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  1. Article ; Online: The N-Terminal Domain of Aβ

    Meirovitch, Eva / Liang, Zhichun / Freed, Jack H

    The journal of physical chemistry. B

    2022  Volume 126, Issue 6, Page(s) 1202–1211

    Abstract: We have developed the stochastic microscopic-order-macroscopic-disorder (MOMD) approach for elucidating dynamic structures in the solid-state ... ...

    Abstract We have developed the stochastic microscopic-order-macroscopic-disorder (MOMD) approach for elucidating dynamic structures in the solid-state from
    MeSH term(s) Amyloid/chemistry ; Amyloid beta-Peptides/chemistry ; Diffusion ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Protein Aggregates
    Chemical Substances Amyloid ; Amyloid beta-Peptides ; Protein Aggregates
    Language English
    Publishing date 2022-02-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1520-5207
    ISSN (online) 1520-5207
    DOI 10.1021/acs.jpcb.1c10131
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: An analysis of double-quantum coherence ESR in an N-spin system: Analytical expressions and predictions.

    Sinha Roy, Aritro / Marohn, John A / Freed, Jack H

    The Journal of chemical physics

    2024  Volume 160, Issue 13

    Abstract: ... we have derived analytical expressions for the DQC signal for a system with N-dipolar coupled spin-1/2 ...

    Abstract Electron spin resonance pulsed dipolar spectroscopy (PDS) has become popular in protein 3D structure analysis. PDS studies yield distance distributions between a pair or multiple pairs of spin probes attached to protein molecules, which can be used directly in structural studies or as constraints in theoretical predictions. Double-quantum coherence (DQC) is a highly sensitive and accurate PDS technique to study protein structures in the solid state and under physiologically relevant conditions. In this work, we have derived analytical expressions for the DQC signal for a system with N-dipolar coupled spin-1/2 particles in the solid state. The expressions are integrated over the relevant spatial parameters to obtain closed form DQC signal expressions. These expressions contain the concentration-dependent "instantaneous diffusion" and the background signal. For micromolar and lower concentrations, these effects are negligible. An approximate analysis is provided for cases of finite pulses. The expressions obtained in this work should improve the analysis of DQC experimental data significantly, and the analytical approach could be extended easily to a wide range of magnetic resonance phenomena.
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3113-6
    ISSN 1089-7690 ; 0021-9606
    ISSN (online) 1089-7690
    ISSN 0021-9606
    DOI 10.1063/5.0200054
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The N-Terminal Domain of Aβ₄₀-Amyloid Fibril: The MOMD Perspective of its Dynamic Structure from NMR Lineshape Analysis

    Meirovitch, Eva / Liang, Zhichun / Freed, Jack H.

    Journal of physical chemistry. 2022 Feb. 05, v. 126, no. 6

    2022  

    Abstract: ... amyloid fibril. Here, we apply it to the N-terminal domain of this fibril. We find that the dynamic structures ... independent. For the core domain, MOMD and MSM disagree on the character of the dynamic structure. For the N ...

    Abstract We have developed the stochastic microscopic-order-macroscopic-disorder (MOMD) approach for elucidating dynamic structures in the solid-state from ²H NMR lineshapes. In MOMD, the probe experiences an effective/collective motional mode. The latter is described by a potential, u, which represents the local spatial-restrictions, a local-motional diffusion tensor, R, and key features of local geometry. Previously we applied MOMD to the well-structured core domain of the 3-fold-symmetric twisted polymorph of the Aβ₄₀-amyloid fibril. Here, we apply it to the N-terminal domain of this fibril. We find that the dynamic structures of the two domains are largely similar but differ in the magnitude and complexity of the key physical parameters. This interpretation differs from previous multisimple-mode (MSM) interpretations of the same experimental data. MSM used for the two domains different combinations of simple motional modes taken to be independent. For the core domain, MOMD and MSM disagree on the character of the dynamic structure. For the N-terminal domain, they even disagree on whether this chain segment is structurally ordered (MOMD finds that it is), and whether it undergoes a phase transition at 260 K where bulklike water located in the fibril matrix freezes (MOMD finds that it does not). These are major differences associated with an important system. While the MOMD description is a physically sound one, there are drawbacks in the MSM descriptions. The results obtained in this study promote our understanding of the dynamic structure of protein aggregates. Thus, they contribute to the effort to pharmacologically control neurodegenerative disorders believed to be caused by such aggregates.
    Keywords freezing ; geometry ; journals ; neurodegenerative diseases ; protein aggregates ; protein structure
    Language English
    Dates of publication 2022-0205
    Size p. 1202-1211.
    Publishing place American Chemical Society
    Document type Article
    ISSN 1520-5207
    DOI 10.1021/acs.jpcb.1c10131
    Database NAL-Catalogue (AGRICOLA)

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  4. Book ; Online ; E-Book: Assessment of communication disorders in adults

    Hegde, M. N. / Freed, Donald B.

    resources and protocols

    2022  

    Abstract: Assessment of Communication Disorders in Adults: Resources and Protocols, Third Edition offers a unique combination of scholarly information, invaluable resources, and time-saving protocols on assessment of communication disorders in adults. Most ... ...

