Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to Pathogen

The tens of thousands of industrial and synthetic chemicals released into the environment have an unknown but potentially significant capacity to interfere with neurodevelopment. Consequently, there is an urgent need for systematic approaches that can identify disruptive chemicals. Little is known about the impact of environmental chemicals on critical periods of developmental neuroplasticity, in large part, due to the challenge of screening thousands of chemicals. Using an integrative bioinformatics approach, we systematically scanned 2001 environmental chemicals and identified 50 chemicals that consistently dysregulate two transcriptional signatures of critical period plasticity. These chemicals included pesticides (e.g., pyridaben), antimicrobials (e.g., bacitracin), metals (e.g., mercury), anesthetics (e.g., halothane), and other chemicals and mixtures (e.g., vehicle emissions). Application of a chemogenomic enrichment analysis and hierarchical clustering across these diverse chemicals identified two clusters of chemicals with one that mimicked an immune response to pathogen, implicating inflammatory pathways and microglia as a common chemically induced neuropathological process. Thus, we established an integrative bioinformatics approach to systematically scan thousands of environmental chemicals for their ability to dysregulate molecular signatures relevant to critical periods of development.

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The Concept and Application of Early Economic Period Threshold: The Case of DCPA in Onions (Allium Cepa)

Weed Science ◽

10.1017/s0043174500081753 ◽

1995 ◽

Vol 43 (4) ◽

pp. 634-639 ◽

Cited By ~ 17

Author(s):

Claudio M. Dunan ◽

Philip Westra ◽

Edward E. Schweizer ◽

Donald W. Lybecker ◽

Frank D. Moore

Keyword(s):

Weed Control ◽

Critical Period ◽

Crop Yields ◽

Economic Feasibility ◽

Control Measures ◽

Economic Losses ◽

Weed Competition ◽

Critical Periods ◽

Control Efficacy ◽

The Impact

The question of when to control weeds traditionally has been approached with the calculation of critical periods (CP) based on crop yields. The concept of economic critical period (ECP) and early (EEPT) and late (LEFT) economic period thresholds are presented as a comprehensive approach to answer the same question based on economic losses and costs of control. ECP is defined as the period when the benefit of controlling weeds is greater than its cost. EEPT and LEFT are the limits of the ECP and can be used to determine when first and last weed control measures should be performed. Calculation of EEPT accounts for the economic losses due to weed competition that occur between planting and postemergence weed control. In this way it is possible to better evaluate the economic feasibility of using preplant or preemergence control tactics. The EEPT for DCPA application is analyzed in the context of onion production in Colorado. The EEPT for DCPA application was calculated from an empirical regression model that assessed the impact of weed load and time of weed removal on onion yields. The EEPT was affected by control efficacy, weed-free yield, DCPA cost, and onion price. DCPA application was economically advisable in only one of 20 fields analyzed because of the tow DCPA efficacy (60%).

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Critical period regulation across multiple timescales

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1820836117 ◽

2020 ◽

Vol 117 (38) ◽

pp. 23242-23251 ◽

Cited By ~ 13

Author(s):

Rebecca K. Reh ◽

Brian G. Dias ◽

Charles A. Nelson ◽

Daniela Kaufer ◽

Janet F. Werker ◽

...

Keyword(s):

Critical Period ◽

Brain Plasticity ◽

Gamma Oscillations ◽

Developmental Time ◽

Brain Regions ◽

Inhibitory Neurons ◽

Critical Periods ◽

Multiple Timescales ◽

Fast Spiking ◽

The Impact

Brain plasticity is dynamically regulated across the life span, peaking during windows of early life. Typically assessed in the physiological range of milliseconds (real time), these trajectories are also influenced on the longer timescales of developmental time (nurture) and evolutionary time (nature), which shape neural architectures that support plasticity. Properly sequenced critical periods of circuit refinement build up complex cognitive functions, such as language, from more primary modalities. Here, we consider recent progress in the biological basis of critical periods as a unifying rubric for understanding plasticity across multiple timescales. Notably, the maturation of parvalbumin-positive (PV) inhibitory neurons is pivotal. These fast-spiking cells generate gamma oscillations associated with critical period plasticity, are sensitive to circadian gene manipulation, emerge at different rates across brain regions, acquire perineuronal nets with age, and may be influenced by epigenetic factors over generations. These features provide further novel insight into the impact of early adversity and neurodevelopmental risk factors for mental disorders.

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Visual experience sculpts whole-cortex spontaneous infraslow activity patterns through an Arc-dependent mechanism

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1711789114 ◽

2017 ◽

Vol 114 (46) ◽

pp. E9952-E9961 ◽

Cited By ~ 8

Author(s):

Andrew W. Kraft ◽

Anish Mitra ◽

Adam Q. Bauer ◽

Abraham Z. Snyder ◽

Marcus E. Raichle ◽

...

