History of Previous Midlife Estradiol Treatment Permanently Alters Interactions of Brain Insulin-like Growth Factor-1 Signaling and Hippocampal Estrogen Synthesis to Enhance Cognitive Aging in a Rat Model of Menopause.

Across species, including humans, elevated levels of brain estrogen receptor (ER) α are associated with enhanced cognitive aging, even in the absence of circulating estrogens. In rodents, short-term estrogen treatment, such as that commonly used in the menopausal transition, results in long-term increases in ERα levels in the hippocampus, leading to enhanced memory long after termination of estrogen treatment. However, mechanisms by which increased levels of brain ERα enhances cognitive aging remain unclear.

Trace gas analysis with laser dispersion spectroscopy.

Trace gas analysis provides a wide range of insights into environmental processes, particularly with regards to global warming and air quality. With the urgent need to identify sources and accurately measure the harmful emissions negatively impacting our planet, Laser Dispersion Spectroscopy (LDS) offers a unique approach. LDS technology measures optical molecular dispersion via a differential phase measurement of light and, operating in the mid-infrared, provides highly sensitive and robust measurements.

Age Impacts the Burden That Reference Memory Imparts on an Increasing Working Memory Load and Modifies Relationships With Cholinergic Activity.

Rodent aging research often utilizes spatial mazes, such as the water radial-arm-maze (WRAM), to evaluate cognition. The WRAM can simultaneously measure spatial working and reference memory, wherein these two memory types are often represented as orthogonal. There is evidence, however, that these two memory forms yield interference at a high working memory load.

Inhibition of Estrogen Sulfotransferase (/EST) Ameliorates Ischemic Acute Kidney Injury in Mice.

Background: Studies have suggested that estrogens may protect mice from AKI. Estrogen sulfotransferase (, or EST) plays an important role in estrogen homeostasis by sulfonating and deactivating estrogens, but studies on the role of in AKI are lacking.

Methods: We used the renal ischemia-reperfusion model to investigate the role of in AKI.

Hepatic Estrogen Sulfotransferase Distantly Sensitizes Mice to Hemorrhagic Shock-Induced Acute Lung Injury.

Hemorrhagic shock (HS) is a potential life-threatening condition that may lead to injury to multiple organs, including the lung. The estrogen sulfotransferase (EST, or SULT1E1) is a conjugating enzyme that sulfonates and deactivates estrogens. In this report, we showed that the expression of Est was markedly induced in the liver but not in the lung of female mice subject to HS and resuscitation.

Estradiol and selective estrogen receptor agonists differentially affect brain monoamines and amino acids levels in transitional and surgical menopausal rat models.

Estrogens have many beneficial effects in the brain. Previously, we evaluated the effects of two models of menopause (surgical vs. transitional) on multiple monoaminergic endpoints in different regions of the adult rat brain in comparison with levels in gonadally intact rats.

Detection of estradiol in rat brain tissues: Contribution of local versus systemic production.

Estrogens play important roles in regulating brain development, brain function, and behavior. Many studies have evaluated these effects using ovariectomized (OVX) rats or mice with different doses of estrogen replacement, assuming that estradiol levels in all regions of the brain are the same as levels achieved in the serum. It is well known, however, that the brain contains all the enzymes necessary to produce estrogens, and that estrogen levels in the brain are determined by both systemic and local production and are region-specific.

Financial Impact of Minor Injury Transfers on a Level 1 Trauma Center.

Background: Trauma centers frequently accept patients from other institutions who are being sent due to the need for a higher level of care. We hypothesized that patients with minor traumatic injuries who are transferred from outside institutions would impart a negative financial impact on the receiving trauma center.

Methods: We performed a retrospective review of all trauma patients admitted to our urban level I trauma center from October 1, 2011, through September 30, 2013.

Effects of Cholinergic Lesions and Cholinesterase Inhibitors on Aromatase and Estrogen Receptor Expression in Different Regions of the Rat Brain.

