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1.
Semin Cell Dev Biol ; 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32522409

RESUMO

Archerfish are well-known for their ballistic hunting behaviour, in which they shoot down aerial prey with a well-aimed jet of water. This unique hunting strategy poses several challenges for visual systems. Archerfish face significant distortion to the appearance of targets due to refraction at the air/water interface, they search for prey against a complex background of foliage, they change prey targeting behaviour as conditions change, and they must make high speed decisions to avoid competition. By studying how archerfish have overcome these challenges, we have been able to understand more about fundamental problems faced by visual systems and the mechanisms used to solve them. In some cases, such as when searching for targets, the visual capabilities of archerfish are functionally similar to those of humans, despite significant differences in neuroanatomy. In other cases, the particular challenge faced by archerfish magnifies fundamental problems generally faced by visual systems, such as recognizing objects given strong viewpoint dependent changes to appearance. The efficiency of archerfish retrieving fallen prey to avoid kleptoparasitism, demonstrates that their visual processing excels in both speed and accuracy. In this review, we attempt to provide an overview of the many facets of visually driven behaviour of archerfish, and how they have been studied. In addition to their hunting technique, archerfish are ideal for visual processing experiments as they can be quickly trained to perform a range of non-ecologically relevant tasks. Their behavioural flexibility moreover, introduces the opportunity to study how experience-dependence and choice affects visual processing.

2.
Commun Biol ; 3(1): 307, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32533058

RESUMO

In non-mammalian vertebrates, some neurons can regenerate after spinal cord injury. One of these, the giant Mauthner (M-) neuron shows a uniquely direct link to a robust survival-critical escape behavior but appears to regenerate poorly. Here we use two-photon microscopy in parallel with behavioral assays in zebrafish to show that the M-axon can regenerate very rapidly and that the recovery of functionality lags by just days. However, we also find that the site of the injury is critical: While regeneration is poor both close and far from the soma, rapid regeneration and recovery of function occurs for injuries between 10% and 50% of total axon length. Our findings show that rapid regeneration and the recovery of function can be studied at remarkable temporal resolution after targeted injury of one single M-axon and that the decision between poor and rapid regeneration can be studied in this one axon.

3.
Sci Rep ; 10(1): 5579, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221356

RESUMO

Biofilms are composed of microorganisms attached to a solid surface or floating on top of a liquid surface. They pose challenges in the field of medicine but can also have useful applications in industry. Regulation of biofilm growth is complex and still largely elusive. Oscillations are thought to be advantageous for biofilms to cope with nutrient starvation and chemical attacks. Recently, a minimal mathematical model has been employed to describe the oscillations in Bacillus subtilis biofilms. In this paper, we investigate four different modifications to that minimal model in order to better understand the oscillations in biofilms. Our first modification is towards making a gradient of metabolites from the center of the biofilm to the periphery. We find that it does not improve the model and is therefore, unnecessary. We then use realistic Michaelis-Menten kinetics to replace the highly simple mass-action kinetics for one of the reactions. Further, we use reversible reactions to mimic the diffusion in biofilms. As the final modification, we check the combined effect of using Michaelis-Menten kinetics and reversible reactions on the model behavior. We find that these two modifications alone or in combination improve the description of the biological scenario.

4.
Proc Natl Acad Sci U S A ; 117(6): 3254-3260, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32001507

RESUMO

The giant Mauthner (M) cell is the largest neuron known in the vertebrate brain. It has enabled major breakthroughs in neuroscience but its ultimate function remains surprisingly unclear: An actual survival value of M cell-mediated escapes has never been supported experimentally and ablating the cell repeatedly failed to eliminate all rapid escapes, suggesting that escapes can equally well be driven by smaller neurons. Here we applied techniques to simultaneously measure escape performance and the state of the giant M axon over an extended period following ablation of its soma. We discovered that the axon survives remarkably long and remains still fully capable of driving rapid escape behavior. By unilaterally removing one of the two M axons and comparing escapes in the same individual that could or could not recruit an M axon, we show that the giant M axon is essential for rapid escapes and that its loss means that rapid escapes are also lost forever. This allowed us to directly test the survival value of the M cell-mediated escapes and to show that the absence of this giant neuron directly affects survival in encounters with a natural predator. These findings not only offer a surprising solution to an old puzzle but demonstrate that even complex brains can trust vital functions to individual neurons. Our findings suggest that mechanisms must have evolved in parallel with the unique significance of these neurons to keep their axons alive and connected.


