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  1. Article ; Online: Dose response of running on blood biomarkers of wellness in generally healthy individuals.

    Nogal, Bartek / Vinogradova, Svetlana / Jorge, Milena / Torkamani, Ali / Fabian, Paul / Blander, Gil

    PloS one

    2023  Volume 18, Issue 11, Page(s) e0293631

    Abstract: Exercise is effective toward delaying or preventing chronic disease, with a large body of evidence supporting its effectiveness. However, less is known about the specific healthspan-promoting effects of exercise on blood biomarkers in the disease-free ... ...

    Abstract Exercise is effective toward delaying or preventing chronic disease, with a large body of evidence supporting its effectiveness. However, less is known about the specific healthspan-promoting effects of exercise on blood biomarkers in the disease-free population. In this work, we examine 23,237 generally healthy individuals who self-report varying weekly running volumes and compare them to 4,428 generally healthy sedentary individuals, as well as 82 professional endurance runners. We estimate the significance of differences among blood biomarkers for groups of increasing running levels using analysis of variance (ANOVA), adjusting for age, gender, and BMI. We attempt and add insight to our observational dataset analysis via two-sample Mendelian randomization (2S-MR) using large independent datasets. We find that self-reported running volume associates with biomarker signatures of improved wellness, with some serum markers apparently being principally modified by BMI, whereas others show a dose-effect with respect to running volume. We further detect hints of sexually dimorphic serum responses in oxygen transport and hormonal traits, and we also observe a tendency toward pronounced modifications in magnesium status in professional endurance athletes. Thus, our results further characterize blood biomarkers of exercise and metabolic health, particularly regarding dose-effect relationships, and better inform personalized advice for training and performance.
    MeSH term(s) Humans ; Running/physiology ; Exercise/physiology ; Athletes ; Biomarkers ; Physical Endurance
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-11-15
    Publishing country United States
    Document type Observational Study ; Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0293631
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Dose response of running on blood biomarkers of wellness in generally healthy individuals.

    Bartek Nogal / Svetlana Vinogradova / Milena Jorge / Ali Torkamani / Paul Fabian / Gil Blander

    PLoS ONE, Vol 18, Iss 11, p e

    2023  Volume 0293631

    Abstract: Exercise is effective toward delaying or preventing chronic disease, with a large body of evidence supporting its effectiveness. However, less is known about the specific healthspan-promoting effects of exercise on blood biomarkers in the disease-free ... ...

    Abstract Exercise is effective toward delaying or preventing chronic disease, with a large body of evidence supporting its effectiveness. However, less is known about the specific healthspan-promoting effects of exercise on blood biomarkers in the disease-free population. In this work, we examine 23,237 generally healthy individuals who self-report varying weekly running volumes and compare them to 4,428 generally healthy sedentary individuals, as well as 82 professional endurance runners. We estimate the significance of differences among blood biomarkers for groups of increasing running levels using analysis of variance (ANOVA), adjusting for age, gender, and BMI. We attempt and add insight to our observational dataset analysis via two-sample Mendelian randomization (2S-MR) using large independent datasets. We find that self-reported running volume associates with biomarker signatures of improved wellness, with some serum markers apparently being principally modified by BMI, whereas others show a dose-effect with respect to running volume. We further detect hints of sexually dimorphic serum responses in oxygen transport and hormonal traits, and we also observe a tendency toward pronounced modifications in magnesium status in professional endurance athletes. Thus, our results further characterize blood biomarkers of exercise and metabolic health, particularly regarding dose-effect relationships, and better inform personalized advice for training and performance.
    Keywords Medicine ; R ; Science ; Q
    Subject code 796
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Gut Microbiota-Informed Precision Nutrition in the Generally Healthy Individual: Are We There Yet?

    Nogal, Bartek / Blumberg, Jeffrey B / Blander, Gil / Jorge, Milena

    Current developments in nutrition

    2021  Volume 5, Issue 9, Page(s) nzab107

    Abstract: Since next generation sequencing facilitated high-throughput and cost-efficient genomics analyses, the human gut metagenome has become an emerging frontier to explore toward precision nutrition. Significant progress has been made in identifying gut ... ...

