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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Roy Otten; Chung Jung Mun; Daniel S. Shaw; Melvin N. Wilson; +1 Authors

    AbstractBackgrounds and aimsDespite the link between stress and addictive behavior in adulthood, little is known about how early life stress in families predicts the early emergence of substance use in adolescence. This study tested a developmental cascade model, proposing that early stressful life events and negative parent–child interaction covary, and both disrupt the refinement of inhibitory control, which evolves into problem behavior in middle/late childhood and subsequent substance use exploration in early adolescence.MethodsData came from the Early Steps Multisite study, a community sample of at‐risk families in the metropolitan US areas of Pittsburgh (Pennsylvania), Eugene (Oregon) and Charlottesville (Virginia) with children aged 2 years at the start of the study and 14 years at the last measurement (n = 364). Structural equation modeling was used to test the proposed model.ResultsEarly stressful life events and negative parent–child interaction assessed at ages 2–5 were negatively related to inhibitory control at ages 7 and 8. Low levels of inhibitory control were prognostic of childhood problem behavior at ages 9 and 10. Finally, late childhood problem behavior was associated with substance use at age 14. Parental drug use was directly related to substance use at age 14.ConclusionsEarly life stress may disrupt child inhibitory control, which can cascade into behavioral and peer problem behavior in childhood and, in turn, heighten the risk for early adolescent substance use.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Article . 2018
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    NARCIS
    Article . 2019
    Data sources: NARCIS
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    Article . 2019 . 2018
    License: CC BY NC
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Radboud Repository
    Article . 2019
    Data sources: Radboud Repository
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Addiction
    Article . 2018
    License: Wiley Online Library User Agreement
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    Article . 2018
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Article . 2018
      Data sources: PubMed Central
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      NARCIS
      Article . 2019
      Data sources: NARCIS
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Article . 2019 . 2018
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Radboud Repository
      Article . 2019
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      Article . 2018
      License: Wiley Online Library User Agreement
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      Article . 2018
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Xia, Frances; Kheirbek, Mazen A.;

    Mood and anxiety disorders are complex heterogeneous syndromes that manifest in dysfunctions across multiple brain regions, cell types, and circuits. Biomarkers using brain-wide activity patterns in humans have proven useful in distinguishing between disorder subtypes and identifying effective treatments. In order to improve biomarker identification, it is crucial to understand the basic circuitry underpinning brain-wide activity patterns. Leveraging a large repertoire of techniques, animal studies have examined roles of specific cell types and circuits in driving maladaptive behavior. Recent advances in multiregion recording techniques, data-driven analysis approaches, and machine-learning-based behavioral analysis tools can further push the boundary of animal studies and bridge the gap with human studies, to assess how brain-wide activity patterns encode and drive emotional behavior. Together, these efforts will allow identifying more precise biomarkers to enhance diagnosis and treatment.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Other literature type . 2020
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Trends in Neurosciences
    Article . 2020
    License: Elsevier TDM
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Other literature type . 2020
      Data sources: PubMed Central
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Trends in Neurosciences
      Article . 2020
      License: Elsevier TDM
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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Mahmoud Aarabi; Hanna Balakier; Siamak Bashar; Sergey I. Moskovtsev; +3 Authors

    Mammalian zygotic development is initiated by sperm-mediated intracellular calcium oscillations, followed by activation of metaphase II-arrested oocytes. Sperm postacrosomal WW binding protein (PAWP) fulfils the criteria set for an oocyte-activating factor by inducing oocyte activation and being stored in the perinuclear theca, the sperm compartment whose content is first released into oocyte cytoplasm during fertilization. However, proof that PAWP initiates mammalian zygotic development relies on demonstration that it acts upstream of oocyte calcium oscillations. Here, we show that PAWP triggers calcium oscillations and pronuclear formation in human and mouse oocytes similar to what is observed during intracytoplasmic sperm injection (ICSI). Most important, sperm-induced calcium oscillations are blocked by coinjection of a competitive inhibitor, derived from the WWI domain-binding motif of PAWP, implying the requirement of sperm PAWP and an oocyte-derived WWI domain protein substrate of PAWP for successful fertilization. Sperm-delivered PAWP is, therefore, a unique protein with a nonredundant role during human and mouse fertilization, required to trigger zygotic development. Presented data confirm our previous findings in nonmammalian models and suggest potential applications of PAWP in the diagnosis and treatment of infertility.-

