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To understand how maize plants adapt to drought, this study examines the role of plasma membrane proton pumps in root growth. This study delves into the physiological mechanisms through which maize plants respond to drought conditions, with a particular emphasis on elucidating the crucial role played by plasma membrane proton pumps in facilitating adaptive changes in root growth. Our results underscore the indispensable nature of these pumps in orchestrating precise modulation of root growth patterns during drought stress, highlighting their profound significance in stress responses. Additionally, the study reveals that osmotic stress alters lipid profiles in the plasma membrane, potentially impacting its functioning and the activity of membrane proteins. To understand the role of plasma membrane (PM) H + -ATPases in the adaptative response to osmotic stress and in the regulation of root growth in maize, we studied the gene expression and enzyme activity of PM H + -ATPases, as well as the changes in plant biomass and total root growth, in the seedlings of two maize cultivars: the drought-tolerant Calo cultivar and the drought-sensitive Abelardo. The seedlings were exposed to simulated drought for 24 h (treatment with 20% PEG). The enzyme activity and gene expression of the MHA4 H + -ATPase increased in the Calo variety but declined in Abelardo plants treated with PEG. The growth of roots in Abelardo plants exposed to 24 h of PEG treatment was reduced to almost 50% of the control. Conversely, for the Calo cultivar, there was no remarkable morpho-physiological difference between the roots of stressed and non-stressed plants. Therefore, the activity of the PM H + -ATPase seems to be an important factor for proper root growth during the adaptation of maize to drought. In addition, osmotic stress also induced changes in the levels of saturated polyisoprenoid alcohols in the plasma membrane fraction of maize roots. The increased levels of this class of lipids might modulate the physico-chemical properties of the PM lipid bilayer and thus affect its functioning and modify the activity of membrane proteins, such as PM H + -ATPases.

Microbial rhodopsins are a family of photoreceptive membrane proteins with a wide distribution across the Tree of Life. Within the candidate phyla radiation (CPR), a diverse group of putatively episymbiotic bacteria, the genetic potential to produce rhodopsins appears to be confined to a small clade of organisms from sunlit environments. Here, we characterize the metabolic context and biophysical features of Saccharibacteria Type-1 rhodopsin sequences derived from metagenomic surveys and show that these proteins function as outward proton pumps. This provides one of the only known mechanisms by which CPR can generate a proton gradient for ATP synthesis. These Saccharibacteria do not encode the genetic machinery to produce all-trans-retinal, the chromophore essential for rhodopsin function, but their rhodopsins are able to rapidly uptake this cofactor when provided in experimental assays. We found consistent evidence for the capacity to produce retinal from β-carotene in microorganisms co-occurring with Saccharibacteria, and this genetic potential was dominated by members of the Actinobacteria, which are known hosts of Saccharibacteria in other habitats. If Actinobacteria serve as hosts for Saccharibacteria in freshwater environments, exchange of retinal for use by rhodopsin may be a feature of their associations.

BackgroundThe Reflux Band, an external upper esophageal sphincter (UES) compression device, reduces esophago-pharyngeal reflux events. This study aimed to assess device efficacy as an adjunct to proton pump inhibitor (PPI) therapy in patients with laryngopharyngeal reflux (LPR).MethodsThis two-phase prospective clinical trial enrolled adults with at least 8 weeks of laryngeal symptoms (sore throat, throat clearing, dysphonia) not using PPI therapy at two tertiary care centers over 26 months. Participants used double dose PPI for 4 weeks in Phase 1 and the external UES compression device nightly along with PPI for 4 weeks in Phase 2. Questionnaire scores and salivary pepsin concentration were measured throughout the study. The primary endpoint of symptom response was defined as reflux symptom index (RSI) score ≤ 13 and/or > 50% reduction in RSI.ResultsThirty-one participants completed the study: 52% male, mean age 47.9 years (SD 14.0), and mean body mass index (BMI) 26.2 kg/m2 (5.1). Primary endpoint was met in 11 (35%) participants after Phase 1 (PPI alone) and 17 (55%) after Phase 2 (Device + PPI). Compared to baseline, mean RSI score (24.1 (10.9)) decreased at end of Phase 1 (PPI alone) (21.9 (9.7); p = 0.06) and significantly decreased at end of Phase 2 (Device + PPI) (15.5 (10.3); p

