Age-associated sex difference in the expression of mitochondria-based redox sensitive proteins and effect of pioglitazone in nonhuman primate brain.

Background: Paraoxonase 2 (PON2) and neuronal uncoupling proteins (UCP4 and UCP5) possess antioxidant, anti-apoptotic activities and minimize accumulation of reactive oxygen species in mitochondria. While age and sex are risk factors for several disorders that are linked with oxidative stress, no study has explored the age- and sex-dependent expression of PON2 isoforms, UCP4 and UCP5 in primate brain or identified a drug to activate UCP4 and UCP5 in vivo. Preclinical studies suggest that the peroxisome proliferator-activated receptor gamma agonist, pioglitazone (PIO), can be neuroprotective, although the mechanism responsible is unclear.

"Essential One Day and Forgotten the Next": Perceptions of Ohio's Early Childhood Workforce on Their Exclusion from the Educator Phase of COVID-19 Vaccine Distribution.

This study explores Ohio Early Childhood and Care (ECEC) workers' perspectives about different prioritization for COVID-19 vaccine distribution between Ohio educators employed in ECEC and prek-12 settings. Days after Ohio's shutdown, ECEC programs began reopening for children of essential workers, and by June 2020 all ECEC programs could reopen with enhanced mitigation strategies, while the prek-12 workforce remained remote as they cautiously returned in-person ranging from 2 to 9 months later. Ohio was 1 of 4 states that, despite contrary Center for Disease Control guidance, excluded ECEC workers from the phase of vaccine distribution in which prek-12 workers were eligible.

Expression of PON2 isoforms varies among brain regions in male and female African green monkeys.

Mitochondrial dysfunction and oxidative stress contribute to the neuropathology of neurodegenerative disorders such as Parkinson's disease (PD). Paraoxonase-2 (PON2) is a mitochondrial protein that mitigates oxidative stress, enhances mitochondrial function and exhibits anti-inflammatory properties. Previously, we have documented sex-based variation in PON2 with higher brain PON2 expression in female (2-fold) as compared to male African green monkeys.

Pioglitazone transiently stimulates paraoxonase-2 expression in male nonhuman primate brain: Implications for sex-specific therapeutics in neurodegenerative disorders.

Paraoxonase-2 (PON2) enhances mitochondria function and protects against oxidative stress. Stimulating its expression has therapeutic potential for diseases where oxidative stress plays a significant role in the pathology, such as Parkinson's disease. Clinical and preclinical evidence suggest that the anti-diabetic drug pioglitazone may provide neuroprotection in Parkinson's disease, Alzheimer's disease, and stroke, but the biochemical pathway(s) responsible has not been fully elucidated.

Sex-based disparity in paraoxonase-2 expression in the brains of African green monkeys.

The development of several neurodegenerative disorders, such as Parkinson's disease, has been linked with decreased mitochondrial performance, leading to oxidative stress as a result of increased production of reactive oxygen species (ROS). Previous studies have established that the mitochondrial enzyme, paraoxonase-2 (PON2), possesses potent antioxidant and anti-inflammatory properties, with its expression linked with lower ROS levels. The aim of this study was to explore the sex-based variations in the protein level of PON2 in different brain regions (striatum, hippocampus, occipital cortex, and dorsolateral prefrontal cortex) of African green monkeys.

PPARγ/PGC1α signaling as a potential therapeutic target for mitochondrial biogenesis in neurodegenerative disorders.

Neurodegenerative diseases represent some of the most devastating neurological disorders, characterized by progressive loss of the structure and function of neurons. Current therapy for neurodegenerative disorders is limited to symptomatic treatment rather than disease modifying interventions, emphasizing the desperate need for improved approaches. Abundant evidence indicates that impaired mitochondrial function plays a crucial role in pathogenesis of many neurodegenerative diseases and so biochemical factors in mitochondria are considered promising targets for pharmacological-based therapies.

Pioglitazone activates paraoxonase-2 in the brain: A novel neuroprotective mechanism.

Paraoxonase-2 regulates reactive oxygen species production in mitochondria. Stimulating its expression has therapeutic potential for diseases where oxidative stress plays a significant role in the pathology. Evidence suggests that the anti-diabetic drug pioglitazone may provide neuroprotection in Parkinson's disease, Alzheimer's disease, brain trauma and ischemia, but the biochemical pathway(s) responsible has not been fully elucidated.

C-terminal phosphorylation of latrophilin-1/ADGRL1 affects the interaction between its fragments.

Latrophilin-1 is an adhesion G protein-coupled receptor that mediates the effect of α-latrotoxin, causing massive release of neurotransmitters from nerve terminals and endocrine cells. Autoproteolysis cleaves latrophilin-1 into two parts: the extracellular N-terminal fragment (NTF) and the heptahelical C-terminal fragment (CTF). NTF and CTF can exist as independent proteins in the plasma membrane, but α-latrotoxin binding to NTF induces their association and G protein-mediated signaling.

Paper-Based Magneto-Resistive Sensor: Modeling, Fabrication, Characterization, and Application.

In this work, we developed and fabricated a paper-based anisotropic magneto-resistive sensor using a sputtered permalloy (Ni 81 Fe 19 ) thin film. To interpret the characteristics of the sensor, we proposed a computational model to capture the influence of the stochastic fiber network of the paper surface and to explain the physics behind the empirically observed difference in paper-based anisotropic magneto-resistance (AMR). Using the model, we verified two main empirical observations: (1) The stochastic fiber network of the paper substrate induces a shift of 45 ∘ in the AMR response of the paper-based Ni 81 Fe 19 thin film compared to a Ni 81 Fe 19 film on a smooth surface as long as the fibrous topography has not become buried.

Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones.

A presynaptic adhesion G-protein-coupled receptor, latrophilin-1, and a postsynaptic transmembrane protein, Lasso/teneurin-2, are implicated in trans-synaptic interaction that contributes to synapse formation. Surprisingly, during neuronal development, a substantial proportion of Lasso is released into the intercellular space by regulated proteolysis, potentially precluding its function in synaptogenesis. We found that released Lasso binds to cell-surface latrophilin-1 on axonal growth cones.

Expression of functional neuronal receptor latrophilin 1 in human acute myeloid leukaemia cells.

Acute myeloid leukaemia (AML) is a blood cancer affecting cells of myeloid lineage. It is characterised by rapid growth of malignant leukocytes that accumulate in the bone marrow and suppress normal haematopoiesis. This systemic disease remains a serious medical burden worldwide.

Blood ordering from the operating room: turnaround time as a quality indicator.

Background: Quality indicators in transfusion medicine are necessary for patient safety and customer satisfaction. The turnaround time (TAT) of issuing red blood cells (RBCs) has emerged as a quality indicator but is not an established benchmark. We examined the TAT for issuing RBCs from the blood bank to the operating rooms (ORs) at Vanderbilt University Medical Center (VUMC) and Stanford University Medical Center (SUMC).

Conformational studies of N(3)-substituted [1,3,4]-oxadiazinan-2-ones.

Pseudoephedrine-based [1,3,4]-oxadiazinan-2-ones acylated at the N(3)-position with either acetyl (2a), propionyl (2b), or phenylacetyl (2c) substituents are known to undergo conformational changes that are observable by (13)C NMR spectroscopy. The conformational properties of new [1,3,4]-oxadiazinan-2-one derivatives 2d-k are examined by X-ray crystallography and variable-temperature (13)C NMR spectroscopy and further evaluated by semiempirical AM1 calculations. The collected data reveal that the conformational changes of the overall ring system are dependent upon the stereoelectronic factors of the N(3)-substituent.