Assuntos
Reação de Fuga/fisiologia , Sistema Nervoso/crescimento & desenvolvimento , Neurônios/citologia , Neurônios/fisiologia , Animais , Axônios/fisiologia , Embrião não Mamífero/fisiologia , Larva/fisiologia , Peixe-Zebra
5.
Biosystems ; 187: 104035, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31614190

RESUMO

Protein damage (partly followed by protein aggregation) plays a significant role in ageing, cancer and in neurodegenerative and other diseases. It is known that the proteinogenic amino acids differ in their susceptibility to non-enzymatic modification, such as hydroxylation, peroxidation, chlorination etc. In a novel bioinformatics approach, we introduce measures to quantify the susceptibility of the 20 standard proteinogenic amino acids to such modification. Based on these amino acid scores, we calculated different susceptibilities for 116,387 proteins, testing various scoring approaches. These approaches are based on review articles, text mining and a combination of both. We also show an application by combining the score information with a tool for visualization.

6.
Cell Mol Life Sci ; 77(3): 467-480, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31776589

RESUMO

Pathogenic microorganisms entail enormous problems for humans, livestock, and crop plants. A better understanding of the different infection strategies of the pathogens enables us to derive optimal treatments to mitigate infectious diseases or develop vaccinations preventing the occurrence of infections altogether. In this review, we highlight the current trends in mathematical modeling approaches and related methods used for understanding host-pathogen interactions. Since these interactions can be described on vastly different temporal and spatial scales as well as abstraction levels, a variety of computational and mathematical approaches are presented. Particular emphasis is placed on dynamic optimization, game theory, and spatial modeling, as they are attracting more and more interest in systems biology. Furthermore, these approaches are often combined to illuminate the complexities of the interactions between pathogens and their host. We also discuss the phenomena of molecular mimicry and crypsis as well as the interplay between defense and counter defense. As a conclusion, we provide an overview of method characteristics to assist non-experts in their decision for modeling approaches and interdisciplinary understanding.


Assuntos
Interações Hospedeiro-Patógeno/fisiologia , Animais , Simulação por Computador , Humanos , Modelos Teóricos , Biologia de Sistemas/métodos
7.
Sensors (Basel) ; 19(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370139

RESUMO

A primary concern in a multitude of industrial processes is the precise monitoring of gaseous substances to ensure proper operating conditions. However, many traditional technologies are not suitable for operation under harsh environmental conditions. Radar-based time-of-flight permittivity measurements have been proposed as alternative but suffer from high cost and limited accuracy in highly cluttered industrial plants. This paper examines the performance limits of low-cost frequency-modulated continuous-wave (FMCW) radar sensors for permittivity measurements. First, the accuracy limits are investigated theoretically and the Cramér-Rao lower bounds for time-of-flight based permittivity and concentration measurements are derived. In addition, Monte-Carlo simulations are carried out to validate the analytical solutions. The capabilities of the measurement concept are then demonstrated with different binary gas mixtures of Helium and Carbon Dioxide in air. A low-cost time-of-flight sensor based on two synchronized fully-integrated millimeter-wave (MMW) radar transceivers is developed and evaluated. A method to compensate systematic deviations caused by the measurement setup is proposed and implemented. The theoretical discussion underlines the necessity of exploiting the information contained in the signal phase to achieve the desired accuracy. Results of various permittivity and gas concentration measurements are in good accordance to reference sensors and measurements with a commercial vector network analyzer (VNA). In conclusion, the proposed radar-based low-cost sensor solution shows promising performance for the intended use in demanding industrial applications.

