scholarly journals What Is a Host? Incorporating the Microbiota into the Damage-Response Framework: TABLE 1

2014 ◽  
Vol 83 (1) ◽  
pp. 2-7 ◽  
Author(s):  
Arturo Casadevall ◽  
Liise-anne Pirofski
Keyword(s):  
Host Immunity ◽  
Emergent Properties ◽  
Microbial Pathogenesis ◽  
Major Focus ◽  
Microbial Diseases ◽  
Late 19Th Century ◽  
Immunological Status ◽  
Damage Response ◽  
Definitional Problem ◽  
Definition Of

Since proof of the germ theory of disease in the late 19th century, a major focus of the fields of microbiology and infectious diseases has been to seek differences between pathogenic and nonpathogenic microbes and the role that the host plays in microbial pathogenesis. Remarkably, despite the increasing recognition that host immunity plays a role in microbial pathogenesis, there has been little discussion about what constitutes a host. Historically, hosts have been viewed in the context of their fitness or immunological status and characterized by adjectives such as immune, immunocompetent, immunosuppressed, immunocompromised, or immunologically impaired. However, in recent years it has become apparent that the microbiota has profound effects on host homeostasis and susceptibility to microbial diseases in addition to its effects on host immunity. This raises the question of how to incorporate the microbiota into defining a host. This definitional problem is further complicated because neither host nor microbial properties are adequate to predict the outcome of host-microbe interaction because this outcome exhibits emergent properties. In this essay, we revisit the damage-response framework (DRF) of microbial pathogenesis and demonstrate how it can incorporate the rapidly accumulating information being generated by the microbiome revolution. We use the tenets of the DRF to put forth the following definition of a host: a host is an entity that houses an associated microbiome/microbiota and interacts with microbes such that the outcome results in damage, benefit, or indifference, thus resulting in the states of symbiosis, colonization, commensalism, latency, and disease.

Challenges of Fear Conditioning Research in the Age of RDoC

2017 ◽  
Vol 225 (3) ◽  
pp. 189-199 ◽  
Author(s):  
Tina B. Lonsdorf ◽  
Jan Richter
Keyword(s):  
Fear Conditioning ◽  
Clinical Diagnosis ◽  
Research Domain Criteria ◽  
Major Focus ◽  
The Future ◽  
Definition Of ◽  
Methodological Considerations ◽  
Research Domain

Abstract. As the criticism of the definition of the phenotype (i.e., clinical diagnosis) represents the major focus of the Research Domain Criteria (RDoC) initiative, it is somewhat surprising that discussions have not yet focused more on specific conceptual and procedural considerations of the suggested RDoC constructs, sub-constructs, and associated paradigms. We argue that we need more precise thinking as well as a conceptual and methodological discussion of RDoC domains and constructs, their interrelationships as well as their experimental operationalization and nomenclature. The present work is intended to start such a debate using fear conditioning as an example. Thereby, we aim to provide thought-provoking impulses on the role of fear conditioning in the age of RDoC as well as conceptual and methodological considerations and suggestions to guide RDoC-based fear conditioning research in the future.

scholarly journals A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1583
Author(s):  
Sara Pescatori ◽  
Francesco Berardinelli ◽  
Jacopo Albanesi ◽  
Paolo Ascenzi ◽  
Maria Marino ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cellular Transformation ◽  
Genome Integrity ◽  
Physiological Effects ◽  
Dna Damages ◽  
Cellular Effects ◽  
Damage Response ◽  
17Β Estradiol ◽  
Cellular Pathways ◽  
Definition Of

17β-estradiol (E2) regulates human physiology both in females and in males. At the same time, E2 acts as a genotoxic substance as it could induce DNA damages, causing the initiation of cellular transformation. Indeed, increased E2 plasma levels are a risk factor for the development of several types of cancers including breast cancer. This paradoxical identity of E2 undermines the foundations of the physiological definition of “hormone” as E2 works both as a homeostatic regulator of body functions and as a genotoxic compound. Here, (i) the molecular circuitries underlying this double face of E2 are reviewed, and (ii) a possible framework to reconcile the intrinsic discrepancies of the E2 function is reported. Indeed, E2 is a regulator of the DNA damage response, which this hormone exploits to calibrate its genotoxicity with its physiological effects. Accordingly, the genes required to maintain genome integrity belong to the E2-controlled cellular signaling network and are essential for the appearance of the E2-induced cellular effects. This concept requires an “upgrade” to the vision of E2 as a “genotoxic hormone”, which balances physiological and detrimental pathways to guarantee human body homeostasis. Deregulation of this equilibrium between cellular pathways would determine the E2 pathological effects.

