scholarly journals Prenatal psychosocial stress-induced behavioral and neuroendocrine abnormalities are associated with sex-specific alterations in synaptic transmission and differentially modulated by maternal environment

2020 ◽  
Author(s):  
Sandra P. Zoubovsky ◽  
Michael T. Williams ◽  
Sarah Hoseus ◽  
Shivani Tumukuntala ◽  
Amy Riesenberg ◽  
...  

ABSTRACTPrenatal stress (PS) is associated with increased vulnerability to affective disorders. Transplacental glucocorticoid passage and stress-induced maternal environment alterations are recognized as potential routes of transmission that can fundamentally alter neurodevelopment. However, molecular mechanisms underlying aberrant emotional outcomes or the individual contributions intrauterine stress versus maternal environment play in shaping these mechanisms remain unknown. Here, we report anxiogenic behaviors, anhedonia, and female hypothalamic-pituitary-adrenal axis hyperactivity as a consequence of psychosocial PS in mice. Sex-specific placental responses to stress and evidence of fetal amygdala programming precede these abnormalities. In adult offspring, we observe amygdalar transcriptional changes demonstrating sex-specific dysfunction in synaptic transmission and neurotransmitter systems. We find these abnormalities are primarily driven by in-utero stress exposure. Importantly, maternal care changes postnatally reverse anxiety-related behaviors and partially rescue gene alterations associated with neurotransmission. Our data demonstrate the influence maternal environment exerts in shaping offspring emotional development despite deleterious effects of intrauterine stress.

2019 ◽  
Vol 62 (3) ◽  
pp. 91-99
Author(s):  
Sogol Gachkar ◽  
Sebastian Nock ◽  
Cathleen Geissler ◽  
Rebecca Oelkrug ◽  
Kornelia Johann ◽  
...  

It is well established that thyroid hormones are required for cardiovascular functions; however, the molecular mechanisms remain incompletely understood, especially the individual contributions of genomic and non-genomic signalling pathways. In this study, we dissected how thyroid hormones modulate aortic contractility. To test the immediate effects of thyroid hormones on vasocontractility, we used a wire myograph to record the contractile response of dissected mouse aortas to the adrenergic agonist phenylephrine in the presence of different doses of T3 (3,3′,5-triiodothyronine). Interestingly, we observed reduced vasoconstriction under low and high T3 concentrations, indicating an inversed U-shaped curve with maximal constrictive capacity at euthyroid conditions. We then tested for possible genomic actions of thyroid hormones on vasocontractility by treating mice for 4 days with 1 mg/L thyroxine in drinking water. The study revealed that in contrast to the non-genomic actions the aortas of these animals were hyperresponsive to the contractile stimulus, an effect not observed in endogenously hyperthyroid TRβ knockout mice. To identify targets of genomic thyroid hormone action, we analysed aortic gene expression by microarray, revealing several altered genes including the well-known thyroid hormone target gene hairless. Taken together, the findings demonstrate that thyroid hormones regulate aortic tone through genomic and non-genomic actions, although genomic actions seem to prevail in vivo. Moreover, we identified several novel thyroid hormone target genes that could provide a better understanding of the molecular changes occurring in the hyperthyroid aorta.


Mediaevistik ◽  
2018 ◽  
Vol 31 (1) ◽  
pp. 366-366
Author(s):  
Albrecht Classen

Eddic poetry constitutes one of the most important genres in Old Norse or Scandinavian literature and has been studied since the earliest time of modern-day philology. The progress we have made in that field is impressive, considering the many excellent editions and translations, not to mention the countless critical studies in monographs and articles. Nevertheless, there is always a great need to revisit, to summarize, to review, and to digest the knowledge gained so far. The present handbook intends to address all those goals and does so, to spell it out right away, exceedingly well. But in contrast to traditional concepts, the individual contributions constitute fully developed critical article, each with a specialized topic elucidating it as comprehensively as possible, and concluding with a section of notes. Those are kept very brief, but the volume rounds it all off with an inclusive, comprehensive bibliography. And there is also a very useful index at the end. At the beginning, we find, following the table of contents, a list of the contributors, unfortunately without emails, a list of translations and abbreviations of the titles of Eddic poems in the Codex Regius and then elsewhere, and a very insightful and pleasant introduction by Carolyne Larrington. She briefly introduces the genre and then summarizes the essential points made by the individual authors. The entire volume is based on the Eddic Network established by the three editors in 2012, and on two workshops held at St. John’s College, Oxford in 2013 and 2014.


