scholarly journals Regeneration: Why junk DNA might matter

2018 ◽  
Author(s):  
Carlos Díaz-Castillo
Keyword(s):  
Natural Variation ◽  
Spatial Organization ◽  
Natural Phenomena ◽  
Collective Knowledge ◽  
Junk Dna ◽  
Research Fields ◽  
Biological Variables ◽  
The Individual

The ability of certain natural species to restore or regenerate missing structures has been a recurrent source of inspiration to forge our collective knowledge, from being used to adorn mythological figures with superhuman powers to permitting controlled reproducible observations that help setting the bases of entire research fields such as experimental biology and regenerative medicine. In spite of being one of the oldest natural phenomena under study, what makes certain species able or unable to regenerate missing parts is still largely a mystery. Recent advancements towards the highly detailed characterization of the sequence, the spatial organization, and the expression of genomes is offering a new standpoint to address the study of the natural variation in regenerative responses. An intriguing observation that has not yet conveniently pursued is that species with remarkable regenerative abilities tend to have genomes loaded with junk DNA (jDNA), i.e., genetic elements presumed to be useless for the benefit of the individual, whereas species for taxa with limited regenerative abilities tend to have jDNA-poor genomes. Here, I use existing knowledge on the role of jDNA as genome evolution facilitator and its non-random chromosome and nuclear distributions to speculate about two non-excluding ways through which the variation in jDNA genomic content might end up enhancing or limiting regenerative responses. The present piece aims to go beyond the confines of correlational studies between biological variables and to lay sensible conceptual grounds for future hypothesis-driven attempts to substantiate the genomic determinants of the natural variation of regenerative responses.

scholarly journals Regeneration: Why junk DNA might matter

2018 ◽  
Author(s):  
Carlos Díaz-Castillo
Keyword(s):  
Natural Variation ◽  
Spatial Organization ◽  
Natural Phenomena ◽  
Collective Knowledge ◽  
Junk Dna ◽  
Research Fields ◽  
Biological Variables ◽  
The Individual

The ability of certain natural species to restore or regenerate missing structures has been a recurrent source of inspiration to forge our collective knowledge, from being used to adorn mythological figures with superhuman powers to permitting controlled reproducible observations that help setting the bases of entire research fields such as experimental biology and regenerative medicine. In spite of being one of the oldest natural phenomena under study, what makes certain species able or unable to regenerate missing parts is still largely a mystery. Recent advancements towards the highly detailed characterization of the sequence, the spatial organization, and the expression of genomes is offering a new standpoint to address the study of the natural variation in regenerative responses. An intriguing observation that has not yet conveniently pursued is that species with remarkable regenerative abilities tend to have genomes loaded with junk DNA (jDNA), i.e., genetic elements presumed to be useless for the benefit of the individual, whereas species for taxa with limited regenerative abilities tend to have jDNA-poor genomes. Here, I use existing knowledge on the role of jDNA as genome evolution facilitator and its non-random chromosome and nuclear distributions to speculate about two non-excluding ways through which the variation in jDNA genomic content might end up enhancing or limiting regenerative responses. The present piece aims to go beyond the confines of correlational studies between biological variables and to lay sensible conceptual grounds for future hypothesis-driven attempts to substantiate the genomic determinants of the natural variation of regenerative responses.

scholarly journals GTPase-Activating Proteins for Cdc42

2002 ◽  
Vol 1 (3) ◽  
pp. 469-480 ◽  
Author(s):  
Gregory R. Smith ◽  
Scott A. Givan ◽  
Paul Cullen ◽  
George F. Sprague
Keyword(s):  
Rho Gtpase ◽  
Invasive Growth ◽  
Gtpase Activating Proteins ◽  
Morphological Defects ◽  
P21 Activated Kinase ◽  
The Individual ◽  
Hydrolysis Of ◽  
Pak Kinase

