Experimental Approaches for Defining the Role of the Ca2+-Modulated ROS-GC System in Retinal Rods of Mouse

Author(s):  
Clint L. Makino ◽  
Teresa Duda ◽  
Alexandre Pertzev ◽  
Rameshwar K. Sharma
2019 ◽  
Vol 317 (5) ◽  
pp. H1039-H1049 ◽  
Author(s):  
Lasse B. Steffensen ◽  
Cheryl A. Conover ◽  
Claus Oxvig

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a well-established role in releasing bioactive insulin-like growth factor-1 (IGF-1) from IGF-binding protein-2, -4, and -5 by proteolytic processing of these. The IGF system has repeatedly been suggested to be involved in the pathology of atherosclerosis, and both PAPP-A and IGF-1 are proposed biomarkers and therapeutic targets for this disease. Several experimental approaches based on atherosclerosis mouse models have been undertaken to obtain causative and mechanistic insight to the role of these molecules in atherogenesis. However, reports seem conflicting. The literature suggests that PAPP-A is detrimental, while IGF-1 is beneficial. This raises important questions that need to be addressed. Here we summarize the various studies and discuss potential underlying explanations for this seemingly inconsistency with the objective of better understanding complexities and limitations when manipulating the IGF system in mouse models of atherosclerosis. A debate clarifying what’s up and what’s down is highly warranted going forward with the ultimate goal of improving atherosclerosis therapy by targeting the IGF system.


2020 ◽  
Vol 375 (1806) ◽  
pp. 20190543 ◽  
Author(s):  
I. Satokangas ◽  
S. H. Martin ◽  
H. Helanterä ◽  
J. Saramäki ◽  
J. Kulmuni

All genes interact with other genes, and their additive effects and epistatic interactions affect an organism's phenotype and fitness. Recent theoretical and empirical work has advanced our understanding of the role of multi-locus interactions in speciation. However, relating different models to one another and to empirical observations is challenging. This review focuses on multi-locus interactions that lead to reproductive isolation (RI) through reduced hybrid fitness. We first review theoretical approaches and show how recent work incorporating a mechanistic understanding of multi-locus interactions recapitulates earlier models, but also makes novel predictions concerning the build-up of RI. These include high variance in the build-up rate of RI among taxa, the emergence of strong incompatibilities producing localized barriers to introgression, and an effect of population size on the build-up of RI. We then review recent experimental approaches to detect multi-locus interactions underlying RI using genomic data. We argue that future studies would benefit from overlapping methods like ancestry disequilibrium scans, genome scans of differentiation and analyses of hybrid gene expression. Finally, we highlight a need for further overlap between theoretical and empirical work, and approaches that predict what kind of patterns multi-locus interactions resulting in incompatibilities will leave in genome-wide polymorphism data. This article is part of the theme issue ‘Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers’.


2005 ◽  
Vol 83 (7) ◽  
pp. 894-910 ◽  
Author(s):  
Steven M Vamosi

Understanding the contribution of ecological interactions to the origin and maintenance of diversity is a fundamental challenge for ecologists and evolutionary biologists, and one that is currently receiving a great deal of attention. Natural enemies (e.g., predators, parasites, and herbivores) are ubiquitous in food webs and are predicted to have significant impacts on phenotypic diversity and on speciation, and extinction rates of their prey. Spurred by the development of a theoretical framework beginning in the late 1970s, there is now a growing body of literature that addresses the effects of enemy–prey interactions on the evolution of prey. A number of theoretical models predict that enemies can produce phenotypic divergence between closely related species, even in the absence of interspecific competition for resources. Effects on diversification of prey are more variable, and enemies may either enhance or depress speciation and extinction rates of their prey. Empirical evidences from a number of study systems, notably those involving predators and prey in aquatic environments and interactions between insects and flowering plants, confirm both predictions. There is now considerable evidence for the role of enemies, especially those that are size-selective or use visual cues when identifying suitable prey, on phenotypic divergence of sympatric and allopatric taxa. Enemies may spur diversification rates in certain groups under some circumstances, and hinder diversification rates in other cases. I suggest that further research should focus on the role of enemies in diversification of prey, with significant insights likely to be the product of applying traditional experimental approaches and emerging comparative phylogenetic methods.


2020 ◽  

Abstract This book contains 23 chapters divided into seven parts. Part I reviews the key hypotheses in invasion ecology that invoke biotic interactions to explain aspects of plant invasion dynamics; and reviews models, theories and hypotheses on how invasion performance and impact of introduced species in recipient ecosystems can be conjectured according to biotic interactions between native and non-native species. Part II deals with positive and negative interactions in the soil. Part III discusses mutualistic interactions that promote plant invasions. Part IV describes antagonistic interactions that hinder plant invasions, while part V presents the consequences of plant invasions for biotic interactions among native species. In part VI, novel techniques and experimental approaches in the study of plant invasions are shown. In the last part, biotic interactions and the management of ecosystems invaded by non-native plants are discussed.


2019 ◽  
Vol 8 (5) ◽  
pp. 725 ◽  
Author(s):  
Dongya Jia ◽  
Xuefei Li ◽  
Federico Bocci ◽  
Shubham Tripathi ◽  
Youyuan Deng ◽  
...  

Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial–mesenchymal transition (EMT). Cells in these hybrid E/M phenotypes often combine epithelial and mesenchymal features and tend to migrate collectively commonly as small clusters. Such collectively migrating cancer cells play a pivotal role in seeding metastases and their presence in cancer patients indicates an adverse prognostic factor. Moreover, cancer cells in hybrid E/M phenotypes tend to be more associated with stemness which endows them with tumor-initiation ability and therapy resistance. Most recently, cells undergoing EMT have been shown to promote immune suppression for better survival. A systematic understanding of the emergence of hybrid E/M phenotypes and the connection of EMT with stemness and immune suppression would contribute to more effective therapeutic strategies. In this review, we first discuss recent efforts combining theoretical and experimental approaches to elucidate mechanisms underlying EMT multi-stability (i.e., the existence of multiple stable phenotypes during EMT) and the properties of hybrid E/M phenotypes. Following we discuss non-cell-autonomous regulation of EMT by cell cooperation and extracellular matrix. Afterwards, we discuss various metrics that can be used to quantify EMT spectrum. We further describe possible mechanisms underlying the formation of clusters of circulating tumor cells. Last but not least, we summarize recent systems biology analysis of the role of EMT in the acquisition of stemness and immune suppression.


1998 ◽  
Vol 274 (3) ◽  
pp. G584-G590 ◽  
Author(s):  
H. F. Hammer ◽  
S. F. Phillips ◽  
M. Camilleri ◽  
R. B. Hanson

Increasing interest is focusing on the role of intestinal tone, distensibility, and mechanosensation in the genesis of abdominal symptoms. Experimental approaches usually feature balloon distension of the bowel with measurements of perception, tone, and compliance and/or elastance; however, the methodologies are standardized incompletely. We examined the reproducibility of repeated assessments of sensory perception, basal tone, and compliance and/or elastance of the rectum during distension. We also evaluated the response to inflations that varied in regard to control of pressure or volume, pattern of distension, and rate of inflation. Five healthy volunteers were studied under two separate protocols. The first featured a series of experiments on each of 5 days; the other consisted of 2 separate days of study. Repeated distensions evoked reproducible responses of sensation and compliance and/or elastance on a single day, providing a conditioning distension preceded them. Day-to-day variability was also sufficiently small to allow valid comparisons to be made on different days in healthy persons. The configuration of the distension profile (phasic, staircase, or ramp) and the rate of inflation (from 1 to 40 ml/s) had little effect on distensibility or perception. Perceptions were sometimes transient and sometimes constant, but no relationship was found between these temporal features and the magnitude of the stimulus. These observations help provide a basis as to how the responses to rectal distension can be best studied.


2019 ◽  
Vol 31 (7) ◽  
pp. 1380-1418 ◽  
Author(s):  
Nima Dehghani ◽  
Ralf D. Wimmer

The thalamus has traditionally been considered as only a relay source of cortical inputs, with hierarchically organized cortical circuits serially transforming thalamic signals to cognitively relevant representations. Given the absence of local excitatory connections within the thalamus, the notion of thalamic relay seemed like a reasonable description over the past several decades. Recent advances in experimental approaches and theory provide a broader perspective on the role of the thalamus in cognitively relevant cortical computations and suggest that only a subset of thalamic circuit motifs fits the relay description. Here, we discuss this perspective and highlight the potential role for the thalamus, and specifically the mediodorsal (MD) nucleus, in the dynamic selection of cortical representations through a combination of intrinsic thalamic computations and output signals that change cortical network functional parameters. We suggest that through the contextual modulation of cortical computation, the thalamus and cortex jointly optimize the information and cost trade-off in an emergent fashion. We emphasize that coordinated experimental and theoretical efforts will provide a path to understanding the role of the thalamus in cognition, along with an understanding to augment cognitive capacity in health and disease.


2016 ◽  
Vol 29 (6-7) ◽  
pp. 585-606 ◽  
Author(s):  
O. Deroy ◽  
N. Faivre ◽  
C. Lunghi ◽  
C. Spence ◽  
M. Aller ◽  
...  

The integration of information has been considered a hallmark of human consciousness, as it requires information being globally availableviawidespread neural interactions. Yet the complex interdependencies between multisensory integration and perceptual awareness, or consciousness, remain to be defined. While perceptual awareness has traditionally been studied in a single sense, in recent years we have witnessed a surge of interest in the role of multisensory integration in perceptual awareness. Based on a recent IMRF symposium on multisensory awareness, this review discusses three key questions from conceptual, methodological and experimental perspectives: (1) What do we study when we study multisensory awareness? (2) What is the relationship between multisensory integration and perceptual awareness? (3) Which experimental approaches are most promising to characterize multisensory awareness? We hope that this review paper will provoke lively discussions, novel experiments, and conceptual considerations to advance our understanding of the multifaceted interplay between multisensory integration and consciousness.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Britta Noebauer ◽  
Alexander Jais ◽  
Jelena Todoric ◽  
Klaus Gossens ◽  
Hedwig Sutterlüty-Fall ◽  
...  

Obesity is a major risk factor for several diseases including diabetes, heart disease, and some forms of cancer and due to its rapidly increasing prevalence it has become one of the biggest problems medicine is facing today. All the more surprising, a substantial percentage of obese patients are metabolically healthy when classified based on insulin resistance and systemic inflammation. Oxysterols are naturally occurring molecules that play important role in various metabolic and inflammatory processes and their levels are elevated in patients suffering from obesity and diabetes. 25-Hydroxycholesterol (25-OHC) is produced in cells from cholesterol by the enzyme cholesterol 25-hydroxylase (Ch25h) and is involved in lipid metabolism, inflammatory processes, and cell proliferation. Here, we investigated the role of hepatic Ch25h in the transition from metabolically healthy obesity to insulin resistance and diabetes. Using several different experimental approaches, we demonstrated the significance of Ch25h on the border of “healthy” and “diseased” states of obesity. Adenovirus-mediated Ch25h overexpression in mice improved glucose tolerance and insulin sensitivity and lowered HOMA-IR. Our data suggest that low hepatic Ch25h levels could be considered a risk marker for unhealthy obesity.


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