Recent evidence documented a protective effect of Class II Human Leukocyte AntigenHuman Leukocyte Antigen (HLA)Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
DRB1*13 on brain health across the lifespan including evidence of reduced neural network variability relative to non-carriers. Here, in an extension of those findings, we evaluated the influence of a large number of Class I and Class II HLAHuman Leukocyte Antigen (HLA)Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
alleles on aging-related changes in neural network variability. Cognitively healthy women (N=178) ranging in age from 28 to 99 years old underwent a magnetoencephalography scan from which neural network variability was calculated and provided a blood sample from which HLAHuman Leukocyte Antigen (HLA)Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
and Apolipoprotein EApolipoprotein E (ApoE)a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories. genotype were determined. The primary analyses assessed the dependence of network variability on age in carriers of a specific HLAHuman Leukocyte Antigen (HLA)Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
allele compared to non-carriers. Effects were considered protective if there was a significant increase of network variability with age in the absence of a given HLAHuman Leukocyte Antigen (HLA)Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant.
allele but not in its presence, and were considered...
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1st Annual Angeliki Georgopoulos Lecture in Brain Sciences
Women's Healthy Brain Aging: Legacy of a Learned Life
Dr. Lisa M. James, PhD
The effect of Apolipoprotein EApolipoprotein E (ApoE)a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.4 on SNISynchronous Neural Interactions (SNI)Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG. in brain cultures
In a previous study, we assessed the SNISynchronous Neural Interactions (SNI)Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG. in a developing neural network in brain cultures on multielectrode arrays (Christopoulos et al. in J Neural Eng 9:046008, 2012). Here, we report on the effects of ApoEApolipoprotein E (ApoE)a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.4 (ApoEApolipoprotein E (ApoE)a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.4) on these neural interactions. We carried out six experiments (five using rodent brain cultures and one using neuroblastoma cultures) in which we recorded local field potentials (LFP) from 59 sites for several days in vitro under the following conditions. In one experiment, we added to the culture media triglyceride (TG)-rich lipoproteins from a human subject with the ApoEApolipoprotein E (ApoE)a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.4/4 genotype, whereas in the other experiments, we added recombinant human ApoEApolipoprotein E (ApoE)a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.4. We found that SNISynchronous Neural Interactions (SNI)Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG. in the ApoEApolipoprotein E (ApoE)a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.4-treated cultures had higher coefficient of SNISynchronous Neural Interactions (SNI)Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG. variation, as compared to control cultures. These findings further document the role of SNISynchronous Neural Interactions (SNI)Zero-lag partial correlations in pairs of MEG time series and denote the strength and polarity (positive or negative) of neuronal interactions. Anomalies in SNIs as assessed by MEG differentiate psychiatric disorders from healthy brain functioning and can discriminate among various brain diseases. From this research, a highly distinctive, unique PTSD SNI signature characterized by miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas has emerged. These findings, in addition to the growing research applying MEG to other psychiatric disorders, highlight the utility of MEG in identifying biomarkers of disease and underscore the potential for broader clinical applications of MEG. as a fundamental aspect of the dynamic organization of neural networks (Langheim et al....
