Distribution of insulin in primate brain following nose-to-brain transport.

Introduction: Nose-to-brain (N2B) insulin delivery has potential for Alzheimer's disease (AD) therapy. However, clinical implementation has been challenging without methods to follow N2B delivery non-invasively. Positron emission tomography (PET) was applied to measure F-18-labeled insulin ([F]FB-insulin) from intranasal dosing to brain uptake in non-human primates following N2B delivery.

Comparisons of 3D printed materials for biomedical imaging applications.

In biomedical imaging, it is desirable that custom-made accessories for restraint, anesthesia, and monitoring can be easily cleaned and not interfere with the imaging quality or analyses. With the rise of 3D printing as a form of rapid prototyping or manufacturing for imaging tools and accessories, it is important to understand which printable materials are durable and not likely to interfere with imaging applications. Here, 15 3D printable materials were evaluated for radiodensity, optical properties, simulated wear, and capacity for repeated cleaning and disinfection.

Pb-214/Bi-214-TCMC-Trastuzumab inhibited growth of ovarian cancer in preclinical mouse models.

Better treatments for ovarian cancer are needed to eliminate residual peritoneal disease after initial debulking surgery. The present study evaluated Trastuzumab to deliver Pb-214/Bi-214 for targeted alpha therapy (TAT) for HER2-positive ovarian cancer in mouse models of residual disease. This study is the first report of TAT using a novel Radon-222 generator to produce short-lived Lead-214 (Pb-214, t = 26.

[C]Paraoxon: Radiosynthesis, Biodistribution and In Vivo Positron Emission Tomography Imaging in Rat.

Synthesis of the acetylcholinesterase inhibitor paraoxon (POX) as a carbon-11 positron emission tomography tracer ([C]POX) and profiling in live rats is reported. Naïve rats intravenously injected with [C]POX showed a rapid decrease in parent tracer to ∼1%, with an increase in radiolabeled serum proteins to 87% and red blood cells (RBCs) to 9%. Protein and RBC leveled over 60 minutes, reflecting covalent modification of proteins by [C]POX.

Polylactide Degradation Activates Immune Cells by Metabolic Reprogramming.

Polylactide (PLA) is the most widely utilized biopolymer in medicine. However, chronic inflammation and excessive fibrosis resulting from its degradation remain significant obstacles to extended clinical use. Immune cell activation has been correlated to the acidity of breakdown products, yet methods to neutralize the pH have not significantly reduced adverse responses.

Deep learning-enabled quantification of simultaneous PET/MRI for cell transplantation monitoring.

Current methods of imaging islet cell transplants for diabetes using magnetic resonance imaging (MRI) are limited by their low sensitivity. Simultaneous positron emission tomography (PET)/MRI has greater sensitivity and ability to visualize cell metabolism. However, this dual-modality tool currently faces two major challenges for monitoring cells.

An extracellular vesicle targeting ligand that binds to Arc proteins and facilitates Arc transport in vivo.

Communication between distant cells can be mediated by extracellular vesicles (EVs) that deliver proteins and RNAs to recipient cells. Little is known about how EVs are targeted to specific cell types. Here, we identify the cell-surface protein Stranded at second (Sas) as a targeting ligand for EVs.

Significant discordance between point of care BNP values obtained by the i-STAT and the Beckman DXI 800, causing confusion in patient management when both methods are used interchangeably by clinicians.

B-type natriuretic peptide (BNP) is used as a biomarker of heart failure. In our hospital point of care (POCT) BNP test is performed in EDTA whole blood using i-STAT (Abbott Laboratories, Abbott Park, IL, USA) and in the clinical laboratory using EDTA plasma and the DXI 800 analyzer (Beckman, Brea, CA, USA). We compared BNP values in 88 patients obtained by using the i-STAT followed by using the DXI 800.

Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models.

Intravascularly administered radiation therapy using beta (β-)-emitting radioisotopes has relied on either intravenously injected radiolabeled peptides that target cancer or radiolabeled microspheres that are trapped in the tumor following intra-arterial delivery. More recently, targeted intravenous radiopeptide therapies have explored the use of alpha (α)-particle emitting radioisotopes, but microspheres radiolabeled with α-particle emitters have not yet been studied. Here, FDA-approved macroaggregated albumin (MAA) particles were radiolabeled with Bismuth-212 (Bi-212-MAA) and evaluated using clonogenic and survival assays and using immune-competent mouse models of breast cancer.

Intra-Arterial Delivery of Radiopharmaceuticals in Oncology: Current Trends and the Future of Alpha-Particle Therapeutics.

A paradigm shift is underway in cancer diagnosis and therapy using radioactivity-based agents called radiopharmaceuticals. In the new strategy, diagnostic imaging measures the tumor uptake of radioactive agent "X" in a patient's specific cancer, and if uptake metrics are realized, the patient can be selected for therapy with radioactive agent "Y". The X and Y represent different radioisotopes that are optimized for each application.

Neural connectivity molecules best identify the heterogeneous clock and dopaminergic cell types in the adult brain.

Our recent single-cell sequencing of most adult circadian neurons indicated notable and unexpected heterogeneity. To address whether other populations are similar, we sequenced a large subset of adult brain dopaminergic neurons. Their gene expression heterogeneity is similar to that of clock neurons, i.

The Role of Extra-motor Networks in Upper Limb Motor Performance Post-stroke.

Background: Motor improvement post-stroke may happen even if resting state functional connectivity between the ipsilesional and contralesional components of the sensorimotor network is not fully recovered. Therefore, we investigated which extra-motor networks might support upper limb motor gains in response to treatment post-stroke.