    Author's details M.N. Hegde,PhD, Don Freed, PhD
    Abstract Assessment of Communication Disorders in Adults: Resources and Protocols, Third Edition offers a unique combination of scholarly information, invaluable resources, and time-saving protocols on assessment of communication disorders in adults. Most resource books offer limited research and scholarly information, thus making them unsuitable as textbooks for academic courses on assessment and diagnosis. Similarly, most traditional textbooks do not include practical, easy-to-use, and time-saving resources and protocols that the practicing clinicians can readily use during assessment sessions. By combining the strengths of traditional textbooks with newer assessment resources and protocols, this one-of-a-kind book offers a single, comprehensive source that is suitable as a textbook and useful as a practical clinical resource. This bestselling and trusted text: Covers the full range of communication disorders in adults, from aphasia to voice disorders Gives a comprehensive outline of basic assessment procedures Provides a set of protocols that are necessary to assess any communication disorder in adults Addresses the multicultural issues in assessing communication disorders in adults and offers an integrated assessment approach that includes the most desirable features of the traditional and several alternative approaches Contains two chapters for each disorder: one on resources that offers scholarly and research background on the disorder and one on resources that describes practical procedures and protocols that save preparation time and effort for the clinician New to the Third Edition: Expanded emphasis and specific guidelines on making a correct differential diagnosis Latest research on the characteristics of communication disorders in adults Review of recent trends on diagnostic assessment with critical recommendations for students and clinicians Updated epidemiological research on communication disorders Revised text to offer more succinct information on assessment tools and diagnostic criteria The latest standardized and informal assessment instruments Student-friendly, step-by-step instructions on how to conduct initial interviews and share final assessment results with patients in each protocol chapter
    Keywords Communicative disorders/Diagnosis ; Communicative disorders/Prevention/Needs assessment ; Medical protocols
    Subject code 616.855
    Language English
    Dates of publication 2022-2022
    Size 1 online resource (446 pages) :, illustrations
    Edition Third edition.
    Publisher Plural Publishing, Inc
    Publishing place San Diego, CA
    Document type Book ; Online ; E-Book
    Note "The third edition of this book, Assessment of Communication Disorders in Adults, is a companion volume to the third edition of the Assessment of Communication Disorders in Children (Hegde & Pomaville, 2017)"--ECIP galley.
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    ISBN 1-63550-195-4 ; 9781635502633 ; 1635502632 ; 978-1-63550-195-7
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  5. Article: Elevated concentration of N-CAM VASE isoforms in schizophrenia.

    Vawter, M P / Frye, M A / Hemperly, J J / VanderPutten, D M / Usen, N / Doherty, P / Saffell, J L / Issa, F / Post, R M / Wyatt, R J / Freed, W J

    Journal of psychiatric research

    2000  Volume 34, Issue 1, Page(s) 25–34

    Abstract: Neural cell adhesion molecule (N-CAM) is a cell recognition molecule, four major isoforms (180, 140 ... 120, and 105-115 kDa) of which are present in brain. N-CAM has several roles in cellular organization ... and CNS development. Previously we have found an elevation in CSF N-CAM 120 kDa in the CSF of patients ...