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao The FASEB Journalarrow_drop_down
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    The FASEB Journal
    Article . 2014
    License: Wiley Online Library User Agreement
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao The FASEB Journalarrow_drop_down
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      The FASEB Journal
      Article . 2014
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Jennie G. Briard; Suria Jahan; Priya Chandran; David Allan; +2 Authors

    The success of hematopoietic stem cell transplantation depends in part on the number and the quality of cells transplanted. Cryoinjuries during freezing and thawing reduce the ability of hematopoietic stem and progenitor cells (HSPCs) to proliferate and differentiate after thawing. Up to 20% of the patients undergoing umbilical cord blood (UCB) transplant experience delayed or failed engraftment, likely because of the inadequate hematopoietic potency of the unit. Therefore, the optimization of cryopreservation protocols, with an emphasis on the preservation of HSPCs, is an important issue. Current protocols typically utilize a 10% dimethyl sulfoxide cryoprotectant solution. This solution ensures 70–80% post-thaw cell viability by diluting intracellular solutes and maintaining the cell volume during cryopreservation. However, this solution fails to fully protect HSPCs, resulting in the loss of potency. Therefore, a new class of cryoprotectants (N-aryl-d-aldonamides) was designed and assessed for the ability to inhibit ice recrystallization and to protect HSPCs against cryoinjury. Several highly active ice recrystallization inhibitors were discovered. When used as additives to the conventional cryoprotectant solution, these nontoxic small molecules improved the preservation of functionally divergent hematopoietic progenitors in the colony-forming unit and long-term culture-initiating cell assays. By contrast, structurally similar compounds that did not inhibit ice recrystallization failed to improve the post-thaw recovery of myeloid progenitors. Together, these results demonstrate that the supplementation of cryopreservation solution with compounds capable of controlling ice recrystallization increases the post-thaw function and potency of HSPCs in UCB. This increase may translate into reduced risk of engraftment failure and allow for greater use of cryopreserved cord blood units.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2016
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    ACS Omega
    Article . 2016
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    ACS Omega
    Article . 2016
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    ACS Omega
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Europe PubMed Central
      Article . 2016
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      ACS Omega
      Article . 2016
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      ACS Omega
      Article . 2016
      License: Standard ACS AuthorChoice/Editors’ Choice Usage Agreement
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      ACS Omega
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Fabrice J. F. Laroche; Sheng Li; Ning Shen; Soo Kyung Hwang; +10 Authors

    Hyperactive sphingosine 1-phosphate (S1P) signaling is associated with a poor prognosis of triple-negative breast cancer (TNBC). Despite recent evidence that links the S1P receptor 1 (S1P1) to TNBC cell survival, its role in TNBC invasion and the underlying mechanisms remain elusive. Combining analyses of human TNBC cells with zebrafish xenografts, we found that phosphorylation of S1P receptor 1 (S1P1) at threonine 236 (T236) is critical for TNBC dissemination. Compared to luminal breast cancer cells, TNBC cells exhibit a significant increase of phospho-S1P1 T236 but not the total S1P1 levels. Misexpression of phosphorylation-defective S1P1 T236A (alanine) decreases TNBC cell migration in vitro and disease invasion in zebrafish xenografts. Pharmacologic disruption of S1P1 T236 phosphorylation, using either a pan-AKT inhibitor (MK2206) or an S1P1 functional antagonist (FTY720, an FDA-approved drug for treating multiple sclerosis), suppresses TNBC cell migration in vitro and tumor invasion in vivo. Finally, we show that human TNBC cells with AKT activation and elevated phospho-S1P1 T236 are sensitive to FTY720-induced cytotoxic effects. These findings indicate that the AKT-enhanced phosphorylation of S1P1 T236 mediates much of the TNBC invasiveness, providing a potential biomarker to select TNBC patients for the clinical application of FTY720.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Cellsarrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Cells
    Other literature type . Article . 2023
    License: CC BY
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    Cells
    Article . 2023
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      Cells
      Other literature type . Article . 2023
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      Cells
      Article . 2023
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    Authors: Spyros Papapetropoulos; Spyros Papapetropoulos; Angela Pontius; Elizabeth Finger; +16 Authors