ABSTRACT The Rho-type GTPase, Cdc42, has been implicated in a variety of functions in the yeast life cycle, including septin organization for cytokinesis, pheromone response, and haploid invasive growth. A group of proteins called GTPase-activating proteins (GAPs) catalyze the hydrolysis of GTP to GDP, thereby inactivating Cdc42. At the time this study began, there was one known GAP, Bem3, and one putative GAP, Rga1, for Cdc42. We identified another putative GAP for Cdc42 and named it Rga2 (Rho GTPase-activating protein 2). We confirmed by genetic and biochemical criteria that Rga1, Rga2, and Bem3 act as GAPs for Cdc42. A detailed characterization of Rga1, Rga2, and Bem3 suggested that they regulate different subsets of Cdc42 function. In particular, deletion of the individual GAPs conferred different phenotypes. For example, deletion of RGA1, but not RGA2 or BEM3, caused hyperinvasive growth. Furthermore, overproduction or loss of Rga1 and Rga2, but not Bem3, affected the two-hybrid interaction of Cdc42 with Ste20, a p21-activated kinase (PAK) kinase required for haploid invasive growth. These results suggest Rga1, and possibly Rga2, facilitate the interaction of Cdc42 with Ste20 to mediate signaling in the haploid invasive growth pathway. Deletion of BEM3 resulted in cells with severe morphological defects not observed in rga1Δ or rga2Δ strains. These data suggest that Bem3 and, to a lesser extent, Rga1 and Rga2 facilitate the role of Cdc42 in septin organization. Thus, it appears that the GAPs play a role in modulating specific aspects of Cdc42 function. Alternatively, the different phenotypes could reflect quantitative rather than qualitative differences in GAP activity in the mutant strains.

Characterization of the action of tachykinin signaling on pulsatile LH secretion in male mice

Endocrinology ◽  
2021 ◽  
Author(s):  
Rajae Talbi ◽  
Ferrari Kaitlin ◽  
Ji Hae Choi ◽  
Achi Gerutshang ◽  
Elizabeth A McCarthy ◽  
...  
Keyword(s):  
Pulse Generator ◽  
Neurokinin A ◽  
Male Mice ◽  
Intact Male ◽  
Stimulatory Action ◽  
The Individual ◽  
Lh Secretion ◽  
Increased Activity

Abstract The alternation of the stimulatory action of the tachykinin neurokinin B (NKB) and the inhibitory action of dynorphin within arcuate (ARH) Kiss1 neurons has been proposed as the mechanism behind the generation of GnRH pulses through the pulsatile release of kisspeptin. However, we have recently documented that GnRH pulses still exist in gonadectomized mice in the absence of tachykinin signaling. Here, we document an increase in basal frequency and amplitude of LH pulses in intact male mice deficient in substance P (SP), neurokinin A (NKA) signaling (Tac1KO) and NKB signaling (Tac2KO and Tacr3KO). Moreover, we offer evidence that a single bolus of the NKB receptor agonist senktide to gonad intact WT males increases the basal release of LH without changing its frequency. Altogether, these data support the dispensable role of the individual tachykinin systems in the generation of LH pulses. Moreover, the increased activity of the GnRH pulse generator in intact KO male mice suggests the existence of compensation by additional mechanisms in the generation of kisspeptin/GnRH pulses.

scholarly journals Structural Basis of Subtilase Cytotoxin SubAB Assembly

2013 ◽  
Vol 288 (38) ◽  
pp. 27505-27516 ◽  
Author(s):  
Jérôme Le Nours ◽  
Adrienne W. Paton ◽  
Emma Byres ◽  
Sally Troy ◽  
Brock P. Herdman ◽  
...  
Keyword(s):  
Dominant Role ◽  
Functional Characterization ◽  
Structural Basis ◽  
Sequence Comparisons ◽  
A Subunit ◽  
The Individual ◽  
A1 Domain ◽  
Cellular Dysfunction

Pathogenic strains of Escherichia coli produce a number of toxins that belong to the AB5 toxin family, which comprise a catalytic A-subunit that induces cellular dysfunction and a B-pentamer that recognizes host glycans. Although the molecular actions of many of the individual subunits of AB5 toxins are well understood, how they self-associate and the effect of this association on cytotoxicity are poorly understood. Here we have solved the structure of the holo-SubAB toxin that, in contrast to other AB5 toxins whose molecular targets are located in the cytosol, cleaves the endoplasmic reticulum chaperone BiP. SubA interacts with SubB in a similar manner to other AB5 toxins via the A2 helix and a conserved disulfide bond that joins the A1 domain with the A2 helix. The structure revealed that the active site of SubA is not occluded by the B-pentamer, and the B-pentamer does not enhance or inhibit the activity of SubA. Structure-based sequence comparisons with other AB5 toxin family members, combined with extensive mutagenesis studies on SubB, show how the hydrophobic patch on top of the B-pentamer plays a dominant role in binding the A-subunit. The structure of SubAB and the accompanying functional characterization of various mutants of SubAB provide a framework for understanding the important role of the B-pentamer in the assembly and the intracellular trafficking of this AB5 toxin.