    Abstract Since next generation sequencing facilitated high-throughput and cost-efficient genomics analyses, the human gut metagenome has become an emerging frontier to explore toward precision nutrition. Significant progress has been made in identifying gut microbial features associated with a wide spectrum of human disease. However, other than a few microbiome-disease relations, there is a dearth of confirmed causal inferences, particularly in generally healthy populations. The relatively high unexplained variability in microbiome compositions in this group warrants caution in applying this complex biomarker toward precision nutrition, because our understanding of what constitutes a healthy microbiome is still rudimentary. Although gut microbiota harbor integrated environmental and host-specific information with the potential to facilitate personalized nutritional and lifestyle advice, these data cannot yet be confidently interpreted toward precise recommendations. Thus, nutritional advice for generally healthy individuals based on personal microbiome composition analysis might not yet be appropriate unless accompanied by established blood and physiological biomarkers.
    Language English
    Publishing date 2021-08-09
    Publishing country United States
    Document type Journal Article
    ISSN 2475-2991
    ISSN (online) 2475-2991
    DOI 10.1093/cdn/nzab107
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Effect of Heat Stress, Dietary Electrolytes, and Vitamins E and C on Growth Performance and Blood Biochemistry of the Broiler Chicken

    Matthew L. Livingston / Anthony Pokoo-Aikins / Thomas Frost / Lisa Laprade / Vy Hoang / Bartek Nogal / Chelsea Phillips / Aaron J. Cowieson

    Frontiers in Animal Science, Vol

    2022  Volume 3

    Abstract: Environmental heat stress creates a detriment to the welfare and performance in broiler chickens. While there are some dietary mineral and vitamin supplements that mitigate this condition, a rapid, plasma-based detection method would improve management ... ...

    Abstract Environmental heat stress creates a detriment to the welfare and performance in broiler chickens. While there are some dietary mineral and vitamin supplements that mitigate this condition, a rapid, plasma-based detection method would improve management response and broaden the scientific understanding of heat stress. A total of 960 broilers were used to determine the effect of heat stress and dietary electrolyte balance on blood biochemistry. Sex sorted chicks were allocated to 48 pens with 20 chicks per pen creating 6 treatments (3 diets x 2 house environments) with eight replicates and fed one of three dietary treatments: a control containing primarily sodium chloride (NaCl), a heat stress formulation containing bicarbonate (NaHCO3), or heat stress fortified with 200 ppm vitamin C and E (NaHCO3 Fortified). Birds were housed in two different temperature-controlled environments either a thermoneutral (Control) or heat stressed (Heat Stress) environment. At day 28, 35 and 42 venous blood was collected and analyzed using rapid detection methods followed by post-mortem veterinary evaluations. Performance was measured at weekly intervals. Mortality was significantly higher in broilers exposed to heat stress as compared to thermoneutral, while broilers that received dietary sodium chloride also had higher mortality than bicarbonate fed birds. Heat stress significantly impacted potassium, hematocrit, uric acid, total protein, globulin, hematocrit, lymphocytes, sodium, and glucose. This study demonstrates that blood biochemistry of broiler chickens is influenced by dietary intervention and changing environmental conditions. This pattern suggests a blood biomarker footprint of sub-optimal nutrition or poor environmental conditions that may provide valuable information into physiological changes in response to dietary electrolytes, vitamins, and heat stress. Furthermore, this footprint may potentiate the development of diagnostic tools, combining biomarkers to determine nutrition and health status of individual broiler ...
    Keywords broiler ; biomarker ; blood physiology ; heat stress ; vitamins ; sodium bicarbonate ; Veterinary medicine ; SF600-1100
    Subject code 630
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Time-course, negative-stain electron microscopy-based analysis for investigating protein-protein interactions at the single-molecule level.

    Nogal, Bartek / Bowman, Charles A / Ward, Andrew B

    The Journal of biological chemistry

    2017  Volume 292, Issue 47, Page(s) 19400–19410

    Abstract: Several biophysical approaches are available to study protein-protein interactions. Most approaches are conducted in bulk solution, and are therefore limited to an average measurement of the ensemble of molecular interactions. Here, we show how single- ... ...