Cholinergic projections have been shown to interact with estrogens in ways that influence synaptic plasticity and cognitive performance. The mechanisms are not well understood. The goal of this study was to investigate whether cholinergic projections influence brain estrogen production by affecting aromatase (ARO), or influence estrogen signaling by affecting estrogen receptor expression.

Comparison of transitional vs surgical menopause on monoamine and amino acid levels in the rat brain.

Loss of ovarian function has important effects on neurotransmitter production and release with corresponding effects on cognitive performance. To date, there has been little direct comparison of the effects of surgical and transitional menopause on neurotransmitter pathways in the brain. In this study, effects on monoamines, monoamine metabolites, and the amino acids tryptophan (TRP) and tyrosine (TYR) were evaluated in adult ovariectomized (OVX) rats and in rats that underwent selective and gradual ovarian follicle depletion by daily injection of 4-vinylcyclohexene-diepoxide (VCD).

Comparison between Modelled and Measured Magnetic Field Scans of Different Planar Coil Topologies for Stress Sensor Applications.

The investigation of planar coils of differing topologies, when combined with a magnetostrictive amorphous ribbon to form a stress-sensitive self-inductor, is an active research area for applications as stress or pressure sensors. Four topologies of planar coil (Circular, Mesh, Meander, and Square) have been constructed using copper track on 30 mm wide PCB substrate. The coils are energized to draw 0.

Pigment analysis by Raman microscopy and portable X-ray fluorescence (pXRF) of thirteenth to fourteenth century illuminations and cuttings from Bologna.

Non-destructive pigment analysis by Raman microscopy (RM) and portable X-ray fluorescence (pXRF) has been carried out on some Bolognese illuminations and cuttings chosen to represent the beginnings, evolution and height of Bolognese illuminated manuscript production. Dating to the thirteenth and fourteenth centuries and held in a private collection, the study provides evidence for the pigments generally used in this period. The results, which are compared with those obtained for other north Italian artwork, show the developments in usage of artistic materials and technique.

A microsomal based method to detect aromatase activity in different brain regions of the rat using ultra performance liquid chromatography-mass spectrometry.

Aromatase (ARO) is a cytochrome P450 enzyme that accounts for local estrogen production in the brain. The goal of this study was to develop a microsomal based assay to sensitively and reliably detect the low levels of ARO activity in different brain regions. Enzyme activity was detected based on the conversion of testosterone to estradiol.

Exome screening to identify loss-of-function mutations in the rhesus macaque for development of preclinical models of human disease.

Background: Exome sequencing has been utilized to identify genetic variants associated with disease in humans. Identification of loss-of-function mutations with exome sequencing in rhesus macaques (Macaca mulatta) could lead to valuable animal models of genetic disease. Attempts have been made to identify variants in rhesus macaques by aligning exome data against the rheMac2 draft genome.

A new rhesus macaque assembly and annotation for next-generation sequencing analyses.

Background: The rhesus macaque (Macaca mulatta) is a key species for advancing biomedical research. Like all draft mammalian genomes, the draft rhesus assembly (rheMac2) has gaps, sequencing errors and misassemblies that have prevented automated annotation pipelines from functioning correctly. Another rhesus macaque assembly, CR_1.

Targeted delivery of Doxorubicin by folic acid-decorated dual functional nanocarrier.

Doxorubicin (DOX) is one of the most commonly used antineoplastic agents, but its clinical application is oftentimes coupled with severe side effects. Selective delivery of DOX to tumors via nanosized drug carrier represents an attractive approach to this problem. Previously, we developed a dual functional nanomicellar carrier, PEG5K-embelin2 (PEG5K-EB2), which was able to deliver paclitaxel (PTX) selectively to tumors and to achieve an enhanced therapeutic effect.

De novo assembly of the common marmoset transcriptome from NextGen mRNA sequences.

