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Article: PET Imaging of the Serotonin 1A Receptor in Major Depressive Disorder: Hierarchical Multivariate Analysis of [

Matheson, Granville J / Zanderigo, Francesca / Miller, Jeffrey M / Bartlett, Elizabeth A / Mann, J John / Ogden, R Todd

bioRxiv : the preprint server for biology

2024

Abstract: The serotonin 1A receptor has been linked to both the pathophysiology of major depressive disorder (MDD) and the antidepressant action of serotonin reuptake inhibitors. Most PET studies of the serotonin 1A receptor in MDD used the receptor antagonist ... ...

Abstract	The serotonin 1A receptor has been linked to both the pathophysiology of major depressive disorder (MDD) and the antidepressant action of serotonin reuptake inhibitors. Most PET studies of the serotonin 1A receptor in MDD used the receptor antagonist radioligand, [carbonyl-
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.12.584569
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Article ; Online: Dynamic Human Brain Imaging with a Portable PET Camera: Comparison to a Standard Scanner.

Bartlett, Elizabeth A / Lesanpezeshki, Mohammad / Anishchenko, Sergey / Shkolnik, Ilia / Ogden, R Todd / Mann, J John / Beylin, David / Miller, Jeffrey M / Zanderigo, Francesca

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2024 Volume 65, Issue 2, Page(s) 320–326

Abstract: Portable, cost-effective PET cameras can radically expand the applicability of PET. We present here a within-participant comparison of fully quantified [ ...

Abstract	Portable, cost-effective PET cameras can radically expand the applicability of PET. We present here a within-participant comparison of fully quantified [
MeSH term(s)	Humans ; Fluorodeoxyglucose F18 ; Glucose/metabolism ; Neocortex/metabolism ; Positron-Emission Tomography/methods ; Neuroimaging
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.122.265309
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Zs.MO 328: Show issues

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Article ; Online: A phase II randomized, placebo-controlled, multicenter trial to evaluate the efficacy of cytomegalovirus PepVax vaccine in preventing cytomegalovirus reactivation and disease after allogeneic hematopoietic stem cell transplant.

Haematologica

2024

Abstract: Not available. ...

Abstract	Not available.
Language	English
Publishing date	2024-02-08
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.284544
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Article: Dysregulation of Amino Acid Transporters in a Rat Model of TLR7-Mediated Maternal Immune Activation.

McColl, Eliza R / Henderson, Jeffrey T / Piquette-Miller, Micheline

Pharmaceutics

2023 Volume 15, Issue 7

Abstract: Maternal immune activation (MIA) during pregnancy is linked to neurodevelopmental disorders in humans. Similarly, the TLR7 agonist imiquimod alters neurodevelopment in rodents. While the mechanisms underlying MIA-mediated neurodevelopmental changes are ... ...

Abstract	Maternal immune activation (MIA) during pregnancy is linked to neurodevelopmental disorders in humans. Similarly, the TLR7 agonist imiquimod alters neurodevelopment in rodents. While the mechanisms underlying MIA-mediated neurodevelopmental changes are unknown, they could involve dysregulation of amino acid transporters essential for neurodevelopment. Therefore, we sought to determine the nature of such transporter changes in both imiquimod-treated rats and human placentas during infection. Pregnant rats received imiquimod on gestational day (GD)14. Transporter expression was measured in placentas and fetal brains via qPCR (GD14.5) and immunoblotting (GD16). To monitor function, fetal brain amino acid levels were measured by HPLC on GD16. Gene expression in the cortex of female fetal brains was further examined by RNAseq on GD19. In human placentas, suspected active infection was associated with decreased ASCT1 and SNAT2 protein expression. Similarly, in imiquimod-treated rats, ASCT1 and SNAT2 protein was also decreased in male placentas, while EAAT2 was decreased in female placentas. CAT3 was increased in female fetal brains. Consistent with this, imiquimod altered amino acid levels in fetal brains, while RNAseq demonstrated changes in expression of several genes implicated in autism. Thus, imiquimod alters amino acid transporter levels in pregnant rats, and similar changes occur in human placentas during active infection. This suggests that changes in expression of amino acid transporters may contribute to effects mediated by MIA toward altered neurodevelopment.
Language	English
Publishing date	2023-07-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15071857
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Article: Protein supersaturation powers innate immune signaling.