Proton pump inhibitors (PPIs) are widely used to suppress gastric acid secretion. Proton pumps belong to the family of ATPase and among them P-ATPase and V-ATPase types regulate intracellular as well as extracellular acid equilibrium. The main aim of the current survey is to present the existing literature putting forth the relation between cancer with both the use of PPIs and proton pumps from positive and negative aspects. To perform an objective study, various types of proton pumps and their relation to cancer have been taken into account. Up to date, the studies have been considered in the time range from 2011 to 2021 via various databases (PubMed, Scopus, and Google Scholar). H+/K+ ATPase, located within the gastric parietal cells, is one of the most important examples of P-ATPases. The findings of the literature review along with criticism were presented as decreased P-ATPase expression can be used as a marker for gastric cancer diagnosis whereas the association of the proton pump with cancer may be mainly due to V-ATPase. In conclusion, molecular, epidemiological, and bioinformatic studies are required to enlighten the subject.

The lumenal pH of an organelle is one of its defining characteristics and central to its biological function. Experiments have elucidated many of the key pH regulatory elements and how they vary from compartment-to-compartment, and continuum mathematical models have played an important role in understanding how these elements (proton pumps, counter-ion fluxes, membrane potential, buffering capacity, etc.) work together to achieve specific pH setpoints. While continuum models have proven successful in describing ion regulation at the cellular length scale, it is unknown if they are valid at the subcellular level where volumes are small, ion numbers may fluctuate wildly, and biochemical heterogeneity is large. Here, we create a discrete, stochastic (DS) model of vesicular acidification to answer this question. We used this simplified model to analyze pH measurements of isolated vesicles containing single proton pumps and compared these results to solutions from a continuum, ordinary differential equations (ODE)-based model. Both models predict similar parameter estimates for the mean proton pumping rate, membrane permeability, etc., but, as expected, the ODE model fails to report on the fluctuations in the system. The stochastic model predicts that pH fluctuations decrease during acidification, but noise analysis of single-vesicle data confirms our finding that the experimental noise is dominated by the fluorescent dye, and it reveals no insight into the true noise in the proton fluctuations. Finally, we again use the reduced DS model explore the acidification of large, lysosome-like vesicles to determine how stochastic elements, such as variations in proton-pump copy number and cycling between on and off states, impact the pH setpoint and fluctuations around this setpoint.

Background: Marginal ulcer bleeding (MUB) is a complication that can occur following several types of surgery. However, few studies exist on it. Therefore, this study aimed to compare the clinical outcomes of MUB with those of peptic ulcer bleeding (PUB). Methods: Between January 2013 and December 2017, 5,076 patients underwent emergent esophagogastroduodenoscopy for suspected upper gastrointestinal bleeding. We retrospectively reviewed and analyzed the medical records of MUB and PUB patients and developed a propensity score matching (PSM) method to adjust for between-group differences in baseline characteristics with 1:2 ratios. Sex, age, body mass index (BMI), underlying diseases, and drugs were included as matching factors. Results: A total of 64 and 678 patients were diagnosed with MUB and PUB, respectively, on emergent esophagogastroduodenoscopy, and 62 and 124 patients with MUB and PUB, respectively, were selected after PSM. Rebleeding was significantly higher in patients with MUB than in those with PUB (57.8% vs 9.1%, p < 0.001). Mortality caused by bleeding was higher in patients with MUB than in those with PUB (4.7% vs. 0.4%, p < 0.001). Multivariate analysis revealed that proton pump inhibitor (PPI) administration (odds ratio [OR], 0.14; 95% confidence interval [CI], 0.03–0.56; p = 0.011) after first bleeding was inversely correlated with MUB rebleeding. Large ulcer size (> 1 cm) (OR, 6.69; 95% CI, 1.95–27.94; p = 0.005) and surgery covering pancreas (OR, 3.97; 95% CI, 1.19–15.04) were independent risk factors for MUB rebleeding. Conclusions: MUB showed a severe clinical course than PUB. Therefore, MUB should be managed more cautiously, especially for large ulcers and pancreatic surgery. Prophylactic PPI administration may be helpful in reducing rebleeding in MUB. [ABSTRACT FROM AUTHOR]

