Signalling centre vortices coordinate collective behaviour in social amoebae

2022 ◽  
Author(s):  
Hugh Z Ford ◽  
Angelika Manhart ◽  
Jonathan R Chubb

Self-sustaining signalling waves provide a source of information in living systems. A classic example is the rotating spiral waves of cAMP (chemoattractant) release that encode Dictyostelium morphogenesis. These patterns remain poorly characterised due to limitations in tracking the signalling behaviour of individual cells in the context of the whole collective. Here, we have imaged Dictyostelium populations over millimetre length scales and track the emergence, structure, progression and biological effects of cAMP waves by monitoring the signalling states and motion of individual cells. Collective migration coincides with a decrease in the period and speed of waves that stem from an increase in the rotational speed and curvature of spiral waves. The dynamics and structure of spiral waves are generated by the vortex motion of the spiral tip. Spiral tip circulation spatially organises a small group of cells into a ring pattern, which also constrains spiral tip motion. Both the cellular ring and tip path gradually contract over time, resulting in the acceleration of spiral rotation and change in global wave dynamics. Aided by mathematical modelling, we show that this contraction is due to an instability driven by a deflection in cell chemotaxis around the spiral tip cAMP field, resulting in a deformation of the cellular ring pattern towards its centre. That is, vortex contraction modulates the source of information which, upon dissemination (excitable signal relay) and decoding (chemotaxis), triggers morphogenesis. By characterising rotating spiral waves at this level of detail, our results describe a mechanism by which information generated by a self-sustaining signal, and disseminated across the population, is modulated at the organisational source.

Author(s):  
Laura-Maria Popescu ◽  
Ileana Nișulescu-Ashrafzadeh

Accounting means normally a basis while making management decisions; it is the information tool in order to highlight the strategies and to confirm their success. There are also cases where the roles are reversed and the management delineates the accounting directions according to the results obtained, thus being transformed from the company management for results to the results themselves. Even if over time, the information and activity monitoring techniques improved, the precision of the economic and financial data remains dependent on the reporting referential and the manipulation technique of the results. The article is meant to highlight the items capable to characterise the choice of a management based on results, the conditions of its development, how the financial and accounting information users are affected, particularly the investors, as well as how it can be detected. It is also highlighted the fact that the management based on results plays a very important role for the apparition and development of the accounting engineering at the level of company by the determination it exercises over the managers while achieving or surpassing the objectives. Thus, there is the issue of a false reflection of the company’s activity, regarded by the prism of the management objectives, making particularly sensitive the passage from the economic reality of the company to the management ideals of the management. The financial and accounting information remains as main source of reflection of the economic activity and of the results of these activities, both for the own managers of the entities and for the large diversity of third parties: providers, customers, employees, investors, banks, State institutions etc., that makes it vulnerable in front of the external actions. It is important that in any management plan, its accounting represents a source of information for the management and not a means of obtaining the results.


1997 ◽  
Vol 94 (25) ◽  
pp. 13719-13723 ◽  
Author(s):  
E. Palsson ◽  
K. J. Lee ◽  
R. E. Goldstein ◽  
J. Franke ◽  
R. H. Kessin ◽  
...  

2018 ◽  
Vol 43 (4) ◽  
pp. 374-393 ◽  
Author(s):  
Pablo Ortega-del-Cerro

The present work analyses fraternal relationships among Spanish naval officers during the eighteenth and nineteenth centuries. The main aim of the article is to understand the important role played by siblings and the changes undergone by fraternal links over time. In order to do this, the article addresses three objectives: characterizing fraternal ties in the Spanish naval officer corps, analyzing fraternal relationships in relation to other family links and to the officer corps’ professional context, and exploring how siblinghood transformed during these two centuries. The main source of information used in this work is the testaments signed by naval officers in Spanish navy bases. The article is divided into two parts, dealing with quantitative and qualitative issues, respectively. The first part examines the proportion of naval officers who had siblings, while the second part studies the kind of relationship that existed between them; three kinds of relationship are proposed: vertical ties, horizontal links, and secondary relationships.


2020 ◽  
Author(s):  
Zhuojun Liu ◽  
Jia Liu ◽  
Tainming Zhang ◽  
Lin Li ◽  
Shuo Zhang ◽  
...  