Gama, Alejandro Rodriguez / Miller, Tayla / Venkatesan, Shriram / Lange, Jeffrey J / Wu, Jianzheng / Song, Xiaoqing / Bradford, Dan / Unruh, Jay R / Halfmann, Randal

bioRxiv : the preprint server for biology

2024

Abstract: Innate immunity protects us in youth but turns against us as we age. The reason for this tradeoff is unclear. Seeking a thermodynamic basis, we focused on death fold domains (DFDs), whose ordered polymerization has been stoichiometrically linked to ... ...

Abstract	Innate immunity protects us in youth but turns against us as we age. The reason for this tradeoff is unclear. Seeking a thermodynamic basis, we focused on death fold domains (DFDs), whose ordered polymerization has been stoichiometrically linked to innate immune signal amplification. We hypothesized that soluble ensembles of DFDs function as phase change batteries that store energy via supersaturation and subsequently release it through nucleated polymerization. Using imaging and FRET-based cytometry to characterize the phase behaviors of all 109 human DFDs, we found that the hubs of innate immune signaling networks encode large nucleation barriers that are intrinsically insulated from cross-pathway activation. We showed via optogenetics that supersaturation drives signal amplification and that the inflammasome is constitutively supersaturated
Language	English
Publishing date	2024-03-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.20.533581
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Article ; Online: Effects of Reduced Dietary Sodium and the DASH Diet on GFR: The DASH-Sodium Trial.

Morales-Alvarez, Martha Catalina / Nissaisorakarn, Voravech / Appel, Lawrence J / Miller, Edgar R / Christenson, Robert H / Rebuck, Heather / Rosas, Sylvia E / William, Jeffrey H / Juraschek, Stephen P

Kidney360

2024 Volume 5, Issue 4, Page(s) 569–576

MeSH term(s)	Humans ; Glomerular Filtration Rate ; Diet, Sodium-Restricted ; Sodium, Dietary/administration & dosage ; Hypertension/diet therapy
Chemical Substances	Sodium, Dietary
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ISSN	2641-7650
ISSN (online)	2641-7650
DOI	10.34067/KID.0000000000000390
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Article ; Online: NK Cells from Human Cytomegalovirus-Seropositive Individuals Have a Distinct Metabolic Profile That Correlates with Elevated mTOR Signaling.

Lozada, John R / Zhang, Bin / Miller, Jeffrey S / Cichocki, Frank

Journal of immunology (Baltimore, Md. : 1950)

2023 Volume 211, Issue 4, Page(s) 539–550

Abstract: CMV can elicit adaptive immune features in both mouse and human NK cells. Mouse Ly49H+ NK cells expand 100- to 1000-fold in response to mouse CMV infection and persist for months after exposure. Human NKG2C+ NK cells also expand after human CMV (HCMV) ... ...

