the copolymer chains penetrate more deeply into the monolayer with increasing temperature at acidic pH than at neutral pH, where the penetration of copolymer chains was moderate and temperature-independent at neutral pH. Interaction of the copolymer-modified liposomes with HeLa cells demonstrated that the copolymer-modified liposomes were adsorbed quickly and efficiently onto the cell surface and that they were internalized more gradually than the unmodified liposomes through endocytosis. Furthermore, the copolymer-modified liposomes enhanced the content release in endosomes with increasing temperature, but no such temperature-dependent enhancement of content release was observed for unmodified liposomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Complex of transferrin with ruthenium for medical applications

DOEpatents

Richards, Powell; Srivastava, Suresh C.; Meinken, George E.

1984-05-15

A novel Ruthenium-transferrin complex, prepared by reacting iron-free human transferrin dissolved in a sodium acetate solution at pH 7 with ruthenium by heating at about 40.degree. C. for about 2 hours, and purifying said complex by means of gel chromotography with pH 7 sodium acetate as eluent. The mono- or di-metal complex produced can be used in nuclear medicine in the diagnosis and/or treatment of tumors and abscesses. Comparative results with Ga-67-citrate, which is the most widely used tumor-localizing agent in nuclear medicine, indicate increased sensitivity of detection and greater tumor uptake with the Ru-transferrin complex.

Effects of Taiwan Roselle anthocyanin treatment and single-walled carbon nanotube addition on the performance of dye-sensitized solar cells

NASA Astrophysics Data System (ADS)

Chou, C. S.; Tsai, P. J.; Wu, P.; Shu, G. G.; Huang, Y. H.; Chen, Y. S.

2014-04-01

This study investigates the relationship between the performance of a dye-sensitized solar cell (DSSC) sensitized by a natural sensitizer of Taiwan Roselle anthocyanin (TRA) and fabrication process conditions of the DSSC. A set of systematic experiments has been carried out at various soaking temperatures, soaking periods, sensitizer concentrations, pH values, and additions of single-walled carbon nanotube (SWCNT). An absorption peak (520 nm) is found for TRA, and it is close to that of the N719 dye (518 nm). At a fixed concentration of TRA and a fixed soaking period, a lower pH of the extract or a lower soaking temperature is found favorable to the formation of pigment cations, which leads to an enhanced power conversion efficiency (η) of DSSC. For instance, by applying 17.53 mg/100ml TRA at 30 for 10 h, as the pH of the extract decreases to 2.00 from 2.33 (the original pH of TRA), the η of DSSC with TiO2+SWCNT electrode increases to 0.67% from 0.11% of a traditional DSSC with TiO2 electrode. This performance improvement can be explained by the combined effect of the pH of sensitizer and the additions of SWCNT, a first investigation in DSSC using the natural sensitizer with SWCNT.

In vitro radiolabel uptake viability assay for Onchocerca microfilariae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Callahan, H.L.; Wakeman, J.M.; Crouch, R.K.

1989-02-01

A radiolabel uptake viability assay for Onchocerca cervicalis using (/sup 3/H)2-deoxy-D-glucose in Hanks' balanced salt solution, pH 7.5, at 30 C is described and compared to the traditional visual motility assay. A correlation of r = 0.92 between the assays was found, with the radiolabel uptake method apparently a more sensitive indicator of microfilarial viability.

Kinetic and mechanistic aspects of sensitized photodegradation of β-lactam antibiotics: microbiological implications.

PubMed

Reynoso, E; Nesci, A; Allegretti, P; Criado, S; Biasutti, M A

2012-01-01

Amoxicillin (Amx) and cephalexin (Cfx) are β-lactam antibiotics widely used in human and veterinary medicine. Two points of interest surrounding these molecules are the photodegradation of the molecules and their microbiological implications, as well as the persistence and bioaccumulation in the environment which may cause resistance to bacterial strains. The kinetic and mechanistic aspects of the photosensitized degradation of Amx and Cfx have been studied in water at pH 7.4 and 10 by stationary and time-resolved methods. Kinetic evidence indicates that the Rose Bengal-sensitized photooxidation of Amx at pH 7.4 proceeds via O(2)((1)Δ(g)) and O(2•-) mechanisms while at pH 10 the degradation path occurs, principally, via O(2)((1)Δ(g)). For Cfx, this process is attributed to O(2)((1)Δ(g)) and O(2•-). Photoproducts, which arise from the addition of oxygen atoms and subsequent oxidation of the groups -CH(3) to -COOH, were detected. For both antibiotics the bacteriostatic activity decreases in parallel to their photodegradation. The results of this study could potentially help scientists to better understand and predict the photodegradability of these antibiotics on living organisms and in different environmental compartments.

Synthesis and characterization of a thermo-sensitive poly( N-methyl acryloylglycine methyl ester) used as a drug release carrier

NASA Astrophysics Data System (ADS)

Deng, Kui-Lin; Zhong, Hai-Bin; Jiao, Yi-Suo; Fan, Ting; Qiao, Xiao; Zhang, Peng-Fei; Ren, Xiao-Bo

2010-06-01

In this article, poly( N-methyl acryloylglycine methyl ester) (PNMAME) was prepared as a novel thermosensitive material with a lower critical solution temperature (LCST) at around 49.5°C. The chemical structures of the monomer NMAME and PNMAME were characterized by 1H NMR and IR measurements. The LCST was investigated systematically as a function of PNMAME concentration, inorganic salt solution and pH value. The results indicated that LCST of PNMAME was obviously dependent on PNMAME concentration and pH. The LCST was increased with a decrease in pH value and PNMAME concentration. To obtain a thermo-sensitive hydrogel with the phase transition temperature close to human body temperature, the copolymerization was conducted between NMAME and N-acryloylglycine ethyl ester (NAGEE). The release behavior of caffeine was evaluated at different temperatures and contents of cross-linkers ( N, N-methylenebis(acrylamide) (NMBA)). The increase of cross-linker content led to a decrease in the release rate of caffeine due to higher crossing density in the hydrogel network. In addition, a faster release of caffeine from the hydrogel with 3% NMBA at 37°C was found in contrast to that at 18°C.

Physicochemical characteristics of Fe3O4 magnetic nanocomposites based on Poly(N-isopropylacrylamide) for anti-cancer drug delivery.

PubMed

Davaran, Soodabeh; Alimirzalu, Samira; Nejati-Koshki, Kazem; Nasrabadi, Hamid Tayef; Akbarzadeh, Abolfazl; Khandaghi, Amir Ahmad; Abbasian, Mojtaba; Alimohammadi, Somayeh

2014-01-01

Hydrogels are a class of polymers that can absorb water or biological fluids and swell to several times their dry volume, dependent on changes in the external environment. In recent years, hydrogels and hydrogel nanocomposites have found a variety of biomedical applications, including drug delivery and cancer treatment. The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics such as enhanced mechanical properties, swelling response, and capability of remote controlled actuation. In this work, synthesis of hydrogel nanocomposites containing magnetic nanoparticles are studied. At first, magnetic nanoparticles (Fe3O4) with an average size 10 nm were prepared. At second approach, thermo and pH-sensitive poly (N-isopropylacrylamide -co-methacrylic acid-co-vinyl pyrrolidone) (NIPAAm-MAA- VP) were prepared. Swelling behavior of co-polymer was studied in buffer solutions with different pH values (pH=5.8, pH=7.4) at 37 °C. Magnetic iron oxide nanoparticles (Fe3O4) and doxorubicin were incorporated into copolymer and drug loading was studied. The release of drug, carried out at different pH and temperatures. Finally, chemical composition, magnetic properties and morphology of doxorubicin-loaded magnetic hydrogel nanocomposites were analyzed by FT- IR, vibrating sample magnetometry (VSM), scanning electron microscopy (SEM). The results indicated that drug loading efficiency was increased by increasing the drug ratio to polymer. Doxorubicin was released more at 40 °C and in acidic pH compared to that 37 °C and basic pH. This study suggested that the poly (NIPAAm-MAA-VP) magnetic hydrogel nanocomposite could be an effective carrier for targeting drug delivery systems of anti-cancer drugs due to its temperature sensitive properties.

Present-day nearshore pH differentially depresses fertilization in congeneric sea urchins.

PubMed

Frieder, Christina A

2014-02-01

Ocean acidification impacts fertilization in some species of sea urchin, but whether sensitivity is great enough to be influenced by present-day pH variability has not been documented. In this study, fertilization in two congeneric sea urchins, Strongylocentrotus purpuratus and S. franciscanus, was found to be sensitive to reduced pH, <7.50, but only within a range of sperm-egg ratios that was species-specific. By further testing fertilization across a broad range of pH, pH-fertilization curves were generated and revealed that S. purpuratus was largely robust to pH, while fertilization in S. franciscanus was sensitive to even modest reductions in pH. Combining the pH-fertilization response curves with pH data collected from these species' habitat demonstrated that relative fertilization success remained high for S. purpuratus but could be as low as 79% for S. franciscanus during periods of naturally low pH. In order for S. franciscanus to maintain high fertilization success in the present and future, adequate adult densities, and thus sufficient sperm-egg ratios, will be required to negate the effects of low pH. In contrast, fertilization of S. purpuratus was robust to a broad range of pH, encompassing both present-day and future ocean acidification scenarios, even though the two congeners have similar habitats.

Analysis of Chameleonic Change of Red Cabbage Depending on Broad pH Range for Dye-Sensitized Solar Cells.

PubMed

Park, Kyung Hee; Kim, Tae Young; Ko, Hyun Seok; Han, Eun Mi; Lee, Suk-Ho; Kim, Jung-Hun; Lee, Jae Wook

2015-08-01

Dye-sensitized solar cells (DSSCs) were assembled using natural dyes extracted from red cabbage as a sensitizer. In this work, we investigated the adsorption characteristics and the electrochemical behavior for harvesting sunlight and electron transfer in red cabbage DSSCs under different solvents and pH. For the red cabbage dye-sensitized electrode adsorbed at pH 3.5, the solar cell yields a short-circuit current density (Jsc) of 1.60 mA/cm2, a photovoltage (Vcc) of 0.46 V, and a fill factor of 0.55, corresponding to an energy conversion efficiency (η) of 0.41%.

Low temperature annealed amorphous indium gallium zinc oxide (a-IGZO) as a pH sensitive layer for applications in field effect based sensors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Narendra; Samtel Centre for Display Technologies, Indian Institute of Technology Kanpur, Kanpur-208016; Kumar, Jitendra

The use of a-IGZO instead of the conventional high-k dielectrics as a pH sensitive layer could lead to the simplification of fabrication steps of field effect based devices. In this work, the pH sensitivities of a-IGZO films directly deposited over a SiO{sub 2}/Si surface were studied utilizing electrolyte-insulator-semiconductor (EIS) structures. Annealing of the films was found to affect the sensitivity of the devices and the device with the film annealed at 400 {sup o}C in N{sub 2} ambience showed the better sensitivity, which reduced with further increase in the annealing temperature to 500 {sup o}C. The increased pH sensitivity withmore » the film annealed at 400 {sup o}C in N{sub 2} gas was attributed to the enhanced lattice oxygen ions (based on the XPS data) and improved C-V characteristics, while the decrease in sensitivity at an increased annealing temperature of 500 {sup o}C was attributed to defects in the films as well as the induced traps at the IGZO/SiO{sub 2} interface based on the stretched accumulation and the peak in the inversion region of C-V curves. This study could help to develop a sensor where the material (a-IGZO here) used as the active layer in a thin film transistors (TFTs) possibly could also be used as the pH sensitive layer without affecting the TFT characteristics, and thus obviating the need of high-K dielectrics for sensitivity enhancement.« less

A graphene oxide pH sensor for wound monitoring.

PubMed

Melai, B; Salvo, P; Calisi, N; Moni, L; Bonini, A; Paoletti, C; Lomonaco, T; Mollica, V; Fuoco, R; Di Francesco, F

2016-08-01

This article describes the fabrication and characterization of a pH sensor for monitoring the wound status. The pH sensitive layer consists of a graphene oxide (GO) layer obtained by drop-casting 5 μΐ of GO dispersion onto the working electrode of a screen-printed substrate. Sensitivity was 31.8 mV/pH with an accuracy of 0.3 unit of pH. Open-circuit potentiometry was carried out to measure pH in an exudate sample. The GO pH sensor proved to be reliable as the comparison with results obtained from a standard glass electrode pH-meter showed negligible differences (<; 0.09 pH units in the worst case) for measurements performed over a period of 4 days.

Deep-Sea DuraFET: A Pressure Tolerant pH Sensor Designed for Global Sensor Networks.

PubMed

Johnson, Kenneth S; Jannasch, Hans W; Coletti, Luke J; Elrod, Virginia A; Martz, Todd R; Takeshita, Yuichiro; Carlson, Robert J; Connery, James G

2016-03-15

Increasing atmospheric carbon dioxide is driving a long-term decrease in ocean pH which is superimposed on daily to seasonal variability. These changes impact ecosystem processes, and they serve as a record of ecosystem metabolism. However, the temporal variability in pH is observed at only a few locations in the ocean because a ship is required to support pH observations of sufficient precision and accuracy. This paper describes a pressure tolerant Ion Sensitive Field Effect Transistor pH sensor that is based on the Honeywell Durafet ISFET die. When combined with a AgCl pseudoreference sensor that is immersed directly in seawater, the system is capable of operating for years at a time on platforms that cycle from depths of several km to the surface. The paper also describes the calibration scheme developed to allow calibrated pH measurements to be derived from the activity of HCl reported by the sensor system over the range of ocean pressure and temperature. Deployments on vertical profiling platforms enable self-calibration in deep waters where pH values are stable. Measurements with the sensor indicate that it is capable of reporting pH with an accuracy of 0.01 or better on the total proton scale and a precision over multiyear periods of 0.005. This system enables a global ocean observing system for ocean pH.

Optimization of Urea-EnFET Based on Ta2O5 Layer with Post Annealing

PubMed Central

Lue, Cheng-En; Yu, Ting-Chun; Yang, Chia-Ming; Pijanowska, Dorota G.; Lai, Chao-Sung

2011-01-01

In this study, the urea-enzymatic field effect transistors (EnFETs) were investigated based on pH-ion sensitive field effect transistors (ISFETs) with tantalum pentoxide (Ta2O5) sensing membranes. In addition, a post N2 annealing was used to improve the sensing properties. At first, the pH sensitivity, hysteresis, drift, and light induced drift of the ISFETs were evaluated. After the covalent bonding process and urease immobilization, the urea sensitivity of the EnFETs were also investigated and compared with the conventional Si3N4 sensing layer. The ISFETs and EnFETs with annealed Ta2O5 sensing membranes showed the best responses, including the highest pH sensitivity (56.9 mV/pH, from pH 2 to pH 12) and also corresponded to the highest urea sensitivity (61 mV/pCurea, from 1 mM to 7.5 mM). Besides, the non-ideal factors of pH hysteresis, time drift, and light induced drift of the annealed samples were also lower than the controlled Ta2O5 and Si3N4 sensing membranes. PMID:22163862

Optimization of urea-EnFET based on Ta2O5 layer with post annealing.

PubMed

Lue, Cheng-En; Yu, Ting-Chun; Yang, Chia-Ming; Pijanowska, Dorota G; Lai, Chao-Sung

2011-01-01

In this study, the urea-enzymatic field effect transistors (EnFETs) were investigated based on pH-ion sensitive field effect transistors (ISFETs) with tantalum pentoxide (Ta(2)O(5)) sensing membranes. In addition, a post N(2) annealing was used to improve the sensing properties. At first, the pH sensitivity, hysteresis, drift, and light induced drift of the ISFETs were evaluated. After the covalent bonding process and urease immobilization, the urea sensitivity of the EnFETs were also investigated and compared with the conventional Si(3)N(4) sensing layer. The ISFETs and EnFETs with annealed Ta(2)O(5) sensing membranes showed the best responses, including the highest pH sensitivity (56.9 mV/pH, from pH 2 to pH 12) and also corresponded to the highest urea sensitivity (61 mV/pC(urea), from 1 mM to 7.5 mM). Besides, the non-ideal factors of pH hysteresis, time drift, and light induced drift of the annealed samples were also lower than the controlled Ta(2)O(5) and Si(3)N(4) sensing membranes.

Imaging of Intracellular pH in Tumor Spheroids Using Genetically Encoded Sensor SypHer2.

PubMed

Zagaynova, Elena V; Druzhkova, Irina N; Mishina, Natalia M; Ignatova, Nadezhda I; Dudenkova, Varvara V; Shirmanova, Marina V

2017-01-01

Intracellular pH (pHi) is one of the most important parameters that regulate the physiological state of cells and tissues. pHi homeostasis is crucial for normal cell functioning. Cancer cells are characterized by having a higher (neutral to slightly alkaline) pHi and lower (acidic) extracellular pH (pHe) compared to normal cells. This is referred to as a "reversed" pH gradient, and is essential in supporting their accelerated growth rate, invasion and migration, and in suppressing anti-tumor immunity, the promotion of metabolic coupling with fibroblasts and in preventing apoptosis. Moreover, abnormal pH, both pHi and pHe, contribute to drug resistance in cancers. Therefore, the development of methods for measuring pH in living tumor cells is likely to lead to better understanding of tumor biology and to open new ways for cancer treatment. Genetically encoded, fluorescent, pH-sensitive probes represent promising instruments enabling the subcellular measurement of pHi with unrivaled specificity and high accuracy. Here, we describe a protocol for pHi imaging at a microscopic level in HeLa tumor spheroids, using the genetically encoded ratiometric (dual-excitation) pHi indicator, SypHer2.

Response of predatory zooplankton populations to the experimental acidification of Little Rock Lake, Wisconsin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sierszen, M.E.; Frost, T.M.

1993-01-01

To assess the effects of lake acidification on large predatory zooplankton, the authors monitored population levels of four limnetic taxa for 6 years in a lake with two basins, one of which was experimentally acidified (2 years at each of three levels: pH 5.6, 5.2 and 4.7). Concentrations of phantom midge (Chaoborus spp.), the most abundant large predator, remained similar in the treatment and reference basins until the fourth year (pH 5.2) when they increased in the treatment basin. In contrast, Epischura lacustris and Leptodora kindtii disappeared from limnetic samples, and water mites declined to near zero upon acidification. Treatmentmore » basin populations of E. lacustris declined sharply during the second year of acidification. The nature of the decline suggested sensitivity of an early life stage during the first year at pH 5.6. Leptodora kindtii showed no population response at pH 5.6, but declined to essentially zero at pH 5.2. Treatment basin populations of water mites fluctuated until declining in the fifth and sixth years (pH 4.7). These changes indicate a variety of direct and indirect responses to lake acidification.« less

Two 1,8- Naphthalimides as Proton-Receptor Fluorescent Sensors for Detecting PH

NASA Astrophysics Data System (ADS)

Wu, H.-L.; Peng, H.-P.; Wang, F.; Zhang, H.; Chen, C.-G.; Zhang, J.-W.; Yang, Z.-H.

2017-01-01

Two proton-receptor sensors for detecting pH change based on 1,8-naphthalimide, N-allyl-4-(4'-N,N-dioctylpropionamide-acetamido-piperazinyl)-1,8-naphthalimide ( 1), and N-(N,N-dioctylpropionamide-acetamido)-4-allyl-1-piperazinyl-1,8-naphthalimide ( 2), were designed, synthesized, and characterized. Photophysical characteristics of the sensors were investigated in different organic solvents and Britton-Robinson buffer/EtOH (1:1, v/v) solution. Sensor 2 displayed a good sensor activity towards protons within the pH range from 3.29 to 6.59, while sensor 1 demonstrated sensitivity to lower pH values from 2.21 to 4.35. The selectivity of the pH sensors toward protons in commonly used buffer solutions and in the presence of metal cations (Na+, K+, Ca2+, Mg2+, Al3+, Pb2+, Fe3+, Ni2+, Zn2+, Cu2+, Hg2+, Ag+, Co2+, Cr3+, Mn2+, and Cd2+) was studied by monitoring the changes in their fluorescence intensity. The results obtained indicate that the synthesized derivatives hold potential for monitoring pH variations between 2.21 and 6.59 in strong acid environments and bio-samples.

High-sensitivity pH sensor using separative extended-gate field-effect transistors with single-walled carbon-nanotube networks

NASA Astrophysics Data System (ADS)

Pyo, Ju-Young; Cho, Won-Ju

2018-04-01

We fabricate high-sensitivity pH sensors using single-walled carbon-nanotube (SWCNT) network thin-film transistors (TFTs). The sensing and transducer parts of the pH sensor are composed of separative extended-sensing gates (ESGs) with SnO2 ion-sensitive membranes and double-gate structure TFTs with thin SWCNT network channels of ∼1 nm and AlO x top-gate insulators formed by the solution-deposition method. To prevent thermal process-induced damages on the SWCNT channel layer due to the post-deposition annealing process and improve the electrical characteristics of the SWCNT-TFTs, microwave irradiation is applied at low temperatures. As a result, a pH sensitivity of 7.6 V/pH, far beyond the Nernst limit, is obtained owing to the capacitive coupling effect between the top- and bottom-gate insulators of the SWCNT-TFTs. Therefore, double-gate structure SWCNT-TFTs with separated ESGs are expected to be highly beneficial for high-sensitivity disposable biosensor applications.

pH regulation of mitochondrial branch chain alpha-keto acid transport and oxidation in rat heart mitochondria.

PubMed

Hutson, S M

1987-07-15

The kinetics of branched chain alpha-keto acid uptake and efflux were studied as a function of varied external and matrix pH. Matrix pH was determined by the distribution of 5,5'-dimethyloxazolidine-2,4-dione. When rat heart mitochondria were incubated under transport conditions at pH 7.0 with succinate as respiratory substrate, the matrix pH was significantly greater than 8.0. Matrix pH remained greater than or equal to 8.0 when the medium pH was varied from 6.3 to 8.3, and it was lowered below 8.0 by addition of 5 mM phosphate or uncoupler. No pH gradient was detectable when mitochondria were incubated in the presence of valinomycin and uncoupler. Efflux of alpha-ketoisocaproate or alpha-ketoisovalerate from rat heart mitochondria obeyed first order kinetics. Varying the external pH from 6.6 to 8.3 had no significant effect on efflux, and at an external pH of 7.0, the first order rate constant for efflux was not affected by decreasing the matrix pH. On the other hand, exchange was sensitive to changes in medium but not matrix pH. The K0.5 for external branched chain alpha-keto acid was lowered by changing the medium pH from 7.6 to 6.3. At medium pH values greater than or equal to 8.0 both K0.5 and Vmax were affected. Uptake was determined either by measuring initial rates or was calculated after measuring the first order approach to a final equilibrium value. Unlike efflux, uptake was sensitive to changes in both external and matrix pH. The rate of branched chain alpha-keto acid uptake was stimulated by decreasing the medium pH from 8.3 to 6.3 and by alkalinization of the mitochondrial matrix. The estimated external pK for proton binding was 6.9. The data indicate that the branched chain alpha-keto acid transporter is asymmetric, that is, binding sites for substrate on the inside and outside of the mitochondrial membrane are not identical. alpha-Ketoisocaproate oxidation was measured at 37 degrees C in isolated mitochondria over the pH range of 6.6 to 8.1. Changes in the rate of branched chain alpha-keto acid oxidation, particularly when ATP was added (increase delta pH), were found to parallel the pH effects observed on branched chain alpha-keto acid uptake. Therefore, transport, and by implication oxidation, can be regulated by pH changes within the physiological range. Furthermore, intracellular pH may affect the degree of compartmentation between the cytosolic and mitochondrial branched chain alpha-keto acid pools.

Biocompatible click chemistry enabled compartment-specific pH measurement inside E. coli.

PubMed

Yang, Maiyun; Jalloh, Abubakar S; Wei, Wei; Zhao, Jing; Wu, Peng; Chen, Peng R

2014-09-19

Bioorthogonal reactions, especially the Cu(I)-catalysed azide-alkyne cycloaddition, have revolutionized our ability to label and manipulate biomolecules under living conditions. The cytotoxicity of Cu(I) ions, however, has hindered the application of this reaction in the internal space of living cells. By systematically surveying a panel of Cu(I)-stabilizing ligands in promoting protein labelling within the cytoplasm of Escherichia coli, we identify a highly efficient and biocompatible catalyst for intracellular modification of proteins by azide-alkyne cycloaddition. This reaction permits us to conjugate an environment-sensitive fluorophore site specifically onto HdeA, an acid-stress chaperone that adopts pH-dependent conformational changes, in both the periplasm and cytoplasm of E. coli. The resulting protein-fluorophore hybrid pH indicators enable compartment-specific pH measurement to determine the pH gradient across the E. coli cytoplasmic membrane. This construct also allows the measurement of E. coli transmembrane potential, and the determination of the proton motive force across its inner membrane under normal and acid-stress conditions.

Nonuniform ocean acidification and attenuation of the ocean carbon sink

NASA Astrophysics Data System (ADS)

Fassbender, Andrea J.; Sabine, Christopher L.; Palevsky, Hilary I.

2017-08-01

Surface ocean carbon chemistry is changing rapidly. Partial pressures of carbon dioxide gas (pCO2) are rising, pH levels are declining, and the ocean's buffer capacity is eroding. Regional differences in short-term pH trends primarily have been attributed to physical and biological processes; however, heterogeneous seawater carbonate chemistry may also be playing an important role. Here we use Surface Ocean CO2 Atlas Version 4 data to develop 12 month gridded climatologies of carbonate system variables and explore the coherent spatial patterns of ocean acidification and attenuation in the ocean carbon sink caused by rising atmospheric pCO2. High-latitude regions exhibit the highest pH and buffer capacity sensitivities to pCO2 increases, while the equatorial Pacific is uniquely insensitive due to a newly defined aqueous CO2 concentration effect. Importantly, dissimilar regional pH trends do not necessarily equate to dissimilar acidity ([H+]) trends, indicating that [H+] is a more useful metric of acidification.

Calculation and affection of pH value of different desulfurization and dehydration rates in the filling station based on Aspen Plus

NASA Astrophysics Data System (ADS)

Lv, J. X.; Wang, B. F.; Nie, L. H.; Xu, R. R.; Zhou, J. Y.; Hao, Y. J.

2018-01-01

The simulation process of the whole CNG filling station are established using Aspen Plus V7.2. The separator (Sep) was used to simulate the desulfurization and dehydration equipment in the gas station, and the flash module separator Flash 2 was used to simulate the gas storage well with proper temperature and environmental pressure. Furthermore, the sensitivity module was used to analyse the behaviour of the dehydration and desulfurization rate, and the residual pH value of the gas storage wells was between 2.2 and 3.3. The results indicated that the effect of water content on pH value is higher than that of hydrogen sulphide in the environment of gas storage wells, and the calculation process of the pH value is feasible. Additionally, the simulation process provides basic data for the subsequent anticorrosive mechanism and work of gas storage well and has great potential for practical applications.

Extracellular pH Regulates Zinc Signaling via an Asp Residue of the Zinc-sensing Receptor (ZnR/GPR39)*

PubMed Central

Cohen, Limor; Asraf, Hila; Sekler, Israel; Hershfinkel, Michal

2012-01-01

Zinc activates a specific Zn2+-sensing receptor, ZnR/GPR39, and thereby triggers cellular signaling leading to epithelial cell proliferation and survival. Epithelial cells that express ZnR, particularly colonocytes, face frequent changes in extracellular pH that are of physiological and pathological implication. Here we show that the ZnR/GPR39-dependent Ca2+ responses in HT29 colonocytes were maximal at pH 7.4 but were reduced by about 50% at pH 7.7 and by about 62% at pH 7.1 and were completely abolished at pH 6.5. Intracellular acidification did not attenuate ZnR/GPR39 activity, indicating that the pH sensor of this protein is located on an extracellular domain. ZnR/GPR39-dependent activation of extracellular-regulated kinase (ERK)1/2 or AKT pathways was abolished at acidic extracellular pH of 6.5. A similar inhibitory effect was monitored for the ZnR/GPR39-dependent up-regulation of Na+/H+ exchange activity at pH 6.5. Focusing on residues putatively facing the extracellular domain, we sought to identify the pH sensor of ZnR/GPR39. Replacing the histidine residues forming the Zn2+ binding site, His17 or His19, or other extracellular-facing histidines to alanine residues did not abolish the pH dependence of ZnR/GPR39. In contrast, replacing Asp313 with alanine resulted in similar Ca2+ responses triggered by ZnR/GPR39 at pH 7.4 or 6.5. This mutant also showed similar activation of ERK1/2 and AKT pathways, and ZnR-dependent up-regulation of Na+/H+ exchange at pH 7.4 and pH 6.5. Substitution of Asp313 to His or Glu residues restored pH sensitivity of the receptor. This indicates that Asp313, which was shown to modulate Zn2+ binding, is an essential residue of the pH sensor of GPR39. In conclusion, ZnR/GPR39 is tuned to sense physiologically relevant changes in extracellular pH that thus regulate ZnR-dependent signaling and ion transport activity. PMID:22879599

Extracellular pH regulates zinc signaling via an Asp residue of the zinc-sensing receptor (ZnR/GPR39).

PubMed

Cohen, Limor; Asraf, Hila; Sekler, Israel; Hershfinkel, Michal

2012-09-28

Zinc activates a specific Zn(2+)-sensing receptor, ZnR/GPR39, and thereby triggers cellular signaling leading to epithelial cell proliferation and survival. Epithelial cells that express ZnR, particularly colonocytes, face frequent changes in extracellular pH that are of physiological and pathological implication. Here we show that the ZnR/GPR39-dependent Ca(2+) responses in HT29 colonocytes were maximal at pH 7.4 but were reduced by about 50% at pH 7.7 and by about 62% at pH 7.1 and were completely abolished at pH 6.5. Intracellular acidification did not attenuate ZnR/GPR39 activity, indicating that the pH sensor of this protein is located on an extracellular domain. ZnR/GPR39-dependent activation of extracellular-regulated kinase (ERK)1/2 or AKT pathways was abolished at acidic extracellular pH of 6.5. A similar inhibitory effect was monitored for the ZnR/GPR39-dependent up-regulation of Na(+)/H(+) exchange activity at pH 6.5. Focusing on residues putatively facing the extracellular domain, we sought to identify the pH sensor of ZnR/GPR39. Replacing the histidine residues forming the Zn(2+) binding site, His(17) or His(19), or other extracellular-facing histidines to alanine residues did not abolish the pH dependence of ZnR/GPR39. In contrast, replacing Asp(313) with alanine resulted in similar Ca(2+) responses triggered by ZnR/GPR39 at pH 7.4 or 6.5. This mutant also showed similar activation of ERK1/2 and AKT pathways, and ZnR-dependent up-regulation of Na(+)/H(+) exchange at pH 7.4 and pH 6.5. Substitution of Asp(313) to His or Glu residues restored pH sensitivity of the receptor. This indicates that Asp(313), which was shown to modulate Zn(2+) binding, is an essential residue of the pH sensor of GPR39. In conclusion, ZnR/GPR39 is tuned to sense physiologically relevant changes in extracellular pH that thus regulate ZnR-dependent signaling and ion transport activity.

Enhanced pH sensitivity of AlGaN/GaN ion-sensitive field effect transistor with Al2O3 synthesized by atomic layer deposition

NASA Astrophysics Data System (ADS)

Wang, Lei; Li, Liuan; Zhang, Tong; Liu, Xinke; Ao, Jin-Ping

2018-01-01

In this study, we evaluated the pH sensitivity enhancement of AlGaN/GaN ion-sensitive field-effect transistor (ISFET) coated by Al2O3 film on the sensing area utilizing atomic layer deposition (ALD). The presence of the Al2O3 film leads to an obvious reduction of surface state density as well as leakage current in the solution, which is beneficial for improving the stability of the ISFET. Furthermore, the sensitivity of the ISFET was improved to 57.8 mV/pH, which is very close to the Nernstian limit at room temperature. The pH sensitivity enhancement can be explained by the higher density of sensing site as well as better surface hydrophilicity.

Three dimensional graphene transistor for ultra-sensitive pH sensing directly in biological media.

PubMed

Ameri, Shideh Kabiri; Singh, Pramod K; Sonkusale, Sameer R

2016-08-31

In this work, pH sensing directly in biological media using three dimensional liquid gated graphene transistors is presented. The sensor is made of suspended network of graphene coated all around with thin layer of hafnium oxide (HfO2), showing high sensitivity and sensing beyond the Debye-screening limit. The performance of the pH sensor is validated by measuring the pH of isotonic buffered, Dulbecco's phosphate buffered saline (DPBS) solution, and of blood serum derived from Sprague-Dawley rat. The pH sensor shows high sensitivity of 71 ± 7 mV/pH even in high ionic strength media with molarities as high as 289 ± 1 mM. High sensitivity of this device is owing to suspension of three dimensional graphene in electrolyte which provides all around liquid gating of graphene, leading to higher electrostatic coupling efficiency of electrolyte to the channel and higher gating control of transistor channel by ions in the electrolyte. Coating graphene with hafnium oxide film (HfO2) provides binding sites for hydrogen ions, which results in higher sensitivity and sensing beyond the Debye-screening limit. The 3D graphene transistor offers the possibility of real-time pH measurement in biological media without the need for desaltation or sample preparation. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigation on properties of P((MAA-co-DMAEMA)-g-EG) polyampholyte nanogels

NASA Astrophysics Data System (ADS)

Deng, Liandong; Zhai, Yinglei; Guo, Shutao; Jin, Fengmin; Xie, Zhaopeng; He, Xiaohua; Dong, Anjie

2009-02-01

P((MAA-co-DMAEMA)-g-EG) polyampholyte nanogels (PANGs) were prepared by distillation-dispersion copolymerization of poly(ethylene glycol) methyl ether methacrylate (MPEGMA), N, N-dimethylaminoethyl methacrylate (DMAEMA), and methacrylic acid (MAA) using acetonitrile (AN) as dispersion medium. The results of FTIR spectra indicate that the composition of P((MAA-co-DMAEMA)-g-EG) PANGs is consistent with the designed structure. The results of TEM and laser particle size analyzer (LPSA) show that P((MAA-co-DMAEMA)-g-EG) PANGs present spherical morphology and a bimodal size distribution after and before swelling. P((MAA-co-DMAEMA)-g-EG) PANGs have typically amphoteric characters responding to pH, whose isoelectric point (IEP) increases with decreasing the ratio of MAA/DMAEMA and equilibrium swelling degree (ESD) is greater than that at IEP when the pH value is distant from IEP. P((MAA-co-DMAEMA)-g-EG) PANGs also represent ionic strength sensitivity. Using the water-soluble chitosan (CS, Mn = 5 kDa) as model drug, in vitro release indicates that CS can be effectively incorporated into PANGs and the release rate of CS at pH 1.89 is an order of magnitude greater than that at pH 8.36. P((MAA-co-DMAEMA)-g-EG) PANGs may be useful in biomedicine, especially in oral drug delivery of biomacromolecule.

Ubiquitin S65 phosphorylation engenders a pH-sensitive conformational switch

PubMed Central

Dong, Xu; Gong, Zhou; Lu, Yun-Bi; Liu, Kan; Qin, Ling-Yun; Ran, Meng-Lin; Zhang, Chang-Li; Liu, Zhu; Zhang, Wei-Ping

2017-01-01

Ubiquitin (Ub) is an important signaling protein. Recent studies have shown that Ub can be enzymatically phosphorylated at S65, and that the resulting pUb exhibits two conformational states—a relaxed state and a retracted state. However, crystallization efforts have yielded only the structure for the relaxed state, which was found similar to that of unmodified Ub. Here we present the solution structures of pUb in both states obtained through refinement against state-specific NMR restraints. We show that the retracted state differs from the relaxed state by the retraction of the last β-strand and by the extension of the second α-helix. Further, we show that at 7.2, the pKa value for the phosphoryl group in the relaxed state is higher by 1.4 units than that in the retracted state. Consequently, pUb exists in equilibrium between protonated and deprotonated forms and between retracted and relaxed states, with protonated/relaxed species enriched at slightly acidic pH and deprotonated/retracted species enriched at slightly basic pH. The heterogeneity of pUb explains the inability of phosphomimetic mutants to fully mimic pUb. The pH-sensitive conformational switch is likely preserved for polyubiquitin, as single-molecule FRET data indicate that pH change leads to quaternary rearrangement of a phosphorylated K63-linked diubiquitin. Because cellular pH varies among compartments and changes upon pathophysiological insults, our finding suggests that pH and Ub phosphorylation confer additional target specificities and enable an additional layer of modulation for Ub signals. PMID:28611216

pH-sensitive fluorescent sensors based on europium(III) complexes.

PubMed

Zhang, Xiaolin; Jiao, Yang; Jing, Xu; Wu, Hongmei; He, Guangjie; Duan, Chunying

2011-03-21

New europium(III) complexes Eu(TTA)(2)-DSQ and Eu(TTA)(3)-DR1 were designed and synthesized as new fluorescent pH probes (where HDSQ = 5-(dimethylamino)-N-(4-(2-((8-hydroxyquinolin-2-yl)methylene)hydrazinecarbonyl)phenyl)naphthalene-1-sulfonamide, DR1 = N(1)-(4-(dimethylamino)benzylidene)-N(2)-(rhodamine-6G) lactamethylene-diamine and TTA = thiophentrifluoroacetone). Eu(TTA)(2)-DSQ exhibited high sensitivity in monitoring pH changes in neutral aqueous solution with negligible background fluorescence. Eu(TTA)(3)-DR1 comprised a green light emitting Rhodamine 6G fluorophore and a Eu(III) moiety as the origin of red light. These pH-sensitive emitter components have pK(a) values of 5.0 and 7.2 respectively, and exhibit isolated protonated steps within one molecule. Luminescence titrations demonstrate that Eu(TTA)(3)-DR1 was able to detect pH values at both near neutral pH and acidic pH ranges, and was also able to detect pH in both cultured cells and in vivo.

Noninvasive, near infrared spectroscopic-measured muscle pH and PO2 indicate tissue perfusion for cardiac surgical patients undergoing cardiopulmonary bypass

NASA Technical Reports Server (NTRS)

Soller, Babs R.; Idwasi, Patrick O.; Balaguer, Jorge; Levin, Steven; Simsir, Sinan A.; Vander Salm, Thomas J.; Collette, Helen; Heard, Stephen O.

2003-01-01

OBJECTIVE: To determine whether near infrared spectroscopic measurement of tissue pH and Po2 has sufficient accuracy to assess variation in tissue perfusion resulting from changes in blood pressure and metabolic demand during cardiopulmonary bypass. DESIGN: Prospective clinical study. SETTING: Academic medical center. SUBJECTS: Eighteen elective cardiac surgical patients. INTERVENTION: Cardiac surgery under cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: A near infrared spectroscopic fiber optic probe was placed over the hypothenar eminence. Reference Po2 and pH sensors were inserted in the abductor digiti minimi (V). Data were collected every 30 secs during surgery and for 6 hrs following cardiopulmonary bypass. Calibration equations developed from one third of the data were used with the remaining data to investigate sensitivity of the near infrared spectroscopic measurement to physiologic changes resulting from cardiopulmonary bypass. Near infrared spectroscopic and reference pH and Po2 measurements were compared for each subject using standard error of prediction. Near infrared spectroscopic pH and Po2 at baseline were compared with values during cardiopulmonary bypass just before rewarming commenced (hypotensive, hypothermic), after rewarming (hypotensive, normothermic) just before discontinuation of cardiopulmonary bypass, and at 6 hrs following cardiopulmonary bypass (normotensive, normothermic) using mixed-model analysis of variance. Near infrared spectroscopic pH and Po2 were well correlated with the invasive measurement of pH (R2 =.84) and Po2 (R 2 =.66) with an average standard error of prediction of 0.022 +/- 0.008 pH units and 6 +/- 3 mm Hg, respectively. The average difference between the invasive and near infrared spectroscopic measurement was near zero for both the pH and Po2 measurements. Near infrared spectroscopic Po2 significantly decreased 50% on initiation of cardiopulmonary bypass and remained depressed throughout the bypass and monitored intensive care period. Near infrared spectroscopic pH decreased significantly during cardiopulmonary bypass, decreased significantly during rewarming, and remained depressed 6 hrs after cardiopulmonary bypass. Diabetic patients responded differently than nondiabetic subjects to cardiopulmonary bypass, with lower muscle pH values (p =.02). CONCLUSIONS: Near infrared spectroscopic-measured muscle pH and Po2 are sensitive to changes in tissue perfusion during cardiopulmonary bypass.

Surface Coatings for Gas Detection via Porous Silicon

NASA Astrophysics Data System (ADS)

Ozdemir, Serdar; Li, Ji-Guang; Gole, James

2009-03-01

Nanopore covered microporous silicon interfaces have been formed via an electrochemical etch for gas sensor applications. Rapid reversible and sensitive gas sensors have been fabricated. The fabricated porous silicon (PS) gas sensors display the advantages of operation at room temperature as well as at a single, readily accessible temperature with an insensitivity to temperature drift; operation in a heat-sunk configuration, ease of coating with gas-selective materials; low cost of fabrication and operation, and the ability to rapidly assess false positives by operating the sensor in a pulsed mode. The PS surface has been modified with unique coatings on the basis of a general theory in order to achieve maximum sensitivity and selectivity. Sensing of NH3, NOx and PH3 at or below the ppm level have been observed. A typical PS nanostructure coated microstructured hybrid configuration when coated with tin oxide (NOx, CO) and gold nanostructures (NH3) provides a greatly increased sensitivity to the indicated gases. Al2O3 coating of the porous silicon using atomic layer deposition and its effect on PH3 sensing has been investigated. 20-100 nm TiO2 nanoparticles have been produced using sol-gel methods to coat PS surfaces and the effects on the selectivity and the sensitivity have been studied.

Diversities and similarities in pH dependency among bacterial NhaB-like Na+/H+ antiporters.

PubMed

Kiriyama, Wakako; Honma, Kei; Hiratsuka, Tomoaki; Takahashi, Itsuka; Nomizu, Takahiro; Takashima, Yuta; Ohtsuka, Masataka; Takahashi, Daiki; Moriyama, Kazuya; Mori, Sayoko; Nishiyama, Shiho; Fukuhara, Masahiro; Nakamura, Tatsunosuke; Shigematsu, Toru; Yamaguchi, Toshio

2013-10-01

NhaB-like antiporters were the second described class of Na(+)/H(+) antiporters, identified in bacteria more than 20 years ago. While nhaB-like gene sequences have been found in a number of bacterial genomes, only a few of the NhaB-like antiporters have been functionally characterized to date. Although earlier studies have identified a few pH-sensitive and -insensitive NhaB-like antiporters, the mechanisms that determine their pH responses still remain elusive. In this study, we sought to investigate the diversities and similarities among bacterial NhaB-like antiporters, with particular emphasis on their pH responsiveness. Our phylogenetic analysis of NhaB-like antiporters, combined with pH profile analyses of activities for representative members of several phylogenetic groups, demonstrated that NhaB-like antiporters could be classified into three distinct types according to the degree of their pH dependencies. Interestingly, pH-insensitive NhaB-like antiporters were only found in a limited proportion of enterobacterial species, which constitute a subcluster that appears to have diverged relatively recently among enterobacterial NhaB-like antiporters. Furthermore, kinetic property analyses of NhaB-like antiporters at different pH values revealed that the degree of pH sensitivity of antiport activities was strongly correlated with the magnitude of pH-dependent change in apparent Km values, suggesting that the dramatic pH sensitivities observed for several NhaB-like antiporters might be mainly due to the significant increases of apparent Km at lower pH. These results strongly suggested the possibility that the loss of pH sensitivity of NhaB-like antiporters had occurred relatively recently, probably via accumulation of the mutations that impair pH-dependent change of Km in the course of molecular evolution.

High-resolution Imaging of pH in Alkaline Sediments and Water Based on a New Rapid Response Fluorescent Planar Optode

NASA Astrophysics Data System (ADS)

Han, Chao; Yao, Lei; Xu, Di; Xie, Xianchuan; Zhang, Chaosheng

2016-05-01

A new dual-lumophore optical sensor combined with a robust RGB referencing method was developed for two-dimensional (2D) pH imaging in alkaline sediments and water. The pH sensor film consisted of a proton-permeable polymer (PVC) in which two dyes with different pH sensitivities and emission colors: (1) chloro phenyl imino propenyl aniline (CPIPA) and (2) the coumarin dye Macrolex® fluorescence yellow 10 GN (MFY-10 GN) were entrapped. Calibration experiments revealed the typical sigmoid function and temperature dependencies. This sensor featured high sensitivity and fast response over the alkaline working ranges from pH 7.5 to pH 10.5. Cross-sensitivity towards ionic strength (IS) was found to be negligible for freshwater when IS <0.1 M. The sensor had a spatial resolution of approximately 22 μm and aresponse time of <120 s when going from pH 7.0 to 9.0. The feasibility of the sensor was demonstrated using the pH microelectrode. An example of pH image obtained in the natrual freshwater sediment and water associated with the photosynthesis of Vallisneria spiral species was also presented, suggesting that the sensor held great promise for the field applications.

High-resolution Imaging of pH in Alkaline Sediments and Water Based on a New Rapid Response Fluorescent Planar Optode

PubMed Central

Han, Chao; Yao, Lei; Xu, Di; Xie, Xianchuan; Zhang, Chaosheng

2016-01-01

A new dual-lumophore optical sensor combined with a robust RGB referencing method was developed for two-dimensional (2D) pH imaging in alkaline sediments and water. The pH sensor film consisted of a proton-permeable polymer (PVC) in which two dyes with different pH sensitivities and emission colors: (1) chloro phenyl imino propenyl aniline (CPIPA) and (2) the coumarin dye Macrolex® fluorescence yellow 10 GN (MFY-10 GN) were entrapped. Calibration experiments revealed the typical sigmoid function and temperature dependencies. This sensor featured high sensitivity and fast response over the alkaline working ranges from pH 7.5 to pH 10.5. Cross-sensitivity towards ionic strength (IS) was found to be negligible for freshwater when IS <0.1 M. The sensor had a spatial resolution of approximately 22 μm and aresponse time of <120 s when going from pH 7.0 to 9.0. The feasibility of the sensor was demonstrated using the pH microelectrode. An example of pH image obtained in the natrual freshwater sediment and water associated with the photosynthesis of Vallisneria spiral species was also presented, suggesting that the sensor held great promise for the field applications. PMID:27199163

Ca2+-associated triphasic pH changes in mitochondria during brown adipocyte activation.

PubMed

Hou, Yanyan; Kitaguchi, Tetsuya; Kriszt, Rókus; Tseng, Yu-Hua; Raghunath, Michael; Suzuki, Madoka

2017-08-01

Brown adipocytes (BAs) are endowed with a high metabolic capacity for energy expenditure due to their high mitochondria content. While mitochondrial pH is dynamically regulated in response to stimulation and, in return, affects various metabolic processes, how mitochondrial pH is regulated during adrenergic stimulation-induced thermogenesis is unknown. We aimed to reveal the spatial and temporal dynamics of mitochondrial pH in stimulated BAs and the mechanisms behind the dynamic pH changes. A mitochondrial targeted pH-sensitive protein, mito-pHluorin, was constructed and transfected to BAs. Transfected BAs were stimulated by an adrenergic agonist, isoproterenol. The pH changes in mitochondria were characterized by dual-color imaging with indicators that monitor mitochondrial membrane potential and heat production. The mechanisms of pH changes were studied by examining the involvement of electron transport chain (ETC) activity and Ca 2+ profiles in mitochondria and the intracellular Ca 2+ store, the endoplasmic reticulum (ER). A triphasic mitochondrial pH change in BAs upon adrenergic stimulation was revealed. In comparison to a thermosensitive dye, we reveal that phases 1 and 2 of the pH increase precede thermogenesis, while phase 3, characterized by a pH decrease, occurs during thermogenesis. The mechanism of pH increase is partially related to ETC. In addition, the pH increase occurs concurrently with an increase in mitochondrial Ca 2+ . This Ca 2+ increase is contributed to by an influx from the ER, and it is further involved in mitochondrial pH regulation. We demonstrate that an increase in mitochondrial pH is implicated as an early event in adrenergically stimulated BAs. We further suggest that this pH increase may play a role in the potentiation of thermogenesis.

Phase angle assessment by bioelectrical impedance analysis and its predictive value for malnutrition risk in hospitalized geriatric patients.

PubMed

Varan, Hacer Dogan; Bolayir, Basak; Kara, Ozgur; Arik, Gunes; Kizilarslanoglu, Muhammet Cemal; Kilic, Mustafa Kemal; Sumer, Fatih; Kuyumcu, Mehmet Emin; Yesil, Yusuf; Yavuz, Burcu Balam; Halil, Meltem; Cankurtaran, Mustafa

2016-12-01

Phase angle (PhA) value determined by bioelectrical impedance analysis (BIA) is an indicator of cell membrane damage and body cell mass. Recent studies have shown that low PhA value is associated with increased nutritional risk in various group of patients. However, there have been only a few studies performed globally assessing the relationship between nutritional risk and PhA in hospitalized geriatric patients. The aim of the study is to evaluate the predictive value of the PhA for malnutrition risk in hospitalized geriatric patients. One hundred and twenty-two hospitalized geriatric patients were included in this cross-sectional study. Comprehensive geriatric assessment tests and BIA measurements were performed within the first 48 h after admission. Nutritional risk state of the patients was determined with NRS-2002. Phase angle values of the patients with malnutrition risk were compared with the patients that did not have the same risk. The independent variables for predicting malnutrition risk were determined. SPSS version 15 was utilized for the statistical analyzes. The patients with malnutrition risk had significantly lower phase angle values than the patients without malnutrition risk (p = 0.003). ROC curve analysis suggested that the optimum PhA cut-off point for malnutrition risk was 4.7° with 79.6 % sensitivity, 64.6 % specificity, 73.9 % positive predictive value, and 73.9 % negative predictive value. BMI, prealbumin, PhA, and Mini Mental State Examination Test scores were the independent variables for predicting malnutrition risk. PhA can be a useful, independent indicator for predicting malnutrition risk in hospitalized geriatric patients.

Single-cell intracellular nano-pH probes.

PubMed

Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

2015-01-01

Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution.

A wide range and highly sensitive optical fiber pH sensor using polyacrylamide hydrogel

NASA Astrophysics Data System (ADS)

Pathak, Akhilesh Kumar; Singh, Vinod Kumar

2017-12-01

In the present study we report the fabrication and characterization of no-core fiber sensor (NCFS) using smart hydrogel coating for pH measurement. The no-core fiber (NCF) is stubbed between two single-mode fibers with SMA connector before immobilizing of smart hydrogel. The wavelength interrogation technique is used to calculate the sensitivity of the proposed sensor. The result shows a high sensitivity of 1.94 nm/pH for a wide range of pH values varied from 3 to 10 with a good linear response. In addition to high sensitivity, the fabricated sensor provides a fast response time with a good stability, repeatability and reproducibility.

Influence of annealing time on pH sensitivity of ZnO sensing membrane for EGFET sensor

NASA Astrophysics Data System (ADS)

Zulkefle, M. A.; Rahman, R. A.; Yusoff, K. A.; Abdullah, W. F. H.; Rusop, M.; Herman, S. H.

2018-05-01

Solid-state materials have becomes essential in recent technological advancements. This study also utilized solid-state material but in form of thin films to sense hydrogen ions in solutions. Fabrication of ZnO thin film was done using sol-gel spin coating technique. In an attempt to increase the pH sensitivity of the produced film, prolonging of annealing time was done. It was found that the increase in annealing time from 15 minutes to 30 minutes had managed to improve the sensitivity by 4.35%. The optimum pH sensitivity and linearity obtained in this study is 50.40 mV/pH and 0.9911 respectively.

Serum-free suspension cultivation of PER.C6(R) cells and recombinant adenovirus production under different pH conditions.