This volume comprises 27 chapters focused on the design and execution of employee survey programs. These chapters reflect the latest advances in technology and analytics and a pervasive emphasis on driving organizational performance and effectiveness. The individual chapters represent the full range of survey-related topics, including design, administration, analysis, feedback, and action-taking. The latest methodological trends and capabilities are discussed including computational linguistics, applications of artificial intelligence, and the use of qualitative methods such as focus groups. Extending beyond traditional employee surveys, contributions include the role of passive data collection as an alternative or supplement in a comprehensive employee listening system. Unique contextual factors are discussed including the use of surveys in a unionized environment. Individual contributions also reflect increasing stakeholder concerns for the protection of privacy among other ethical considerations. Finally, significant clarifications to the literature are provided on the use of surveys for measuring organization culture, strategic climate, and employee engagement.


Author(s):  
J. Adam Carter ◽  
Emma C. Gordon ◽  
Benjamin W. Jarvis

In this introductory chapter, the volume’s editors provide a theoretical background to the volume’s topic and a brief overview of the papers included. The chapter is divided into five parts: Section 1 explains the main contours of the knowledge-first approach, as it was initially advanced by Timothy Williamson in Knowledge and its Limits. In Sections 2–3, some of the key philosophical motivations for the knowledge-first approach are reviewed, and several key contemporary research themes associated with this approach in epistemology, the philosophy of mind and elsewhere are outlined and briefly discussed. The volume’s papers are divided into two broad categories: foundational issues and applications and new directions. Section 4 discusses briefly the scope and aim of the volume as the editors have conceived it, and Section 5 offers an overview of each of the individual contributions in the volume.


2021 ◽  
Vol 11 (5) ◽  
pp. 2228
Author(s):  
Daniela Galli ◽  
Cecilia Carubbi ◽  
Elena Masselli ◽  
Mauro Vaccarezza ◽  
Valentina Presta ◽  
...  

Reactive Oxygen Species (ROS) are molecules naturally produced by cells. If their levels are too high, the cellular antioxidant machinery intervenes to bring back their quantity to physiological conditions. Since aging often induces malfunctioning in this machinery, ROS are considered an effective cause of age-associated diseases. Exercise stimulates ROS production on one side, and the antioxidant systems on the other side. The effects of exercise on oxidative stress markers have been shown in blood, vascular tissue, brain, cardiac and skeletal muscle, both in young and aged people. However, the intensity and volume of exercise and the individual subject characteristics are important to envisage future strategies to adequately personalize the balance of the oxidant/antioxidant environment. Here, we reviewed the literature that deals with the effects of physical activity on redox balance in young and aged people, with insights into the molecular mechanisms involved. Although many molecular pathways are involved, we are still far from a comprehensive view of the mechanisms that stand behind the effects of physical activity during aging. Although we believe that future precision medicine will be able to transform exercise administration from wellness to targeted prevention, as yet we admit that the topic is still in its infancy.


2021 ◽  
Vol 50 (1) ◽  
pp. 3-11
Author(s):  
Barbara Schulte ◽  
Marina Svensson

This special issue approaches information and communication technologies (ICT) visions and their realisation/implementation at various levels, among different actors and from various perspectives. Conceptually, we distinguish three different dimensions, even though those overlap in the individual contributions as well as in empirical reality – namely ideational, instrumental, and relational. The different contributions address both visions formulated by the Chinese state and by individual actors such as entrepreneurs. Even though the conditions for the use of ICT in China are deeply affected by state governance, this governance is in no way tantamount to one single government. As this issue’s contributions show, state attempts at building a stable cyber-governance are in need of allies and, depending on the allies’ visions and other, competitive visions, the outcomes of these dynamics are seldom truthful realisations of one original grand masterplan.


e-Neuroforum ◽  
2017 ◽  
Vol 23 (4) ◽  
Author(s):  
Jens Rettig ◽  
David R. Stevens