Methods: Both resting state functional connectivity and upper limb capacity were measured prior to and after an 8-week intervention of task-specific training in 29 human participants [59.

Identification of orphan ligand-receptor relationships using a cell-based CRISPRa enrichment screening platform.

Secreted proteins, which include cytokines, hormones, and growth factors, are extracellular ligands that control key signaling pathways mediating cell-cell communication within and between tissues and organs. Many drugs target secreted ligands and their cell surface receptors. Still, there are hundreds of secreted human proteins that either have no identified receptors ('orphans') or are likely to act through cell surface receptors that have not yet been characterized.

Interferon-β Decreases the Hypermetabolic State of Red Blood Cells from Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is an inflammatory disease characterized by damage to the myelin sheath surrounding axons in the central nervous system. While the exact mechanism of this destruction is unknown, excess nitric oxide (NO) and adenosine triphosphate (ATP) have been measured in tissues and fluids obtained from people with MS. Here, incubation of interferon-beta (IFN-β), an MS drug with an unknown mechanism of action, with red blood cells (RBCs) obtained from people with MS provide evidence of a potential hypermetabolic state in the MS RBC that is decreased with IFN-β intervention.

Albumin Glycation Affects the Delivery of C-Peptide to the Red Blood Cells.

Serum albumin is a prominent plasma protein that becomes modified in hyperglycemic conditions. In a process known as glycation, these modifications can change the structure and function of proteins, which decrease ligand binding capabilities and alter the bioavailability of ligands. C-peptide is a molecule that binds to the red blood cell (RBC) and stimulates the release of adenosine triphosphate (ATP), which is known to participate in the regulation of blood flow.

Affinity requirements for control of synaptic targeting and neuronal cell survival by heterophilic IgSF cell adhesion molecules.

Neurons in the developing brain express many different cell adhesion molecules (CAMs) on their surfaces. CAM-binding affinities can vary by more than 200-fold, but the significance of these variations is unknown. Interactions between the immunoglobulin superfamily CAM DIP-α and its binding partners, Dpr10 and Dpr6, control synaptic targeting and survival of Drosophila optic lobe neurons.

Sticks and Stones, a conserved cell surface ligand for the Type IIa RPTP Lar, regulates neural circuit wiring in .

Type IIa receptor-like protein tyrosine phosphatases (RPTPs) are essential for neural development. They have cell adhesion molecule (CAM)-like extracellular domains that interact with cell-surface ligands and coreceptors. We identified the immunoglobulin superfamily CAM Sticks and Stones (Sns) as a new partner for the Type IIa RPTP Lar.

White matter integrity of contralesional and transcallosal tracts may predict response to upper limb task-specific training in chronic stroke.

Objective: To investigate white matter (WM) plasticity induced by intensive upper limb (UL) task specific training (TST) in chronic stroke.

Methods: Diffusion tensor imaging data and UL function measured by the Action Research Arm Test (ARAT) were collected in 30 individuals with chronic stroke prior to and after intensive TST. ANOVAs tested the effects of training on the entire sample and on the Responders [ΔARAT ≥ 5.

Neural mechanism of spatio-chromatic opponency in the Drosophila amacrine neurons.

Visual animals detect spatial variations of light intensity and wavelength composition. Opponent coding is a common strategy for reducing information redundancy. Neurons equipped with both spatial and spectral opponency have been identified in vertebrates but not yet in insects.

Investigation of neurons that express Dpr/DIP cell adhesion molecules.

reproductive behaviors are directed by neurons. A reanalysis of genomic studies shows that genes encoding and immunoglobulin superfamily (IgSF) members are expressed in neurons. We find that each and ( ∩ ) overlapping expression pattern is similar in both sexes, but there are dimorphisms in neuronal morphology and cell number.

Biological Distribution and Metabolic Profiles of Carbon-11 and Fluorine-18 Tracers of VX- and Sarin-Analogs in Sprague-Dawley Rats.

Organophosphorus esters (OPs) were originally developed as pesticides but were repurposed as easily manufactured, inexpensive, and highly toxic chemical warfare agents. Acute OP toxicity is primarily due to inhibition of acetylcholinesterase (AChE), an enzyme in the central and peripheral nervous system. OP inhibition of AChE can be reversed using oxime reactivators but many show poor CNS penetration, indicating a need for new clinically viable reactivators.

A C-peptide complex with albumin and Zn increases measurable GLUT1 levels in membranes of human red blood cells.

People with type 1 diabetes (T1D) require exogenous administration of insulin, which stimulates the translocation of the GLUT4 glucose transporter to cell membranes. However, most bloodstream cells contain GLUT1 and are not directly affected by insulin. Here, we report that C-peptide, the 31-amino acid peptide secreted in equal amounts with insulin in vivo, is part of a 3-component complex that affects red blood cell (RBC) membranes.

Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging.

Purpose: The development of molecularly targeted tracers is likely to improve the accuracy of diagnostic, screening, and therapeutic tools. Despite the many therapeutic antibodies that are FDA-approved with known toxicity, only a limited number of antibody-dye conjugates have been introduced to the clinic. Thorough evaluation of the safety, stability, and pharmacokinetics of antibody conjugates in the clinical setting compared with their parental components could accelerate the clinical approval of antibodies as agents for molecular imaging.

A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions.

Cell-surface protein-protein interactions (PPIs) mediate cell-cell communication, recognition, and responses. We executed an interactome screen of 564 human cell-surface and secreted proteins, most of which are immunoglobulin superfamily (IgSF) proteins, using a high-throughput, automated ELISA-based screening platform employing a pooled-protein strategy to test all 318,096 PPI combinations. Screen results, augmented by phylogenetic homology analysis, revealed ∼380 previously unreported PPIs.