About 20% of all irrigated land is adversely affected by salinity hazards and therefore understanding plant defense mechanisms against salinity will have great impact on plant productivity. In the last decades, comprehension of salinity resistance at molecular level has been achieved through the identification of key genes encoding biomarker proteins underpinning salinity tolerance. Implication of the vacuolar transport systems in plant salinity tolerance is one example of these central mechanisms rendering tolerance to saline stress. One important organelle in plant cells is the central vacuole that plays pivotal multiple roles in cell functioning under normal and stress conditions. This review thus attempts to address different lines of evidence supporting the role of the vacuolar membrane transport systems in plant salinity tolerance. Vacuolar transport systems include Na+(K+)/H+ antiporters, V-ATPase, V-PPase, Ca2+/H+ exchangers, Ca2+-ATPase, ion channels, aquaporins, and ABC transporters. They contribute essentially in retaining a high cytosolic K+/Na+ ratio, K+ level, sequestrating Na+ and Cl− into vacuoles, as well as regulation of other salinity responsive pathways. However, little is known about the regulation and functions of some of the vacuolar transporters under salinity stress and therefore need more exploration and focus. Numerous studies demonstrated that the activities of the vacuolar transporters are upregulated in response to salinity stress, confirming their central roles in salinity tolerance mechanism. The second line of evidence is that manipulation of one of the genes encoding the vacuolar transport proteins results in some successful improvement of plant salinity tolerance. Therefore, transgene pyramiding of more than one gene for developing genotypes with better and strong salinity tolerance and productivity should gain more attention in future research. In addition, we should move step further and verify the experimental data obtained from either a greenhouse or controlled environment into field trials in order to support our claims. [ABSTRACT FROM AUTHOR]

Saccharomyces cerevisiae sake yeast strain Kyokai no. 7 (K7) and its relatives carry a homozygous loss-of-function mutation in the RIM15 gene, which encodes a Greatwall family protein kinase. Disruption of RIM15 in nonsake yeast strains leads to improved alcoholic fermentation, indicating that the defect in Rim15p is associated with the enhanced fermentation performance of sake yeast cells. In order to understand how Rim15p mediates fermentation control, we here focused on target-of-rapamycin protein kinase complex 1 (TORC1) and protein phosphatase 2A with the B55δ regulatory subunit (PP2AB55δ), complexes that are known to act upstream and downstream of Rim15p, respectively. Several lines of evidence, including our previous transcriptomic analysis data, suggested enhanced TORC1 signaling in sake yeast cells during sake fermentation. Fermentation tests of the TORC1-related mutants using a laboratory strain revealed that TORC1 signaling positively regulates the initial fermentation rate in a Rim15p-dependent manner. Deletion of the CDC55 gene, encoding B55δ, abolished the high fermentation performance of Rim15p-deficient laboratory yeast and sake yeast cells, indicating that PP2AB55δ mediates the fermentation control by TORC1 and Rim15p. The TORC1-Greatwall-PP2AB55δ pathway similarly affected the fermentation rate in the fission yeast Schizosaccharomyces pombe, strongly suggesting that the evolutionarily conserved pathway governs alcoholic fermentation in yeasts. It is likely that elevated PP2AB55δ activity accounts for the high fermentation performance of sake yeast cells. Heterozygous loss-of-function mutations in CDC55 found in K7-related sake strains may indicate that the Rim15p-deficient phenotypes are disadvantageous to cell survival.IMPORTANCE The biochemical processes and enzymes responsible for glycolysis and alcoholic fermentation by the yeast S. cerevisiae have long been the subject of scientific research. Nevertheless, the factors determining fermentation performance in vivo are not fully understood. As a result, the industrial breeding of yeast strains has required empirical characterization of fermentation by screening numerous mutants through laborious fermentation tests. To establish a rational and efficient breeding strategy, key regulators of alcoholic fermentation need to be identified. In the present study, we focused on how sake yeast strains of S. cerevisiae have acquired high alcoholic fermentation performance. Our findings provide a rational molecular basis to design yeast strains with optimal fermentation performance for production of alcoholic beverages and bioethanol. In addition, as the evolutionarily conserved TORC1-Greatwall-PP2AB55δ pathway plays a major role in the glycolytic control, our work may contribute to research on carbohydrate metabolism in higher eukaryotes.