Abstract Background: The more selective second-generation BTK inhibitors (BTKis) Acalabrutinib and Zanubrutinib and the first-generation BTK inhibitor (BTKi) Ibrutinib are highlighted by their clinical effectiveness in mantle cell lymphoma (MCL), however, similarities and differences of their biological and molecular effects on anti-survival of MCL cells induced by these BTKis with distinct binding selectivity against BTK remain largely unknown. Methods: AlamarBlue assays were performed to define cytotoxicity of BTKis against MCL cells, Jeko-1 and Mino. Cleaved PARP and caspase-3 levels were examined by immunoblot analysis to study BTKi-induced apoptotic effects. Biological effects of BTKis on MCL-cell chemotaxis and lipid droplet (LD) accumulation were examined in Jeko-1, Mino and primary MCL cells via Transwell and Stimulated Raman scattering imaging analysis respectively. Enzyme-linked immunoassays were used to determine CCL3 and CCL4 levels in MCL-cell culture supernatants. RNA-seq analyses identified BTKi targets which were validated by quantitative RT-PCR (qRT-PCR) and immunoblot analysis. Results: Acalabrutinib and Zanubrutinib induced moderate apoptosis in Ibrutinib high-sensitive JeKo-1 cells and Ibrutinib low-sensitive Mino cells, which was accompanied by cleaved PARP and caspase-3. Such effects might be caused by the stronger ability of Ibrutinib to upregulate the expression of pro-apoptotic genes, such as HRK, GADD45A , and ATM , in JeKo-1 cells than in Mino cells, and the expression of such apoptotic genes was slightly changed by Acalabrutinib and Zanubrutinib in both JeKo-1 and Mino cells. Further, Acalabrutinib, Zanubrutinib and Ibrutinib reduced MCL-cell chemotaxis with similar efficiency, due to their similar abilities to downmodulate chemokines, such as CCL3 and CCL4. Also, these three BTKis similarly suppressed MCL-cell LD accumulation via downregulating lipogenic factors, DGAT2, SCD, ENPP2 and ACACA without significant differences. Conclusion: BTKis demonstrated differential capacities to induce MCL-cell apoptosis due to their distinct capabilities to regulate the expression of apoptosis-related genes, and similar biological and molecular inhibitory effects on MCL-cell chemotaxis and LD accumulation.


2005 ◽  
Vol 91 (4) ◽  
pp. 373-379 ◽  
Author(s):  
Francesco Perrone ◽  
Maurizio Marangolo ◽  
Francesco Di Costanzo ◽  
Giuseppe Colucci ◽  
Lazzaro Repetto ◽  
...  

Background Clinical trials with non-profit promoters are frequently performed in oncology and represent a highly valuable source of information. Methods To describe the costs of insurance policies and their determinants, data were collected from 12 Italian non-profit promoters of cancer trials. The cost of policies was expressed as per-patient premium. Results Sixty-two quotations issued by only two companies were collected, relative to 44 trials proposed for quotation between December 1998 and February 2003. Only the date of quotation was significantly associated with the cost (P = 0.0003) of quotations by Company A for policies with a deductible, with cost increasing over time. Date of quotation (P = 0.0002), sample size (P = 0.008) and number of study arms (P = 0.02) were independently associated with the cost of no-deductible policies quoted by Company A. Only the number of study arms was significantly associated with cost (P = 0.0001) in no-deductible policies quoted by Company B. Conclusion There is insufficient competition among companies for insurance of cancer trials with non-profit promoters. Many variables that affect the trial risk profile from a clinical perspective are not associated with insurance cost. Date of quotation is among the strongest determinants of the cost, which has sharply increased over time. This trend may become a serious problem for non-profit promoters of cancer clinical trials.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3540-3540 ◽  
Author(s):  
C. Gallo-Stampino ◽  
G. Rizzardi ◽  
S. Toma ◽  
A. Corti ◽  
P. Scifo ◽  
...  

3540 Background: NGRhTNF is a vascular targeting agent (VTA) exploiting a tumour homing peptide (CNGRCG) selectively binding angiogenic vessels in solid tumours where NGRhTNF specific binding relies on dynamic interactions with TNF-receptors and aminopeptidase N (CD13). NGRhTNF combines activity on tumour vascular permeability and direct anticancer activity. Consistently, mouse preclinical data indicate significant synergy between low dose NGRhTNF and cytotoxic agents. Methods: 4 dose levels of NGRhTNF (0.2 up to 1.6 mcg/sqm) have been administered q 3 w in 16 patients. Main end-points included safety, anticancer activity and pharmacokinetic.Measurement of circulating tumor and endothelial cells (CTC and CEC), sTNFRI and s TNFRII, along with plasma cyto-chemokine profile have been performed. Results: 16 patients were enrolled (6F/10M);median age 60,range 43–73). Toxicity was limited to constitutional symptoms, and chills were the most frequent event (40%). Over a median follow-up of 15 weeks, stable disease was achieved in 44% of patients, with long lasting disease control in 2 cases (27 and 75 weeks, with establishment of indication to radical surgery after 75 weeks, presently tumor free after removal of the residual tumor mass). In these 2 patients, VEGF, MMP-9, CA125, significantly decreased over time. DCE-MRI indicates that NGRhTNF increases vascular permeability after first drug exposure, particularly at the dose of 0.4 mcg/sqm, while following multiple infusions it exerts an antivascular effect, as demonstrated by the decrease of Ktrans values. Moreover NGRhTNF is able to elicit inflammatory and immune responses over time, as indicated by the modulation of expression of multiple cyto-chemokines. Finally, changes in CTC levels over time consistently matched the clinical outcome. Conclusions: Low dose NGRhTNF has an optimal safety profile along with anticancer activity acting on tumour vasculature and inducing relevant biological effects, thus rendering the agent suitable for a development both as monotherapy and in combination with chemotherapeutics. The phase II program is due to start in early 2007. [Table: see text]


