scholarly journals A gated relaxation oscillator controls morphogenetic movements in bacteria

2017 ◽  
Author(s):  
Mathilde Guzzo ◽  
Seán M. Murray ◽  
Eugénie Martineau ◽  
Sébastien Lhospice ◽  
Grégory Baronian ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Myxococcus Xanthus ◽  
Dynamic Control ◽  
Relaxation Oscillator ◽  
Critical Importance ◽  
Gtpase Activating Protein ◽  
Wide Range ◽  
Direction Of Movement ◽  
Polarity Reversals ◽  
Cellular Development

SummaryDynamic control of cell polarity is of critical importance for many aspects of cellular development and motility. In Myxococcus xanthus, a G-protein and its cognate GTPase-activating protein establish a polarity axis that defines the direction of movement of the cell and which can be rapidly inverted by the Frz chemosensory system. Although vital for collective cell behaviours, how Frz triggers this switch has remained unknown. Here, we use genetics, imaging and mathematical modelling to show that Frz controls polarity reversals via a gated relaxation oscillator. FrzX, which we newly identify as the primary Frz output, provides the gating and thus acts as the trigger for reversals. Slow relocalisation of the polarity protein RomR then creates a refractory period during which another switch cannot be triggered. A secondary Frz output, FrzZ, decreases this delay allowing rapid reversals when required. This architecture thus results in a highly tunable switch that allows a wide range of motility responses.

scholarly journals MglC, a Paralog of Myxococcus xanthus GTPase-Activating Protein MglB, Plays a Divergent Role in Motility Regulation

2015 ◽  
Vol 198 (3) ◽  
pp. 510-520 ◽  
Author(s):  
Anna L. McLoon ◽  
Kristin Wuichet ◽  
Michael Häsler ◽  
Daniela Keilberg ◽  
Dobromir Szadkowski ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Cell Polarity ◽  
Response Regulator ◽  
Myxococcus Xanthus ◽  
Social Behaviors ◽  
Gliding Motility ◽  
Cellular Polarity ◽  
Gtpase Activating Protein ◽  
Content Type ◽  
Motility Regulation

ABSTRACTIn order to optimize interactions with their environment and one another, bacteria regulate their motility. In the case of the rod-shaped cells ofMyxococcus xanthus, regulated motility is essential for social behaviors.M. xanthusmoves over surfaces using type IV pilus-dependent motility and gliding motility. These two motility systems are coordinated by a protein module that controls cell polarity and consists of three polarly localized proteins, the small G protein MglA, the cognate MglA GTPase-activating protein MglB, and the response regulator RomR. Cellular reversals are induced by the Frz chemosensory system, and the output response regulator of this system, FrzZ, interfaces with the MglA/MglB/RomR module to invert cell polarity. Using a computational approach, we identify a paralog of MglB, MXAN_5770 (MglC). Genetic epistasis experiments demonstrate that MglC functions in the same pathway as MglA, MglB, RomR, and FrzZ and is important for regulating cellular reversals. Like MglB, MglC localizes to the cell poles asymmetrically and with a large cluster at the lagging pole. Correct polar localization of MglC depends on RomR and MglB. Consistently, MglC interacts directly with MglB and the C-terminal output domain of RomR, and we identified a surface of MglC that is necessary for the interaction with MglB and for MglC function. Together, our findings identify an additional member of theM. xanthuspolarity module involved in regulating motility and demonstrate how gene duplication followed by functional divergence can add a layer of control to the complex cellular processes of motility and motility regulation.IMPORTANCEGene duplication and the subsequent divergence of the duplicated genes are important evolutionary mechanisms for increasing both biological complexity and regulation of biological processes. The bacteriumMyxococcus xanthusis a soil bacterium with an unusually large genome that carries out several social processes, including predation of other bacterial species and formation of multicellular, spore-filled fruiting bodies. One feature of the largeM. xanthusgenome is that it contains many gene duplications. Here, we compare the products of one example of gene duplication and divergence, in which a paralog of the cognate MglA GTPase-activating protein MglB has acquired a different and opposing role in the regulation of cellular polarity and motility, processes critical to the bacterium's social behaviors.

scholarly journals The polarity of myxobacterial gliding is regulated by direct interactions between the gliding motors and the Ras homolog MglA