    Abstract Several biophysical approaches are available to study protein-protein interactions. Most approaches are conducted in bulk solution, and are therefore limited to an average measurement of the ensemble of molecular interactions. Here, we show how single-particle EM can enrich our understanding of protein-protein interactions at the single-molecule level and potentially capture states that are unobservable with ensemble methods because they are below the limit of detection or not conducted on an appropriate time scale. Using the HIV-1 envelope glycoprotein (Env) and its interaction with receptor CD4-binding site neutralizing antibodies as a model system, we both corroborate ensemble kinetics-derived parameters and demonstrate how time-course EM can further dissect stoichiometric states of complexes that are not readily observable with other methods. Visualization of the kinetics and stoichiometry of Env-antibody complexes demonstrated the applicability of our approach to qualitatively and semi-quantitatively differentiate two highly similar neutralizing antibodies. Furthermore, implementation of machine-learning techniques for sorting class averages of these complexes into discrete subclasses of particles helped reduce human bias. Our data provide proof of concept that single-particle EM can be used to generate a "visual" kinetic profile that should be amenable to studying many other protein-protein interactions, is relatively simple and complementary to well-established biophysical approaches. Moreover, our method provides critical insights into broadly neutralizing antibody recognition of Env, which may inform vaccine immunogen design and immunotherapeutic development.
    MeSH term(s) Antibodies, Monoclonal ; Antibodies, Neutralizing/chemistry ; Antibodies, Neutralizing/metabolism ; CD4 Antigens/immunology ; CD4 Antigens/metabolism ; HIV Antibodies/chemistry ; HIV Antibodies/metabolism ; Humans ; Image Processing, Computer-Assisted ; Macromolecular Substances/ultrastructure ; Microscopy, Electron ; Protein Binding ; Protein Conformation ; Protein Interaction Domains and Motifs ; env Gene Products, Human Immunodeficiency Virus/chemistry ; env Gene Products, Human Immunodeficiency Virus/metabolism
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Neutralizing ; CD4 Antigens ; HIV Antibodies ; Macromolecular Substances ; env Gene Products, Human Immunodeficiency Virus
    Language English
    Publishing date 2017-09-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M117.808352
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Focusing antibody responses to the fusion peptide in rhesus macaques.

    Cottrell, Christopher A / Pratap, Payal P / Cirelli, Kimberly M / Carnathan, Diane G / Enemuo, Chiamaka A / Antanasijevic, Aleksandar / Ozorowski, Gabriel / Sewall, Leigh M / Gao, Hongmei / Greene, Kelli M / Allen, Joel D / Ngo, Julia T / Choe, Yury / Nogal, Bartek / Silva, Murillo / Bhiman, Jinal / Pauthner, Matthias / Irvine, Darrell J / Montefiori, David /
    Crispin, Max / Burton, Dennis R / Silvestri, Guido / Crotty, Shane / Ward, Andrew B

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an ... ...

    Abstract Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to elicit immune responses against the conserved fusion peptide. Antibody specificities and GC responses were tracked longitudinally using electron microscopy polyclonal epitope mapping (EMPEM) and lymph node fine-needle aspirates, respectively. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.
    Language English
    Publishing date 2023-06-27
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.06.26.545779
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: From structure to sequence: Antibody discovery using cryoEM.

    Antanasijevic, Aleksandar / Bowman, Charles A / Kirchdoerfer, Robert N / Cottrell, Christopher A / Ozorowski, Gabriel / Upadhyay, Amit A / Cirelli, Kimberly M / Carnathan, Diane G / Enemuo, Chiamaka A / Sewall, Leigh M / Nogal, Bartek / Zhao, Fangzhu / Groschel, Bettina / Schief, William R / Sok, Devin / Silvestri, Guido / Crotty, Shane / Bosinger, Steven E / Ward, Andrew B

    Science advances

    2022  Volume 8, Issue 3, Page(s) eabk2039

    Abstract: One of the rate-limiting steps in analyzing immune responses to vaccines or infections is the isolation and characterization of monoclonal antibodies. Here, we present a hybrid structural and bioinformatic approach to directly assign the heavy and light ... ...

    Abstract One of the rate-limiting steps in analyzing immune responses to vaccines or infections is the isolation and characterization of monoclonal antibodies. Here, we present a hybrid structural and bioinformatic approach to directly assign the heavy and light chains, identify complementarity-determining regions, and discover sequences from cryoEM density maps of serum-derived polyclonal antibodies bound to an antigen. When combined with next-generation sequencing of immune repertoires, we were able to specifically identify clonal family members, synthesize the monoclonal antibodies, and confirm that they interact with the antigen in a manner equivalent to the corresponding polyclonal antibodies. This structure-based approach for identification of monoclonal antibodies from polyclonal sera opens new avenues for analysis of immune responses and iterative vaccine design.
    Language English
    Publishing date 2022-01-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abk2039
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Mapping Polyclonal Antibody Responses in Non-human Primates Vaccinated with HIV Env Trimer Subunit Vaccines.

    Nogal, Bartek / Bianchi, Matteo / Cottrell, Christopher A / Kirchdoerfer, Robert N / Sewall, Leigh M / Turner, Hannah L / Zhao, Fangzhu / Sok, Devin / Burton, Dennis R / Hangartner, Lars / Ward, Andrew B

    Cell reports

    2020  Volume 30, Issue 11, Page(s) 3755–3765.e7

    Abstract: Rational immunogen design aims to focus antibody responses to vulnerable sites on primary antigens. Given the size of these antigens, there is, however, potential for eliciting unwanted, off-target responses. Here, we use our electron microscopy ... ...