Background: Nonhuman primates are important for both biomedical studies and understanding human evolution. Although research in these areas has mostly focused on Old World primates, such as the rhesus macaque, the common marmoset (Callithrix jacchus), a New World primate, offers important advantages in comparison to other primates, such as an accelerated lifespan. To conduct Next Generation expression studies or to study primate evolution, a high quality annotation of the marmoset genome is required.

Estrogen sulfotransferase/SULT1E1 promotes human adipogenesis.

Estrogen sulfotransferase (EST/SULT1E1) is known to catalyze the sulfoconjugation and deactivation of estrogens. The goal of this study is to determine whether and how EST plays a role in human adipogenesis. By using human primary adipose-derived stem cells (ASCs) and whole-fat tissues from the abdominal subcutaneous fat of obese and nonobese subjects, we showed that the expression of EST was low in preadipocytes but increased upon differentiation.

The decline in pulsatile GnRH release, as reflected by circulating LH concentrations, during the infant-juvenile transition in the agonadal male rhesus monkey (Macaca mulatta) is associated with a reduction in kisspeptin content of KNDy neurons of the arcuate nucleus in the hypothalamus.

Puberty in primates is timed by 2 hypothalamic events: during late infancy a decline in pulsatile GnRH release occurs, leading to a hypogonadotropic state that maintains quiescence of the prepubertal gonad; and in late juvenile development, pulsatile GnRH release is reactivated and puberty initiated, a phase of development that is dependent on kisspeptin signaling. In the present study, we determined whether the arrest of GnRH pulsatility in infancy was associated with a change in kisspeptin expression in the mediobasal hypothalamus (MBH). Kisspeptin was determined using immunohistochemistry in coronal hypothalamic sections from agonadal male rhesus monkeys during early infancy when GnRH release as reflected by circulating LH concentrations was robust and compared with that in juveniles in which GnRH pulsatility was arrested.

Incorporation of a selective sigma-2 receptor ligand enhances uptake of liposomes by multiple cancer cells.

Background: The sigma-2 receptor is an attractive target for tumor imaging and targeted therapy because it is overexpressed in multiple types of solid tumors, including prostate cancer, breast cancer, and lung cancer. SV119 is a synthetic small molecule that binds to sigma-2 receptors with high affinity and specificity. This study investigates the utility of SV119 in mediating the selective targeting of liposomal vectors in various types of cancer cells.

Recognition of novel objects and their location in rats with selective cholinergic lesion of the medial septum.

The importance of cholinergic neurons projecting from the medial septum (MS) of the basal forebrain to the hippocampus in memory function has been controversial. The aim of this study was to determine whether loss of cholinergic neurons in the MS disrupts object and/or object location recognition in male Sprague-Dawley rats. Animals received intraseptal injections of either vehicle, or the selective cholinergic immunotoxin 192 IgG-saporin (SAP).

Core competencies for research training in the clinical pharmaceutical sciences.

Objective: To identify and apply core competencies for training students enrolled in the clinical pharmaceutical scientist PhD training program at the University of Pittsburgh School of Pharmacy.

Design: Faculty members reached consensus on the required core competencies for the program and mapped them to curricular and experiential requirements.

Assessment: A rubric was created based on core competencies spanning 8 major categories of proficiency, and competencies of clinical versus traditional PhD training were delineated.

Evaluation of a combined therapeutic regimen of 8-OH-DPAT and environmental enrichment after experimental traumatic brain injury.

When provided individually, both the serotonin (5-HT(1A))-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and environmental enrichment (EE) enhance behavioral outcome and reduce histopathology after experimental traumatic brain injury (TBI). The aim of this study was to determine whether combining these therapies would yield greater benefit than either used alone. Anesthetized adult male rats received a cortical impact or sham injury and then were randomly assigned to enriched or standard (STD) housing, where either 8-OH-DPAT (0.