scholarly journals Evolutionary Changes in Left-Right Visceral Asymmetry in Astyanax Cavefish

2020 ◽  
Author(s):  
Li Ma ◽  
Mandy Ng ◽  
Janet Shi ◽  
Aniket V. Gore ◽  
Daniel Castranova ◽  
...  
Keyword(s):  
Genetic Effect ◽  
Internal Organs ◽  
Lateral Plate ◽  
Astyanax Mexicanus ◽  
Regulatory Changes ◽  
Evolutionary Changes ◽  
Fish Sperm ◽  
Liver And Pancreas ◽  
Underlying Mechanisms ◽  
The Right

SummaryVertebrates show conserved left-right (L-R) asymmetry of internal organs controlled by Nodal-Pitx2/Lefty signaling [1-3]. Modifications in L-R asymmetry occur in mutants [4] and rarely in humans [5], but little is known about natural L-R changes during evolution. Here we describe changes in L-R asymmetry in Astyanax mexicanus, a teleost with ancestral surface (surface fish) and derived cave (cavefish) morphs [6]. In teleosts, Nodal-Pitx2 signaling is activated in the left lateral plate mesoderm (LPM), the cardiac tube jogs to the left and loops to the right (D-looping), and the liver and pancreas form on opposite sides of the midline. Surface fish show conventional L-R patterning, but cavefish can show Nodal-Pitx2 expression in the right LPM or bilaterally, left (L)-looping hearts, and reversed liver and pancreas asymmetry, and these reversals have no effect on survival. The Lefty1 Nodal antagonist is expressed along the surface fish and cavefish midlines, but expression of the Lefty2 antagonist is absent in the LPM of most cavefish embryos, suggesting a role for lefty2 (lft2) in changing organ asymmetry. Although CRISPR-Cas9 lft2 editing affected D-looping in surface fish, the cavefish lft2 gene showed no coding mutations, and was expressed normally during cavefish gastrulation, suggesting downregulation by regulatory changes. Reciprocal hybridization, the fertilization of cavefish eggs with surface fish sperm and vice versa, indicated that the change in cavefish L-R asymmetry is a maternal genetic effect. Our studies reveal natural changes in internal organ asymmetry during evolution and introduce A. mexicanus as a new model to study the underlying mechanisms.

scholarly journals Maternal control of visceral asymmetry evolution in Astyanax cavefish

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li Ma ◽  
Mandy Ng ◽  
Janet Shi ◽  
Aniket V. Gore ◽  
Daniel Castranova ◽  
...  
Keyword(s):  
Heart Development ◽  
Nodal Signaling ◽  
Lateral Plate Mesoderm ◽  
Visceral Organ ◽  
Maternal Control ◽  
Lateral Plate ◽  
Astyanax Mexicanus ◽  
Evolutionary Changes ◽  
Liver And Pancreas ◽  
Surface Dwelling

AbstractThe direction of visceral organ asymmetry is highly conserved during vertebrate evolution with heart development biased to the left and pancreas and liver development restricted to opposing sides of the midline. Here we show that reversals in visceral organ asymmetry have evolved in Astyanax mexicanus, a teleost species with interfertile surface-dwelling (surface fish) and cave-dwelling (cavefish) forms. Visceral organ asymmetry is conventional in surface fish but some cavefish have evolved reversals in heart, liver, and pancreas development. Corresponding changes in the normally left-sided expression of the Nodal-Pitx2/Lefty signaling system are also present in the cavefish lateral plate mesoderm (LPM). The Nodal antagonists lefty1 (lft1) and lefty2 (lft2), which confine Nodal signaling to the left LPM, are expressed in most surface fish, however, lft2, but not lft1, expression is absent during somitogenesis of most cavefish. Despite this difference, multiple lines of evidence suggested that evolutionary changes in L-R patterning are controlled upstream of Nodal-Pitx2/Lefty signaling. Accordingly, reciprocal hybridization of cavefish and surface fish showed that modifications of heart asymmetry are present in hybrids derived from cavefish mothers but not from surface fish mothers. The results indicate that changes in visceral asymmetry during cavefish evolution are influenced by maternal genetic effects.