    A comprehensive review of published literature was conducted to elucidate the genetics, neuropathology, imaging findings, prevalence, clinical course, diagnosis/clinical evaluation, potential biomarkers, and current and proposed treatments for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare, debilitating, and life-threatening neurodegenerative disorder for which disease-modifying therapies are not currently available. Details on potential efficacy endpoints for future interventional clinical trials in patients with ALSP and data related to the burden of the disease on patients and caregivers were also reviewed. The information in this position paper lays a foundation to establish an effective clinical rationale and address the clinical gaps for creation of a robust strategy to develop therapeutic agents for ALSP, as well as design future clinical trials, that have clinically meaningful and convergent endpoints.

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    Frontiers in Neurology
    Article
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    Frontiers in Neurology
    Article . 2022
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    Frontiers in Neurology
    Article . 2022
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    Scholarship@Western
    Other literature type . 2022
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      Frontiers in Neurology
      Article
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      Frontiers in Neurology
      Article . 2022
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      Frontiers in Neurology
      Article . 2022
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      Scholarship@Western
      Other literature type . 2022
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    Authors: B. Ogan Mancarci; Lilah Toker; Shreejoy J. Tripathy; Brenna Li; +3 Authors

    Establishing the molecular diversity of cell types is crucial for the study of the nervous system. We compiled a cross-laboratory database of mouse brain cell type-specific transcriptomes from 36 major cell types from across the mammalian brain using rigorously curated published data from pooled cell type microarray and single-cell RNA-sequencing (RNA-seq) studies. We used these data to identify cell type-specific marker genes, discovering a substantial number of novel markers, many of which we validated using computational and experimental approaches. We further demonstrate that summarized expression of marker gene sets (MGSs) in bulk tissue data can be used to estimate the relative cell type abundance across samples. To facilitate use of this expanding resource, we provide a user-friendly web interface at www.neuroexpresso.org. Visual Abstract

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    Europe PubMed Central
    Article . 2017
    Data sources: PubMed Central
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    bioRxiv
    Preprint . 2016
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    eNeuro
    Article . Preprint
    License: CC BY
    Data sources: UnpayWall
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    eNeuro
    Article . 2017
    License: CC BY NC SA
    Data sources: Crossref
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      Europe PubMed Central
      Article . 2017
      Data sources: PubMed Central
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      bioRxiv
      Preprint . 2016
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      eNeuro
      Article . Preprint
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      eNeuro
      Article . 2017
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    Authors: Ryan M. Jones; Lulu Deng; Kogee Leung; Dallan McMahon; +2 Authors

    Focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening recently entered clinical testing for targeted drug delivery to the brain. Sources of variability exist in the current procedures, motivating the development of real-time monitoring and control techniques to improve treatment safety and efficacy. Here we used three-dimensional (3D) transcranial microbubble imaging to calibrate FUS exposure levels for volumetric BBB opening. Methods: Using a sparse hemispherical transmit/receive ultrasound phased array, pulsed ultrasound was focused transcranially into the thalamus of rabbits during microbubble infusion and multi-channel 3D beamforming was performed online with receiver signals captured at the subharmonic frequency. Pressures were increased pulse-by-pulse until subharmonic activity was detected on acoustic imaging (psub), and tissue volumes surrounding the calibration point were exposed at 50-100%psub via rapid electronic beam steering. Results: Spatially-coherent subharmonic microbubble activity was successfully reconstructed transcranially in vivo during calibration sonications. Multi-point exposures induced volumetric regions of elevated BBB permeability assessed via contrast-enhanced magnetic resonance imaging (MRI). At exposure levels ≥75%psub, MRI and histological examination occasionally revealed tissue damage, whereas sonications at 50%psub were performed safely. Substantial intra-grid variability of FUS-induced bioeffects was observed via MRI, prompting future development of multi-point calibration schemes for improved treatment consistency. Receiver array sparsity and sensor configuration had substantial impacts on subharmonic detection sensitivity, and are factors that should be considered when designing next-generation clinical FUS brain therapy systems. Conclusion: Our findings suggest that 3D subharmonic imaging can be used to calibrate exposure levels for safe FUS-induced volumetric BBB opening, and should be explored further as a method for cavitation-mediated treatment guidance.

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    Europe PubMed Central
    Article . 2018
    Data sources: PubMed Central
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    Europe PubMed Central
    Article . 2018
    Data sources: PubMed Central
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    Theranostics
    Article . 2018
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    https://pubmed.ncbi.nlm.nih.go...
    Other literature type . 2018
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      Europe PubMed Central
      Article . 2018
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      Europe PubMed Central
      Article . 2018
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      Theranostics
      Article . 2018
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      https://pubmed.ncbi.nlm.nih.go...
      Other literature type . 2018
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    Authors: Selena Ahmed; Shauna Downs; Jessica Fanzo;

    The food system is responsible for some of society's most pressing sustainability challenges. Dietary guidelines are one policy tool to help address the multiple sustainability challenges associated with food systems through dietary recommendations that better support environmental and human well-being. This article develops and applies a sustainability framework scoring tool comprised of four key dimensions (environmental, economic, human health, and sociocultural and political) and 32 sub-dimensions of sustainable food systems for the analysis and modification of national dietary guidelines. Two coders pilot tested the framework to quantify the occurrence of sustainability dimensions and sub-dimensions in national and regional dietary guidelines of 12 randomly selected high-income and upper-middle income countries including Albania, Australia, Brazil, the Grenadines, Grenada, Qatar, Netherlands, Nordic Countries, St. Vincent, Sweden, Thailand, the United Kingdom, and the United States. Sustainability Dimension Scores (SDS) were calculated as a percentage of the occurrence of the eight sub-dimensions comprising each sustainability dimension and Total Sustainability Scores (TSS) were calculated as a percentage of the occurrence of the 32 sub-dimensions in each guideline. Inter-rater reliability of TSS and SDS indicated high validity of applying the sustainability framework for dietary guidelines. SDS varied between the four sustainability dimensions with human health being the most represented in the dietary guidelines examined, as hypothesized (average SDS score of 83%; range from 50 to 100%). Significant differences (p < 0.0001) were found in mean SDS between the four sustainability dimensions. Overall, results indicate that the ecological (average SDS score of 31%; range from 0 to 100%) economic (average SDS score of 29%; range from 0 to 100%), and socio-cultural and political (average SDS score of 44%; range of 0–100%) dimensions of sustainability are underrepresented in the examined national dietary guidelines with significant differences in SDS between guidelines (p < 0.0001). TSS varied by country between 12 and 74% with a mean score of 36% (± 20%). Brazil had the highest TSS (74%) followed by Australia (69%). The sustainability framework presented here can be applied by policy makers, researchers, and practitioners to identify gaps and opportunities to modify national dietary guidelines and associated programs for transforming food systems through diets that support planetary health.

