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Summer F Acevedo - One of the best experts on this subject based on the ideXlab platform.

  • ywhae 14 3 3e a potential novel Genetic Risk Factor and csf biomarker for hiv neurocognitive impairment
    Journal of NeuroVirology, 2013
    Co-Authors: Diana Morales, Rosa Hechavarria, Valerie Wojna, Summer F Acevedo
    Abstract:

    YWHAE (14-3-3e) protein levels are considered to be a reliable biomarker for neurodegeneration. The YWHAE protein interacts both directly and indirectly with human immunodeficiency virus (HIV) accessory proteins, leading to cell death. The purpose of this study was to examine the relationship between YWHAE polymorphisms and HIV-associated neurocognitive disorder (HAND) and the relationship between YWHAE protein levels and HAND. A cross-sectional study using random samples of HIV-seropositive (n = 20) and HIV-seronegative (controls) (n = 16) women from the Hispanic-Latino Longitudinal Cohort of Women was conducted. Individuals who are HIV-seropositive and heterozygous at the rs4790084/rs1204828 loci in the YWHAE gene were 3× more likely to display reduced cognitive functioning, to have received a HAND diagnosis, and to have less YHWAE protein expressed than homozygotes. Western blots from cerebral spinal fluid indicate that the HIV-seropositive women with HAND expressed 4.5× less YWHAE compared to HIV-seropositive cognitively normal women (94 % sensitivity, 84 % specificity; HIV-seropositive vs. controls). Therefore, polymorphism in YWHAE may be a Genetic Risk Factor for HAND and levels of YWHAE protein are a likely biomarker for neurocognitive status in HIV-seropositive women.

  • YWHAE/14-3-3ε: a potential novel Genetic Risk Factor and CSF biomarker for HIV neurocognitive impairment
    Journal of NeuroVirology, 2013
    Co-Authors: Diana Morales, Rosa Hechavarria, Valerie Wojna, Summer F Acevedo
    Abstract:

    YWHAE (14-3-3e) protein levels are considered to be a reliable biomarker for neurodegeneration. The YWHAE protein interacts both directly and indirectly with human immunodeficiency virus (HIV) accessory proteins, leading to cell death. The purpose of this study was to examine the relationship between YWHAE polymorphisms and HIV-associated neurocognitive disorder (HAND) and the relationship between YWHAE protein levels and HAND. A cross-sectional study using random samples of HIV-seropositive (n = 20) and HIV-seronegative (controls) (n = 16) women from the Hispanic-Latino Longitudinal Cohort of Women was conducted. Individuals who are HIV-seropositive and heterozygous at the rs4790084/rs1204828 loci in the YWHAE gene were 3× more likely to display reduced cognitive functioning, to have received a HAND diagnosis, and to have less YHWAE protein expressed than homozygotes. Western blots from cerebral spinal fluid indicate that the HIV-seropositive women with HAND expressed 4.5× less YWHAE compared to HIV-seropositive cognitively normal women (94 % sensitivity, 84 % specificity; HIV-seropositive vs. controls). Therefore, polymorphism in YWHAE may be a Genetic Risk Factor for HAND and levels of YWHAE protein are a likely biomarker for neurocognitive status in HIV-seropositive women.

Florie Demiautte - One of the best experts on this subject based on the ideXlab platform.

  • Alzheimer’s Genetic Risk Factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner
    Molecular Psychiatry, 2020
    Co-Authors: Fanny Eysert, Audrey Coulon, Emmanuelle Boscher, Anaїs-camille Vreulx, Amandine Flaig, Tiago Mendes, Sandrine Hughes, Benjamin Grenier-boley, Xavier Hanoulle, Florie Demiautte
    Abstract:

    Although APP metabolism is being intensively investigated, a large fraction of its modulators is yet to be characterized. In this context, we combined two genome-wide high-content screenings to assess the functional impact of miRNAs and genes on APP metabolism and the signaling pathways involved. This approach highlighted the involvement of FERMT2 (or Kindlin-2), a Genetic Risk Factor of Alzheimer’s disease (AD), as a potential key modulator of axon guidance, a neuronal process that depends on the regulation of APP metabolism. We found that FERMT2 directly interacts with APP to modulate its metabolism, and that FERMT2 underexpression impacts axonal growth, synaptic connectivity, and long-term potentiation in an APP-dependent manner. Last, the rs7143400-T allele, which is associated with an increased AD Risk and localized within the 3′UTR of FERMT2, induced a downregulation of FERMT2 expression through binding of miR-4504 among others. This miRNA is mainly expressed in neurons and significantly overexpressed in AD brains compared to controls. Altogether, our data provide strong evidence for a detrimental effect of FERMT2 underexpression in neurons and insight into how this may influence AD pathogenesis.

