scholarly journals Different Roles of Membrane Potentials in Electrotaxis and Chemotaxis of Dictyostelium Cells

2011 ◽  
Vol 10 (9) ◽  
pp. 1251-1256 ◽  
Author(s):  
Run-chi Gao ◽  
Xiao-dong Zhang ◽  
Yao-hui Sun ◽  
Yoichiro Kamimura ◽  
Alex Mogilner ◽  
...  
Keyword(s):  
Electric Fields ◽  
Membrane Potentials ◽  
Extracellular Ph ◽  
Acidic Ph ◽  
Alkaline Ph ◽  
Microelectrode Recording ◽  
Random Motility ◽  
Content Type ◽  
Chemotactic Index

ABSTRACT Many types of cells migrate directionally in direct current (DC) electric fields (EFs), a phenomenon termed galvanotaxis or electrotaxis. The directional sensing mechanisms responsible for this response to EFs, however, remain unknown. Exposing cells to an EF causes changes in plasma membrane potentials ( V m ). Exploiting the ability of Dictyostelium cells to tolerate drastic V m changes, we investigated the role of V m in electrotaxis and, in parallel, in chemotaxis. We used three independent factors to control V m : extracellular pH, extracellular [K + ], and electroporation. Changes in V m were monitored with microelectrode recording techniques. Depolarized V m was observed under acidic (pH 5.0) and alkaline (pH 9.0) conditions as well as under higher extracellular [K + ] conditions. Electroporation permeabilized the cell membrane and significantly reduced the V m , which gradually recovered over 40 min. We then recorded the electrotactic behaviors of Dictyostelium cells with a defined V m using these three techniques. The directionality (directedness of electrotaxis) was quantified and compared to that of chemotaxis (chemotactic index). We found that a reduced V m significantly impaired electrotaxis without significantly affecting random motility or chemotaxis. We conclude that extracellular pH, [K + ], and electroporation all significantly affected electrotaxis, which appeared to be mediated by the changes in V m . The initial directional sensing mechanisms for electrotaxis therefore differ from those of chemotaxis and may be mediated by changes in resting V m .

scholarly journals The pH-Responsive Transcription Factors YlRim101 and Mhy1 Regulate Alkaline pH-Induced Filamentation in the Dimorphic Yeast Yarrowia lipolytica

mSphere ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Tao Shu ◽  
Xin-Yu He ◽  
Jia-Wen Chen ◽  
Yi-Sheng Mao ◽  
Xiang-Dong Gao
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Yarrowia Lipolytica ◽  
Regulatory Mechanism ◽  
Cell Wall Protein ◽  
Alkaline Ph ◽  
Dimorphic Fungi ◽  
Content Type ◽  
Dimorphic Yeast

ABSTRACT Environmental pH influences cell growth and differentiation. In the dimorphic yeast Yarrowia lipolytica, neutral-alkaline pH strongly induces the yeast-to-filament transition. However, the regulatory mechanism that governs alkaline pH-induced filamentation has been unclear. Here, we show that the pH-responsive transcription factor Y. lipolytica Rim101 (YlRim101) is a major regulator of alkaline-induced filamentation, since the deletion of YlRIM101 severely impaired filamentation at alkaline pH, whereas the constitutively active YlRIM1011-330 mutant mildly induced filamentation at acidic pH. YlRim101 controls the expression of the majority of alkaline-regulated cell wall protein genes. One of these, the cell surface glycosidase gene YlPHR1, plays a critical role in growth, cell wall function, and filamentation at alkaline pH. This finding suggests that YlRim101 promotes filamentation at alkaline pH via controlling the expression of these genes. We also show that, in addition to YlRim101, the Msn2/Msn4-like transcription factor Mhy1 is highly upregulated at alkaline pH and is essential for filamentation. However, unlike YlRim101, which specifically regulates alkaline-induced filamentation, Mhy1 regulates both alkaline- and glucose-induced filamentation, since the deletion of MHY1 abolished them both, whereas the overexpression of MHY1 induced strong filamentation irrespective of the pH or the presence of glucose. Finally, we show that YlRim101 and Mhy1 positively coregulate seven cell wall protein genes at alkaline pH, including YlPHR1 and five cell surface adhesin-like genes, three of which appear to promote filamentation. Together, these results reveal a conserved role of YlRim101 and a novel role of Mhy1 in the regulation of alkaline-induced filamentation in Y. lipolytica. IMPORTANCE The regulatory mechanism that governs pH-regulated filamentation is not clear in dimorphic fungi except in Candida albicans. Here, we investigated the regulation of alkaline pH-induced filamentation in Yarrowia lipolytica, a dimorphic yeast distantly related to C. albicans. Our results show that the transcription factor YlRim101 and the Msn2/Msn4-like transcription factor Mhy1 are the major regulators that promote filamentation at alkaline pH. They control the expression of a number of cell wall protein genes important for cell wall organization and filamentation. Our results suggest that the Rim101/PacC homologs play a conserved role in pH-regulated filamentation in dimorphic fungi.