8.
Nat Commun ; 10(1): 2459, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31150008

RESUMO

The original version of this Article contained an error in the spelling of the author Jule Müller, which was incorrectly given as Julia Müller. Additionally, in Fig. 4a, the blue-red colour scale for fold change in ageing/disease regulation included a blue stripe in place of a red stripe at the right-hand end of the scale. These errors have been corrected in both the PDF and HTML versions of the Article.

9.
Viruses ; 11(5)2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100972

RESUMO

Influenza A virus is recognized today as one of the most challenging viruses that threatens both human and animal health worldwide. Understanding the control mechanisms of influenza infection and dynamics is crucial and could result in effective future treatment strategies. Many kinetic models based on differential equations have been developed in recent decades to capture viral dynamics within a host. These models differ in their complexity in terms of number of species elements and number of reactions. Here, we present a new approach to understanding the overall structure of twelve influenza A virus infection models and their relationship to each other. To this end, we apply chemical organization theory to obtain a hierarchical decomposition of the models into chemical organizations. The decomposition is based on the model structure (reaction rules) but is independent of kinetic details such as rate constants. We found different types of model structures ranging from two to eight organizations. Furthermore, the model's organizations imply a partial order among models entailing a hierarchy of model, revealing a high model diversity with respect to their long-term behavior. Our methods and results can be helpful in model development and model integration, also beyond the influenza area.

10.
Sci Rep ; 9(1): 2980, 2019 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-30814590

RESUMO

The recently evolved field of synthetic biology has revolutionized the way we think of biology as an "engineerable" discipline. The newly sprouted branch is constantly in need of simple, cost-effective and automatable DNA-assembly methods. We have developed a reliable DNA-assembly system, ZeBRα (Zero-Background Redα), for cloning multiple DNA-fragments seamlessly with very high efficiency. The hallmarks of ZeBRα are the greatly reduced hands-on time and costs and yet excellent efficiency and flexibility. ZeBRα combines a "zero-background vector" with a highly efficient in vitro recombination method. The suicide-gene in the vector acts as placeholder, and is replaced by the fragments-of-interest, ensuring the exclusive survival of the successful recombinants. Thereby the background from uncut or re-ligated vector is absent and screening for recombinant colonies is unnecessary. Multiple fragments-of-interest can be assembled into the empty vector by a recombinogenic E. coli-lysate (SLiCE) with a total time requirement of less than 48 h. We have significantly simplified the preparation of the high recombination-competent E. coli-lysate compared to the original protocol. ZeBRα is the least labor intensive among comparable state-of-the-art assembly/cloning methods without a trade-off in efficiency.

11.
Front Cell Neurosci ; 13: 43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809130

RESUMO

During the last decades it became increasingly evident that electrical synapses are capable of activity-dependent plasticity. However, measuring the actual strength of electrical transmission remains difficult. Usually changes in coupling strength can only be inferred indirectly from measures such as the coupling coefficient and the coupling conductance. Because these are affected by both junctional and non-junctional conductance, plastic changes can potentially be due to both components. Furthermore, these techniques also require the blocking of chemical transmission, so that processes that involve crosstalk between chemical and electrical synapses will be suppressed. To directly examine the magnitude of errors that can occur, we use dual whole-cell current- and voltage-clamp recordings from the soma of the pair of easily accessible, electrically coupled Retzius cells in the leech to simultaneously determine coupling coefficients, coupling conductances and directly measured gap junctional currents. We present the first direct and comparative analysis of gap junction conductance using all three methods and analyze how each method would characterize the response of gap junctions to serotonin. The traditional coupling coefficients showed severe deficits in assessing the symmetry and strength of electrical synapses. These were reduced when coupling conductances were determined and were absent in the direct method. Additionally, both coupling coefficient and coupling conductance caused large and systematic errors in assessing the size and time course of the serotonin-induced changes of gap junctional currents. Most importantly, both measurements can easily be misinterpreted as implying long-term gap junctional plasticity, although the direct measurements confirm its absence. We thus show directly that coupling coefficients and coupling conductances can severely confound plastic changes in membrane and junctional conductance. Wherever possible, voltage clamp measurements should be chosen to accurately characterize the timing and strength of plasticity of electrical synapses. However, we also demonstrate that coupling coefficients can still yield a qualitatively correct picture when amended by independent measurements of the course of membrane resistance during the experiments.