scholarly journals Antagonistic interactions in the zebrafish midline prior to the emergence of asymmetric gene expression are important for left–right patterning

2016 ◽  
Vol 371 (1710) ◽  
pp. 20150402 ◽  
Author(s):  
Rebecca D. Burdine ◽  
Daniel T. Grimes
Keyword(s):  
Gene Expression ◽  
Lateral Plate Mesoderm ◽  
Internal Organs ◽  
Lateral Plate ◽  
Left Right Asymmetry ◽  
Antagonistic Interactions

Left–right (L-R) asymmetry of the internal organs of vertebrates is presaged by domains of asymmetric gene expression in the lateral plate mesoderm (LPM) during somitogenesis. Ciliated L-R coordinators (LRCs) are critical for biasing the initiation of asymmetrically expressed genes, such as nodal and pitx2 , to the left LPM. Other midline structures, including the notochord and floorplate, are then required to maintain these asymmetries. Here we report an unexpected role for the zebrafish EGF-CFC gene one-eyed pinhead ( oep ) in the midline to promote pitx2 expression in the LPM. Late zygotic oep (LZ oep ) mutants have strongly reduced or absent pitx2 expression in the LPM, but this expression can be rescued to strong levels by restoring oep in midline structures only. Furthermore, removing midline structures from LZ oep embryos can rescue pitx2 expression in the LPM, suggesting the midline is a source of an LPM pitx2 repressor that is itself inhibited by oep . Reducing lefty1 activity in LZ oep embryos mimics removal of the midline, implicating lefty1 in the midline-derived repression. Together, this suggests a model where Oep in the midline functions to overcome a midline-derived repressor, involving lefty1 , to allow for the expression of left side-specific genes in the LPM. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

scholarly journals From social regulation of competition to competition as social regulation: transformations in the socioeconomic governance of the European Union

2017 ◽  
pp. 53-68 ◽  
Author(s):  
Antonios Roumpakis ◽  
Theo Papadopoulos
Keyword(s):  
Industrial Relations ◽  
Social Regulation ◽  
The European Union ◽  
Wage Setting ◽  
Regulatory Changes ◽  
European Court ◽  
The Right ◽  
New Procedures ◽  
The Eu

This chapter studies the character of contemporary socioeconomic governance in the EU. It draws on empirical evidence capturing the type and extent of regulatory changes in the fields of industrial relations, corporate governance, and the coordination of macro-economic policy in the EU. The effects of these changes are long term, cumulative, and mutually reinforcing and should be seen as integral elements of a relatively coherent project to establish a form of transnational polity in Europe that privileges competition as its regulatory rationale. Indeed, the European Court of Justice (ECJ) has been institutionally prioritising market freedoms and competition over labour rights, and especially the right to collective action in an emerging transnational regulatory field in the EU. Meanwhile, the new procedures of European macro-economic coordination construe national wage setting, collective bargaining institutions, and, more generally, social policy as adjustment variables serving primarily the purpose of promoting or restoring member states' economic competitiveness.

scholarly journals Education in the Mais Médicos program: the gap between proposals and implementation

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Erika Maria Sampaio Rocha ◽  
Thiago Dias Sarti ◽  
George Dantas de Azevedo ◽  
Jonathan Filippon ◽  
Carlos Eduardo Gomes Siqueira ◽  
...  
Keyword(s):  
Rural Areas ◽  
Public Institutions ◽  
Private Institutions ◽  
The Public ◽  
Regulatory Changes ◽  
The Social ◽  
Vacancy Distribution ◽  
The Right ◽  
Institutional Actors ◽  
Distribution Of Physicians