scholarly journals Sterol-Response Pathways Mediate Alkaline Survival in Diverse Fungi

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Hannah E. Brown ◽  
Calla L. Telzrow ◽  
Joseph W. Saelens ◽  
Larissa Fernandes ◽  
J. Andrew Alspaugh
Keyword(s):  
Cryptococcus Neoformans ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Membrane Integrity ◽  
Extracellular Ph ◽  
Alkaline Ph ◽  
Content Type ◽  
Alkaline Environment ◽  
Ph Response ◽  
The Impact

ABSTRACT The ability for cells to maintain homeostasis in the presence of extracellular stress is essential for their survival. Stress adaptations are especially important for microbial pathogens to respond to rapidly changing conditions, such as those encountered during the transition from the environment to the infected host. Many fungal pathogens have acquired the ability to quickly adapt to changes in extracellular pH to promote their survival in the various microenvironments encountered during a host infection. For example, the fungus-specific Rim/Pal alkaline response pathway has been well characterized in many fungal pathogens, including Cryptococcus neoformans. However, alternative mechanisms for sensing and responding to host pH have yet to be extensively studied. Recent observations from a genetic screen suggest that the C. neoformans sterol homeostasis pathway is required for growth at elevated pH. This work explores interactions among mechanisms of membrane homeostasis, alkaline pH tolerance, and Rim pathway activation. We find that the sterol homeostasis pathway is necessary for growth in an alkaline environment and that an elevated pH is sufficient to induce Sre1 activation. This pH-mediated activation of the Sre1 transcription factor is linked to the biosynthesis of ergosterol but is not dependent on Rim pathway signaling, suggesting that these two pathways are responding to alkaline pH independently. Furthermore, we discover that C. neoformans is more susceptible to membrane-targeting antifungals under alkaline conditions, highlighting the impact of microenvironmental pH on the treatment of invasive fungal infections. Together, these findings further connect membrane integrity and composition with the fungal pH response and pathogenesis. IMPORTANCE The work described here further elucidates how microorganisms sense and adapt to changes in their environment to establish infections in the human host. Specifically, we uncover a novel mechanism by which an opportunistic human fungal pathogen, Cryptococcus neoformans, responds to increases in extracellular pH in order to survive and thrive within the relatively alkaline environment of the human lung. This mechanism, which is intimately linked with fungal membrane sterol homeostasis, is independent of the previously well-studied alkaline response Rim pathway. Furthermore, this ergosterol-dependent alkaline pH response is present in Candida albicans, indicating that this mechanism spans diverse fungal species. These results are also relevant for novel antimicrobial drug development as we show that currently used ergosterol-targeting antifungals are more active in alkaline environments.

scholarly journals Aspergillus nidulans Ambient pH Signaling Does Not Require Endocytosis

2015 ◽  
Vol 14 (6) ◽  
pp. 545-553 ◽  
Author(s):  
Daniel Lucena-Agell ◽  
Antonio Galindo ◽  
Herbert N. Arst ◽  
Miguel A. Peñalva
Keyword(s):  
Plasma Membrane ◽  
Aspergillus Nidulans ◽  
Hyphal Growth ◽  
Proteolytic Processing ◽  
Current Evidence ◽  
Dependent Manner ◽  
Incomplete Block ◽  
Alkaline Ph ◽  
Content Type