Keyword(s):

Spontaneous Activity ◽

Resting State ◽

Critical Period ◽

Visual Experience ◽

Visual Deprivation ◽

Critical Periods ◽

Sensory Evoked ◽

The Impact ◽

Dependent Mechanism ◽

Visual Network

Decades of work in experimental animals has established the importance of visual experience during critical periods for the development of normal sensory-evoked responses in the visual cortex. However, much less is known concerning the impact of early visual experience on the systems-level organization of spontaneous activity. Human resting-state fMRI has revealed that infraslow fluctuations in spontaneous activity are organized into stereotyped spatiotemporal patterns across the entire brain. Furthermore, the organization of spontaneous infraslow activity (ISA) is plastic in that it can be modulated by learning and experience, suggesting heightened sensitivity to change during critical periods. Here we used wide-field optical intrinsic signal imaging in mice to examine whole-cortex spontaneous ISA patterns. Using monocular or binocular visual deprivation, we examined the effects of critical period visual experience on the development of ISA correlation and latency patterns within and across cortical resting-state networks. Visual modification with monocular lid suturing reduced correlation between left and right cortices (homotopic correlation) within the visual network, but had little effect on internetwork correlation. In contrast, visual deprivation with binocular lid suturing resulted in increased visual homotopic correlation and increased anti-correlation between the visual network and several extravisual networks, suggesting cross-modal plasticity. These network-level changes were markedly attenuated in mice with genetic deletion of Arc, a gene known to be critical for activity-dependent synaptic plasticity. Taken together, our results suggest that critical period visual experience induces global changes in spontaneous ISA relationships, both within the visual network and across networks, through an Arc-dependent mechanism.

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Exile, Diaspora, and Return

10.1093/oso/9780190693961.001.0001 ◽

2017 ◽

Cited By ~ 1

Author(s):

Luis Roniger ◽

Leonardo Senkman ◽

Saúl Sosnowski ◽

Mario Sznajder

Keyword(s):

Systematic Analysis ◽

The Arts ◽

Scientific Disciplines ◽

Early Twenty ◽

Transnational Connections ◽

Late Twentieth ◽

Institutional Impact ◽

Global Arena ◽

Education Science ◽

The Impact

This book explores how Argentina, Chile, Paraguay, and Uruguay have been affected by postexilic relocations, transnational migrant displacements, and diasporas. It provides a systematic analysis of the formation of exile communities and diaspora politics, the politics of return, and the agenda of democratization in the late twentieth and early twenty-first centuries, focusing on the impact of intellectuals, academics, activists, and public figures who had experienced exile on the reconstitution and transformation of their societies following democratization. Readers are offered a kaleidoscope of intellectual itineraries, debates, and contributions held in the public domain by individuals who confronted and fought authoritarian rule. The book covers their contributions to the restructuring and transformation of scientific disciplines and of the humanities and the arts, as well as their collective institutional impact on higher education, science and technology, and public institutions. Bringing together sociopolitical, cultural, and policy analysis with the testimonies of dozens of intellectuals, academics, political activists, and policymakers, the book addresses the impact of exile on people’s lives and on their fractured experiences, the debates and prospects of return, the challenges of dis-exile and postexilic trends, and, finally, the ways in which those who experienced exile impacted democratized institutions, public culture, and discourse. It also follows some crucial shifts in the frontiers of citizenship, moving analysis to transnational connections and permanent diasporas, including the diasporas of knowledge that increasingly changed the very meaning of being national and transnational, while connecting those countries to the global arena.

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Transglutaminases and Obesity in Humans: Association of F13A1 to Adipocyte Hypertrophy and Adipose Tissue Immune Response

International Journal of Molecular Sciences ◽

10.3390/ijms21218289 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8289

Author(s):

Mari T. Kaartinen ◽

Mansi Arora ◽

Sini Heinonen ◽

Aila Rissanen ◽

Jaakko Kaprio ◽

...

Keyword(s):

Immune Response ◽

Adipose Tissue ◽

Family Members ◽

Enrichment Analysis ◽

Human Adipose Tissue ◽

Adipocyte Size ◽

Gene Enrichment ◽

Adipocyte Hypertrophy ◽

Mz Twins

Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of TGM family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy–lean twin pairs. We report that F13A1 is the only TGM family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte F13A1 to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of F13A1 to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of F13A1 (ΔHeavy–Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of F13A1 in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation.

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Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Cells ◽

10.3390/cells10040868 ◽

2021 ◽

Vol 10 (4) ◽

pp. 868

Author(s):

Fabiana Albani Zambuzi ◽

Priscilla Mariane Cardoso-Silva ◽

Ricardo Cardoso Castro ◽

Caroline Fontanari ◽

Flavio da Silva Emery ◽

...

Keyword(s):

Immune Response ◽

Hematological Malignancies ◽

M2 Macrophage ◽

M2 Polarization ◽

Tnf Α ◽

Monocytes And Macrophages ◽

Ifn Γ ◽

And Function ◽

The Impact

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

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NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽

10.3390/cancers13122999 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2999

Author(s):

Deborah Reynaud ◽

Roland Abi Nahed ◽

Nicolas Lemaitre ◽

Pierre-Adrien Bolze ◽

Wael Traboulsi ◽

...