12.
PLoS One ; 14(2): e0212187, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30779817

RESUMO

Molecular mimicry is the formation of specific molecules by microbial pathogens to avoid recognition and attack by the immune system of the host. Several pathogenic Ascomycota and Zygomycota show such a behaviour by utilizing human complement factor H to hide in the blood stream. We call this type of mimicry molecular crypsis. Such a crypsis can reach a point where the immune system can no longer clearly distinguish between self and non-self cells. Thus, a trade-off between attacking disguised pathogens and erroneously attacking host cells has to be made. Based on signalling theory and protein-interaction modelling, we here present a mathematical model of molecular crypsis of pathogenic fungi using the example of Candida albicans. We tackle the question whether perfect crypsis is feasible, which would imply that protection of human cells by complement factors would be useless. The model identifies pathogen abundance relative to host cell abundance as the predominant factor influencing successful or unsuccessful molecular crypsis. If pathogen cells gain a (locally) quantitative advantage over host cells, even autoreactivity may occur. Our new model enables insights into the mechanisms of candidiasis-induced sepsis and complement-associated autoimmune diseases.


Assuntos
Doenças Autoimunes/metabolismo , Candida albicans/metabolismo , Candidíase/metabolismo , Fator H do Complemento/metabolismo , Modelos Biológicos , Sepse/metabolismo , Humanos
13.
ISME J ; 13(2): 537-546, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30301945

RESUMO

Microorganisms encounter a diversity of chemical stimuli that trigger individual responses and influence population dynamics. However, microbial behavior under the influence of different incentives and microbial decision-making is poorly understood. Benthic marine diatoms that react to sexual attractants as well as to nutrient gradients face such multiple constraints. Here, we document and model behavioral complexity and context-sensitive responses of these motile unicellular algae to sex pheromones and the nutrient silicate. Throughout the life cycle of the model diatom Seminavis robusta nutrient-starved cells localize sources of silicate by combined chemokinetic and chemotactic motility. However, with an increasing need for sex to restore the initial cell size, a change in behavior favoring the attraction-pheromone-guided search for a mating partner takes place. When sex becomes inevitable to prevent cell death, safeguard mechanisms are abandoned, and cells prioritize the search for mating partners. Such selection processes help to explain biofilm organization and to understand species interactions in complex communities.


Assuntos
Quimiotaxia , Diatomáceas/fisiologia , Modelos Biológicos , Biofilmes
14.
Sci Rep ; 8(1): 17541, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30510264

RESUMO

In animal husbandry, livestock industry and research facilities, anaesthetic agents are frequently used to moderate stressful intervention. For mammals and birds, procedures have been established to fine-tune anaesthesia according to the intervention. In ectothermic vertebrates, however, and despite changes in legislation and growing evidence on their cognitive abilities, the presently available information is insufficient to make similarly informed decisions. Here we suggest a straightforward way for rapidly filling this gap. By recording from a command neuron in the brain of fish whose crucial role requires it to integrate and process information from all sensory systems and to relay it to motor output pathways, the specific effects of candidate anaesthesia on central processing of sensory information can directly and efficiently be probed. Our approach allows a rapid and reliable way of deciding if and at which concentration a given anaesthetic affects the central nervous system and sensory processing. We employ our method to four anaesthetics commonly used in fish and demonstrate that our method quickly and with small numbers of animals provides the critical data for informed decisions on anaesthetic use.