scholarly journals The Role of the Title in the Characterization of the Hero in G.I. Gazdanov’s Story "Black Swans"

2021 ◽  
pp. 63-74
Author(s):  
Anastasia Kukhtenkova
Keyword(s):  
The Self ◽  
Main Character ◽  
Black Swans ◽  
The Individual ◽  
Individual Style ◽  
Black Color

The article deals with the role of the heading as a symbol in the characterization of the hero of the story by Gazdanov «Black Swans". The author of the article describes the actualization of the heading and the character's characteristics by taking into account the artistic psychologism. The frequency of repetition of the heading close to the end of the text is one of the individual style features of the writer's linguopoetics ("The Flight", "The Bombay", "The Iron Lord", etc.). There is a comparison between the vocabulary and text fields of the heading associative stimulus presented in the article. The psychological autobiography of the story hero is depicted by the textual interaction of the components of the heading. The black color corresponds to the refugee implication, suicide and uniqueness of the main character. The image of swans denotes Pavlov's longing for freedom, for the search of  illusions as an attempt to get rid of courageous loneliness, as well as his desire to unravel the existential mystery. The use of the syntactic lexeme "black swans" denotes the intertextual key message of the works by Gazdanov - that is "the inner journey", which is associated with the confessional narrative and the self-analysis of the hero-narrator

Two approaches to the love of God in medieval Jewish thought: The concept of devequt in the works of Ibn Ezra and Judah Halevi

1999 ◽  
Vol 28 (2) ◽  
pp. 139-151
Author(s):  
Aaron Hughes
Keyword(s):  
Jewish People ◽  
Natural Phenomena ◽  
Historical Experience ◽  
Jewish Thought ◽  
Love Of God ◽  
The Individual ◽  
The Ideal

Both Abraham Ibn Ezra and Judah Halevi claim that the ideal relationship between the individual and God is founded on love and culminates in the individual cleaving ( devequt) to God. Although they use the same term to describe this telos, they envisage the means to it in different ways. A closer analysis of this term reveals that this difference is rooted in their respective ideas concerning the role of philosophy in Judaism. Ibn Ezra, a rationalist, claims that the individual loves God through the observation of natural phenomena. Halevi, however, claims that the love of God is grounded in the historical experience of the Jewish people.

How Judges Can Think: The Use of Expert’s Knowledge as Proof in Civil Proceedings

Global Jurist ◽  
2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Marcello Gaboardi
Keyword(s):  
Scientific Knowledge ◽  
Judicial Discretion ◽  
Natural Phenomena ◽  
Expert Evidence ◽  
Theoretical Possibility ◽  
Civil Proceedings ◽  
The Common ◽  
The Individual ◽  
Case Basis

Abstract The classic account of the role of expert in civil proceedings revolves around a crucial notion. The idea is that the role the expert plays is correlated with an evident lack of technical or scientific knowledge within the context of the judiciary. Such an approach involves several questions ranging from how to perceive the need to supplement the basic judicial knowledge to whether there is such a thing as a binding aspect in the expert evidence. For civil lawyers the expert needs to be appointed depending on judicial discretion. The appointment of expert requires judicial evaluation on a case-by-case basis. Whether or not the attorneys encourage the judge to appoint an expert, the court remains capable of recognizing that certain facts are more likely candidates to a technical or scientific assessment. If the judge is persuaded that the case can be decided regardless the opinion of an expert, the decision can be based solely on the judicial knowledge and skills. On the contrary, the common law tradition leaves the attorneys with a burden of submitting to the court the technical or scientific knowledge they deem necessary for the judgment. In this different perspective, the judge is basically called upon to evaluate the expert witnesses and select their convincing statements through the cross-examination of the parties. In both systems, the crucial question is how technical or scientific knowledge can be translated for legal decisionmaking. The judge and the expert use different languages and approach the factual questions very differently. Scientists offer empirical research studies and make general statements about natural phenomena; lawyers focus their attention on the individual decisionmaking required in the courtroom. Nonetheless, disputes involving technical or scientific issues make it inevitable that the judge and the expert face with the problem of mutual understanding. The way in which legal scholars have usually managed those differences is by adopting a structured cooperation between the judge and the expert. By construing such a relationship as a form of mutual training, they find some room for warranting an effective gatekeeping role to the judge. But such a cooperation is more a theoretical possibility than a pragmatic opportunity. Instead, reshaping the expert evidence into a lay judge can offer a concrete opportunity to entrench the scientific or technical knowledge of the court in several cases.