PubMed

Xie, Liangzhi; Pilbrough, Warren; Metallo, Christian; Zhong, Tanya; Pikus, Lana; Leung, John; Auniņs, John G; Zhou, Weichang

2002-12-05

PER.C6(R) cell growth, metabolism, and adenovirus production were studied in head-to-head comparisons in stirred bioreactors under different pH conditions. Cell growth rate was found to be similar in the pH range of 7.1-7.6, while a long lag phase and a slower growth rate were observed at pH 6.8. The specific consumption rates of glucose and glutamine decreased rapidly over time during batch cell growth, as did the specific lactate and ammonium production rates. Cell metabolism in both infected and uninfected cultures was very sensitive to culture pH, resulting in dramatic differences in glucose/glutamine consumption and lactate/ammonium production under different pH conditions. It appeared that glucose metabolism was suppressed at low pH but the efficiency of energy production from glucose was enhanced. Adenovirus infection resulted in profound changes in cell growth and metabolism. Cell growth was largely arrested under all pH conditions, while glucose consumption and lactate production were elevated post virus infection. Virus infection induced a reduction in glutamine consumption at low pH but an increase at high pH. The optimal pH for adenovirus production was found to be 7.3 under the experimental conditions used in the study. Deviations from this optimum resulted in significant reductions of virus productivity. The results indicate that culture pH is a very critical process parameter in PER.C6(R) cell culture and adenovirus production. Copyright 2002 Wiley Periodicals, Inc.

Design, calibration and application of broad-range optical nanosensors for determining intracellular pH.

PubMed

Søndergaard, Rikke V; Henriksen, Jonas R; Andresen, Thomas L

2014-12-01

Particle-based nanosensors offer a tool for determining the pH in the endosomal-lysosomal system of living cells. Measurements providing absolute values of pH have so far been restricted by the limited sensitivity range of nanosensors, calibration challenges and the complexity of image analysis. This protocol describes the design and application of a polyacrylamide-based nanosensor (∼60 nm) that covalently incorporates two pH-sensitive fluorophores, fluorescein (FS) and Oregon Green (OG), to broaden the sensitivity range of the sensor (pH 3.1-7.0), and uses the pH-insensitive fluorophore rhodamine as a reference fluorophore. The nanosensors are spontaneously taken up via endocytosis and directed to the lysosomes where dynamic changes in pH can be measured with live-cell confocal microscopy. The most important focus areas of the protocol are the choice of pH-sensitive fluorophores, the design of calibration buffers, the determination of the effective range and especially the description of how to critically evaluate results. The entire procedure typically takes 2-3 weeks.

PH-sensitive fluorescence detection by diffuse fluorescence tomography

NASA Astrophysics Data System (ADS)

Li, Jiao; Gao, Feng; Duan, Linjing; Wang, Xin; Zhang, Limin; Zhao, Huijuan

2012-03-01

The importance of cellular pH has been shown clearly in the study of cell activity, pathological feature, drug metabolism, etc. Monitoring pH changes of living cells and imaging the regions with abnormal pH values in vivo could provide the physiologic and pathologic information for the research of the cell biology, pharmacokinetics, diagnostics and therapeutics of certain diseases such as cancer. Thus, pH-sensitive fluorescence imaging of bulk tissues has been attracting great attention in the regime of near-infrared diffuse fluorescence tomography (DFT), an efficient small-animal imaging tool. In this paper, the feasibility of quantifying pH-sensitive fluorescence targets in turbid medium is investigated using both time-domain and steady-state DFT methods. By use of the specifically designed time-domain and continuous-wave systems and the previously proposed image reconstruction scheme, we validate the method through 2-dimensional imaging experiments on a small-animal-sized phantom with multiply targets of distinct pH values. The results show that the approach can localize the targets with reasonable accuracy and achieve quantitative reconstruction of the pH-sensitive fluorescent yield.

Highly selective optical fluoride ion sensor with submicromolar detection limit based on aluminum(III) octaethylporphyrin in thin polymeric film.

PubMed

Badr, Ibrahim H A; Meyerhoff, Mark E

2005-04-20

A highly selective, sensitive, and reversible fluoride optical sensing film based on aluminum(III)octaethylporphyrin as a fluoride ionophore and a lipophilic pH indicator as the optical transducer is described. The fluoride optical sensing films exhibit a submicromolar detection limit and high discrimination for fluoride over several lipophilic anions such as nitrate, perchlorate, and thiocyanate.

Highly Sensitive and Wide-Dynamic-Range Multichannel Optical-Fiber pH Sensor Based on PWM Technique.

PubMed

Khan, Md Rajibur Rahaman; Kang, Shin-Won

2016-11-09

In this study, we propose a highly sensitive multichannel pH sensor that is based on an optical-fiber pulse width modulation (PWM) technique. According to the optical-fiber PWM method, the received sensing signal's pulse width changes when the optical-fiber pH sensing-element of the array comes into contact with pH buffer solutions. The proposed optical-fiber PWM pH-sensing system offers a linear sensing response over a wide range of pH values from 2 to 12, with a high pH-sensing ability. The sensitivity of the proposed pH sensor is 0.46 µs/pH, and the correlation coefficient R² is approximately 0.997. Additional advantages of the proposed optical-fiber PWM pH sensor include a short/fast response-time of about 8 s, good reproducibility properties with a relative standard deviation (RSD) of about 0.019, easy fabrication, low cost, small size, reusability of the optical-fiber sensing-element, and the capability of remote sensing. Finally, the performance of the proposed PWM pH sensor was compared with that of potentiometric, optical-fiber modal interferometer, and optical-fiber Fabry-Perot interferometer pH sensors with respect to dynamic range width, linearity as well as response and recovery times. We observed that the proposed sensing systems have better sensing abilities than the above-mentioned pH sensors.

Highly Sensitive and Wide-Dynamic-Range Multichannel Optical-Fiber pH Sensor Based on PWM Technique

PubMed Central

Khan, Md. Rajibur Rahaman; Kang, Shin-Won

2016-01-01

In this study, we propose a highly sensitive multichannel pH sensor that is based on an optical-fiber pulse width modulation (PWM) technique. According to the optical-fiber PWM method, the received sensing signal’s pulse width changes when the optical-fiber pH sensing-element of the array comes into contact with pH buffer solutions. The proposed optical-fiber PWM pH-sensing system offers a linear sensing response over a wide range of pH values from 2 to 12, with a high pH-sensing ability. The sensitivity of the proposed pH sensor is 0.46 µs/pH, and the correlation coefficient R2 is approximately 0.997. Additional advantages of the proposed optical-fiber PWM pH sensor include a short/fast response-time of about 8 s, good reproducibility properties with a relative standard deviation (RSD) of about 0.019, easy fabrication, low cost, small size, reusability of the optical-fiber sensing-element, and the capability of remote sensing. Finally, the performance of the proposed PWM pH sensor was compared with that of potentiometric, optical-fiber modal interferometer, and optical-fiber Fabry–Perot interferometer pH sensors with respect to dynamic range width, linearity as well as response and recovery times. We observed that the proposed sensing systems have better sensing abilities than the above-mentioned pH sensors. PMID:27834865

Fliposomes: pH-triggered conformational flip of new trans-2-aminocyclohexanol-based amphiphiles causes instant cargo release in liposomes.

PubMed

Liu, Xin; Zheng, Yu; Samoshina, Nataliya M; Franz, Andreas H; Guo, Xin; Samoshin, Vyacheslav V

2012-12-01

A new type of pH-sensitive liposomes (fliposomes) was designed based on the amphiphiles that are able to perform a pH-triggered conformational flip (flipids). This flip disrupts the liposome membrane and causes rapid release of the liposome cargo, specifically in response to lowered pH. The flipids (1) and (2) are equipped with a trans-2-aminocyclohexanol conformational switch. pH-sensitive fliposomes containing one or both of these flipids, as well as POPC and PEG ceramide, were constructed and characterized. These compositions were stable at 4°C and pH 7.4 for several months. Fliposomes loaded with ANTS/DPX performed an unusually quick content release within a few seconds at pH below 8.5 (in case of 2) and 6.0 (in case of 1). This difference in pH sensitivity demonstrates a potential for the custom design of flipids by variation of the amino group to target areas with specific pH values. The pH titration curves for the fliposome leakage parallel the curves for the acid-induced conformational flip of 1 and 2 studied by ¹H NMR. A plausible mechanism of pH sensitivity starts with an acid-triggered conformational flip of 1 or 2, which changes the molecular size and shape, shortens the lipid tails, and perturbs the liposome membrane, resulting in the content leakage.

Dual-pH Sensitive Charge-reversal Nanocomplex for Tumor-targeted Drug Delivery with Enhanced Anticancer Activity.

PubMed

Zhou, Qing; Hou, Yilin; Zhang, Li; Wang, Jianlin; Qiao, Youbei; Guo, Songyan; Fan, Li; Yang, Tiehong; Zhu, Lin; Wu, Hong

2017-01-01

Poly(β-L-malic acid) (PMLA), a natural aliphatic polyester, has been proven to be a promising carrier for anti-cancer drugs. In spite of excellent bio-compatibility, the application of PMLA as the drug carrier for cancer therapy is limited by its low cellular uptake efficiency. The strong negative charge of PMLA impedes its uptake by cancer cells because of the electrostatic repulsion. In this study, a dual pH-sensitive charge-reversal PMLA-based nanocomplex (PMLA-PEI-DOX-TAT@PEG-DMMA) was developed for effective tumor-targeted drug delivery, enhanced cellular uptake, and intracellular drug release. The prepared nanocomplex showed a negative surface charge at the physiological pH, which could protect the nanocomplex from the attack of plasma proteins and recognition by the reticuloendothelial system, so as to prolong its circulation time. While at the tumor extracellular pH 6.8, the DMMA was hydrolyzed, leading to the charge reversal and exposure of the TAT on the polymeric micelles, thus enhancing the cellular internalization. Then, the polymeric micelles underwent dissociation and drug release in response to the acidic pH in the lyso/endosomal compartments of the tumor cell. Both in vitro and in vivo efficacy studies indicated that the nanocomplex significantly inhibited the tumor growth while the treatment showed negligible systemic toxicity, suggesting that the developed dual pH-sensitive PMLA-based nanocomplex would be a promising drug delivery system for tumor-targeted drug delivery with enhanced anticancer activity.

Dual-pH Sensitive Charge-reversal Nanocomplex for Tumor-targeted Drug Delivery with Enhanced Anticancer Activity

PubMed Central

Zhou, Qing; Hou, Yilin; Zhang, Li; Wang, Jianlin; Qiao, Youbei; Guo, Songyan; Fan, Li; Yang, Tiehong; Zhu, Lin; Wu, Hong

2017-01-01

Poly(β-L-malic acid) (PMLA), a natural aliphatic polyester, has been proven to be a promising carrier for anti-cancer drugs. In spite of excellent bio-compatibility, the application of PMLA as the drug carrier for cancer therapy is limited by its low cellular uptake efficiency. The strong negative charge of PMLA impedes its uptake by cancer cells because of the electrostatic repulsion. In this study, a dual pH-sensitive charge-reversal PMLA-based nanocomplex (PMLA-PEI-DOX-TAT@PEG-DMMA) was developed for effective tumor-targeted drug delivery, enhanced cellular uptake, and intracellular drug release. The prepared nanocomplex showed a negative surface charge at the physiological pH, which could protect the nanocomplex from the attack of plasma proteins and recognition by the reticuloendothelial system, so as to prolong its circulation time. While at the tumor extracellular pH 6.8, the DMMA was hydrolyzed, leading to the charge reversal and exposure of the TAT on the polymeric micelles, thus enhancing the cellular internalization. Then, the polymeric micelles underwent dissociation and drug release in response to the acidic pH in the lyso/endosomal compartments of the tumor cell. Both in vitro and in vivo efficacy studies indicated that the nanocomplex significantly inhibited the tumor growth while the treatment showed negligible systemic toxicity, suggesting that the developed dual pH-sensitive PMLA-based nanocomplex would be a promising drug delivery system for tumor-targeted drug delivery with enhanced anticancer activity. PMID:28638469

A new fluorescence-based method to monitor the pH in the thylakoid lumen using GFP variants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Hong; Pu, Xiaojun; Wang, Lu

The ΔpH-dependent/Tat pathway is unique for using only the proton motive force for driving proteins transport across the thylakoid membrane in chloroplasts. 9-aminoacridine fluorescence quenching is widely used to monitor the ΔpH developed across the thylakoid membrane in the light. However, this method suffers from limited sensitivity to low ΔpH values and to spurious fluorescence signals due to membrane binding. In order to develop a more sensitive method for monitoring the real pH of the thylakoid lumen without these problems we transformed Arabidopsis thaliana with a ratiometric pH-sensitive GFP variant (termed pHluorin) targeted to the lumen by the prOE17 transitmore » peptide. Positive transgenic plants displayed localization of pHluorin in the chloroplast by confocal microscopy, and fractionation experiments revealed that it is in the lumen. The pHluorin signal was the strongest in very young plants and diminished as the plants matured. The pHluorin released from the lumen displayed the expected fluorescence intensity changes in response to pH titration. The fluorescence signal in isolated chloroplasts responded to illumination in a manner consistent with light-dependent lumen acidification. Future experiments will exploit the use of this new pH-indicating probe of the thylakoid lumen to examine the influence of the thylakoid ΔpH on ATP synthesis and protein transport.« less

Simultaneous Determination of Oxygen and pH Inside Microfluidic Devices Using Core-Shell Nanosensors.

PubMed

Ehgartner, Josef; Strobl, Martin; Bolivar, Juan M; Rabl, Dominik; Rothbauer, Mario; Ertl, Peter; Borisov, Sergey M; Mayr, Torsten

2016-10-04

A powerful online analysis setup for the simultaneous detection of oxygen and pH is presented. It features core-shell nanosensors, which enable contactless and inexpensive read-out using adapted oxygen meters via modified dual lifetime referencing in the frequency domain (phase shift measurements). Lipophilic indicator dyes were incorporated into core-shell structured poly(styrene-block-vinylpyrrolidone) nanoparticles (average diameter = 180 nm) yielding oxygen nanosensors and pH nanosensors by applying different preparation protocols. The oxygen indicator platinum(II) meso-tetra(4-fluorophenyl) tetrabenzoporphyrin (PtTPTBPF) was entrapped into the polystyrene core (oxygen nanosensors) and a pH sensitive BF 2 -chelated tetraarylazadipyrromethene dye (aza-BODIPY) was incorporated into the polyvinylpyrrolidone shell (pH nanosensors). The brightness of the pH nanoparticles was increased by more than 3 times using a light harvesting system. The nanosensors have several advantages such as being excitable with red light, emitting in the near-infrared spectral region, showing a high stability in aqueous media even at high particle concentrations, high ionic strength, or high protein concentrations and are spectrally compatible with the used read-out device. The resolution for oxygen of the setup is 0.5-2.0 hPa (approximately 0.02-0.08 mg/L of dissolved oxygen) at low oxygen concentrations (<50 hPa) and 4-8 hPa (approximately 0.16-0.32 mg/L of dissolved oxygen) at ambient air oxygen concentrations (approximately 200 hPa at 980 mbar air pressure) at room temperature. The pH resolution is 0.03-0.1 pH units within the dynamic range (apparent pK a 7.23 ± 1.0) of the nanosensors. The sensors were used for online monitoring of pH changes during the enzymatic transformation of Penicillin G to 6-aminopenicillanic acid catalyzed by Penicillin G acylase in miniaturized stirred batch reactors or continuous flow microreactors.

Fine-particle pH for Beijing winter haze as inferred from different thermodynamic equilibrium models

NASA Astrophysics Data System (ADS)

Song, Shaojie; Gao, Meng; Xu, Weiqi; Shao, Jingyuan; Shi, Guoliang; Wang, Shuxiao; Wang, Yuxuan; Sun, Yele; McElroy, Michael B.

2018-05-01

pH is an important property of aerosol particles but is difficult to measure directly. Several studies have estimated the pH values for fine particles in northern China winter haze using thermodynamic models (i.e., E-AIM and ISORROPIA) and ambient measurements. The reported pH values differ widely, ranging from close to 0 (highly acidic) to as high as 7 (neutral). In order to understand the reason for this discrepancy, we calculated pH values using these models with different assumptions with regard to model inputs and particle phase states. We find that the large discrepancy is due primarily to differences in the model assumptions adopted in previous studies. Calculations using only aerosol-phase composition as inputs (i.e., reverse mode) are sensitive to the measurement errors of ionic species, and inferred pH values exhibit a bimodal distribution, with peaks between -2 and 2 and between 7 and 10, depending on whether anions or cations are in excess. Calculations using total (gas plus aerosol phase) measurements as inputs (i.e., forward mode) are affected much less by these measurement errors. In future studies, the reverse mode should be avoided whereas the forward mode should be used. Forward-mode calculations in this and previous studies collectively indicate a moderately acidic condition (pH from about 4 to about 5) for fine particles in northern China winter haze, indicating further that ammonia plays an important role in determining this property. The assumed particle phase state, either stable (solid plus liquid) or metastable (only liquid), does not significantly impact pH predictions. The unrealistic pH values of about 7 in a few previous studies (using the standard ISORROPIA model and stable state assumption) resulted from coding errors in the model, which have been identified and fixed in this study.

Effects of pH and Iminosugar Pharmacological Chaperones on Lysosomal Glycosidase Structure and Stability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lieberman, Raquel L.; D’aquino, J. Alejandro; Ringe, Dagmar

2009-06-05

Human lysosomal enzymes acid-{beta}-glucosidase (GCase) and acid-{alpha}-galactosidase ({alpha}-Gal A) hydrolyze the sphingolipids glucosyl- and globotriaosylceramide, respectively, and mutations in these enzymes lead to the lipid metabolism disorders Gaucher and Fabry disease, respectively. We have investigated the structure and stability of GCase and {alpha}-Gal A in a neutral-pH environment reflective of the endoplasmic reticulum and an acidic-pH environment reflective of the lysosome. These details are important for the development of pharmacological chaperone therapy for Gaucher and Fabry disease, in which small molecules bind mutant enzymes in the ER to enable the mutant enzyme to meet quality control requirements for lysosomal trafficking.more » We report crystal structures of apo GCase at pH 4.5, at pH 5.5, and in complex with the pharmacological chaperone isofagomine (IFG) at pH 7.5. We also present thermostability analysis of GCase at pH 7.4 and 5.2 using differential scanning calorimetry. We compare our results with analogous experiments using {alpha}-Gal A and the chaperone 1-deoxygalactonijirimycin (DGJ), including the first structure of {alpha}-Gal A with DGJ. Both GCase and {alpha}-Gal A are more stable at lysosomal pH with and without their respective iminosugars bound, and notably, the stability of the GCase-IFG complex is pH sensitive. We show that the conformations of the active site loops in GCase are sensitive to ligand binding but not pH, whereas analogous galactose- or DGJ-dependent conformational changes in {alpha}-Gal A are not seen. Thermodynamic parameters obtained from {alpha}-Gal A unfolding indicate two-state, van't Hoff unfolding in the absence of the iminosugar at neutral and lysosomal pH, and non-two-state unfolding in the presence of DGJ. Taken together, these results provide insight into how GCase and {alpha}-Gal A are thermodynamically stabilized by iminosugars and suggest strategies for the development of new pharmacological chaperones for lysosomal storage disorders.« less

Fluoride-sensitivity of growth and acid production of oral Actinomyces: comparison with oral Streptococcus.

PubMed

Kawashima, Junko; Nakajo, Kazuko; Washio, Jumpei; Mayanagi, Gen; Shimauchi, Hidetoshi; Takahashi, Nobuhiro

2013-12-01

Actinomyces are predominant oral bacteria; however, their cariogenic potential in terms of acid production and fluoride sensitivity has not been elucidated in detail and compared with that of other caries-associated oral bacteria, such as Streptococcus. Therefore, this study aimed to elucidate and compare the acid production and growth of Actinomyces and Streptococcus in the presence of bicarbonate and fluoride to mimic conditions in the oral cavity. Acid production from glucose was measured by pH-stat at pH 5.5 and 7.0 under anaerobic conditions. Growth rate was assessed by optical density in anaerobic culture. Although Actinomyces produced acid at a lower rate than did Streptococcus, their acid production was more tolerant of fluoride (IDacid production 50 = 110-170 ppm at pH 7.0 and 10-13 ppm at pH 5.5) than that of Streptococcus (IDacid production 50 = 36-53 ppm at pH 7.0 and 6.3-6.5 ppm at pH 5.5). Bicarbonate increased acid production by Actinomyces with prominent succinate production and enhanced their fluoride tolerance (IDacid production 50 = 220-320 ppm at pH 7.0 and 33-52 ppm at pH 5.5). Bicarbonate had no effect on these variables in Streptococcus. In addition, although the growth rate of Actinomyces was lower than that of Streptococcus, Actinomyces growth was more tolerant of fluoride (IDgrowth 50 = 130-160 ppm) than was that of Streptococcus (IDgrowth 50 = 27-36 ppm). These results indicate that oral Actinomyces are more tolerant of fluoride than oral Streptococcus, and bicarbonate enhances the fluoride tolerance of oral Actinomyces. Because of the limited number of species tested here, further study is needed to generalize these findings to the genus level. © 2013 The Societies and Wiley Publishing Asia Pty Ltd.

Sensitive detection of strong acidic condition by a novel rhodamine-based fluorescent pH chemosensor.

PubMed

Tan, Jia-Lian; Yang, Ting-Ting; Liu, Yu; Zhang, Xue; Cheng, Shu-Jin; Zuo, Hua; He, Huawei

2016-05-01

A novel rhodamine-based fluorescent pH probe responding to extremely low pH values has been synthesized and characterized. This probe showed an excellent photophysical response to pH on the basis that the colorless spirocyclic structure under basic conditions opened to a colored and highly fluorescent form under extreme acidity. The quantitative relationship between fluorescence intensity and pH value (1.75-2.62) was consistent with the equilibrium equation pH = pKa + log[(Imax - I)/(I - Imin)]. This sensitive pH probe was also characterized with good reversibility and no interaction with interfering metal ions, and was successfully applied to image Escherichia coli under strong acidity. Copyright © 2015 John Wiley & Sons, Ltd.

A protein-dye hybrid system as a narrow range tunable intracellular pH sensor.

PubMed

Anees, Palapuravan; Sudheesh, Karivachery V; Jayamurthy, Purushothaman; Chandrika, Arunkumar R; Omkumar, Ramakrishnapillai V; Ajayaghosh, Ayyappanpillai

2016-11-18

Accurate monitoring of pH variations inside cells is important for the early diagnosis of diseases such as cancer. Even though a variety of different pH sensors are available, construction of a custom-made sensor array for measuring minute variations in a narrow biological pH window, using easily available constituents, is a challenge. Here we report two-component hybrid sensors derived from a protein and organic dye nanoparticles whose sensitivity range can be tuned by choosing different ratios of the components, to monitor the minute pH variations in a given system. The dye interacts noncovalently with the protein at lower pH and covalently at higher pH, triggering two distinguishable fluorescent signals at 700 and 480 nm, respectively. The pH sensitivity region of the probe can be tuned for every unit of the pH window resulting in custom-made pH sensors. These narrow range tunable pH sensors have been used to monitor pH variations in HeLa cells using the fluorescence imaging technique.

Trilayer TMDC Heterostructures for MOSFETs and Nanobiosensors

NASA Astrophysics Data System (ADS)

Datta, Kanak; Shadman, Abir; Rahman, Ehsanur; Khosru, Quazi D. M.

2017-02-01

Two dimensional materials such as transition metal dichalcogenides (TMDC) and their bi-layer/tri-layer heterostructures have become the focus of intense research and investigation in recent years due to their promising applications in electronics and optoelectronics. In this work, we have explored device level performance of trilayer TMDC heterostructure (MoS2/MX2/MoS2; M = Mo or, W and X = S or, Se) metal oxide semiconductor field effect transistors (MOSFETs) in the quantum ballistic regime. Our simulation shows that device `on' current can be improved by inserting a WS2 monolayer between two MoS2 monolayers. Application of biaxial tensile strain reveals a reduction in drain current which can be attributed to the lowering of carrier effective mass with increased tensile strain. In addition, it is found that gate underlap geometry improves electrostatic device performance by improving sub-threshold swing. However, increase in channel resistance reduces drain current. Besides exploring the prospect of these materials in device performance, novel trilayer TMDC heterostructure double gate field effect transistors (FETs) are proposed for sensing Nano biomolecules as well as for pH sensing. Bottom gate operation ensures these FETs operating beyond Nernst limit of 59 mV/pH. Simulation results found in this work reveal that scaling of bottom gate oxide results in better sensitivity while top oxide scaling exhibits an opposite trend. It is also found that, for identical operating conditions, proposed TMDC FET pH sensors show super-Nernst sensitivity indicating these materials as potential candidates in implementing such sensor. Besides pH sensing, all these materials show high sensitivity in the sub-threshold region as a channel material in nanobiosensor while MoS2/WS2/MoS2 FET shows the least sensitivity among them.

Fabrication of triple-labeled polyelectrolyte microcapsules for localized ratiometric pH sensing.

PubMed

Song, Xiaoxue; Li, Huanbin; Tong, Weijun; Gao, Changyou

2014-02-15

Encapsulation of pH sensitive fluorophores as reporting molecules provides a powerful approach to visualize the transportation of multilayer capsules. In this study, two pH sensitive dyes (fluorescein and oregon green) and one pH insensitive dye (rhodamine B) were simultaneously labeled on the microcapsules to fabricate ratiometric pH sensors. The fluorescence of the triple-labeled microcapsule sensors was robust and nearly independent of other intracellular species. With a dynamic pH measurement range of 3.3-6.5, the microcapsules can report their localized pH at a real time. Cell culture experiments showed that the microcapsules could be internalized by RAW 246.7 cells naturally and finally accumulated in acidic organelles with a pH value of 5.08 ± 0.59 (mean ± s.d.; n=162). Copyright © 2013 Elsevier Inc. All rights reserved.

Polyaniline deposition on tilted fiber Bragg grating for pH sensing

NASA Astrophysics Data System (ADS)

Lopez Aldaba, A.; González-Vila, Á.; Debliquy, M.; Lopez-Amo, M.; Caucheteur, C.; Lahem, D.

2017-04-01

In this paper, we present the results of a new pH sensor based on a polyaniline (PAni) coating on the surface of a tilted fiber Bragg grating. The pH-sensitive PAni was deposited by in situ chemical oxidative polymerization. The performance of the fabricated pH sensor was tested and the obtained pH values were compared with the results obtained using a pH meter device. It was found that the sensor exhibits response to pH changes in the range of 2-12, achieving a sensitivity of 46 pm/pH with a maximum error due to the hysteresis effect of +/-1.14 pH. The main advantages of this PAni-TFBG pH sensor are biochemical compatibility, temperature independence, long-term stability and remote realtime multipoint sensing features. This type of sensor could be used for biochemical applications, pipeline corrosion monitoring or remote-multipoint measurements.

pH-Sensitive Liposomes: Possible Clinical Implications

NASA Astrophysics Data System (ADS)

Yatvin, M. B.; Kreutz, W.; Horwitz, B. A.; Shinitzky, M.

1980-12-01

When pH-sensitive molecules are incorporated into liposomes, drugs can be specifically released from these vesicles by a change of pH in the ambient serum. Liposomes containing the pH-sensitive lipid palmitoyl homocysteine (PHC) were constructed so that the greatest pH differential (6.0 to 7.4) of drug release was obtained near physiological temperature. Such liposomes could be useful clinically if they enable drugs to be targeted to areas of the body in which pH is less than physiological, such as primary tumors and metastases or sites of inflammation and infection.

Identification of nasopharyngeal carcinoma from photoluminescence spectra of 3C-SiC nanocrystals

NASA Astrophysics Data System (ADS)

Wang, Li-Fen; Guo, Jun-Hong; Huang, Zhi-Chun; Gu, Jian-Sen; Feng, Li-Ren; Liu, Li-Zhe

2017-09-01

The identification of intracellular pH (pHi) during carcinogenesis progression plays a crucial role in the studies of biochemistry, cytology, and clinical medicine. In this work, 3C-SiC nanocrystals (NCs), which can effectively monitor the pH environment by using the linear relation between photoluminescence intensity and surface OH- and H+ concentration, are adapted as fluorescent probes for monitoring carcinogenesis progression of nasopharyngeal carcinoma. Our results demonstrated that 3C-SiC NCs are compatible with living cells and have low cytotoxicity. The pHi measurements in different carcinogenesis environments indicate the validity and sensitivity of this technology in identifying nasopharyngeal carcinoma in application.

Complex of transferrin with ruthenium for medical applications

DOEpatents

Richards, P.; Srivastava, S.C.; Meinken, G.E.

1984-05-15

A novel ruthenium-transferrin complex is disclosed which is prepared by reacting iron-free human transferrin dissolved in a sodium acetate solution at pH 7 with ruthenium by heating at about 40 C for about 2 hours. The complex is purified by means of gel chromotography with pH 7 sodium acetate as eluent. The mono- or di-metal complex produced can be used in nuclear medicine in the diagnosis and/or treatment of tumors and abscesses. Comparative results with Ga-67-citrate, which is the most widely used tumor-localizing agent in nuclear medicine, indicate increased sensitivity of detection and greater tumor uptake with the Ru-transferrin complex. No Drawings

Complex of transferrin with ruthenium for medical applications. [Ru 97, Ru 103

DOEpatents

Richards, P.; Srivastava, S.C.; Meinken, G.E.

1980-11-03

A novel Ruthenium-transferrin complex, prepared by reacting iron-free human transferrin dissolved in a sodium acetate solution at pH 7 with ruthenium by heating at about 40/sup 0/C for about 2 hours, and purifying said complex by means of gel chromatography with pH 7 sodium acetate as eluent. The mono- or di-metal complex produced can be used in nuclear medicine in the diagnosis and/or treatment of tumors and abscesses. Comparitive results with Ga-67-citrate, which is the most widely used tumor-localizing agent in nuclear medicine, indicate increased sensitivity of detection and greater tumor uptake with the Ru-transferrin complex.

Activation of multiple pH-regulatory pathways in granulocytes by a phosphotyrosine phosphatase antagonist.

PubMed Central

Bianchini, L; Nanda, A; Wasan, S; Grinstein, S

1994-01-01

Activated phagocytes undergo a massive burst of metabolic acid generation, yet must be able to maintain their cytosolic pH (pHi) within physiological limits. Peroxides of vanadate (V(4+)-OOH), potent inhibitors of phosphotyrosine phosphatases, have recently been shown to produce activation of the respiratory burst in HL60 granulocytes. We therefore investigated the effects of V(4+)-OOH on pHi homoeostasis in HL60 granulocytes, using a pH-sensitive fluorescent dye. V(4+)-OOH stimulation induced a biphasic pH change: a transient cytosolic acidification followed by a significant alkalinization. The initial acidification was prevented by inhibition of the NADPH oxidase and was absent in undifferentiated cells lacking oxidase activity. Analysis of the alkalinization phase demonstrated the involvement of the Na+/H+ antiporter, and also provided evidence for activation of two alternative H(+)-extrusion pathways: a bafilomycin-sensitive component, likely reflecting vacuolar-type H(+)-ATPase activity, and a Zn(2+)-sensitive H(+)-conductive pathway. Our results indicate that V(4+)-OOH stimulation not only activated the NADPH oxidase but concomitantly stimulated H(+)-extrusion pathways, enabling the cells to compensate for the massive production of intracellular H+ associated with the respiratory burst. PMID:8043000

Phase transition behavior of novel pH-sensitive polyaspartamide derivatives grafted with 1-(3-aminopropyl)imidazole.

PubMed

Seo, Kwangwon; Kim, Dukjoon

2006-09-15

New pH-sensitive polyaspartamide derivatives were synthesized by grafting 1-(3-aminopropyl)imidazole and/or O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) 5000 on polysuccinimide for application in intracellular drug delivery systems. The DS of 1-(3-aminopropyl)imidazole was adjusted by the feed molar ratio, and the structure of the prepared polymer was confirmed using FT-IR and 1H NMR spectroscopy. Their pH-sensitive properties were characterized by light transmittance measurements, and the particle size and its distribution were investigated by dynamic light scattering measurements at varying pH values. The pH-sensitive phase transition was clearly observed in polymer solutions with a high substitution of 1-(3-aminopropyl)imidazole. The prepared polymers showed a high buffering capacity between pH 5 and 7, and this increased with the DS of 1-(3-aminopropyl)imidazole. The pH dependence of the aggregation and de-aggregation behavior was examined using a fluorescence spectrometer. For MPEG/imidazole-g-polyaspartamides with a DS of 1-(3-aminopropyl)imidazole over 82%, self aggregates associated with the hydrophobic interactions of the unprotonated imidazole groups were observed at pH values above 7, and their mean size was over 200 nm, while the aggregates of polymers were dissociated at pH values below 7 by the protonation of imidazole groups. These pH-sensitive polyaspartamide derivatives are potential basic candidates for intracellular drug delivery carriers triggered by small pH changes.

Nonsteroidal anti-inflammatory drugs inhibit gastric peroxidase activity.

PubMed

Banerjee, R K

1990-06-20

The peroxidase activity of the mitochondrial fraction of rat gastric mucosa was inhibited with various nonsteroidal anti-inflammatory drugs (NSAIDs) in vitro. Indomethacin was found to be more effective than phenylbutazone (PB) or acetylsalicylic acid (ASA). Mouse gastric peroxidase was also very sensitive to indomethacin inhibition. Indomethacin has no significant effect on submaxillary gland peroxidase activity of either of the species studied. Purified rat gastric peroxidase activity was inhibited 75% with 0.15 mM indomethacin showing half-maximal inhibition at 0.04 mM. The inhibition could be withdrawn by increasing the concentration of iodide but not by H2O2. NSAIDs inhibit gastric peroxidase activity more effectively at acid pH (pH 5.2) than at neutral pH. Spectral studies showed a bathochromic shift of the Soret band of the enzyme with indomethacin indicating its interaction at or near the heme part of the enzyme.

Destabilization and Treatment of Emulsified Oils in Wastewaters by Electrocoagulation.

PubMed

Genc, Ayten; Bakirci, Busra

2016-11-01

  In this study, the optimum operating conditions for the treatment of emulsified oils by electrocoagulation were determined depending on droplet stability analysis. Zeta potential measurements were used as the indication of oil droplet charges. In addition, the effects of pH and ionic conductivity on the droplet sizes and surface charges were investigated. The studied emulsified oil droplet sizes were more sensitive to changes in pH rather than salt concentration. The droplets became larger and unstable in alkaline conditions. As the initial pH of wastewaters increased, the oil removal efficiency increased during the electrocoagulation experiments as well. The use of iron or aluminum electrodes resulted in higher removal efficiencies in comparison to stainless steel electrodes. In addition, the energy consumption for aluminum electrodes was much lower than iron electrodes. To obtain 98% oil removal efficiency, distance between the electrodes was recommended to be less than or equal to 1 cm.

New Optical Sensing Materials for Application in Marine Research

NASA Astrophysics Data System (ADS)

Borisov, S.; Klimant, I.

2012-04-01

Optical chemosensors are versatile analytical tools which find application in numerous fields of science and technology. They proved to be a promising alternative to electrochemical methods and are applied increasingly often in marine research. However, not all state-of-the- art optical chemosensors are suitable for these demanding applications since they do not fully fulfil the requirements of high luminescence brightness, high chemical- and photochemical stability or their spectral properties are not adequate. Therefore, development of new advanced sensing materials is still of utmost importance. Here we present a set of novel optical sensing materials recently developed in the Institute of Analytical Chemistry and Food Chemistry which are optimized for marine applications. Particularly, we present new NIR indicators and sensors for oxygen and pH which feature high brightness and low level of autofluorescence. The oxygen sensors rely on highly photostable metal complexes of benzoporphyrins and azabenzoporphyrins and enable several important applications such as simultaneous monitoring of oxygen and chlorophyll or ultra-fast oxygen monitoring (Eddy correlation). We also developed ulta-sensitive oxygen optodes which enable monitoring in nM range and are primary designed for investigation of oxygen minimum zones. The dynamic range of our new NIR pH indicators based on aza-BODIPY dyes is optimized for the marine environment. A highly sensitive NIR luminescent phosphor (chromium(III) doped yttrium aluminium borate) can be used for non-invasive temperature measurements. Notably, the oxygen, pH sensors and temperature sensors are fully compatible with the commercially available fiber-optic readers (Firesting from PyroScience). An optical CO2 sensor for marine applications employs novel diketopyrrolopyrrol indicators and enables ratiometric imaging using a CCD camera. Oxygen, pH and temperature sensors suitable for lifetime and ratiometric imaging of analytes distribution are also realized. To enable versatility of applications we also obtained a range of nano- and microparticles suitable for intra- and extracellular imaging of the above analytes. Bright ratiometric 2-photon-excitable probes were also developed. Magnetic microparticles are demonstrated to be very promising tools for imaging of oxygen, temperature and other parameters in biofilms, corals etc. since they combine the sensing function with the possibility of external manipulation.

A novel FbFP-based biosensor toolbox for sensitive in vivo determination of intracellular pH.

PubMed

Rupprecht, Christian; Wingen, Marcus; Potzkei, Janko; Gensch, Thomas; Jaeger, Karl-Erich; Drepper, Thomas

2017-09-20

The intracellular pH is an important modulator of various bio(techno)logical processes such as enzymatic conversion of metabolites or transport across the cell membrane. Changes of intracellular pH due to altered proton distribution can thus cause dysfunction of cellular processes. Consequently, accurate monitoring of intracellular pH allows elucidating the pH-dependency of (patho)physiological and biotechnological processes. In this context, genetically encoded biosensors represent a powerful tool to determine intracellular pH values non-invasively and with high spatiotemporal resolution. We have constructed a toolbox of novel genetically encoded FRET-based pH biosensors (named Fluorescence Biosensors for pH or FluBpH) that utilizes the FMN-binding fluorescent protein EcFbFP as donor domain. In contrast to many fluorescent proteins of the GFP family, EcFbFP exhibits a remarkable tolerance towards acidic pH (pK a ∼3.2). To cover the broad range of physiologically relevant pH values, three EYFP variants exhibiting pK a values of 5.7, 6.1 and 7.5 were used as pH-sensing FRET acceptor domains. The resulting biosensors FluBpH 5.7, FluBpH 6.1 and FluBpH 7.5 were calibrated in vitro and in vivo to accurately evaluate their pH indicator properties. To demonstrate the in vivo applicability of FluBpH, changes of intracellular pH were ratiometrically measured in E. coli cells during acid stress. Copyright © 2017 Elsevier B.V. All rights reserved.

An All-Solid-State pH Sensor Employing Fluorine-Terminated Polycrystalline Boron-Doped Diamond as a pH-Insensitive Solution-Gate Field-Effect Transistor.

PubMed

Shintani, Yukihiro; Kobayashi, Mikinori; Kawarada, Hiroshi

2017-05-05

A fluorine-terminated polycrystalline boron-doped diamond surface is successfully employed as a pH-insensitive SGFET (solution-gate field-effect transistor) for an all-solid-state pH sensor. The fluorinated polycrystalline boron-doped diamond (BDD) channel possesses a pH-insensitivity of less than 3mV/pH compared with a pH-sensitive oxygenated channel. With differential FET (field-effect transistor) sensing, a sensitivity of 27 mv/pH was obtained in the pH range of 2-10; therefore, it demonstrated excellent performance for an all-solid-state pH sensor with a pH-sensitive oxygen-terminated polycrystalline BDD SGFET and a platinum quasi-reference electrode, respectively.

The pH sensitive properties of carboxymethyl chitosan nanoparticles cross-linked with calcium ions.

PubMed

Kalliola, Simo; Repo, Eveliina; Srivastava, Varsha; Heiskanen, Juha P; Sirviö, Juho Antti; Liimatainen, Henrikki; Sillanpää, Mika

2017-05-01

In environmental applications the applied materials are required to be non-toxic and biodegradable. Carboxymethyl chitosan nanoparticles cross-linked with Ca 2+ ions (CMC-Ca) fulfill these requirements, and they are also renewable. These nanoparticles were applied to oil-spill treatment in our previous study and here we focused on enhancing their properties. It was found that while the divalent Ca 2+ ions are crucial for the formation of the CMC-Ca, the attractive interaction between NH 3 + and COO - groups contributed significantly to the formation and stability of the CMC-Ca. The stability decreased as a function of pH due to the deprotonation of the amino groups. Therefore, the nanoparticles were found to be fundamentally pH sensitive in solution, if the pH deviated from the pH (7-9) that was used in the synthesis of the nanoparticles. The pH sensitive CMC-Ca synthesized in pH 7 and 8 were most stable in the studied conditions and could find applications in oil-spill treatment or controlled-release of substances. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Hyperpolarized 15N-pyridine Derivatives as pH-Sensitive MRI Agents

PubMed Central

Jiang, Weina; Lumata, Lloyd; Chen, Wei; Zhang, Shanrong; Kovacs, Zoltan; Sherry, A. Dean; Khemtong, Chalermchai

2015-01-01

Highly sensitive MR imaging agents that can accurately and rapidly monitor changes in pH would have diagnostic and prognostic value for many diseases. Here, we report an investigation of hyperpolarized 15N-pyridine derivatives as ultrasensitive pH-sensitive imaging probes. These molecules are easily polarized to high levels using standard dynamic nuclear polarization (DNP) techniques and their 15N chemical shifts were found to be highly sensitive to pH. These probes displayed sharp 15N resonances and large differences in chemical shifts (Δδ >90 ppm) between their free base and protonated forms. These favorable features make these agents highly suitable candidates for the detection of small changes in tissue pH near physiological values. PMID:25774436

Safe and efficient pH sensitive tumor targeting modified liposomes with minimal cytotoxicity.

PubMed

Wang, Lilin; Geng, Di; Su, Haijia

2014-11-01

Incorporating the pH-sensitivity of octylamine grafted poly aspartic acid (PASP) with the biocompatibility of liposomes, a novel pH sensitive drug delivery system, octylamine-graft-PASP (PASP-g-C8) modified liposomes (OPLPs), was obtained. Since hydrophobic chains have been grafted into PASP backbones, the octylamine chain could act as the "anchor" to implant onto liposomes. The structure of PASP-g-C8, involving long-chain and hydrophobic anchors can significantly enhance the stability of the drug carrier. The shortcoming of single PASP chain modified liposomes (PLPs), that cannot sustain a slow and controlled release especially in a physiological pH solution (resembling normal tissues of pH 7.4) is thus overcome. Drug release experiments were carried out and the result showed that OPLPs sustained a slow and steady release in comparison with PLPs in the physiological pH 7.4 environment. However, OPLPs can provide a fast release in subacid environment (pH 5.0 of resembled tumor tissues). The results of diameter analysis and zeta potential demonstrated that OPLPs presented a larger diameter and higher electronegativity. Furthermore, in the "chain-anchor" structure of PASP-g-C8, the degree of substitution (DS) of the "anchor" is a remarkable factor to alter the pH-sensitivity of OPLPs. The in vitro tumor inhibition and cell toxicity studies revealed that tumor cells treated with OPLPs survived only 35.0% after 48 h whereas normal cells survived 100% in the same condition. The pH sensitive OPLPs are promising tumor targeting drug delivery with high tumor inhibition and insignificant cytotoxicity. Copyright © 2014. Published by Elsevier B.V.

Design and validation of a new ratiometric intracellular pH imaging probe using lanthanide-doped upconverting nanoparticles.

PubMed

Du, Shuoren; Hernández-Gil, Javier; Dong, Hao; Zheng, Xiaoyu; Lyu, Guangming; Bañobre-López, Manuel; Gallo, Juan; Sun, Ling-Dong; Yan, Chun-Hua; Long, Nicholas J

2017-10-17

pH homeostasis is strictly controlled at a subcellular level. A deregulation of the intra/extra/subcellular pH environment is associated with a number of diseases and as such, the monitoring of the pH state of cells and tissues is a valuable diagnostic tool. To date, only a few tools have been developed to measure the pH in living cells with the spatial resolution needed for intracellular imaging. Among the techniques available, only optical imaging offers enough resolution and biocompatibility to be proposed for subcellular pH monitoring. We present herein a ratiometric probe based on upconversion nanoparticles modified with a pH sensitive moiety for the quantitative imaging of pH at the subcellular level in living cells. This system provides the properties required for live cell quantitative imaging i.e. positive cellular uptake, biocompatibility, long wavelength excitation, sensitive response to pH within a biologically relevant range, and self-referenced signal.

A single-walled carbon nanotube thin film-based pH-sensing microfluidic chip.

PubMed

Li, Cheng Ai; Han, Kwi Nam; Pham, Xuan-Hung; Seong, Gi Hun

2014-04-21

A novel microfluidic pH-sensing chip was developed based on pH-sensitive single-walled carbon nanotubes (SWCNTs). In this study, the SWCNT thin film acted both as an electrode and a pH-sensitive membrane. The potentiometric pH response was observed by electronic structure changes in the semiconducting SWCNTs in response to the pH level. In a microfluidic chip consisting of a SWCNT pH-sensing working electrode and an Ag/AgCl reference electrode, the calibration plot exhibited promising pH-sensing performance with an ideal Nernstian response of 59.71 mV pH(-1) between pH 3 and 11 (standard deviation of the sensitivity is 1.5 mV pH(-1), R(2) = 0.985). Moreover, the SWCNT electrode in the microfluidic device showed no significant variation at any pH value in the range of the flow rate between 0.1 and 15 μl min(-1). The selectivity coefficients of the SWCNT electrode revealed good selectivity against common interfering ions.

Fabrication of pH sensitive nanovalves using smart surface coated nanopores

NASA Astrophysics Data System (ADS)

Nieto-Soto, A. M.; Diaz-Maldonado, D. K.; Rios Angarita, F. A.

2017-01-01

A pH sensitive nanovalve was fabricated using different smart surfaces covalently attached to an anodized aluminium oxide membrane (AAO). The smart surfaces were synthesized using a mixture of aliphatic and aminated silanes. Effect on the contact angle of the aliphatic silane chain length was evaluated. The smart surface, in conjunction with a nanoporous membrane, allowed the formation of a hydrophobic plug which controlled the transport of the molecule safranine depending on the pH of the solution. It was demonstrated that mixtures of butyl and methyl-trimethoxysilane with aminopropyl-trimethoxysilane were able to perform as effective nanovalves creating a plug that remained closed at pH>7 and opened up at pH<5.

Multiparameter flow cytometry of a pH sensitive ligand bound to receptors and inside cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fay, S.P.; Habbersett, R.; Posner, R.G.

1993-01-01

Because fluoresceinated ligands of the neutrophil formyl peptide receptor can be protonated either upon binding to the receptor on the cell surface or in acidified intracellular compartments, the authors synthesized a ligand conjugated to the pH sensitive fluorescent probe SNAFL (CHO-Met-Leu-Phe-Phe-Lys-SNAFL). In the three laser flow cytometer at LANL, protonated dye is excited at 488 nm and emits at 530 nm; unprotonated dye is excited at 568 nm and emits at 650 nm. Detection at the isobestic and isoemissive points at 528 and 600 nm is used to keep track of variations in ligand concentration from sample to sample. Themore » SNAFL-ligand bound to HL-60 cells (which overexpress the formyl peptide receptor) was compared to the free ligand in solution over a pH range from 6.5 to 9.0. The results suggest that the ligand bound to cell surface receptors was protonated in the binding pocket, possibly by virtue of its proximity to His 90, based on sequence data. When the cells were raised from 4[degrees] to 37[degrees], they also observed a time-dependent acidification of the ligand, indicative of ligand-receptor processing beginning 3-4 minutes after internalization.« less

Formulation design space for stable, pH sensitive crystalline nifedipine nanoparticles.

PubMed

Jog, Rajan; Unachukwu, Kenechi; Burgess, Diane J

2016-11-30

Enteric coated formulations protect drugs from degrading in the harsh environment of the stomach (acidic pH and enzymes), and promotes drug delivery to and absorption into the duodenum and/or later parts of the intestine. Four DoE models were applied to optimize formulation parameters for the preparation of pH sensitive nifedipine nanoparticles. Stability studies were performed on the optimized formulations to monitor any possible variation in particle size distribution, homogeneity index, surface charge and drug release (pH 1.2 and pH 6.8). Stability studies were performed for 3 months at 4°C, 25°C and 40°C. A combination of Eudragit ® L 100-55 and polyvinyl alcohol was determined to be the most effective in stabilizing the nanoparticle suspension. The average particle size distribution, polydispersity index and surface charge of the optimized pH sensitive nifedipine nanoparticles were determined to be 131.86±8.21nm, 0.135±0.008 and -7.631±0.146mV, respectively. Following three months storage, it was observed that the formulations stored at 4°C were stable in terms of particle size distribution, polydispersity index, surface charge, drug loading and drug release, whereas those stored at 25°C and 40°C were relatively unstable. A predictive model to prepare stable pH sensitive nifedipine nanoparticles, was successfully developed using multiple linear regression analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical crosslinking of acrylic acid to form biocompatible pH sensitive hydrogel reinforced with cellulose nanocrystals (CNC)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Lim Sze; Ahmad, Ishak; Lazim, Mohd Azwani Shah Mat

2014-09-03

The purpose of this study is to produce a novel pH and temperature sensitive hydrogel, composed of poly(acrylic acid) (PAA) and cellulose nanocrystal (CNC). CNC was extracted from kenaf fiber through a series of alkali and bleaching treatments followed by acid hydrolysis. The PAA was then subjected to chemical cross-linking using the cross-linking agent (N,N-methylenebisacrylamide) with CNC entrapped in PAA matrix. The mixture was casted onto petri dish to obtain disc shape hydrogel. The effects of reaction conditions such as the ratio of PAA and CNC on the swelling behavior of the hydrogel obtained towards pH and temperature were studied.more » The obtained hydrogel was further subjected to different tests such swelling test for swelling behaviour at different pH and temperature along with scanning electron microscopy (SEM) for morphology analysis. The hydrogel obtained showed excellent pH sensitivity and obtained maximum swelling at pH 7. Besides that, hydrogel obtained showed significant increase in swelling ratio when temperature of swelling medium was increased from 25°C to 37°C. SEM micrograph showed that the pore size of the hydrogel decreases with increase of CNC content proving that the hydrogel structure became more rigid with addition of CNC. The PAA/CNC hydrogel with such excellent sensitivity towards pH and temperature can be developed further as drug carrier.« less

A cell-surface-anchored ratiometric i-motif sensor for extracellular pH detection.

PubMed

Ying, Le; Xie, Nuli; Yang, Yanjing; Yang, Xiaohai; Zhou, Qifeng; Yin, Bincheng; Huang, Jin; Wang, Kemin

2016-06-14

A FRET-based sensor is anchored on the cell surface through streptavidin-biotin interactions. Due to the excellent properties of the pH-sensitive i-motif structure, the sensor can detect extracellular pH with high sensitivity and excellent reversibility.

Trichoderma-Induced Acidification Is an Early Trigger for Changes in Arabidopsis Root Growth and Determines Fungal Phytostimulation

PubMed Central

Pelagio-Flores, Ramón; Esparza-Reynoso, Saraí; Garnica-Vergara, Amira; López-Bucio, José; Herrera-Estrella, Alfredo

2017-01-01

Trichoderma spp. are common rhizosphere inhabitants widely used as biological control agents and their role as plant growth promoting fungi has been established. Although soil pH influences several fungal and plant functional traits such as growth and nutrition, little is known about its influence in rhizospheric or mutualistic interactions. The role of pH in the Trichoderma–Arabidopsis interaction was studied by determining primary root growth and lateral root formation, root meristem status and cell viability, quiescent center (QC) integrity, and auxin inducible gene expression. Primary root growth phenotypes in wild type seedlings and STOP1 mutants allowed identification of a putative root pH sensing pathway likely operating in plant–fungus recognition. Acidification by Trichoderma induced auxin redistribution within Arabidopsis columella root cap cells, causing root tip bending and growth inhibition. Root growth stoppage correlated with decreased cell division and with the loss of QC integrity and cell viability, which were reversed by buffering the medium. In addition, stop1, an Arabidopsis mutant sensitive to low pH, was oversensitive to T. atroviride primary root growth repression, providing genetic evidence that a pH root sensing mechanism reprograms root architecture during the interaction. Our results indicate that root sensing of pH mediates the interaction of Trichoderma with plants. PMID:28567051

Control of Gastric H,K-ATPase Activity by Cations, Voltage and Intracellular pH Analyzed by Voltage Clamp Fluorometry in Xenopus Oocytes

PubMed Central

Dürr, Katharina L.; Tavraz, Neslihan N.; Friedrich, Thomas

2012-01-01

Whereas electrogenic partial reactions of the Na,K-ATPase have been studied in depth, much less is known about the influence of the membrane potential on the electroneutrally operating gastric H,K-ATPase. In this work, we investigated site-specifically fluorescence-labeled H,K-ATPase expressed in Xenopus oocytes by voltage clamp fluorometry to monitor the voltage-dependent distribution between E1P and E2P states and measured Rb+ uptake under various ionic and pH conditions. The steady-state E1P/E2P distribution, as indicated by the voltage-dependent fluorescence amplitudes and the Rb+ uptake activity were highly sensitive to small changes in intracellular pH, whereas even large extracellular pH changes affected neither the E1P/E2P distribution nor transport activity. Notably, intracellular acidification by approximately 0.5 pH units shifted V0.5, the voltage, at which the E1P/E2P ratio is 50∶50, by −100 mV. This was paralleled by an approximately two-fold acceleration of the forward rate constant of the E1P→E2P transition and a similar increase in the rate of steady-state cation transport. The temperature dependence of Rb+ uptake yielded an activation energy of ∼90 kJ/mol, suggesting that ion transport is rate-limited by a major conformational transition. The pronounced sensitivity towards intracellular pH suggests that proton uptake from the cytoplasmic side controls the level of phosphoenzyme entering the E1P→E2P conformational transition, thus limiting ion transport of the gastric H,K-ATPase. These findings highlight the significance of cellular mechanisms contributing to increased proton availability in the cytoplasm of gastric parietal cells. Furthermore, we show that extracellular Na+ profoundly alters the voltage-dependent E1P/E2P distribution indicating that Na+ ions can act as surrogates for protons regarding the E2P→E1P transition. The complexity of the intra- and extracellular cation effects can be rationalized by a kinetic model suggesting that cations reach the binding sites through a rather high-field intra- and a rather low-field extracellular access channel, with fractional electrical distances of ∼0.5 and ∼0.2, respectively. PMID:22448261

Arsenic toxicity in the water weed Wolffia arrhiza measured using Pulse Amplitude Modulation Fluorometry (PAM) measurements of photosynthesis.