Assuntos
Anestésicos/farmacologia , Encéfalo/metabolismo , Carpa Dourada/fisiologia , Neurônios/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Animais
15.
J Exp Biol ; 221(Pt 24)2018 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-30530768

RESUMO

Archerfish are well known for using jets of water to dislodge distant aerial prey from twigs or leaves. This Review gives a brief overview of a number of skills that the fish need to secure prey with their shooting technique. Archerfish are opportunistic hunters and, even in the wild, shoot at artificial objects to determine whether these are rewarding. They can detect non-moving targets and use efficient search strategies with characteristics of human visual search. Their learning of how to engage targets can be remarkably efficient and can show impressive degrees of generalization, including learning from observation. In other cases, however, the fish seem unable to learn and it requires some understanding of the ecological and biophysical constraints to appreciate why. The act of shooting has turned out not to be of a simple all-or-none character. Rather, the fish adjust the volume of water fired according to target size and use fine adjustments in the timing of their mouth opening and closing manoeuvre to adjust the hydrodynamic stability of their jets to target distance. As soon as prey is dislodged and starts falling, the fish make rapid and yet sophisticated multi-dimensional decisions to secure their prey against many intraspecific and interspecific competitors. Although it is not known why and how archerfish evolved an ability to shoot in the first place, I suggest that the evolution of shooting has strongly pushed the co-evolution of diverse other skills that are needed to secure a catch.


Assuntos
Aprendizagem , Perciformes/fisiologia , Comportamento Predatório , Percepção Visual , Animais , Evolução Biológica
16.
Cancers (Basel) ; 10(11)2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30380648

RESUMO

After five years of endocrine therapy, patients with ER+ (estrogen receptor positive) breast cancer face the question of the benefit of further treatment. Ten years of endocrine therapy has been demonstrated to improve survival compared to five years. However, the individual benefit of continuation remains unclear. Therefore, markers for predicting benefit from endocrine treatment and extended endocrine treatment are desperately needed. In this study the dynamics over time of the tumor cells circulating in peripheral blood of patients, circulating tumor cells/ circulating epithelial tumor cells (CTC/CETC), as the systemic part of the tumor were investigated in 36 patients with ER+ primary breast cancer. CTC/CETCs were monitored serially during and after endocrine therapy. After termination of endocrine therapy 12 patients showed an increase in CTC/CETCs, with 8 of 12 suffering relapse. No change or a reduction was observed in 24 patients, with 2 of 24 suffering relapse. Initial tumor size was marginally prognostic (p = 0.053) but not nodal status nor the mere number of CTC/CETCs. Only the trajectory of CTC/CETCs was a statistically significant predictor of relapse free survival (increasing cell numbers: mean = 940 days vs. stable/decreasing cell numbers mean not reached). Individual cases demonstrated that an increase of CTC/CETCs after discontinuation of tamoxifen therapy could be stopped by resuming the endocrine therapy.

17.
Front Microbiol ; 9: 2313, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30333805

RESUMO

Alternative splicing (AS) is an important regulatory mechanism in eukaryotes but only little is known about its impact in fungi. Human fungal pathogens are of high clinical interest causing recurrent or life-threatening infections. AS can be well-investigated genome-wide and quantitatively with the powerful technology of RNA-Seq. Here, we systematically studied AS in human fungal pathogens based on RNA-Seq data. To do so, we investigated its effect in seven fungi during conditions simulating ex vivo infection processes and during in vitro stress. Genes undergoing AS are species-specific and act independently from differentially expressed genes pointing to an independent mechanism to change abundance and functionality. Candida species stand out with a low number of introns with higher and more varying lengths and more alternative splice sites. Moreover, we identified a functional difference between response to host and other stress conditions: During stress, AS affects more genes and is involved in diverse regulatory functions. In contrast, during response-to-host conditions, genes undergoing AS have membrane functionalities and might be involved in the interaction with the host. We assume that AS plays a crucial regulatory role in pathogenic fungi and is important in both response to host and stress conditions.