2014 ◽  
Vol 112 (2) ◽  
pp. E186-E193 ◽  
Author(s):  
Beiyan Nan ◽  
Jigar N. Bandaria ◽  
Kathy Y. Guo ◽  
Xue Fan ◽  
Amirpasha Moghtaderi ◽  
...  
Keyword(s):  
Spatial Distribution ◽  
Cell Polarity ◽  
Myxococcus Xanthus ◽  
Proton Motive Force ◽  
Gliding Motility ◽  
Cellular Polarity ◽  
Gtpase Activating Protein ◽  
Chemosensory Pathway ◽  
Ras Family ◽  
Ras Family Proteins

Gliding motility in Myxococcus xanthus is powered by flagella stator homologs that move in helical trajectories using proton motive force. The Frz chemosensory pathway regulates the cell polarity axis through MglA, a Ras family GTPase; however, little is known about how MglA establishes the polarity of gliding, because the gliding motors move simultaneously in opposite directions. Here we examined the localization and dynamics of MglA and gliding motors in high spatial and time resolution. We determined that MglA localizes not only at the cell poles, but also along the cell bodies, forming a decreasing concentration gradient toward the lagging cell pole. MglA directly interacts with the motor protein AglR, and the spatial distribution of AglR reversals is positively correlated with the MglA gradient. Thus, the motors moving toward lagging cell poles are less likely to reverse, generating stronger forward propulsion. MglB, the GTPase-activating protein of MglA, regulates motor reversal by maintaining the MglA gradient. Our results suggest a mechanism whereby bacteria use Ras family proteins to modulate cellular polarity.

scholarly journals Wide range continuously tunable and fast thermal switching based on compressible graphene composite foams

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tingting Du ◽  
Zixin Xiong ◽  
Luis Delgado ◽  
Weizhi Liao ◽  
Joseph Peoples ◽  
...  
Keyword(s):  
Thermal Management ◽  
Dynamic Control ◽  
Operating Conditions ◽  
Dynamic Thermal Management ◽  
Graphene Composite ◽  
Continuous Tuning ◽  
Composite Foams ◽  
Wide Range ◽  
Thermal Switches ◽  
Thermal Switching

AbstractThermal switches have gained intense interest recently for enabling dynamic thermal management of electronic devices and batteries that need to function at dramatically varied ambient or operating conditions. However, current approaches have limitations such as the lack of continuous tunability, low switching ratio, low speed, and not being scalable. Here, a continuously tunable, wide-range, and fast thermal switching approach is proposed and demonstrated using compressible graphene composite foams. Large (~8x) continuous tuning of the thermal resistance is achieved from the uncompressed to the fully compressed state. Environmental chamber experiments show that our variable thermal resistor can precisely stabilize the operating temperature of a heat generating device while the ambient temperature varies continuously by ~10 °C or the heat generation rate varies by a factor of 2.7. This thermal device is promising for dynamic control of operating temperatures in battery thermal management, space conditioning, vehicle thermal comfort, and thermal energy storage.

Pediatric Examination of Educational Readiness

PEDIATRICS ◽  
1980 ◽  
Vol 66 (3) ◽  
pp. 472-473
Author(s):  
C. Keith Conners
Keyword(s):  
School Age ◽  
Critical Importance ◽  
Wide Range ◽  
Child Adaptation ◽  
Range Of Functions

For many years pediatricians have carried out both informal and systematic assessments of behavior in children, with the early motor assessments of Ilg and Ames perhaps being the most well-known. Levine et al (p 341) have responded to the need for a structured assessment of more complex behavioral functions of the school age child with the PEER (Pediatric Examination of Educational Readiness). This instrument will no doubt be welcomed for several reasons: it is brief, systematic, covers a wide range of functions, and fits readily into the pediatrician's repertoire. One can only applaud this effort to provide a systematic, quantitative framework for assessing functions of critical importance to child adaptation and development.