PubMed

Ritchie, Raymond J; Mekjinda, Nutsara

2016-10-01

Accumulation of arsenic in plants is a serious South-east Asian environmental problem. Photosynthesis in the small aquatic angiosperm Wolffia arrhiza is very sensitive to arsenic toxicity, particularly in water below pH 7 where arsenite (As (OH)3) (AsIII) is the dominant form; at pH >7 AsO4(2-) (As(V) predominates). A blue-diode PAM (Pulse Amplitude Fluorometer) machine was used to monitor photosynthesis in Wolffia. Maximum gross photosynthesis (Pgmax) and not maximum yield (Ymax) is the most reliable indicator of arsenic toxicity. The toxicity of arsenite As(III) and arsenate (H2AsO4(2-)) As(V) vary with pH. As(V) was less toxic than As(III) at both pH 5 and pH 8 but both forms of arsenic were toxic (>90% inhibition) at below 0.1molm(-3) when incubated in arsenic for 24h. Arsenite toxicity was apparent after 1h based on Pgmax and gradually increased over 7h but there was no apparent effect on Ymax or photosynthetic efficiency (α0). Copyright © 2016 Elsevier Inc. All rights reserved.

Economic Analysis of Earning a PhD Degree After Completion of a PharmD Degree

PubMed Central

Murawski, Matthew M.

2011-01-01

Objective To determine the net present value (NPV) and internal rate of return (IRR) for earning a doctor of philosophy (PhD) degree and pursuing careers commonly associated with that degree after completion of a doctor of pharmacy (PharmD) degree compared to entering pharmacy practice directly upon completion of the PharmD degree. Methods Income profiles were constructed based on 2008 annual salary data. NPV and IRR were calculated for careers resulting from the PhD degree and compared to those of the practicing community pharmacist. Trends in IRR also were examined across career paths from 1982 to 2008. A priori assumptions were developed and sensitivity analyses were conducted. Results The NPVs for all careers associated with the PhD degree were negative compared to that of the practicing community pharmacist. IRRs ranged from -1.4% to 1.3% for PhD careers. Longitudinal examination of IRRs indicated a negative trend from 1982 to 2008. Conclusions Economic financial incentives for PharmD graduates to pursue graduate school are lacking. The study illustrates the need to consider financial incentives when developing recruitment methods for PharmD graduates to pharmacy graduate programs. PMID:21451769

pH-sensitive nanocarrier based on gold/silver core-shell nanoparticles decorated multi-walled carbon manotubes for tracing drug release in living cells.

PubMed

Chen, Peng; Wang, Zhuyuan; Zong, Shenfei; Zhu, Dan; Chen, Hui; Zhang, Yizhi; Wu, Lei; Cui, Yiping

2016-01-15

We fabricate a multifunctional nanocarrier based on multi-walled carbon nanotubes (MWCNTs) decorated with gold/silver core-shell nanoparticles (Au@Ag NPs) and fluorescein isothiocyanate (FITC) for tracking the intracellular drug release process. In the demonstrated nanocarrier, the Au@Ag NPs adsorbed on the surface of MWCNTs were labeled with the pH-dependent SERS reporter 4-Mercaptobenzoic acid (4MBA) for SERS based pH sensing. FITC was conjugated on MWCNTs to provide fluorescence signal for tracing the MWCNTs. Fluorescent doxorubicin (DOX) was used as the model drug which can be loaded onto MWCNTs via π-π stacking and released from the MWCNTs under acidic condition. By detecting the SERS spectrum of 4MBA, the pH value around the nanocarrier could be monitored. Besides, by tracing the fluorescence of FITC and DOX, we can also investigate the drug release process in cells. Experimental results show that the proposed nanocarrier retained a well pH-sensitive performance in living cells, and the DOX detached from MWCNTs inside the lysosomes and entered into the cytoplasm with the MWCNTs being left in lysosomes. To further investigate the drug release dynamics, 2-D color-gradient pH mapping were plotted, which were calculated from the SERS spectra of 4MBA. The detailed release process and carrier distribution have been recorded as environmental pH changes during cell endocytosis. Furthermore, we also confirmed that the proposed nanocarrier has a good biocompatibility. It indicates that the designed nanocarrier have a great potential in intraceable drug delivery, cancer cells imaging and pH monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

Trace Elements in Calcifying Marine Invertebrates Indicate Diverse Sensitivities to the Seawater Carbonate System

NASA Astrophysics Data System (ADS)

Doss, W. C.

2015-12-01

Surface ocean absorption of anthropogenic CO2 emissions resulting in ocean acidification may interfere with the ability of calcifying marine organisms to biomineralize, since the drop in pH is accompanied by reductions in CaCO3 saturation state. However, recent experiments show that net calcification rates of cultured benthic invertebrate taxa exhibit diverse responses to pCO2-induced changes in saturation state (Ries et al., 2009). Advancement of geochemical tools as biomineralization indicators will enable us to better understand these results and therefore help predict the impacts of ongoing and future decrease in seawater pH on marine organisms. Here we build upon previous work on these specimens by measuring the elemental composition of biogenic calcite and aragonite precipitated in four pCO2 treatments (400; 600; 900; and 2850 ppm). Element ratios (including Sr/Ca, Mg/Ca, Li/Ca, B/Ca, U/Ca, Ba/Ca, Cd/Ca, and Zn/Ca) were analyzed in 18 macro-invertebrate species representing seven phyla (crustacea, cnidaria, echinoidea, rhodophyta, chlorophyta, gastropoda, bivalvia, annelida), then compared to growth rate data and experimental seawater carbonate system parameters: [CO32-], [HCO3-], pH, saturation state, and DIC. Correlations between calcite or aragonite composition and seawater carbonate chemistry are highly taxa-specific, but do not resemble trends observed in growth rate for all species. Apparent carbonate system sensitivities vary widely by element, ranging from strongly correlated to no significant response. Interpretation of these results is guided by mounting evidence for the capacity of individual species to modulate pH and/or saturation state at the site of calcification in response to ambient seawater chemistry. Such biomineralization pathways and strategies in turn likely influence elemental fractionation during CaCO3 precipitation. Ries, J.B., A.L. Cohen, A.L., and D.C. McCorkle (2009), Marine calcifiers exhibit mixed responses to CO2-induced ocean acidification, Geology, 37(12), 1131-1134.

Effects of simulated acid rain on soil and soil solution chemistry in a monsoon evergreen broad-leaved forest in southern China.

PubMed

Qiu, Qingyan; Wu, Jianping; Liang, Guohua; Liu, Juxiu; Chu, Guowei; Zhou, Guoyi; Zhang, Deqiang

2015-05-01

Acid rain is an environmental problem of increasing concern in China. In this study, a laboratory leaching column experiment with acid forest soil was set up to investigate the responses of soil and soil solution chemistry to simulated acid rain (SAR). Five pH levels of SAR were set: 2.5, 3.0, 3.5, 4.0, and 4.5 (as a control, CK). The results showed that soil acidification would occur when the pH of SAR was ≤3.5. The concentrations of NO₃(-)and Ca(2+) in the soil increased significantly when the pH of SAR fell 3.5. The concentration of SO₄(2-) in the soil increased significantly when the pH of SAR was <4.0. The effects of SAR on soil solution chemistry became increasingly apparent as the experiment proceeded (except for Na(+) and dissolved organic carbon (DOC)). The net exports of NO₃(-), SO₄(2-), Mg(2+), and Ca(2+) increased about 42-86% under pH 2.5 treatment as compared to CK. The Ca(2+) was sensitive to SAR, and the soil could release Ca(2+) through mineral weathering to mitigate soil acidification. The concentration of exchangeable Al(3+) in the soil increased with increasing the acidity of SAR. The releases of soluble Al and Fe were SAR pH dependent, and their net exports under pH 2.5 treatment were 19.6 and 5.5 times, respectively, higher than that under CK. The net export of DOC was reduced by 12-29% under SAR treatments as compared to CK. Our results indicate the chemical constituents in the soil are more sensitive to SAR than those in the soil solution, and the effects of SAR on soil solution chemistry depend not only on the intensity of SAR but also on the duration of SAR addition. The soil and soil solution chemistry in this region may not be affected by current precipitation (pH≈4.5) in short term, but the soil and soil leachate chemistry may change dramatically if the pH of precipitation were below 3.5 and 3.0, respectively.

Establishing upper limits on neuronal activity-evoked pH changes with APT-CEST MRI at 7 T.

PubMed

Khlebnikov, Vitaliy; Siero, Jeroen C W; Bhogal, Alex A; Luijten, Peter R; Klomp, Dennis W J; Hoogduin, Hans

2018-07-01

To detect neuronal activity-evoked pH changes by amide proton transfer-chemical exchange saturation transfer (APT-CEST) MRI at 7 T. Three healthy subjects participated in the study. A low-power 3-dimensional APT-CEST sequence was optimized through the Bloch-McConnell equations. pH sensitivity of the sequence was estimated both in phantoms and in vivo. The feasibility of pH-functional MRI was tested in Bloch-McConnell-simulated data using the optimized sequence. In healthy subjects, the visual stimuli were used to evoke transient pH changes in the visual cortex, and a 3-dimensional APT-CEST volume was acquired at the pH-sensitive frequency offset of 3.5 ppm every 12.6 s. In theory, a three-component general linear model was capable of separating the effects of blood oxygenation level-dependent contrast and pH. The Bloch-McConnell equations indicated that a change in pH of 0.03 should be measurable at the experimentally determined temporal signal-to-noise ratio of 108. However, only a blood oxygenation level-dependent effect in the visual cortex could be discerned during the visual stimuli experiments performed in the healthy subjects. The results of this study suggest that if indeed there are any transient brain pH changes in response to visual stimuli, those are under 0.03 units pH change, which is extremely difficult to detect using the existent techniques. Magn Reson Med 80:126-136, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Single-cell intracellular nano-pH probes†

PubMed Central

Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

2016-01-01

Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution. PMID:27708772

Survival, blood osmolality, and gill morphology of juvenile yellow perch, rock bass, black crappie, and largemouth bass exposed to acidified soft water

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCormick, J.H.; Jensen, K.M.; Leino, R.L.

1989-01-01

When exposed to a range of pH from 7.0 to 4.0 in soft water (1 mg Ca(2+)/L), juvenile rock bass Ambloplites rupestris, black crappie Pomoxis nigromaculatus, and largemouth bass Micropterus salmoides showed a capacity to osmoregulate and survive for up to 30 d at pH 4.5 and above. Juvenile yellow perch Perca flavescens maintained osmoregulatory control through 58 d at pH 5.0. All four species lost osmoregulatory control at pH 4.0, and death of fish ensued within a few days after blood osmolality declined to about 200 mosmol/kg or less (normal values, about 300 mosmol/kg). After 58 d of exposuremore » of pH 4.0, mean blood osmolality of yellow perch was 218 mosmol/kg, and these fish were severely emaciated and moribund. Rock bass, black crappie, and largemouth bass all died by days 29, 16, and 9, respectively, when exposed to pH 4.0. Examination of gills showed progressively increased pathology with longer exposures to lower than normal pH. Among fish exposed to low pH, gill hyperplasia was present most often, but epithelial hypertrophy, chloride-cell proliferation, chloride-cell degeneration, edema, and vacuolization of the tissues also were observed. Morphological changes that were observed in the three centrarchids at pH values above pH 4.0 suggested that gill pathology may be a more sensitive indicator of potentially lethal acid stress than blood osmolality.« less

Rapid pH change due to bacteriorhodopsin measured with a tin-oxide electrode.

PubMed Central

Robertson, B; Lukashev, E P

1995-01-01

The photocurrent transient generated by bacteriorhodopsin (bR) on a tin-oxide electrode is due to pH change and not to charge displacement as previously assumed. Films of either randomly oriented or highly oriented purple membranes were deposited on transparent electrodes made of tin-oxide-coated glass. The membranes contained either wild-type or D96N-mutant bR. When excited with yellow light through the glass, the bR pumps protons across the membrane. The result is a rapid local pH change as well as a charge displacement. Experiments with these films show that it is the pH change rather than the displacement that produces the current transient. The calibration for the transient pH measurement is given. The sensitivity of a tin-oxide electrode to a transient pH change is very much larger than its sensitivity to a steady-state pH change. PMID:7787036

Fluorescent pH sensor based on Ag@SiO2 core-shell nanoparticle.

PubMed

Bai, Zhenhua; Chen, Rui; Si, Peng; Huang, Youju; Sun, Handong; Kim, Dong-Hwan

2013-06-26

We have demonstrated a novel method for the preparation of a fluorescence-based pH sensor by combining the plasmon resonance band of Ag core and pH sensitive dye (HPTS). A thickness-variable silica shell is placed between Ag core and HPTS dye to achieve the maximum fluorescence enhancement. At the shell thickness of 8 nm, the fluorescence intensity increases 4 and 9 times when the sensor is excited at 405 and 455 nm, respectively. At the same time, the fluorescence intensity shows a good sensitivity toward pH value in the range of 5-9, and the ratio of emission intensity at 513 nm excited at 455 nm to that excited at 405 nm versus the pH value in the range of 5-9 is determined. It is believed that the present pH sensor has the potential for determining pH real time in the biological sample.

A self-amplified transistor immunosensor under dual gate operation: highly sensitive detection of hepatitis B surface antigen

NASA Astrophysics Data System (ADS)

Lee, I.-K.; Jeun, M.; Jang, H.-J.; Cho, W.-J.; Lee, K. H.

2015-10-01

Ion-sensitive field-effect transistors (ISFETs), although they have attracted considerable attention as effective immunosensors, have still not been adopted for practical applications owing to several problems: (1) the poor sensitivity caused by the short Debye screening length in media with high ion concentration, (2) time-consuming preconditioning processes for achieving the highly-diluted media, and (3) the low durability caused by undesirable ions such as sodium chloride in the media. Here, we propose a highly sensitive immunosensor based on a self-amplified transistor under dual gate operation (immuno-DG ISFET) for the detection of hepatitis B surface antigen. To address the challenges in current ISFET-based immunosensors, we have enhanced the sensitivity of an immunosensor by precisely tailoring the nanostructure of the transistor. In the pH sensing test, the immuno-DG ISFET showed superior sensitivity (2085.53 mV per pH) to both standard ISFET under single gate operation (58.88 mV per pH) and DG ISFET with a non-tailored transistor (381.14 mV per pH). Moreover, concerning the detection of hepatitis B surface antigens (HBsAg) using the immuno-DG ISFET, we have successfully detected trace amounts of HBsAg (22.5 fg mL-1) in a non-diluted 1× PBS medium with a high sensitivity of 690 mV. Our results demonstrate that the proposed immuno-DG ISFET can be a biosensor platform for practical use in the diagnosis of various diseases.Ion-sensitive field-effect transistors (ISFETs), although they have attracted considerable attention as effective immunosensors, have still not been adopted for practical applications owing to several problems: (1) the poor sensitivity caused by the short Debye screening length in media with high ion concentration, (2) time-consuming preconditioning processes for achieving the highly-diluted media, and (3) the low durability caused by undesirable ions such as sodium chloride in the media. Here, we propose a highly sensitive immunosensor based on a self-amplified transistor under dual gate operation (immuno-DG ISFET) for the detection of hepatitis B surface antigen. To address the challenges in current ISFET-based immunosensors, we have enhanced the sensitivity of an immunosensor by precisely tailoring the nanostructure of the transistor. In the pH sensing test, the immuno-DG ISFET showed superior sensitivity (2085.53 mV per pH) to both standard ISFET under single gate operation (58.88 mV per pH) and DG ISFET with a non-tailored transistor (381.14 mV per pH). Moreover, concerning the detection of hepatitis B surface antigens (HBsAg) using the immuno-DG ISFET, we have successfully detected trace amounts of HBsAg (22.5 fg mL-1) in a non-diluted 1× PBS medium with a high sensitivity of 690 mV. Our results demonstrate that the proposed immuno-DG ISFET can be a biosensor platform for practical use in the diagnosis of various diseases. Electronic supplementary information (ESI) available: Material preparation, surface functionalization and anti-HBsAg immobilization. See DOI: 10.1039/c5nr03146j

Dimerization of Organic Dyes on Luminescent Gold Nanoparticles for Ratiometric pH Sensing.

PubMed

Sun, Shasha; Ning, Xuhui; Zhang, Greg; Wang, Yen-Chung; Peng, Chuanqi; Zheng, Jie

2016-02-12

Synergistic effects arising from the conjugation of organic dyes onto non-luminescent metal nanoparticles (NPs) have greatly broadened their applications in both imaging and sensing. Herein, we report that conjugation of a well-known pH-insensitive dye, tetramethyl-rhodamine (TAMRA), to pH-insensitive luminescent gold nanoparticles (AuNPs) can lead to an ultrasmall nanoindicator that can fluorescently report local pH in a ratiometric way. Such synergy originated from the dimerization of TAMRA on AuNPs, of which geometry was very sensitive to surface charges of the AuNPs and can be reversely modulated through protonation of surrounding glutathione ligands. Not limited to pH-insensitive dyes, this pH-dependent dimerization can also enhance the pH sensitivity of fluorescein, a well-known pH-sensitive dye, within a larger pH range, opening up a new pathway to design ultrasmall fluorescent ratiometric nanoindicators with tunable wavelengths and pH response ranges. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

TMC-1 mediates alkaline sensation in C. elegans through nociceptive neurons

PubMed Central

Wang, Xiang; Li, Guang; Liu, Jie; Liu, Jianfeng; Xu, X.Z. Shawn

2016-01-01

Noxious pH triggers pungent taste and nocifensive behavior. While the mechanisms underlying acidic pH sensation has been extensively characterized, little is known about how animals sense alkaline pH in the environment. TMC genes encode a family of evolutionarily conserved membrane proteins, whose functions are largely unknown. Here, we characterize C. elegans TMC-1 which was suggested to form a Na+-sensitive channel mediating salt chemosensation. Interestingly, we find that TMC-1 is required for worms to avoid noxious alkaline environment. Alkaline pH evokes an inward current in nociceptive neurons, which is primarily mediated by TMC-1 and to a lesser extent by the TRP channel OSM-9. However, unlike OSM-9 which is sensitive to both acidic and alkaline pH, TMC-1 is only required for alkali-activated current, revealing a specificity for alkaline sensation. Ectopic expression of TMC-1 confers alkaline sensitivity to alkali-insensitive cells. Our results identify an unexpected role for TMCs in alkaline sensation and nociception. PMID:27321925

Engineering polyelectrolyte multilayer structure at the nanometer length scale by tuning polymer solution conformation.

NASA Astrophysics Data System (ADS)

Boddohi, Soheil; Killingsworth, Christopher; Kipper, Matt

2008-03-01

Chitosan (a weak polycation) and heparin (a strong polyanion) are used to make polyelectrolyte multilayers (PEM). PEM thickness and composition are determined as a function of solution pH (4.6 to 5.8) and ionic strength (0.1 to 0.5 M). Over this range, increasing pH increases the PEM thickness; however, the sensitivity to changes in pH is a strong function of ionic strength. The PEM thickness data are correlated to the polymer conformation in solution. Polyelectrolyte conformation in solution is characterized by gel permeation chromatography (GPC). The highest sensitivity of PEM structure to pH is obtained at intermediate ionic strength. Different interactions govern the conformation and adsorption phenomena at low and high ionic strength, leading to reduced sensitivity to solution pH at extreme ionic strengths. The correspondence between PEM thickness and polymer solution conformation offers opportunities to tune polymer thin film structure at the nanometer length scale by controlling simple, reproducible processing conditions.

Copper levels and changes in pH induce oxidative stress in the tissue of curimbata (Prochilodus lineatus).

PubMed

Carvalho, Cleoni dos Santos; Bernusso, Vanessa Aline; Fernandes, Marisa Narciso

2015-10-01

We analyzed the effect of exposure to 25% 96 h-LC50 of copper at low (24.5 μg L(-1) Cu, pH 4.5), neutral (7.25 μg L(-1) Cu, pH 7.0) and high pH (4.0 μg L(-1) Cu, pH 8.0) at 20 °C on antioxidant defenses and oxidative stress in the liver, gills and white muscle of the fish Prochilodus lineatus. Water at pH 4.5 and 8.0 affected the enzymatic and non-enzymatic antioxidant systems of the liver and gills, but not of the white muscles of P. lineatus, when compared to water at pH 7.0. After Cu exposure, SOD (superoxide dismutase), GPx (glutathione peroxidase), GR (glutathione reductase) and GST (glutathione S-transferase) activities increased and CAT (catalase) activity decreased in the liver at water at pH 4.5 and 8.0. Meanwhile, the activities of SOD, CAT, GPx, GR and GST increased in the gills at these pHs. SOD and CAT activities increased in the white muscle after Cu exposure at pH 8.0 and GPx, GR and GST activities decreased after Cu exposure at pH 4.5 and 8.0. LPO levels decreased in the liver and gills of fish that were exposed to water at pH 4.5 and 8.0 and, after Cu exposure, the LPO level increased in the liver, gills and white muscle of fish that were exposed to water at pH 4.5 and 8.0, when compared to the control group at pH 7.0. The metallothionein (MT) concentration increased in the liver of fish in water at pH 4.5 and 8.0 and the gill of fish in water at pH 8.0. After Cu exposure, MT in the liver and gills was significantly elevated in fish exposed to water at pH 4.5 and 8.0, but remained at levels similar to the control group in the white muscle. These results indicate a differing sensitivity of fish organs and tissues to essential metals, such as copper, and that toxicity may be relevant at environmental concentrations. These results indicate that the effect of Cu on the response of antioxidant defense systems is determined by water pH. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced antimicrobial activity and structural transitions of a nanofibrillated cellulose-nisin bio-composite suspension.

PubMed

Weishaupt, Ramon; Heuberger, Lukas; Siqueira, Gilberto; Gutt, Beatrice; Zimmermann, Tanja; Maniura-Weber, Katharina; Salentinig, Stefan; Faccio, Greta

2018-05-16

The occurrence of resistance to antibiotics has posed a high demand for novel strategies to fight bacterial infections. Antimicrobial peptides (AMPs) are a promising alternative to con-ventional antibiotics. However, their poor solubility in water and sensitivity to degradation has limited their application. Here we report the design of a smart, pH-responsive antimicro-bial nanobiocomposite material based on the AMP nisin and oxidized nanofibrillated cellulose (TONFC). Morphological transformations of the nano-scale structure of nisin functionalized TONFC fibrils were discovered at pH values between pH 5.8 and 8.0 using small angle X-ray scattering (SAXS). Complementary zeta potential measurements indicate that electrostatic-attractions between the negatively charged TONFC surface and the positively charged nisin molecules are responsible for the integration of nisin. Contrary, shifting the pH level or in-creasing the ionic strength reduce the nisin binding capacity of TONFC. Biological evaluation studies using a bioluminescence-based reporter strain of Bacillus subtilis and a clinically rele-vant strain of Staphylococcus aureus indicated a significantly higher antimicrobial activity of the TONFC-nisin biocomposite compared to the pure nisin against both strains under physio-logical pH and ionic strength conditions. The in-depth characterization of this new class of an-timicrobial bio-composite material based on nanocellulose and nisin, may guide the rational design of sustainable antimicrobial materials.

Evaluation and source attribution of freshwater contributions to Kinvarra Bay, Ireland, using (222)Rn, EC and stable isotopes as natural indicators.

PubMed

Schubert, Michael; Knoeller, Kay; Rocha, Carlos; Einsiedl, Florian

2015-03-01

Freshwater discharge into the coastal sea is of general interest for two reasons: (i) It acts as vehicle for the transport of contaminants or nutrients into the ocean, and (ii) it indicates the loss of significant volumes of freshwater that might be needed for irrigation or drinking water supply. Due to the large-scale and long-term nature of the related hydrological processes, locating and quantitatively assessing freshwater discharge into the sea require naturally occurring tracers that allow fast, inexpensive and straightforward detection. In several studies, the standard water parameters electrical conductivity (EC) and pH have proven their suitability in this regard. However, while distribution patterns of EC and pH in the coastal sea indicate freshwater discharge in general, a separation between discharging surface water and submarine groundwater discharge (SGD) is not possible with these alone. The naturally occurring radionuclide radon-222 has been shown to be useful in the quantification of SGD and its distinction from surface runoff. This study aimed to evaluate and compare the informative value of the three parameters-EC, pH and radon concentration-in detecting and quantifying SGD by carrying out a case study in a bay located in western Ireland. The results reveal that radon activity is the most sensitive parameter for detecting SGD. However, only the combined evaluation of radon, EC and pH allows a quantitative allocation of groundwater and surface water contributions to the overall freshwater discharge into the sea. This conclusion is independently supported by stable isotope data measured on selected samples.

Equivalence of litmus paper and intragastric pH probes for intragastric pH monitoring in the intensive care unit.

PubMed

Levine, R L; Fromm, R E; Mojtahedzadeh, M; Baghaie, A A; Opekun, A R

1994-06-01

To compare the accuracy of litmus paper-determined gastric pH to a nasogastric graphite antimony pH probe. A prospective clinical trial of gastric pH determination in patients enrolled in a study of histamine-2-receptor (H2) antagonists. The medical intensive care unit (ICU) of a 450-bed county hospital. Critically ill ICU patients requiring stress ulcer prophylaxis. Using a crossover design, the patients were randomized to initially receive an H2 antagonist by continuous infusion or intravenous bolus, and subsequently were crossed over to the other limb of the study. Gastric pH was determined using pH-sensitive litmus paper at the initiation of each limb of the study and at 1, 2, 4, and 8 hrs after the initiation of H2 receptor antagonist therapy. In addition, gastric pH was continuously determined over the same time period utilizing a graphite antimony pH probe. Gastric pH measurements determined with litmus paper and intragastric pH probes demonstrated an excellent correlation (r2 = .93, p < .001). McNemar's test of correlated proportions could not demonstrate a significant difference between the two monitoring methods (chi-square = 0.5, p > .47), and the kappa statistic (0.95, p < .001) demonstrated excellent concordance. Bias measurement was 0.01 (95% confidence interval = -0.155 to 0.176). Measurement of intragastric pH, using pH-sensitive litmus paper, is both sensitive and specific when utilizing a graphite antimony nasogastric pH probe as a reference standard. Litmus paper-determined gastric pH testing is both easy to perform and inexpensive. Therefore, based on the current data, we believe this technique (i.e., litmus paper determined gastric pH testing) to be the method of choice for determination of intragastric pH in patients at risk for stress gastric ulcers in the medical ICU.

Monodispersed calcium carbonate nanoparticles modulate local pH and inhibit tumor growth in vivo

NASA Astrophysics Data System (ADS)

Som, Avik; Raliya, Ramesh; Tian, Limei; Akers, Walter; Ippolito, Joseph E.; Singamaneni, Srikanth; Biswas, Pratim; Achilefu, Samuel

2016-06-01

The acidic extracellular environment of tumors potentiates their aggressiveness and metastasis, but few methods exist to selectively modulate the extracellular pH (pHe) environment of tumors. Transient flushing of biological systems with alkaline fluids or proton pump inhibitors is impractical and nonselective. Here we report a nanoparticles-based strategy to intentionally modulate the pHe in tumors. Biochemical simulations indicate that the dissolution of calcium carbonate nanoparticles (nano-CaCO3) in vivo increases pH asymptotically to 7.4. We developed two independent facile methods to synthesize monodisperse non-doped vaterite nano-CaCO3 with distinct size range between 20 and 300 nm. Using murine models of cancer, we demonstrate that the selective accumulation of nano-CaCO3 in tumors increases tumor pH over time. The associated induction of tumor growth stasis is putatively interpreted as a pHe increase. This study establishes an approach to prepare nano-CaCO3 over a wide particle size range, a formulation that stabilizes the nanomaterials in aqueous solutions, and a pH-sensitive nano-platform capable of modulating the acidic environment of cancer for potential therapeutic benefits.The acidic extracellular environment of tumors potentiates their aggressiveness and metastasis, but few methods exist to selectively modulate the extracellular pH (pHe) environment of tumors. Transient flushing of biological systems with alkaline fluids or proton pump inhibitors is impractical and nonselective. Here we report a nanoparticles-based strategy to intentionally modulate the pHe in tumors. Biochemical simulations indicate that the dissolution of calcium carbonate nanoparticles (nano-CaCO3) in vivo increases pH asymptotically to 7.4. We developed two independent facile methods to synthesize monodisperse non-doped vaterite nano-CaCO3 with distinct size range between 20 and 300 nm. Using murine models of cancer, we demonstrate that the selective accumulation of nano-CaCO3 in tumors increases tumor pH over time. The associated induction of tumor growth stasis is putatively interpreted as a pHe increase. This study establishes an approach to prepare nano-CaCO3 over a wide particle size range, a formulation that stabilizes the nanomaterials in aqueous solutions, and a pH-sensitive nano-platform capable of modulating the acidic environment of cancer for potential therapeutic benefits. Electronic supplementary information (ESI) available: Summary of experiments, theoretical schema of effect, synthesis schema, X-Ray diffraction results, TEM of effects of different solvents on particles in various solvents. See DOI: 10.1039/c5nr06162h

Biocompatible click chemistry enabled compartment-specific pH measurement inside E. coli

PubMed Central

Yang, Maiyun; Jalloh, Abubakar S.; Wei, Wei

2014-01-01

Bioorthogonal reactions, especially the Cu(I)-catalyzed azide-alkyne cycloaddition, have revolutionized our ability to label and manipulate biomolecules under living conditions. The cytotoxicity of Cu(I) ions, however, has hindered the application of this reaction in the internal space of living cells. By systematically surveying a panel of Cu(I)-stabilizing ligands in promoting protein labeling within the cytoplasm of E. coli, here we identify a highly efficient and biocompatible catalyst for intracellular modification of proteins by azide-alkyne cycloaddition. This reaction permits us to conjugate an environment-sensitive fluorophore site-specifically onto HdeA, an acid-stress chaperone that adopts pH-dependent conformational changes, in both the periplasm and cytoplasm of E. coli. The resulting protein-fluorophore hybrid pH indicators enable compartment-specific pH measurement to determine the pH gradient across the E. coli cytoplasmic membrane. This construct also allows the measurement of E. coli transmembrane potential, and the determination of the proton motive force across its inner membrane under normal and acid-stress conditions. PMID:25236616

An Impedance-Based Mold Sensor with on-Chip Optical Reference

PubMed Central

Papireddy Vinayaka, Poornachandra; van den Driesche, Sander; Blank, Roland; Tahir, Muhammad Waseem; Frodl, Mathias; Lang, Walter; Vellekoop, Michael J.

2016-01-01

A new miniaturized sensor system with an internal optical reference for the detection of mold growth is presented. The sensor chip comprises a reaction chamber provided with a culture medium that promotes the growth of mold species from mold spores. The mold detection is performed by measuring impedance changes with integrated electrodes fabricated inside the reaction chamber. The impedance change in the culture medium is caused by shifts in the pH (i.e., from 5.5 to 8) as the mold grows. In order to determine the absolute pH value without the need for calibration, a methyl red indicator dye has been added to the culture medium. It changes the color of the medium as the pH passes specific values. This colorimetric principle now acts as a reference measurement. It also allows the sensitivity of the impedance sensor to be established in terms of impedance change per pH unit. Major mold species that are involved in the contamination of food, paper and indoor environments, like Fusarium oxysporum, Fusarium incarnatum, Eurotium amstelodami, Aspergillus penicillioides and Aspergillus restrictus, have been successfully analyzed on-chip. PMID:27690039

Seizure Termination by Acidosis Depends on ASIC1a

PubMed Central

Ziemann, Adam E.; Schnizler, Mikael K.; Albert, Gregory W.; Severson, Meryl A.; Howard, Matthew A.; Welsh, Michael J.; Wemmie, John A.

2008-01-01

SUMMARY Most seizures stop spontaneously. However, the molecular mechanisms remain unknown. Earlier observations that seizures reduce brain pH and that acidosis inhibits seizures indicated that acidosis halts epileptic activity. Because acid–sensing ion channel–1a (ASIC1a) shows exquisite sensitivity to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a to terminate seizures. Disrupting mouse ASIC1a increased the severity of chemoconvulsant–induced seizures, whereas overexpressing ASIC1a had the opposite effect. ASIC1a did not affect seizure threshold or onset, but shortened seizure duration and prevented progression. CO2 inhalation, long known to lower brain pH and inhibit seizures, also required ASIC1a to interrupt tonic–clonic seizures. Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone. These findings identify ASIC1a as a key element in seizure termination when brain pH falls. The results suggest a molecular mechanism for how the brain stops seizures and suggest new therapeutic strategies. PMID:18536711

Sensitive SERS-pH sensing in biological media using metal carbonyl functionalized planar substrates.

PubMed

Kong, Kien Voon; Dinish, U S; Lau, Weber Kam On; Olivo, Malini

2014-04-15

Conventional nanoparticle based Surface enhanced Raman scattering (SERS) technique for pH sensing often fails due to the aggregation of particles when detecting in acidic medium or biosamples having high ionic strength. Here, We develop SERS based pH sensing using a novel Raman reporter, arene chromium tricarbonyl linked aminothiophenol (Cr(CO)3-ATP), functionalized onto a nano-roughened planar substrates coated with gold. Unlike the SERS spectrum of the ATP molecule that dominates in the 400-1700 cm(-1) region, which is highly interfered by bio-molecules signals, metal carbonyl-ATP (Cr(CO)3)-ATP) offers the advantage of monitoring the pH dependent strong CO stretching vibrations in the mid-IR (1800-2200 cm(-1)) range. Raman signal of the CO stretching vibrations at ~1820 cm(-1) has strong dependency on the pH value of the environment, where its peak undergo noticeable shift as the pH of the medium is varied from 3.0 to 9.0. The sensor showed better sensitivity in the acidic range of the pH. We also demonstrate the pH sensing in a urine sample, which has high ionic strength and our data closely correlate to the value obtained from conventional sensor. In future, this study may lead to a sensitive chip based pH sensing platform in bio-fluids for the early diagnosis of diseases. © 2013 Published by Elsevier B.V.

Light-Immune pH Sensor with SiC-Based Electrolyte-Insulator-Semiconductor Structure

NASA Astrophysics Data System (ADS)

Lin, Yi-Ting; Huang, Chien-Shiang; Chow, Lee; Lan, Jyun-Ming; Yang, Chia-Ming; Chang, Liann-Be; Lai, Chao-Sung

2013-12-01

An electrolyte-insulator-semiconductor (EIS) structure with high-band-gap semiconductor of silicon carbide is demonstrated as a pH sensor in this report. Two different sensing membranes, i.e., gadolinium oxide (Gd2O3) and hafnium oxide (HfO2), were investigated. The HfO2 film deposited by atomic layer deposition (ALD) at low temperature shows high pH sensing properties with a sensitivity of 52.35 mV/pH and a low signal of 4.95 mV due to light interference. The EIS structures with silicon carbide can provide better visible light immunity due to its high band gap that allows pH detection in an outdoor environment without degradation of pH sensitivity.

Injection moulded microneedle sensor for real-time wireless pH monitoring.

PubMed

Mirza, Khalid B; Zuliani, Claudio; Hou, Benjamin; Ng, Fu Siong; Peters, Nicholas S; Toumazou, Christofer

2017-07-01

This paper describes the development of an array of individually addressable pH sensitive microneedles using injection moulding and their integration within a portable device for real-time wireless recording of pH distributions in biological samples. The fabricated microneedles are subjected to gold patterning followed by electrodeposition of iridium oxide to sensitize them to 0.07 units of pH change. Miniaturised electronics suitable for the sensors readout, analog-to-digital conversion and wireless transmission of the potentiometric data are embodied within the device, enabling it to measure real-time pH of soft biological samples such as muscles. In this paper, real-time recording of the cardiac pH distribution, during ischemia followed by reperfusion cycles in cardiac muscles of male Wistar rats has been demonstrated by using the microneedle array.

Modeling CO2 degassing and pH in a stream-aquifer system

USGS Publications Warehouse

Choi, J.; Hulseapple, S.M.; Conklin, M.H.; Harvey, J.W.

1998-01-01

Pinal Creek, Arizona receives an inflow of ground water with high dissolved inorganic carbon (57-75 mg/l) and low pH (5.8-6.3). There is an observed increase of in-stream pH from approximately 6.0-7.8 over the 3 km downstream of the point of groundwater inflow. We hypothesized that CO2 gas-exchange was the most important factor causing the pH increase in this stream-aquifer system. An existing transport model, for coupled ground water-surface water systems (OTIS), was modified to include carbonate equilibria and CO2 degassing, used to simulate alkalinity, total dissolved inorganic carbon (C(T)), and pH in Pinal Creek. Because of the non-linear relation between pH and C(T), the modified transport model used the numerical iteration method to solve the non-linearity. The transport model parameters were determined by the injection of two tracers, bromide and propane. The resulting simulations of alkalinity, C(T) and pH reproduced, without fitting, the overall trends in downstream concentrations. A multi-parametric sensitivity analysis (MPSA) was used to identify the relative sensitivities of the predictions to six of the physical and chemical parameters used in the transport model. MPSA results implied that C(T) and pH in stream water were controlled by the mixing of ground water with stream water and CO2 degassing. The relative importance of these two processes varied spatially depending on the hydrologic conditions, such as stream flow velocity and whether a reach gained or lost stream water caused by the interaction with the ground water. The coupled transport model with CO2 degassing and generalized sensitivity analysis presented in this study can be applied to evaluate carbon transport and pH in other coupled stream-ground water systems.An existing transport model for coupled groundwater-surface water systems was modified to include carbonate equilibria and CO2 degassing. The modified model was used to simulate alkalinity, total dissolved inorganic carbon (CT) and pH in Pinal Creek. The model used the numerical iteration method to solve the nonlinear relation between pH and CT. A multi-parametric sensitivity analysis (MPSA) was used to identify the relative sensitivities of the predictions to six of the physical and chemical parameters used in the transport model. MPSA results implied that CT and pH in the stream water were controlled by the mixing of groundwater with stream water and CO2 degassing.

Smartphone-Based pH Sensor for Home Monitoring of Pulmonary Exacerbations in Cystic Fibrosis

PubMed Central

Sun, Alexander; Phelps, Tom; Yao, Chengyang; Venkatesh, A. G.; Conrad, Douglas; Hall, Drew A.

2017-01-01

Currently, Cystic Fibrosis (CF) patients lack the ability to track their lung health at home, relying instead on doctor checkups leading to delayed treatment and lung damage. By leveraging the ubiquity of the smartphone to lower costs and increase portability, a smartphone-based peripheral pH measurement device was designed to attach directly to the headphone port to harvest power and communicate with a smartphone application. This platform was tested using prepared pH buffers and sputum samples from CF patients. The system matches within ~0.03 pH of a benchtop pH meter while fully powering itself and communicating with a Samsung Galaxy S3 smartphone paired with either a glass or Iridium Oxide (IrOx) electrode. The IrOx electrodes were found to have 25% higher sensitivity than the glass probes at the expense of larger drift and matrix sensitivity that can be addressed with proper calibration. The smartphone-based platform has been demonstrated as a portable replacement for laboratory pH meters, and supports both highly robust glass probes and the sensitive and miniature IrOx electrodes with calibration. This tool can enable more frequent pH sputum tracking for CF patients to help detect the onset of pulmonary exacerbation to provide timely and appropriate treatment before serious damage occurs. PMID:28556804

Smartphone-Based pH Sensor for Home Monitoring of Pulmonary Exacerbations in Cystic Fibrosis.

PubMed

Sun, Alexander; Phelps, Tom; Yao, Chengyang; Venkatesh, A G; Conrad, Douglas; Hall, Drew A

2017-05-30

Currently, Cystic Fibrosis (CF) patients lack the ability to track their lung health at home, relying instead on doctor checkups leading to delayed treatment and lung damage. By leveraging the ubiquity of the smartphone to lower costs and increase portability, a smartphone-based peripheral pH measurement device was designed to attach directly to the headphone port to harvest power and communicate with a smartphone application. This platform was tested using prepared pH buffers and sputum samples from CF patients. The system matches within ~0.03 pH of a benchtop pH meter while fully powering itself and communicating with a Samsung Galaxy S3 smartphone paired with either a glass or Iridium Oxide (IrOx) electrode. The IrOx electrodes were found to have 25% higher sensitivity than the glass probes at the expense of larger drift and matrix sensitivity that can be addressed with proper calibration. The smartphone-based platform has been demonstrated as a portable replacement for laboratory pH meters, and supports both highly robust glass probes and the sensitive and miniature IrOx electrodes with calibration. This tool can enable more frequent pH sputum tracking for CF patients to help detect the onset of pulmonary exacerbation to provide timely and appropriate treatment before serious damage occurs.

Evaluation of end-tidal CO2 pressure at the anaerobic threshold for detecting and assessing pulmonary hypertension.

PubMed

Higashi, Akifumi; Dohi, Yoshihiro; Yamabe, Sayuri; Kinoshita, Hiroki; Sada, Yoshiharu; Kitagawa, Toshiro; Hidaka, Takayuki; Kurisu, Satoshi; Yamamoto, Hideya; Yasunobu, Yuji; Kihara, Yasuki

2017-11-01

Cardiopulmonary exercise testing (CPET) is useful for the evaluation of patients with suspected or confirmed pulmonary hypertension (PH). End-tidal carbon dioxide pressure (PETCO 2 ) during exercise is reduced with elevated pulmonary artery pressure. However, the utility of ventilatory parameters such as CPET for detecting PH remains unclear. We conducted a review in 155 patients who underwent right heart catheterization and CPET. Fifty-nine patients had PH [mean pulmonary arterial pressure (mPAP) ≥25 mmHg]. There was an inverse correlation between PETCO 2 at the anaerobic threshold (AT) and mPAP (r = -0.66; P < 0.01). Multiple regression analysis showed that PETCO 2 at the AT was independently associated with an elevated mPAP (P = 0.04). The sensitivity and specificity of CPET for PH were 80 and 86%, respectively, when the cut-off value identified by receiver operating characteristic curve analysis for PETCO 2 at the AT was ≤34.7 mmHg. A combination of echocardiography and CPET improved the sensitivity in detecting PH without markedly reducing specificity (sensitivity 87%, specificity 85%). Evaluation of PETCO 2 at the AT is useful for estimating pulmonary pressure. A combination of CPET and previous screening algorithms for PH may enhance the diagnostic ability of PH.

The Metalloprotease of Listeria monocytogenes Is Regulated by pH▿

PubMed Central

Forster, Brian M.; Bitar, Alan Pavinski; Slepkov, Emily R.; Kota, Karthik J.; Sondermann, Holger; Marquis, Hélène

2011-01-01

Listeria monocytogenes is an intracytosolic bacterial pathogen. Among the factors contributing to escape from vacuoles are a phosphatidylcholine phospholipase C (PC-PLC) and a metalloprotease (Mpl). Both enzymes are translocated across the bacterial membrane as inactive proproteins, whose propeptides serve in part to maintain them in association with the bacterium. We have shown that PC-PLC maturation is regulated by Mpl and pH and that Mpl maturation occurs by autocatalysis. In this study, we tested the hypothesis that Mpl activity is pH regulated. To synchronize the effect of pH on bacteria, the cytosolic pH of infected cells was manipulated immediately after radiolabeling de novo-synthesized bacterial proteins. Immunoprecipitation of secreted Mpl from host cell lysates revealed the presence of the propeptide and catalytic domain in samples treated at pH 6.5 but not at pH 7.3. The zymogen was present in small amounts under all conditions. Since proteases often remain associated with their respective propeptide following autocatalysis, we aimed at determining whether pH regulates autocatalysis or secretion of the processed enzyme. For this purpose, we used an Mpl construct that contains a Flag tag at the N terminus of its catalytic domain and antibodies that can distinguish N-terminal and non-N-terminal Flag. By fluorescence microscopy, we observed the Mpl zymogen associated with the bacterium at physiological pH but not following acidification. Mature Mpl was not detected in association with the bacterium at either pH. Using purified proteins, we determined that processing of the PC-PLC propeptide by mature Mpl is also pH sensitive. These results indicate that pH regulates the activity of Mpl on itself and on PC-PLC. PMID:21803995

Relative significances of pH and substrate starch level to roles of Streptococcus bovis S1 in rumen acidosis.

PubMed

Chen, Lianmin; Liu, Shimin; Wang, Hongrong; Wang, Mengzhi; Yu, Lihuai

2016-12-01

To clarify the relative importance of pH and substrate starch level in fermentation characteristics and regulatory mechanism of Streptococcus bovis S1 in rumen acidosis, an in vitro fermentation of three levels of soluble starch (1, 3 and 9 g/L) was established with pH in the media were maintained constant at 5.5 or 6.5. The results showed that the dominant product of S. bovis S1 was lactate at both pH, the production depended on the starch level, and more lactate was produced at pH 6.5 than that at pH 5.5 (P < 0.001). At pH 5.5, the activity of lactate dehydrogenase (LDH) and α-amylase (α-AMY), their abundances, the relative expressions of LDH, PFL (gene encoding pyruvate formate-lyase), CCPA (gene encoding global catabolite control protein A) and α-AMY genes were higher than those at pH 6.5 (P < 0.05), whereas the concentration of fructose-1,6-diphosphate (FDP) was lower. The activity of LDH, α-AMY and FDP, and the relative expressions of LDH, PFL, CCPA and α-AMY genes were, in general, positively related to the starch level. The canonical regression analysis indicated that the pH had more profound effect compared with the starch level, in terms of the acid productions, enzyme activity and gene expressions. It was concluded that the fermentation of S. bovis was regulated at the transcription level in response to both pH and substrate starch concentration, but more sensitive to pH changes.

The Expression of Petunia Strigolactone Pathway Genes is Altered as Part of the Endogenous Developmental Program

PubMed Central

Drummond, Revel S. M.; Sheehan, Hester; Simons, Joanne L.; Martínez-Sánchez, N. Marcela; Turner, Rebecca M.; Putterill, Joanna; Snowden, Kimberley C.

2012-01-01

Analysis of mutants with increased branching has revealed the strigolactone synthesis/perception pathway which regulates branching in plants. However, whether variation in this well conserved developmental signaling system contributes to the unique plant architectures of different species is yet to be determined. We examined petunia orthologs of the Arabidopsis MAX1 and MAX2 genes to characterize their role in petunia architecture. A single ortholog of MAX1, PhMAX1 which encodes a cytochrome P450, was identified and was able to complement the max1 mutant of Arabidopsis. Petunia has two copies of the MAX2 gene, PhMAX2A and PhMAX2B which encode F-Box proteins. Differences in the transcript levels of these two MAX2-like genes suggest diverging functions. Unlike PhMAX2B, PhMAX2A mRNA levels change in leaves of differing age/position on the plant. Nonetheless, this gene functionally complements the Arabidopsis max2 mutant indicating that the biochemical activity of the PhMAX2A protein is not significantly different from MAX2. The expression of the petunia strigolactone pathway genes (PhCCD7, PhCCD8, PhMAX1, PhMAX2A, and PhMAX2B) was then further investigated throughout the development of wild-type petunia plants. Three of these genes showed changes in mRNA levels over a development series. Alterations to the expression patterns of these genes may influence the branching growth habit of plants by changing strigolactone production and/or sensitivity. These changes could allow both subtle and dramatic changes to branching within and between species. PMID:22645562

Pulmonary Delivery of Anti-Tubercular Drugs Using Ligand Anchored pH Sensitive Liposomes for the Treatment of Pulmonary Tuberculosis.

PubMed

Bhardwaj, Ankur; Grobler, Anne; Rath, Goutam; Goyal, Amit Kumar; Jain, Amit Kumar; Mehta, Abhinav

2016-01-01

Mycobacterium tuberculosis (M. TB) remains the prime cause of bacterial mortality and morbidity world-wide. Therefore, effective delivery and targeting of drug to the cellular tropics is essentially required to generate significant results for tuberculosis treatment. The aim of the present study was to develop and characterize ligand anchored pH sensitive liposomes (TPSL) as dry powder inhaler for the targeted delivery of drugs in the target site i.e. lungs. Ligand anchored PSL (TPSL) was prepared by thin film hydration for the combined delivery of Isoniazid (INH) and Ciprofloxacin HCl (CIP HCl) using 4-aminophenyl-α-D mannopyranoside (Man) as surface functionalized ligand and characterized using different parameters. It was observed that size of the ligand anchored liposomes (TPSL) was slightly more than the non-ligand anchored liposomes (PSL). Drug release was studied at different pH for 24 hrs and it was observed that liposomes exhibited slow release at alkaline pH (58-64%) as compared to macrophage pH (81-87%) where it increased dramatically due to the destabilization of pH sensitive liposome (PSL). In vitro cellular uptake study showed that much higher concentration was achieved in the alveolar macrophage using ligand anchored liposomes as compared to its counterpart. In vivo study showed that maximum drug accumulation was achieved in the lung by delivering drug using ligand anchored PSL as compared to conventional PSL. It was concluded that ligand anchored pH sensitive liposome is one of the promising systems for the targeted drug therapy in pulmonary tuberculosis.

The Effect of Curcumin on Intracellular pH (pHi), Membrane Hyperpolarization and Sperm Motility.

PubMed

Naz, Rajesh K

2014-04-01

Curcumin has shown to affect sperm motility and function in vitro and fertility in vivo. The molecular mechanism(s) by which curcumin affects sperm motility has not been delineated. Since modulation of intracellular pH (pHi) and plasma membrane polarization is involved in sperm motility, the present study was conducted to investigate the effect of curcumin on these sperm (human and murine) parameters. The effect of curcumin on sperm forward motility was examined by counting percentages of forward moving sperm. The effect of curcumin on intracellular pH (pHi) was measured by the fluorescent pH indicator 2,7-bicarboxyethyl-5,6-carboxyfluorescein-acetoxymethyl ester (BCECF-AM). The effect of curcumin on plasma membrane polarization was examined using the fluorescence sensitive dye bis (1,3-dibarbituric acid)-trimethine oxanol [DiBAC4(3)]. Curcumin caused a concentration-dependent (p<0.05) decrease in forward motility of both human and mouse sperm. It also caused a concentration-dependent decrease in intracellular pH (pHi) in both human and mouse sperm. Curcumin induced significant (p<0.05) hyperpolarization of the plasma membrane in both human and mouse sperm. These findings indicate that curcumin inhibits sperm forward motility by intracellular acidification and hyperpolarization of sperm plasma membrane. This is the first study to our knowledge which examined the effect of curcumin on sperm pHi and membrane polarization that affect sperm forward motility. These exciting findings will have application in deciphering the signal transduction pathway involved in sperm motility and function and in development of a novel non-steroidal contraceptive for infertility.