A Causal Perspective on the Analysis of Signal and Noise Correlations and Their Role in Population Coding

2014 ◽  
Vol 26 (6) ◽  
pp. 999-1054 ◽  
Author(s):  
Daniel Chicharro
Keyword(s):  
Causal Structure ◽  
Functional Model ◽  
Population Coding ◽  
Neuronal Responses ◽  
Information Theoretic ◽  
Nonparametric Approach ◽  
The Individual ◽  
System Configurations

The role of correlations between neuronal responses is crucial to understanding the neural code. A framework used to study this role comprises a breakdown of the mutual information between stimuli and responses into terms that aim to account for different coding modalities and the distinction between different notions of independence. Here we complete the list of types of independence and distinguish activity independence (related to total correlations), conditional independence (related to noise correlations), signal independence (related to signal correlations), coding independence (related to information transmission), and information independence (related to redundancy). For each type, we identify the probabilistic criterion that defines it, indicate the information-theoretic measure used as statistic to test for it, and provide a graphical criterion to recognize the causal configurations of stimuli and responses that lead to its existence. Using this causal analysis, we first provide sufficiency conditions relating these types. Second, we differentiate the use of the measures as statistics to test for the existence of independence from their use for quantification. We indicate that signal and noise correlation cannot be quantified separately. Third, we explicitly define alternative system configurations used to construct the measures, in which noise correlations or noise and signal correlations are eliminated. Accordingly, we examine which measures are meaningful only as a comparison across configurations and which ones provide a characterization of the actually observed responses without resorting to other configurations. Fourth, we compare the commonly used nonparametric approach to eliminate noise correlations with a functional (model-based) approach, showing that the former approach does not remove those effects of noise correlations captured by the tuning properties of the individual neurons, and implies nonlocal causal structure manipulations. These results improve the interpretation of the measures on the framework and help in understanding how to apply it to analyze the role of correlations.

scholarly journals Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 802-810 ◽  
Author(s):  
Eveliina Ihanus ◽  
Liisa M. Uotila ◽  
Anne Toivanen ◽  
Minna Varis ◽  
Carl G. Gahmberg
Keyword(s):  
Binding Sites ◽  
Functional Role ◽  
Intercellular Adhesion Molecule ◽  
Red Cell ◽  
Specific Expression ◽  
Β2 Integrin ◽  
The Third ◽  
The Individual

Abstract Intercellular adhesion molecule 4 (ICAM-4) is a unique member of the ICAM family because of its specific expression on erythroid cells and ability to interact with several types of integrins expressed on blood and endothelial cells. The first reported receptors for ICAM-4 were CD11a/CD18 and CD11b/CD18. In contrast to these 2, the cellular ligands and the functional role of the third β2 integrin, CD11c/CD18, have not been well defined. Here, we show that ICAM-4 functions as a ligand for the monocyte/macrophage-specific CD11c/CD18. Deletion of the individual immunoglobulin domains of ICAM-4 demonstrated that both its domains contain binding sites for CD11c/CD18. Analysis of a panel of ICAM-4 point mutants identified residues that affected binding to the integrin. By molecular modeling the important residues were predicted to cluster in 2 distinct but spatially close regions of the first domain with an extension to the second domain spatially distant from the other residues. We also identified 2 peptides derived from sequences of ICAM-4 that are capable of modulating the binding to CD11c/CD18. CD11c/CD18 is expressed on macrophages in spleen and bone marrow. Inhibition of erythrophagocytosis by anti–ICAM-4 and anti-integrin antibodies suggests a role for these interactions in removal of senescent red cells.

scholarly journals People Power: Supporting activities with a social benefit

2016 ◽  
pp. 35-50
Author(s):  
Edward Gardiner
Keyword(s):  
Social Innovation ◽  
Building Blocks ◽  
Social Benefit ◽  
Personal Attributes ◽  
Entrepreneurial Success ◽  
Collective Knowledge ◽  
Behavioural Science ◽  
The Individual ◽  
Taking Action

Many people around the world are taking action to address the problems that matter to them and their community, from anti-social behaviour to unaffordable healthcare to institutional corruption. Many more people have the potential to make a difference in their community. Their collective knowledge, skills, abilities and personal attributes are the building blocks of social change. While there is a growing emphasis on the role of disciplines such as design, behavioural science and digital technology in social innovation, people need to develop and exchange a range of attributes to understand problems and implement ideas. In this article I review some of the individual and environmental factors that are predictive of creative performance and entrepreneurial success, and highlight areas of opportunity for how to help more people get involved in activities with a social benefit.

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