ABSTRACT Aspergillus nidulans (Pal) ambient pH signaling takes place in cortical structures containing components of the ESCRT pathway, which are hijacked by the alkaline pH-activated, ubiquitin-modified version of the arrestin-like protein PalF and taken to the plasma membrane. There, ESCRTs scaffold the assembly of dedicated Pal proteins acting downstream. The molecular details of this pathway, which results in the two-step proteolytic processing of the transcription factor PacC, have received considerable attention due to the key role that it plays in fungal pathogenicity. While current evidence strongly indicates that the pH signaling role of ESCRT complexes is limited to plasma membrane-associated structures where PacC proteolysis would take place, the localization of the PalB protease, which almost certainly catalyzes the first and only pH-regulated proteolytic step, had not been investigated. In view of ESCRT participation, this formally leaves open the possibility that PalB activation requires endocytic internalization. As endocytosis is essential for hyphal growth, nonlethal endocytic mutations are predicted to cause an incomplete block. We used a SynA internalization assay to measure the extent to which any given mutation prevents endocytosis. We show that none of the tested mutations impairing endocytosis to different degrees, including slaB1 , conditionally causing a complete block, have any effect on the activation of the pathway. We further show that PalB, like PalA and PalC, localizes to cortical structures in an alkaline pH-dependent manner. Therefore, signaling through the Pal pathway does not involve endocytosis.

The role of uranium peroxide studtite on the retention of Cs, Sr and Se(VI)

2009 ◽  
Vol 1193 ◽  
Author(s):  
Javier Gimenez ◽  
Rosa Sureda ◽  
Joan de Pablo ◽  
Ignasi Casas ◽  
Xavier Martinez-Llado ◽  
...  
Keyword(s):  
Nuclear Fuel ◽  
Spent Nuclear Fuel ◽  
Acidic Ph ◽  
Alkaline Ph ◽  
Icp Ms ◽  
Uranium Peroxide ◽  
Element Speciation ◽  
Solid Phases ◽  
Positively Charged

AbstractThe formation of uranyl secondary solid phases onto the spent nuclear fuel surface might influence the radionuclide concentration in solution via, among others, sorption processes. In this work, the incorporation of some radionuclides onto the uranium peroxide studtite, UO2O2·4H2O, has been tested.The study was carried out in batch experiments where a known amount of studtite (0.05 g) was put in contact with 20 cm3 of radionuclide solution. Once equilibrium was reached, radionuclide concentrations in solution were determined by ICP-MS. The radionuclide amount attached to the solid was calculated from the mass balance. The S/V values of the experiments were also determined from BET specific solid surface area measurements.In this work, data on sorption of caesium, strontium, and selenium as a function of pH are presented. The behaviour of caesium and strontium are similar: a relatively high amount of radionuclide is sorbed at neutral to alkaline pH while there is almost no sorption at acidic pH. On the other hand, in the case of selenium, the sorption maximum occurs at acidic pH and there is almost no sorption at alkaline pH. The different behavior of the radionuclides is related to the element speciation in solution and the surface charge of the solid. Strontium and caesium are sorbed at alkaline pH because they are positively charged in solution and the surface of the studtite is negatively charged (>O- groups) while selenium(VI) sorbs at acidic pH because the surface of the studtite is positively charged, and the predominant selenium(VI) species in solution is anionic.These preliminary data indicate that the sorption capacity of uranyl secondary solid phases such as studtite is an important process to be considered when establishing the migration of different radionuclides released from spent nuclear fuel.

Effect of Extracellular pH on GABA-Activated Current in Rat Recombinant Receptors and Thin Hypothalamic Slices

1999 ◽  
Vol 82 (3) ◽  
pp. 1233-1243 ◽  
Author(s):  
Ren-Qi Huang ◽  
Glenn H. Dillon
Keyword(s):  
Extracellular Ph ◽  
Dependent Manner ◽  
Acidic Ph ◽  
Alkaline Ph ◽  
Gaba Concentration ◽  
Open Probability ◽  
Α Subunit ◽  
Recombinant Receptors ◽  
Channel Opening ◽  
Recombinant Type