    Abstract Rational immunogen design aims to focus antibody responses to vulnerable sites on primary antigens. Given the size of these antigens, there is, however, potential for eliciting unwanted, off-target responses. Here, we use our electron microscopy polyclonal epitope mapping approach to describe the antibody specificities elicited by immunization of non-human primates with soluble HIV envelope trimers and subsequent repeated viral challenge. An increased diversity of epitopes recognized and the approach angle by which these antibodies bind constitute a hallmark of the humoral response in most protected animals. We also show that fusion peptide-specific antibodies are likely responsible for some neutralization breadth. Moreover, cryoelectron microscopy (cryo-EM) analysis of a fully protected animal reveals a high degree of clonality within a subset of putatively neutralizing antibodies, enabling a detailed molecular description of the antibody paratope. Our results provide important insights into the immune response against a vaccine candidate that entered into clinical trials in 2019.
    MeSH term(s) Animals ; Antibodies, Neutralizing/immunology ; Antibody Formation/immunology ; Cross Reactions/immunology ; Cryoelectron Microscopy ; Epitopes/chemistry ; Epitopes/immunology ; HEK293 Cells ; HIV Antibodies/chemistry ; HIV Antibodies/immunology ; Humans ; Immunity, Humoral ; Macaca mulatta ; Models, Molecular ; Protein Multimerization ; Vaccination ; Vaccines, Subunit/immunology ; env Gene Products, Human Immunodeficiency Virus/immunology
    Chemical Substances Antibodies, Neutralizing ; Epitopes ; HIV Antibodies ; Vaccines, Subunit ; env Gene Products, Human Immunodeficiency Virus
    Language English
    Publishing date 2020-03-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2020.02.061
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Select host cell proteins coelute with monoclonal antibodies in protein A chromatography.

    Nogal, Bartek / Chhiba, Krishan / Emery, Jefferson C

    Biotechnology progress

    2012  Volume 28, Issue 2, Page(s) 454–458

    Abstract: The most significant factor contributing to the presence of host cell protein (HCP) impurities in Protein A chromatography eluates is their association with the product monoclonal antibodies (mAbs) has been reported previously, and it has been suggested ... ...

    Abstract The most significant factor contributing to the presence of host cell protein (HCP) impurities in Protein A chromatography eluates is their association with the product monoclonal antibodies (mAbs) has been reported previously, and it has been suggested that more efficacious column washes may be developed by targeting the disruption of the mAbs-HCP interaction. However, characterization of this interaction is not straight forward as it is likely to involve multiple proteins and/or types of interaction. This work is an attempt to begin to understand the contribution of HCP subpopulations and/or mAb interaction propensity to the variability in HCP levels in the Protein A eluate. We performed a flowthrough (FT) recycling study with product respiking using two antibody molecules of apparently different HCP interaction propensities. In each case, the ELISA assay showed depletion of select subpopulations of HCP in Protein A eluates in subsequent column runs, while the feedstock HCP in the FTs remained unchanged from its native harvested cell culture fluid (HCCF) levels. In a separate study, the final FT from each molecule's recycling study was cross-spiked with various mAbs. In this case, Protein A eluate levels remained low for all but two molecules which were known as having high apparent HCP interaction propensity. The results of these studies suggest that mAbs may preferentially bind to select subsets of HCPs, and the degree of interaction and/or identity of the associated HCPs may vary depending on the mAb.
    MeSH term(s) Animals ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/isolation & purification ; CHO Cells ; Chromatography, Affinity ; Cricetinae ; Immunoglobulin G/chemistry ; Immunoglobulin G/isolation & purification ; Protein Binding ; Proteins/chemistry ; Proteins/isolation & purification ; Staphylococcal Protein A/chemistry
    Chemical Substances Antibodies, Monoclonal ; Immunoglobulin G ; Proteins ; Staphylococcal Protein A
    Language English
    Publishing date 2012-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 165657-0
    ISSN 1520-6033 ; 8756-7938
    ISSN (online) 1520-6033
    ISSN 8756-7938
    DOI 10.1002/btpr.1514
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Publisher Correction: Longitudinal analysis of biomarker data from a personalized nutrition platform in healthy subjects.

    Westerman, Kenneth / Reaver, Ashley / Roy, Catherine / Ploch, Margaret / Sharoni, Erin / Nogal, Bartek / Sinclair, David A / Katz, David L / Blumberg, Jeffrey B / Blander, Gil

    Scientific reports

    2018  Volume 8, Issue 1, Page(s) 16778

    Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ...

    Abstract A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
    Language English
    Publishing date 2018-11-08
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-35249-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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