Functional Contacts With a Range of Splicing Proteins Suggest a Central Role for Brr2p in the Dynamic Control of the Order of Events in Spliceosomes ofSaccharomyces cerevisiae

Genetics ◽  
2001 ◽  
Vol 157 (4) ◽  
pp. 1451-1467 ◽  
Author(s):  
Rob W van Nues ◽  
Jean D Beggs
Keyword(s):  
Protein Interactions ◽  
Dynamic Control ◽  
Splicing Factors ◽  
Functional Protein ◽  
U6 Snrna ◽  
Wide Range ◽  
Snrnp Protein ◽  
Associated Proteins ◽  
Step Factor ◽  
Hybrid Screening

AbstractMapping of functional protein interactions will help in understanding conformational rearrangements that occur within large complexes like spliceosomes. Because the U5 snRNP plays a central role in pre-mRNA splicing, we undertook exhaustive two-hybrid screening with Brr2p, Prp8p, and other U5 snRNP-associated proteins. DExH-box protein Brr2p interacted specifically with five splicing factors: Prp8p, DEAH-box protein Prp16p, U1 snRNP protein Snp1p, second-step factor Slu7p, and U4/U6.U5 tri-snRNP protein Snu66p, which is required for splicing at low temperatures. Co-immunoprecipitation experiments confirmed direct or indirect interactions of Prp16p, Prp8p, Snu66p, and Snp1p with Brr2p and led us to propose that Brr2p mediates the recruitment of Prp16p to the spliceosome. We provide evidence that the prp8-1 allele disrupts an interaction with Brr2p, and we propose that Prp8p modulates U4/U6 snRNA duplex unwinding through another interaction with Brr2p. The interactions of Brr2p with a wide range of proteins suggest a particular function for the C-terminal half, bringing forward the hypothesis that, apart from U4/U6 duplex unwinding, Brr2p promotes other RNA rearrangements, acting synergistically with other spliceosomal proteins, including the structurally related Prp2p and Prp16p. Overall, these protein interaction studies shed light on how splicing factors regulate the order of events in the large spliceosome complex.

scholarly journals Cell-Biological Studies of Osmotic Shock Response in Streptomyces spp

2016 ◽  
Vol 199 (1) ◽  
Author(s):  
Katsuya Fuchino ◽  
Klas Flärdh ◽  
Paul Dyson ◽  
Nora Ausmees
Keyword(s):  
Cell Wall ◽  
Cell Polarity ◽  
Tip Growth ◽  
Biological Study ◽  
Polar Growth ◽  
Hyphal Branching ◽  
Content Type ◽  
Biological Studies ◽  
Wide Range ◽  
Tip Extension

ABSTRACT Most bacteria are likely to face osmotic challenges, but there is yet much to learn about how such environmental changes affect the architecture of bacterial cells. Here, we report a cell-biological study in model organisms of the genus Streptomyces, which are actinobacteria that grow in a highly polarized fashion to form branching hyphae. The characteristic apical growth of Streptomyces hyphae is orchestrated by protein assemblies, called polarisomes, which contain coiled-coil proteins DivIVA and Scy, and recruit cell wall synthesis complexes and the stress-bearing cytoskeleton of FilP to the tip regions of the hyphae. We monitored cell growth and cell-architectural changes by time-lapse microscopy in osmotic upshift experiments. Hyperosmotic shock caused arrest of growth, loss of turgor, and hypercondensation of chromosomes. The recovery period was protracted, presumably due to the dehydrated state of the cytoplasm, before hyphae could restore their turgor and start to grow again. In most hyphae, this regrowth did not take place at the original hyphal tips. Instead, cell polarity was reprogrammed, and polarisomes were redistributed to new sites, leading to the emergence of multiple lateral branches from which growth occurred. Factors known to regulate the branching pattern of Streptomyces hyphae, such as the serine/threonine kinase AfsK and Scy, were not involved in reprogramming of cell polarity, indicating that different mechanisms may act under different environmental conditions to control hyphal branching. Our observations of hyphal morphology during the stress response indicate that turgor and sufficient hydration of cytoplasm are required for Streptomyces tip growth. IMPORTANCE Polar growth is an intricate manner of growth for accomplishing a complicated morphology, employed by a wide range of organisms across the kingdoms of life. The tip extension of Streptomyces hyphae is one of the most pronounced examples of polar growth among bacteria. The expansion of the cell wall by tip extension is thought to be facilitated by the turgor pressure, but it was unknown how external osmotic change influences Streptomyces tip growth. We report here that severe hyperosmotic stress causes cessation of growth, followed by reprogramming of cell polarity and rearrangement of growth zones to promote lateral hyphal branching. This phenomenon may represent a strategy of hyphal organisms to avoid osmotic stress encountered by the growing hyphal tip.

