Hasil untuk "physics.gen-ph"

Y. Surendranath, M. Kanan, D. Nocera

Jayasankar Jasti, Hiro Furukawa, E. Gonzales et al.

A. Pezzulo, X. Tang, M. J. Hoegger et al.

Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although bacterial lung infection and the resulting inflammation cause most of the morbidity and mortality, how the loss of CFTR function first disrupts airway host defence has remained uncertain. To investigate the abnormalities that impair elimination when a bacterium lands on the pristine surface of a newborn CF airway, we interrogated the viability of individual bacteria immobilized on solid grids and placed onto the airway surface. As a model, we studied CF pigs, which spontaneously develop hallmark features of CF lung disease. At birth, their lungs lack infection and inflammation, but have a reduced ability to eradicate bacteria. Here we show that in newborn wild-type pigs, the thin layer of airway surface liquid (ASL) rapidly kills bacteria in vivo, when removed from the lung and in primary epithelial cultures. Lack of CFTR reduces bacterial killing. We found that the ASL pH was more acidic in CF pigs, and reducing pH inhibited the antimicrobial activity of ASL. Reducing ASL pH diminished bacterial killing in wild-type pigs, and, conversely, increasing ASL pH rescued killing in CF pigs. These results directly link the initial host defence defect to the loss of CFTR, an anion channel that facilitates HCO3− transport. Without CFTR, airway epithelial HCO3− secretion is defective, the ASL pH falls and inhibits antimicrobial function, and thereby impairs the killing of bacteria that enter the newborn lung. These findings suggest that increasing ASL pH might prevent the initial infection in patients with CF, and that assaying bacterial killing could report on the benefit of therapeutic interventions.

A. Roos, W. Boron

R. V. Benjaminsen, Maria A Mattebjerg, J. Henriksen et al.

Polycations such as polyethylenimine (PEI) are used in many novel nonviral vector designs and there are continuous efforts to increase our mechanistic understanding of their interactions with cells. Even so, the mechanism of polyplex escape from the endosomal/lysosomal pathway after internalization is still elusive. The "proton sponge " hypothesis remains the most generally accepted mechanism, although it is heavily debated. This hypothesis is associated with the large buffering capacity of PEI and other polycations, which has been interpreted to cause an increase in lysosomal pH even though no conclusive proof has been provided. In the present study, we have used a nanoparticle pH sensor that was developed for pH measurements in the endosomal/lysosomal pathway. We have carried out quantitative measurements of lysosomal pH as a function of PEI content and correlate the results to the "proton sponge " hypothesis. Our measurements show that PEI does not induce change in lysosomal pH as previously suggested and quantification of PEI concentrations in lysosomes makes it uncertain that the "proton sponge " effect is the dominant mechanism of polyplex escape.

Saba M. Ali, G. Yosipovitch

The "acid mantle" is a topic not only of historical interest, but also of clinical significance and has recently been linked to vital stratum corneum function. Despite compelling basic science evidence placing skin pH as a key factor in barrier homeostasis, stratum corneum integrity, and antimicrobial defense, application of the acid mantle concept in clinical care is lacking. We review recent basic science investigations into skin pH, discuss skin disorders characterized by aberrant pH, and finally discuss practical application for preservation of the acid mantle. Recognizing factors that alter skin pH and selecting products that preserve the acid mantle is of prime importance in treating dermatologic patients.

Hai‐Long Jiang, Dawei Feng, Kecheng Wang et al.

Y. Ni, Jishan Wu

Jianquan Luo, Y. Wan

J. Jiang, Yujing Zhang, Kaimin Li et al.

P. Swietach, R. Vaughan-Jones, A. Harris et al.

D. O'Hanlon, T. Moench, R. Cone

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

Katherine M. Strickler, A. Fremier, C. Goldberg

D. Ling, W. Park, Sin‐jung Park et al.

P. Lund, A. Tramonti, D. De Biase

S. Percival, Sara M. McCarty, J. Hunt et al.

M. Kühl, Y. Cohen, T. Dalsgaard et al.

J. H. Poulsen, H. Fischer, B. Illek et al.

E. Wambu, Audre Jerop Kurui

Soil adsorbents continue to attract increasingly high numbers of researchers in water defluoridation studies. An aspect of solution parameters, that is the aqueous adsorption of fluoride onto soil adsorbents in defluoridation studies, has been reviewed and reported. The pH was found to be the main factor controlling fluoride adsorption on the popular soil adsorbents including: aluminosilicates, iron (hydr)oxides, aluminum (hydr) oxides, apatites, carbonaceous minerals, calcareous soils and zeolites and the other key parameters being temperature, time of contact, and co-existent ions. Fluoride adsorption onto metal-exchanged zeolites and hydroxyapatites (optimum pH = 4–10), iron (hydro) oxide minerals (pH = 2–7), and carbonaceous minerals (pH = 4–12) is relatively pHindependent, and high amounts of fluoride are able to sorb upon the surfaces of these minerals in a wide range of pH values. However, montmorillonites (optimum pH = 5–6), aluminum (hydro)oxide minerals (pH = 5–7), and calcareous minerals (pH = 5–6) only sorb significant amount of fluoride in a narrow range of pH values. The fluoride adsorption onto the latter class of minerals, also generally occurring at slightly above room temperatures, appears to be highly specific and not strongly affected by the presence of coexistent anions including: PO 4 3− , SO 4 2− , Cl − , and NO 3 −.

J. Neumann, A. Jagendorf