    Abstract Neural cell adhesion molecule (N-CAM) is a cell recognition molecule, four major isoforms (180, 140, 120, and 105-115 kDa) of which are present in brain. N-CAM has several roles in cellular organization and CNS development. Previously we have found an elevation in CSF N-CAM 120 kDa in the CSF of patients with schizophrenia, bipolar disorder, and depression. We now report an increase in the variable alternative spliced exon (VASE), a 10 amino acid sequence inserted into the fourth N-CAM domain, in the CSF of patients with schizophrenia, but not in bipolar disorder or depression. VASE-immunoreactive (VASE-ir) bands were measured in CSF from patients with schizophrenia (n = 14), bipolar disorder I (n = 7), bipolar disorder II (n = 9), unipolar depression (n = 17) and matched controls (n = 37) by Western immunoblotting. Three VASE-ir bands were distinguished in lumbar CSF corresponding to heavy (165 kDa), medium (155 kDa) and low (140 kDa) MW. A logarithmic transformation was applied to the VASE protein units and analyzed with a MANOVA. There was a 51% and 45% increase in VASE heavy (p = 0.0008) and medium (p = 0.04) MW protein, respectively, in patients with schizophrenia as compared with normal controls. Current neuroleptic treatment in patients with schizophrenia had no effect on CSF VASE concentrations. VASE concentration correlated significantly with behavioral ratings in patients with schizophrenia but not affective disorders. Thus, VASE immunoreactivity is increased in schizophrenia but not in affective disorders. These results provide further evidence of an abnormality of N-CAM protein in chronic schizophrenia and suggest differences between schizophrenia and affective disorders in regulation of N-CAM.
    MeSH term(s) Alternative Splicing/genetics ; Antibody Specificity/genetics ; Bipolar Disorder/diagnosis ; Blotting, Western ; Depressive Disorder/diagnosis ; Exons/genetics ; Humans ; Immune Sera ; Immunoproteins/cerebrospinal fluid ; Neural Cell Adhesion Molecules/cerebrospinal fluid ; Neural Cell Adhesion Molecules/genetics ; Protein Isoforms/cerebrospinal fluid ; Protein Isoforms/genetics ; Psychiatric Status Rating Scales ; Recombinant Fusion Proteins/cerebrospinal fluid ; Schizophrenia/cerebrospinal fluid ; Schizophrenia/diagnosis ; Schizophrenia/genetics
    Chemical Substances Immune Sera ; Immunoproteins ; Neural Cell Adhesion Molecules ; Protein Isoforms ; Recombinant Fusion Proteins
    Language English
    Publishing date 2000-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 3148-3
    ISSN 1879-1379 ; 0022-3956
    ISSN (online) 1879-1379
    ISSN 0022-3956
    DOI 10.1016/s0022-3956(99)00026-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Antibodies to the buried N terminus of rhinovirus VP4 exhibit cross-serotypic neutralization.

    Katpally, Umesh / Fu, Tong-Ming / Freed, Daniel C / Casimiro, Danilo R / Smith, Thomas J

    Journal of virology

    2009  Volume 83, Issue 14, Page(s) 7040–7048

    Abstract: ... and transiently displays the buried N termini of viral protein 1 (VP1) and VP4. Here, further evidence ... for this "breathing" phenomenon is presented, using antibodies to several peptides representing the N terminus of VP4 ... Furthermore, there is evidence that the N termini of VP4 are interacting with each other upon extrusion ...

    Abstract Development of a vaccine for the common cold has been thwarted by the fact that there are more than 100 serotypes of human rhinovirus (HRV). We previously demonstrated that the HRV14 capsid is dynamic and transiently displays the buried N termini of viral protein 1 (VP1) and VP4. Here, further evidence for this "breathing" phenomenon is presented, using antibodies to several peptides representing the N terminus of VP4. The antibodies form stable complexes with intact HRV14 virions and neutralize infectivity. Since this region of VP4 is highly conserved among all of the rhinoviruses, antiviral activity by these anti-VP4 antibodies is cross-serotypic. The antibodies inhibit HRV16 infectivity in a temperature- and time-dependent manner consistent with the breathing behavior. Monoclonal and polyclonal antibodies raised against the 30-residue peptide do not react with peptides shorter than 24 residues, suggesting that these peptides are adopting three-dimensional conformations that are highly dependent upon the length of the peptide. Furthermore, there is evidence that the N termini of VP4 are interacting with each other upon extrusion from the capsid. A Ser5Cys mutation in VP4 yields an infectious virus that forms cysteine cross-links in VP4 when the virus is incubated at room temperature but not at 4 degrees C. The fact that all of the VP4s are involved in this cross-linking process strongly suggests that VP4 forms specific oligomers upon extrusion. Together these results suggest that it may be possible to develop a pan-serotypic peptide vaccine to HRV, but its design will likely require details about the oligomeric structure of the exposed termini.
    MeSH term(s) Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Antibodies, Viral/immunology ; Capsid Proteins/chemistry ; Capsid Proteins/genetics ; Capsid Proteins/immunology ; Cell Line ; Cross Reactions ; Epitope Mapping ; Humans ; Molecular Sequence Data ; Neutralization Tests ; Picornaviridae Infections/immunology ; Picornaviridae Infections/virology ; Rabbits ; Rhinovirus/chemistry ; Rhinovirus/genetics ; Rhinovirus/immunology
    Chemical Substances Antibodies, Viral ; Capsid Proteins
    Language English
    Publishing date 2009-04-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.00557-09
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  7. Article ; Online: Evidence of a role for soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) machinery in HIV-1 assembly and release.