scholarly journals The Role of Host-Generated H2S in Microbial Pathogenesis: New Perspectives on Tuberculosis

2020 ◽  
Vol 10 ◽  
Author(s):  
Md. Aejazur Rahman ◽  
Joel N. Glasgow ◽  
Sajid Nadeem ◽  
Vineel P. Reddy ◽  
Ritesh R. Sevalkar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Host Immunity ◽  
Microbial Pathogens ◽  
Microbial Pathogenesis ◽  
Enzymatic Production ◽  
Growth And Survival ◽  
Wide Range

For centuries, hydrogen sulfide (H2S) was considered primarily as a poisonous gas and environmental hazard. However, with the discovery of prokaryotic and eukaryotic enzymes for H2S production, breakdown, and utilization, H2S has emerged as an important signaling molecule in a wide range of physiological and pathological processes. Hence, H2S is considered a gasotransmitter along with nitric oxide (•NO) and carbon monoxide (CO). Surprisingly, despite having overlapping functions with •NO and CO, the role of host H2S in microbial pathogenesis is understudied and represents a gap in our knowledge. Given the numerous reports that followed the discovery of •NO and CO and their respective roles in microbial pathogenesis, we anticipate a rapid increase in studies that further define the importance of H2S in microbial pathogenesis, which may lead to new virulence paradigms. Therefore, this review provides an overview of sulfide chemistry, enzymatic production of H2S, and the importance of H2S in metabolism and immunity in response to microbial pathogens. We then describe our current understanding of the role of host-derived H2S in tuberculosis (TB) disease, including its influences on host immunity and bioenergetics, and on Mycobacterium tuberculosis (Mtb) growth and survival. Finally, this review discusses the utility of H2S-donor compounds, inhibitors of H2S-producing enzymes, and their potential clinical significance.

scholarly journals Inhabiting Relingos: Horizontal Harlem, Told Vertically

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Hannah Huxley
Keyword(s):  
19Th Century ◽  
Latin American ◽  
Rapid Growth ◽  
Critical Approach ◽  
Late 19Th Century ◽  
Rich Variety ◽  
Academic Scholarship ◽  
Cultural Renaissance ◽  
American Author ◽  
Definition Of

 From the period of its development during the late 19th century, Harlem has experienced rapid growth, both spatially and aesthetically. A rich variety of literature has emerged, and continues to emerge, from its diverse and multicultural scene, prompting a new critical approach in academic scholarship. This thesis explores the transnational impact of Harlem, from the emergence of its cultural renaissance to its contemporary aesthetic presence. Specifically, it will consider the recently published work of Latin-American author Valeria Luiselli, discussing the transnational dimensions of her novel, and the re-definition of Harlem as a space without aesthetic or spatial boundaries.

Conclusion

2013 ◽  
Author(s):  
David Wengrow
Keyword(s):  
Bronze Age ◽  
Fourth Century ◽  
Emergent Properties ◽  
Institutional Dynamics ◽  
Mechanical Reproduction ◽  
Elite Culture ◽  
Specific Distribution ◽  
History Of ◽  
Definition Of ◽  
Visual Record

This book concludes with a discussion of the emergent properties of cognition. It first considers an essay published in 1942 by Rudolph Wittkower entitled “Marvels of the East: A Study in the History of Monsters,” which documented the transmission of a particular style of ethnographic description (and depiction) from its earliest known sources in hand-copied manuscripts of the fourth century BC to the age of the printing press. The monsters in question fall mostly under this book's definition of “composites.” The book proceeds by examining how the counterfactual properties of composite figures were offset against two distinct forms of intuitive knowledge, one universal and the other historically contingent. It suggests that the specific distribution of composite figures in the visual record must be situated within the institutional dynamics of elite culture, and within particular strategies of governance that first took root during the Bronze Age, including the dissemination of officially sanctioned images through mechanical reproduction.

The Scientific Hypothesis Today

2019 ◽  
pp. 31-60
Author(s):  
Bradley E. Alger
Keyword(s):  
Scientific Method ◽  
Karl Popper ◽  
Major Focus ◽  
Critical Rationalism ◽  
Multiple Hypotheses ◽  
Scientific Hypothesis ◽  
Strong Inference ◽  
Key Features ◽  
Definition Of ◽  
Good Hypothesis