Growth of ponderosa pine seedlings as affected by air pollution

NASA Astrophysics Data System (ADS)

Momen, B.; Anderson, P. D.; Houpis, J. L. J.; Helms, J. A.

The effect of air pollution on seedling survival and competitive ability is important to natural and artificial regeneration of forest trees. Although biochemical and physiological processes are sensitive indicators of pollution stress, the cumulative effects of air pollutants on seedling vigor and competitive ability may be assessed directly from whole-plant growth characteristics such as diameter, height, and photosynthetic area. A few studies that have examined intraspecific variation in seedling response to air pollution indicate that genotypic differences are important in assessing potential effects of air pollution on forest regeneration. Here, we studied the effects of acid rain (no-rain, pH 5.1 rain, pH 3.0 rain) and ozone (filtered, ambient, twice-ambient) in the field on height, diameter, volume, the height:diameter ratio, maximum needle length, and time to reach maximum needle length in seedlings of three families of ponderosa pine ( Pinus ponderosa Dougl. ex Laws). Seedling diameter, height, volume, and height:diameter ratio related significantly to their pre-treatment values. Twice-ambient ozone decreased seedling diameter compared with ozone-filtered air. A significant family-by-ozone interaction was detected for seedling height, as the height of only one of the three families was decreased by twice-ambient ozone compared with the ambient level. Seedling diameter was larger and the height:diameter ratio was smaller under pH 3.0 rain compared to either the no-rain or the pH 5.1-rain treatment. This suggests greater seedling vigor, perhaps due to a foliar fertilization effect of the pH 3.0 rain.

Succinoglycan Production Contributes to Acidic pH Tolerance in Sinorhizobium meliloti Rm1021.

PubMed

Hawkins, Justin P; Geddes, Barney A; Oresnik, Ivan J

2017-12-01

In this work, the hypothesis that exopolysaccharide plays a role in the survival of Sinorhizobium meliloti at low pH levels is addressed. When S. meliloti was grown at pH 5.75, synthesis of succinoglycan increased, whereas synthesis of galactoglucan decreased. Succinoglycan that was isolated from cultures grown at low pH had a lower degree of polymerization relative to that which was isolated from cultures grown at neutral pH, suggesting that low-molecular weight (LMW) succinoglycan might play a role in adaptation to low pH. Mutants unable to produce succinoglycan or only able to produce high-molecular weight polysaccharide were found to be sensitive to low pH. However, strains unable to produce LMW polysaccharide were 10-fold more sensitive. In response to low pH, transcription of genes encoding proteins for succinoglycan, glycogen, and cyclic β(1-2) glucans biosynthesis increased, while those encoding proteins necessary for the biosynthesis of galactoglucan decreased. While changes in pH did not affect the production of glycogen or cyclic β(1-2) glucan, it was found that the inability to produce cyclic β(1-2) glucan did contribute to pH tolerance in the absence of succinoglycan. Finally, in addition to being sensitive to low pH, a strain carrying mutations in exoK and exsH, which encode the glycanases responsible for the cleavage of succinoglycan to LMW succinoglycan, exhibited a delay in nodulation and was uncompetitive for nodule occupancy. Taken together, the data suggest that the role for LMW succinoglycan in nodule development may be to enhance survival in the colonized curled root hair.

The combination of pH monitoring in the most distal esophagus and symptom association analysis markedly improves the clinical value of esophageal pH tests.

PubMed

Hall, Mats Guerrero Garcia; Wenner, Jörgen; Öberg, Stefan

2016-01-01

The poor sensitivity of esophageal pH monitoring substantially limits the clinical value of the test. The aim of this study was to compare the diagnostic accuracy of esophageal pH monitoring and symptom association analysis performed at the conventional level with that obtained in the most distal esophagus. Eighty-two patients with typical reflux symptoms and 49 asymptomatic subjects underwent dual 48-h pH monitoring with the electrodes positioned immediately above, and 6 cm above the squamo-columnar junction (SCJ). The degree of esophageal acid exposure and the temporal relationship between reflux events and symptoms were evaluated. The sensitivity of pH recording and the diagnostic yield of Symptom Association Probability (SAP) were significantly higher for pH monitoring performed at the distal compared with the conventional level (82% versus 65%, p<0.001 and 74% versus 62%, p<0.001, respectively). The greatest improvement was observed in patients with non-erosive disease. In this group, the sensitivity increased from 46% at the standard level to 66% immediately above the SCJ, and with the combination of a positive SAP as a marker for a positive pH test, the diagnostic yield further increased to 94%. The diagnostic accuracy of esophageal pH monitoring in the most distal esophagus is superior to that performed at the conventional level and it is further improved with the combination of symptom association analysis. PH monitoring with the pH electrode positioned immediately above the SCJ should be introduced in clinical practice and always combined with symptom association analysis.

Molecular Basis of Circadian Photoreception

DTIC Science & Technology

2006-06-30

dusk transitions . For example, proper circadian entrainment permits animals to inhabit precise “temporal niches” that minimize exposure to predation...into the spectral sensitivity of any unidentified circadian photoreceptors. Such a study in the golden hamster (Mesocricetus auratus) indicated a...0.05–0.3mM GTP-Tris; (280–300 mOsm, pH 7.3). Liquid junction potentials (-14mV) were corrected. In darkness, most cells had series resistance ᝺MΩ

Multifunctional pH-sensitive polymeric nanoparticles for theranostics evaluated experimentally in cancer

NASA Astrophysics Data System (ADS)

Liu, Yongjun; Feng, Lixia; Liu, Tingxian; Zhang, Li; Yao, Yao; Yu, Dexin; Wang, Linlin; Zhang, Na

2014-02-01

A multifunctional pH-sensitive polymeric nanoparticle system was developed for simultaneous tumor magnetic resonance imaging (MRI) and therapy. The nanoparticles were self-assembled using the multi-block polymer poly(lactic acid)-poly(ethylene glycol)-poly(l-lysine)-diethylenetriamine pentaacetic acid (PLA-PEG-PLL-DTPA) and the pH-sensitive material poly(l-histidine)-poly(ethylene glycol)-biotin (PLH-PEG-biotin). The anti-hepatocellular carcinoma (HCC) drug sorafenib was encapsulated inside the nanoparticles. Gd ions were chelated to the DTPA groups which were distributed on the nanoparticle surface. Biotinylated vascular endothelial growth factor receptor (VEGFR) antibodies were linked to the surface biotin groups of nanoparticles through the avidin linker to form the target pH-sensitive theranostic nanoparticles (TPTN). TPTN exhibited spherical or ellipsoidal shapes, uniform particle size distribution (181.4 +/- 3.4 nm), positive zeta potential (14.95 +/- 0.60 mV), high encapsulation efficiency (95.02 +/- 1.47%) and drug loading (2.38 +/- 0.04%). The pH-sensitive sorafenib release from TPTN was observed under different pH values (47.81% at pH = 7.4 and 99.32% at pH = 5.0, respectively). In cell cytotoxicity studies, TPTN showed similar antitumor effect against HepG2 cells compared to solubilized sorafenib solution after pre-incubation in acid PBS (pH = 5.0) for 1 h in vitro (P > 0.05). In in vivo anti-tumor studies, TPTN showed significantly higher antitumor effect in H22 tumor (VEGFR overexpressed cell line) bearing mice compared to the solubilized sorafenib solution (oral or i.v. administration) group (P < 0.05). In the MRI test, the T1 relaxivity value of TPTN was 17.300 mM-1 s-1 which was 3.6 times higher than Magnevist® (r1 = 4.8 mM-1 s-1). As a positive contrast agent, TPTN exhibited higher resolution and longer imaging time (more than 90 min) in the MRI diagnosis of tumor-bearing mice compared to Magnevist® (more than 60 min). Furthermore, histological examination of TBN (blank TPTN, without sorafenib loaded) showed no visible tissue toxicity compared to normal saline. Thus, TPTN possessed dual-loading drugs and imaging agents, active targeting and pH-triggered drug release properties in one platform with good biocompatibility. All of these results indicated that TPTN was a promising theranostic carrier which could be a platform for the development of novel multifunctional theranostic agents.A multifunctional pH-sensitive polymeric nanoparticle system was developed for simultaneous tumor magnetic resonance imaging (MRI) and therapy. The nanoparticles were self-assembled using the multi-block polymer poly(lactic acid)-poly(ethylene glycol)-poly(l-lysine)-diethylenetriamine pentaacetic acid (PLA-PEG-PLL-DTPA) and the pH-sensitive material poly(l-histidine)-poly(ethylene glycol)-biotin (PLH-PEG-biotin). The anti-hepatocellular carcinoma (HCC) drug sorafenib was encapsulated inside the nanoparticles. Gd ions were chelated to the DTPA groups which were distributed on the nanoparticle surface. Biotinylated vascular endothelial growth factor receptor (VEGFR) antibodies were linked to the surface biotin groups of nanoparticles through the avidin linker to form the target pH-sensitive theranostic nanoparticles (TPTN). TPTN exhibited spherical or ellipsoidal shapes, uniform particle size distribution (181.4 +/- 3.4 nm), positive zeta potential (14.95 +/- 0.60 mV), high encapsulation efficiency (95.02 +/- 1.47%) and drug loading (2.38 +/- 0.04%). The pH-sensitive sorafenib release from TPTN was observed under different pH values (47.81% at pH = 7.4 and 99.32% at pH = 5.0, respectively). In cell cytotoxicity studies, TPTN showed similar antitumor effect against HepG2 cells compared to solubilized sorafenib solution after pre-incubation in acid PBS (pH = 5.0) for 1 h in vitro (P > 0.05). In in vivo anti-tumor studies, TPTN showed significantly higher antitumor effect in H22 tumor (VEGFR overexpressed cell line) bearing mice compared to the solubilized sorafenib solution (oral or i.v. administration) group (P < 0.05). In the MRI test, the T1 relaxivity value of TPTN was 17.300 mM-1 s-1 which was 3.6 times higher than Magnevist® (r1 = 4.8 mM-1 s-1). As a positive contrast agent, TPTN exhibited higher resolution and longer imaging time (more than 90 min) in the MRI diagnosis of tumor-bearing mice compared to Magnevist® (more than 60 min). Furthermore, histological examination of TBN (blank TPTN, without sorafenib loaded) showed no visible tissue toxicity compared to normal saline. Thus, TPTN possessed dual-loading drugs and imaging agents, active targeting and pH-triggered drug release properties in one platform with good biocompatibility. All of these results indicated that TPTN was a promising theranostic carrier which could be a platform for the development of novel multifunctional theranostic agents. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr05647c

Generation and Characterization of Environmentally Sensitive Variants of the β-Galactosidase from Lactobacillus delbrueckii subsp. bulgaricus

PubMed Central

Yoast, Sienna; Adams, Robin M.; Mainzer, Stanley E.; Moon, Keith; Palombella, Anthony L.; Schmidt, Brian F.

1994-01-01

A method is described for generating and screening variants of the β-galactosidase from Lactobacillus delbrueckii subsp. bulgaricus sensitive to several environmental stresses, with potential application in the food industry. Chemical mutagenesis with hydroxylamine or methoxylamine was performed on the β-galactosidase gene carried on an Escherichia coli expression vector. Mutants sensitive to cold, heat, low pH, low magnesium concentration, and the presence of urea were isolated by screening for reduced color development on β-galactosidase indicator plates. The mutations responsible for three variant β-galactosidases were localized, and the base substitutions were determined by DNA sequencing. The amino acid alterations associated with one low-pH-sensitive (pHs) and two urea-sensitive (Us) variants correspond to P584L (pHs1), G400S/R479Q (Us26), and G167E/E168K/E363K/V492M (Us17), respectively. Mutant pHs1 is also heat, cold, low magnesium, and urea sensitive; Us26 is also cold sensitive; and Us17 is also low-pH sensitive. PMID:16349230

Direct effect of acid rain on leaf chlorophyll content of terrestrial plants in China.

PubMed

Du, Enzai; Dong, Dan; Zeng, Xuetong; Sun, Zhengzhong; Jiang, Xiaofei; de Vries, Wim

2017-12-15

Anthropogenic emissions of acid precursors in China have resulted in widespread acid rain since the 1980s. Although efforts have been made to assess the indirect, soil mediated ecological effects of acid rain, a systematic assessment of the direct foliage injury by acid rain across terrestrial plants is lacking. Leaf chlorophyll content is an important indicator of direct foliage damage and strongly related to plant productivity. We synthesized data from published literature on experiments of simulated acid rain, by directly exposing plants to acid solutions with varying pH levels, to assess the direct effect of acid rain on leaf chlorophyll content across 67 terrestrial plants in China. Our results indicate that acid rain substantially reduces leaf chlorophyll content by 6.71% per pH unit across the recorded plant species. The direct reduction of leaf chlorophyll content due to acid rain exposure showed no significant difference across calcicole, ubiquist or calcifuge species, implying that soil acidity preference does not influence the sensitivity to leaf injury by acid rain. On average, the direct effects of acid rain on leaf chlorophyll on trees, shrubs and herbs were comparable. The effects, however varied across functional groups and economic use types. Specifically, leaf chlorophyll content of deciduous species was more sensitive to acid rain in comparison to evergreen species. Moreover, vegetables and fruit trees were more sensitive to acid rain than other economically used plants. Our findings imply a potential production reduction and economic loss due to the direct foliage damage by acid rain. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of short-term acidification on nitrification and nitrifying bacterial community dynamics in soilless cultivation media.

PubMed

Cytryn, Eddie; Levkovitch, Irit; Negreanu, Yael; Dowd, Scot; Frenk, Sammy; Silber, Avner

2012-09-01

Soilless medium-based horticulture systems are highly prevalent due to their capacity to optimize growth of high-cash crops. However, these systems are highly dynamic and more sensitive to physiochemical and pH perturbations than traditional soil-based systems, especially during nitrification associated with ammonia-based fertilization. The objective of this study was to assess the impact of nitrification-generated acidification on ammonia oxidation rates and nitrifying bacterial community dynamics in soilless growth media. To achieve this goal, perlite soilless growth medium from a commercial bell pepper greenhouse was incubated with ammonium in bench-scale microcosm experiments. Initial quantitative real-time PCR analysis indicated that betaproteobacterial ammonia oxidizers were significantly more abundant than ammonia-oxidizing archaea, and therefore, research focused on this group. Ammonia oxidation rates were highest between 0 and 9 days, when pH values dropped from 7.4 to 4.9. Pyrosequencing of betaproteobacterial ammonia-oxidizing amoA gene fragments indicated that r-strategist-like Nitrosomonas was the dominant ammonia-oxidizing bacterial genus during this period, seemingly due to the high ammonium concentration and optimal growth conditions in the soilless media. Reduction of pH to levels below 4.8 resulted in a significant decrease in both ammonia oxidation rates and the diversity of ammonia-oxidizing bacteria, with increased relative abundance of the r-strategist-like Nitrosospira. Nitrite oxidizers (Nitrospira and Nitrobacter) were on the whole more abundant and less sensitive to acidification than ammonia oxidizers. This study demonstrates that nitrification and nitrifying bacterial community dynamics in high-N-load intensive soilless growth media may be significantly different from those in in-terra agricultural systems.

Impact of Short-Term Acidification on Nitrification and Nitrifying Bacterial Community Dynamics in Soilless Cultivation Media

PubMed Central

Levkovitch, Irit; Negreanu, Yael; Dowd, Scot; Frenk, Sammy; Silber, Avner

2012-01-01

Soilless medium-based horticulture systems are highly prevalent due to their capacity to optimize growth of high-cash crops. However, these systems are highly dynamic and more sensitive to physiochemical and pH perturbations than traditional soil-based systems, especially during nitrification associated with ammonia-based fertilization. The objective of this study was to assess the impact of nitrification-generated acidification on ammonia oxidation rates and nitrifying bacterial community dynamics in soilless growth media. To achieve this goal, perlite soilless growth medium from a commercial bell pepper greenhouse was incubated with ammonium in bench-scale microcosm experiments. Initial quantitative real-time PCR analysis indicated that betaproteobacterial ammonia oxidizers were significantly more abundant than ammonia-oxidizing archaea, and therefore, research focused on this group. Ammonia oxidation rates were highest between 0 and 9 days, when pH values dropped from 7.4 to 4.9. Pyrosequencing of betaproteobacterial ammonia-oxidizing amoA gene fragments indicated that r-strategist-like Nitrosomonas was the dominant ammonia-oxidizing bacterial genus during this period, seemingly due to the high ammonium concentration and optimal growth conditions in the soilless media. Reduction of pH to levels below 4.8 resulted in a significant decrease in both ammonia oxidation rates and the diversity of ammonia-oxidizing bacteria, with increased relative abundance of the r-strategist-like Nitrosospira. Nitrite oxidizers (Nitrospira and Nitrobacter) were on the whole more abundant and less sensitive to acidification than ammonia oxidizers. This study demonstrates that nitrification and nitrifying bacterial community dynamics in high-N-load intensive soilless growth media may be significantly different from those in in-terra agricultural systems. PMID:22773643

Ag Nanoparticles-enhanced Fluorescence of Terbium-Deferasirox Complexes for the Highly Sensitive Determination of Deferasirox.

PubMed

Abolhasani, Jafar; Naderali, Roza; Hassanzadeh, Javad

2016-01-01

We describe the effect of different sized gold and silver nanoparticles on the terbium sensitized fluorescence of deferasirox. It is indicated that silver nanostructures, especially 18 nm Ag nanoparticles (AgNPs), have a remarkable amplifying effect compared to Au nanoparticles. Based on this observation, a highly sensitive and selective method was developed for the determination of deferasirox. Effects of various parameters like AgNPs and Tb(3+) concentration and pH of media were investigated. Under the optimal conditions, a calibration curve was plotted as the fluorescence intensities versus the concentration of deferasirox in the range of 0.1 to 200 nmol L(-1), and detection limit of 0.03 nmol L(-1) was obtained. The method has good linearity, recovery, reproducibility and sensitivity, and was satisfactorily applied for the determination of deferasirox in urine and pharmaceutical samples.

Histidine residues in the Na+-coupled ascorbic acid transporter-2 (SVCT2) are central regulators of SVCT2 function, modulating pH sensitivity, transporter kinetics, Na+ cooperativity, conformational stability, and subcellular localization.

PubMed

Ormazabal, Valeska; Zuñiga, Felipe A; Escobar, Elizabeth; Aylwin, Carlos; Salas-Burgos, Alexis; Godoy, Alejandro; Reyes, Alejandro M; Vera, Juan Carlos; Rivas, Coralia I

2010-11-19

Na(+)-coupled ascorbic acid transporter-2 (SVCT2) activity is impaired at acid pH, but little is known about the molecular determinants that define the transporter pH sensitivity. SVCT2 contains six histidine residues in its primary sequence, three of which are exofacial in the transporter secondary structure model. We used site-directed mutagenesis and treatment with diethylpyrocarbonate to identify histidine residues responsible for SVCT2 pH sensitivity. We conclude that five histidine residues, His(109), His(203), His(206), His(269), and His(413), are central regulators of SVCT2 function, participating to different degrees in modulating pH sensitivity, transporter kinetics, Na(+) cooperativity, conformational stability, and subcellular localization. Our results are compatible with a model in which (i) a single exofacial histidine residue, His(413), localized in the exofacial loop IV that connects transmembrane helices VII-VIII defines the pH sensitivity of SVCT2 through a mechanism involving a marked attenuation of the activation by Na(+) and loss of Na(+) cooperativity, which leads to a decreased V(max) without altering the transport K(m); (ii) exofacial histidine residues His(203), His(206), and His(413) may be involved in maintaining a functional interaction between exofacial loops II and IV and influence the general folding of the transporter; (iii) histidines 203, 206, 269, and 413 affect the transporter kinetics by modulating the apparent transport K(m); and (iv) histidine 109, localized at the center of transmembrane helix I, might be fundamental for the interaction of SVCT2 with the transported substrate ascorbic acid. Thus, histidine residues are central regulators of SVCT2 function.

Formulation and comparative in vitro evaluation of various dexamethasone-loaded pH-sensitive polymeric nanoparticles intended for dermal applications.

PubMed

Sahle, Fitsum Feleke; Gerecke, Christian; Kleuser, Burkhard; Bodmeier, Roland

2017-01-10

pH-sensitive nanoparticles have a great potential for dermal and transfollicular drug delivery. In this study, pH-sensitive, dexamethasone-loaded Eudragit ® L 100, Eudragit ® L 100-55, Eudragit ® S 100, HPMCP-50, HPMCP-55 and cellulose acetate phthalate nanoparticles were prepared by nanoprecipitation and characterized. The pH-dependent swelling, erosion, dissolution and drug release kinetics were investigated in vitro using dynamic light scattering and Franz diffusion cells, respectively. Their toxicity potential was assessed by the ROS and MTT assays. 100-700nm nanoparticles with high drug loading and entrapment efficiency were obtained. The nanoparticles bear no toxicity potential. Cellulose phthalates nanoparticles were more sensitive to pH than acrylates nanoparticles. They dissolved in 10mM pH 7.5 buffer and released>80% of the drug within 7h. The acrylate nanoparticles dissolved in 40mM pH 7.5 buffer and released 65-70% of the drug within 7h. The nanoparticles remained intact in 10 and 40mM pH 6.0 buffers (HPMCP nanoparticles dissolved in 40mM pH 6.0 buffer) and released slowly. The nanoparticles properties could be modulated by blending the different polymers. In conclusion, various pH-sensitive nanoparticles that could release differently on the skin surface and dissolve and release in the hair follicles were obtained. Copyright © 2016 Elsevier B.V. All rights reserved.

Acidic conditions induce the suppression of CD86 and CD54 expression in THP-1 cells.

PubMed

Mitachi, Takafumi; Mezaki, Minori; Yamashita, Kunihiko; Itagaki, Hiroshi

2018-01-01

To evaluate the sensitization potential of chemicals in cosmetics, using non-animal methods, a number of in vitro safety tests have been designed. Current assays are based on the expression of cell surface markers, such as CD86 and CD54, which are associated with the activation of dendritic cells, in skin sensitization tests. However, these markers are influenced by culture conditions through activating danger signals. In this study, we investigated the relationship between extracellular pH and the expression of the skin sensitization test human cell line activation test (h-CLAT) markers CD86 and CD54. We measured expression levels after THP-1 cells were exposed to representative contact allergens, i.e., 2,4-dinitrochlorobenzene and imidazolidinyl urea, under acidic conditions. These conditions were set by exposure to hydrochloric acid, lactic acid, and citric acid. An acidic extracellular pH (6-7) suppressed the augmentation of CD86 and CD54 levels by the sensitizer. Additionally, when the CD86/CD54 expression levels were suppressed, a reduction in the intracellular pH was confirmed. Furthermore, we observed that Na + /H + exchanger 1 (NHE-1), a protein that contributes to the regulation of extracellular/intracellular pH, is involved in CD86 and CD54 expression. These findings suggest that the extracellular/intracellular pH has substantial effects on in vitro skin sensitization markers and should be considered in evaluations of the safety of mixtures and commercial products in the future.

Novel polymerizable surfactants with pH-sensitive amphiphilicity and cell membrane disruption for efficient siRNA delivery.

PubMed

Wang, Xu-Li; Ramusovic, Sergej; Nguyen, Thanh; Lu, Zheng-Rong

2007-01-01

Small interfering RNA (siRNA) is a promising new therapeutic modality that can specifically silence disease-related genes. The main challenge for successful clinical development of therapeutic siRNA is the lack of efficient delivery systems. In this study, we have designed and synthesized a small library of novel multifunctional siRNA carriers, polymerizable surfactants with pH-sensitive amphiphilicity based on the hypothesis that pH-sensitive amphiphilicity and environmentally sensitive siRNA release can result in efficient siRNA delivery. The polymerizable surfactants comprise a protonatable amino head group, two cysteine residues, and two lipophilic tails. The surfactants demonstrated pH-sensitive amphiphilic hemolytic activity or cell membrane disruption with rat red blood cells. Most of the surfactants resulted in low hemolysis at pH 7.4 and high hemolysis at reduced pH (6.5 and 5.4). The pH-sensitive cell membrane disruption can facilitate endosomal-lysosomal escape of siRNA delivery systems at the endosomal-lysosomal pH. The surfactants formed compact nanoparticles (160-260 nm) with siRNA at N/P ratios of 8 and 10 via charge complexation with the amino head group, lipophilic condensation, and autoxidative polymerization of dithiols. The siRNA complexes with the surfactants demonstrated low cytotoxicity. The cellular siRNA delivery efficiency and RNAi activity of the surfactants correlated well with their pH-sensitive amphiphilic cell membrane disruption. The surfactants mediated 40-88% silencing of luciferase expression with 100 nM siRNA and 35-75% with 20 nM siRNA in U87-luc cells. Some of the surfactants resulted in similar or higher gene silencing efficiency than TransFast. EHCO with no hemolytic activity at pH 7.4 and 6.5 and high hemolytic activity at pH 5.4 resulted in the best siRNA delivery efficiency. The polymerizable surfactants with pH-sensitive amphiphilicity are promising for efficient siRNA delivery.

Improving on the diagnostic characteristics of echocardiography for pulmonary hypertension.

PubMed

Broderick-Forsgren, Kathleen; Davenport, Clemontina A; Sivak, Joseph A; Hargett, Charles William; Foster, Michael C; Monteagudo, Andrew; Armour, Alicia; Rajagopal, Sudarshan; Arges, Kristine; Velazquez, Eric J; Samad, Zainab

2017-09-01

This retrospective study evaluated the diagnostic characteristics of a combination of echocardiographic parameters for pulmonary hypertension (PH). Right ventricular systolic pressure (RVSP) estimation by echocardiography (echo) is used to screen for PH. However, the sensitivity of this method is suboptimal. We hypothesized that RVSP estimation in conjunction with other echo parameters would improve the value of echo for PH. The Duke Echo database was queried for adult patients with known or suspected PH who had undergone both echo and right heart catheterization (RHC) within a 24 h period between 1/1/2008 and 12/31/2013. Patients with complex congenital heart disease, heart transplantation, ventricular assist device, or on mechanical ventilation at time of study were excluded. Diagnostic characteristics of several echo parameters (right atrial enlargement, pulmonary artery (PA) enlargement, RV enlargement, RV dysfunction, and RVSP) for PH (mean PA pressure 25 mmHg on RHC) were evaluated among 1007 patients. RVSP ≥40 had a sensitivity of 77% (accuracy 77), while RVSP ≥35 had the highest sensitivity at 88% (81% accuracy). PA enlargement had the lowest sensitivity at 17%. The area under the curve (AUC) for RVSP was 0.844. A model including RVSP, RA, PA, RV enlargement and RV dysfunction had a higher AUC (AUC = 0.87) than RVSP alone. The value of echo as a screening test for PH is improved by a model incorporating a lower RVSP in addition to other right heart parameters. These findings need to be validated in prospective cohorts.

An investigation into the potential of phenothiazinium-based photo-sensitisers to act as PDT agents.

PubMed

Harris, F; Sayed, Z; Hussain, S; Phoenix, D A

2004-11-01

There is an urgent need for effective cancer treatments and increasingly, photo-dynamic therapy (PDT) is being used to fulfil this need as it offers a number of advantages over traditional cancer treatments. Here, the potential of a series of phenothiazinium-based photo-sensitisers (PhBPs) as PDT agents is tested. PhBPs were incubated with EMT-6 tumour cells and erythrocytes respectively under dark and light conditions (3.15Jcm(-2) over 30min). "Comet assay" and haemolytic assay were then used to assess cellular photo-damage induced by these PhBPs. Additionally, in vitro assays were used to determine light adsorption characteristics, singlet oxygen yields (ΦΔPhBP) and lipophilicity (logP) of these PhBPs. "Comet assay" showed EMT-6 incubation with PhBPs under light conditions to produce DNA "tails", which were circa 35μm long, indicating the presence of DNA photo-damage. Corresponding incubations under dark conditions led to no such damage. The majority of the PhBPs tested possessed significant singlet oxygen yields (ΦΔPhBP>0.7), suggesting the general use of type II mechanisms for photo-sensitization, and were generally lipophilic (logP>0). Incubation of erythrocytes with these PhBPs in the dark produced between 6% and 19% haemolysis. These levels were generally unaffected by illumination except in the case of DMMB, which showed haemolytic levels increasing from 11% to 61%. It is suggested that DNA may be the primary target for the photo-dynamic anti-tumour activity of the PhBPs tested with the exception of DMMB, which may potentially also target tumour cell membranes.

pH Optimum of Hemagglutinin-Mediated Membrane Fusion Determines Sensitivity of Influenza A Viruses to the Interferon-Induced Antiviral State and IFITMs.

PubMed

Gerlach, Thomas; Hensen, Luca; Matrosovich, Tatyana; Bergmann, Janina; Winkler, Michael; Peteranderl, Christin; Klenk, Hans-Dieter; Weber, Friedemann; Herold, Susanne; Pöhlmann, Stefan; Matrosovich, Mikhail

2017-06-01

The replication and pathogenicity of influenza A viruses (IAVs) critically depend on their ability to tolerate the antiviral interferon (IFN) response. To determine a potential role for the IAV hemagglutinin (HA) in viral sensitivity to IFN, we studied the restriction of IAV infection in IFN-β-treated human epithelial cells by using 2:6 recombinant IAVs that shared six gene segments of A/Puerto Rico/8/1934 virus (PR8) and contained HAs and neuraminidases of representative avian, human, and zoonotic H5N1 and H7N9 viruses. In A549 and Calu-3 cells, viruses displaying a higher pH optimum of HA-mediated membrane fusion, H5N1-PR8 and H7N9-PR8, were less sensitive to the IFN-induced antiviral state than their counterparts with HAs from duck and human viruses, which fused at a lower pH. The association between a high pH optimum of fusion and reduced IFN sensitivity was confirmed by using HA point mutants of A/Hong Kong/1/1968-PR8 that differed solely by their fusion properties. Furthermore, similar effects of the viral fusion pH on IFN sensitivity were observed in experiments with (i) primary human type II alveolar epithelial cells and differentiated cultures of human airway epithelial cells, (ii) nonrecombinant zoonotic and pandemic IAVs, and (iii) preparations of IFN-α and IFN-λ1. A higher pH of membrane fusion and reduced sensitivity to IFN correlated with lower restriction of the viruses in MDCK cells stably expressing the IFN-inducible transmembrane proteins IFITM2 and IFITM3, which are known to inhibit viral fusion. Our results reveal that the pH optimum of HA-driven membrane fusion of IAVs is a determinant of their sensitivity to IFN and IFITM proteins. IMPORTANCE The IFN system constitutes an important innate defense against viral infection. Substantial information is available on how IAVs avoid detection by sensors of the IFN system and disable IFN signaling pathways. Much less is known about the ability of IAVs to tolerate the antiviral activity of IFN-induced cellular proteins. The IFN-induced proteins of the IFITM family block IAV entry into target cells and can restrict viral spread and pathogenicity. Here we show for the first time that the sensitivity of IAVs to the IFN-induced antiviral state and IFITM2 and IFITM3 proteins depends on the pH value at which the viral HA undergoes a conformational transition and mediates membrane fusion. Our data imply that the high pH optimum of membrane fusion typical of zoonotic IAVs of gallinaceous poultry, such as H5N1 and H7N9, may contribute to their enhanced virulence in humans. Copyright © 2017 American Society for Microbiology.

pH Optimum of Hemagglutinin-Mediated Membrane Fusion Determines Sensitivity of Influenza A Viruses to the Interferon-Induced Antiviral State and IFITMs

PubMed Central

Gerlach, Thomas; Hensen, Luca; Matrosovich, Tatyana; Bergmann, Janina; Winkler, Michael; Peteranderl, Christin; Klenk, Hans-Dieter; Herold, Susanne

2017-01-01

ABSTRACT The replication and pathogenicity of influenza A viruses (IAVs) critically depend on their ability to tolerate the antiviral interferon (IFN) response. To determine a potential role for the IAV hemagglutinin (HA) in viral sensitivity to IFN, we studied the restriction of IAV infection in IFN-β-treated human epithelial cells by using 2:6 recombinant IAVs that shared six gene segments of A/Puerto Rico/8/1934 virus (PR8) and contained HAs and neuraminidases of representative avian, human, and zoonotic H5N1 and H7N9 viruses. In A549 and Calu-3 cells, viruses displaying a higher pH optimum of HA-mediated membrane fusion, H5N1-PR8 and H7N9-PR8, were less sensitive to the IFN-induced antiviral state than their counterparts with HAs from duck and human viruses, which fused at a lower pH. The association between a high pH optimum of fusion and reduced IFN sensitivity was confirmed by using HA point mutants of A/Hong Kong/1/1968-PR8 that differed solely by their fusion properties. Furthermore, similar effects of the viral fusion pH on IFN sensitivity were observed in experiments with (i) primary human type II alveolar epithelial cells and differentiated cultures of human airway epithelial cells, (ii) nonrecombinant zoonotic and pandemic IAVs, and (iii) preparations of IFN-α and IFN-λ1. A higher pH of membrane fusion and reduced sensitivity to IFN correlated with lower restriction of the viruses in MDCK cells stably expressing the IFN-inducible transmembrane proteins IFITM2 and IFITM3, which are known to inhibit viral fusion. Our results reveal that the pH optimum of HA-driven membrane fusion of IAVs is a determinant of their sensitivity to IFN and IFITM proteins. IMPORTANCE The IFN system constitutes an important innate defense against viral infection. Substantial information is available on how IAVs avoid detection by sensors of the IFN system and disable IFN signaling pathways. Much less is known about the ability of IAVs to tolerate the antiviral activity of IFN-induced cellular proteins. The IFN-induced proteins of the IFITM family block IAV entry into target cells and can restrict viral spread and pathogenicity. Here we show for the first time that the sensitivity of IAVs to the IFN-induced antiviral state and IFITM2 and IFITM3 proteins depends on the pH value at which the viral HA undergoes a conformational transition and mediates membrane fusion. Our data imply that the high pH optimum of membrane fusion typical of zoonotic IAVs of gallinaceous poultry, such as H5N1 and H7N9, may contribute to their enhanced virulence in humans. PMID:28356532

Colorimetric and Fluorescent Bimodal Ratiometric Probes for pH Sensing of Living Cells.

PubMed

Liu, Yuan-Yuan; Wu, Ming; Zhu, Li-Na; Feng, Xi-Zeng; Kong, De-Ming

2015-06-01

pH measurement is widely used in many fields. Ratiometric pH sensing is an important way to improve the detection accuracy. Herein, five water-soluble cationic porphyrin derivatives were synthesized and their optical property changes with pH value were investigated. Their pH-dependent assembly/disassembly behaviors caused significant changes in both absorption and fluorescence spectra, thus making them promising bimodal ratiometric probes for both colorimetric and fluorescent pH sensing. Different substituent identity and position confer these probes with different sensitive pH-sensing ranges, and the substituent position gives a larger effect. By selecting different porphyrins, different signal intensity ratios and different fluorescence excitation wavelengths, sensitive pH sensing can be achieved in the range of 2.1-8.0. Having demonstrated the excellent reversibility, good accuracy and low cytotoxicity of the probes, they were successfully applied in pH sensing inside living cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High pH-Sensitive TRPA1 Activation in Odontoblasts Regulates Mineralization.

PubMed

Kimura, M; Sase, T; Higashikawa, A; Sato, M; Sato, T; Tazaki, M; Shibukawa, Y

2016-08-01

Calcium hydroxide and mineral trioxide aggregate are widely used for indirect and direct pulp capping and root canal filling. Their dissociation into Ca(2+) and OH(-) in dental pulp creates an alkaline environment, which activates reparative/reactionary dentinogenesis. However, the mechanisms by which odontoblasts detect the pH of the extracellular environment remain unclear. We examined the alkali-sensitive intracellular Ca(2+) signaling pathway in rat odontoblasts. In the presence or absence of extracellular Ca(2+), application of alkaline solution increased intracellular Ca(2+) concentration, or [Ca(2+)]i Alkaline solution-induced [Ca(2+)]i increases depended on extracellular pH (8.5 to 10.5) in both the absence and the presence of extracellular Ca(2+) The amplitude was smaller in the absence than in the presence of extracellular Ca(2+) Each increase in [Ca(2+)]i, activated by pH 7.5, 8.5, or 9.5, depended on extracellular Ca(2+) concentration; the equilibrium binding constant for extracellular Ca(2+) concentration decreased as extracellular pH increased (1.04 mM at pH 7.5 to 0.11 mM at pH 9.5). Repeated applications of alkaline solution did not have a desensitizing effect on alkali-induced [Ca(2+)]i increases and inward currents. In the presence of extracellular Ca(2+), alkaline solution-induced [Ca(2+)]i increases were suppressed by application of an antagonist of transient receptor potential ankyrin subfamily member 1 (TRPA1) channels. Ca(2+) exclusion efficiency during alkaline solution-induced [Ca(2+)]i increases was reduced by a Na(+)-Ca(2+) exchanger antagonist. Alizarin red and von Kossa staining revealed increased mineralization levels under repeated high pH stimulation, whereas the TRPA1 antagonist strongly reduced this effect. These findings indicate that alkaline stimuli-such as the alkaline environment inside dental pulp treated with calcium hydroxide or mineral trioxide aggregate-activate Ca(2+) mobilization via Ca(2+) influx mediated by TRPA1 channels and intracellular Ca(2+) release in odontoblasts. High pH-sensing mechanisms in odontoblasts are important for activating dentinogenesis induced by an alkaline environment. © International & American Associations for Dental Research 2016.

Tertiary-amine-containing thermo- and pH-sensitive hydrophilic ABA triblock copolymers: effect of different tertiary amines on thermally induced sol-gel transitions.

PubMed

Henn, Daniel M; Wright, Roger A E; Woodcock, Jeremiah W; Hu, Bin; Zhao, Bin

2014-03-11

This Article reports on the synthesis of a series of well-defined, tertiary-amine-containing ABA triblock copolymers, composed of a poly(ethylene oxide) (PEO) central block and thermo- and pH-sensitive outer blocks, and the study of the effect of different tertiary amines on thermally induced sol-gel transition temperatures (T(sol-gel)) of their 10 wt % aqueous solutions. The doubly responsive ABA triblock copolymers were prepared from a difunctional PEO macroinitiator by atom transfer radical polymerization of methoxydi(ethylene glycol) methacrylate and ethoxydi(ethylene glycol) methacrylate at a feed molar ratio of 30:70 with ∼5 mol % of either N,N-diethylaminoethyl methacrylate (DEAEMA), N,N-diisopropylaminoethyl methacrylate, or N,N-di(n-butyl)aminoethyl methacrylate. The chain lengths of thermosensitive outer blocks and the molar contents of tertiary amines were very similar for all copolymers. Using rheological measurements, we determined the pH dependences of T(sol-gel) of 10 wt % aqueous solutions of these copolymers in a phosphate buffer. The T(sol-gel) versus pH curves of all polymers exhibited a sigmoidal shape. The T(sol-gel) increased with decreasing pH; the changes were small on both high and low pH sides. At a specific pH, the T(sol-gel) decreased with increasing the hydrophobicity of the tertiary amine, and upon decreasing pH the onset pH value for the T(sol-gel) to begin to increase noticeably was lower for the more hydrophobic tertiary amine-containing copolymer. In addition, we studied the effect of different tertiary amines on the release behavior of FITC-dextran from 10 wt % micellar gels in an acidic medium at 37 and 27 °C. The release profiles for three studied hydrogels at 37 °C were essentially the same, suggesting that the release was dominated by the diffusion of FITC-dextran. At 27 °C, the release was significantly faster for the DEAEMA-containing copolymer, indicating that both diffusion and gel dissolution contributed to the release at this temperature.

Handedness inversion in preparing chiral 4, 4'-biphenylene-silica nanostructures

NASA Astrophysics Data System (ADS)

Li, Yi; Wang, Hairui; Wang, Liwen; Zhou, Feng; Chen, Yuanli; Li, Baozong; Yang, Yonggang

2011-04-01

An anionic gelator, D-C12ValC10COONa, derived from D-valine can cause physical gels in water and organic solvents. Helical 4, 4'-biphenylene-silica nanotubes and nanoribbons were prepared using it with 3-aminopropyltrimethoxysilane as a co-structure-directing agent and 4, 4'-bis(triethoxysilyl)-1, 1'-biphenyl (BTESB) as precursor. It was found that the handedness of the hybrid silica nanotubes/nanoribbons is sensitive to the pH value and the concentration of the reaction mixtures. However, handedness inversion was not found by changing the reaction temperature. Circular dichroism spectra of the 4, 4'-biphenylene-silica nanotubes indicated that the chirality of the organic self-assemblies were successfully transferred to the twist of the biphenylene rings through the co-structure-directing agent. The handedness of the 4, 4'-biphenylene rings was also tunable by changing the pH value and the concentration of the reaction mixtures. The FESEM images and CD spectra taken after different reaction times indicated that the handedness inversion occurred after adding BTESB.

Dual stimuli responsive self-reporting material for chemical reservoir coating

NASA Astrophysics Data System (ADS)

Lee, Tae Hee; Song, Young Kyu; Park, Sun Hee; Park, Young Il; Noh, Seung Man; Kim, Jin Chul

2018-03-01

In this study, we introduce a novel dual stimuli responsive self-reporting thiol-epoxy thermoset (DSRTET) coatings which can detect both crack occurrence and pH variation. For crack detection, microcapsule containing tetraphenylethylene (TPE) which exhibits aggregation induced emission (AIE) effect was prepared via multi-step emulsion polymerization and dispersed in DSRTET coatings. For pH variation detection, commercial thymol blue as a pH indicator was added into the polymer matrix. The effect of microcapsule contents in DSRTET on their curing behavior, material properties, and crack sensitivity was characterized using an oscillatory rheology, rigid body pendulum test (RPT), nano-indentation test (NST), universal test machine (UTM) and scratch tester. It was revealed that crack sensitivity of DSRTET coatings was greatly influenced by material properties as well as microcapsule content. The color transition of DSRTET coatings in response to acid or base solution were quantitatively investigated using a multi-angle spectrophotometer after simple acid and base solution drop tests. The color of DSRTET coatings changed from a pale green to red for acidic solution and to blue for basic solution. Finally, The DSRTET used in this study was applied to laboratory scale chemical reservoirs in order to verify the potential as a dual stimuli response self-reporting coating which can detect both crack in coating material and chemical spill caused by the leakage or breakage of the reservoir part.

A reagent strip for measuring the specific gravity of urine.

PubMed

Burkhardt, A E; Johnston, K G; Waszak, C E; Jackson, C E; Shafer, S R

1982-10-01

A solid-phase reagent for determination of urinary specific gravity (relative density) is described. This reagent strip, similar to others in the "N-Multistix" series (Ames), contains a polyacid whose acidity is sensitive to the ionic concentration in the urine in which it is immersed. As the acidity of the polyacid changes, pH changes are detected by a pH indicator within the reagent strip. In comparison studies, 84.4% of relative densities as measured with these reagent strips were within 0.005 of the corresponding results with a total-solids meter, and 89.9% were within 0.005 of the corresponding urinometer results. Adding a correction of +0.005 to the reagent-strip results for urines with high pH increased the percentage of results within 0.005 of the comparison method to 90.7% (TS meter) and 92.9% (urinometer). Lot-to-lot variability and reader-to-reader variability were both low. Reagent strip results are not affected by glucose, may be increased by albumin, and correlate with urea concentrations.

A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles

PubMed Central

Wang, Chensu; Wang, Yiguang; Li, Yang; Bodemann, Brian; Zhao, Tian; Ma, Xinpeng; Huang, Gang; Hu, Zeping; DeBerardinis, Ralph J.; White, Michael A.; Gao, Jinming

2015-01-01

Endosomes, lysosomes and related catabolic organelles are a dynamic continuum of vacuolar structures that impact a number of cell physiological processes such as protein/lipid metabolism, nutrient sensing and cell survival. Here we develop a library of ultra-pH-sensitive fluorescent nanoparticles with chemical properties that allow fine-scale, multiplexed, spatio-temporal perturbation and quantification of catabolic organelle maturation at single organelle resolution to support quantitative investigation of these processes in living cells. Deployment in cells allows quantification of the proton accumulation rate in endosomes; illumination of previously unrecognized regulatory mechanisms coupling pH transitions to endosomal coat protein exchange; discovery of distinct pH thresholds required for mTORC1 activation by free amino acids versus proteins; broad-scale characterization of the consequence of endosomal pH transitions on cellular metabolomic profiles; and functionalization of a context-specific metabolic vulnerability in lung cancer cells. Together, these biological applications indicate the robustness and adaptability of this nanotechnology-enabled ‘detection and perturbation' strategy. PMID:26437053

On-line focusing of flavin derivatives using Dynamic pH junction-sweeping capillary electrophoresis with laser-induced fluorescence detection.

PubMed

Britz-McKibbin, Philip; Otsuka, Koji; Terabe, Shigeru

2002-08-01

Simple yet effective methods to enhance concentration sensitivity is needed for capillary electrophoresis (CE) to become a practical method to analyze trace levels of analytes in real samples. In this report, the development of a novel on-line preconcentration technique combining dynamic pH junction and sweeping modes of focusing is applied to the sensitive and selective analysis of three flavin derivatives: riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Picomolar (pM) detectability of flavins by CE with laser-induced fluorescence (LIF) detection is demonstrated through effective focusing of large sample volumes (up to 22% capillary length) using a dual pH junction-sweeping focusing mode. This results in greater than a 1,200-fold improvement in sensitivity relative to conventional injection methods, giving a limit of detection (S/N = 3) of approximately 4.0 pM for FAD and FMN. Flavin focusing is examined in terms of analyte mobility dependence on buffer pH, borate complexation and SDS interaction. Dynamic pH junction-sweeping extends on-line focusing to both neutral (hydrophobic) and weakly acidic (hydrophilic) species and is considered useful in cases when either conventional sweeping or dynamic pH junction techniques used alone are less effective for certain classes of analytes. Enhanced focusing performance by this hyphenated method was demonstrated by greater than a 4-fold reduction in flavin bandwidth, as compared to either sweeping or dynamic pH junction, reflected by analyte detector bandwidths <0.20 cm. Novel on-line focusing strategies are required to improve sensitivity in CE, which may be applied toward more effective biochemical analysis methods for diverse types of analytes.

Novel pH responsive polymethacrylic acid-chitosan-polyethylene glycol nanoparticles for oral peptide delivery.

PubMed

Sajeesh, S; Sharma, Chandra P

2006-02-01

In present study, novel pH sensitive polymethacrylic acid-chitosan-polyethylene glycol (PCP) nanoparticles were prepared under mild aqueous conditions via polyelectrolyte complexation. Free radical polymerization of methacrylic acid (MAA) was carried out in presence of chitosan (CS) and polyethylene glycol (PEG) using a water-soluble initiator and particles were obtained spontaneously during polymerization without using organic solvents or surfactants/steric stabilizers. Dried particles were analyzed by scanning electron microscopy (SEM) and particles dispersed in phosphate buffer (pH 7.0) were visualized under transmission electron microscope (TEM). SEM studies indicated that PCP particles have an aggregated and irregular morphology, however, TEM revealed that these aggregated particles were composed of smaller fragments with size less than 1 micron. Insulin and bovine serum albumin (BSA) as model proteins were incorporated into the nanoparticles by diffusion filling method and their in vitro release characteristics were evaluated at pH 1.2 and 7.4. PCP nanoparticles exhibited good protein encapsulation efficiency and pH responsive release profile was observed under in vitro conditions. Trypsin inhibitory effect of these PCP nanoparticles was studied using casein substrate and these particles displayed lesser inhibitory effect than reference polymer carbopol. Preliminary investigation suggests that these particles can serve as good candidate for oral peptide delivery. Copyright 2005 Wiley Periodicals, Inc.

Hemoglobin function and allosteric regulation in semi-fossorial rodents (family Sciuridae) with different altitudinal ranges.

PubMed

Revsbech, Inge G; Tufts, Danielle M; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E; Storz, Jay F; Fago, Angela

2013-11-15

Semi-fossorial ground squirrels face challenges to respiratory gas transport associated with the chronic hypoxia and hypercapnia of underground burrows, and such challenges are compounded in species that are native to high altitude. During hibernation, such species must also contend with vicissitudes of blood gas concentrations and plasma pH caused by episodic breathing. Here, we report an analysis of hemoglobin (Hb) function in six species of marmotine ground squirrels with different altitudinal distributions. Regardless of their native altitude, all species have high Hb-O2 affinities, mainly due to suppressed sensitivities to allosteric effectors [2,3-diphosphoglycerate (DPG) and chloride ions]. This suppressed anion sensitivity is surprising given that all canonical anion-binding sites are conserved. Two sciurid species, the golden-mantled and thirteen-lined ground squirrel, have Hb-O2 affinities that are characterized by high pH sensitivity and low thermal sensitivity relative to the Hbs of humans and other mammals. The pronounced Bohr effect is surprising in light of highly unusual amino acid substitutions at the C-termini that are known to abolish the Bohr effect in human HbA. Taken together, the high O2 affinity of sciurid Hbs suggests an enhanced capacity for pulmonary O2 loading under hypoxic and hypercapnic conditions, while the large Bohr effect should help to ensure efficient O2 unloading in tissue capillaries. In spite of the relatively low thermal sensitivities of the sciurid Hbs, our results indicate that the effect of hypothermia on Hb oxygenation is the main factor contributing to the increased blood-O2 affinity in hibernating ground squirrels.

Study of the structural organization of cyclodextrin-DNA complex loaded anionic and pH-sensitive liposomes

NASA Astrophysics Data System (ADS)

Silva, Sônia M. L.; Coelho, Letícia N.; Malachias, Ângelo; Perez, Carlos A.; Pesquero, Jorge L.; Magalhães-Paniago, Rogério; de Oliveira, Mônica C.

2011-04-01

The present study investigated the effect of the 6-monodeoxy-6-monoamine-β-cyclodextrin(Am-β-CD)/DNA (Am-β-CD/DNA) complex, as well as of culture medium components and proteins, at pH 7.4 and 5.0, on membranes of anionic and pH-sensitive liposomes comprised of DOPE-CHEMS, using energy dispersive X-ray diffraction (EDXD). At pH 7.4, the Am-β-CD/DNA complex induced the appearance of lamellar and hexagonal phases of DOPE. However, at pH 5.0, only non-lamellar phases could be observed. The presence of biological components led to a disruption of lipid order, but the pH-sensitivity of liposomes was maintained.

Aqueous corrosion and corrosion-sensitive embrittlement of Fe{sub 3}Al-based and lean-aluminum iron aluminides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, J.G.; Buchanan, R.A.

Aqueous corrosion and corrosion-sensitive embrittlement of iron aluminides were characterized as functions of environment, alloying content, notch sensitivity, and strain rate. Polarization resistance and cyclic anodic polarization evaluations were performed in 3.5 wt % NaCl, 200 ppM Cl{sup {minus}} (pH = 4), and 1 N NaOH solutions. In the mild acid-chloride solution [200 ppM Cl{sup {minus}} (pH = 4)], the pitting-corrosion resistance of the new lean-aluminum iron aluminides (FAP-Y and CM-Mo) was comparable to that of the Fe{sub 3}Al-based FAL-Mo. In the higher-chloride 3.5 wt % NaCl, the resistance of CM-Mo was slightly less but FAP-Y showed quite similar behaviormore » to FAL-Mo. In 1 N NaOH solution, all materials exhibited ideal passive behavior. Under slow-strain-rate test conditions in the mild acid-chloride electrolyte, prior work had shown the ductilities (% elongations) of Fe{sub 3}Al-based materials to be {approximately}7% and {approximately}1% at the freely-corroding and hydrogen-charging potentials, respectively. Present studied on the lean-aluminum materials have shown the ductilities to be {approximately}17% and {approximately}5%, respectively. Thus, the present results indicate that these new materials have reasonably-good aqueous-corrosion properties in chloride environments and significantly-enhanced ductilities under aqueous corrosion conditions. The strain rate and notch sensitivities of high-aluminum iron aluminide (FA-129) were investigated by performing slow-strain-rate tests. The notch sensitivity was independent of strain rate and the notch sensitivity in the aqueous environment was similar to that in air.« less

Branched GDGT-based paleotemperature reconstruction of the last 30,000 years in humid monsoon region of Southeast China

NASA Astrophysics Data System (ADS)

Wang, M.

