Family Climate and Intention to Use Cannabis as Predictors of Cannabis Use and Cannabis-Related Problems among Young University Students.

Determining the predictive variables associated with cannabis use and cannabis-related problems can ease the identification of young cannabis consumers who can benefit from prevention interventions. This study aimed: (1) to describe, among university students, the cannabis use and cannabis-use problems, intention to use cannabis and family climate based on the gender and the people the student lives with; (2) to explore whether the family climate and intention to use cannabis are predictors of cannabis use and cannabis-related problems. The sample was composed of 339 Spanish undergraduates (51.

Determinants of Cue-Elicited Alcohol Craving and Perceived Realism in Virtual Reality Environments among Patients with Alcohol Use Disorder.

The identification of variables that can modulate the efficacy of cue exposure using virtual reality (VR) is crucial. This study aimed to explore determinant variables of cue-elicited alcohol craving and perceived realism (PR) of environments and alcoholic beverages during a VR cue-exposure session among alcohol use disorder (AUD) outpatients. A prospective cohort study was conducted amongst 72 outpatients with AUD from a clinical setting.

Correction: Quorum sensing and stress-activated MAPK signaling repress yeast to hypha transition in the fission yeast Schizosaccharomyces japonicus.

[This corrects the article DOI: 10.1371/journal.pgen.

Quorum sensing and stress-activated MAPK signaling repress yeast to hypha transition in the fission yeast Schizosaccharomyces japonicus.

Quorum sensing (QS), a mechanism of microbial communication dependent on cell density, governs developmental decisions in many bacteria and in some pathogenic and non-pathogenic fungi including yeasts. In these simple eukaryotes this response is mediated by the release into the growth medium of quorum-sensing molecules (QSMs) whose concentration increases proportionally to the population density. To date the occurrence of QS is restricted to a few yeast species.

Differential functional regulation of protein kinase C (PKC) orthologs in fission yeast.

The two PKC orthologs Pck1 and Pck2 in the fission yeast operate in a redundant fashion to control essential functions, including morphogenesis and cell wall biosynthesis, as well as the activity of the cell integrity pathway and its core element, the MAPK Pmk1. We show here that, despite the strong structural similarity and functional redundancy of these two enzymes, the mechanisms regulating their maturation, activation, and stabilization have a remarkably distinct biological impact on both kinases. We found that, in contrast to Pck2, putative phosphorylation of Pck1 within the conserved activation loop, turn, and hydrophobic motifs is essential for Pck1 stability and biological functions.

Multiple crosstalk between TOR and the cell integrity MAPK signaling pathway in fission yeast.

In eukaryotic cells, the highly conserved Target of Rapamycin (TOR) and the Mitogen Activated Protein Kinase (MAPK) signaling pathways elicit adaptive responses to extra- and intracellular conditions by regulating essential cellular functions. However, the nature of the functional relationships between both pathways is not fully understood. In the fission yeast Schizosaccharomyces pombe the cell integrity MAPK pathway (CIP) regulates morphogenesis, cell wall structure and ionic homeostasis.

Distinct biological activity of threonine monophosphorylated MAPK isoforms during the stress response in fission yeast.

Mitogen-activated protein kinases (MAPKs) define a specific group of eukaryotic protein kinases which regulate a number of cellular functions by transducing extracellular signals to intracellular responses. Unlike other protein kinases, catalytic activation of MAPKs by MAPKKs depends on dual phosphorylation at two tyrosine and threonine residues within the conserved TXY motif, and this has been proposed to occur in an ordered fashion, where the initial phosphorylation on tyrosine is followed by phosphorylation at the threonine residue. However, monophosphorylated MAPKs also exist in vivo, and although threonine phosphorylated isoforms retain some catalytic activity, their functional significance remains to be further elucidated.

Multiple layers of regulation influence cell integrity control by the PKC ortholog Pck2 in fission yeast.

The fission yeast protein kinase C (PKC) ortholog Pck2 controls cell wall synthesis and is a major upstream activator of the cell integrity pathway (CIP) and its core component, the MAP kinase Pmk1 (also known as Spm1), in response to environmental stimuli. We show that in vivo phosphorylation of Pck2 at the conserved T842 activation loop during growth and in response to different stresses is mediated by the phosphoinositide-dependent kinase (PDK) ortholog Ksg1 and an autophosphorylation mechanism. However, T842 phosphorylation is not essential for Pmk1 activation, and putative phosphorylation at T846 might play an additional role in Pck2 catalytic activation and downstream signaling.