We studied the effects of extracellular pH (pHo) on γ-aminobutyric acid (GABA)–mediated Cl− current in rat hypothalamic neurons and recombinant type-A GABA (GABAA) receptors stably expressed in human embryonic kidney cells (HEK 293), using whole cell and outside-out patch-clamp recordings. In α3β2γ2s receptors, acidic pH decreased, whereas alkaline pH increased the response to GABA in a reversible and concentration-dependent manner. Acidification shifted the GABA concentration-response curve to the right, significantly increasing the EC50 for GABA without appreciably changing the slope or maximal current induced by GABA. We obtained similar effects of pH in α1β2γ2 receptors and in GABA-activated currents recorded from thin hypothalamic brain slices. In outside-out patches recorded from α3β2γ2 recombinant receptors, membrane patches were exposed to 5 μM GABA at control (7.3), acidic (6.4), or alkaline (8.4) pH. GABA activated main and subconductance states of 24 and 16 pS, respectively, in α3β2γ2 receptors. Alkaline pHo increased channel opening frequency and decreased the duration of the long closed state, resulting in an increase in open probability (from 0.0801 ± 0.015 in pH 7.3 to 0.138 ± 0.02 in pH 8.4). Exposure of the channels to acidic pHo had the opposite effects on open probability (decreased to 0.006 ± 0.0001). Taken together, our results indicate that the function of GABAA receptors is modulated by extracellular pH. The proton effect is similar in recombinant and native receptors and is dependent on GABA concentration. In addition, the effect appears to be independent of the α-subunit isoform, and is due to the ability of H+ to alter the frequency of channel opening. Our findings indicate that GABAergic signaling in the CNS may be significantly altered during conditions that increase or decrease pH.

scholarly journals Sharply Tuned pH Response of Genetic Competence Regulation in Streptococcus mutans: a Microfluidic Study of the Environmental Sensitivity ofcomX

2015 ◽  
Vol 81 (16) ◽  
pp. 5622-5631 ◽  
Author(s):  
Minjun Son ◽  
Delaram Ghoreishi ◽  
Sang-Joon Ahn ◽  
Robert A. Burne ◽  
Stephen J. Hagen
Keyword(s):  
Streptococcus Mutans ◽  
Physiological State ◽  
Transient State ◽  
Extracellular Ph ◽  
Genetic Competence ◽  
Content Type ◽  
Ph Response ◽  
Ph Range ◽  
Secreted Peptides

ABSTRACTGenetic competence inStreptococcus mutansis a transient state that is regulated in response to multiple environmental inputs. These include extracellular pH and the concentrations of two secreted peptides, designated CSP (competence-stimulating peptide) and XIP (comX-inducing peptide). The role of environmental cues in regulating competence can be difficult to disentangle from the effects of the organism's physiological state and its chemical modification of its environment. We used microfluidics to control the extracellular environment and study the activation of the key competence genecomX. We find that thecomXpromoter (PcomX) responds to XIP or CSP only when the extracellular pH lies within a narrow window, about 1 pH unit wide, near pH 7. Within this pH range, CSP elicits a strong PcomXresponse from a subpopulation of cells, whereas outside this range the proportion of cells expressingcomXdeclines sharply. Likewise, PcomXis most sensitive to XIP only within a narrow pH window. While previous work suggested thatcomXmay become refractory to CSP or XIP stimulus as cells exit early exponential phase, our microfluidic data show that extracellular pH dominates in determining sensitivity to XIP and CSP. The data are most consistent with an effect of pH on the ComR/ComS system, which has direct control over transcription ofcomXinS. mutans.

Transport and fluctuations in nonlinear-dissipative systems: role of interparticle collisions

1999 ◽  
Vol 4 ◽  
pp. 31-86 ◽  
Author(s):  
R. Katilius ◽  
A. Matulionis ◽  
R. Raguotis ◽  
I. Matulionienė
Keyword(s):  
Electric Fields ◽  
Carrier Density ◽  
Experimental Results ◽  
Dissipative Systems ◽  
Doped Semiconductors ◽  
Electron Diffusion ◽  
Electron Collisions ◽  
Electric Noise ◽  
Diffusion Phenomena

The goal of the paper is to overview contemporary theoretical and experimental research of the microwave electric noise and fluctuations of hot carriers in semiconductors, revealing sensitivity of the noise spectra to non-linearity in the applied electric field strength and, especially, in the carrier density. During the last years, investigation of electronic noise and electron diffusion phenomena in doped semiconductors was in a rapid progress. By combining analytic and Monte Carlo methods as well as the available experimental results on noise, it became possible to obtain the electron diffusion coefficients in the range of electric fields where inter-electron collisions are important and Price’s relation is not necessarily valid. Correspondingly, a special attention to the role of inter-electron collisions and of the non-linearity in the carrier density while shaping electric noise and diffusion phenomena in the non-equilibrium states will be paid. The basic and up-to-date information will be presented on methods and advances in this contemporary field - the field in which methods of non-linear analytic and computational analysis are indispensable while seeking coherent understanding and interpretation of experimental results.