Abstract: Introduction: The scarcity and inequalities in the geographical distribution of physicians challenge the consolidation of the right to health and create migratory flows that increase health inequities. Due to their complex and multidimensional characteristics, they demand multisectoral political approaches, considering several factors related to the availability and area of practice of medical doctors, as well as the social vulnerability of local populations. Objective: This study aimed at analysing results of the “Mais Médicos” (More Doctors) Program Educational Axis in Brazil. Methodology: A documental research was conducted, highlighting the location and the public or private nature of new undergraduate medical school vacancies between the years 2013 until 2017, which were then compared to the goals and strategies outlined in the official Program documents. Results: The Educational Axis reached important milestones despite the resistance of some institutional actors. The Program extended its undergraduate vacancies by 7696 places, 22.48% of that in public institutions and 77.52% in private ones. Vacancy distribution prioritized cities in rural areas of Brazil, at the same instance bringing forward significant regulatory changes for undergraduate medical courses. However, political disputes with representatives of medical societies and stakeholders interested in favouring the private educational and healthcare sectors surface in the official discourses and documents. These factors weakened the program normative body, creating a hiatus between its core objectives and respective implementation. Evidence related to the concentration of vacancies in the Southeast regions allow the maintenance of a known unequal workforce distribution, despite a proportionally bigger increase in the Midwest, North and Northeast regions. Conclusion: The predominance of vacancies in private institutions and the weakening of the new undergraduate courses monitoring instruments can compromise changes in the graduate students’ profiles, which are necessary for the fixation of physicians in strategic geographic areas to promote Primary Healthcare.

scholarly journals Time Perception through the Processing of Verb Tenses: An ERP study regarding Mental Time Travel

2020 ◽  
Author(s):  
Charalabos Papageorgiou ◽  
Anastasios E. Giannopoulos ◽  
Athanasios S. Fokas ◽  
Paul M. Thompson ◽  
Nikolaos C. Kapsalis ◽  
...  
Keyword(s):  
Right Hemisphere ◽  
Brain Regions ◽  
Time Travel ◽  
Temporal Organization ◽  
Mental Time Travel ◽  
Precentral Gyrus ◽  
Alpha Oscillations ◽  
Biological Time ◽  
Underlying Mechanisms ◽  
The Right

ABSTRACTHumans are equipped with the so-called Mental Time Travel (MTT) ability, which allows them to consciously construct and elaborate past or future scenes. The mechanisms underlying MTT remain elusive. This study focused on the late positive potential (LPP) and alpha oscillations, considering that LPP covaries with the temporal continuity whereas the alpha oscillations index the temporal organization of perception. To that end, subjects were asked to focus on performing two mental functions engaging working memory, which involved mental self-projection into either the present-past (PP) border or the present-future (PF) border. To evaluate underlying mechanisms, the evoked frontal late positive potentials (LPP) as well as their cortical sources were analyzed via the standardized low-resolution brain electromagnetic tomography (sLORETA) technique. The LPP amplitudes - in the left lateral prefrontal areas that were elicited during PF tasks - were significantly higher than those associated with PP, whereas opposite patterns were observed in the central and right prefrontal areas. Crucially, the LPP activations of both the PP and PF self-projections overlapped with the brain’s default mode network and related interacting areas. Finally, we found enhanced alpha-related activation with respect to PP in comparison to PF, predominantly over the right hemisphere central brain regions (specifically, the precentral gyrus). These findings confirm that the two types of self-projection, as reflected by the frontally-distributed LPP, share common cortical resources that recruit different brain regions in a balanced way. This balanced distribution of brain activation might signify that biological time tends to behave in a homeostatic way.

scholarly journals Rare case of coronary spastic angina during treatment of invasive group A streptococcal sepsis

2021 ◽  
Vol 14 (8) ◽  
pp. e244693 ◽  
Author(s):  
Tatsuya Sakagami ◽  
Takeshi Tsuji
Keyword(s):  
Atrioventricular Block ◽  
Coronary Spasm ◽  
Channel Blockade ◽  
Complete Atrioventricular Block ◽  
Calcium Channel Blockade ◽  
Invasive Group ◽  
Group A ◽  
Underlying Mechanisms ◽  
The Right ◽  
Complete Atrioventricular