Abstract	CMV can elicit adaptive immune features in both mouse and human NK cells. Mouse Ly49H+ NK cells expand 100- to 1000-fold in response to mouse CMV infection and persist for months after exposure. Human NKG2C+ NK cells also expand after human CMV (HCMV) infection and persist for months. The clonal expansion of adaptive NK cells is likely an energy-intensive process, and the metabolic requirements that support adaptive NK cell expansion and persistence remain largely uncharacterized. We previously reported that NK cells from HCMV-seropositive donors had increased maximum capacity for both glycolysis and mitochondrial oxidative phosphorylation relative to NK cells from HCMV-seronegative donors. In this article, we report an extension of this work in which we analyzed the metabolomes of NK cells from HCMV-seropositive donors with NKG2C+ expansions and NK cells from HCMV seronegative donors without such expansions. NK cells from HCMV+ donors exhibited striking elevations in purine and pyrimidine deoxyribonucleotides, along with moderate increases in plasma membrane components. Mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that, as a part of mTOR complex 1 (mTORC1), bridges nutrient signaling to metabolic processes necessary for cell growth. Signaling through mTORC1 induces both nucleotide and lipid synthesis. We observed elevated mTORC1 signaling on activation in both NKG2C- and NKG2C+ NK cells from HCMV+ donors relative to those from HCMV- donors, demonstrating a correlation between higher mTORC1 activity and synthesis of key metabolites for cell growth and division.
MeSH term(s)	Humans ; Animals ; Mice ; Cytomegalovirus ; Cytomegalovirus Infections ; Killer Cells, Natural ; TOR Serine-Threonine Kinases/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Metabolome ; NK Cell Lectin-Like Receptor Subfamily C/metabolism
Chemical Substances	TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; NK Cell Lectin-Like Receptor Subfamily C
Language	English
Publishing date	2023-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2200851
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Zs.MG 28: Show issues

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Article ; Online: Challenges to the broad application of allogeneic natural killer cell immunotherapy of cancer.

Kennedy, Philippa R / Felices, Martin / Miller, Jeffrey S

Stem cell research & therapy

2022 Volume 13, Issue 1, Page(s) 165

Abstract: Natural killer (NK) cells are innate immune cells that recognize malignant cells through a wide array of germline-encoded receptors. Triggering of activating receptors results in cytotoxicity and broad immune system activation. The former is achieved ... ...

Abstract	Natural killer (NK) cells are innate immune cells that recognize malignant cells through a wide array of germline-encoded receptors. Triggering of activating receptors results in cytotoxicity and broad immune system activation. The former is achieved through release of cytotoxic granules and presentation of death receptor ligands, while the latter is mediated by inflammatory cytokines, such as interferon-γ and tumor necrosis factor α. Early success with ex vivo activation of NK cells and adoptive transfer suggest they are a safe therapeutic with promising responses in advanced hematologic malignancies. In particular, adoptive NK cell therapies can serve as a 'bridge' to potentially curative allogeneic stem cell transplantation. In addition, strategies are being developed that expand large numbers of cells from limited starting material and mature NK cells from precursors. Together, these make 'off-the-shelf' NK cells possible to treat a wide range of cancers. Research efforts have focused on creating a range of tools that increase targeting of therapeutic NK cells toward cancer-from therapeutic antibodies that drive antibody-dependent cellular cytotoxicity, to chimeric antigen receptors. As these novel therapies start to show promise in clinical trials, the field is rapidly moving toward addressing other challenges that limit NK cell therapeutics and the goal to treat solid tumors. This review describes the state of therapeutic NK cell targeting of tumors; discusses the challenges that need to be addressed before NK cells can be applied as a wide-ranging treatment for cancer; and points to some of the innovations that are being developed to surmount these challenges. Suppressive cells in the tumor microenvironment pose a direct threat to therapeutic NK cells, through presentation of inhibitory ligands and secretion of suppressive cytokines and metabolites. The nutrient- and oxygen-starved conditions under which NK cells must function necessitate an understanding of therapeutic NK cell metabolism that is still emerging. Prior to these challenges, NK cells must find their way into and persist in the tumor itself. Finally, the desirability of a 'single-shot' NK cell treatment and the problems and benefits of a short-lived rejection-prone NK cellular product are discussed.
MeSH term(s)	Cytokines ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy/methods ; Immunotherapy, Adoptive/methods ; Killer Cells, Natural ; Ligands ; Neoplasms/therapy ; Tumor Microenvironment
Chemical Substances	Cytokines ; Ligands
Language	English
Publishing date	2022-04-12
Publishing country	England
Document type	Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-022-02769-4
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Article ; Online: Guidance on Which Calibrators in a Metrologically Traceable Calibration Hierarchy Must Be Commutable with Clinical Samples.