Long-term management of patients with multiple brain metastases after shaped beam radiosurgery

2004 ◽  
pp. 406-412
Author(s):  
Paul Okunieff ◽  
Michael C. Schell ◽  
Russell Ruo ◽  
E. Ronald Hale ◽  
Walter G. O'Dell ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tumor Control ◽  
Content Type ◽  
Negative Results ◽  
Multiple Metastases ◽  
Extracranial Disease ◽  
Successful Control ◽  
The Brain

✓ The role of radiosurgery in the treatment of patients with advanced-stage metastatic disease is currently under debate. Previous randomized studies have not consistently supported the use of radiosurgery to treat patients with numbers of brain metastases. In negative-results studies, however, intracranial tumor control was high but extracranial disease progressed; thus, patient survival was not greatly affected, although neurocognitive function was generally maintained until death. Because the future promises improved systemic (extracranial) therapy, the successful control of brain disease is that much more crucial. Thus, for selected patients with multiple metastases to the brain who remain in good neurological condition, aggressive lesion-targeting radiosurgery should be very useful. Although a major limitation to success of this therapy is the lack of control of extracranial disease in most patients, it is clear that well-designed, aggressive treatment substantially decreases the progression of brain metastases and also improves neurocognitive survival. The authors present the management and a methodology for rational treatment of a patient with breast cancer who has harbored 24 brain metastases during a 3-year period.

scholarly journals Vulnerable adults in police custody

2019 ◽  
Vol 22 (1) ◽  
pp. 5-8
Author(s):  
Ian Cummins
Keyword(s):  
Design Methodology ◽  
Research Literature ◽  
Police Custody ◽  
England And Wales ◽  
Content Type ◽  
Increased Risk ◽  
Vulnerable Adults

Purpose The purpose of this paper is to discuss the recent National Appropriate Adult Network (NAAN) report on the role of the appropriate adult. Design/methodology/approach This paper is based on the NAAN report and a review of relevant policy and research literature. Findings There to Help 2 highlights that there are still significant gaps in the provision of appropriate adult schemes across England and Wales. These gaps potentially place vulnerable adults at increased risk. Originality/value This paper is a review of recent research.

Financial access and economic development: the moderating role of financial consumer protection

2019 ◽  
Vol 15 (4) ◽  
pp. 406-424 ◽  
Author(s):  
Maryam Kriese ◽  
Joshua Yindenaba Abor ◽  
Elikplimi Agbloyor
Keyword(s):  
Economic Development ◽  
World Bank ◽  
Financial Literacy ◽  
Compliance Monitoring ◽  
Financial Access ◽  
Policy Makers ◽  
Content Type ◽  
The World Bank ◽  
Moderating Role

Purpose The purpose of this paper is to examine the moderating role of financial consumer protection (FCP) in the access–development nexus. Design/methodology/approach The study is based on cross-country data on 102 countries surveyed in the World Bank Global Survey on FCP and Financial Literacy (2013). The White heteroscedasticity adjusted regressions and Two-stage least squares regressions (2SLS) are used for the estimation. Findings Interactions between FCP regulations that foster fair treatment, disclosure, dispute resolution and recourse and financial access have positive net effects on economic development. However, there is no sufficient evidence to suggest that interactions between financial access and enforcement and compliance monitoring regulations have a significant effect on economic development. Practical implications First, policy makers should continue with efforts aimed at instituting FCP regimes as part of strategies aimed at broadening access to financial services for enhanced economic development. Second, instituting FCP regimes per se may not be enough. Policy makers need to consider possible intervening factors such as the provision of adequate resources and supervisory authority, for compliance monitoring and enforcement to achieve the expected positive effect on economic development. Originality/value This study extends evidence in the law–finance–growth literature by providing empirical evidence on the effect of legal institution specific to the protection of retail financial consumers on the access–development nexus using a nouvel data set, the World Bank Global survey on FCP and Financial Literacy (2013).

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