The underlying mechanisms of coronary spastic angina (CSA) is not well understood. It is unclear if an infection can trigger coronary vasospasm; the co-occurrence of sepsis and CSA has rarely been reported. We describe the case of a 47-year-old man who suddenly developed a complete atrioventricular block and an episode of cardiac arrest while undergoing treatment for sepsis secondary to invasive group A streptococci. Emergency coronary angiography and provocation revealed spasm of the right coronary artery, which had led to the atrioventricular block. The spasm was relieved following administration of calcium-channel blockade, and no subsequent recurrence was documented. Due to several underlying mechanisms, sepsis may be a potential risk factor of coronary spasm and episodes of this condition have been missed or misdiagnosed. Physicians should be aware of CSA as a potential complication during treatment of sepsis.

scholarly journals Atrial Fibrillation Progression Is Associated with Cell Senescence Burden as Determined by p53 and p16 Expression

2019 ◽  
Vol 9 (1) ◽  
pp. 36
Author(s):  
Laurence Jesel ◽  
Malak Abbas ◽  
Sin-Hee Park ◽  
Kensuke Matsushita ◽  
Michel Kindo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Surgery ◽  
Open Heart Surgery ◽  
Right Atrial ◽  
Atrial Remodeling ◽  
Inflammatory Proteins ◽  
Underlying Mechanisms ◽  
The Right ◽  
New Evidence

Background: Whilst the link between aging and thrombogenicity in atrial fibrillation (AF) is well established, the cellular underlying mechanisms are unknown. In AF, the role of senescence in tissue remodeling and prothrombotic state remains unclear. Aims: We investigated the link between AF and senescence by comparing the expression of senescence markers (p53 and p16), with prothrombotic and inflammatory proteins in right atrial appendages from patients in AF and sinus rhythm (SR). Methods: The right atrial appendages of 147 patients undergoing open-heart surgery were harvested. Twenty-one non-valvular AF patients, including paroxysmal (PAF) or permanent AF (PmAF), were matched with 21 SR patients according to CHA2DS2-VASc score and treatment. Protein expression was assessed by tissue lysates Western blot analysis. Results: The expression of p53, p16, and tissue factor (TF) was significantly increased in AF compared to SR (0.91 ± 0.31 vs. 0.58 ± 0.31, p = 0.001; 0.76 ± 0.32 vs. 0.35 ± 0.18, p = 0.0001; 0.88 ± 0.32 vs. 0.68 ± 0.29, p = 0.045, respectively). Expression of endothelial NO synthase (eNOS) was lower in AF (0.25 ± 0.15 vs. 0.35 ± 0.12, p = 0.023). There was a stepwise increase of p53, p16, TF, matrix metalloproteinase-9, and an eNOS progressive decrease between SR, PAF, and PmAF. AF was the only predictive factor of p53 and p16 elevation in multivariate analysis. Conclusions: The study brought new evidence indicating that AF progression is strongly related to human atrial senescence burden and points at a link between senescence, thrombogenicity, endothelial dysfunction and atrial remodeling.

Arterial pressure-flow relations in the awake standing dog

1975 ◽  
Vol 229 (5) ◽  
pp. 1261-1270 ◽  
Author(s):  
W Enrlich ◽  
FV Schrijen ◽  
TA Solomon ◽  
E Rodriguez-Lopez ◽  
RL Riley
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Rate Increase ◽  
Diastolic Pressure ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Right Atrial ◽  
Heart Rate Increase ◽  
Underlying Mechanisms ◽  
The Right

The transient circulatory changes following paced heart rate increase are reported from 133 trials with 6 unanesthetized dogs with chronically implanted monitoring devices for heart rate, cardiac output, aortic blood pressure, and mean right atrial pressure. In 62 trials with 2 of the dogs, pulmonary artery, and left ventricular end-diastolic pressure, as well as left ventricular dP/dt were also studied. The sequence of changes in pressures and flows is analyzed in terms of probable underlying mechanisms, particularly with respect to the nature of vascular resistances. The rise in aortic pressure and flow during the first 3 s of paced heart rate increase, before arterial stretch receptor reflexes become active, is more consistent with an effective downstream pressure of about 49 mmHg, presumably at the arteriolar level, than with an effective downstream pressure close to 0 mmHg at the right atrial level. In the pulmonary circulation where vascular reflex effects are less prominent, the pattern of pulmonary arterial pressure and flow for the entire 30 s of observation is consistent with an effective downstream pressure of 9 mmHg, presumably at the alveolar or pulmonary arteriolar level, rather than at the level of the left ventricular end-diastolic pressure.