Chapter 2 begins by reviewing the concept of the Scientific Method, as well as many outdated definitions of “hypothesis.” The discussion leads to the modern definition of the hypothesis as a conjectural explanation for a phenomenon; it is testable and falsifiable. The hypothesis serves as a blueprint and a summary of an investigation. Certain criticisms of the hypothesis and hypothesis-driven research are based on the older definitions of the term, and the book returns to them later. This chapter identifies and defines, with simple, nontechnical examples, concepts associated with the hypothesis, such as prediction and direct and indirect measurements. The philosophical programs of Karl Popper and John Platt, Critical Rationalism and Strong Inference, respectively, form a major focus of the chapter. The chapter explores the complexities of the concepts of falsification and corroboration and the importance of having multiple hypotheses. The chapter introduces the idea of the implicit hypothesis and ends with the presentation and discussion of key features of a good hypothesis.

scholarly journals Can Artificial Intelligence Make Art without Artists? Ask the Viewer

Arts ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 35 ◽  
Author(s):  
Sofian Audry ◽  
Jon Ippolito
Keyword(s):  
Artificial Intelligence ◽  
Emergent Properties ◽  
Art Making ◽  
Definition Of

The question of whether machines can make art provokes very different answers from pioneers in the field. Harold Cohen refuses to ascribe creativity to his art-making robot AARON, while Leonel Moura argues that since his “Artbots” generate pictures from emergent properties that could not have been predicted by their creator, “they have at least some degree of creativity.” Although the question of whether machines can be artists seems to fall squarely on our definition of the latter, a solution to this philosophical impasse may ironically lie in redirecting the question away from the artist and toward the viewer.

scholarly journals Pathogenesis of COVID-19 from the Perspective of the Damage-Response Framework

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Liise-anne Pirofski ◽  
Arturo Casadevall
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Vulnerable Populations ◽  
Clinical Manifestations ◽  
Medical Community ◽  
New Disease ◽  
Microbial Pathogenesis ◽  
Significant Challenge ◽  
Immune Mediated ◽  
Damage Response

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents the medical community with a significant challenge. COVID-19 is an entirely new disease with disparate clinical manifestations that are difficult to reconcile with a single pathogenic principle. Here, we explain how the flexible paradigm of the “damage-response framework” (DRF) of microbial pathogenesis can organize the varied manifestations of COVID-19 into a synthesis that accounts for differences in susceptibility of vulnerable populations as well as for differing manifestations of COVID-19 disease. By focusing on mechanisms of host damage, particularly immune-mediated damage, the DRF provides a lens to understand COVID-19 pathogenesis and to consider how potential therapies could alter the outcome of this disease.

scholarly journals Virulence factors and their mechanisms of action: the view from a damage–response framework

2009 ◽  
Vol 7 (S1) ◽  
pp. S2-S18 ◽  
Author(s):  
Arturo Casadevall ◽  
Liise-anne Pirofski
Keyword(s):  
Immune Responses ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Host Response ◽  
Host Factors ◽  
Microbial Pathogenesis ◽  
Pathogenic Potential ◽  
Susceptible Host ◽  
Damage Response ◽  
Practical Level

The virulence factor concept has been a powerful engine in driving research and the intellectual flow in the fields of microbial pathogenesis and infectious diseases. This review analyzes virulence factors from the viewpoint of the damage–response framework of microbial pathogenesis, which defines virulence factor as microbial components that can damage a susceptible host. At a practical level, the finding that effective immune responses often target virulence factors provides a roadmap for future vaccine design. However, there are significant limitations to this concept, which are rooted in the inability to define virulence and virulence factors in the absence of host factors and the host response. In fact, this concept appears to work best for certain types of bacterial pathogens, being less well suited for viruses and commensal organisms with pathogenic potential.

scholarly journals The Development of Sports: A Comparative Analysis of the Early Institutionalization of Traditional Sports and E-Sports

2019 ◽  
Vol 15 (1) ◽  
pp. 51-72 ◽  
Author(s):  
Rory Summerley
Keyword(s):  
Comparative Analysis ◽  
19Th Century ◽  
Analytical Approach ◽  
Late 19Th Century ◽  
Factors Affecting ◽  
Traditional Sports ◽  
Similarities And Differences ◽  
Definition Of

This article takes the definition of a sport as “an institutionalized game” under which both “traditional sports” and “E-sports” fall. It takes a comparative analytical approach that examines the historical documentation and cultural output of these two major categories of sports and their early institutionalization. Given the increasing interest in, engagement with and spectator numbers of E-sports, it is worth considering the key similarities and differences between various institutions. This article examines traditional sports institutions from the mid-19th to late 19th century alongside E-sports institutions that emerged from the mid-1990s to the present day. Firstly, the processes of institutionalization are analyzed with these examples in mind and, secondly, are compared to draw out the significant differences and similarities between the factors affecting early institutionalization.

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