Premise: The consequences of acidity for plant performance are profound, yet the prevalence and causes of low pH in bromeliad tank water are unknown despite its functional relevance to key members of many neotropical plant communities. Methods: We investigated tank water pH for eight bromeliad species in the field and for the widely occurring Guzmania monostachia in varying light. We compared pH changes over time between plant and artificial tanks containing a solution combined from several plants. Aquaporin transcripts were measured for field plants at two levels of pH. We investigated relationships between pH, leaf hydraulic conductance, and CO2 concentration in greenhouse plants and tested proton pump activity using a stimulator and inhibitor. Results: Mean tank water pH for the eight species was 4.7 ± 0.06 and was lower for G. monostachia in higher light. The pH of the solution in artificial tanks, unlike in plants, did not decrease over time. Aquaporin transcription was higher for plants with lower pH, but leaf hydraulic conductance did not differ, suggesting that the pH did not influence water uptake. Tank pH and CO2 concentration were inversely related. Fusicoccin enhanced a decrease in tank pH, whereas orthovanadate did not. Conclusions: Guzmania monostachia acidified its tank water via leaf proton pumps, which appeared responsive to light. Low pH increased aquaporin transcripts but did not influence leaf hydraulic conductance, hence may be more relevant to nutrient uptake. [ABSTRACT FROM AUTHOR]

Educational Objective: At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus. Objective: Barrett's esophagus (BE) is a well‐known risk factor for esophageal adenocarcinoma (EAC). Gastric H+/K+ ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H+/K+ ATPase proton pumps. Study Design: In vitro translational. Methods: BAR‐T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus‐encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing. Results: Top canonical pathways associated with protein‐coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR‐T cells included those involved in the tumor microenvironment and epithelial–mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300‐CBP, I‐BET‐151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer. Conclusions: These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE. Level of Evidence: NA Laryngoscope, 133:59–69, 2023 [ABSTRACT FROM AUTHOR]

In aerobic cells, the proton gradient that drives ATP synthesis is created by three different proton pumps-membrane enzymes of the respiratory electron transport chain known as complex I, III, and IV. Despite the striking dissimilarity of structures and apparent differences in molecular mechanisms of proton pumping, all three enzymes have much in common and employ the same universal physical principles of converting redox energy to proton pumping. In this study, we describe a simple mathematical model that illustrates the general principles of redox-driven proton pumps and discuss their implementation in complex I, III, and IV of the respiratory chain.

Simple Summary: Tumor associated macrophages (TAMs) support disease progression by providing tumor cells cytokines and chemokines necessary for malignant growth and nutrient support. In the tumor microenvironment (TME), TAMs often rewire their metabolism to reprogram their functions, which includes changes in the production of angiogenic factors and cytokines. These promote the pro-tumor function of the TAMs as well as the blunt T cell's effector function, which at least, in part, explains the failure or sub-optimal efficacies of TAM-directed therapeutic approaches and immunotherapies. In recent times, much of these are attributed to the altered metabolism of the TAMs in the TME. Therefore, understanding the metabolic changes of the myeloid cells of the TME is an essential step in developing novel therapeutic approaches targeting immune cell metabolism. This review article aims to summarize the recent findings on the metabolism of TAMs, and how the altered metabolism of these innate immune cells shapes the tumor microenvironment and the anti-tumor immunity. Cancer cells possess a high metabolic demand for their rapid proliferation, survival, and progression and thus create an acidic and hypoxic tumor microenvironment (TME) deprived of nutrients. Moreover, acidity within the TME is the central regulator of tumor immunity that influences the metabolism of the immune cells and orchestrates the local and systemic immunity, thus, the TME has a major impact on tumor progression and resistance to anti-cancer therapy. Specifically, myeloid cells, which include myeloid-derived suppressor cells (MDSC), dendritic cells, and tumor-associated macrophages (TAMs), often reprogram their energy metabolism, resulting in stimulating the angiogenesis and immunosuppression of tumors. This review summarizes the recent findings of glucose, amino acids, and fatty acid metabolism changes of the tumor-associated macrophages (TAMs), and how the altered metabolism shapes the TME and anti-tumor immunity. Multiple proton pumps/transporters are involved in maintaining the alkaline intracellular pH which is necessary for the glycolytic metabolism of the myeloid cells and acidic TME. We highlighted the roles of these proteins in modulating the cellular metabolism of TAMs and their potential as therapeutic targets for improving immune checkpoint therapy. [ABSTRACT FROM AUTHOR]