Miller, W Greg / Greenberg, Neil / Panteghini, Mauro / Budd, Jeffrey R / Johansen, Jesper V

Clinical chemistry

2023 Volume 69, Issue 3, Page(s) 228–238

Abstract: Equivalent results for the same measurand in clinical samples (CSs), measured using different end-user in-vitro diagnostic medical devices (IVD-MDs), are essential for the application of clinical practice guidelines for diagnosis, treatment, monitoring, ... ...

Abstract	Equivalent results for the same measurand in clinical samples (CSs), measured using different end-user in-vitro diagnostic medical devices (IVD-MDs), are essential for the application of clinical practice guidelines for diagnosis, treatment, monitoring, or risk assessment. The International Organization for Standardization (ISO) document 17511:2020 specifies how to establish metrological traceability to the highest available reference system component to enable equivalent results among IVD-MDs. Commutability with CSs is an essential property of a reference material used as a calibrator in a calibration hierarchy. However, not all calibrators in a calibration hierarchy are required to be commutable; different calibration hierarchies have different requirements for which calibrators must be commutable with CSs. Because assessment of commutability is a substantial effort, it is therefore important to determine which calibrators need to be commutable when implementing a calibration hierarchy. We provide guidance on which calibrators must be commutable with CSs, when a correction for any noncommutability bias is appropriate, and when commutability of a calibrator with CSs is not required for various types of calibration hierarchies described in ISO 17511:2020.
MeSH term(s)	Humans ; Calibration ; Reference Standards
Language	English
Publishing date	2023-01-16
Publishing country	England
Document type	Journal Article
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1093/clinchem/hvac226
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Article ; Online: Fascial plane approach to anesthetizing the radial, median, and ulnar nerves: an educational review.

Moody, Alastair E / Miller, Sarah T / Tupinio, Maegan R / Newberry, Cynthia M / Mangleson, John / Swenson, Jeffrey D

Regional anesthesia and pain medicine

2024 Volume 49, Issue 4, Page(s) 285–288

Abstract: Brachial plexus block provides effective anesthesia and analgesia for upper extremity surgery but requires injection of large anesthetic volumes near major vascular structures. Moreover, the extensive motor and sensory loss produced by plexus block often ...

Abstract	Brachial plexus block provides effective anesthesia and analgesia for upper extremity surgery but requires injection of large anesthetic volumes near major vascular structures. Moreover, the extensive motor and sensory loss produced by plexus block often exceeds the neural distribution needed for corresponding surgical procedures.High-resolution ultrasound facilitates selective nerve blocks at nearly every level of the upper extremity. We present fascial plane injection techniques for selective radial, median, and ulnar nerve blocks. These techniques can be used to match sensory distribution with specific surgical procedures. They are performed using low anesthetic volumes and without proximity to nerves or vascular structures. In this article, fresh cadaver dissections with corresponding ultrasound images are used to demonstrate stepwise fascial plane techniques for the radial, median, and ulnar nerves. These techniques are performed using familiar anatomic landmarks.Practical applications of these techniques are demonstrated for commonly performed procedures of the upper extremity. Corresponding injection volumes with duration of postoperative analgesia are presented. Selected injections are described for both surgical anesthesia and postoperative analgesia.Selective fascial plane injections can provide surgical anesthesia and postoperative analgesia in settings that might otherwise require much larger volumes of local anesthetic. These selective nerve blocks can match sensory loss with the anatomic pain distribution in each patient. Reliable techniques for selective nerve blocks of the upper extremity can expand the capabilities for ultrasound-guided regional anesthesia.
MeSH term(s)	Humans ; Anesthetics, Local ; Brachial Plexus/diagnostic imaging ; Brachial Plexus Block/methods ; Ulnar Nerve/diagnostic imaging ; Ultrasonography, Interventional/methods ; Upper Extremity/surgery
Chemical Substances	Anesthetics, Local
Language	English
Publishing date	2024-04-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1425299-5
ISSN	1532-8651 ; 1098-7339 ; 0146-521X
ISSN (online)	1532-8651
ISSN	1098-7339 ; 0146-521X
DOI	10.1136/rapm-2023-104794
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