18.
Sci Rep ; 8(1): 12579, 2018 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30135467

RESUMO

Electrical synapses are formed by two unrelated gap junction protein families, the primordial innexins (invertebrates) or the connexins (vertebrates). Although molecularly different, innexin- and connexin-based electrical synapses are strikingly similar in their membrane topology. However, it remains unclear if this similarity extends also to more sophisticated functions such as long-term potentiation which is only known in connexin-based synapses. Here we show that this capacity is not unique to connexin-based synapses. Using a method that allowed us to quantitatively measure gap-junction conductance we provide the first and unequivocal evidence of long-term potentiation in an innexin-based electrical synapse. Our findings suggest that long-term potentiation is a property that has likely existed already in ancestral gap junctions. They therefore could provide a highly potent system to dissect shared molecular mechanisms of electrical synapse plasticity.


Assuntos
Conexinas/metabolismo , Sinapses Elétricas/metabolismo , Potenciação de Longa Duração , Sequência de Aminoácidos , Animais , Cálcio/metabolismo , Conexinas/química , Espaço Intracelular/metabolismo , Sanguessugas/metabolismo , Sanguessugas/fisiologia , Fosforilação , Transmissão Sináptica
19.
J R Soc Interface ; 15(142)2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29720453

RESUMO

As a part of the complement system, factor H regulates phagocytosis and helps differentiate between a body's own and foreign cells. Owing to mimicry efforts, some pathogenic microorganisms such as Candida albicans are able to bind factor H on their cell surfaces and, thus, become similar to host cells. This implies that the decision between self and foreign is not clear-cut, which leads to a classification problem for the immune system. Here, two different alleles determining the binding affinity of factor H are relevant. Those alleles differ in the SNP Y402H; they are known to be associated with susceptibility to certain diseases. Interestingly, the fraction of both alleles differs in ethnic groups. The game-theoretical model proposed in this article explains the coexistence of both alleles by a battle of the sexes game and investigates the trade-off between pathogen detection and protection of host cells. Further, we discuss the ethnicity-dependent frequencies of the alleles. Moreover, the model elucidates the mimicry efforts by pathogenic microorganisms.


Assuntos
Alelos , Predisposição Genética para Doença , Modelos Biológicos , Polimorfismo de Nucleotídeo Único , Candida albicans , Candidíase/genética , Candidíase/metabolismo , Fator H do Complemento/genética , Fator H do Complemento/metabolismo , Feminino , Humanos , Masculino
20.
J Exp Biol ; 221(Pt 14)2018 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-29798847

RESUMO

Archerfish dislodge aerial prey with water jets and use their predictive C-starts to secure it. Their C-starts turn the fish to the later point of impact and set the speed so that the fish arrive just in time. The starts are adjusted on the basis of information on speed, direction, timing and horizontal start position of prey movement - sampled during less than 100 ms after prey starts falling. Presently, it is unclear whether one essential parameter, the initial height of prey, can also be determined during this brief sampling time. Shooters and probably also observing bystanders already know target height - used to hit and to shape their jets - and would simply have to feed this information into their C-start circuitry. We challenged archerfish by launching initially invisible prey objects either from the expected height level, at which the fish were looking and at which they fired shots, or from more lateral positions and a lower or higher initial height. The arrangement was designed so that an analysis of the direction and the linear speed chosen by the starting fish could determine whether the C-start information is based on the expected height or on the actual height, which can be detected only after hidden prey has begun falling. Our findings demonstrate that the fish quickly estimate initial height during the initial falling phase of prey and do not simply use the expected height level to which they were cued.


Assuntos
Percepção de Profundidade , Perciformes/fisiologia , Comportamento Predatório , Animais , Percepção de Movimento , Movimento
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