  • alzheimer s Genetic Risk Factor fermt2 kindlin 2 controls axonal growth and synaptic plasticity in an app dependent manner
    Molecular Psychiatry, 2020
    Co-Authors: Fanny Eysert, Audrey Coulon, Emmanuelle Boscher, Anaїs-camille Vreulx, Amandine Flaig, Tiago Mendes, Sandrine Hughes, Xavier Hanoulle, Benjamin Grenierboley, Florie Demiautte
    Abstract:

    Although APP metabolism is being intensively investigated, a large fraction of its modulators is yet to be characterized. In this context, we combined two genome-wide high-content screenings to assess the functional impact of miRNAs and genes on APP metabolism and the signaling pathways involved. This approach highlighted the involvement of FERMT2 (or Kindlin-2), a Genetic Risk Factor of Alzheimer's disease (AD), as a potential key modulator of axon guidance, a neuronal process that depends on the regulation of APP metabolism. We found that FERMT2 directly interacts with APP to modulate its metabolism, and that FERMT2 underexpression impacts axonal growth, synaptic connectivity, and long-term potentiation in an APP-dependent manner. Last, the rs7143400-T allele, which is associated with an increased AD Risk and localized within the 3'UTR of FERMT2, induced a downregulation of FERMT2 expression through binding of miR-4504 among others. This miRNA is mainly expressed in neurons and significantly overexpressed in AD brains compared to controls. Altogether, our data provide strong evidence for a detrimental effect of FERMT2 underexpression in neurons and insight into how this may influence AD pathogenesis.

  • alzheimer s Genetic Risk Factor fermt2 kindlin 2 controls axonal growth and synaptic plasticity in an app dependent manner
    bioRxiv, 2020
    Co-Authors: Fanny Eysert, Audrey Coulon, Emmanuelle Boscher, Anaїs-camille Vreulx, Amandine Flaig, Tiago Mendes, Sandrine Hughes, Xavier Hanoulle, Benjamin Grenierboley, Florie Demiautte
    Abstract:

    Although APP metabolism is being intensively investigated, a large fraction of its modulators are yet to be characterized. In this context, we combined two genome-wide high-content screenings to assess the functional impact of miRNAs and genes on APP metabolism and the signaling pathways involved. This approach highlighted the involvement of FERMT2 (or Kindlin-2), a Genetic Risk Factor of Alzheimer′s disease (AD), as a potential key modulator of axon guidance; a neuronal process dependent on the APP metabolism regulation. We found that FERMT2 directly interacts with APP to modulate its metabolism and that FERMT2 under-expression impacts axonal growth, synaptic connectivity and long-term potentiation in an APP-dependent manner. Lastly, the rs7143400-T allele, which is associated with an increased AD Risk and localized within the 3′UTR of FERMT2, induced a down-regulation of FERMT2 expression through binding of miR-4504 among others. This miRNA is mainly expressed in neurons and significantly overexpressed in AD brains compared to controls. Altogether, our data provide strong evidence for a detrimental effect of FERMT2 under-expression in neurons and insight on how this may influence AD pathogenesis.

Toshiyuki Miyata - One of the best experts on this subject based on the ideXlab platform.

  • elisa based detection system for protein s k196e mutation a Genetic Risk Factor for venous thromboembolism
    PLOS ONE, 2015
    Co-Authors: Keiko Maruyama, Masashi Akiyama, Koichi Kokame, Akiko Sekiya, Eriko Morishita, Toshiyuki Miyata
    Abstract:

    Protein S (PS) acts as a coFactor for activated protein C in the plasma anticoagulant system. PS Lys196-to-Glu (K196E) mutation is a Genetic Risk Factor for venous thromboembolism in Japanese individuals. Because of the substantial overlap in PS anticoagulant activity between KK (wild-type) and KE (heterozygous) genotypes, it is difficult to identify PS K196E carriers by measuring PS activity. Here, we generated monoclonal antibodies specific to the PS K196E mutant and developed a simple and reliable method for the identification of PS K196E carriers. We immunized mice with a keyhole limpet hemocyanin-conjugated synthetic peptide with Glu196. The hybridoma cells were screened for the binding ability of the produced antibodies to recombinant mutant EGF-like domains of PS (Ile117–Glu283). We obtained three hybridoma cell lines producing PS K196E mutation-specific antibodies. We established a sandwich enzyme-linked immunosorbent assay (ELISA) system in which the PS K196E mutation-specific monoclonal antibody was used as a detection antibody. We measured human plasma samples by using this system and successfully discriminated 11 individuals with the KE genotype from 122 individuals with the KK genotype. The ELISA system using the PS K196E mutation-specific antibody is a useful tool for the rapid identification of PS K196E carriers, who are at a higher Risk for venous thromboembolism.