AbstractThe release of neurotransmitters at synapses belongs to the most important processes in the central nervous system. In the last decades much has been learned about the molecular mechanisms which form the basis for this fundamental process. Highly regulated exocytosis, based on the SNARE (soluble N-ethylmaleimide-sensitive attachment protein receptor) complex and its regulatory molecules is the signature specialization of the nervous system and is shared by neurons and neuroendocrine cells. Cells of the immune system use a similar mechanism to release cytotoxic materials from secretory granules at contacts with virally or bacterially infected cells or cancer cells, in order to remove these threats. These contact zones have been termed immunological synapses in reference to the highly specific targeted exocytosis of effector molecules. Recent findings indicate that mutations in SNARE or SNARE-interacting proteins are the basis of a number of devastating immunological diseases. While SNARE complexes are ubiquitous and mediate a wide variety of membrane fusion events it is surprising that in many cases the SNARE proteins involved in immunological synapses are the same molecules which mediate regulated exocytosis of transmitters and hormones in neurons and neuroendocrine cells. These similarities raise the possibility that results obtained at immunological synapses may be applicable, in particular in the area of presynaptic function, to neuronal synapses. Since immunological synapses (IS) are assembled and disassembled in about a half an hour, the use of immune cells isolated from human blood allows not only the study of the molecular mechanisms of synaptic transmission in human cells, but is particularly suited to the examination of the assembly and disassembly of these “synapses” via live imaging. In this overview we discuss areas of similarity between synapses of the nervous and immune systems and in the process will refer to results of our experiments of the last few years.


2005 ◽  
Vol 16 (4) ◽  
pp. 1606-1616 ◽  
Author(s):  
David Michaelson ◽  
Wasif Ali ◽  
Vi K. Chiu ◽  
Martin Bergo ◽  
Joseph Silletti ◽  
...  

The CAAX motif at the C terminus of most monomeric GTPases is required for membrane targeting because it signals for a series of three posttranslational modifications that include isoprenylation, endoproteolytic release of the C-terminal– AAX amino acids, and carboxyl methylation of the newly exposed isoprenylcysteine. The individual contributions of these modifications to protein trafficking and function are unknown. To address this issue, we performed a series of experiments with mouse embryonic fibroblasts (MEFs) lacking Rce1 (responsible for removal of the –AAX sequence) or Icmt (responsible for carboxyl methylation of the isoprenylcysteine). In MEFs lacking Rce1 or Icmt, farnesylated Ras proteins were mislocalized. In contrast, the intracellular localizations of geranylgeranylated Rho GTPases were not perturbed. Consistent with the latter finding, RhoGDI binding and actin remodeling were normal in Rce1- and Icmt-deficient cells. Swapping geranylgeranylation for farnesylation on Ras proteins or vice versa on Rho proteins reversed the differential sensitivities to Rce1 and Icmt deficiency. These results suggest that postprenylation CAAX processing is required for proper localization of farnesylated Ras but not geranygeranylated Rho proteins.


Metrika ◽  
2021 ◽  
Author(s):  
Joscha Krause ◽  
Jan Pablo Burgard ◽  
Domingo Morales

AbstractRegional prevalence estimation requires the use of suitable statistical methods on epidemiologic data with substantial local detail. Small area estimation with medical treatment records as covariates marks a promising combination for this purpose. However, medical routine data often has strong internal correlation due to diagnosis-related grouping in the records. Depending on the strength of the correlation, the space spanned by the covariates can become rank-deficient. In this case, prevalence estimates suffer from unacceptable uncertainty as the individual contributions of the covariates to the model cannot be identified properly. We propose an area-level logit mixed model for regional prevalence estimation with a new fitting algorithm to solve this problem. We extend the Laplace approximation to the log-likelihood by an $$\ell _2$$ ℓ 2 -penalty in order to stabilize the estimation process in the presence of covariate rank-deficiency. Empirical best predictors under the model and a parametric bootstrap for mean squared error estimation are presented. A Monte Carlo simulation study is conducted to evaluate the properties of our methodology in a controlled environment. We further provide an empirical application where the district-level prevalence of multiple sclerosis in Germany is estimated using health insurance records.


2021 ◽  
pp. 074355842110069
Author(s):  
Gabriel Velez

In post-conflict and transitional settings, adolescents are important civic and political actors as potential peacebuilders. Policy and programming often focus on promoting prosocial outcomes for these younger generations, but there has been growing attention to their perspectives and psychological development. Drawing on theory in developmental psychology, adolescents interpret and respond to context in forming ideas about key concepts like peace, understanding society and their place in it, and constructing their orientations toward peace. This study extends current literature by exploring how Colombian adolescents describe peace within the context of a peace process in their country. Ninety-six 15- to 18-year-olds in and around Bogotá, Colombia, were interviewed about peace. Their responses were analyzed inductively using an adapted thematic analysis. Findings indicated that the individual was central to how respondents talked about peace; that is, peace begins and depends on the internal states. From this basis, individuals then created peace through interpersonal relations. There were some differences by respondents’ SES, such as in how respondents described peace as requiring equality in society, but none found for gender or age. This study demonstrates the need to provide concrete opportunities for these adolescents to see individual contributions and broader interpersonal peace as possible.


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