    Joshi, Anjali / Garg, Himanshu / Ablan, Sherimay D / Freed, Eric O

    The Journal of biological chemistry

    2011  Volume 286, Issue 34, Page(s) 29861–29871

    Abstract: ... The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins constitute ...

    Abstract Retrovirus assembly is a complex process that requires the orchestrated participation of viral components and host-cell factors. The concerted movement of different viral proteins to specific sites in the plasma membrane allows for virus particle assembly and ultimately budding and maturation of infectious virions. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins constitute the minimal machinery that catalyzes the fusion of intracellular vesicles with the plasma membrane, thus regulating protein trafficking. Using siRNA and dominant negative approaches we demonstrate here that generalized disruption of the host SNARE machinery results in a significant reduction in human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus particle production. Further analysis of the mechanism involved revealed a defect at the level of HIV-1 Gag localization to the plasma membrane. Our findings demonstrate for the first time a role of SNARE proteins in HIV-1 assembly and release, likely by affecting cellular trafficking pathways required for Gag transport and association with the plasma membrane.
    MeSH term(s) Biological Transport/genetics ; Cell Membrane/genetics ; Cell Membrane/metabolism ; HIV-1/physiology ; HeLa Cells ; Humans ; Infectious Anemia Virus, Equine/physiology ; SNARE Proteins/genetics ; SNARE Proteins/metabolism ; Virus Assembly/physiology ; Virus Release/physiology ; gag Gene Products, Human Immunodeficiency Virus/genetics ; gag Gene Products, Human Immunodeficiency Virus/metabolism
    Chemical Substances SNARE Proteins ; gag Gene Products, Human Immunodeficiency Virus
    Language English
    Publishing date 2011-06-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M111.241521
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Does the association between objective and subjective memory vary by age among healthy older adults?

    Freed, Sara A / Sprague, Briana N / Ross, Lesley A

    Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition

    2022  Volume 31, Issue 2, Page(s) 249–262

    Abstract: Subjective memory is commonly used as an indicator of older adults' objective memory in clinical screening; however, the correspondence between subjective and objective memory across different ages is unclear. The current study examined age-varying ... ...

    Abstract Subjective memory is commonly used as an indicator of older adults' objective memory in clinical screening; however, the correspondence between subjective and objective memory across different ages is unclear. The current study examined age-varying associations between subjective and objective memory in a cross-sectional sample of healthy older adults from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (
    MeSH term(s) Humans ; Aged ; Cross-Sectional Studies ; Health Status ; Memory Disorders/psychology
    Language English
    Publishing date 2022-11-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1482447-4
    ISSN 1744-4128 ; 1382-5585
    ISSN (online) 1744-4128
    ISSN 1382-5585
    DOI 10.1080/13825585.2022.2143471
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: N,N-dimethylglycine, betaine, and seizures.

    Freed, W J

    Archives of neurology

    1984  Volume 41, Issue 11, Page(s) 1129–1130

    MeSH term(s) Betaine/therapeutic use ; Epilepsy/drug therapy ; Glycine/analogs & derivatives ; Humans ; Sarcosine/analogs & derivatives ; Sarcosine/therapeutic use
    Chemical Substances Betaine (3SCV180C9W) ; dimethylglycine (7797M4CPPA) ; Glycine (TE7660XO1C) ; Sarcosine (Z711V88R5F)
    Language English
    Publishing date 1984-11
    Publishing country United States
    Document type Letter
    ZDB-ID 80049-1
    ISSN 1538-3687 ; 0003-9942
    ISSN (online) 1538-3687
    ISSN 0003-9942
    DOI 10.1001/archneur.1984.04050220023004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Data Processing and Germline Variant Calling with the Sentieon Pipeline.

    Aldana, Rafael / Freed, Donald

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2493, Page(s) 1–19

    Abstract: Public and private genomic sequencing initiatives generate ever-increasing amounts of genomic data creating a need for improved solutions for genomics data processing (Stephens et al.PLoS Biol 13:e1002195, 2015). The ... ...

    Abstract Public and private genomic sequencing initiatives generate ever-increasing amounts of genomic data creating a need for improved solutions for genomics data processing (Stephens et al.PLoS Biol 13:e1002195, 2015). The Sentieon
    MeSH term(s) Genomics/methods ; Germ Cells ; High-Throughput Nucleotide Sequencing/methods ; Software
    Language English
    Publishing date 2022-06-25
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2293-3_1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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