2017-12-01

The use of bacterial branched glycerol dialkyl glycerol tetraethers (brGDGTs) to reconstruct mean annual air temperatures (MAATs) and environmental pH from soils has sparked significant interest in the terrestrial paleoclimate community. However, the reconstruction of these climate proxies from peat bogs is rare in monsoonal regions of the East Asia. This research was carried out on a core from the Shuizhuyang (SZY) peat bog located in Fujian Province. Branched GDGT (brGDGT) indexes were used for reconstructing the paleoclimate of the last 30 cal ka. The aim was to evaluate quantitatively the MAAT and pH values since the Last Glacial Maximum (LGM) in the subtropical zone of China. Results show that the CBT-MBT'-derived MAAT at MIS 3 is about 15.6 °C on average, which is followed by a significant fall at the LGM (11.7-12.1 °C). The temperature difference between the LGM and the present-day value is as high as 5.8 °C. The synchronous variation of biomarker and pollen proxies indicates that replacement of subtropical evergreen broadleaved forests by coldtolerant, deciduous broadleaved forests was driven by the significant drop in air temperature. Our results also indicate that the Younger Dryas event lasted from about 12.9 to about 11.3 cal ka, and cooling event at 3.2 cal ka in the late Holocene was detected, showing the sensitivity of peat bogs to rapid cooling. Our pH reconstructions indicate that the pH of the bog rose during Heinrich 1 and Bølling-Allerød periods, probably due to low precipitation, and were lowest in the Holocene thermal maximum between 8 ka and 2.5 ka, probably due to higher precipitation. The decoupling of reconstructed MAAT and pH during particularly deglaciation and YD periods supports the hypothesis that the variations in temperature and precipitation are not always synchronous.

Development of Fast Response In-situ Sensors for Simultaneous Measurements of Seawater Carbon Dioxide Parameters

NASA Astrophysics Data System (ADS)

Wang, A. Z.; Sonnichsen, F. N.; Chu, S. N.; Bradley, A. M.; Hoering, K.

2016-02-01

The marine CO2 (inorganic carbon) system is characterized by four primary parameters - total dissolved inorganic carbon (DIC), total alkalinity (TA), partial pressure of CO2 (pCO2), and pH. These parameters are central to the study of the marine carbon cycle and ocean acidification. Simultaneous measurements of two of the four CO2 parameters are required to fully resolve the seawater CO2 system, and DIC is one of the preferred parameters. A self-calibrating, in-situ sensor, Channelized Optical System (CHANOS), has recently been developed to provide simultaneous measurements of both DIC and pH, resolving carbonate chemistry with a single system. CHANOS is among the first to achieve simultaneous, in-situ measurements of a desired pair of CO2 parameters. DIC and pH channels both use flow-through, spectrophotometric methods to detect relative absorbances of the acid and base forms of a pH-sensitive indicator. The precision of CHANOS in laboratory and in-situ tests are ±0.002 and ±3.0 µmol kg-1 for pH and DIC, respectively. In-situ comparison with bottle sampling and analyses indicate that the accuracies for pH and DIC are ±0.004 and ±5.0 µmol kg-1, respectively. It has been demonstrated that CHANOS can make in-situ, climatology-quality measurements to resolve the CO2 system in dynamic aquatic environments. To further improve response time of the sensor, especially for DIC measurements, a new generation of CHANOS-DIC is under development. The new system adapts the recently developed spectrophotometric DIC method to achieve flow-through CO2 equilibration between an acidified sample and an indicator solution with a response time as fast as 22s. Continuous measurements are also achievable. Because of the fast response of CHANOS measurements, it is versatile and suitable for deployments on both fixed (e.g. buoys) and mobile (e.g., AUV, ROV, and profilers) platforms.

Implications of down regulation of rcsA and rcsA-regulated colanic acid biosynthesis genes in increased acid sensitivity and enhanced curli and biofilm production in enterohemorrhagic Escherichia coli O157:H7

USDA-ARS?s Scientific Manuscript database

Enterohemorrhagic Escherichia coli (E. coli) O157:H7 strain 86-24, originally linked to a disease outbreak in the western USA in 1982, exhibits acid resistance as indicated by its ability to survive exposure to acidic conditions (pH2.5) for several hours. The strain 86-24 is a poor biofilm producer ...

A pH-sensitive red fluorescent protein compatible with hydrophobic resin embedding

NASA Astrophysics Data System (ADS)

Guo, Wenyan; Gang, Yadong; Liu, Xiuli; Zhou, Hongfu; Zeng, Shaoqun

2017-02-01

pH sensitive fluorescent proteins enabling chemical reactivation in resin are useful tools for fluorescence microimaging. EYFP or EGFP improved from GFP in jellyfish are good for such applications. For simultaneous two-color imaging, a suitable red fluorescent protein is of urgent need. Here a pH sensitive red fluorescent protein, pHuji, is selected and verified to be compatible with hydrophobic resin embedding and thus may be promising for dual-colour chemical reactivation imaging in conjunction with EGFP or EYFP.

pH-Dependent Optical Properties of Synthetic Fluorescent Imidazoles

PubMed Central

Berezin, Mikhail Y.; Kao, Jeff; Achilefu, Samuel

2010-01-01

An imidazole moiety is often found as an integral part of fluorophores in a variety of fluorescent proteins and many such proteins possess pH dependent light emission. In contrast, synthetic fluorescent compounds with incorporated imidazoles are rare and have not been studied as pH probes. In this report, the richness of imidazole optical properties, including pH sensitivity, was demonstrated via a novel imidazole-based fluorophore 1H-imidazol-5-yl-vinyl-benz[e]indolium. Three species corresponding to protonated, neutral and deprotonated imidazoles were identified in the broad range of pH 1-12. The absorption and emission bands of each species were assigned by comparative spectral analysis with synthesized mono- and di-N-methylated fluorescent imidazole analogues. pKa analysis in the ground and the excited states showed photoacidic properties of the fluorescent imidazoles due to the excited state proton transfer (ESPT). This effect was negligible for substituted imidazoles. The assessment of a pH sensitive center in the imidazole ring revealed the switching of the pH sensitive centers from 1-N in the ground state to 3-N in the excited state. The effect was attributed to the unique kind of the excited state charge transfer (ESCT) resulting in a positive charge swapping between two nitrogens. PMID:19212987

Temperature and pH sensors based on graphenic materials.

PubMed

Salvo, P; Calisi, N; Melai, B; Cortigiani, B; Mannini, M; Caneschi, A; Lorenzetti, G; Paoletti, C; Lomonaco, T; Paolicchi, A; Scataglini, I; Dini, V; Romanelli, M; Fuoco, R; Di Francesco, F

2017-05-15

Point-of-care applications and patients' real-time monitoring outside a clinical setting would require disposable and durable sensors to provide better therapies and quality of life for patients. This paper describes the fabrication and performances of a temperature and a pH sensor on a biocompatible and wearable board for healthcare applications. The temperature sensor was based on a reduced graphene oxide (rGO) layer that changed its electrical resistivity with the temperature. When tested in a human serum sample between 25 and 43°C, the sensor had a sensitivity of 110±10Ω/°C and an error of 0.4±0.1°C compared with the reference value set in a thermostatic bath. The pH sensor, based on a graphene oxide (GO) sensitive layer, had a sensitivity of 40±4mV/pH in the pH range between 4 and 10. Five sensor prototypes were tested in a human serum sample over one week and the maximum deviation of the average response from reference values obtained by a glass electrode was 0.2pH units. For biological applications, the temperature and pH sensors were successfully tested for in vitro cytotoxicity with human fibroblast cells (MRC-5) over 24h. Copyright © 2017 Elsevier B.V. All rights reserved.

pH-Sensitive Interactions between Cellulose Nanocrystals and DOPC Liposomes.

PubMed

Navon, Yotam; Radavidson, Harisoa; Putaux, Jean-Luc; Jean, Bruno; Heux, Laurent

2017-09-11

The interaction of 1,2 dioleolyl-sn-glycero-3-phosphatidylcholine (DOPC) vesicles with cellulose nanocrystals (CNCs) using several complementary techniques. Dynamic light scattering, zeta-potential, cryo-transmission electron microscopy and isothermal titration calorimetry (ITC) analyses confirmed the formation of pH-dependent CNC-liposome complexes. ITC was used to characterize the thermodynamic properties of this interaction. Positive values of enthalpy were found at pH lower than 5 where the charge sign of the constituents was opposite. The association was more pronounced at lower pH, as indicated by the higher values of association constant. We suggest that the positive enthalpy is derived from the release of counterions from the particle hydration shell during the association and that the charge of the vesicles plays a significant role in this interaction.

Switching of actin-myosin motors by voltage-induced pH bias in vitro.

PubMed

Hatori, Kuniyuki; Iwase, Takahiro; Wada, Reito

2016-08-01

ATP-driven motor proteins, which function in cell motility and organelle transport, have potential applications as bio-inspired micro-devices; however, their control remains unsatisfactory. Here, we show rapid-velocity control of actin filaments interacting with myosin motors using voltage applied to Pt electrodes in an in vitro motility system, by which immediate increases and decreases in velocity were induced beside the cathode and anode, respectively. Indicator dye revealed pH changes after voltage application, and alternate voltage switching allowed actin filaments to cyclically alter their velocity in response to these changes. This principle provides a basis for on-demand control of not only motor proteins but also pH-sensitive events at a microscopic level. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulator of G-protein signaling 2 (RGS2) suppresses premature calcium release in mouse eggs

PubMed Central

Bernhardt, Miranda L.; Lowther, Katie M.; Padilla-Banks, Elizabeth; McDonough, Caitlin E.; Lee, Katherine N.; Evsikov, Alexei V.; Uliasz, Tracy F.; Chidiac, Peter; Williams, Carmen J.; Mehlmann, Lisa M.

2015-01-01

During oocyte maturation, capacity and sensitivity of Ca2+ signaling machinery increases dramatically, preparing the metaphase II (MII)-arrested egg for fertilization. Upon sperm-egg fusion, Ca2+ release from IP3-sensitive endoplasmic reticulum stores results in cytoplasmic Ca2+ oscillations that drive egg activation and initiate early embryo development. Premature Ca2+ release can cause parthenogenetic activation prior to fertilization; thus, preventing inappropriate Ca2+ signaling is crucial for ensuring robust MII arrest. Here, we show that regulator of G-protein signaling 2 (RGS2) suppresses Ca2+ release in MII eggs. Rgs2 mRNA was recruited for translation during oocyte maturation, resulting in ∼20-fold more RGS2 protein in MII eggs than in fully grown immature oocytes. Rgs2-siRNA-injected oocytes matured to MII; however, they had increased sensitivity to low pH and acetylcholine (ACh), which caused inappropriate Ca2+ release and premature egg activation. When matured in vitro, RGS2-depleted eggs underwent spontaneous Ca2+ increases that were sufficient to cause premature zona pellucida conversion. Rgs2−/− females had reduced litter sizes, and their eggs had increased sensitivity to low pH and ACh. Rgs2−/− eggs also underwent premature zona pellucida conversion in vivo. These findings indicate that RGS2 functions as a brake to suppress premature Ca2+ release in eggs that are poised on the brink of development. PMID:26160904

Phase-sensitive optical coherence tomography characterization of pulse-induced trabecular meshwork displacement in ex vivo nonhuman primate eyes

NASA Astrophysics Data System (ADS)

Li, Peng; Reif, Roberto; Zhi, Zhongwei; Martin, Elizabeth; Shen, Tueng T.; Johnstone, Murray; Wang, Ruikang K.

2012-07-01

Glaucoma is a blinding disease for which intraocular pressure (IOP) is the only treatable risk factor. The mean IOP is regulated through the aqueous outflow system, which contains the trabecular meshwork (TM). Considerable evidence indicates that trabecular tissue movement regulates the aqueous outflow and becomes abnormal during glaucoma; however, such motion has thus far escaped detection. The purpose of this study is to describe anovel use of a phase-sensitive optical coherence tomography (PhS-OCT) method to assess pulse-dependent TM movement. For this study, we used enucleated monkey eyes, each mounted in an anterior segment holder. A perfusion system was used to control the mean IOP as well as to provide IOP sinusoidal transients (amplitude 3 mmHg, frequency 1 pulse/second) in all experiments. Measurements were carried out at seven graded mean IOPs (5, 8, 10, 20, 30, 40, and 50 mm Hg). We demonstrate that PhS-OCT is sensitive enough to image/visualize TM movement synchronous with the pulse-induced IOP transients, providing quantitative measurements of dynamic parameters such as velocity, displacement, and strain rate that are important for assessing the biomechanical compliance of the TM. We find that the largest TM displacement is in the area closest to Schlemm's canal (SC) endothelium. While maintaining constant ocular pulse amplitude, an increase of mean IOP results in a decrease of TM displacement and mean size of the SC. These results demonstrate that the PhS-OCT is a useful imaging technique capable of assessing functional properties necessary to maintain IOP in a healthy range, offering a new diagnostic alternative for glaucoma.

Sonochemical synthesis of a multi-responsive regenerable water-stable zinc(II) fluorescent probe for highly selective, sensitive and real-time sensing of benzaldehyde, ferric ion and PH.

PubMed

Wang, Xin Rui; Wang, Xing Ze; Li, Yong; Liu, Kun; Liu, Shi Xin; Du, Jing; Huang, Zhuo; Luo, Yan; Huo, Jian Zhong; Wu, Xiang Xia; Liu, Yuan Yuan; Ding, Bin

2018-06-01

In this work, a novel water-stable coordination polymer with {4 4 } network topology {[Zn(L) 2 (NO 3 ) 2 ]} n (1) (L = 4,4'-Bis(triazol-1-ylmethyl)biphenyl) has been synthesized through the hydrothermal and sonochemical approaches. 1 has been characterized by single crystal X-ray diffraction, powder X-ray diffraction (PXRD), Fourier Transform Infrared Spectroscopy, UV-vis absorption spectrum and scanning electron microscopy (SEM). PXRD patterns of the as-synthesized samples 1 have confirmed the purity of the bulky samples. In the sonochemical preparation approaches, different ultrasound irradiation power and ultrasound time were also used in order to investigate the impact factor for morphology and size of nano-structured 1. Photo-luminescence studies have revealed that 1 can efficiently distinguish Fe 3+ from Fe 2+ and other metal ions. On the other hand, 1 also can exhibit a highly sensitive, excellently selective and real-time detection of benzaldehyde and pH through photo-luminescence quenching process. As for 1, density functional theory (DFT) and time-dependent DFT (TDDFT) theory has been applied to calculate these spectroscopic data, the result agree with the experimental results for detection of benzaldehyde. Photo-luminescent recyclability results indicated 1 can be reused at least five times in the detection process. To the best of our knowledge, this is the first example of a multi-responsive regenerable luminescent sensor for highly selective, sensitive and real-time sensing of Fe 3+ over Fe 2+ , benzaldehyde and pH values. Copyright © 2018 Elsevier B.V. All rights reserved.

A generic approach to engineer antibody pH-switches using combinatorial histidine scanning libraries and yeast display.

PubMed

Schröter, Christian; Günther, Ralf; Rhiel, Laura; Becker, Stefan; Toleikis, Lars; Doerner, Achim; Becker, Janine; Schönemann, Andreas; Nasu, Daichi; Neuteboom, Berend; Kolmar, Harald; Hock, Björn

2015-01-01

There is growing interest in the fast and robust engineering of protein pH-sensitivity that aims to reduce binding at acidic pH, compared to neutral pH. Here, we describe a novel strategy for the incorporation of pH-sensitive antigen binding functions into antibody variable domains using combinatorial histidine scanning libraries and yeast surface display. The strategy allows simultaneous screening for both, high affinity binding at pH 7.4 and pH-sensitivity, and excludes conventional negative selection steps. As proof of concept, we applied this strategy to incorporate pH-dependent antigen binding into the complementary-determining regions of adalimumab. After 3 consecutive rounds of separate heavy and light chain library screening, pH-sensitive variants could be isolated. Heavy and light chain mutations were combined, resulting in 3 full-length antibody variants that revealed sharp, reversible pH-dependent binding profiles. Dissociation rate constants at pH 6.0 increased 230- to 780-fold, while high affinity binding at pH 7.4 in the sub-nanomolar range was retained. Furthermore, binding to huFcRn and thermal stability were not affected by histidine substitutions. Overall, this study emphasizes a generalizable strategy for engineering pH-switch functions potentially applicable to a variety of antibodies and further proteins-based therapeutics.

Evaluation of clinical methods for diagnosing bacterial vaginosis.

PubMed

Gutman, Robert E; Peipert, Jeffrey F; Weitzen, Sherry; Blume, Jeffrey

2005-03-01

To determine whether the current clinical criteria for diagnosing bacterial vaginosis can be simplified by using 2 clinical criteria rather than the standard 3 of 4 criteria (Amsel's criteria). This was a prospective observational study of 269 women undergoing a vaginal examination in the Women's Primary Care Center, Division of Research, or Colposcopy Clinic at Women & Infants Hospital. All 4 clinical criteria for diagnosing bacterial vaginosis were collected, and Gram stain was used as the gold standard. Sensitivity and specificity were calculated for each individual criterion, combinations of criteria, and a colorimetric pH and amine card. Receiver operating characteristic curve was generated to estimate the preferred pH and percentage of clue cells for diagnosing bacterial vaginosis. The prevalence of bacterial vaginosis in our study population was 38.7%. Vaginal pH was the most sensitive of all the criteria, at 89%, and a positive amine odor was the individual criteria with the highest specificity, at 93%. Similar specificity was seen with combinations of 2 criteria and Amsel's criteria. Receiver operating characteristic curve analysis yielded a preferred pH and percentage of clue cells of 5.0 and 20%, respectively. However, a pH of 4.5 or greater improves sensitivity with minimal loss of specificity. The clinical criteria for diagnosing bacterial vaginosis can be simplified to 2 clinical criteria without loss of sensitivity and specificity.

The pH-dependent assembly of Chaplin E from Streptomyces coelicolor.

PubMed

Dokouhaki, Mina; Hung, Andrew; Day, Li; Gras, Sally L

2017-05-01

Chaplin E, is one of five self-assembling peptides secreted by Streptomyces coelicolor that assist aerial growth by lowering the surface tension of water. Although the surface activity of a mixture of chaplin peptides has observed to depend on pH, it is unclear how the solvent environment (i.e. pH) influences the structure, assembly and subsequent functionality of these individual peptides. In this study, the conformation and fibril forming propensity of the Chaplin E peptide was assessed as a function of pH using a combination of experimental measurements and molecular dynamics simulations. At an acidic pH of 3.0, Chaplin E retained a random coil structure, whereas at the isoelectric point of 6.7 or a basic pH of 10.0, Chaplin E rapidly formed amyloid fibrils rich in β-sheet structure with high efficiency (>93%). Molecular dynamics simulations indicate the persistence of greater α-helical content at the N-terminus at high pH; this is likely partly due to the lack of electrostatic repulsion between residues His6 and Lys10. Since fibril formation was observed at high but not at low pH, we propose that the presence of an N-terminal α-helix in the monomeric form of Chaplin E is required for aggregation and conversion to β-amyloid fibrils. The pH sensitivity of Chaplin E peptide structure provides a route to control peptide assembly and may be important for the physiological function of this peptide, as a surface active agent in the transition from vegetative to aerial growth and could assist Streptomyces coelicolor in response to environmental fluctuations in pH. Copyright © 2017 Elsevier Inc. All rights reserved.

Ion sensitivity of large-area epitaxial graphene film on SiC substrate

NASA Astrophysics Data System (ADS)

Mitsuno, Takanori; Taniguchi, Yoshiaki; Ohno, Yasuhide; Nagase, Masao

2017-11-01

We investigated the intrinsic ion sensitivity of graphene field-effect transistors (FETs) fabricated by a resist-free stencil mask lithography process from a large-scale graphene film epitaxially grown on a SiC substrate. A pH-adjusted phosphate-buffered solution was used for the measurement to eliminate the interference of other ions on the graphene FET's ion sensitivity. The charge neutrality point shifted negligibly with changing pH for the pH-adjusted phosphate-buffered solution, whereas for the mixed buffer solution, it shifted toward the negative gate voltage owing to the decrease in the concentration of phthalate ions. This phenomenon is contrary to that observed in previous reports. Overall, our results indicate that the graphene film is intrinsically insensitive to ions except for those with functional groups that interact with the graphene surface.

Probabilistic evaluation of shallow groundwater resources at a hypothetical carbon sequestration site

DOE PAGES

Dai, Zhenxue; Keating, Elizabeth; Bacon, Diana H.; ...

2014-03-07

Carbon sequestration in geologic reservoirs is an important approach for mitigating greenhouse gases emissions to the atmosphere. This study first develops an integrated Monte Carlo method for simulating CO 2 and brine leakage from carbon sequestration and subsequent geochemical interactions in shallow aquifers. Then, we estimate probability distributions of five risk proxies related to the likelihood and volume of changes in pH, total dissolved solids, and trace concentrations of lead, arsenic, and cadmium for two possible consequence thresholds. The results indicate that shallow groundwater resources may degrade locally around leakage points by reduced pH and increased total dissolved solids (TDS).more » The volumes of pH and TDS plumes are most sensitive to aquifer porosity, permeability, and CO 2 and brine leakage rates. The estimated plume size of pH change is the largest, while that of cadmium is the smallest among the risk proxies. Plume volume distributions of arsenic and lead are similar to those of TDS. The scientific results from this study provide substantial insight for understanding risks of deep fluids leaking into shallow aquifers, determining the area of review, and designing monitoring networks at carbon sequestration sites.« less

pH-Responsive Triblock Copolymeric Micelles Decorated with a Cell-Penetrating Peptide Provide Efficient Doxorubicin Delivery

NASA Astrophysics Data System (ADS)

Ng, Khen Eng; Amin, Mohd Cairul Iqbal Mohd; Katas, Haliza; Amjad, Muhammad Wahab; Butt, Adeel Masood; Kesharwani, Prashant; Iyer, Arun K.

2016-12-01

This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly- l-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10-7 M) and encapsulated doxorubicin in the core region, with a 34.2% ( w/ w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7.4 to 5.0. Doxorubicin release was pH-dependent, with about 65% released at pH 5.0, and 32% at pH 7.4. Cellular uptake, assessed by confocal microscopy and flow cytometry, was enhanced by using doxorubicin-loaded CA-PEI-pArg PMs, as compared to free doxorubicin and DOX-loaded CA-PEI PMs. Moreover, 24-h incubation of these PMs with a human breast cancer cell line produced greater cytotoxicity than free doxorubicin. These results indicate that pH-responsive CA-PEI-pArg micelles could provide a versatile delivery system for targeted cancer therapy using hydrophobic drugs.

Novel Conjugated Polymers Prepared by Direct (Hetero) arylation: An Eco-Friendly Tool for Organic Electronics.

PubMed

Liu, Fuchuan; Zhang, Yangqian; Wang, Hang; Zhang, Shiming

2018-02-13

The phthalimide (PhI) moiety has been attracting more attention as an excellent acceptor building block in donor-acceptor (D-A) conjugated polymers. In this paper; three D-A conjugated polymers with or without thiocarbonyl moieties are successfully prepared by the direct (hetero)-arylation polymerization (DHAP), which is an atom efficient and facile synthetic strategy to obtain polymer materials. Compared with the traditional carbon-carbon coupling reactions, this method possesses more advantages, including: fewer synthetic steps, avoidance of the preparation of the organometallic reagents, higher atom economy and fewer toxic byproducts, better compatibility with chemically sensitive functional groups and so on. All three of these designed PhI-based polymers exhibited favourable optoelectronic and thermal performance. The optical, thermodynamic and electrochemical properties of the synthesized polymers were systematically investigated using ultraviolet-visible (UV-vis) spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and cyclic voltammetry (CV). The results of these three polymers indicated that thionation of the carbonyl was a highly effective methods to improve the properties of PhI-based polymers; and provided impetus for the development of thionated PhI derivatives for organic electronic applications.

PhenoWorld: a new paradigm to screen rodent behavior

PubMed Central

Castelhano-Carlos, M; Costa, P S; Russig, H; Sousa, N

2014-01-01

Modeling depression in animals has inherent complexities that are augmented by intrinsic difficulties to measure the characteristic features of the disorder. Herein, we describe the PhenoWorld (PhW), a new setting in which groups of six rats lived in an ethological enriched environment, and have their feeding, locomotor activity, sleeping and social behavior automatically monitored. A battery of emotional and cognitive tests was used to characterize the behavioral phenotype of animals living in the PhW and in standard conditions (in groups of six and two rats), after exposure to an unpredictable chronic mild stress paradigm (uCMS) and antidepressants. Data reveal that animals living in the PhW displayed similar, but more striking, behavioral differences when exposed to uCMS, such as increased behavioral despair shown in the forced swimming test, resting/sleep behavior disturbances and reduced social interactions. Moreover, several PhW-cage behaviors, such as spontaneous will to go for food or exercise in running wheels, proved to be sensitive indicators of depressive-like behavior. In summary, this new ethological enriched paradigm adds significant discriminative power to screen depressive-like behavior, in particularly rodent's hedonic behavior. PMID:26126181

A Simple Experiment for Visualizing Diffusion

ERIC Educational Resources Information Center

Helseth, L. E.

2011-01-01

We propose a simple and fascinating experiment for studying diffusion in gels using a pH-sensitive dye. By doping agar with methyl red, we obtain a gel which rapidly reacts to changes in pH by changing its absorption spectrum. The pH gradients can be followed using a digital camera, and we demonstrate here that the pH-sensitive colour changes can…

A visual assay and spectrophotometric determination of LLM-105 explosive using detection of gold nanoparticle aggregation at two pH values.

PubMed

He, Yi; Cheng, Yang

2016-08-01

We report a simple, rapid, and sensitive assay for visual and spectrophotometric detection of the 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) explosive. The assay is based on different interactions between LLM-105 and gold nanoparticle (AuNP) dispersions at two pH values, leading to the formation of dispersed or aggregated AuNPs. Two AuNP dispersions at two pH values were applied to recognize and detect LLM-105 instead of traditional AuNP dispersion under an aptotic pH to improve the anti-interference ability. The developed assay showed excellent sensitivity with a detection limit of 3 ng/mL, and the presence of as low as 0.2 μg/mL LLM-105 can be directly detected with the bare eye. This sensitivity is about six orders of magnitude higher than that of the reported traditional assays. Additionally, the assay exhibited good selectivity toward LLM-105 over other explosives, sulfur-containing compounds, and amines. Graphical abstract A simple, sensitive, and selective assay for LLM-105 was developed based on the pH-dependent interaction between the LLM-105 explosive and gold nanoparticle dispersion.

pH responsive label-assisted click chemistry triggered sensitivity amplification for ultrasensitive electrochemical detection of carbohydrate antigen 24-2.

PubMed

Zheng, Yun; Zhao, Lihua; Ma, Zhanfang

2018-05-15

Sensitivity amplification strategy by implementing click chemistry in the construction of biosensing interface can efficiently improve the performance of immunosensor. Herein, we developed a sandwich-type amperometric immunosensor for ultrasensitive detection of carbohydrate antigen 24-2 (CA 242) based on pH responsive label-assisted click chemistry triggered sensitivity amplification strategy. The sensitivity of amperometric immunosensor relies on the current response differences (ΔI) caused by per unit concentration target analyte. The pH responsive Cu 2+ -loaded polydopamine (CuPDA) particles conjugated with detection antibodies were employed as labels, which can release Cu(II) ions by regulating pH. In the presence of ascorbic acid (reductant), Cu(II) ions were reduced to Cu(I) ions. Azide-functionalized double-stranded DNA (dsDNA) as signal enhancer was immobilized on the substrate through Cu + -catalyzed azide/alkyne cycloaddition reaction. With the help of the click reaction, the ΔI caused by target was elevated prominently, resulting in sensitivity amplification of the immunosensor. Under optimal condition, the proposed immunosensor exhibited excellent performance with linear range from 0.0001 to 100 U mL -1 and ultralow detection limit of 20.74 μU mL -1 . This work successfully combines click chemistry with pH-responsive labels in sandwich-type amperometric immunosensor, providing a promising sensitivity amplification strategy to construct immunosensing platform for analysis of other tumor marker. Copyright © 2018 Elsevier B.V. All rights reserved.

Anchoring antibodies to membranes using a diphtheria toxin T domain-ZZ fusion protein as a pH sensitive membrane anchor.

PubMed

Nizard, P; Liger, D; Gaillard, C; Gillet, D

1998-08-14

We have constructed a fusion protein, T-ZZ, in which the IgG-Fc binding protein ZZ was fused to the C-terminus of the diphtheria toxin transmembrane domain (T domain). While soluble at neutral pH, T-ZZ retained the capacity of the T domain to bind to phospholipid membranes at acidic pH. Once anchored to the membrane, the ZZ part of the protein was capable of binding mouse monoclonal or rabbit polyclonal IgG. Our results show that the T-ZZ protein can function as a pH sensitive membrane anchor for the linkage of IgG to the membrane of lipid vesicles, adherent and non-adherent cells.

The pH Stability of Foot-and-Mouth Disease Virus Particles Is Modulated by Residues Located at the Pentameric Interface and in the N Terminus of VP1.

PubMed

Caridi, Flavia; Vázquez-Calvo, Angela; Sobrino, Francisco; Martín-Acebes, Miguel A

2015-05-01

The picornavirus foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects important livestock species. The FMDV capsid is highly acid labile, and viral particles lose infectivity due to their disassembly at pH values slightly below neutrality. This acid sensitivity is related to the mechanism of viral uncoating and genome penetration from endosomes. In this study, we have analyzed the molecular basis of FMDV acid-induced disassembly by isolating and characterizing a panel of novel FMDV mutants differing in acid sensitivity. Amino acid replacements altering virion stability were preferentially distributed in two different regions of the capsid: the N terminus of VP1 and the pentameric interface. Even more, the acid labile phenotype induced by a mutation located at the pentameric interface in VP3 could be compensated by introduction of an amino acid substitution in the N terminus of VP1. These results indicate that the acid sensitivity of FMDV can be considered a multifactorial trait and that virion stability is the fine-tuned product of the interaction between residues from different capsid proteins, in particular those located within the N terminus of VP1 or close to the pentameric interface. The viral capsid protects the viral genome from environmental factors and contributes to virus dissemination and infection. Thus, understanding of the molecular mechanisms that modulate capsid stability is of interest for the basic knowledge of the biology of viruses and as a tool to improve the stability of conventional vaccines based on inactivated virions or empty capsids. Using foot-and-mouth disease virus (FMDV), which displays a capsid with extreme acid sensitivity, we have performed a genetic study to identify the molecular determinants involved in capsid stability. A panel of FMDV mutants with differential sensitivity to acidic pH was generated and characterized, and the results showed that two different regions of FMDV capsid contribute to modulating viral particle stability. These results provide new insights into the molecular mechanisms of acid-mediated FMDV uncoating. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Migration of 75Se(IV) in crushed Beishan granite: Effects of the iron content.

PubMed

He, Jiangang; Ma, Bin; Kang, Mingliang; Wang, Chunli; Nie, Zhe; Liu, Chunli

2017-02-15

The diffusion of selenite (labeled with 75 Se) in compacted Beishan granite (BsG) was investigated using the in-diffusion capillary method at pH values from ∼2.0 to ∼11.0 under oxic and anoxic conditions. The results indicate that the apparent diffusion coefficient (D a ) values of selenite in BsG always reached the minimum at approximately pH 5. Unexpectedly, the D a values under oxic conditions are nearly one order of magnitude lower than those under the anoxic conditions. Further characterization reveals the existence of redox-sensitive Fe(II)-containing components, which can be responsible for the great difference in D a values. Fe(2p) X-ray photoelectron spectroscopy (XPS) results show that more Fe(III)-oxyhydroxide coating is formed on the granite's surface under aerobic conditions than is formed under anaerobic conditions. Correspondingly, Se(3d) spectra indicate that more selenium is sorbed under oxic conditions, and the sorbed amount always reached the maximum at pH values from ∼4 to ∼5. A linear combination fit of X-ray absorption near edge structure (XANES) spectroscopy data revealed that Se(0) was formed under anoxic condition and that selenite preferred to form inner-sphere complexes with Fe(III)-oxyhydroxide. Overall, this study indicates that natural Fe-bearing minerals can greatly attenuate selenite diffusion and the retardation would be enhanced under aerobic conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Isolation and Properties of Enterococcus hirae Mutants Defective in the Potassium/Proton Antiport System

PubMed Central

Kakinuma, Yoshimi; Igarashi, Kazuei

1999-01-01

A K+/H+ antiporter regulates cytoplasmic pH in Enterococcus hirae growing at alkaline pH. Mutants defective in this antiport activity were alkaline pH sensitive. One mutant, Pop1, lacked both K+/methylamine exchange at pH 9.5 and concomitant acidification of cytoplasmic pH. Pop1 grew well at pHs below 8 but did not at pHs above 9, conditions under which cytoplasmic pH was not fully acidified. PMID:10383981

Occurrence of killer Candida glabrata clinical isolates

PubMed Central

Arroyo-Helguera, O; Penas Alejandro, De Las; Irene, Castaño

2012-01-01

In this work we characterized the occurrence of killer activity in 64 Candida glabrata clinical isolates under different conditions. We found that only 6.25 % of the clinical isolates tested were positive for killer activity against a Saccharomyces cerevisiae W303 sensitive strain. Sensitivity of killer activity to different values of pH and temperatures was analyzed. We found that the killer activity presented by all isolates was resistant to every pH and temperature tested, although optimal activity was found at a range of pH values from 4 to 7 and at 37°C. We did not observe extrachromosomal genetic elements associated with killer activity in any of the positive C. glabrata isolates. The killer effect was due to a decrease in viability and DNA fragmentation in sensitive yeast. PMID:24031902

Evanescent Properties of Optical Diffraction from 2-Dimensional Hexagonal Photonic Crystals and Their Sensor Applications.

PubMed

Liao, Yu-Yang; Chen, Yung-Tsan; Chen, Chien-Chun; Huang, Jian-Jang

2018-04-03

The sensitivity of traditional diffraction grating sensors is limited by the spatial resolution of the measurement setup. Thus, a large space is required to improve sensor performance. Here, we demonstrate a compact hexagonal photonic crystal (PhC) optical sensor with high sensitivity. PhCs are able to diffract optical beams to various angles in azimuthal space. The critical wavelength that satisfies the phase matching or becomes evanescent was used to benchmark the refractive index of a target analyte applied on a PhC sensor. Using a glucose solution as an example, our sensor demonstrated very high sensitivity and a low limit of detection. This shows that the diffraction mechanism of hexagonal photonic crystals can be used for sensors when compact size is a concern.

Metabolic Study of Cancer Cells Using a pH Sensitive Hydrogel Nanofiber Light Addressable Potentiometric Sensor.

PubMed

Shaibani, Parmiss Mojir; Etayash, Hashem; Naicker, Selvaraj; Kaur, Kamaljit; Thundat, Thomas

2017-01-27

We report a simple, fast, and cost-effective approach that measures cancer cell metabolism and their response to anticancer drugs in real time. Using a Light Addressable Potentiometric Sensor integrated with pH sensitive hydrogel nanofibers (NF-LAPS), we detect localized changes in pH of the media as cancer cells consume glucose and release lactate. NF-LAPS shows a sensitivity response of 74 mV/pH for cancer cells. Cancer cells (MDA MB231) showed a response of ∼0.4 unit change in pH compared to virtually no change observed for normal cells (MCF10A). We also observed a drop in pH for the multidrug-resistant cancer cells (MDA-MB-435MDR) in the presence of doxorubicin. However, inhibition of the metabolic enzymes such as hexokinase and lactate dehydrogenase-A suggested an improvement in the efficacy of doxorubicin by decreasing the level of acidification. This approach, based on extracellular acidification, enhances our understanding of cancer cell metabolic modes and their response to chemotherapies, which will help in the development of better treatments, including choice of drugs and dosages.

Extracellular pH monitoring for use in closed-loop vagus nerve stimulation

NASA Astrophysics Data System (ADS)

Cork, Simon C.; Eftekhar, Amir; Mirza, Khalid B.; Zuliani, Claudio; Nikolic, Konstantin; Gardiner, James V.; Bloom, Stephen R.; Toumazou, Christofer

2018-02-01

Objective. Vagal nerve stimulation (VNS) has shown potential benefits for obesity treatment; however, current devices lack physiological feedback, which limit their efficacy. Changes in extracellular pH (pHe) have shown to be correlated with neural activity, but have traditionally been measured with glass microelectrodes, which limit their in vivo applicability. Approach. Iridium oxide has previously been shown to be sensitive to fluctuations in pH and is biocompatible. Iridium oxide microelectrodes were inserted into the subdiaphragmatic vagus nerve of anaesthetised rats. Introduction of the gut hormone cholecystokinin (CCK) or distension of the stomach was used to elicit vagal nerve activity. Main results. Iridium oxide microelectrodes have sufficient pH sensitivity to readily detect changes in pHe associated with both CCK and gastric distension. Furthermore, a custom-made Matlab script was able to use these changes in pHe to automatically trigger an implanted VNS device. Significance. This is the first study to show pHe changes in peripheral nerves in vivo. In addition, the demonstration that iridium oxide microelectrodes are sufficiently pH sensitive as to measure changes in pHe associated with physiological stimuli means they have the potential to be integrated into closed-loop neurostimulating devices.

Molecular mechanism of a COOH-terminal gating determinant in the ROMK channel revealed by a Bartter's disease mutation

PubMed Central

Flagg, Thomas P; Yoo, Dana; Sciortino, Christopher M; Tate, Margaret; Romero, Michael F; Welling, Paul A

2002-01-01

The ROMK subtypes of inward-rectifier K+ channels mediate potassium secretion and regulate NaCl reabsorption in the kidney. Loss-of-function mutations in this pH-sensitive K+ channel cause Bartter's disease, a familial salt wasting nephropathy. One disease-causing mutation truncates the extreme COOH-terminus and induces a closed gating conformation. Here we identify a region within the deleted domain that plays an important role in pH-dependent gating. The domain contains a structural element that functionally interacts with the pH sensor in the cytoplasmic NH2-terminus to set a physiological range of pH sensitivity. Removal of the domain shifts the pKa towards alkaline pH values, causing channel inactivation under physiological conditions. Suppressor mutations within the pH sensor rescued channel gating and trans addition of the cognate peptide restored pH sensitivity. A specific interdomain interaction was revealed in an in vitro protein-protein binding assay between the NH2- and COOH-terminal cytoplasmic domains expressed as bacterial fusion proteins. These results provide new insights into the molecular mechanisms underlying Kir channel regulation and channel gating defects that are associated with Bartter's disease. PMID:12381810

Quantifying Laryngopharyngeal Reflux in Singers: Perceptual and Objective Findings

PubMed Central

Lewis, Vicki M.

2017-01-01

This study examines the relationship between laryngopharyngeal reflux (LPR) symptoms and oropharyngeal pH levels in singers. We hypothesized that reported symptoms would correlate with objective measures of pH levels from the oropharynx, including the number and total duration of reflux episodes. Twenty professional/semiprofessional singers completed the Reflux Symptom Index (RSI) and underwent oropharyngeal pH monitoring. Mild, moderate, or severe pH exposure was recorded during oropharyngeal pH monitoring. Correlations were performed to examine potential relationships between reflux symptoms and duration of LPR episodes. Symptom severity did not correlate with pH levels; however, we found a number of covariances of interest. Large sample sizes are necessary to determine if true correlations exist. Our results suggest that singers may exhibit enhanced sensitivity to LPR and may therefore manifest symptoms, even in response to subtle changes in pH. This study emphasizes the importance of sensitive and objective measures of reflux severity as well as consideration of the cumulative time of reflux exposure in addition to the number of reflux episodes. PMID:29098155

Determination of phenformin hydrochloride using molecular imprinting technology coupled with flow-injection chemiluminescence.

PubMed

Liu, Zhenbo; Jia, Fengyan; Wang, Wenwen; Wang, Cuixia; Liu, Yongming

2012-01-01

A novel method was developed using molecular imprinting technology (MIT) coupled with flow-injection chemiluminescence (FI-CL) for highly sensitive detection of phenformin hydrochloride (PH). The phenformin imprinted polymer was synthesized with methacrylic acid (MAA) as a functional monomer and ethylene glycol dimethacrylate (EGDMA) as a cross-linker. Newly synthesized molecularly imprinted polymer (MIP) particles were packed into a column as a selective recognition element for determination of PH. A CL method for the determination of PH was developed based on the CL reaction of PH with N-bromosuccinimide sensitized by eosin Y in basic media. The optimization of detection conditions was investigated. The CL intensity responded linearly to the concentration of PH in the range 0.09-2.0 µg/mL, with a correlation coefficient of 0.9920. The detection limit was 0.031 µg/mL. The relative standard deviation for the determination of 1.0 µg/mL PH solution was 1.0% (n = 11). The method was applied to the determination of PH in urine samples, with satisfactory results. Copyright © 2011 John Wiley & Sons, Ltd.

pH sensitive quantum dot-anthraquinone nanoconjugates

NASA Astrophysics Data System (ADS)

Ruedas-Rama, Maria Jose; Hall, Elizabeth A. H.

2014-05-01

Semiconductor quantum dots (QDs) have been shown to be highly sensitive to electron or charge transfer processes, which may alter their optical properties. This feature can be exploited for different sensing applications. Here, we demonstrate that QD-anthraquinone conjugates can function as electron transfer-based pH nanosensors. The attachment of the anthraquinones on the surface of QDs results in the reduction of electron hole recombination, and therefore a quenching of the photoluminescence intensity. For some anthraquinone derivatives tested, the quenching mechanism is simply caused by an electron transfer process from QDs to the anthraquinone, functioning as an electron acceptor. For others, electron transfer and energy transfer (FRET) processes were found. A detailed analysis of the quenching processes for CdSe/ZnS QD of two different sizes is presented. The photoluminescence quenching phenomenon of QDs is consistent with the pH sensitive anthraquinone redox chemistry. The resultant family of pH nanosensors shows pKa ranging ˜5-8, being ideal for applications of pH determination in physiological samples like blood or serum, for intracellular pH determination, and for more acidic cellular compartments such as endosomes and lysosomes. The nanosensors showed high selectivity towards many metal cations, including the most physiologically important cations which exist at high concentration in living cells. The reversibility of the proposed systems was also demonstrated. The nanosensors were applied in the determination of pH in samples mimicking the intracellular environment. Finally, the possibility of incorporating a reference QD to achieve quantitative ratiometric measurements was investigated.

Plasmonic gold nanostar for biomedical sensing

NASA Astrophysics Data System (ADS)

Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew M.; Vo-Dinh, Tuan

2014-03-01

Cancer has become one of most significant death reasons and causes approximately 7.9 million human deaths worldwide each year. The challenge to detect cancer at an early stage makes cancer-related biomarkers sensing attract more and more research interest and efforts. Surface-enhanced Raman scattering (SERS) provides a promising method for various biomarkers (DNA, RNA, protein, et al.) detection due to its high sensitivity, specificity and capability for multiple analytes detection. Raman spectroscopy is a non-destructive photon-scattering technique, which provides molecule-specific information on molecular vibrational energy levels. SERS takes advantage of plasmonic effects and can enhance Raman signal up to 1015 at "hot spots". Due to its excellent sensitivity, SERS has been capable of achieving single-molecule detection limit. Local pH environment has been identified to be a potential biomarker for cancer diagnosis since solid cancer contains highly acidic environments. A near-infrared (NIR) SERS nanoprobe based on gold nanostars for pH sensing is developed for future cancer detection. Near-infrared (NIR) light is more suitable for in vivo applications because of its low attenuation rate and tissue auto fluorescence. SERS spectrum of pH reporter under various pH environments is monitored and used for pH sensing. Furthermore, density functional theory (DFT) calculation is performed to investigate Raman spectra changes with pH at the molecular level. The study demonstrates that SERS is a sensitive tool to monitor minor molecular structural changes due to local pH environment for cancer detection.

High sensitivity pH sensing on the BEOL of industrial FDSOI transistors

NASA Astrophysics Data System (ADS)

Rahhal, Lama; Ayele, Getenet Tesega; Monfray, Stéphane; Cloarec, Jean-Pierre; Fornacciari, Benjamin; Pardoux, Eric; Chevalier, Celine; Ecoffey, Serge; Drouin, Dominique; Morin, Pierre; Garnier, Philippe; Boeuf, Frederic; Souifi, Abdelkader

2017-08-01

In this work we demonstrate the use of Fully Depleted Silicon On Insulator (FDSOI) transistors as pH sensors with a 23 nm silicon nitride sensing layer built in the Back-End-Of-Line (BEOL). The back end process to deposit the sensing layer and fabricate the electrical structures needed for testing is detailed. A series of tests employing different pH buffer solutions has been performed on transistors of different geometries, controlled via the back gate. The main findings show a shift of the drain current (ID) as a function of the back gate voltage (VB) when different pH buffer solutions are probed in the range of pH 6 to pH 8. This shift is observed at VB voltages swept from 0 V to 3 V, demonstrating the sensor operation at low voltage. A high sensitivity of up to 250 mV/pH unit (more than 4-fold larger than Nernstian response) is observed on FDSOI MOS transistors of 0.06 μm gate length and 0.08 μm gate width. She is currently working as a Postdoctoral researcher at Institut des nanotechnologies de Lyon in collaboration with STMicroelectronics and Université de Sherbrook (Canada) working on ;Integration of ultra-low-power gas and pH sensors with advanced technologies;. Her research interest includes selection, machining, optimisation and electrical characterisation of the sensitive layer for a low power consumption gas sensor based on advanced MOS transistors.

Intelligent pH indicator film composed of agar/potato starch and anthocyanin extracts from purple sweet potato.

PubMed

Choi, Inyoung; Lee, Jun Young; Lacroix, Monique; Han, Jaejoon

2017-03-01

A new colorimetric pH indicator film was developed using agar, potato starch, and natural dyes extracted from purple sweet potato, Ipomoea batatas. Both agar and potato starch are solid matrices used to immobilize natural dyes, anthocyanins. The ultraviolet-visible (UV-vis) spectrum of anthocyanin extract solutions and agar/potato starch films with anthocyanins showed color variations to different pH values (pH 2.0-10.0). Fourier transform infrared (FT-IR) and UV-vis region spectra showed compatibility between agar, starch, and anthocyanin extracts. Color variations of pH indicator films were measured by a colorimeter after immersion in different pH buffers. An application test was conducted for potential use as a meat spoilage sensor. The pH indicator films showed pH changes and spoilage point of pork samples, changing from red to green. Therefore, the developed pH indicator films could be used as a diagnostic tool for the detection of food spoilage. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhancing cisplatin delivery to hepatocellular carcinoma HepG2 cells using dual sensitive smart nanocomposite.

PubMed

Salimi, Farzaneh; Dilmaghani, Karim Akbari; Alizadeh, Effat; Akbarzadeh, Abolfazl; Davaran, Soodabeh

2017-07-07

Targeted entrance and accumulation of higher doses of drugs into malignant cells could help in intensification of tumor specific cytotoxicity. A dual-responsive nanogel, poly(N-isopropylacrylamide)-co-poly(N,N-(dimethylamino)ethyl methacrylate) [P(NIPAM-co-DMA)] containing N-isopropylacrylamide (NIPAM) as thermoresponsive monomer and N,N-(dimethylamino)ethyl methacrylate (DMA) as pH-responsive monomer and methylene-bis-acrylamide (MBA) as cross-linking agent, was synthesized by free radical emulsion polymerization. Cisplatin along with magnetic Fe 3 O 4 nanoparticles (MNPs) was loaded into the nanogel by physically embedding the magnetic nanoparticles into hydrogel matrix after gelation to obtain drug-loaded magnetic nanocomposite [P(NIPAM-co-DMA)/Fe 3 O 4 ]. Drug loading efficiencies and drug release profiles of cisplatin-loaded P(NIPAM-co-DMA) nanogel and P(NIPAM-co-DMA)/Fe 3 O 4 nanocomposite were evaluated in vitro for controlled drug delivery in different temperature and pH conditions. Finally, the anticancer activity of P(NIPAM-co-DMA)/Fe 3 O 4 nanocomposite on human liver HepG2 cells was evaluated. Nanogel and nanocomposite showed significantly higher (p < .05) cisplatin release at 40 °C compared to 37 °C and at pH 5.7 compared to pH 7.4, demonstrating their temperature and pH sensitivity, respectively. The cytotoxicity assay of drug free nanogel on HepG2 cell line indicated that the nanogel is biocompatible and suitable as drug carrier. Moreover, MTT assay revealed that the cisplatin-loaded nanocomposite represented significant superior cytotoxicity (p < .05) to HepG2 cells as compared with free cisplatin.

Rising CO2 Levels Will Intensify Phytoplankton Blooms in Eutrophic and Hypertrophic Lakes

PubMed Central

Verspagen, Jolanda M. H.; Van de Waal, Dedmer B.; Finke, Jan F.; Visser, Petra M.; Van Donk, Ellen; Huisman, Jef

2014-01-01

Harmful algal blooms threaten the water quality of many eutrophic and hypertrophic lakes and cause severe ecological and economic damage worldwide. Dense blooms often deplete the dissolved CO2 concentration and raise pH. Yet, quantitative prediction of the feedbacks between phytoplankton growth, CO2 drawdown and the inorganic carbon chemistry of aquatic ecosystems has received surprisingly little attention. Here, we develop a mathematical model to predict dynamic changes in dissolved inorganic carbon (DIC), pH and alkalinity during phytoplankton bloom development. We tested the model in chemostat experiments with the freshwater cyanobacterium Microcystis aeruginosa at different CO2 levels. The experiments showed that dense blooms sequestered large amounts of atmospheric CO2, not only by their own biomass production but also by inducing a high pH and alkalinity that enhanced the capacity for DIC storage in the system. We used the model to explore how phytoplankton blooms of eutrophic waters will respond to rising CO2 levels. The model predicts that (1) dense phytoplankton blooms in low- and moderately alkaline waters can deplete the dissolved CO2 concentration to limiting levels and raise the pH over a relatively wide range of atmospheric CO2 conditions, (2) rising atmospheric CO2 levels will enhance phytoplankton blooms in low- and moderately alkaline waters with high nutrient loads, and (3) above some threshold, rising atmospheric CO2 will alleviate phytoplankton blooms from carbon limitation, resulting in less intense CO2 depletion and a lesser increase in pH. Sensitivity analysis indicated that the model predictions were qualitatively robust. Quantitatively, the predictions were sensitive to variation in lake depth, DIC input and CO2 gas transfer across the air-water interface, but relatively robust to variation in the carbon uptake mechanisms of phytoplankton. In total, these findings warn that rising CO2 levels may result in a marked intensification of phytoplankton blooms in eutrophic and hypertrophic waters. PMID:25119996

High Sensitivity pH Sensor Based on Porous Silicon (PSi) Extended Gate Field-Effect Transistor

PubMed Central

Al-Hardan, Naif H.; Abdul Hamid, Muhammad Azmi; Ahmed, Naser M.; Jalar, Azman; Shamsudin, Roslinda; Othman, Norinsan Kamil; Kar Keng, Lim; Chiu, Weesiong; Al-Rawi, Hamzah N.

2016-01-01

In this study, porous silicon (PSi) was prepared and tested as an extended gate field-effect transistor (EGFET) for pH sensing. The prepared PSi has pore sizes in the range of 500 to 750 nm with a depth of approximately 42 µm. The results of testing PSi for hydrogen ion sensing in different pH buffer solutions reveal that the PSi has a sensitivity value of 66 mV/pH that is considered a super Nernstian value. The sensor considers stability to be in the pH range of 2 to 12. The hysteresis values of the prepared PSi sensor were approximately 8.2 and 10.5 mV in the low and high pH loop, respectively. The result of this study reveals a promising application of PSi in the field for detecting hydrogen ions in different solutions. PMID:27338381

High Sensitivity pH Sensor Based on Porous Silicon (PSi) Extended Gate Field-Effect Transistor.