scholarly journals Memory-Enhancing Effect of a Phytosome Containing the Combined Extract of Mulberry Fruit and Ginger in an Animal Model of Ischemic Stroke with Metabolic Syndrome

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Jintanaporn Wattanathorn ◽  
Nut Palachai ◽  
Wipawee Thukham-mee ◽  
Supaporn Muchimapura
Keyword(s):  
Metabolic Syndrome ◽  
Ischemic Stroke ◽  
Erk Pathway ◽  
Enhancing Effect ◽  
Neuron Density ◽  
Mulberry Fruit ◽  
Extracellular Signal ◽  
Male Wistar Rats ◽  
Underlying Mechanisms ◽  
The Right

The prevalence of dementia following cerebral ischemia in metabolic syndrome (MetS) condition is increasing, and most of the cases are often severe. Unfortunately, no effective strategy for treating this condition is available. Based on the positive modulation effect of a polyphenol-rich substance on dementia and the improvement in bioavailability and stability of polyphenols induced by the phytosome technique together with the use of the synergistic concept, we hypothesized that a phytosome containing the combined extract of mulberry fruit and ginger (PMG) should mitigate dementia and memory impairment following ischemic stroke in MetS. MetS was induced in male Wistar rats weighing 180-200 g by exposure to a 16-week feeding period of high-carbohydrate high-fat (HCHF) diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg·kg-1 BW 21 days before and 21 days after the occlusion of the right middle cerebral artery (Rt. MCAO). Then, their spatial memory was determined and the possible underlying mechanisms explored via the alterations of acetylcholinesterase (AChE), neuron density, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), and signal transduction via extracellular signal-regulated kinase (ERK) pathway in both the cerebral cortex and the hippocampus. It was found that PMG significantly enhanced memory. It also decreased AChE, IL-6, and MDA but increased SOD, CAT, GSH-Px, neuron density, and phosphorylation of ERK. These data suggested the cognitive enhancing effect of PMG. The possible underlying mechanisms might occur partly via the improvement of cholinergic function via the ERK pathway together with the decrease in neurodegeneration induced by the reduction of oxidative stress and inflammation. However, a subchronic toxicity study is also required to assure the safety of PMG consumption before moving forward to a clinical trial study.

Morphometric Characterization and Finite Element Modeling of the Physiological Tricuspid Valve

2009 ◽  
Author(s):  
Marco Stevanella ◽  
Emiliano Votta ◽  
Massimo Lemma ◽  
Carlo Antona ◽  
Alberto Redaelli
Keyword(s):  
Finite Element ◽  
Tricuspid Valve ◽  
Heart Valves ◽  
Heart Surgery ◽  
Biomechanical Analysis ◽  
Left Heart ◽  
Mortality And Morbidity ◽  
Functional Tricuspid Regurgitation ◽  
Underlying Mechanisms ◽  
The Right

The tricuspid valve (TV) is the right atrio-ventricular valve. The most common TV disease is secondary or functional tricuspid regurgitation (FTR), an important complication of left-sided valvular heart lesions, which frequently persists after mitral and aortic valve operations. FTR is associated with high mortality and morbidity and requires surgical intervention, the preferential solution being TV repair through techniques such as annuloplasty performed during left heart surgery. However, significant residual regurgitation persists or recurs in 10% to 20% after annuloplasty, thus highlighting the incomplete understanding of the underlying mechanisms and the need for deeper insight into TV pathophysiology. At this purpose finite element models (FEMs) could be adopted, as suggested by their effective application to the biomechanical analysis of left heart valves. However, while for those several data are available regarding morphology and tissue mechanical properties, such information is missing for the TV, making it difficult to implement a FEM of the TV.

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