Rho2 palmitoylation is required for plasma membrane localization and proper signaling to the fission yeast cell integrity mitogen- activated protein kinase pathway.

The fission yeast small GTPase Rho2 regulates morphogenesis and is an upstream activator of the cell integrity pathway, whose key element, mitogen-activated protein kinase (MAPK) Pmk1, becomes activated by multiple environmental stimuli and controls several cellular functions. Here we demonstrate that farnesylated Rho2 becomes palmitoylated in vivo at cysteine-196 within its carboxyl end and that this modification allows its specific targeting to the plasma membrane. Unlike that of other palmitoylated and prenylated GTPases, the Rho2 control of morphogenesis and Pmk1 activity is strictly dependent upon plasma membrane localization and is not found in other cellular membranes.

Rho1 GTPase and PKC ortholog Pck1 are upstream activators of the cell integrity MAPK pathway in fission yeast.

In the fission yeast Schizosaccharomyces pombe the cell integrity pathway (CIP) orchestrates multiple biological processes like cell wall maintenance and ionic homeostasis by fine tuning activation of MAPK Pmk1 in response to various environmental conditions. The small GTPase Rho2 positively regulates the CIP through protein kinase C ortholog Pck2. However, Pmk1 retains some function in mutants lacking either Rho2 or Pck2, suggesting the existence of additional upstream regulatory elements to modulate its activity depending on the nature of the environmental stimulus.

Role of the fission yeast cell integrity MAPK pathway in response to glucose limitation.

Background: Glucose is a signaling molecule which regulates multiple events in eukaryotic organisms and the most preferred carbon source in the fission yeast Schizosaccharomyces pombe. The ability of this yeast to grow in the absence of glucose becomes strongly limited due to lack of enzymes of the glyoxylate cycle that support diauxic growth. The stress-activated protein kinase (SAPK) pathway and its effectors, Sty1 MAPK and transcription factor Atf1, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bisphosphatase.

Biological significance of nuclear localization of mitogen-activated protein kinase Pmk1 in fission yeast.

Mitogen-activated protein kinase (MAPK) signaling pathways play a fundamental role in the response of eukaryotic cells to environmental changes. Also, much evidence shows that the stimulus-dependent nuclear targeting of this class of regulatory kinases is crucial for adequate regulation of distinct cellular events. In the fission yeast Schizosaccharomyces pombe, the cell integrity MAPK pathway, whose central element is the MAPK Pmk1, regulates multiple processes such as cell wall integrity, vacuole fusion, cytokinesis, and ionic homeostasis.

Rga4, a Rho-GAP from fission yeast: Finding specificity within promiscuity.

Regulation by signaling molecules of pathways involved in determining cell size and shape is fundamental to understand morphogenesis. In eukaryotic cells, Rho GTPases modulate cellular events by acting as molecular switches. GTPase Activating Proteins (GAPs) control the fine-tuning of Rho GTPase activity as downregulators that promote their inactive state.

Fission yeast receptor of activated C kinase (RACK1) ortholog Cpc2 regulates mitotic commitment through Wee1 kinase.

In the fission yeast Schizosaccharomyces pombe, Wee1-dependent inhibitory phosphorylation of the highly conserved Cdc2/Cdk1 kinase determines the mitotic onset when cells have reached a defined size. The receptor of activated C kinase (RACK1) is a scaffolding protein strongly conserved among eukaryotes which binds to other proteins to regulate multiple processes in mammalian cells, including the modulation of cell cycle progression during G(1)/S transition. We have recently described that Cpc2, the fission yeast ortholog to RACK1, controls from the ribosome the activation of MAPK cascades and the cellular defense against oxidative stress by positively regulating the translation of specific genes whose products participate in the above processes.

Rga4 modulates the activity of the fission yeast cell integrity MAPK pathway by acting as a Rho2 GTPase-activating protein.

Rho GTPase-activating proteins (GAPs) are responsible for the inactivation of Rho GTPases, which are involved in the regulation of critical biological responses in eukaryotic cells, ranging from cell cycle control to cellular morphogenesis. The genome of fission yeast Schizosaccharomyces pombe contains six genes coding for putative Rho GTPases, whereas nine genes code for predicted Rho GAPs (Rga1 to Rga9). One of them, Rga4, has been recently described as a Cdc42 GAP, involved in the control of cell diameter and symmetry in fission yeast.

Role for RACK1 orthologue Cpc2 in the modulation of stress response in fission yeast.