PubMed

Al-Hardan, Naif H; Abdul Hamid, Muhammad Azmi; Ahmed, Naser M; Jalar, Azman; Shamsudin, Roslinda; Othman, Norinsan Kamil; Kar Keng, Lim; Chiu, Weesiong; Al-Rawi, Hamzah N

2016-06-07

In this study, porous silicon (PSi) was prepared and tested as an extended gate field-effect transistor (EGFET) for pH sensing. The prepared PSi has pore sizes in the range of 500 to 750 nm with a depth of approximately 42 µm. The results of testing PSi for hydrogen ion sensing in different pH buffer solutions reveal that the PSi has a sensitivity value of 66 mV/pH that is considered a super Nernstian value. The sensor considers stability to be in the pH range of 2 to 12. The hysteresis values of the prepared PSi sensor were approximately 8.2 and 10.5 mV in the low and high pH loop, respectively. The result of this study reveals a promising application of PSi in the field for detecting hydrogen ions in different solutions.

Identifying Candidate Genes that Underlie Cellular pH Sensitivity in Serotonin Neurons Using Transcriptomics: A Potential Role for Kir5.1 Channels

PubMed Central

Puissant, Madeleine M.; Mouradian, Gary C.; Liu, Pengyuan; Hodges, Matthew R.

2017-01-01

Ventilation is continuously adjusted by a neural network to maintain blood gases and pH. Acute CO2 and/or pH regulation requires neural feedback from brainstem cells that encode CO2/pH to modulate ventilation, including but not limited to brainstem serotonin (5-HT) neurons. Brainstem 5-HT neurons modulate ventilation and are stimulated by hypercapnic acidosis, the sensitivity of which increases with increasing postnatal age. The proper function of brainstem 5-HT neurons, particularly during post-natal development is critical given that multiple abnormalities in the 5-HT system have been identified in victims of Sudden Infant Death Syndrome. Here, we tested the hypothesis that there are age-dependent increases in expression of pH-sensitive ion channels in brainstem 5-HT neurons, which may underlie their cellular CO2/pH sensitivity. Midline raphe neurons were acutely dissociated from neonatal and mature transgenic SSePet-eGFP rats [which have enhanced green fluorescent protein (eGFP) expression in all 5-HT neurons] and sorted with fluorescence-activated cell sorting (FACS) into 5-HT-enriched and non-5-HT cell pools for subsequent RNA extraction, cDNA library preparation and RNA sequencing. Overlapping differential expression analyses pointed to age-dependent shifts in multiple ion channels, including but not limited to the pH-sensitive potassium ion (K+) channel genes kcnj10 (Kir4.1), kcnj16 (Kir5.1), kcnk1 (TWIK-1), kcnk3 (TASK-1) and kcnk9 (TASK-3). Intracellular contents isolated from single adult eGFP+ 5-HT neurons confirmed gene expression of Kir4.1, Kir5.1 and other K+ channels, but also showed heterogeneity in the expression of multiple genes. 5-HT neuron-enriched cell pools from selected post-natal ages showed increases in Kir4.1, Kir5.1, and TWIK-1, fitting with age-dependent increases in Kir4.1 and Kir5.1 protein expression in raphe tissue samples. Immunofluorescence imaging confirmed Kir5.1 protein was co-localized to brainstem neurons and glia including 5-HT neurons as expected. However, Kir4.1 protein expression was restricted to glia, suggesting that it may not contribute to 5-HT neuron pH sensitivity. Although there are caveats to this approach, the data suggest that pH-sensitive Kir5.1 channels may underlie cellular CO2/pH chemosensitivity in brainstem 5-HT neurons. PMID:28270749

The influence of pH on the in vitro permeation of rhodium through human skin.

PubMed

Jansen Van Rensburg, Sané; Franken, Anja; Du Plessis, Jeanetta; Du Plessis, Johannes Lodewykus

2017-06-01

Workers in precious metals refineries are at risk of exposure to salt compounds of the platinum group metals through inhalation, as well as through the skin. Rhodium salt permeation through the skin has previously been proven using rhodium trichloride (RhCl 3 ) dissolved in synthetic sweat at a pH of 6.5. However, the skin surface pH of refinery workers may be lower than 6.5. The aim of this study was to investigate the influence of pH 6.5 and 4.5 on the in vitro permeation of rhodium through intact Caucasian skin using Franz diffusion cells. A concentration of 0.3 mg mL -1 rhodium was used and analyses were performed using inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectrometry. Results indicated a cumulative increase in permeation over 24 h. Rhodium permeation after 12 h was significantly greater at pH 4.5 (1.56 ± 0.24 ng cm -2 ) than at 6.5 (0.85 ± 0.13 ng cm -2 ; p = 0.02). At both pH levels, there was a highly significant difference ( p < 0.01) between the mass of rhodium remaining in the skin (1428.68 ± 224.67 ng cm -2 at pH 4.5 and 1029.90 ± 115.96 ng cm -2 at pH 6.5) and the mass that diffused through (0.88 ± 0.17 ng cm -2 at pH 4.5 and 0.62 ± 0.10 ng cm -2 at pH 6.5). From these findings, it is evident that an acidic working environment or low skin surface pH may enhance permeation of rhodium salts, contributing to sensitization and adverse health effects.

Development of a pH sensor using nanoporous nanostructures of NiO.

PubMed

Ibupoto, Z H; Khun, K; Willander, M

2014-09-01

Glass is the conventional material used in pH electrodes to monitor pH in various applications. However, the glass-based pH electrode has some limitations for particular applications. The glass sensor is limited in the use of in vivo biomedical, clinical or food applications because of the brittleness of glass, its large size, the difficulty in measuring small volumes and the absence of deformation (inflexibility). Nanostructure-based pH sensors are very sensitive, reliable, fast and applicable towards in vivo measurements. In this study, nanoporous NiO nanostructures are synthesized on a gold-coated glass substrate by a hydrothermal route using poly(vinyl alcohol) (PVA) as a stabilizer. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques were used for the morphological and crystalline studies. The grown NiO nanostructures are uniform and dense, and they possess good crystallinity. A pH sensor based on these NiO nanostructures was developed by testing the different pH values from 2-12 of phosphate buffered saline solution. The proposed pH sensor showed robust sensitivity of -43.74 ± 0.80 mV/pH and a quick response time of less than 10 s. Moreover, the repeatability, reproducibility and stability of the presented pH sensor were also studied.

pH induced contrast in viscoelasticity imaging of biopolymers

PubMed Central

Yapp, R D; Insana, M F

2009-01-01

Understanding contrast mechanisms and identifying discriminating features is at the heart of diagnostic imaging development. This report focuses on how pH influences the viscoelastic properties of biopolymers to better understand the effects of extracellular pH on breast tumour elasticity imaging. Extracellular pH is known to decrease as much as 1 pH unit in breast tumours, thus creating a dangerous environment that increases cellular mutatation rates and therapeutic resistance. We used a gelatin hydrogel phantom to isolate the effects of pH on a polymer network with similarities to the extracellular matrix in breast stroma. Using compressive unconfined creep and stress relaxation measurements, we systematically measured the viscoelastic features sensitive to pH by way of time domain models and complex modulus analysis. These results are used to determine the sensitivity of quasi-static ultrasonic elasticity imaging to pH. We found a strong elastic response of the polymer network to pH, such that the matrix stiffness decreases as pH was reduced, however the viscous response of the medium to pH was negligible. While physiological features of breast stroma such as proteoglycans and vascular networks are not included in our hydrogel model, observations in this study provide insight into viscoelastic features specific to pH changes in the collagenous stromal network. These observations suggest that the large contrast common in breast tumours with desmoplasia may be reduced under acidic conditions, and that viscoelastic features are unlikely to improve discriminability. PMID:19174599

Mobilization and acquisition of sparingly soluble P-Sources by Brassica cultivars under P-starved environment II. Rhizospheric pH changes, redesigned root architecture and pi-uptake kinetics.

PubMed

Akhtar, Muhammad Shahbaz; Oki, Yoko; Adachi, Tadashi

2009-11-01

Non-mycorrhizal Brassica does not produce specialized root structures such as cluster or dauciform roots but is an effective user of P compared with other crops. In addition to P-uptake, utilization and remobilization activity, acquisition of orthophosphate (Pi) from extracellular sparingly P-sources or unavailable bound P-forms can be enhanced by biochemical rescue mechanisms such copious H(+)-efflux and/or carboxylates exudation into rhizosphere by roots via plasmalemma H(+) ATPase and anion channels triggered by P-starvation. To visualize the dissolution of sparingly soluble Ca-phosphate (Ca-P), newly formed Ca-P was suspended in agar containing other essential nutrients. With NH(4)(+) applied as the N source, the precipitate dissolved in the root vicinity can be ascribed to rhizosphere acidification, whereas no dissolution occurred with nitrate nutrition. To observe in situ rhizospheric pH changes, images were recorded after embedding the roots in agar containing bromocresol purple as a pH indicator. P-tolerant cultivar showed a greater decrease in pH than the sensitive cultivar in the culture media (the appearance of typical patterns of various colors of pH indicator in the root vicinity), and at stress P-level this acidification was more prominent. In experiment 2, low P-tolerant class-I cultivars (Oscar and Con-II) showed a greater decrease in solution media pH than low P-sensitive class-II (Gold Rush and RL-18) cultivars, and P-contents of the cultivars was inversely related to decrease in culture media pH. To elucidate P-stress-induced remodeling and redesigning in a root architectural system, cultivars were grown in rhizoboxes in experiment 3. The elongation rates of primary roots increased as P-supply increased, but the elongation rates of the branched zones of primary roots decreased. The length of the lateral roots and topological index values increased when cultivars were exposed to a P-stress environment. To elucidate Pi-uptake kinetics, parameters related to P influx: maximal transport rate (V(max)), the Michaelis-Menten constant (K(m)), and the external concentration when net uptake is zero (C(min)) were tested in experiment 4. Lower K(m) and C(min) values were better indicative of the P-uptake ability of the class-I cultivars, evidencing their adaptability to P-starved environmental cues. In experiment 5, class-I cultivars exuded two- to threefold more carboxylates than class-II cultivars under the P-stress environment. The amount and types of carboxylates exuded from the roots of P-starved plants differed from those of plants grown under P-sufficient conditions. Nevertheless, the exudation rate of both class-I and class-II cultivars decreased with time, and the highest exudation rate was found after the first 4 h of carboxylates collection. Higher P uptake by class-I cultivars was significantly related to the drop in root medium pH, which can be ascribed to H(+)-efflux from the roots supplied with sparingly soluble rock-P and Ca(3)(PO(4))(2). These classical rescue strategies provided the basis of P-solubilization and acquisition from sparingly soluble P-sources by Brassica cultivars to thrive in a typically stressful environment.

Aerosol pH buffering in the southeastern US: Fine particles remain highly acidic despite large reductions in sulfate

NASA Astrophysics Data System (ADS)

Weber, R. J.; Guo, H.; Russell, A. G.; Nenes, A.

2015-12-01

pH is a critical aerosol property that impacts many atmospheric processes, including biogenic secondary organic aerosol formation, gas-particle phase partitioning, and mineral dust or redox metal mobilization. Particle pH has also been linked to adverse health effects. Using a comprehensive data set from the Southern Oxidant and Aerosol Study (SOAS) as the basis for thermodynamic modeling, we have shown that particles are currently highly acidic in the southeastern US, with pH between 0 and 2. Sulfate and ammonium are the main acid-base components that determine particle pH in this region, however they have different sources and their concentrations are changing. Over 15 years of network data show that sulfur dioxide emission reductions have resulted in a roughly 70 percent decrease in sulfate, whereas ammonia emissions, mainly link to agricultural activities, have been largely steady, as have gas phase ammonia concentrations. This has led to the view that particles are becoming more neutralized. However, sensitivity analysis, based on thermodynamic modeling, to changing sulfate concentrations indicates that particles have remained highly acidic over the past decade, despite the large reductions in sulfate. Furthermore, anticipated continued reductions of sulfate and relatively constant ammonia emissions into the future will not significantly change particle pH until sulfate drops to clean continental background levels. The result reshapes our expectation of future particle pH and implies that atmospheric processes and adverse health effects linked to particle acidity will remain unchanged for some time into the future.

Characteristics of strain-sensitive photonic crystal cavities in a flexible substrate.

PubMed

No, You-Shin; Choi, Jae-Hyuck; Kim, Kyoung-Ho; Park, Hong-Gyu

2016-11-14

High-index semiconductor photonic crystal (PhC) cavities in a flexible substrate support strong and tunable optical resonances that can be used for highly sensitive and spatially localized detection of mechanical deformations in physical systems. Here, we report theoretical studies and fundamental understandings of resonant behavior of an optical mode excited in strain-sensitive rod-type PhC cavities consisting of high-index dielectric nanorods embedded in a low-index flexible polymer substrate. Using the three-dimensional finite-difference time-domain simulation method, we calculated two-dimensional transverse-electric-like photonic band diagrams and the three-dimensional dispersion surfaces near the first Γ-point band edge of unidirectionally strained PhCs. A broken rotational symmetry in the PhCs modifies the photonic band structures and results in the asymmetric distributions and different levels of changes in normalized frequencies near the first Γ-point band edge in the reciprocal space, which consequently reveals strain-dependent directional optical losses and selected emission patterns. The calculated electric fields, resonant wavelengths, and quality factors of the band-edge modes in the strained PhCs show an excellent agreement with the results of qualitative analysis of modified dispersion surfaces. Furthermore, polarization-resolved time-averaged Poynting vectors exhibit characteristic dipole-like emission patterns with preferentially selected linear polarizations, originating from the asymmetric band structures in the strained PhCs.

Sensitization of thermotolerant SCK cells to hyperthermia and freezing with reduction of intracellular pH: implications for cryosurgery.

PubMed

Burgher, Abram H; Swanlund, David J; Griffin, Robert J; Song, Chang W; Bischof, John C; Roberts, Kenneth P

2003-03-01

During cryosurgery, cells frozen slowly at the outer part of the ice ball undergo severe dehydration and are subject to solute effects injury, which may be caused in part by protein denaturation. This study was undertaken to determine whether heat shock proteins (HSPs), the molecular chaperones that stabilize proteins against denaturation, have a protective effect on cells during slow freezing. In addition, we aimed to determine whether acidic conditions, similar to those found in many solid tumors, would effect this protection. SCK cells were frozen at 5 degrees C/min to -10 degrees C or -20 degrees C before or after induction of thermotolerance, and at neutral or low pH conditions. Lethal damage was determined by clonogenics. Clonogenic survival was decreased by 50% in thermotolerant cells frozen to -10 degrees C after culture in acidic conditions (pH 6.6) compared with non-thermotolerant cells cultured at neutral pH. Induction of thermotolerance alone or low pH alone did not significantly sensitize SCK cells to freezing. All treatment groups were equally susceptible to killing when frozen to -20 degrees C. Our results show that induction of thermal tolerance does not protect SCK cells against subsequent freezing injury and that a low pH environment actually sensitizes these cells to freeze injury. Copyright 2003 Wiley-Liss, Inc.

Analytical nanosphere sensors using quantum dot-enzyme conjugates for urea and creatinine.

PubMed

Ruedas-Rama, Maria J; Hall, Elizabeth A H

2010-11-01

An enzyme-linked analytical nanosphere sensor (ANSor) is described, responding to enzyme-substrate turnover in the vicinity of a quantum dot (QD) due to coimmobilized enzyme and pH sensitive ligand. QD capping by mercapto-alkanoic acids were rejected as a pH sensitive ligand, but with the use of a layer-by-layer assembly on mercaptopropionic capped QDs and an intermediate poly(allylamine hydrochloride) layer, anthraquinone sulfonate (calcium red, CaR) was introduced to modify the pKa in the immobilized system > 8. QD-CaR absorption shows spectral overlap with QD530 emission at all pHs and gives a complex pH dependent fluorescence resonance energy transfer (FRET) efficiency, due to excited state proton transfer (λ(ex) = 540 nm; λ(em) = 585 nm). In contrast QD615-CaR with spectral overlap between the QD and CaR gave a strong and reproducible pH response. QD-urease and QD-creatinine deiminase conjugates could be linked with pH changes produced by enzyme degradation of urea and creatinine, respectively. Close coupling between the pH sensitive QD and enzyme conjugate maximized signal compared with solution based assays: QD-urease and QD-CD bioconjugates were tested in model biological media (Dulbecco's modified Eagle's Medium and fetal calf serum) and in urine, showing a response in 3-4 min.

A pH-responsive emulsion stabilized by alginate-grafted anisotropic silica and its application in the controlled release of λ-cyhalothrin.

PubMed

Chen, Kai; Yu, Gaobo; He, Furui; Zhou, Qingfeng; Xiao, Dunchao; Li, Jiacheng; Feng, Yuhong

2017-11-15

Alginate (Alg) was grafted on the surface of anisotropic silica (SiO 2 -x) via the Ugi reaction (Alg-SiO 2 -1, Alg-SiO 2 -2, and Alg-SiO 2 -4). Compared with pristine SiO 2 -x, modified SiO 2 -x is more sensitive to pH. Three stable liquid paraffin-in-water emulsions were prepared with Alg-SiO2-1, Alg-SiO2-2, and Alg-SiO2-4. Alg-SiO 2 -2 exhibited satisfactory emulsification ability. The emulsions became more stable as emulsion pH varied from 2.0 to 6.2 because of polymer chain interactions that led to the formation of a three-dimensional network. When the emulsion pH varied from 6.2 to 8.0, the particle charge increased, in turn increasing interparticle the electrostatic interactions that increased emulsion stability. When the emulsion pH was 9.0, the subsequent decrease in particle charge, decreased the emulsion stability. The model drug λ-cyhalothrin was embedded in the emulsions. A sustained-release assay demonstrated that increasing emulsion pH from 3.0 to 8.0 decreased cumulative drug release from the emulsion from 99.7% to 13.5%. This result indicated that the emulsion is a pH triggered drug delivery system. The sustained-release curves of λ-cyhalothrin are describable by the Weibull model. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro characterization of pH-sensitive azithromycin-loaded methoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) micelles.

PubMed

Teng, Fangfang; Deng, Peizong; Song, Zhimei; Zhou, Feilong; Feng, Runliang; Liu, Na

2017-06-15

In order to improve azithromycin's antibacterial activity in acidic medium, monomethoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) copolymer was synthesized through allylation, free radical addition, ring-opening polymerization and amidation reactions with methoxy poly (ethylene glycol) as raw material. Drug loading capacity and encapsulation efficiency of azithromycin-loaded micelles prepared via thin film hydration method were 11.58±0.86% and 96.06±1.93%, respectively. The drug-loaded micelles showed pH-dependent property in the respects of particle size, zeta potential at the range of pH 5.5-7.8. It could control drug in vitro release and demonstrate higher release rate at pH 6.0 than that at pH 7.4. In vitro antibacterial experiment indicated that the activity of azithromycin-loaded micelles against S. aureus was superior to free azithromycin in medium at both pH 6.0 and pH 7.4. Using fluorescein as substitute with pH-dependent fluorescence decrease property, laser confocal fluorescence microscopy analysis confirmed that cellular uptake of micelles was improved due to protonation of copolymer's imidazole groups at pH 6.0. The enhanced cellular uptake and release of drug caused its activity enhancement in acidic medium when compared with free drug. The micellar drug delivery system should be potential application in the field of bacterial infection treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Intracellular distribution of Photofrin in malignant and normal endothelial cell lines.

PubMed

Saczko, J; Mazurkiewicz, M; Chwiłkowska, A; Kulbacka, J; Kramer, G; Ługowski, M; Snietura, M; Banaś, T

2007-01-01

Compared to current treatments including surgery, radiation therapy, and chemotherapy, PDT offers the advantage of an effective and selective method of destroying diseased tissues without damaging surrounding healthy tissues. One of the aspects of antitumour effectiveness of PDT is related to the distribution of photosensitizing drugs. The localization of photosensitizers in cytoplasmic organelles during PDT plays a major role in the cell destruction; therefore, intracellular localization of Ph in malignant and normal cells was investigated. The cell lines used throughout the study were: human malignant A549, MCF-7, Me45 and normal endothelial cell line HUV-EC-C. After incubation with Ph cells were examined using fluorescence and confocal microscopy to visualize the photosensitizer accumulation. For cytoplasm and mitochondria identification, cells were stained with CellTracker Green and MitoTracker Green, respectively. Distribution of Ph was different in malignant and normal cells and dependent on the incubation time. The maximal concentration of Ph in two malignant cell lines (A549 and MCF-7) was observed after 4 hours of incubation, and the most intensive signal was observed around the nuclear envelope. Intracellular distribution of Ph in the Me45 cell line showed that the fluorescence emitted by Ph overlaid that from MitoTracker. This indicates preferential accumulation of the sensitizer in mitochondria. Our results based on the mitochondrial localization support the idea that PDT can contribute to elimination of malignant cells by inducing apoptosis, which is of physiological significance.

Design and evaluation of pH-sensitive liposomes constructed by poly(2-ethyl-2-oxazoline)-cholesterol hemisuccinate for doxorubicin delivery.

PubMed

Xu, Huan; Hu, Meina; Yu, Xiu; Li, Yan; Fu, Yuanshan; Zhou, Xiaoxia; Zhang, Di; Li, Jianying

2015-04-01

In this study, a novel material, poly(2-ethyl-2-oxazoline)-cholesterol hemisuccinate (PEtOz-CHEMS), was synthesized to construct pH-sensitive liposomes. The structure of PEtOz-CHEMS was confirmed by thin-layer chromatography, Fourier transform infrared spectroscopy, and (1)H NMR. Anticancer fluorescent drug doxorubicin (DOX) was encapsulated into the liposomes. Compared with conventional liposomes (CL), CHEMS modified liposomes (CH-L) and PEGylated liposomes (PEG-L), the PEtOzylated liposomes (PEtOz-L) showed an acidic pH-induced increase in particle size. At pH 6.4, the heme release of PEtOz-L group was close to that of the positive control group, whereas that of CL, CH-L and PEG-L was close to that of the negative control group. In vitro drug release studies demonstrated that DOX was released from PEtOz-L in a pH-dependent manner, and the release of DOX from conventional DOX liposomes (CL-DOX), DOX loaded CH-L (CH-DOX-L) and PEGylated DOX liposomes (PEG-DOX-L) had no pronounced differences under each pH medium. In vitro cellular uptake assays showed that PEtOz-DOX-L indicated a significant fluorescence intensity at pH 6.4 compared with at pH 7.4. CL-DOX, CH-DOX-L and PEG-DOX-L did not achieve any obvious diversity at different pH conditions. Confocal laser scanning microscopy images showed that PEtOz-DOX-L can fuse with the endosomal membrane under acidic conditions of endosome, release DOX into the cytoplasm, then gather into the nucleus. Therefore, PEtOz can help liposomes achieve "endosomal escape". The in vitro cytotoxicity experiment results on A375 cells showed that PEtOz-DOX-L resulted in lower cell viability than CL-DOX, CH-DOX-L and PEG-DOX-L under low pH conditions. These results confirm that the pH-responsive PEtOz was a promising material for intracellular targeted delivery system and might be used for overcoming the "PEG dilemma". Copyright © 2015 Elsevier B.V. All rights reserved.

The application of pH-sensitive fluorescent dyes in lactic acid bacteria reveals distinct extrusion systems for unmodified and conjugated dyes.

PubMed

Glaasker, E; Konings, W N; Poolman, B

1996-01-01

Intracellular pH in bacteria can be measured efficiently between internal pH values of 6.5 and 8.5 with the fluorescent pH indicator 2',7'-bis-(2-carboxyethyl)-5[and-6]-carboxyfluorescein (BCECF). A new fluorescent pH probe with a lower pKa(app) than BCECF was synthesized from fluorescein isothiocyanate and glutamate. The new probe, N-(fluorescein thio-ureanyl)-glutamate (FTUG), was much less sensitive to changes in concentrations of KCl than was BCECF. Similar to BCECF, an efflux of FTUG independent of the proton motive force, but dependent on ATP, was observed both in Lactobacillus plantarum and Lactococcus lactis. Corrections for probe efflux allowed accurate measurements of the pHin. Similar intracellular pH values were determined with FTUG and BCECF, in the range where both probes can be applied, and the pH values correlated well with those estimated from the distribution of radio-labelled benzoic acid. Since FITC can easily be coupled to substrates containing an amino group, it is possible to develop other FITC derivatives as well. The mechanisms of probe excretion and the nature of the excreted product(s) were studied in further detail for BCECF and FTUG. BCECF was excreted from wild-type L. lactis in an unmodified form as was determined by chromatographic and mass spectrometry analysis. In the case of FTUG, the excreted product was a conjugated derivative. Unmodified FTUG was not excreted, although it was present in cellular extracts from L. lactis. Exit of BCECF was completely inhibited in a BCECF efflux mutant (Bef-) of L. lactis, whereas FTUG-conjugate efflux in this mutant was similar to the wild-type. Addition of indomethacin, a known inhibitor of BCECF efflux in human epithelial cells, resulted in complete inhibition of BCECF efflux in wild-type L. lactis, whereas FTUG-conjugate exit was only slightly affected. The results of the mutant and inhibitor studies suggest that FTUG-conjugate and BCECF efflux in L. lactis are mediated by different ATP-driven extrusion systems for organic anions.

The influence of the loop between residues 223-235 in beetle luciferase bioluminescence spectra: a solvent gate for the active site of pH-sensitive luciferases.

PubMed

Viviani, Vadim R; Silva Neto, Antonio J; Arnoldi, Frederico G C; Barbosa, João A R G; Ohmiya, Yoshihiro

2008-01-01

Beetle luciferases emit a wide range of bioluminescence colors, ranging from green to red. Firefly luciferases can shift the spectrum to red in response to pH and temperature changes, whereas click beetle and railroadworm luciferases do not. Despite many studies on firefly luciferases, the origin of pH-sensitivity is far from being understood. Through comparative site-directed mutagenesis and modeling studies, using the pH-sensitive luciferases (Macrolampis and Cratomorphus distinctus fireflies) and the pH-insensitive luciferases (Pyrearinus termitilluminans, Phrixotrix viviani and Phrixotrix hirtus) cloned by our group, here we show that substitutions dramatically affecting bioluminescence colors in both groups of luciferases are clustered in the loop between residues 223-235 (Photinus pyralis sequence). The substitutions at positions 227, 228 and 229 (P. pyralis sequence) cause dramatic redshift and temporal shift in both groups of luciferases, indicating their involvement in labile interactions. Modeling studies showed that the residues Y227 and N229 are buried in the protein core, fixing the loop to other structural elements participating at the bottom of the luciferin binding site. Changes in pH and temperature (in firefly luciferases), as well as point mutations in this loop, may disrupt the interactions of these structural elements exposing the active site and modulating bioluminescence colors.

In Situ Monitoring of Pb2+ Leaching from the Galvanic Joint Surface in a Prepared Chlorinated Drinking Water.

PubMed

Ma, Xiangmeng; Armas, Stephanie M; Soliman, Mikhael; Lytle, Darren A; Chumbimuni-Torres, Karin; Tetard, Laurene; Lee, Woo Hyoung

2018-02-20

A novel method using a micro-ion-selective electrode (micro-ISE) technique was developed for in situ lead monitoring at the water-metal interface of a brass-leaded solder galvanic joint in a prepared chlorinated drinking water environment. The developed lead micro-ISE (100 μm tip diameter) showed excellent performance toward soluble lead (Pb 2+ ) with sensitivity of 22.2 ± 0.5 mV decade -1 and limit of detection (LOD) of 1.22 × 10 -6 M (0.25 mg L -1 ). The response time was less than 10 s with a working pH range of 2.0-7.0. Using the lead micro-ISE, lead concentration microprofiles were measured from the bulk to the metal surface (within 50 μm) over time. Combined with two-dimensional (2D) pH mapping, this work clearly demonstrated that Pb 2+ ions build-up across the lead anode surface was substantial, nonuniform, and dependent on local surface pH. A large pH gradient (ΔpH = 6.0) developed across the brass and leaded-tin solder joint coupon. Local pH decreases were observed above the leaded solder to a pH as low as 4.0, indicating it was anodic relative to the brass. The low pH above the leaded solder supported elevated lead levels where even small local pH differences of 0.6 units (ΔpH = 0.6) resulted in about four times higher surface lead concentrations (42.9 vs 11.6 mg L -1 ) and 5 times higher fluxes (18.5 × 10 -6 vs 3.5 × 10 -6 mg cm -2 s -1 ). Continuous surface lead leaching monitoring was also conducted for 16 h.

A tunable pH-sensing system based on Ag nanoclusters capped by hyperbranched polyethyleneimine with different molecular weights.

PubMed

Qu, Fei; Zou, Xuan; Kong, Rongmei; You, Jinmao

2016-01-01

In this assay, a tunable pH sensing system was developed based on Ag nanoclusters (Ag NCs) capped by hyperbranched polyethyleneimine (PEI) with different molecular weights (abbreviated as Ag NC-PEIs). For instance, when the molecular weight of PEI was 600 or 1800, the fluorescence intensities of Ag NCs exhibited a linear fashion over the pH range 4.10-7.96; when the molecular weight of PEI was 25,000, the pH linear range was from 4.78 to 7.96; when the molecular weight of PEI was 70,000, the pH linear range was 6.09-8.95. According to the molecular weight of PEI 600/1800, 25,000, and 70,000, the color change point was pH 4.10-4.78, 5.33-6.09, and 6.09-6.80, respectively. Therefore, Ag NC-PEI 600 and 1800 were proper to acid conditions; Ag NC-PEI 25,000 was sensitive to weak acid media; while Ag NC-PEI 70,000 was adapted to neutral solution. The tunable and selective color change points brought an excellent feature of Ag NC-PEIs as visual pH indicators, which was flexible and applicable to a variety of environments. Besides, the ratios of absorbance at 415 nm and 268 nm of Ag NCs also showed linear relationships with pH variations. Therefore, there were three ways of this system for sensing pH values, including fluorescence assay, ultraviolet-visible measurement, and visual detection, suggesting that this tunable pH-sensing platform was more feasible, reliable, and accurate. Copyright © 2015 Elsevier B.V. All rights reserved.

Presynaptic pH and vesicle fusion in Drosophila larvae neurones.

PubMed

Caldwell, Lesley; Harries, Peter; Sydlik, Sebastian; Schwiening, Christof J

2013-11-01

Both intracellular pH (pHi) and synaptic cleft pH change during neuronal activity yet little is known about how these pH shifts might affect synaptic transmission by influencing vesicle fusion. To address this we imaged pH- and Ca(2+) -sensitive fluorescent indicators (HPTS, Oregon green) in boutons at neuromuscular junctions. Electrical stimulation of motor nerves evoked presynaptic Ca(2+) i rises and pHi falls (∼0.1 pH units) followed by recovery of both Ca(2+) i and pHi. The plasma-membrane calcium ATPase (PMCA) inhibitor, 5(6)-carboxyeosin diacetate, slowed both the calcium recovery and the acidification. To investigate a possible calcium-independent role for the pHi shifts in modulating vesicle fusion we recorded post-synaptic miniature end-plate potential (mEPP) and current (mEPC) frequency in Ca(2+) -free solution. Acidification by propionate superfusion, NH(4)(+) withdrawal, or the inhibition of acid extrusion on the Na(+)/H(+) exchanger (NHE) induced a rise in miniature frequency. Furthermore, the inhibition of acid extrusion enhanced the rise induced by propionate addition and NH(4)(+) removal. In the presence of NH(4)(+), 10 out of 23 cells showed, after a delay, one or more rises in miniature frequency. These findings suggest that Ca(2+) -dependent pHi shifts, caused by the PMCA and regulated by NHE, may stimulate vesicle release. Furthermore, in the presence of membrane permeant buffers, exocytosed acid or its equivalents may enhance release through positive feedback. This hitherto neglected pH signalling, and the potential feedback role of vesicular acid, could explain some important neuronal excitability changes associated with altered pH and its buffering. Copyright © 2013 Wiley Periodicals, Inc.

Glow discharge electrolysis plasma initiated preparation of temperature/pH dual sensitivity reed hemicellulose-based hydrogels.

PubMed

Zhang, Wenming; Zhu, Sha; Bai, Yunping; Xi, Ning; Wang, Shaoyang; Bian, Yang; Li, Xiaowei; Zhang, Yucang

2015-05-20

The temperature/pH dual sensitivity reed hemicellulose-based hydrogels have been prepared through glow discharge electrolysis plasma (GDEP). The effect of different discharge voltages on the temperature and pH response performance of reed hemicellulose-based hydrogels was inspected, and the formation mechanism, deswelling behaviors of reed hemicellulose-based hydrogels were also discussed. At the same time, infrared spectroscopy (FT-IR), scanning differential thermal analysis (DSC) and scanning electron microscope (SEM) were adopted to characterize the structure, phase transformation behaviors and microstructure of hydrogels. It turned out to be that all reed hemicellulose-based hydrogels had a double sensitivity to temperature and pH, and their phase transition temperatures were all approximately 33 °C, as well as the deswelling dynamics met the first model. In addition, the hydrogel (TPRH-3), under discharge voltage 600 V, was more sensitive to temperature and pH and had higher deswelling ratio. Copyright © 2015 Elsevier Ltd. All rights reserved.

Injectable and body temperature sensitive hydrogels based on chitosan and hyaluronic acid for pH sensitive drug release.

PubMed

Zhang, Wei; Jin, Xin; Li, Heng; Zhang, Run-Run; Wu, Cheng-Wei

2018-04-15

Hydrogels based on chitosan/hyaluronic acid/β-sodium glycerophosphate demonstrate injectability, body temperature sensitivity, pH sensitive drug release and adhesion to cancer cell. The drug (doxorubicin) loaded hydrogel precursor solutions are injectable and turn to hydrogels when the temperature is increased to body temperature. The acidic condition (pH 4.00) can trigger the release of drug and the cancer cell (Hela) can adhere to the surface of the hydrogels, which will be beneficial for tumor site-specific administration of drug. The mechanical strength, the gelation temperature, and the drug release behavior can be tuned by varying hyaluronic acid content. The mechanisms were characterized using dynamic mechanical analysis, Fourier transform infrared spectroscopy, scanning electron microscopy and fluorescence microscopy. The carboxyl group in hyaluronic acid can form the hydrogen bondings with the protonated amine in chitosan, which promotes the increase of mechanical strength of the hydrogels and depresses the initial burst release of drug from the hydrogel. Copyright © 2018 Elsevier Ltd. All rights reserved.

Potentiation of pH-sensitive polymer-modified liposomes with cationic lipid inclusion as antigen delivery carriers for cancer immunotherapy.

PubMed

Yoshizaki, Yuta; Yuba, Eiji; Sakaguchi, Naoki; Koiwai, Kazunori; Harada, Atsushi; Kono, Kenji

2014-09-01

Cationic lipid-incorporated liposomes modified with pH-sensitive polymers were prepared by introducing 3, 5-didodecyloxybenzamidine as a cationic lipid to egg yolk phosphatidylcholine liposomes modified with 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG) as a pH-sensitive polymer. These liposomes were stable at neutral pH, but were destabilized below pH 6.0 because MGlu-HPG changed its characteristics from hydrophilic to hydrophobic in response to the pH decrease. Cationic lipid inclusion improved their pH sensitivity at weakly acidic pH and association of liposomes with murine dendritic cell (DC) lines. Cationic lipid-incorporated liposomes delivered entrapped ovalbumin (OVA) molecules not only to cytosol but also to endosome/lysosome. Treatment with cationic lipid-incorporated liposomes induced up-regulation of antigen presentation-involved molecules on DCs, the promotion of cytokine production, and antigen presentation via both major histocompatibility complex (MHC) class I and II molecules. Especially, antigen presentation via MHC class II was promoted by cationic lipid inclusion, which might correspond to efficient endosome/lysosome delivery of OVA. Subcutaneous administration of OVA-loaded cationic lipid-incorporated liposomes induced antigen-specific antibody production in serum and Th1-dominant immune responses in the spleen. Furthermore, administration of the cationic lipid-incorporated liposomes to mice bearing E.G7-OVA tumor more significantly reduced the tumor volume than liposomes without cationic lipids. Therefore, cationic lipid inclusion into pH-sensitive polymer-modified liposomes, which can achieve both efficient antigen intracellular delivery and activation of antigen presenting cell, is an effective approach to develop antigen carriers for efficient cancer immunotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Self-assembled micelles based on pH-sensitive PAE-g-MPEG-cholesterol block copolymer for anticancer drug delivery.

PubMed

Zhang, Can Yang; Xiong, Di; Sun, Yao; Zhao, Bin; Lin, Wen Jing; Zhang, Li Juan

2014-01-01

A novel amphiphilic triblock pH-sensitive poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-g-MPEG-Chol) was designed and synthesized via the Michael-type step polymerization and esterification condensation method. The synthesized copolymer was determined with proton nuclear magnetic resonance and gel permeation chromatography. The grafting percentages of MPEG and cholesterol were determined as 10.93% and 62.02%, calculated from the area of the characteristic peaks, respectively. The amphiphilic copolymer was confirmed to self-assemble into core/shell micelles in aqueous solution at low concentrations. The critical micelle concentrations were 6.92 and 15.14 mg/L at pH of 7.4 and 6.0, respectively, obviously influenced by the changes of pH values. The solubility of pH-responsive PAE segment could be transformed depending on the different values of pH because of protonation-deprotonation of the amino groups, resulting in pH sensitivity of the copolymer. The average particle size of micelles increased from 125 nm to 165 nm with the pH decreasing, and the zeta potential was also significantly changed. Doxorubicin (DOX) was entrapped into the polymeric micelles with a high drug loading level. The in vitro DOX release from the micelles was distinctly enhanced with the pH decreasing from 7.4 to 6.0. Toxicity testing proved that the DOX-loaded micelles exhibited high cytotoxicity in HepG2 cells, whereas the copolymer showed low toxicity. The results demonstrated how pH-sensitive PAE-g-MPEG-Chol micelles were proved to be a potential vector in hydrophobic drug delivery for tumor therapy.

Self-assembled micelles based on pH-sensitive PAE-g-MPEG-cholesterol block copolymer for anticancer drug delivery

PubMed Central

Zhang, Can Yang; Xiong, Di; Sun, Yao; Zhao, Bin; Lin, Wen Jing; Zhang, Li Juan

2014-01-01

A novel amphiphilic triblock pH-sensitive poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-g-MPEG-Chol) was designed and synthesized via the Michael-type step polymerization and esterification condensation method. The synthesized copolymer was determined with proton nuclear magnetic resonance and gel permeation chromatography. The grafting percentages of MPEG and cholesterol were determined as 10.93% and 62.02%, calculated from the area of the characteristic peaks, respectively. The amphiphilic copolymer was confirmed to self-assemble into core/shell micelles in aqueous solution at low concentrations. The critical micelle concentrations were 6.92 and 15.14 mg/L at pH of 7.4 and 6.0, respectively, obviously influenced by the changes of pH values. The solubility of pH-responsive PAE segment could be transformed depending on the different values of pH because of protonation–deprotonation of the amino groups, resulting in pH sensitivity of the copolymer. The average particle size of micelles increased from 125 nm to 165 nm with the pH decreasing, and the zeta potential was also significantly changed. Doxorubicin (DOX) was entrapped into the polymeric micelles with a high drug loading level. The in vitro DOX release from the micelles was distinctly enhanced with the pH decreasing from 7.4 to 6.0. Toxicity testing proved that the DOX-loaded micelles exhibited high cytotoxicity in HepG2 cells, whereas the copolymer showed low toxicity. The results demonstrated how pH-sensitive PAE-g-MPEG-Chol micelles were proved to be a potential vector in hydrophobic drug delivery for tumor therapy. PMID:25364250

The chemistry, physiology and pathology of pH in cancer

PubMed Central

Swietach, Pawel; Vaughan-Jones, Richard D.; Harris, Adrian L.; Hulikova, Alzbeta

2014-01-01

Cell survival is conditional on the maintenance of a favourable acid–base balance (pH). Owing to intensive respiratory CO2 and lactic acid production, cancer cells are exposed continuously to large acid–base fluxes, which would disturb pH if uncorrected. The large cellular reservoir of H+-binding sites can buffer pH changes but, on its own, is inadequate to regulate intracellular pH. To stabilize intracellular pH at a favourable level, cells control trans-membrane traffic of H+-ions (or their chemical equivalents, e.g. ) using specialized transporter proteins sensitive to pH. In poorly perfused tumours, additional diffusion-reaction mechanisms, involving carbonic anhydrase (CA) enzymes, fine-tune control extracellular pH. The ability of H+-ions to change the ionization state of proteins underlies the exquisite pH sensitivity of cellular behaviour, including key processes in cancer formation and metastasis (proliferation, cell cycle, transformation, migration). Elevated metabolism, weakened cell-to-capillary diffusive coupling, and adaptations involving H+/H+-equivalent transporters and extracellular-facing CAs give cancer cells the means to manipulate micro-environmental acidity, a cancer hallmark. Through genetic instability, the cellular apparatus for regulating and sensing pH is able to adapt to extracellular acidity, driving disease progression. The therapeutic potential of disturbing this sequence by targeting H+/H+-equivalent transporters, buffering or CAs is being investigated, using monoclonal antibodies and small-molecule inhibitors. PMID:24493747

The chemistry, physiology and pathology of pH in cancer.

PubMed

Swietach, Pawel; Vaughan-Jones, Richard D; Harris, Adrian L; Hulikova, Alzbeta

2014-03-19

Cell survival is conditional on the maintenance of a favourable acid-base balance (pH). Owing to intensive respiratory CO2 and lactic acid production, cancer cells are exposed continuously to large acid-base fluxes, which would disturb pH if uncorrected. The large cellular reservoir of H(+)-binding sites can buffer pH changes but, on its own, is inadequate to regulate intracellular pH. To stabilize intracellular pH at a favourable level, cells control trans-membrane traffic of H(+)-ions (or their chemical equivalents, e.g. ) using specialized transporter proteins sensitive to pH. In poorly perfused tumours, additional diffusion-reaction mechanisms, involving carbonic anhydrase (CA) enzymes, fine-tune control extracellular pH. The ability of H(+)-ions to change the ionization state of proteins underlies the exquisite pH sensitivity of cellular behaviour, including key processes in cancer formation and metastasis (proliferation, cell cycle, transformation, migration). Elevated metabolism, weakened cell-to-capillary diffusive coupling, and adaptations involving H(+)/H(+)-equivalent transporters and extracellular-facing CAs give cancer cells the means to manipulate micro-environmental acidity, a cancer hallmark. Through genetic instability, the cellular apparatus for regulating and sensing pH is able to adapt to extracellular acidity, driving disease progression. The therapeutic potential of disturbing this sequence by targeting H(+)/H(+)-equivalent transporters, buffering or CAs is being investigated, using monoclonal antibodies and small-molecule inhibitors.

Hemoglobin function and allosteric regulation in semi-fossorial rodents (family Sciuridae) with different altitudinal ranges

PubMed Central

Revsbech, Inge G.; Tufts, Danielle M.; Projecto-Garcia, Joana; Moriyama, Hideaki; Weber, Roy E.; Storz, Jay F.; Fago, Angela

2013-01-01

SUMMARY Semi-fossorial ground squirrels face challenges to respiratory gas transport associated with the chronic hypoxia and hypercapnia of underground burrows, and such challenges are compounded in species that are native to high altitude. During hibernation, such species must also contend with vicissitudes of blood gas concentrations and plasma pH caused by episodic breathing. Here, we report an analysis of hemoglobin (Hb) function in six species of marmotine ground squirrels with different altitudinal distributions. Regardless of their native altitude, all species have high Hb–O2 affinities, mainly due to suppressed sensitivities to allosteric effectors [2,3-diphosphoglycerate (DPG) and chloride ions]. This suppressed anion sensitivity is surprising given that all canonical anion-binding sites are conserved. Two sciurid species, the golden-mantled and thirteen-lined ground squirrel, have Hb–O2 affinities that are characterized by high pH sensitivity and low thermal sensitivity relative to the Hbs of humans and other mammals. The pronounced Bohr effect is surprising in light of highly unusual amino acid substitutions at the C-termini that are known to abolish the Bohr effect in human HbA. Taken together, the high O2 affinity of sciurid Hbs suggests an enhanced capacity for pulmonary O2 loading under hypoxic and hypercapnic conditions, while the large Bohr effect should help to ensure efficient O2 unloading in tissue capillaries. In spite of the relatively low thermal sensitivities of the sciurid Hbs, our results indicate that the effect of hypothermia on Hb oxygenation is the main factor contributing to the increased blood–O2 affinity in hibernating ground squirrels. PMID:24172889

A strategy for oral chemotherapy via dual pH-sensitive polyelectrolyte complex nanoparticles to achieve gastric survivability, intestinal permeability, hemodynamic stability and intracellular activity.

PubMed

Deng, Liandong; Dong, Hongxu; Dong, Anjie; Zhang, Jianhua

2015-11-01

Efficient oral administration of anticancer agents requires a nanocarrier to long survive in the stomach, effectively penetrate across the small intestine, tightly retain the drug during bloodstream and quickly release drug in tumor cells. Herein a kind of dual pH-sensitive polyelectrolyte complex nanoparticles (CNPs) was developed by employing electrostatic interaction between positively charged chitosan (CS) and negative poly (L-glutamic acid) grafted polyethylene glycol-doxorubicin conjugate nanoparticles (PG-g-PEG-hyd-DOX NPs) with acid-labile hydrazone linkages. The obtained NPs and CNPs were characterized for their morphology, particle size, ζ-potential, pH-sensitivity under the simulated physiological conditions, drug release, as well as in vivo antitumor activity and biodistribution. The results indicated that CNPs can remain intact structure in pH range from 3.0 to 6.5. After detaching CS layer due to the pH-induced deprotonation with increasing pH to 7.4 in the mucus layer of the small intestine, the inner NPs would be released and effectively absorbed into blood circulation via opening the tight junctions by CS. PG-g-PEG-hyd-DOX NPs with demonstrated long-circulating properties can be accumulated in the tumor via EPR effect and dump the drug within tumor cells by acid-cleavage of hydrazone bonds between PG-g-PEG and DOX, achieving high therapeutic efficacy and low systemic toxicity. These results suggest that the design presented here, combining the functions of the gastrointestinal pH-sensitive electrostatic complex and intracellular acid-sensitive macromolecular prodrugs NPs, can sequentially overcome the biological barriers of oral anticancer drug delivery, which thus provides a promising nanomedicine platform for oral chemotherapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of pH-sensitive hydrogels by conductimetry and calorimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheppard, N.F. Jr.; Chen, Jey-Hsin; Lawson, H.C.

1993-12-31

The total and freezing water contents, and electrical conductivity of pH-sensitive hydrogels formed from poly(hydroxyethyl methacrylate - co - dimethylaminoethyl methacrylate) were measured as a function of copolymer composition and pH. For an 80/20 HEMA/DMAEMA gel (mole ratio), the water content increases from 37% at pH 10 of the bathing solution value at pH 10 to 90% at low pH. The difference between total and freezing water content in the gels is approximately 25%, consistent with values reported in the literature. An examination of the results in the context of the Yasuda free- volume model suggests that freezing water content,more » rather than total water content, may be suitable for modelling of hydrogel conductivity.« less

Thermal sterilization of heat-sensitive products using high-temperature short-time sterilization.

PubMed

Mann, A; Kiefer, M; Leuenberger, H

2001-03-01

High-temperature short-time (HTST) sterilization with a continuous-flow sterilizer, developed for this study, was evaluated. The evaluation was performed with respect to (a) the chemical degradation of two heat-sensitive drugs in HTST range (140-160 degrees C) and (b) the microbiological effect of HTST sterilization. Degradation kinetics of two heat-sensitive drugs showed that a high peak temperature sterilization process resulted in less chemical degradation for the same microbiological effect than a low peak temperature process. Both drugs investigated could be sterilized with acceptable degradation at HTST conditions. For the evaluation of the microbiological effect, Bacillus stearothermophilus ATCC 7953 spores were used as indicator bacteria. Indicator spore kinetics (D(T), z value, k, and E(a)), were determined in the HTST range. A comparison between the Bigelow model (z value concept) and the Arrhenius model, used to describe the temperature coefficient of the microbial inactivation, demonstrated that the Bigelow model is more accurate in prediction of D(T) values in the HTST range. The temperature coefficient decreased with increasing temperature. The influence of Ca(2+) ions and pH value on the heat resistance of the indicator spores, which is known under typical sterilization conditions, did not change under HTST conditions.

Serum-Stable, Long-Circulating, pH-Sensitive PEGylated Liposomes.

PubMed

Bertrand, Nicolas; Simard, Pierre; Leroux, Jean-Christophe

2017-01-01

pH-sensitive liposomes have been designed to deliver active compounds, specifically to acidic intracellular organelles, and to augment their cytoplasmic concentrations. These systems combine the protective effects of other liposomal formulations with specific environment-controlled drug release. They are stable at physiological pH, but abruptly discharge their contents when endocytosed into acidic compartments, allowing the drug to be released before it is exposed to the harsh environment of the lysosomes.Serum-stable formulations with minimal leakage at physiological pH and rapid drug release at pH 5.0 to 5.5 can be easily prepared by inserting a hydrophobically modified N-isopropylacrylamide/methacrylic acid copolymer (poly(NIPAM-co-MAA)) in the lipid bilayer of sterically stabilized liposomes. The present chapter describes polymer synthesis, as well as the preparation and characterization of large unilamellar pH-sensitive vesicles.

Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution.

PubMed

Zhao, Boyang; Sedlak, Joseph C; Srinivas, Raja; Creixell, Pau; Pritchard, Justin R; Tidor, Bruce; Lauffenburger, Douglas A; Hemann, Michael T

2016-03-24

The prevailing approach to addressing secondary drug resistance in cancer focuses on treating the resistance mechanisms at relapse. However, the dynamic nature of clonal evolution, along with potential fitness costs and cost compensations, may present exploitable vulnerabilities-a notion that we term "temporal collateral sensitivity." Using a combined pharmacological screen and drug resistance selection approach in a murine model of Ph(+) acute lymphoblastic leukemia, we indeed find that temporal and/or persistent collateral sensitivity to non-classical BCR-ABL1 drugs arises in emergent tumor subpopulations during the evolution of resistance toward initial treatment with BCR-ABL1-targeted inhibitors. We determined the sensitization mechanism via genotypic, phenotypic, signaling, and binding measurements in combination with computational models and demonstrated significant overall survival extension in mice. Additional stochastic mathematical models and small-molecule screens extended our insights, indicating the value of focusing on evolutionary trajectories and pharmacological profiles to identify new strategies to treat dynamic tumor vulnerabilities. Copyright © 2016 Elsevier Inc. All rights reserved.

The Structure-Dependent Electric Release and Enhanced Oxidation of Drug in Graphene Oxide-Based Nanocarrier Loaded with Anticancer Herbal Drug Berberine.

PubMed

Yu, Danni; Ruan, Pan; Meng, Ziyuan; Zhou, Jianping

2015-08-01

The aim of the current investigation is to explore graphene oxide (GO) special electric and electrochemical properties in modulating and tuning drug delivery in tumor special environment of electrophysiology. The electric-sensitive drug release and redox behavior of GO-bearing berberine (Ber) was studied. Drug release in cell potential was applied in a designed electrode system: tumor environment was simulated at pH 6.2 with 0.1 V pulse voltage, whereas the normal was at pH 7.4 with 0.2 V. Quite different from the pH-depended profile, the electricity-triggered behavior indicated a high correlation with the carriers' structure: GO-based nanocomposite showed a burst release on its special "skin effect," whereas the PEGylated ones released slowly owing to the electroviscous effect of polymer. Cyclic voltammetry was used to investigate the redox behaviors of colloid PEGylated GO toward absorbed Ber in pH 5.8 and 7.2 solutions. After drug loading, the oxidation of Ber was enhanced in a neutral environment, whereas the enhancement of PEG-GO was in an acidic one, which means a possible increased susceptibility of their biotransformation in vivo. The studies designed in this work may help to establish a kind of carrier system for the sensitive delivery and metabolic regulation of drugs according to the different electrophysiological environment in tumor therapy. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Dual-wavelength photothermal optical coherence tomography for blood oxygen saturation measurement

NASA Astrophysics Data System (ADS)

Yin, Biwei; Kuranov, Roman V.; McElroy, Austin B.; Milner, Thomas E.