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The Number of Cysteine Residues per Mole in Apolipoprotein EApolipoprotein E (ApoE)a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories. Is Associated With the Severity of Post-traumatic Stress DisorderPost-traumatic Stress Disorder (PTSD)A complex psychiatric syndrome that develops in response to trauma exposure. Individuals with PTSD experience intrusive recollections or reexperiencing of the traumatic event, avoidance of trauma reminders, emotional numbing, and hyperarousal. In addition, PTSD is associated with high rates of concomitant physical and mental health problems, increased health care use, and impairment in social and occupational functioning. Almost 7% of the general population and up to 30% of veterans meet lifetime criteria for PTSD. Indeed, PTSD is one of the most common psychiatric disorders, representing a significant and costly public health concern. Re-Experiencing Symptoms
Apolipoprotien E (ApoEApolipoprotein E (ApoE)a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories.) is involved in critical neural functions and is associated with various neuropsychiatric disorders. ApoEApolipoprotein E (ApoE)a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories. exists in three isoforms that differ in the number of cysteine residues per mole (CysR/mole). This study evaluated associations between this informative ordinal biochemical scale (CysR/mole) and symptom severity in veterans with posttraumatic stress disorder (PTSDPost-traumatic Stress Disorder (PTSD)A complex psychiatric syndrome that develops in response to trauma exposure. Individuals with PTSD experience intrusive recollections or reexperiencing of the traumatic event, avoidance of trauma reminders, emotional numbing, and hyperarousal. In addition, PTSD is associated with high rates of concomitant physical and mental health problems, increased health care use, and impairment in social and occupational functioning. Almost 7% of the general population and up to 30% of veterans meet lifetime criteria for PTSD. Indeed, PTSD is one of the most common psychiatric disorders, representing a significant and costly public health concern.) or subthreshold PTSDPost-traumatic Stress Disorder (PTSD)A complex psychiatric syndrome that develops in response to trauma exposure. Individuals with PTSD experience intrusive recollections or reexperiencing of the traumatic event, avoidance of trauma reminders, emotional numbing, and hyperarousal. In addition, PTSD is associated with high rates of concomitant physical and mental health problems, increased health care use, and impairment in social and occupational functioning. Almost 7% of the general population and up to 30% of veterans meet lifetime criteria for PTSD. Indeed, PTSD is one of the most common psychiatric disorders, representing a significant and costly public health concern.. Results demonstrated a significant negative relationship between the CysR/mole and severity of PTSDPost-traumatic Stress Disorder (PTSD)A complex psychiatric syndrome that develops in response to trauma exposure. Individuals with PTSD experience intrusive recollections or reexperiencing of the traumatic event, avoidance of trauma reminders, emotional numbing, and hyperarousal. In addition, PTSD is associated with high rates of concomitant physical and mental health problems, increased health care use, and impairment in social and occupational functioning. Almost 7% of the general population and up to 30% of veterans meet lifetime criteria for PTSD. Indeed, PTSD is one of the most common psychiatric disorders, representing a significant and costly public health concern. re-experiencing symptoms, adjusted for trauma. The findings suggest a genetic influence on PTSDPost-traumatic Stress Disorder (PTSD)A complex psychiatric syndrome that develops in response to trauma exposure. Individuals with PTSD experience intrusive recollections or reexperiencing of the traumatic event, avoidance of trauma reminders, emotional numbing, and hyperarousal. In addition, PTSD is associated with high rates of concomitant physical and mental health problems, increased health care use, and impairment in social and occupational functioning. Almost 7% of the general population and up to 30% of veterans meet lifetime criteria for PTSD. Indeed, PTSD is one of the most common psychiatric disorders, representing a significant and costly public health concern. symptomatology and dovetail with recent advances regarding the molecular mechanisms underlying the differential effects of ApoEApolipoprotein E (ApoE)a plasma lipoprotein discovered in 1973 (Shore and Shore 1973). It binds low-density lipoprotein receptors, thereby facilitating cellular lipoprotein exchange and metabolism. The human apoE polypeptide consists of 299 amino acids and comprises three polymorphisms resulting from single amino acid substitutions. Three isoforms (E4, E3, and E2) are the result of cysteine^aEUR"arginine interchanges at two sites, namely residues 112 and 158; however, other genetic variants have been described. These three isoforms, each differentially affecting protein function, result in six phenotypes: three homozygotes (E4/4, E3/3, E2/2) and three heterozygotes (E4/3, E4/2, E3/2). With respect to the number of cysteine residues per mole, E2/2 contains 4, E3/2 contains 3, E4/2 and E3/3 each contain 2, E4/3 contains 1, and E4/4 contains 0. The number of cysteine residues per mole (CysR/mole) provides a numerical, biochemical scale in lieu of the genotype-based categories. in the brain.