The receptor of activated C kinase (RACK1) is a protein highly conserved among eukaryotes. In mammalian cells, RACK1 functions as an adaptor to favor protein kinase C (PKC)-mediated phosphorylation and subsequent activation of c-Jun NH(2)-terminal kinase mitogen-activated protein kinase. Cpc2, the RACK1 orthologue in the fission yeast Schizosaccharomyces pombe, is involved in the control of G2/M transition and interacts with Pck2, a PKC-type protein member of the cell integrity Pmk1 mitogen-activated protein kinase (MAPK) pathway.

Stress-activated protein kinase-mediated down-regulation of the cell integrity pathway mitogen-activated protein kinase Pmk1p by protein phosphatases.

Fission yeast mitogen-activated protein kinase (MAPK) Pmk1p is involved in morphogenesis, cytokinesis, and ion homeostasis as part of the cell integrity pathway, and it becomes activated under multiple stresses, including hyper- or hypotonic conditions, glucose deprivation, cell wall-damaging compounds, and oxidative stress. The only protein phosphatase known to dephosphorylate and inactivate Pmk1p is Pmp1p. We show here that the stress-activated protein kinase (SAPK) pathway and its main effector, Sty1p MAPK, are essential for proper deactivation of Pmk1p under hypertonic stress in a process regulated by Atf1p transcription factor.

Transduction of centrifugation-induced gravity forces through mitogen-activated protein kinase pathways in the fission yeast Schizosaccharomyces pombe.

Centrifugation of cells of Schizosaccharomyces pombe in liquid medium prompted a marked activation of Sty1 and Pmk1, which are the effector mitogen-activated protein kinases (MAPKs) of the stress-activated protein kinase pathway and the cell-integrity pathway, respectively. Transduction of the centrifugation signals showed a sensitivity threshold above which the response was dependent on time and temperature. Centrifugation-induced phosphorylation of Sty1 and Pmk1 required the presence of the main functional components of the respective signalling cascades, i.

Stress-induced response, localization, and regulation of the Pmk1 cell integrity pathway in Schizosaccharomyces pombe.

Mitogen-activated protein kinase (MAPK) signaling pathways are critical for the sensing and response of eukaryotic cells to extracellular changes. In Schizosaccharomyces pombe, MAPK Pmk1/Spm1 has been involved in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis, as part of the so-called cell integrity pathway together with MAPK kinase kinase Mkh1 and MAPK kinase Pek1. We show that Pmk1 is activated in multiple stress situations, including hyper- or hypotonic stress, glucose deprivation, presence of cell wall-damaging compounds, and oxidative stress induced by hydrogen peroxide or pro-oxidants.

Functional characterization of Schizosaccharomyces pombe neutral trehalase altered in phosphorylatable serine residues.

The activation of neutral trehalase (Ntp1) by metabolic and physical stresses in Schizosaccharomyces pombe is dependent on protein kinases Pka1 or Sck1. Mutant ntp1 alleles altered for potentially phosphorylatable serine residues within the regulatory domain of the enzyme were integrated under the control of the native promoter in an ntp1-deleted background. The trehalase variants were expressed to a level similar to that of wild type trehalase from control cells.

A cooperative role for Atf1 and Pap1 in the detoxification of the oxidative stress induced by glucose deprivation in Schizosaccharomyces pombe.

In Schizosaccharomyces pombe, glucose concentrations below a certain threshold trigger the stress-activated protein kinase (SAPK) signal transduction pathway and promote increased transcription of Atf1-dependent genes coding for the general stress response. Removal of glucose specifically induces the nuclear accumulation of green fluorescent protein-labeled Pap1 (GFP-Pap1) and the expression of genes dependent on this transcription factor. In contrast, depletion of the nitrogen source triggers the SAPK pathway but does not activate Pap1-dependent gene transcription, indicating that carbon stress rather than growth arrest leads to an endogenous oxidative condition that favors nuclear accumulation of Pap1.

Transcriptional and post-translational regulation of neutral trehalase in Schizosaccharomyces pombe during thermal stress.

In the fission yeast Schizosaccharomyces pombe, a heat shock enhances transcription of the ntp1(+) gene, encoding the hydrolytic enzyme neutral trehalase. As compared to wild-type cells, cells devoid of the MAP kinase Sty1p showed a strong decrease in ntp1(+) expression induced by the temperature upshift, indicating that the stress-activated protein kinase (SAPK) pathway regulates the expression of this gene during heat shock. The transcription factor Atf1p, which is the main downstream target for Sty1p in the SAPK pathway, appears to be involved in such control, since ntp1(+) expression under heat shock proved to be significantly blocked in atf1(+)-disrupted cells.