2013-03-01

We report design and demonstration of a dual wavelength photothermal (DWP) optical coherence tomography (OCT) system for imaging of a phantom microvessel and measurement of hemoglobin oxygen saturation (SO2) level. The DWP-OCT system contains a swept-source (SS) two-beam phase-sensitive (PhS) OCT system (1060 nm) and two intensity modulated photothermal excitation lasers (770 nm and 800 nm). The PhS-OCT probe beam (1060 nm) and photothermal excitation beams are combined into one single-mode optical fiber. A galvanometer based two-dimensional achromatic scanning system is designed to provide 14 μm lateral resolution for the PhS-OCT probe beam (1060 nm) and 13 μm lateral resolution for photothermal excitation beams. DWP-OCT system's sensitivity is 102 dB, axial resolution is 13 μm in tissue and uses a real-time digital dispersion compensation algorithm. Noise floor for optical pathlength measurements is 300 pm in the signal frequency range (380-400 Hz) of photothermal modulation frequencies. Blood SO2 level is calculated from measured optical pathlength (op) signal in a 300 μm diameter microvessel phantom introduced by the two photothermal excitation beams. En-face and B-scan images of a phantom microvessel are recorded, and six blood samples' SO2 levels are measured using DWP-OCT and compared with values provided by a commercial blood oximeter. A mathematical model indicates thermal diffusion introduces a systematic artifact that over-estimates SO2 values and is consistent with measured data.

Spectrophotometric and cytochemical analyses of phosphatase activity in Beta vulgaris L.

PubMed

Pesacreta, T C; Bennett, A B; Lucas, W J

1986-03-01

Spectrophotometric and cytochemical methods were used to investigate the localization and/or the sensitivity of phosphatase activities in aldehyde-fixed beet leaves and membrane fractions. The nonspecific acid phosphatase substrates, p-nitrophenyl phosphate and beta-glycerol phosphate, each exhibited unique spectrophotometric patterns of hydrolysis as a function of pH. Additionally, beta-glycerol phosphatase activity was primarily present on the tonoplast, whereas p-nitrophenyl phosphatase was present on the plasma membrane. Because of the unique pH response of each enzyme and their different localization, we conclude that they cannot be entirely "nonspecific." The spectrophotometric pattern of ATP hydrolysis differed from that of p-nitrophenol phosphate in that it decreased at pH 5.0-5.5 and was greatly inhibited by 10 mM sodium fluoride; however, both activities were on the plasma membrane. Therefore, we conclude that these activities represent either two enzymes or only one enzyme that differs in its ability to hydrolyze these two substrates. Generally, enzymatically produced lead deposits on the plasma membrane of non-vascular cells were as frequent and large as those on phloem cells; frequently, deposits on sieve element plasma membranes were relatively small. We therefore conclude that there is no evidence for the presence of relatively intense ATPase activity on the plasma membrane of phloem cells in beet leaf, in contrast to other species. Studies with membrane fractions indicated that formaldehyde could completely inhibit the inhibitor-sensitive phosphatase activities in mitochondrial and vacuolar fractions while preserving significant activity in the plasma membrane fraction.

Electrostatic Assemblies of Well-Dispersed AgNPs on the Surface of Electrospun Nanofibers as Highly Active SERS Substrates for Wide-Range pH Sensing.

PubMed

Yang, Tong; Ma, Jun; Zhen, Shu Jun; Huang, Cheng Zhi

2016-06-15

Surface-enhanced Raman scattering (SERS) has shown high promise in analysis and bioanalysis, wherein noble metal nanoparticles (NMNPs) such as silver nanoparticles were employed as substrates because of their strong localized surface plasmon resonance (LSPR) properties. However, SERS-based pH sensing was restricted because of the aggregation of NMNPs in acidic medium or biosamples with high ionic strength. Herein, by using the electrostatic interaction as a driving force, AgNPs are assembled on the surface of ethylene imine polymer (PEI)/poly(vinyl alcohol) (PVA) electrospun nanofibers, which are then applied as highly sensitive and reproducible SERS substrate with an enhancement factor (EF) of 10(7)-10(8). When p-aminothiophenol (p-ATP) is used as an indicator with its b2 mode, a good and wide linear response to pH ranging from 2.56 to 11.20 could be available, and the as-prepared nanocomposite fibers then could be fabricated as excellent pH sensors in complicated biological samples such as urine, considering that the pH of urine could reflect the acid-base status of a person. This work not only emerges a cost-effective, direct, and convenient approach to homogeneously decorate AgNPs on the surface of polymer nanofibers but also supplies a route for preparing other noble metal nanofibrous sensing membranes.

Flexible pH-Sensing Hydrogel Fibers for Epidermal Applications.

PubMed

Tamayol, Ali; Akbari, Mohsen; Zilberman, Yael; Comotto, Mattia; Lesha, Emal; Serex, Ludovic; Bagherifard, Sara; Chen, Yu; Fu, Guoqing; Ameri, Shideh Kabiri; Ruan, Weitong; Miller, Eric L; Dokmeci, Mehmet R; Sonkusale, Sameer; Khademhosseini, Ali

2016-03-01

Epidermal pH is an indication of the skin's physiological condition. For example, pH of wound can be correlated to angiogenesis, protease activity, bacterial infection, etc. Chronic nonhealing wounds are known to have an elevated alkaline environment, while healing process occurs more readily in an acidic environment. Thus, dermal patches capable of continuous pH measurement can be used as point-of-care systems for monitoring skin disorder and the wound healing process. Here, pH-responsive hydrogel fibers are presented that can be used for long-term monitoring of epidermal wound condition. pH-responsive dyes are loaded into mesoporous microparticles and incorporated into hydrogel fibers using a microfluidic spinning system. The fabricated pH-responsive microfibers are flexible and can create conformal contact with skin. The response of pH-sensitive fibers with different compositions and thicknesses are characterized. The suggested technique is scalable and can be used to fabricate hydrogel-based wound dressings with clinically relevant dimensions. Images of the pH-sensing fibers during real-time pH measurement can be captured with a smart phone camera for convenient readout on-site. Through image processing, a quantitative pH map of the hydrogel fibers and the underlying tissue can be extracted. The developed skin dressing can act as a point-of-care device for monitoring the wound healing process. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gene encoding the group B streptococcal protein R4, its presence in clinical reference laboratory isolates & R4 protein pepsin sensitivity.

PubMed

Smith, B L; Flores, A; Dechaine, J; Krepela, J; Bergdall, A; Ferrieri, P

2004-05-01

R proteins were first identified by Lancefield in group B Streptococcus (GBS) as resistant to trypsin at pH8 and sensitive to pepsin at pH2. The R4 protein found predominantly in type III and some type II and V invasive isolates conforms to these criteria. The Rib protein, although structurally and epidemiologically similar to R4, was reported as resistant to both proteases. We report here the gene encoding the R4 protein from a type III group B streptococcal isolate (76-043) well characterized in our laboratory. Trypsin extracted GBS proteins were assayed for protease sensitivities by double-diffusion Ouchterlony using varying conditions for the enzyme pepsin. Standard haemoglobin assay was used to examine pepsin enzymatic activity. Thirty clinical isolates of varying protein profiles identified by double-diffusion from our reference strain laboratory were screened by PCR and Southern technique. SDS-PAGE gel purified R4 amino acid sequences were determined and used to design oligonucleotide primers for screening a 76-043 genomic library. R4 was sensitive to pepsin at pH2 but appeared resistant at pH4, the reported pH used for Rib. By standard haemoglobin assay and trypsin extract studies of R4 protein, pepsin was shown to be active at pH2, yet easily inactivated; assays of GBS surface proteins are critical at pH2. Of the amino acids initially sequenced from R4, 88 per cent (61/69) showed identity to Rib; the r4 nucleotide sequence was identical to that of rib. All isolates with strong positive protein reactions for R4 were positive in both PCR and Southern technique, whereas isolates expressing alpha, beta, R1/R4, and R5 (BPS) protein profiles were not. Sequenced PCR products aligned with identity to the R4 and Rib nucleotide sequences and confirmed the identity of these proteins and their molecular sequences.

Mitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders

PubMed Central

Vawter, MP; Tomita, H; Meng, F; Bolstad, B; Li, J; Evans, S; Choudary, P; Atz, M; Shao, L; Neal, C; Walsh, DM; Burmeister, M; Speed, T; Myers, R; Jones, EG; Watson, SJ; Akil, H; Bunney, WE

2010-01-01

Mitochondrial defects in gene expression have been implicated in the pathophysiology of bipolar disorder and schizophrenia. We have now contrasted control brains with low pH versus high pH and showed that 28% of genes in mitochondrial-related pathways meet criteria for differential expression. A majority of genes in the mitochondrial, chaperone and proteasome pathways of nuclear DNA-encoded gene expression were decreased with decreased brain pH, whereas a majority of genes in the apoptotic and reactive oxygen stress pathways showed an increased gene expression with a decreased brain pH. There was a significant increase in mitochondrial DNA copy number and mitochondrial DNA gene expression with increased agonal duration. To minimize effects of agonal-pH state on mood disorder comparisons, two classic approaches were used, removing all subjects with low pH and agonal factors from analysis, or grouping low and high pH as a separate variable. Three groups of potential candidate genes emerged that may be mood disorder related: (a) genes that showed no sensitivity to pH but were differentially expressed in bipolar disorder or major depressive disorder; (b) genes that were altered by agonal-pH in one direction but altered in mood disorder in the opposite direction to agonal-pH and (c) genes with agonal-pH sensitivity that displayed the same direction of changes in mood disorder. Genes from these categories such as NR4A1 and HSPA2 were confirmed with Q-PCR. The interpretation of postmortem brain studies involving broad mitochondrial gene expression and related pathway alterations must be monitored against the strong effect of agonal-pH state. Genes with the least sensitivity to agonal-pH could present a starting point for candidate gene search in neuropsychiatric disorders. PMID:16636682

pH and redox-responsive mixed micelles for enhanced intracellular drug release.

PubMed

Cai, Mengtan; Zhu, Kun; Qiu, Yongbin; Liu, Xinrong; Chen, Yuanwei; Luo, Xianglin

2014-04-01

In order to prepare pH and redox sensitive micelles, amphiphilic copolymers of poly (epsilon-caprolactone)-b-poly(2-(diethylamino) ethyl methacrylate) (PCL-PDEA) and disulfide-linked poly(ethyl glycol)-poly(epsilon-caprolactone) (mPEG-SS-PCL) were synthesized. The double-sensitive micelles were prepared simply by solvent-evaporating method with the mixed two copolymers. The pH sensitivity of the mixed micelles was confirmed by the change of micelle diameter/diameter distribution measured by dynamic lighting scattering (DLS) and the redox sensitivity of the mixed micelles was testified by the change of micellar morphous observed by scanning electron microscope (SEM). In vitro drug release showed that drug-loaded mixed micelles (mass ratio 5:5) could achieve above 90% of drug release under low pH and reducing condition within 10h. Moreover, the drug-loaded mixed micelles (mass ratio 5:5) showed the largest cellular toxicity compared with other drug-loaded micelles, while blank mixed micelles exhibited no toxicity. These results meant that the mixed micelles composed by the two amphiphilic copolymers can enhance intracellular drug release. It is concluded that the newly developed mixed micelles can serve as a potential drug delivery system for anticancer drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Kinetics of steel slag leaching: Batch tests and modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Windt, Laurent, E-mail: laurent.dewindt@mines-paristech.fr; Chaurand, Perrine; Rose, Jerome

2011-02-15

Reusing steel slag as an aggregate for road construction requires to characterize the leaching kinetics and metal releases. In this study, basic oxygen furnace (BOF) steel slag were subjected to batch leaching tests at liquid to solid ratios (L/S) of 10 and 100 over 30 days; the leachate chemistry being regularly sampled in time. A geochemical model of the steel slag is developed and validated from experimental data, particularly the evolution with leaching of mineralogical composition of the slag and trace element speciation. Kinetics is necessary for modeling the primary phase leaching, whereas a simple thermodynamic equilibrium approach can bemore » used for secondary phase precipitation. The proposed model simulates the kinetically-controlled dissolution (hydrolysis) of primary phases, the precipitation of secondary phases (C-S-H, hydroxide and spinel), the pH and redox conditions, and the progressive release of major elements as well as the metals Cr and V. Modeling indicates that the dilution effect of the L/S ratio is often coupled to solubility-controlled processes, which are sensitive to both the pH and the redox potential. A sensitivity analysis of kinetic uncertainties on the modeling of element releases is performed.« less

Structural, functional and pH sensitive release characteristics of water-soluble polysaccharide from the seeds of Albizia lebbeck L.

PubMed

Kumar Varma, Chekuri Ashok; Jayaram Kumar, K

2017-11-01

Plant polysaccharides, generally regarded as safe (GRAS), are gaining importance as excipients in drug delivery. Therefore, the current paper presents the studies on structural, functional and drug release study of water soluble polysaccharide (ALPS) from seeds of Albizia lebbeck L. High swelling, water holding capacity, foam stability and lower moisture content suggests its use as additive in food preparations. The apparent molecular weight of polysaccharide was found to be 1.98×10 2 kDa. Monosaccharide composition analysis indicated that ALPS consists of mannose (4.06%), rhamnose (22.79%), glucose (38.9%), galactose (17.84%) and xylose (16.42%). Micromeritic properties revealed that the polysaccharide possess potential for pharmaceutical applications. From the surface charge analysis, ALPS was found to be non-ionic polysaccharide. Morphological study reveals the polysaccharide with irregular particle shape and rough surface. Fourier transformed infrared spectroscopy (FTIR) study confirms the carbohydrate nature of polysaccharide. From the thermogravimetric analysis (TGA) data, the second mass loss (243-340°C) attributed to polysaccharide degradation. The drug release profile reveals the use of polysaccharide for the preparation of pH sensitive pharmaceutical dosage forms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hepatocyte-targeted delivery using ph-sensitive liposomes loaded with lactosylnorcantharidin phospholipid complex: preparation, characterization, and therapeutic evaluation in vivo and in vitro.

PubMed

Qiao-ling, Z; Yi, Z; Min, G; Di-jia, Y; Xiao-feng, Z; Yang, L; Jing-yu, X; Ying, W; Zong-lin, G; Kong-lang, X; Ai-jun, Z; Wei-liang, C; Lin-sen, S; Xue-nong, Z; Qiang, Z

2012-01-01

Liposomes loaded with lactosyl-norcantharidin phospholipid complex (LPC) were prepared, in which soybean phosphatidylcholine was used to improve the liposolubility of lactosyl-norcantharidin (Lac-NCTD). The pH-sensitive LPC liposomes (pH-LPC-lips) were obtained by electrostatic adsorption of the carboxymethyl chitosan onto the surface of the liposomes. The in vitro drug release of pH-LPC-lips and LPC-lips was investigated in dissolution media with pH ranging from 1.0 to 8.0. The in vitro antitumor activity and cellular uptake of Lac-NCTD and its liposomes to HepG2 cells were studied. The pH-LPC-lips demonstrated strong cytotoxicity against the cells and easily permeated the cell membrane. The in vivo antitumor activities of Lac-NCTD and its liposomes were evaluated in mice bearing H22 liver tumors. The pH-LPC-lips displayed the best tumor inhibitory effect. The optical imaging results indicated that Cy7- labeled pH-LPC-lips showed excellent hepatocyte specificity in H22 tumor-bearing mice. Therefore, pH-LPC-lips can be regarded as liver-targeting agents that combine targeting and active releasing.

Experimental acidification of Little Rock Lake (Wisconsin): fish research approach and early responses.

PubMed

Swenson, W A; McCormick, J H; Simonson, T D; Jensen, K M; Eaton, J G

1989-01-01

One goal of research at Little Rock Lake, Wisconsin, is to enhance understanding of lake acidification effects on warm- and cool-water fishery resources. The Little Rock Lake fish assemblage is characteristic of many acid sensitive waters in North America and is dominated by yellow perch (Percidae) and sunfishes (Centrarchidae). Analyses of reproduction, early survival and growth rates in the field were designed around the differing reproductive modes of these taxa. Complementary laboratory research on early life stages was conducted to assist in isolating direct effect mechanisms and to determine the reliability of laboratory results in predicting field response. Preliminary findings suggest that lake acidification to pH 5.6 has not influenced reproductive activity of the four most abundant fish species. However, the field results suggest that year-class failure of rock bass (Ambloplites rupestris) may be occurring due to reduced survival of early life stages. Reduced growth and food conversion efficiency of Age 0 largemouth bass (Micropterus salmoides) is also suggested. The laboratory bioassays indicate rock bass is the most acid-sensitive Little Rock Lake species tested. However, rock bass fry survival was not significantly affected until pH was reduced from 5.6 to 5.0.

Phase-sensitive optical coherence tomography-based vibrometry using a highly phase-stable akinetic swept laser source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Applegate, Brian E.; Park, Jesung; Carbajal, Esteban

Phase-sensitive Optical Coherence Tomography (PhOCT) is an emerging tool for in vivo investigation of the vibratory function of the intact middle and inner ear. PhOCT is able to resolve micron scale tissue morphology in three dimensions as well as measure picometer scale motion at each spatial position. Most PhOCT systems to date have relied upon the phase stability offered by spectrometer detection. On the other hand swept laser source based PhOCT offers a number of advantages including balanced detection, long imaging depths, and high imaging speeds. Unfortunately the inherent phase instability of traditional swept laser sources has necessitated complex usermore » developed hardware/software solutions to restore phase sensitivity. Here we present recent results using a prototype swept laser that overcomes these issues. The akinetic swept laser is electronically tuned and precisely controls sweeps without any mechanical movement, which results in high phase stability. We have developed an optical fiber based PhOCT system around the akinetic laser source that had a 1550 nm center wavelength and a sweep rate of 140 kHz. The stability of the system was measured to be 4.4 pm with a calibrated reflector, thus demonstrating near shot noise limited performance. Using this PhOCT system, we have acquired structural and vibratory measurements of the middle ear in a mouse model, post mortem. The quality of the results suggest that the akinetic laser source is a superior laser source for PhOCT with many advantages that greatly reduces the required complexity of the imaging system.« less

Effect of Environmental Factors on Intra-Specific Inhibitory Activity of Carnobacterium maltaromaticum

PubMed Central

Bowman, John P.; Ratkowsky, David A.; Tamplin, Mark

2017-01-01

Carnobacterium maltaromaticum is frequently associated with foods having extended shelf-life due to its inhibitory activity to other bacteria. The quantification of such inhibition interactions affected by various environmental factors is limited. This study investigated the effect of environmental factors relevant to vacuum-packaged beef on inhibition between two model isolates of C. maltaromaticum, D0h and D8c, specifically D8c sensitivity to D0h inhibition and D0h inhibitor production. The effects of temperature (−1, 7, 15, 25 °C), atmosphere (aerobic and anaerobic), pH (5.5, 6, 6.5), lactic acid (0, 25, 50 mM) and glucose (0, 0.56, 5.55 mM) on D8c sensitivity (diameter of an inhibition zone) were measured. The effects of pH, glucose, lactic acid and atmosphere on D0h inhibitor production were measured at 25 °C. Sensitivity of D8c was the highest at 15 °C, under aerobic atmosphere, at higher concentrations of undissociated lactic acid and glucose, and at pH 5.5 (p < 0.001). pH significantly affected D0h inhibitor production (p < 0.001), which was the highest at pH 6.5. The effect of lactic acid depended upon pH level; at relatively low pH (5.5), lactic acid decreased the production rate (arbitrary inhibition unit (AU)/mL/h). This study provides a quantitative description of intra-species interactions, studied in in vitro environments that are relevant to vacuum-packaged beef. PMID:28906433

Development of a direct competitive enzyme-linked immunosorbent assay for parathion residue in food samples.

PubMed

Gui, Wen-Jun; Liu, Yi-Hua; Wang, Chun-Mei; Liang, Xiao; Zhu, Guo-Nian

2009-10-01

A heterologous direct competitive enzyme-linked immunosorbent assay (ELISA) for parathion residue determination is described based on a monoclonal antibody and a new competitor. The effects of several physicochemical factors, such as methanol concentration, ionic strength, pH value, and sample matrix, on the performance of the ELISA were optimized for the sake of obtaining a satisfactory assay sensitivity. Results showed that when the assay medium was in the optimized condition (phosphate buffer solution [PBS] containing 10% [v/v] methanol and 0.2 mol/L NaCl at a pH value of 5.0), the sensitivity (estimated as the IC(50) value) and the limit of detection (LOD, estimated as the IC(10) value) were 1.19 and 0.08 ng/ml, respectively. The precision investigation indicated that the intraassay precision values all were below 10% and that the interassay precision values ranged from 4.89 to 19.12%. In addition, the developed ELISA showed a good linear correlation (r(2)=0.9962) to gas chromatography within the analyte's concentration range of 0.1 to 16 ng/ml. When applied to the fortified samples (parathion adding level: 5-15 microg/kg), the developed ELISA presented mean recoveries of 127.46, 122.52, 91.92, 124.01, 129.72, 99.37, and 87.17% for tomato, cucumber, banana, apple, orange, pear, and sugarcane, respectively. Results indicated that the established ELISA is a potential tool for parathion residue determination.

Field-scale modeling of acidity production and remediation efficiency during in situ reductive dechlorination

NASA Astrophysics Data System (ADS)

Brovelli, A.; Robinson, C. E.; Barry, D. A.; Gerhard, J.

2009-12-01

Enhanced reductive dechlorination is a viable technology for in situ remediation of chlorinated solvent DNAPL source areas. Although in recent years increased understanding of this technology has led to more rapid dechlorination rates, complete dechlorination can be hindered by unfavorable conditions. Hydrochloric acid produced from dechlorination and organic acids generated from electron donor fermentation can lead to significant groundwater acidification. Adverse pH conditions can inhibit the activity of dehalogenating microorganisms and thus slow or stall the remediation process. The extent of acidification likely to occur at a contaminated site depends on a number of factors including (1) the extent of dechlorination, (2) the pH-sensitivity of dechlorinating bacteria, and (3) the geochemical composition of the soil and water, in particular the soil’s natural buffering capacity. The substantial mass of solvents available for dechlorination when treating DNAPL source zones means that these applications are particularly susceptible to acidification. In this study a reactive transport biogeochemical model was developed to investigate the chemical and physical parameters that control the build-up of acidity and subsequent remediation efficiency. The model accounts for the site water chemistry, mineral precipitation and dissolution kinetics, electron donor fermentation, gas phase formation, competing electron-accepting processes (e.g., sulfate and iron reduction) and the sensitivity of microbial processes to pH. Confidence in the model was achieved by simulating a well-documented field study, for which the 2-D field scale model was able to reproduce long-term variations of pH, and the concurrent build up of reaction products. Sensitivity analyses indicated the groundwater flow velocity is able to reduce acidity build-up when the rate of advection is comparable or larger than the rate of dechlorination. The extent of pH change is highly dependent on the presence of calcite in soil, the availability of competing electron acceptors (in particular dissolved sulfates) and the efficiency with which microbes utilize electron donor. This work is part of SABRE (Source Area BioREmediation), a collaborative international research project that aimed to evaluate and improve enhanced bioremediation of chlorinated solvent source zones.

Intracellular delivery and antitumor effects of pH-sensitive liposomes based on zwitterionic oligopeptide lipids.

PubMed

Mo, Ran; Sun, Qiong; Li, Nan; Zhang, Can

2013-04-01

pH-sensitive liposomes (HHG2C(18)-L and PEGHG2C(18)-L) based on zwitterionic oligopeptide lipids as anticancer drug carriers were developed and evaluated for effective intracellular delivery and enhanced antitumor activity. The amino acid-based lipids, 1,5-dioctadecyl-l-glutamyl 2-histidyl-hexahydrobenzoic acid (HHG2C(18)) and 1,5-distearyl N-(N-α-(4-mPEG2000) butanedione)-histidyl-l-glutamate (PEGHG2C(18)), were synthesized, which have the multistage pH-response to tumor microenvironmental pH (pH(e), pH 6.0-7.0) and endosomal/lysosomal pH (pH(i), pH 4.0-6.0) successively. HHG2C(18)-L contains HHG2C(18), while PEGHG2C(18)-L includes HHG2C(18) and PEGHG2C(18). Both of them displayed the capability of charge conversion to the surrounding pH. The zeta potentials of HHG2C(18)-L and PEGHG2C(18)-L were negative at pH 7.4, whereas positive at pH 6.5 and more positive at lower pH. Coumarin 6-loaded HHG2C(18)-L (C6/HHG2C(18)-L) and PEGHG2C(18)-L (C6/PEGHG2C(18)-L) showed higher tumor cellular uptake due to electrostatic absorptive endocytosis at pH(e) (pH 6.5), produced proton sponge effect for endo-lysosomal escape, and accumulated to the mitochondria based on stronger positive charge by the hydrolysis of a pH-sensitive linker at pH(i) (pH 5.5 and pH 4.5). Furthermore, temsirolimus (CCI-779)-loaded HHG2C(18)-L (CCI-779/HHG2C(18)-L) and PEGHG2C(18)-L (CCI-779/PEGHG2C(18)-L) had significantly higher antiproliferative and apoptosis inducing effects toward the human renal carcinoma (A498) cells at pH 6.5 relative to that at pH 7.4. The half maximal inhibitory concentration (IC50) of CCI-779/HHG2C(18)-L and CCI-779/PEGHG2C(18)-L were about 3 μg/mL and 5 μg/mL at pH 6.5, 1.67-fold and 1.60-fold improved relative to that at pH 7.4, respectively. The total apoptotic ratio of CCI-779/HHG2C(18)-L and CCI-779/PEGHG2C(18)-L increased from 9.90% and 7.78% at pH 7.4 to 19.53% and 12.10% at pH 6.5, respectively. In vivo, CCI-779/PEGHG2C(18)-L after intravenous administration presented remarkably higher bioavailability and blood persistence compared with unPEGylated CCI-779/HHG2C(18)-L, and had the strongest antitumor efficacy against xenograft renal cancer (Renca) tumor models. Accordingly, the results provide the feasibility of using pH-sensitive zwitterionic oligopeptide lipids to extend the applications of liposomes to efficient anticancer drug delivery in cancer therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

New Amino-Acid-Based β-Phosphorylated Nitroxides for Probing Acidic pH in Biological Systems by EPR Spectroscopy.

PubMed

Thétiot-Laurent, Sophie; Gosset, Gaëlle; Clément, Jean-Louis; Cassien, Mathieu; Mercier, Anne; Siri, Didier; Gaudel-Siri, Anouk; Rockenbauer, Antal; Culcasi, Marcel; Pietri, Sylvia

2017-02-01

There is increasing interest in measuring pH in biological samples by using nitroxides with pH-dependent electron paramagnetic resonance (EPR) spectra. Aiming to improve the spectral sensitivity (Δa X ) of these probes (i.e., the difference between the EPR hyperfine splitting (hfs) in their protonated and unprotonated forms), we characterized a series of novel linear α-carboxy, α'-diethoxyphosphoryl nitroxides constructed on an amino acid core and featuring an (α or α')-C-H bond. In buffer, the three main hfs (a N , a H , and a P ) of their EPR spectra vary reversibly with pH and, from a P or a H titration curves, a two- to fourfold increase in sensitivity was achieved compared to reference imidazoline or imidazolidine nitroxides. The crystallized carboxylate 10 b (pK a ≈3.6), which demonstrated low cytotoxicity and good resistance to bioreduction, was applied to probe stomach acidity in rats. The results pave the way to a novel generation of highly sensitive EPR pH markers. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of protons on the mechanical response of rat muscle nociceptive fibers and neurons in vitro.

PubMed

Hotta, Norio; Kubo, Asako; Mizumura, Kazue

2015-03-01

Strong exercise makes muscle acidic, and painful. The stimulus that activates muscle nociceptors in such instance may be protons. Reportedly, however, not many afferents are excited by protons alone. We, therefore, posited that protons sensitize muscular nociceptors to mechanical stimuli. We examined effects of protons on mechanical sensitivity of muscle nociceptors by single-fiber recording from rat muscle-nerve preparations in vitro and by whole cell patch-clamp recording of mechanically activated (MA) currents from cultured rat dorsal root ganglion neurons. We recorded 38 Aδ- and C-fibers. Their response magnitude was increased by both pH 6.2 and pH 6.8; in addition the mechanical threshold was lowered by pH 6.2. Decrease in the threshold by pH6.2 was also observed in MA currents. Presently observed sensitization by protons could be involved in several types of ischemic muscle pain, and may also be involved in cardiovascular and respiratory controls during exercise. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

NMR structure of navel orangeworm moth pheromone-binding protein (AtraPBP1): implications for pH-sensitive pheromone detection.

PubMed

Xu, Xianzhong; Xu, Wei; Rayo, Josep; Ishida, Yuko; Leal, Walter S; Ames, James B

2010-02-23

The navel orangeworm, Amyelois transitella (Walker), is an agricultural insect pest that can be controlled by disrupting male-female communication with sex pheromones, a technique known as mating disruption. Insect pheromone-binding proteins (PBPs) provide fast transport of hydrophobic pheromones through the aqueous sensillar lymph and promote sensitive delivery of pheromones to receptors. Here we present the three-dimensional structure of a PBP from A. transitella (AtraPBP1) in solution at pH 4.5 determined by nuclear magnetic resonance (NMR) spectroscopy. Pulsed-field gradient NMR diffusion experiments, multiangle light scattering, and (15)N NMR relaxation analysis indicate that AtraPBP1 forms a stable monomer in solution at pH 4.5 in contrast to forming mostly dimers at pH 7. The NMR structure of AtraPBP1 at pH 4.5 contains seven alpha-helices (alpha1, L8-L23; alpha2, D27-F36; alpha3, R46-V62; alpha4, A73-M78; alpha5, D84-S100; alpha6, R107-L125; alpha7, M131-E141) that adopt an overall main-chain fold similar to that of PBPs found in Antheraea polyphemus and Bombyx mori. The AtraPBP1 structure is stabilized by three disulfide bonds formed by C19/C54, C50/C108, and C97/C117 and salt bridges formed by H69/E60, H70/E57, H80/E132, H95/E141, and H123/D40. All five His residues are cationic at pH 4.5, whereas H80 and H95 become neutral at pH 7.0. The C-terminal helix (alpha7) contains hydrophobic residues (M131, V133, V134, V135, V138, L139, and A140) that contact conserved residues (W37, L59, A73, F76, A77, I94, V111, and V115) suggested to interact with bound pheromone. Our NMR studies reveal that acid-induced formation of the C-terminal helix at pH 4.5 is triggered by a histidine protonation switch that promotes rapid release of bound pheromone under acidic conditions.

Influence of pH on the acute toxicity of ammonia to juvenile freshwater mussels (fatmucket, Lampsills siliquoidea)

USGS Publications Warehouse

Wang, N.; Erickson, R.J.; Ingersoll, C.G.; Ivey, C.D.; Brunson, E.L.; Augspurger, T.; Barnhart, M.C.

2008-01-01

The objective of the present study was to evaluate the influence of pH on the toxicity of ammonia to juvenile freshwater mussels. Acute 96-h ammonia toxicity tests were conducted with 10-d-old juvenile mussels (fatmucket, Lampsilis siliquoidea) at five pH levels ranging from 6.5 to 9.0 in flow-through diluter systems at 20??C. Acute 48-h tests with amphipods (Hyalella azteca) and 96-h tests with oligochaetes (Lumbriculus variegatus) were conducted concurrently under the same test conditions to determine the sensitivity of mussels relative to these two commonly tested benthic invertebrate species. During the exposure, pH levels were maintained within 0.1 of a pH unit and ammonia concentrations were relatively constant through time (coefficient of variation for ammonia concentrations ranged from 2 to 30% with a median value of 7.9%). The median effective concentrations (EC50s) of total ammonia nitrogen (N) for mussels were at least two to six times lower than the EC50s for amphipods and oligochaetes, and the EC50s for mussels decreased with increasing pH and ranged from 88 mg N/L at pH 6.6 to 0.96 mg N/L at pH 9.0. The EC50s for mussels were at or below the final acute values used to derive the U.S. Environmental Protection Agency's acute water quality criterion (WQC). However, the quantitative relationship between pH and ammonia toxicity to juvenile mussels was similar to the average relationship for other taxa reported in the WQC. These results indicate that including mussel toxicity data in a revision to the WQC would lower the acute criterion but not change the WQC mathematical representation of the relative effect of pH on ammonia toxicity. ?? 2008 SETAC.

Zr/ZrO2 sensors for in situ measurement of pH in high-temperature and -pressure aqueous solutions.

PubMed

Zhang, R H; Zhang, X T; Hu, S M

2008-04-15

The aim of this study is to develop new pH sensors that can be used to test and monitor hydrogen ion activity in hydrothermal conditions. A Zr/ZrO2 oxidation electrode is fabricated for in situ pH measurement of high-temperature aqueous solutions. This sensor responds rapidly and precisely to pH over a wide range of temperature and pressure. The Zr/ZrO2 electrode was made by oxidizing zirconium metal wire with Na2CO3 melt, which produced a thin film of ZrO2 on its surface. Thus, an oxidation-reduction electrode was produced. The Zr/ZrO2 electrode has a good electrochemical stability over a wide range of pH in high-temperature aqueous solutions when used with a Ag/AgCl reference electrode. Measurements of the Zr/ZrO2 sensor potential against a Ag/AgCl reference electrode is shown to vary linearly with pH between temperatures 20 and 200 degrees C. The slope of the potential versus pH at high temperature is slightly below the theoretical value indicated by the Nernst equation; such deviation is attributed to the fact that the sensor is not strictly at equilibrium with the solution to be tested in a short period of time. The Zr/ZrO2 sensor can be calibrated over the conditions that exist in the natural deep-seawater. Our studies showed that the Zr/ZrO2 electrode is a suitable pH sensor for the hydrothermal systems at midocean ridge or other geothermal systems with the high-temperature environment. Yttria-stabilized zirconia sensors have also been used to investigate the pH of hydrothermal fluids in hot springs vents at midocean ridge. These sensors, however, are not sensitive below 200 degrees C. Zr/ZrO2 sensors have wider temperature range and can be severed as good alternative sensors for measuring the pH of hydrothermal fluids.

TAME5OX, abiotic siderophore analogue to enterobactin involving 8-hydroxyquinoline subunits: Thermodynamic and photophysical studies

NASA Astrophysics Data System (ADS)

Akbar, Rifat; Baral, Minati; Kanungo, B. K.

2015-05-01

The synthesis, thermodynamic and photophysical properties of trivalent metal complexes of biomimetic nonadentate analogue, 5,5‧-(2-(((8-hydroxyquinolin-5-yl)methylamino)methyl)-2-methylpropane-1,3-diyl)bis(azanediyl)bis(methylene)diquinolin-8-ol (TAME5OX), have been described. Combination of absorption and emission spectrophotometry, potentiometry, electrospray mass spectrometry, IR, and theoretical investigation were used to fully characterize metal (Fe+3, Al+3 and Cr+3) chelates of TAME5OX. In solution, TAME5OX forms protonated complexes [M(H3L)]3+ below pH 3.4, which consecutively deprotonates through one to three-proton processes with rise of pH. The formation constants (Log β11n) of neutral complexes formed at or above physiological pH, have been determined to be 30.18, 23.27 and 22.02 with pM values of 31.16, 18.07 and 18.12 for Fe+3, Al+3 and Cr+3 ions, respectively, calculated at pH 7.4, indicating TAME5OX is a powerful among synthetic metal chelator. The results clearly demonstrate that the ligand in a tripodal orchestration firmly binds these ions over wide pH range and forms distorted octahedral complexes. The binding and the coordination event could be monitored from absorption and fluorescence spectroscopy. The high thermodynamic stability in water at physiological pH of ferric complex of TAME5OX indicates that these complexes are resistant to hydrolysis and therefore are well suited for the development of device for applications as probes. The ligand displays high sensitive fluorescence enhancement to Al3+ at pH 7.4, in water. Moreover, TAME5OX can distinguish Al3+ from Fe3+ and Cr3+ via two different sensing mechanisms: photoinduced electron transfer (PET) for Al3+ and internal charge transfer (ICT) for Fe3+ and Cr3+. Density functional theory was employed for optimization and evaluation of vibrational modes, NBO analysis, excitation and emission properties of the different species of metal complexes observed by solution studies.

TAME5OX, abiotic siderophore analogue to enterobactin involving 8-hydroxyquinoline subunits: thermodynamic and photophysical studies.

PubMed

Akbar, Rifat; Baral, Minati; Kanungo, B K

2015-05-05

The synthesis, thermodynamic and photophysical properties of trivalent metal complexes of biomimetic nonadentate analogue, 5,5'-(2-(((8-hydroxyquinolin-5-yl)methylamino)methyl)-2-methylpropane-1,3-diyl)bis(azanediyl)bis(methylene)diquinolin-8-ol (TAME5OX), have been described. Combination of absorption and emission spectrophotometry, potentiometry, electrospray mass spectrometry, IR, and theoretical investigation were used to fully characterize metal (Fe(+3), Al(+3) and Cr(+3)) chelates of TAME5OX. In solution, TAME5OX forms protonated complexes [M(H3L)](3+) below pH 3.4, which consecutively deprotonates through one to three-proton processes with rise of pH. The formation constants (Logβ11n) of neutral complexes formed at or above physiological pH, have been determined to be 30.18, 23.27 and 22.02 with pM values of 31.16, 18.07 and 18.12 for Fe(+3), Al(+3) and Cr(+3) ions, respectively, calculated at pH 7.4, indicating TAME5OX is a powerful among synthetic metal chelator. The results clearly demonstrate that the ligand in a tripodal orchestration firmly binds these ions over wide pH range and forms distorted octahedral complexes. The binding and the coordination event could be monitored from absorption and fluorescence spectroscopy. The high thermodynamic stability in water at physiological pH of ferric complex of TAME5OX indicates that these complexes are resistant to hydrolysis and therefore are well suited for the development of device for applications as probes. The ligand displays high sensitive fluorescence enhancement to Al(3+) at pH 7.4, in water. Moreover, TAME5OX can distinguish Al(3+) from Fe(3+) and Cr(3+) via two different sensing mechanisms: photoinduced electron transfer (PET) for Al(3+) and internal charge transfer (ICT) for Fe(3+) and Cr(3+). Density functional theory was employed for optimization and evaluation of vibrational modes, NBO analysis, excitation and emission properties of the different species of metal complexes observed by solution studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Polycrystalline silicon ion sensitive field effect transistors

NASA Astrophysics Data System (ADS)

Yan, F.; Estrela, P.; Mo, Y.; Migliorato, P.; Maeda, H.; Inoue, S.; Shimoda, T.

2005-01-01

We report the operation of polycrystalline silicon ion sensitive field effect transistors. These devices can be fabricated on inexpensive disposable substrates such as glass or plastics and are, therefore, promising candidates for low cost single-use intelligent multisensors. In this work we have developed an extended gate structure with a Si3N4 sensing layer. Nearly ideal pH sensitivity (54mV /pH) and stable operation have been achieved. Temperature effects have been characterized. A penicillin sensor has been fabricated by functionalizing the sensing area with penicillinase. The sensitivity to penicillin G is about 10mV/mM, in solutions with concentration lower than the saturation value, which is about 7 mM.

The sensitivity and significance analysis of parameters in the model of pH regulation on lactic acid production by Lactobacillus bulgaricus.

PubMed

Liu, Ke; Zeng, Xiangmiao; Qiao, Lei; Li, Xisheng; Yang, Yubo; Dai, Cuihong; Hou, Aiju; Xu, Dechang

2014-01-01

The excessive production of lactic acid by L. bulgaricus during yogurt storage is a phenomenon we are always tried to prevent. The methods used in industry either control the post-acidification inefficiently or kill the probiotics in yogurt. Genetic methods of changing the activity of one enzyme related to lactic acid metabolism make the bacteria short of energy to growth, although they are efficient ways in controlling lactic acid production. A model of pH-induced promoter regulation on the production of lactic acid by L. bulgaricus was built. The modelled lactic acid metabolism without pH-induced promoter regulation fitted well with wild type L. bulgaricus (R2LAC = 0.943, R2LA = 0.942). Both the local sensitivity analysis and Sobol sensitivity analysis indicated parameters Tmax, GR, KLR, S, V0, V1 and dLR were sensitive. In order to guide the future biology experiments, three adjustable parameters, KLR, V0 and V1, were chosen for further simulations. V0 had little effect on lactic acid production if the pH-induced promoter could be well induced when pH decreased to its threshold. KLR and V1 both exhibited great influence on the producing of lactic acid. The proposed method of introducing a pH-induced promoter to regulate a repressor gene could restrain the synthesis of lactic acid if an appropriate strength of promoter and/or an appropriate strength of ribosome binding sequence (RBS) in lacR gene has been designed.

Anilinomethylrhodamines: pH sensitive probes with tunable photophysical properties by substituent effect.

PubMed

Best, Quinn A; Liu, Chuangjun; van Hoveln, Paul D; McCarroll, Matthew E; Scott, Colleen N

2013-10-18

A series of pH dependent rhodamine analogues possessing an anilino-methyl moiety was developed and shown to exhibit a unique photophysical response to pH. These anilinomethylrhodamines (AnMR) maintain a colorless, nonfluorescent spirocyclic structure at high pH. The spirocyclic structures open in mildly acidic conditions and are weakly fluorescent; however, at very low pH, the fluorescence is greatly enhanced. The equilibrium constants of these processes show a linear response to substituent effects, which was demonstrated by the Hammett equation.

Polymer immobilized enzyme optrodes for the detection of penicillin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulp, T.J.; Camins, I.; Angel, S.M.

The preparation and performance of two enzyme-based fiber-optic sensors (optrodes) capable of detecting penicillin are described. Each sensor consists of a polymer membrane that is covalently attached to the tip of a glass optical fiber. The membrane contains the enzyme penicillinase and a pH-sensitive fluorescent dye. A signal is produced when the enzyme catalyzes the cleavage of the ..beta..-lactam ring of penicillin to produce penicilloic acid and, consequently, a pH change in the microenvironment of the membrane. The sensors differ in the way the polymer membrane is constructed and in the type of pH indicator dye used. Both optrodes exhibitmore » response times (40-60 s) significantly lower than those of the corresponding enzyme electrodes (2 min). Each gives a linear response over the concentration range of 0.00025 to 0.01 M penicillin G, when measured in a 0.005 M phosphate buffer. The data indicate that these immobilization strategies produce similar results and may be considered complementary alternatives in future enzyme optrode applications.« less

Photoconductivity, pH Sensitivity, Noise, and Channel Length Effects in Si Nanowire FET Sensors

NASA Astrophysics Data System (ADS)

Gasparyan, Ferdinand; Zadorozhnyi, Ihor; Khondkaryan, Hrant; Arakelyan, Armen; Vitusevich, Svetlana

2018-03-01

Silicon nanowire (NW) field-effect transistor (FET) sensors of various lengths were fabricated. Transport properties of Si NW FET sensors were investigated involving noise spectroscopy and current-voltage (I-V) characterization. The static I-V dependencies demonstrate the high quality of fabricated silicon FETs without leakage current. Transport and noise properties of NW FET structures were investigated under different light illumination conditions, as well as in sensor configuration in an aqueous solution with different pH values. Furthermore, we studied channel length effects on the photoconductivity, noise, and pH sensitivity. The magnitude of the channel current is approximately inversely proportional to the length of the current channel, and the pH sensitivity increases with the increase of channel length approaching the Nernst limit value of 59.5 mV/pH. We demonstrate that dominant 1/f-noise can be screened by the generation-recombination plateau at certain pH of the solution or external optical excitation. The characteristic frequency of the generation-recombination noise component decreases with increasing of illumination power. Moreover, it is shown that the measured value of the slope of 1/f-noise spectral density dependence on the current channel length is 2.7 which is close to the theoretically predicted value of 3.

Fluorescent Probes for Sensitive and Selective Detection of pH Changes in Live Cells in Visible and Near-infrared Channels.

PubMed

Fang, Mingxi; Adhikari, Rashmi; Bi, Jianheng; Mazi, Wafa; Dorh, Nethaniah; Wang, Jianbo; Conner, Nathan; Ainsley, Jon; Karabencheva-Christova, Tatyana G; Luo, Fen-Tair; Tiwari, Ashutosh; Liu, Haiying

2017-12-28

We report five fluorescent probes based on coumarin-hybridized fluorescent dyes with spirolactam ring structures (A-E) to detect pH changes in live cell by monitoring visible and near-infrared fluorescence changes. Under physiological or basic conditions, the fluorescent probes A, B, C, D and E preserve their spirolactam ring-closed forms and only display fluorescent peaks in the visible region corresponding to coumarin moieties at 497, 483, 498, 497 and 482 nm, respectively. However, at acidic pH, the rings of the spirolactam forms of the fluorescent probes A, B, C, D and E open up, generating new near-infrared fluorescence peaks at 711, 696, 707, 715, and 697 nm, respectively, through significantly extended π-conjugation to coumarin moieties of the fluorophores. The fluorescent probes B and E can be applied to visualize pH changes by monitoring visible as well as near-infrared fluorescence changes. This helps avoid fluorescence imaging blind spots at neutral or basic pH, which typical pH fluorescent probes encounter. The probes exhibit high sensitivity to pH changes, excellent photostability, low auto-fluorescence background and good cell membrane permeability.

A wireless pH sensor using magnetoelasticity for measurement of body fluid acidity.

PubMed

Pang, Pengfei; Gao, Xianjuan; Xiao, Xilin; Yang, Wenyue; Cai, Qingyun; Yao, Shouzhuo

2007-04-01

The determination of body fluid acidity using a wireless magnetoelastic pH-sensitive sensor is described. The sensor was fabricated by casting a layer of pH-sensitive polymer on a magnetoelastic ribbon. In response to an externally applied time-varying magnetic field, the magnetoelastic sensor mechanically vibrates at a characteristic frequency that is inversely dependent upon the mass of the pH polymer film, which varies as the film swells and shrinks in response to pH. As the magnetoelastic sensor is magnetostrictive, the mechanical vibrations of the sensor launch magnetic flux that can be detected remotely using a pickup coil. The sensor can be used for direct measurements of body fluid acidity without a pretreatment of the sample by using a filtration membrane. A reversible and linear response was obtained between pH 5.0 and 8.0 with a measurement resolution of pH 0.1 and a slope of 0.2 kHz pH(-1). Since there are no physical connections between the sensor and the instrument, the sensor can be applied to in vivo and in situ monitoring of the physiological pH and its fluctuations.

Fiber optic pH sensor with self-assembled polymer multilayer nanocoatings.

PubMed

Shao, Li-Yang; Yin, Ming-Jie; Tam, Hwa-Yaw; Albert, Jacques

2013-01-24

A fiber-optic pH sensor based on a tilted fiber Bragg grating (TFBG) with electrostatic self-assembly multilayer sensing film is presented. The pH sensitive polymeric film, poly(diallyldimethylammonium chloride) (PDDA) and poly(acrylic acid) (PAA) was deposited on the circumference of the TFBG with the layer-by-layer (LbL) electrostatic self-assembly technique. The PDDA/PAA film exhibits a reduction in refractive index by swelling in different pH solutions. This effect results in wavelength shifts and transmission changes in the spectrum of the TFBG. The peak amplitude of the dominant spectral fringes over a certain window of the transmission spectrum, obtained by FFT analysis, has a near-linear pH sensitivity of 117 arbitrary unit (a.u.)/pH unit and an accuracy of ±1 a.u. (in the range of pH 4.66 to pH 6.02). The thickness and surface morphology of the sensing multilayer film were characterized to investigate their effects on the sensor's performance. The dynamic response of the sensor also has been studied (10 s rise time and 18 s fall time for a sensor with six bilayers of PDDA/PAA).

Mid-infrared refractive index sensing using optimized slotted photonic crystal waveguides

NASA Astrophysics Data System (ADS)

Kassa-Baghdouche, Lazhar; Cassan, Eric

2018-02-01

Slotted photonic crystal waveguides (SPCWs) were designed to act as refractive index sensing devices at mid-infrared (IR) wavelengths around λ = 3.6 μm. In particular, effort was made to engineer the input and output slot waveguide interfaces in order to increase the effective sensitivity through resonant tapering. A slotted PhC waveguide immersed in air and liquid cladding layers was considered. To determine the performance of the sensor, the sensitivity of the device was estimated by calculating the shift in the upper band edge of the output transmission spectrum. The results showed that the sensitivity of a conventionally designed SPCW followed by modifications in the structure parameter yielded a 510 nm shift in the wavelength position of the upper band edge, indicating a sensitivity of more than 1150 nm per refractive index unit (RIU) with an insertion loss level of -0.3 dB. This work demonstrates the viability of photonic crystal waveguide high sensitivity devices in the Mid-IR, following a transposition of the concepts inherited from the telecom band and an optimization of the design, in particular a minimization of photonic device insertion losses.

A pH-based biosensor for detection of arsenic in drinking water.

PubMed

de Mora, K; Joshi, N; Balint, B L; Ward, F B; Elfick, A; French, C E

2011-05-01

Arsenic contaminated groundwater is estimated to affect over 100 million people worldwide, with Bangladesh and West Bengal being among the worst affected regions. A simple, cheap, accurate and disposable device is required for arsenic field testing. We have previously described a novel biosensor for arsenic in which the output is a change in pH, which can be detected visually as a colour change by the use of a pH indicator. Here, we present an improved formulation allowing sensitive and accurate detection of less than 10 ppb arsenate with static overnight incubation. Furthermore, we describe a cheap and simple high-throughput system for simultaneous monitoring of pH in multiple assays over time. Up to 50 samples can be monitored continuously over the desired time period. Cells can be stored and distributed in either air-dried or freeze-dried form. This system was successfully tested on arsenic-contaminated groundwater samples from the South East region of Hungary. We hope to continue to develop this sensor to produce a device suitable for field trials.

Poly methacrylic acid modified CDHA nanocomposites as potential pH responsive drug delivery vehicles.

PubMed

Victor, Sunita Prem; Sharma, Chandra P

2013-08-01

The objective of this study was to prepare pH sensitive polymethacrylic acid-calcium deficient hydroxyapatite (CDHA) nanocomposites. The CDHA nanoparticles were prepared by coprecipitation method. The modification of CDHA by methacrylic acid (MA) was achieved by AIBN initiated free radical polymerization with sodium bisulphite as catalyst followed by emulsion technique. These nanocomposites with a half life of 8h consisted of high aspect ratio, needle like particles and exhibited an increase in swelling behaviour with pH. The in vivo potential of the nanocomposites was evaluated in vitro by the results of cell aggregation, protein adsorption, MTT assay and haemolytic activity. The invitro loading and release studies using albumin as a model drug indicate that the nanocomposites gave better loading when compared to the CDHA nanoparticles and altered the drug release rates. The nanocomposites also exhibited good uptake on C6 glioma cells as studied by fluorescence microscopy. The results obtained suggest that these nanocomposites have great potential for oral controlled protein delivery and can be extended further for intracellular drug delivery applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Highly sensitive antibody-aptamer sensor for vascular endothelial growth factor based on hybridization chain reaction and pH meter/indicator.

PubMed

Xu, Huifeng; Kou, Fangxia; Ye, Hongzhi; Wang, Zongwen; Huang, Suixin; Liu, Xianxiang; Zhu, Xi; Lin, Zhenyu; Chen, Guonan

2017-12-01

Vascular endothelial growth factor (VEGF) is a crucial signaling protein for the tumor growth and metastasis, which is also acted as the biomarkers for various diseases. In this research, we fabricate an aptamer-antibody sensor for point-of-care test of VEGF. Firstly, target VEGF is captured by antibody immobilized on the microplate, and then binds with aptamer to form the sandwich structure. Next, with the assist of glucose oxidase (GOx)-functionalized ssDNAs, hybridization chain reaction occurs using the aptamer as the primer. Thus, GOx are greatly gathered on the microplate, which catalyzes the oxidization of glucose, leading to the pH change. As a result, the detect limit at a signal-to-noise was estimated to be 0.5pg/mL of target by pH meter, and 1.6pg/mL of VEGF was able to be distinguished by naked eyes. Meanwhile, this method has been used assay VEGF in the serum with the satisfactory results. Copyright © 2017. Published by Elsevier B.V.

Coral calcifying fluid pH is modulated by seawater carbonate chemistry not solely seawater pH

PubMed Central

Tambutté, E.; Carpenter, R. C.; Edmunds, P. J.; Evensen, N. R.; Allemand, D.; Ferrier-Pagès, C.; Tambutté, S.; Venn, A. A.