Author(s):  
Samuel R Kuo ◽  
Natalia A Trayanova

Atrial fibrillation (AF) is believed to be perpetuated by recirculating spiral waves. Atrial structures are often characterized with action potentials of varying morphologies; however, the role of the structure-dependent atrial electrophysiological heterogeneity in spiral wave behaviour is not well understood. The purpose of this study is to determine the effect of action potential morphology heterogeneity associated with the major atrial structures in spiral wave maintenance. The present study also focuses on how this effect is further modulated by the presence of the inherent periodicity in atrial structure. The goals of the study are achieved through the simulation of electrical behaviour in a two-dimensional atrial tissue model that incorporates the representation of action potentials in various structurally distinct regions in the right atrium. Periodic boundary conditions are then imposed to form a cylinder (quasi three-dimensional), thus allowing exploration of the additional effect of structure periodicity on spiral wave behaviour. Transmembrane potential maps and phase singularity traces are analysed to determine effects on spiral wave behaviour. Results demonstrate that the prolonged refractoriness of the crista terminalis (CT) affects the pattern of spiral wave reentry, while the variation in action potential morphology of the other structures does not. The CT anchors the spiral waves, preventing them from drifting away. Spiral wave dynamics is altered when the ends of the sheet are spliced together to form a cylinder. The main effect of the continuous surface is the generation of secondary spiral waves which influences the primary rotors. The interaction of the primary and secondary spiral waves decreased as cylinder diameter increased.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Innokentiy A. Kastalskiy ◽  
Evgeniya V. Pankratova ◽  
Evgeny M. Mirkes ◽  
Victor B. Kazantsev ◽  
Alexander N. Gorban

AbstractThe dynamics of epidemics depend on how people's behavior changes during an outbreak. At the beginning of the epidemic, people do not know about the virus, then, after the outbreak of epidemics and alarm, they begin to comply with the restrictions and the spreading of epidemics may decline. Over time, some people get tired/frustrated by the restrictions and stop following them (exhaustion), especially if the number of new cases drops down. After resting for a while, they can follow the restrictions again. But during this pause the second wave can come and become even stronger then the first one. Studies based on SIR models do not predict the observed quick exit from the first wave of epidemics. Social dynamics should be considered. The appearance of the second wave also depends on social factors. Many generalizations of the SIR model have been developed that take into account the weakening of immunity over time, the evolution of the virus, vaccination and other medical and biological details. However, these more sophisticated models do not explain the apparent differences in outbreak profiles between countries with different intrinsic socio-cultural features. In our work, a system of models of the COVID-19 pandemic is proposed, combining the dynamics of social stress with classical epidemic models. Social stress is described by the tools of sociophysics. The combination of a dynamic SIR-type model with the classical triad of stages of the general adaptation syndrome, alarm-resistance-exhaustion, makes it possible to describe with high accuracy the available statistical data for 13 countries. The sets of kinetic constants corresponding to optimal fit of model to data were found. These constants characterize the ability of society to mobilize efforts against epidemics and maintain this concentration over time and can further help in the development of management strategies specific to a particular society.


2021 ◽  
Vol 42 (2) ◽  
pp. 31-48
Author(s):  
Tereza Hejzlarová ◽  
Martin Rychlík

This study deals with haircare, hair ornaments, hairstyles, and hairrelated rituals of the Southern Altaians (Altai Kizhi, Telengits) and their development over time. Haircare has played an important role in Altaian society for centuries. It has been a ritual symbol, an indicator of gender, age, marital or social status. In context, hair has played a significant cultural and social role across societies and historical periods around the world. For this reason, haircare has also been sometimes included among the so-called cultural or human universals, i.e. phenomena that are common to all known human cultures in time and space. The source of information for this study was the authors’ own field research, relevant literature and visual sources documenting the broader context of haircare. The issue is viewed from historical and cultural perspectives, with the main focus on the current haircare of the Altaian people in connection with changes compared to the past. The study focuses on selected phenomena that proved to be the most important in the field research in terms of their existence and the role they currently play in Altaian society. It does not therefore aim to cover the full breadth of the topic, but leaves room for further research on sub-topics.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Rupamanjari Majumder ◽  
Iolanda Feola ◽  
Alexander S Teplenin ◽  
Antoine AF de Vries ◽  
Alexander V Panfilov ◽  
...  

Propagation of non-linear waves is key to the functioning of diverse biological systems. Such waves can organize into spirals, rotating around a core, whose properties determine the overall wave dynamics. Theoretically, manipulation of a spiral wave core should lead to full spatiotemporal control over its dynamics. However, this theory lacks supportive evidence (even at a conceptual level), making it thus a long-standing hypothesis. Here, we propose a new phenomenological concept that involves artificially dragging spiral waves by their cores, to prove the aforementioned hypothesis in silico, with subsequent in vitro validation in optogenetically modified monolayers of rat atrial cardiomyocytes. We thereby connect previously established, but unrelated concepts of spiral wave attraction, anchoring and unpinning to demonstrate that core manipulation, through controlled displacement of heterogeneities in excitable media, allows forced movement of spiral waves along pre-defined trajectories. Consequently, we impose real-time spatiotemporal control over spiral wave dynamics in a biological system.


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