The Cell Polarity PTK7 Receptor Is Expressed in Myeloid Cells and Acts as a Modulator of the Chemotherapeutic Response in AML Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1571-1571 ◽  
Author(s):  
Thomas Prebet ◽  
Anne Catherine Lhoumeau ◽  
Christine Arnoulet ◽  
Anais Aulas ◽  
Sylvie Marchetto ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tyrosine Kinase ◽  
Cell Polarity ◽  
Cell Lines ◽  
Tyrosine Kinase Receptor ◽  
Epithelial Tissue ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Wide Range

Abstract Abstract 1571 Poster Board I-596 The pseudo tyrosine kinase receptor 7 (PTK7) is an orphean tyrosine kinase receptor assigned to the planar cell polarity pathway (PCP). It has been recently described and plays a major role during embryogenesis and epithelial tissue organisation. To date there is no report in the litterature considering a potential implication in hematopoiesis. In silico and in vitro analysis found that PTK7 was also expressed in normal myeloid progenitors and CD34+ CD38- bone marrow cells in humans. Preliminary results from our team showed that PTK7 was also expressed in various leukemic cell lines such Jurkat, TF-1 or KG-1a. We decided to perform a wide range multicolour immunophenotyping screen on patients with acute myeloid leukemia (AML) at diagnosis and to investigate the role of PTK7 in AML in vitro. More than 250 patient samples were evaluated and we demonstrated that PTK7 was largely expressed in AML as 72% of the samples were PTK7 positive. Its expression mostly correlates with granulocytic lineage differentiation. PTK7 expression was associated with a lower WBC count at diagnosis and a lower frequency of extramedullary disease whatever was FAB subtype. Interestingly, PTK7 expression was associated with some cytogenetic subgroups including CBF-AML and APL. There was no correlation with molecular subgroups (i.e. FLT3-ITD/NPM1/CEBPA status). Overall Survival and Relapse Free Survival were evaluated in non-APL patients treated with induction chemo (n=182). Patients with PTK7 positive AML are more resistant to anthracycline-based frontline therapy with a significantly reduced Relapse Free Survival in a multivariate analysis model integrating all pre treatment variables (2 year probability of RFS= 29% vs 66% for PTK7 negative patients, p= 0.003). Forrest plot analysis showed that the negative impact of PTK7 expression was the most significant in intermediate cytogenetic risk subgroup and when PTK7 was aberrantly expressed in M4-M5 FAB subtypes. There was no demonstrated impact on CR. In cultured cells, expression of PTK7 promotes leukemia cell migration, cell survival and resistance to anthracyclin-induced apoptosis. There was no effect of PTK7 expression on cell proliferation in tritiated thymidine assay. In the absence of known inhibitor of PTK7, we produced a soluble recombinant PTK7-Fc protein that efficiently competes for PTK7 functions in cell migration and survival assays in cell lines and primary AML samples. These data were confirmed using a shRNA strategy. We conclude that PTK7 is a PCP component expressed in the myeloid progenitor compartment that conveys promigratory and anti-apoptotic signal to leukemia cells. Its use as a potential biomarker or therapeutical target should be investigated. Disclosures No relevant conflicts of interest to declare.

A Theory of Moral Choice

2011 ◽  
Author(s):  
Kristen Renwick Monroe
Keyword(s):  
Cognitive Science ◽  
Empirical Analysis ◽  
Political Behavior ◽  
Psychological Factors ◽  
Identity Theory ◽  
Moral Behavior ◽  
Primate Behavior ◽  
Critical Importance ◽  
Moral Choice ◽  
Wide Range

This chapter contemplates the broader themes and implications of this work and constructs a new theory of moral choice. Most existing theories designed to guide moral behavior and examine the ethical acts of others fail to adequately capture what appeared in this volume's analysis to be the critical importance of psychological factors. The chapter thus proposes a new, empirically based identity theory of moral choice. It sketches the outlines of this theory and how it was derived from empirical analysis. The chapter then notes important literature in a wide range of fields, from linguistics and cognitive science to primate behavior and neuroscience, which offers scientific underpinnings for the theory. Finally, the chapter suggests how this theory can usefully help us understand other forms of ethical political behavior.

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