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    Frontiers in Sustainable Food Systems
    Article . 2019
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    Frontiers in Sustainable Food Systems
    Article
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    Data sources: UnpayWall
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    DOAJ-Articles
    Article . 2019
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      Frontiers in Sustainable Food Systems
      Article . 2019
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      Frontiers in Sustainable Food Systems
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      DOAJ-Articles
      Article . 2019
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    Authors: Natalia B. Fernandez; Natalia B. Fernandez; Patrik Vuilleumier; Patrik Vuilleumier; +4 Authors

    Congenital amusia in its most common form is a disorder characterized by a musical pitch processing deficit. Although pitch is involved in conveying emotion in music, the implications for pitch deficits on musical emotion judgements is still under debate. Relatedly, both limited and spared musical emotion recognition was reported in amusia in conditions where emotion cues were not determined by musical mode or dissonance. Additionally, assumed links between musical abilities and visuo-spatial attention processes need further investigation in congenital amusics. Hence, we here test to what extent musical emotions can influence attentional performance. Fifteen congenital amusic adults and fifteen healthy controls matched for age and education were assessed in three attentional conditions: executive control (distractor inhibition), alerting, and orienting (spatial shift) while music expressing either joy, tenderness, sadness, or tension was presented. Visual target detection was in the normal range for both accuracy and response times in the amusic relative to the control participants. Moreover, in both groups, music exposure produced facilitating effects on selective attention that appeared to be driven by the arousal dimension of musical emotional content, with faster correct target detection during joyful compared to sad music. These findings corroborate the idea that pitch processing deficits related to congenital amusia do not impede other cognitive domains, particularly visual attention. Furthermore, our study uncovers an intact influence of music and its emotional content on the attentional abilities of amusic individuals. The results highlight the domain-selectivity of the pitch disorder in congenital amusia, which largely spares the development of visual attention and affective systems.

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    Authors: Roy Otten; Chung Jung Mun; Daniel S. Shaw; Melvin N. Wilson; +1 Authors

    AbstractBackgrounds and aimsDespite the link between stress and addictive behavior in adulthood, little is known about how early life stress in families predicts the early emergence of substance use in adolescence. This study tested a developmental cascade model, proposing that early stressful life events and negative parent–child interaction covary, and both disrupt the refinement of inhibitory control, which evolves into problem behavior in middle/late childhood and subsequent substance use exploration in early adolescence.MethodsData came from the Early Steps Multisite study, a community sample of at‐risk families in the metropolitan US areas of Pittsburgh (Pennsylvania), Eugene (Oregon) and Charlottesville (Virginia) with children aged 2 years at the start of the study and 14 years at the last measurement (n = 364). Structural equation modeling was used to test the proposed model.ResultsEarly stressful life events and negative parent–child interaction assessed at ages 2–5 were negatively related to inhibitory control at ages 7 and 8. Low levels of inhibitory control were prognostic of childhood problem behavior at ages 9 and 10. Finally, late childhood problem behavior was associated with substance use at age 14. Parental drug use was directly related to substance use at age 14.ConclusionsEarly life stress may disrupt child inhibitory control, which can cascade into behavioral and peer problem behavior in childhood and, in turn, heighten the risk for early adolescent substance use.

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    Europe PubMed Central
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    Radboud Repository
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    Authors: Xia, Frances; Kheirbek, Mazen A.;

    Mood and anxiety disorders are complex heterogeneous syndromes that manifest in dysfunctions across multiple brain regions, cell types, and circuits. Biomarkers using brain-wide activity patterns in humans have proven useful in distinguishing between disorder subtypes and identifying effective treatments. In order to improve biomarker identification, it is crucial to understand the basic circuitry underpinning brain-wide activity patterns. Leveraging a large repertoire of techniques, animal studies have examined roles of specific cell types and circuits in driving maladaptive behavior. Recent advances in multiregion recording techniques, data-driven analysis approaches, and machine-learning-based behavioral analysis tools can further push the boundary of animal studies and bridge the gap with human studies, to assess how brain-wide activity patterns encode and drive emotional behavior. Together, these efforts will allow identifying more precise biomarkers to enhance diagnosis and treatment.

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    Other literature type . 2020
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    Trends in Neurosciences
    Article . 2020
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