Keyword(s):

Immune Response ◽

Tumor Cells ◽

Major Gene ◽

Critical Role ◽

Orthotopic Model ◽

Independent Manner ◽

Maternal Immune Response ◽

The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

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Structural variations in papaya genomes

BMC Genomics ◽

10.1186/s12864-021-07665-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zhenyang Liao ◽

Xunxiao Zhang ◽

Shengcheng Zhang ◽

Zhicong Lin ◽

Xingtan Zhang ◽

...

Keyword(s):

Agronomic Traits ◽

Enrichment Analysis ◽

Copy Number Variant ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Structural Variations ◽

Reproduction Traits ◽

Depth Study ◽

Environmental Adaptability ◽

The Impact

Abstract Background Structural variations (SVs) are a type of mutations that have not been widely detected in plant genomes and studies in animals have shown their role in the process of domestication. An in-depth study of SVs will help us to further understand the impact of SVs on the phenotype and environmental adaptability during papaya domestication and provide genomic resources for the development of molecular markers. Results We detected a total of 8083 SVs, including 5260 deletions, 552 tandem duplications and 2271 insertions with deletion being the predominant, indicating the universality of deletion in the evolution of papaya genome. The distribution of these SVs is non-random in each chromosome. A total of 1794 genes overlaps with SV, of which 1350 genes are expressed in at least one tissue. The weighted correlation network analysis (WGCNA) of these expressed genes reveals co-expression relationship between SVs-genes and different tissues, and functional enrichment analysis shows their role in biological growth and environmental responses. We also identified some domesticated SVs genes related to environmental adaptability, sexual reproduction, and important agronomic traits during the domestication of papaya. Analysis of artificially selected copy number variant genes (CNV-genes) also revealed genes associated with plant growth and environmental stress. Conclusions SVs played an indispensable role in the process of papaya domestication, especially in the reproduction traits of hermaphrodite plants. The detection of genome-wide SVs and CNV-genes between cultivated gynodioecious populations and wild dioecious populations provides a reference for further understanding of the evolution process from male to hermaphrodite in papaya.

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Adolescence as a “critical period” in the heritage language use. Polish in Germany

Open Linguistics ◽

10.1515/opli-2021-0019 ◽

2021 ◽

Vol 7 (1) ◽

pp. 301-315

Author(s):

Hanna Pułaczewska

Keyword(s):

Role Models ◽

Personal Development ◽

Critical Period ◽

Growing Up ◽

Age Related ◽

The Media ◽

Role Of Parents ◽

Qualitative Part ◽

The Impact

Abstract In the article, we consider the impact of adolescence upon the usage of Polish in Polish-German bilinguals raised and living in Germany and demonstrate how adolescence surfaces as a socially based “critical period” in this usage using results from a survey and interviews conducted with 30 teenagers. In the quantitative part of the study, we seek to establish whether adolescents’ age affected the pattern and quantity of their usage of Polish in the media and contacts with age peers, whether the latter two facets of growing up with Polish were interrelated, and which other factors affected peer-relevant activities in Polish. Both age and peer contact turned out to significantly affect the use of the media in Polish, while peer contact in Polish was affected by the parental use of Polish in parent-child communication. The qualitative part presents the context and motivation for using Polish by the youths in peer-relevant activities. We integrate the results with insights provided by child development psychology from the perspective of language socialisation theory and interpret the age-related decline of interest in the Polish media as an effect of a diminishing role of parents and the increasing role of age peers as role models in personal development.

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Demand Response Coupled with Dynamic Thermal Rating for Increased Transformer Reserve and Lifetime

Energies ◽

10.3390/en14051378 ◽

2021 ◽

Vol 14 (5) ◽

pp. 1378

Author(s):

Ildar Daminov ◽

Rémy Rigo-Mariani ◽

Raphael Caire ◽

Anton Prokhorov ◽

Marie-Cécile Alvarez-Hérault

Keyword(s):

Ambient Temperature ◽

Demand Response ◽

Thermal Model ◽

Critical Period ◽

Optimization Problem ◽

Integrated Management ◽

Critical Periods ◽

Network Access ◽

Maximal Amplitude ◽

Demand Response Program

(1) Background: This paper proposes a strategy coupling Demand Response Program with Dynamic Thermal Rating to ensure a transformer reserve for the load connection. This solution is an alternative to expensive grid reinforcements. (2) Methods: The proposed methodology firstly considers the N-1 mode under strict assumptions on load and ambient temperature and then identifies critical periods of the year when transformer constraints are violated. For each critical period, the integrated management/sizing problem is solved in YALMIP to find the minimal Demand Response needed to ensure a load connection. However, due to the nonlinear thermal model of transformers, the optimization problem becomes intractable at long periods. To overcome this problem, a validated piece-wise linearization is applied here. (3) Results: It is possible to increase reserve margins significantly compared to conventional approaches. These high reserve margins could be achieved for relatively small Demand Response volumes. For instance, a reserve margin of 75% (of transformer nominal rating) can be ensured if only 1% of the annual energy is curtailed. Moreover, the maximal amplitude of Demand Response (in kW) should be activated only 2–3 h during a year. (4) Conclusions: Improvements for combining Demand Response with Dynamic Thermal Rating are suggested. Results could be used to develop consumer connection agreements with variable network access.

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