  • Dysfunction of protein C anticoagulant system, main Genetic Risk Factor for venous thromboembolism in Northeast Asians
    Journal of thrombosis and thrombolysis, 2013
    Co-Authors: Tong Yin, Toshiyuki Miyata
    Abstract:

    Venous thromboembolism (VTE) is a life threatening medical disorder worldwide. A great deal of evidence suggests that prevalence of VTE varies significantly among ethnic populations, with consistently lower incidence found in Asians. While the distribution of Genetic Risk Factors may vary among races, Genetic Risk Factors can play a major role among individuals with different Genetic backgrounds. Two clinically evaluated low-frequency Genetic mutations that predispose to VTE--the Factor V Leiden mutation and prothrombin G20210A mutation--are found predominantly in Caucasians, and virtually never in Asians. The findings of a recent Genetic study of VTE in northeast Asians, which greatly advanced our knowledge in this area, indicate that the most frequent Genetic Risk Factors for VTE in northeast Asians can be attributed to a dysfunction of the protein C anticoagulant system. Several low-frequency Genetic mutations, PROS1 p.Lys196Glu in Japanese and PROC p.Arg189Trp and p.Lys193del in Chinese, are significantly associated with increased Risk for VTE, with odds ratio more than 2 through the reduced protein C anticoagulant activity. Construction of a multiFactorial model based on the Genetic Risk Factors in the protein C anticoagulant system could facilitate Genetic counseling for VTE Risk in these populations. The influence of prevalent Genetic mutations on the Risk of VTE should be further investigated in Asian countries.

Diana Morales - One of the best experts on this subject based on the ideXlab platform.

  • ywhae 14 3 3e a potential novel Genetic Risk Factor and csf biomarker for hiv neurocognitive impairment
    Journal of NeuroVirology, 2013
    Co-Authors: Diana Morales, Rosa Hechavarria, Valerie Wojna, Summer F Acevedo
    Abstract:

    YWHAE (14-3-3e) protein levels are considered to be a reliable biomarker for neurodegeneration. The YWHAE protein interacts both directly and indirectly with human immunodeficiency virus (HIV) accessory proteins, leading to cell death. The purpose of this study was to examine the relationship between YWHAE polymorphisms and HIV-associated neurocognitive disorder (HAND) and the relationship between YWHAE protein levels and HAND. A cross-sectional study using random samples of HIV-seropositive (n = 20) and HIV-seronegative (controls) (n = 16) women from the Hispanic-Latino Longitudinal Cohort of Women was conducted. Individuals who are HIV-seropositive and heterozygous at the rs4790084/rs1204828 loci in the YWHAE gene were 3× more likely to display reduced cognitive functioning, to have received a HAND diagnosis, and to have less YHWAE protein expressed than homozygotes. Western blots from cerebral spinal fluid indicate that the HIV-seropositive women with HAND expressed 4.5× less YWHAE compared to HIV-seropositive cognitively normal women (94 % sensitivity, 84 % specificity; HIV-seropositive vs. controls). Therefore, polymorphism in YWHAE may be a Genetic Risk Factor for HAND and levels of YWHAE protein are a likely biomarker for neurocognitive status in HIV-seropositive women.

  • YWHAE/14-3-3ε: a potential novel Genetic Risk Factor and CSF biomarker for HIV neurocognitive impairment
    Journal of NeuroVirology, 2013
    Co-Authors: Diana Morales, Rosa Hechavarria, Valerie Wojna, Summer F Acevedo
    Abstract:

    YWHAE (14-3-3e) protein levels are considered to be a reliable biomarker for neurodegeneration. The YWHAE protein interacts both directly and indirectly with human immunodeficiency virus (HIV) accessory proteins, leading to cell death. The purpose of this study was to examine the relationship between YWHAE polymorphisms and HIV-associated neurocognitive disorder (HAND) and the relationship between YWHAE protein levels and HAND. A cross-sectional study using random samples of HIV-seropositive (n = 20) and HIV-seronegative (controls) (n = 16) women from the Hispanic-Latino Longitudinal Cohort of Women was conducted. Individuals who are HIV-seropositive and heterozygous at the rs4790084/rs1204828 loci in the YWHAE gene were 3× more likely to display reduced cognitive functioning, to have received a HAND diagnosis, and to have less YHWAE protein expressed than homozygotes. Western blots from cerebral spinal fluid indicate that the HIV-seropositive women with HAND expressed 4.5× less YWHAE compared to HIV-seropositive cognitively normal women (94 % sensitivity, 84 % specificity; HIV-seropositive vs. controls). Therefore, polymorphism in YWHAE may be a Genetic Risk Factor for HAND and levels of YWHAE protein are a likely biomarker for neurocognitive status in HIV-seropositive women.

Mathew Varghese - One of the best experts on this subject based on the ideXlab platform.