2017-01-01

Reef coral calcification depends on regulation of pH in the internal calcifying fluid (CF) in which the coral skeleton forms. However, little is known about calcifying fluid pH (pHCF) regulation, despite its importance in determining the response of corals to ocean acidification. Here, we investigate pHCF in the coral Stylophora pistillata in seawater maintained at constant pH with manipulated carbonate chemistry to alter dissolved inorganic carbon (DIC) concentration, and therefore total alkalinity (AT). We also investigate the intracellular pH of calcifying cells, photosynthesis, respiration and calcification rates under the same conditions. Our results show that despite constant pH in the surrounding seawater, pHCF is sensitive to shifts in carbonate chemistry associated with changes in [DIC] and [AT], revealing that seawater pH is not the sole driver of pHCF. Notably, when we synthesize our results with published data, we identify linear relationships of pHCF with the seawater [DIC]/[H+] ratio, [AT]/ [H+] ratio and []. Our findings contribute new insights into the mechanisms determining the sensitivity of coral calcification to changes in seawater carbonate chemistry, which are needed for predicting effects of environmental change on coral reefs and for robust interpretations of isotopic palaeoenvironmental records in coral skeletons. PMID:28100813

Evaluating nanoparticle sensor design for intracellular pH measurements.

PubMed

Benjaminsen, Rikke V; Sun, Honghao; Henriksen, Jonas R; Christensen, Nynne M; Almdal, Kristoffer; Andresen, Thomas L

2011-07-26

Particle-based nanosensors have over the past decade been designed for optical fluorescent-based ratiometric measurements of pH in living cells. However, quantitative and time-resolved intracellular measurements of pH in endosomes and lysosomes using particle nanosensors are challenging, and there is a need to improve measurement methodology. In the present paper, we have successfully carried out time-resolved pH measurements in endosomes and lyosomes in living cells using nanoparticle sensors and show the importance of sensor choice for successful quantification. We have studied two nanoparticle-based sensor systems that are internalized by endocytosis and elucidated important factors in nanosensor design that should be considered in future development of new sensors. From our experiments it is clear that it is highly important to use sensors that have a broad measurement range, as erroneous quantification of pH is an unfortunate result when measuring pH too close to the limit of the sensitive range of the sensors. Triple-labeled nanosensors with a pH measurement range of 3.2-7.0, which was synthesized by adding two pH-sensitive fluorophores with different pK(a) to each sensor, seem to be a solution to some of the earlier problems found when measuring pH in the endosome-lysosome pathway.

Fast loading ester fluorescent Ca2+ and pH indicators into pollen of Pyrus pyrifolia.

PubMed

Qu, Haiyong; Jiang, Xueting; Shi, Zebin; Liu, Lianmei; Zhang, Shaoling

2012-01-01

Loading of Ca(2+)-sensitive fluorescent probes into plant cells is an essential step to measure activities of free Ca(2+) ions in cytoplasm with a fluorescent imaging technique. Fluo-3 is one of the most suitable Ca(2+) indicators for CLSM. We loaded pollen with fluo-3/AM at three different temperatures. Fluo-3/AM was successfully loaded into pollen at both low (4°C) and high (37°C) temperatures. However, high loading temperature was best suited for pollen, because germination rate of pollen and growth of pollen tubes were relatively little impaired and loading time was shortened. Moreover, Ca(2+) distribution increased in the three apertures of pollen after hydration and showed a Ca(2+) gradient, similar to the tip of growing pollen tubes. The same protocol can be used with the AM-forms of other fluorescent dyes for effective labeling. When loading BCECF-AM into pollen at high temperature, the pollen did not show a pH gradient after hydration. Ca(2+) activities and fluxes had the same periodicity as pollen germination, but pH did not show the same phase and mostly lagged behind. However, the clear zone was alkaline when pollen tube growth was slowed or stopped and turned acidic when growth recovered. It is likely that apical pH(i) regulated pollen tube growth.

Changes in stream chemistry and biology in response to reduced levels of acid deposition during 1987-2003 in the Neversink River Basin, Catskill Mountains

USGS Publications Warehouse

Burns, Douglas A.; Riva-Murray, K.; Bode, R.W.; Passy, S.

2008-01-01

Atmospheric acid deposition has decreased in the northeastern United States since the 1970s, resulting in modest increases in pH, acid-neutralizing capacity (ANC), and decreases in inorganic monomeric aluminum (AlIM) concentrations since stream chemistry monitoring began in the 1980s in the acid-sensitive upper Neversink River basin in the Catskill Mountains of New York. Stream pH has increased by 0.01 units/year during 1987-2003 at three sites in the Neversink basin as determined by Seasonal Kendall trend analysis. In light of this observed decrease in stream acidity, we sampled 12 stream sites within the Neversink River watershed for water chemistry, macroinvertebrates, fish, and periphytic diatoms in 2003 to compare with a similar data set collected in 1987. Metrics and indices that reflect sensitivity to stream acidity were developed with these biological data to determine whether changes in stream biota over the intervening 16 years parallel those of stream chemistry. Statistical comparisons of data on stream chemistry and an acid biological assessment profile (Acid BAP) derived from invertebrate data showed no significant differences between the two years. For pH and ANC, however, values in 2003 were generally lower than those in 1987; this difference likely resulted from higher streamflow in summer 2003. Despite these likely flow-induced changes in summer 2003, an ordination and cluster analysis of macroinvertebrate taxa based on the Acid BAP indicated that the most acidic sites in the upstream half of the East Branch Neversink River form a statistically significant separate cluster consistent with less acidic stream conditions. This analysis is consistent with limited recovery of invertebrate species in the most acidic reaches of the river, but will require additional improvement in stream chemistry before a stronger conclusion can be drawn. Data on the fish and periphytic diatom communities in 2003 indicate that slimy sculpin had not extended their habitat to upstream reaches that previously were devoid of this acid-intolerant species in 1987; a diatom acid-tolerance index indicates continued high-acid impact throughout most of the East Branch and headwaters of the West Branch Neversink River. ?? 2007 Elsevier Ltd. All rights reserved.

Effect of Salt Concentration on the pH Responses of Strong and Weak Polyelectrolyte Brushes.

PubMed

Zhang, Jian; Kou, Ran; Liu, Guangming

2017-07-11

Strong polyelectrolyte brushes (SPB) and weak polyelectrolyte brushes (WPB) have different origins with response to pH, which makes their pH-responsive properties sensitive to salt concentration in different ways. Herein, we have employed poly[2-(methacryloyloxy)ethyl trimethylammonium chloride] (PMETAC) and poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) brushes as model systems for SPB and WPB, respectively, to investigate the effect of salt concentration on the pH responses of SPB and WPB using several surface-sensitive techniques. The pH-responsive properties of the PMETAC brushes are governed by the reorganization of the interchain hydrogen bonds between the grafted chains, whereas the pH response of the PDMAEMA brushes is controlled by the charge of the grafted chains. The response of the properties of the PMETAC brushes including hydration, conformation, and surface wettability becomes weaker with increasing salt concentration induced by the competitive adsorption of counterions to the brushes between OH - and Cl - . The weakening of the pH response of the PMETAC brushes is more remarkable at the relatively high pH values. The pH response of the PDMAEMA brushes also exhibits a salt-concentration dependence. As the salt concentration increases, the weakening of the pH response of the PDMAEMA brushes is attributed to the decrease in osmotic pressure within the brushes at relatively low pH values.

Performance evaluation of three on-site adulterant detection devices for urine specimens.

PubMed

Peace, Michelle R; Tarnai, Lisa D

2002-10-01

The performance of three on-site adulterant detection devices that assess the integrity of urine specimens collected for drug-of-abuse testing was evaluated: the Intect 7, MASK Ultra Screen, and Adultacheck 4. Intect 7 simultaneously tests creatinine, nitrite, glutaraldehyde, pH, specific gravity, and the presence of bleach and pyridinium chlorochromate (PCC). Mask Ultra Screen tests creatinine, nitrite, pH, specific gravity, and oxidants, and Adultacheck 4 tests creatinine, nitrite, glutaraldehyde, and pH. Urine specimens were prepared with the Substance Abuse and Mental Health Administration regulated analytes at 50% above the cut-off concentrations. Stealth, Urine Luck, Instant Clean ADD-IT-ive, and KLEAR were added individually to the drug-added urine specimens so that their concentrations reflected the "optimum" usage reported in their package inserts and 25% above and below that optimum. Stealth is reported to be peroxidase; Urine Luck is believed to be PCC; Instant Clean ADD-it-ive reportedly contains glutaraldehyde, and Klear is a nitrite. The following diluents/adulterants were added at 25%, 33%, and 50% of the volume of drug-added urine: distilled water, bleach, ammonia, and vinegar. Of the devices tested, Intect 7 proved to be the most sensitive, and it correctly indicated the presence of adulterant or diluent in all samples tested. In order to do so, all indication pads had to be assessed in concert. Adultacheck 4 specifically assesses four characteristics of urine integrity and is therefore very limited in detecting the use of several popular adulterants that are commercially available. Although it correctly assessed the four characteristics, it did not detect the use of Stealth, Urine Luck, or Instant Clean ADD-it-ive. Mask Ultra Screen can potentially detect a broader range of adulterants than Adultacheck 4. However, in practice, it only detected them at levels well above their optimum usage, making it less efficacious than Intect 7. Clearly, the specific identification of an adulterant is a trade-off for sensitive detection of several adulterants.

Viper and Cobra Venom Neutralization by Alginate Coated Multicomponent Polyvalent Antivenom Administered by the Oral Route

PubMed Central

Bhattacharya, Sourav; Chakraborty, Mousumi; Mukhopadhyay, Piyasi; Kundu, P. P.; Mishra, Roshnara

2014-01-01

Background Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals. Methodology/Principal Findings To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom. Conclusions/Significance Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom. Further research in this direction can strategize to counter such dilemma in snake bite management by promoting control release and oral antivenom rendered as a first aid. PMID:25102172

Fluorescence Lifetime Imaging Microscopy (FLIM) of quantum dots in living cells

NASA Astrophysics Data System (ADS)

Nadeau, Jay; Carlini, Lina

2013-02-01

Fluorescence lifetime imaging microscopy (FLIM) is an emerging imaging technique that can indicate environmental factors such as pH and redox potential by the effect of these factors on the fluorescence lifetimes of fluorophores. Semiconductor quantum dots (QDs) are highly sensitive to environment and so are ideal for use in FLIM, although certain experimental parameters must be carefully considered for QD imaging to account for their long lifetimes and two-photon behavior. We image the uptake of three types of QDs in cultured fibroblasts and show some preliminary results on the effects of endosomes and lysosomes on QD lifetimes. These results indicate the feasibility of FLIM for studies using QDs in live cells.

WO3 nanoparticle-based conformable pH sensor.

PubMed

Santos, Lídia; Neto, Joana P; Crespo, Ana; Nunes, Daniela; Costa, Nuno; Fonseca, Isabel M; Barquinha, Pedro; Pereira, Luís; Silva, Jorge; Martins, Rodrigo; Fortunato, Elvira

2014-08-13

pH is a vital physiological parameter that can be used for disease diagnosis and treatment as well as in monitoring other biological processes. Metal/metal oxide based pH sensors have several advantages regarding their reliability, miniaturization, and cost-effectiveness, which are critical characteristics for in vivo applications. In this work, WO3 nanoparticles were electrodeposited on flexible substrates over metal electrodes with a sensing area of 1 mm(2). These sensors show a sensitivity of -56.7 ± 1.3 mV/pH, in a wide pH range of 9 to 5. A proof of concept is also demonstrated using a flexible reference electrode in solid electrolyte with a curved surface. A good balance between the performance parameters (sensitivity), the production costs, and simplicity of the sensors was accomplished, as required for wearable biomedical devices.

Engineering the metal sensitive sites in Macrolampis sp2 firefly luciferase and use as a novel bioluminescent ratiometric biosensor for heavy metals.

PubMed

Gabriel, Gabriele V M; Viviani, Vadim R

2016-12-01

Most luminescent biosensors for heavy metals are fluorescent and rely on intensity measurements, whereas a few are ratiometric and rely on spectral changes. Bioluminescent biosensors for heavy metals are less common. Firefly luciferases have been coupled to responsive promoters for mercury and arsenium, and used as light on biosensors. Firefly luciferase bioluminescence spectrum is naturally sensitive to heavy metal cations such as zinc and mercury and to pH. Although pH sensitivity of firefly luciferases was shown to be useful for ratiometric estimation of intracellular pH, its potential use for ratiometric estimation of heavy metals was never considered. Using the yellow-emitting Macrolampis sp2 firefly luciferase and site-directed mutagenesis, we show that the residues H310 and E354 constitute two critical sites for metal sensitivity that can be engineered to increase sensitivity to zinc, nickel, and mercury. A linear relationship between cation concentration and the ratio of bioluminescence intensities at 550 and 610 nm allowed, for the first time, the ratiometric estimation of heavy metals concentrations down to 0.10 mM, demonstrating the potential applicability of firefly luciferases as enzymatic and intracellular ratiometric metal biosensors.

Radiation sensitivity of poliovirus, a model for norovirus, inoculated in oyster ( Crassostrea gigas) and culture broth under different conditions

NASA Astrophysics Data System (ADS)

Jung, Pil-Mun; Park, Jae Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Baek, Min; Chung, Young-Jin; Lee, Ju-Woon

2009-07-01

Poliovirus is a recognized surrogate for norovirus, pathogen in water and food, due to the structural and genetic similarity. Although radiation sensitivity of poliovirus in water or media had been reported, there has been no research in food model such as shellfish. In this study, oyster ( Crassostrea gigas) was incubated in artificial seawater contaminated with poliovirus, and thus radiation sensitivity of poliovirus was determined in inoculated oyster. The effects of ionizing radiation on the sensitivity of poliovirus were also evaluated under different conditions such as pH (4-7) and salt concentration (1-15%) in culture broth, and temperature during irradiation. The D10 value of poliovirus in PBS buffer, virus culture broth and oyster was determined to 0.46, 2.84 and 2.94 kGy, respectively. The initial plaque forming unit (PFU) of poliovirus in culture broth was slightly decreased as the decrease of pH and the increase of salt concentration, but radiation sensitivity was not affected by pH and salt contents. However, radiation resistance of poliovirus was increased at frozen state. These results provide the basic information for the inactivation of pathogenic virus in foods by using irradiation.

A highly sensitive nanoscale pH-sensor using Au nanoparticles linked by a multifunctional Raman-active reporter molecule

NASA Astrophysics Data System (ADS)

Lawson, Latevi S.; Chan, James W.; Huser, Thomas

2014-06-01

Chemical sensing on the nanoscale has been breaking new ground since the discovery of surface enhanced Raman scattering (SERS). For nanoparticles, controlled particle aggregation is necessary to achieve the largest SERS enhancements. Therefore, aggregating agents such as salts or linker molecules are used in conjunction with chemically sensitive reporters in order to develop robust environmentally sensitive SERS probes. While salt-induced colloidal nanosphere aggregates have produced robust SERS signals, their variability in aggregate size contributes significantly to poor SERS signal reproducibility, which can complicate their use in in vitro cellular studies. Such systems often also lack reproducibility in spectral measurements between different nanoparticle clusters. Preaggregation of colloids via linkers followed by surface functionalization with reporter molecules results in the linker occupying valuable SERS hotspot volume which could otherwise be utilized by additional reporter molecules. Ideally, both functionalities should be obtained from a single molecule. Here, we report the use of 3,5-dimercaptobenzoic acid, a single multifunctional molecule that creates SERS hotspots via the controlled aggregation of nanoparticles, and also reports pH values. We show that 3,5-dimercaptobenzoic acid bound to Au nanospheres results in an excellent pH nanoprobe, producing very robust, and highly reproducible SERS signals that can report pH across the entire physiological range with excellent pH resolution. To demonstrate the efficacy of our novel pH reporters, these probes were also used to image both the particle and pH distribution in the cytoplasm of human induced pluripotent stem cells (hiPSCs).Chemical sensing on the nanoscale has been breaking new ground since the discovery of surface enhanced Raman scattering (SERS). For nanoparticles, controlled particle aggregation is necessary to achieve the largest SERS enhancements. Therefore, aggregating agents such as salts or linker molecules are used in conjunction with chemically sensitive reporters in order to develop robust environmentally sensitive SERS probes. While salt-induced colloidal nanosphere aggregates have produced robust SERS signals, their variability in aggregate size contributes significantly to poor SERS signal reproducibility, which can complicate their use in in vitro cellular studies. Such systems often also lack reproducibility in spectral measurements between different nanoparticle clusters. Preaggregation of colloids via linkers followed by surface functionalization with reporter molecules results in the linker occupying valuable SERS hotspot volume which could otherwise be utilized by additional reporter molecules. Ideally, both functionalities should be obtained from a single molecule. Here, we report the use of 3,5-dimercaptobenzoic acid, a single multifunctional molecule that creates SERS hotspots via the controlled aggregation of nanoparticles, and also reports pH values. We show that 3,5-dimercaptobenzoic acid bound to Au nanospheres results in an excellent pH nanoprobe, producing very robust, and highly reproducible SERS signals that can report pH across the entire physiological range with excellent pH resolution. To demonstrate the efficacy of our novel pH reporters, these probes were also used to image both the particle and pH distribution in the cytoplasm of human induced pluripotent stem cells (hiPSCs). Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr06277e

pH sensitive thiolated cationic hydrogel for oral insulin delivery.

PubMed

Sonia, T A; Sharma, Chandra P

2014-04-01

The objective of this work is to study the efficacy of pH sensitive thiolated Polydimethylaminoethylmethacrylate for oral delivery of insulin. Synthesis of pH sensitive thiolated Polydimethylaminoethylmethacrylate (PDCPA) was carried out by crosslinking Polymethacrylic acid with thiolated Polydimethylaminoethylmethacrylate (PDCys) via carbodiimide chemistry. Prior to in vivo experiment, various physicochemical and biological characterisation were carried out to evaluate the efficacy of PDCPA. Modification was confirmed by IR and NMR spectroscopy. The particle size was found to be 284 nm with a zeta potential of 37.3+/-1.58 mV. Texture analyser measurements showed that PDCPA is more mucoadhesive than the parent polymer. Transepithelial electrical measurements showed a reduction of greater than 50% on incubation with PDCPA particles. Permeation studies showed that PDCPA is more permeable than the parent polymer. On in vivo evaluation on male diabetic rats, insulin loaded PDCPA exhibited a blood glucose reduction of 19%.

Citizen science identifies the effects of nitrogen deposition, climate and tree species on epiphytic lichens across the UK.

PubMed

Welden, N A; Wolseley, P A; Ashmore, M R

2018-01-01

A national citizen survey quantified the abundance of epiphytic lichens that are known to be either sensitive or tolerant to nitrogen (N) deposition. Records were collected across the UK from over 10,000 individual trees of 22 deciduous species. Mean abundance of tolerant and sensitive lichens was related to mean N deposition rates and climatic variables at a 5 km scale, and the response of lichens was compared on the three most common trees (Quercus, Fraxinus and Acer) and by assigning all 22 tree species to three bark pH groups. The abundance of N-sensitive lichens on trunks decreased with increasing total N deposition, while that of N-tolerant lichens increased. The abundance of N-sensitive lichens on trunks was reduced close to a busy road, while the abundance of N-tolerant lichens increased. The abundance of N-tolerant lichen species on trunks was lower on Quercus and other low bark pH species, but the abundance of N-sensitive lichens was similar on different tree species. Lichen abundance relationships with total N deposition did not differ between tree species or bark pH groups. The response of N-sensitive lichens to reduced nitrogen was greater than to oxidised N, and the response of N-tolerant lichens was greater to oxidised N than to reduced N. There were differences in the response of N-sensitive and N-tolerant lichens to rainfall, humidity and temperature. Relationships with N deposition and climatic variables were similar for lichen presence on twigs as for lichen abundance on trunks, but N-sensitive lichens increased, rather than decreased, on twigs of Quercus/low bark pH species. The results demonstrate the unique power of citizen science to detect and quantify the air pollution impacts over a wide geographical range, and specifically to contribute to understanding of lichen responses to different chemical forms of N deposition, local pollution sources and bark chemistry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Benzothiazole-Based AIEgen with Tunable Excited-State Intramolecular Proton Transfer and Restricted Intramolecular Rotation Processes for Highly Sensitive Physiological pH Sensing.

PubMed

Li, Kai; Feng, Qi; Niu, Guangle; Zhang, Weijie; Li, Yuanyuan; Kang, Miaomiao; Xu, Kui; He, Juan; Hou, Hongwei; Tang, Ben Zhong

2018-04-23

In this work, a benzothiazole-based aggregation-induced emission luminogen (AIEgen) of 2-(5-(4-carboxyphenyl)-2-hydroxyphenyl)benzothiazole (3) was designed and synthesized, which exhibited multifluorescence emissions in different dispersed or aggregated states based on tunable excited-state intramolecular proton transfer (ESIPT) and restricted intramolecular rotation (RIR) processes. 3 was successfully used as a ratiometric fluorescent chemosensor for the detection of pH, which exhibited reversible acid/base-switched yellow/cyan emission transition. More importantly, the pH jump of 3 was very precipitous from 7.0 to 8.0 with a midpoint of 7.5, which was well matched with the physiological pH. This feature makes 3 very suitable for the highly sensitive detection of pH fluctuation in biosamples and neutral water samples. 3 was also successfully used as a ratiometric fluorescence chemosensor for the detection of acidic and basic organic vapors in test papers.

Nanosensor aided photoacoustic measurement of pH in vivo

NASA Astrophysics Data System (ADS)

Ray, Aniruddha; Yoon, Hyung Ki; Kopelman, Raoul; Wang, Xueding

2013-03-01

pH plays a critical role in many aspects of cell and tissues physiology. Lower pH is also a typical characteristic of arthritic joints and tumor tissues. These pH anomalies are also exploited in different drug delivery mechanisms. Here we present, a new method of pH sensing in vivo using spectroscopic photoacoustic measurements facilitated by pH sensitive nanosensors. The nanosensors consist of Seminaphtharhodafluor (SNARF), a pH sensitive dye, encapsulated in a specially designed polyacrylamide hydrogel matrix with a hydrophobic core. The photoacoustic intensity ratio between the excitation wavelengths of 585nm and 565nm increases in the pH range from 6.0 to 8.0 and is used to determine the pH of the local environment. These nanosensors are biodegradable, biocompatible, have a long plasma lifetime and can be targeted to any type of cells or tissues by surface modification using proper targeting moieties. The encapsulation of the dye prevents the interaction of the dye with proteins in plasma and also reduces the dye degradation. The SNARF dye in its free form loses 90% of its absorbance in presence of albumin, a protein found in abundance in plasma, and this has severely limited its adaptation to in vivo environments. In comparison, the SNARF nanosensors lose only 16% of their absorbance in the same environment. We employ these nanosensors to demonstrate the feasibility of pH sensing in vivo through photoacoustic measurements on a rat joint model.

pH-Assisted control over the binding and relocation of an acridine guest between a macrocyclic nanocarrier and natural DNA.

PubMed

Sayed, Mhejabeen; Pal, Haridas

2015-04-14

The differential binding affinity of the hydroxypropyl-β-cyclodextrin (HPβCD) macrocycle, a drug delivery vehicle, towards the protonated and deprotonated forms of the well-known DNA binder and model anticancer drug acridine has been exploited as a strategy for dye-drug transportation and pH-responsive delivery to a natural DNA target. From pH-sensitive changes in the ground state absorption and steady-state fluorescence characteristics of the studied acridine dye-HPβCD-DNA ternary system and strongly supported by fluorescence lifetime, fluorescence anisotropy, Job's plots, (1)H NMR and circular dichroism results, it is revealed that in a moderately alkaline solution (pH ∼ 8.5), the dye can be predominantly bound to the HPβCD macrocycle and when the pH is lowered to a moderately acidic region (pH ∼ 4), the dye efficiently detaches from the HPβCD cavity and almost exclusively binds to DNA. In the present study we are thus able to construct a pH-sensitive supramolecular assembly where pH acts as a simple stimulus for controlled uptake and targeted release of the dye-drug. As pH is an essential and sensitive factor in various biological processes, a simple yet reliable pH-sensitive model such as is demonstrated here can have promising applications in the host-assisted delivery of prodrug to the target sites, such as cancer or tumour microenvironments, with an enhanced stability, bioavailability and activity, and also in the design of new fluorescent probes, sensors and smart materials for applications in nano-science.

Strain-specific variation in a soilborne phytopathogenic fungus for the expression of genes involved in pH signal transduction pathway, pathogenesis and saprophytic survival in response to environmental pH changes.

PubMed

Daval, Stéphanie; Lebreton, Lionel; Gracianne, Cécile; Guillerm-Erckelboudt, Anne-Yvonne; Boutin, Morgane; Marchi, Muriel; Gazengel, Kévin; Sarniguet, Alain

2013-12-01

The soilborne fungus Gaeumannomyces graminis var. tritici (Ggt) causes take-all, a wheat root disease. In an original strain-specific way, a previous study indicates that inside the Ggt species, some strains grow preferentially at acidic pH and other strains at neutral/alkaline pH. The most important mechanism for a fungal response to the environmental pH is the Pal pathway which integrates the products of the six pal genes and the transcription factor PacC. To evaluate whether the Ggt strain-specific growth in function of the ambient pH is mediated via the Pal pathway, a transcriptional study of the genes encoding this pathway was carried out. This study provided the first evidence that the pH signalling pathway similar to those described in other fungi operated in Ggt. The pacC gene was induced at neutral pH whatever the strain. In an original way, the expression of Ggt genes coding for the different Pal proteins depended on the strain and on the ambient pH. In the strain growing better at acidic pH, few pal genes were pH-regulated, and some were overexpressed at neutral pH when regulated. In the strain growing better at neutral pH, underexpression of most of the pal genes at neutral pH occurred. The strains displayed higher gene expression in the ambient pH that unfavoured their growth as if it was a compensation system. All pH taken together, a globally weaker Pal transcript level occurred in the strains that were less sensitive to acidic pH, and on the contrary, the strain growing better on neutral pH showed higher Pal mRNA levels. The expression of genes involved in pathogenesis and saprophytic growth was also regulated by the ambient pH and the strain: each gene displayed a specific pH-regulation that was similar between strains. But all pH taken together, the global transcript levels of four out of six genes were higher in the strain growing better on neutral pH. Altogether, for the first time, the results show that inside a species, conditions affecting environmental pH modulate the expression of genes in an original strain-specific way. Copyright © 2013 Elsevier Inc. All rights reserved.

Mechanism of Bacterial Inactivation by (+)-Limonene and Its Potential Use in Food Preservation Combined Processes

PubMed Central

Espina, Laura; Gelaw, Tilahun K.; de Lamo-Castellví, Sílvia; Pagán, Rafael; García-Gonzalo, Diego

2013-01-01

This work explores the bactericidal effect of (+)-limonene, the major constituent of citrus fruits' essential oils, against E. coli. The degree of E. coli BJ4 inactivation achieved by (+)-limonene was influenced by the pH of the treatment medium, being more bactericidal at pH 4.0 than at pH 7.0. Deletion of rpoS and exposure to a sub-lethal heat or an acid shock did not modify E. coli BJ4 resistance to (+)-limonene. However, exposure to a sub-lethal cold shock decreased its resistance to (+)-limonene. Although no sub-lethal injury was detected in the cell envelopes after exposure to (+)-limonene by the selective-plating technique, the uptake of propidium iodide by inactivated E. coli BJ4 cells pointed out these structures as important targets in the mechanism of action. Attenuated Total Reflectance Infrared Microspectroscopy (ATR-IRMS) allowed identification of altered E. coli BJ4 structures after (+)-limonene treatments as a function of the treatment pH: β-sheet proteins at pH 4.0 and phosphodiester bonds at pH 7.0. The increased sensitivity to (+)-limonene observed at pH 4.0 in an E. coli MC4100 lptD4213 mutant with an increased outer membrane permeability along with the identification of altered β-sheet proteins by ATR-IRMS indicated the importance of this structure in the mechanism of action of (+)-limonene. The study of mechanism of inactivation by (+)-limonene led to the design of a synergistic combined process with heat for the inactivation of the pathogen E. coli O157:H7 in fruit juices. These results show the potential of (+)-limonene in food preservation, either acting alone or in combination with lethal heat treatments. PMID:23424676

Mechanism of Fine-tuning pH Sensors in Proprotein Convertases: IDENTIFICATION OF A pH-SENSING HISTIDINE PAIR IN THE PROPEPTIDE OF PROPROTEIN CONVERTASE 1/3.

PubMed

Williamson, Danielle M; Elferich, Johannes; Shinde, Ujwal

2015-09-18

The propeptides of proprotein convertases (PCs) regulate activation of cognate protease domains by sensing pH of their organellar compartments as they transit the secretory pathway. Earlier experimental work identified a conserved histidine-encoded pH sensor within the propeptide of the canonical PC, furin. To date, whether protonation of this conserved histidine is solely responsible for PC activation has remained unclear because of the observation that various PC paralogues are activated at different organellar pH values. To ascertain additional determinants of PC activation, we analyzed PC1/3, a paralogue of furin that is activated at a pH of ∼5.4. Using biophysical, biochemical, and cell-based methods, we mimicked the protonation status of various histidines within the propeptide of PC1/3 and examined how such alterations can modulate pH-dependent protease activation. Our results indicate that whereas the conserved histidine plays a crucial role in pH sensing and activation of this protease an additional histidine acts as a "gatekeeper" that fine-tunes the sensitivity of the PC1/3 propeptide to facilitate the release inhibition at higher proton concentrations when compared with furin. Coupled with earlier analyses that highlighted the enrichment of the amino acid histidine within propeptides of secreted eukaryotic proteases, our work elucidates how secreted proteases have evolved to exploit the pH of the secretory pathway by altering the spatial juxtaposition of titratable groups to regulate their activity in a spatiotemporal fashion. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Mechanism of bacterial inactivation by (+)-limonene and its potential use in food preservation combined processes.

PubMed

Espina, Laura; Gelaw, Tilahun K; de Lamo-Castellví, Sílvia; Pagán, Rafael; García-Gonzalo, Diego

2013-01-01

This work explores the bactericidal effect of (+)-limonene, the major constituent of citrus fruits' essential oils, against E. coli. The degree of E. coli BJ4 inactivation achieved by (+)-limonene was influenced by the pH of the treatment medium, being more bactericidal at pH 4.0 than at pH 7.0. Deletion of rpoS and exposure to a sub-lethal heat or an acid shock did not modify E. coli BJ4 resistance to (+)-limonene. However, exposure to a sub-lethal cold shock decreased its resistance to (+)-limonene. Although no sub-lethal injury was detected in the cell envelopes after exposure to (+)-limonene by the selective-plating technique, the uptake of propidium iodide by inactivated E. coli BJ4 cells pointed out these structures as important targets in the mechanism of action. Attenuated Total Reflectance Infrared Microspectroscopy (ATR-IRMS) allowed identification of altered E. coli BJ4 structures after (+)-limonene treatments as a function of the treatment pH: β-sheet proteins at pH 4.0 and phosphodiester bonds at pH 7.0. The increased sensitivity to (+)-limonene observed at pH 4.0 in an E. coli MC4100 lptD4213 mutant with an increased outer membrane permeability along with the identification of altered β-sheet proteins by ATR-IRMS indicated the importance of this structure in the mechanism of action of (+)-limonene. The study of mechanism of inactivation by (+)-limonene led to the design of a synergistic combined process with heat for the inactivation of the pathogen E. coli O157:H7 in fruit juices. These results show the potential of (+)-limonene in food preservation, either acting alone or in combination with lethal heat treatments.

The potential role of oral pH in the persistence of Trichomonas gallinae in Cooper's Hawks (Accipiter cooperii).

PubMed

Urban, Elizabeth H; Mannan, R William

2014-01-01

Trichomoniasis, caused by the protozoan Trichomonas gallinae, affects a variety of species worldwide including avivorious raptors. Existing information suggests that the disease is most prevalent in young birds, and differential susceptibility to trichomoniasis among individuals in different age groups was documented in Cooper's Hawks (Accipiter cooperii) nesting in Tucson, Arizona. In that population, 85% of nestling Cooper's Hawks had T. gallinae in their oral cavity, compared to only 1% of breeding-age hawks. Trichomonads generally are sensitive to environmental pH and we explored the possibility that differences in oral pH may contribute to the differential prevalence of infection between age groups. We measured the pH of the fluid in the oral cavity in 375 Cooper's Hawks from three age groups (nestlings, fledglings, and breeding age) in Tucson, Arizona, in 2010 and 2011 and clinically tested for T. gallinae in a subsample of hawks. Oral pH of nestlings (∼ 6.8) was 7.3 times less acidic than in fledgling or breeding Cooper's Hawks (∼ 6.1). The incidence of T. gallinae was higher in nestlings (16%) than in either fledglings or breeding hawks (0%). Our findings indicate that oral pH becomes more acidic in Cooper's Hawks soon after they leave the nest. Trichomonas gallinae thrives when pH is between 6.5 and 7.5 (optimum 7.2), but is less viable in more acidic conditions. Higher levels of acidity in the oral cavity of fledglings and breeding Cooper's Hawks may reduce their susceptibility to trichomoniasis, and play a role in the differential prevalence of infection among age groups.

Effect of pH on the Structure and DNA Binding of the FOXP2 Forkhead Domain.

PubMed

Blane, Ashleigh; Fanucchi, Sylvia

2015-06-30

Forkhead box P2 (FOXP2) is a transcription factor expressed in cardiovascular, intestinal, and neural tissues during embryonic development and is implicated in language development. FOXP2 like other FOX proteins contains a DNA binding domain known as the forkhead domain (FHD). The FHD interacts with DNA by inserting helix 3 into the major groove. One of these DNA-protein interactions is a direct hydrogen bond that is formed with His554. FOXP2 is localized in the nuclear compartment that has a pH of 7.5. Histidine contains an imidazole side chain in which the amino group typically has a pKa of ~6.5. It seems possible that pH fluctuations around 6.5 may result in changes in the protonation state of His554 and thus the ability of the FOXP2 FHD to bind DNA. To investigate the effect of pH on the FHD, both the structure and the binding affinity were studied in the pH range of 5-9. This was done in the presence and absence of DNA. The structure was assessed using size exclusion chromatography, far-UV circular dichroism, and intrinsic and extrinsic fluorescence. The results indicated that while pH did not affect the secondary structure in the presence or absence of DNA, the tertiary structure was pH sensitive and the protein was less compact at low pH. Furthermore, the presence of DNA caused the protein to become more compact at low pH and also had the potential to increase the dimerization propensity. Fluorescence anisotropy was used to investigate the effect of pH on the FOXP2 FHD DNA binding affinity. It was found that pH had a direct effect on binding affinity. This was attributed to the altered hydrogen bonding patterns upon protonation or deprotonation of His554. These results could implicate pH as a means of regulating transcription by the FOXP2 FHD, which may also have repercussions for the behavior of this protein in cancer cells.

Responses of glomus cells to hypoxia and acidosis are uncoupled, reciprocal and linked to ASIC3 expression: selectivity of chemosensory transduction

PubMed Central

Lu, Yongjun; Whiteis, Carol A; Sluka, Kathleen A; Chapleau, Mark W; Abboud, François M

2013-01-01

Carotid body glomus cells are the primary sites of chemotransduction of hypoxaemia and acidosis in peripheral arterial chemoreceptors. They exhibit pronounced morphological heterogeneity. A quantitative assessment of their functional capacity to differentiate between these two major chemical signals has remained undefined. We tested the hypothesis that there is a differential sensory transduction of hypoxia and acidosis at the level of glomus cells. We measured cytoplasmic Ca2+ concentration in individual glomus cells, isolated in clusters from rat carotid bodies, in response to hypoxia ( mmHg) and to acidosis at pH 6.8. More than two-thirds (68%) were sensitive to both hypoxia and acidosis, 19% were exclusively sensitive to hypoxia and 13% exclusively sensitive to acidosis. Those sensitive to both revealed significant preferential sensitivity to either hypoxia or to acidosis. This uncoupling and reciprocity was recapitulated in a mouse model by altering the expression of the acid-sensing ion channel 3 (ASIC3) which we had identified earlier in glomus cells. Increased expression of ASIC3 in transgenic mice increased pH sensitivity while reducing cyanide sensitivity. Conversely, deletion of ASIC3 in the knockout mouse reduced pH sensitivity while the relative sensitivity to cyanide or to hypoxia was increased. In this work, we quantify functional differences among glomus cells and show reciprocal sensitivity to acidosis and hypoxia in most glomus cells. We speculate that this selective chemotransduction of glomus cells by either stimulus may result in the activation of different afferents that are preferentially more sensitive to either hypoxia or acidosis, and thus may evoke different and more specific autonomic adjustments to either stimulus. PMID:23165770

New Pseudomonad Utilizing Methanol for Growth

PubMed Central

Chalfan, Y.; Mateles, R. I.

1972-01-01

A bacterium capable of rapid growth on methanol as sole carbon source was isolated and classified as a new pseudomonad. Its doubling time was about 100 min at 32 to 37 C, and it grew well at methanol concentrations up to 2%. The organism was sensitive to phosphate, but reasonable cell densities could be obtained by using pH control. Cell yields of about 31%, based on methanol consumed, were obtained. The amino acid pattern of the protein indicated that the bacterium holds promise as a source of single-cell protein. Images PMID:4110421

Inactivation of human and simian rotaviruses by ozone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaughn, J.M.; Chen, Y.S.; Lindburg, K.

1987-09-01

The inactivation of simian rotavirus Sa-11 and human rotavirus type 2 (Wa) by ozone was compared at 4/sup 0/C by using single-particle virus stocks. Although the human strain was clearly more sensitive, both virus types were rapidly inactivated by ozone concentrations of 0.25 mg/liter or greater at all pH levels tested. Comparison of the virucidal activity of ozone with that of chlorine in identical experiments indicated little significant difference in rotavirus-inactivating efficiencies when the disinfectants were used at concentrations of 0.25 mg/liter or greater.

Microencapsulation Technology for Corrosion Mitigation by Smart Coatings

NASA Technical Reports Server (NTRS)

Buhrow, Jerry; Li, Wenyan; Jolley, Scott; Calle, Luz M.

2011-01-01

A multifunctional, smart coating for the autonomous control of corrosion is being developed based on micro-encapsulation technology. Corrosion indicators as well as corrosion inhibitors have been incorporated into microcapsules, blended into several paint systems, and tested for corrosion detection and protection effectiveness. This paper summarizes the development, optimization, and testing of microcapsules specifically designed to be incorporated into a smart coating that will deliver corrosion inhibitors to mitigate corrosion autonomously. Key words: smart coating, corrosion inhibition, microencapsulation, microcapsule, pH sensitive microcapsule, corrosion inhibitor, corrosion protection pain

pH-Induced Modulation of One- and Two-Photon Absorption Properties in a Naphthalene-Based Molecular Probe.

PubMed

Murugan, N Arul; Kongsted, Jacob; Ågren, Hans

2013-08-13

Presently, there is a great demand for small probe molecules that can be used for two-photon excitation microscopy (TPM)-based monitoring of intracellular and intraorganelle activity and pH. The candidate molecules should ideally possess a large two-photon absorption cross section with optical properties sensitive to pH changes. In the present work, we investigate the potential of a methoxy napthalene (MONAP) derivative for its suitability to serve as a pH sensor using TPM. Using an integrated approach rooted in hybrid quantum mechanics/molecular mechanics, the structures, dynamics, and the one- and two-photon properties of the probe in dimethylformamide solvent are studied. It is found that the protonated form is responsible for the optical property of MONAP at moderately low pH, for which the calculated pH-induced red shift is in good agreement with experiments. A 2-fold increase in the two-photon absorption cross section in the IR region of the spectrum is predicted for the moderately low pH form of the probe, suggesting that this can be a potential probe for pH monitoring of living cells. We also propose some design principles aimed at obtaining control of the absorption spectral range of the probe by structural tuning. Our work indicates that the integrated approach employed is capable of capturing the pH-induced changes in structure and optical properties of organic molecular probes and that such in silico tools can be used to draw structure-property relationships to design novel molecular probes suitable for a specific application.

CIP (cleaning-in-place) stability of AlGaN/GaN pH sensors.

PubMed

Linkohr, St; Pletschen, W; Schwarz, S U; Anzt, J; Cimalla, V; Ambacher, O

2013-02-20

The CIP stability of pH sensitive ion-sensitive field-effect transistors based on AlGaN/GaN heterostructures was investigated. For epitaxial AlGaN/GaN films with high structural quality, CIP tests did not degrade the sensor surface and pH sensitivities of 55-58 mV/pH were achieved. Several different passivation schemes based on SiO(x), SiN(x), AlN, and nanocrystalline diamond were compared with special attention given to compatibility to standard microelectronic device technologies as well as biocompatibility of the passivation films. The CIP stability was evaluated with a main focus on the morphological stability. All stacks containing a SiO₂ or an AlN layer were etched by the NaOH solution in the CIP process. Reliable passivations withstanding the NaOH solution were provided by stacks of ICP-CVD grown and sputtered SiN(x) as well as diamond reinforced passivations. Drift levels about 0.001 pH/h and stable sensitivity over several CIP cycles were achieved for optimized sensor structures. Copyright © 2012 Elsevier B.V. All rights reserved.

Simultaneous pH-sensitive and oxygen-sensitive MRI of human gliomas at 3 T using multi-echo amine proton chemical exchange saturation transfer spin-and-gradient echo echo-planar imaging (CEST-SAGE-EPI).

PubMed

Harris, Robert J; Yao, Jingwen; Chakhoyan, Ararat; Raymond, Catalina; Leu, Kevin; Liau, Linda M; Nghiemphu, Phioanh L; Lai, Albert; Salamon, Noriko; Pope, Whitney B; Cloughesy, Timothy F; Ellingson, Benjamin M

2018-04-06

To introduce a new pH-sensitive and oxygen-sensitive MRI technique using amine proton CEST echo spin-and-gradient echo (SAGE) EPI (CEST-SAGE-EPI). pH-weighting was obtained using CEST estimations of magnetization transfer ratio asymmetry (MTR asym ) at 3 ppm, and oxygen-weighting was obtained using R2' measurements. Glutamine concentration, pH, and relaxation rates were varied in phantoms to validate simulations and estimate relaxation rates. The values of MTR asym and R2' in normal-appearing white matter, T 2 hyperintensity, contrast enhancement, and macroscopic necrosis were measured in 47 gliomas. Simulation and phantom results confirmed an increase in MTR asym with decreasing pH. The CEST-SAGE-EPI estimates of R 2 , R2*, and R2' varied linearly with gadolinium diethylenetriamine penta-acetic acid concentration (R 2  = 6.2 mM -1 ·sec -1 and R2* = 6.9 mM -1 ·sec -1 ). The CEST-SAGE-EPI and Carr-Purcell-Meiboom-Gill estimates of R 2 (R 2  = 0.9943) and multi-echo gradient-echo estimates of R2* (R 2  = 0.9727) were highly correlated. T 2 lesions had lower R2' and higher MTR asym compared with normal-appearing white matter, suggesting lower hypoxia and high acidity, whereas contrast-enhancement tumor regions had elevated R2' and MTR asym , indicating high hypoxia and acidity. The CEST-SAGE-EPI technique provides simultaneous pH-sensitive and oxygen-sensitive image contrasts for evaluation of the brain tumor microenvironment. Advantages include fast whole-brain acquisition, in-line B 0 correction, and simultaneous estimation of CEST effects, R 2 , R2*, and R2' at 3 T. © 2018 International Society for Magnetic Resonance in Medicine.

Histone H3 phosphorylation in GBM: a new rational to guide the use of kinase inhibitors in anti-GBM therapy.

PubMed

Pacaud, Romain; Cheray, Mathilde; Nadaradjane, Arulraj; Vallette, François M; Cartron, Pierre-François

2015-01-01

Histones post-translational modifications (PTMs) are crucial components of diverse processes that modulate chromatin. Among the histones PTMs, the histones phosphorylation appears such crucial since it plays a significant role into DNA repair structure, transcription and chromatin compaction during cell division and apoptosis. However, little is known about the prognostic value of the histone phosphorylation in human cancer. This point could be considerate such as an important gap in anti-cancer therapy since the use of adequate kinase inhibitors could remedy to the aberrant histone phosphorylation associated with a poor prognosis factor. To remedy at this situation, we analyzed the phosphorylation level of histone H3 at the residues T3, T6, S10, S28, Y41 and T45 in a collection of 42 glioblastoma multiformes (GBM). Our data indicated that the high level of pH3T6, pH3S10 and pH3Y41 are signatures associated with a poor prognosis of overall survival (OS) of GBM treated with the "temozolomide and irradiation standard" treatment of GBM (named TMZ+Irad treatment). Our data also showed that these signatures are correlated with the high activity of kinases already described as writers of the pH3T6, pH3S10 and pH3Y41 i.e. the PKC, Aurora-B and JAK2, respectively. Finally, our analysis revealed that the use of Enzastaurin, AZD1152, and AZD1480 abrogated the high level of pH3T6, pH3S10 and pH3Y41 while increasing the sensitivity to the "temozolomide and irradiation"-induced cell death. To conclude, it appears that this work provides biomarkers for patient stratification for a therapy including kinase inhibitors.

Formulation of a stable parenteral product; Clonidine Hydrochloride Injection.

PubMed

Kostecka, D; Duncan, M R; Wagenknecht, D

1998-01-01

Clonidine Hydrochloride Injection (Duraclon) is a clear, colorless, preservative-free, pyrogen free, aqueous solution of clonidine hydrochloride. The indication for this product is for use as an adjunct in pain management, administered epidurally, when opiates are insufficient. The drug formulation was evaluated under both normal and stress conditions in the preformulation/formulation studies. The list of studies conducted includes a light sensitivity study, an oxygen sensitivity study, a pH/stability study, a stopper compatibility evaluation, a freeze-thaw study, and a stability study. Samples from the light, oxygen, pH/stability, and stability studies were evaluated for color, visual clarity, pH, potency, and chromatographic purity. Samples from the freeze-thaw study were evaluated for all of the above except chromatographic purity. The results for these studies demonstrate the stability of the product as formulated. The pH of this unbuffered product was consistently within the acceptance criteria. The product remained clear and colorless for the duration of each study. The values obtained for the potency and chromatographic purity assays showed no evidence of degradation. The reasons for the lack of degradation can be found in the molecular structure of the drug substance and the formulation of the drug product. Since the molecular structure is that of a Schiff base, it is theoretically possible, although difficult, to cleave the molecule. A catalyst would be required, and none of the possible catalysts are present in the formulation. The molecule could also be cleaved upon exposure to light, and the evidence indicates that the molecule does interact with light. This interaction is not to the degree, however, that product stability is affected. The formulation contains only the active drug substance and sodium chloride in water for injection with a pH of approximately 6. Although the product is unbuffered, the influence of the stoppers and glass vials upon the formulation pH was minimal. In addition, the stopper compatibility of the product is enhanced by the absence of chelating agents, preservatives, acids, and bases. Since the dilute concentrations of both the active and excipient are well below their solubility limits, no solubility related issues would be expected upon freezing and subsequent thawing. Clonidine Hydrochloride Injection, as formulated, does not require protection from light, oxygen, or freezing. The product shows acceptable stability within the pH range, and the rubber closure is compatible with the product. Real time stability data combined with statistical projections support a 36-month expiration date.

Correlation between pH and irritant effect of cleansers marketed for dry skin.

PubMed

Baranda, Lourdes; González-Amaro, Roberto; Torres-Alvarez, Bertha; Alvarez, Carmen; Ramírez, Victoria

2002-08-01

Although it is important that dermatologists and the general population know the irritation potential of products marketed for dry skin used for body cleansing, this information is not usually available. To assess the irritative effect of different soaps and liquid cleansers recommended for sensitive skin. To study the correlation of the irritation effect of each substance with its pH and with the presence or absence of syndet in the product. Seventeen products marketed for dry skin and 12 common soaps used by the general population were studied. Fresh soap emulsions (8%) were applied to the volar side of the right forearm of 30 individuals with sensitive skin for 5 consecutive days using aluminum chambers. The appearance of irritation (erythema, scaling and fissures) was recorded, scored, and expressed in an Irritation index (IrIn). The pH of each solution was measured. Products with a low IrIn were White Dove (Dove, Lever Pond's, Toronto, Ontario, Canada), Dove Baby, Cetaphil (bar) (Cetaphil, Gulderma Lab., Forth Worth, TX, USA), Dove liquid cleanser for hands, Dove pink, and Aderma (Adenma, Pierre Fabre, Dermo-Cosmetique, Boulagne, France). Most corresponded to syndet products. Among the most used brand-name soap, Camay Classic (Camay, Procter & Gamble de Mexico, México, U.F.) had the lowest IrIn. Dove Baby was the only product with a neutral pH. A significant correlation between pH and the IrIn of cleansers was found (P < 0.006). Most products recommended for sensitive skin have a considerable irritation effect, which is related to the pH of the product. Better regulation of advertisement specifications including the pH level and type of cleanser contained is necessary for the majority of soaps and cleansers.

The V-ATPase is expressed in the choroid plexus and mediates cAMP-induced intracellular pH alterations.

PubMed

Christensen, Henriette L; Păunescu, Teodor G; Matchkov, Vladimir; Barbuskaite, Dagne; Brown, Dennis; Damkier, Helle H; Praetorius, Jeppe

2017-01-01

The cerebrospinal fluid (CSF) pH influences brain interstitial pH and, therefore, brain function. We hypothesized that the choroid plexus epithelium (CPE) expresses the vacuolar H + -ATPase (V-ATPase) as an acid extrusion mechanism in the luminal membrane to counteract detrimental elevations in CSF pH. The expression of mRNA corresponding to several V-ATPase subunits was demonstrated by RT-PCR analysis of CPE cells (CPECs) isolated by fluorescence-activated cell sorting. Immunofluorescence and electron microscopy localized the V-ATPase primarily in intracellular vesicles with only a minor fraction in the luminal microvillus area. The vesicles did not translocate to the luminal membrane in two in vivo models of hypocapnia-induced alkalosis. The Na + -independent intracellular pH (pH i ) recovery from acidification was studied in freshly isolated clusters of CPECs. At extracellular pH (pH o ) 7.4, the cells failed to display significant concanamycin A-sensitive pH i recovery (i.e., V-ATPase activity). The recovery rate in the absence of Na + amounted to <10% of the pH i recovery rate observed in the presence of Na + Recovery of pH i was faster at pH o 7.8 and was abolished at pH o 7.0. The concanamycin A-sensitive pH i recovery was stimulated by cAMP at pH 7.4 in vitro, but intraventricular infusion of the membrane-permeant cAMP analog 8-CPT-cAMP did not result in trafficking of the V-ATPase. In conclusion, we find evidence for the expression of a minor fraction of V-ATPase in the luminal membrane of CPECs. This fraction does not contribute to enhanced acid extrusion at high extracellular pH, but seems to be activated by cAMP in a trafficking-independent manner. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Catchment and atmospheric effects on acidity of lakes in the northeastern United States

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, R.B.; Anderson, D.S.; Rhodes, T.E.

1995-06-01

Sedimentary evidence from 12 lakes in northeastern United States reveals that both catchment and atmospheric processes have caused changes in lake acidity. Diatom remains indicate pH 5.2 to 5.8 (one lake 6.8) for one to two centuries before impacts on the catchment by Euro-americans. These low-alkalinity lakes were very sensitive to altered fluxes of base cations and acids. Several lakes increased in pH by 0.2 to 0.6 unit in the 1800s and early 1900s when their catchments were logged. Re-acidification of some of the lakes was initially due to forest succession. Older sediment from one of the lakes also showsmore » alkalization by natural disturbance, and acidification paralleling forest succession. However, much of the recent acidification, to uniquely low levels by the 1970s is due to high sulfur deposition.« less

Controlling Disulfide Bond Formation and Crystal Growth from 2-Mercaptobenzoic Acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rowland, Clare E.; Cantos, P. M.; Toby, B. H.

2011-03-02

We report disulfide bond formation from 2-mercaptobenzoic acid (2-MBA) under hydrothermal conditions as a function of pH. Under acidic conditions, 2-MBA remains unchanged. Upon increasing pH, however, we observe 50% oxidation to 2,2'-disulfanediyldibenzoic acid (2,2'-DSBA), which is isolated as a cocrystal of both the thiol and disulfide molecules. At neutral pH, we observe complete oxidation and concurrent crystal growth. The pH sensitivity of this system allows targeting crystals of specific composition from simple building units through a straightforward pH manipulation.