Assessment of image quality and scatter and leakage radiation of an integrated MR-LINAC system.

Purpose: To assess the image quality, scatter, and leakage radiation of an integrated magnetic resonance linear accelerator (MR-LINAC or MRL) system.

Methods: A large American College of Radiology (ACR) magnetic resonance imaging (MRI) accreditation phantom was used to evaluate the MRI capabilities of the integrated MRL system compared with those of other diagnostic MRI systems. Multiple sets of T1 and T2/PD images were acquired with the linear accelerator positioned at various angles and with the radiation beam on and off.

The additive effect of aging on sepsis-induced cognitive impairment and neuroinflammation.

Systemic inflammation is emerging as a significant driver of cognitive decline in the aged and vulnerable brain. In sepsis survivors animals low-grade brain inflammation occurs, suggesting that sepsis is able to induce in microglia a primed-like state. The purpose of this study is to analyze the role of sepsis-induced brain inflammation in the progression of the physiological process of brain aging.

Mesenchymal stem cells inhibit T cell activation by releasing TGF-β1 from TGF-β1/GARP complex.

Intervention with mesenchymal stem cells (MSCs) reveals a promising therapeutic tool to treat transplantation and autoimmune disease due to their immunoregulation capability. But the mechanisms of action are not fully investigated yet. Transforming growth factor-β1 (TGF-β1) exhibit multiple effects in migration, differentiation, and immunomodulation of MSCs.

Minimally invasive monitoring of CD4 T cells at multiple mucosal tissues after intranasal vaccination in rhesus macaques.

Studies in nonhuman primates (NHP) for prospective immune cell monitoring subsequent to infection and/or vaccination usually rely on periodic sampling of the blood samples with only occasional collections of biopsies from mucosal tissues because of safety concerns and practical constraints. Here we present evidence in support of cytobrush sampling of oral, rectal, and genital mucosal tissues as a minimally invasive approach for the phenotypic analyses of different T cells subsets de novo as well as prospectively after intranasal immunization in rhesus macaques. Significant percentages of viable lymphocytes were obtained consistently from both naïve and chronically SIV-infected rhesus macaques.

Macrophages as a potential tumor-microenvironment target for noninvasive imaging of early response to anticancer therapy.

As a result of therapy-induced apoptosis, peripheral blood monocytes are recruited to tumors, where they become tumor-associated macrophages (TAMs). To date, few studies have investigated noninvasive molecular imaging for assessment of macrophage infiltration in response to therapy-induced apoptosis. Here, noninvasive assessment of changes in tumor accumulation of TAMs was proposed as a new way to measure early tumor response to anticancer therapy.

Model for Estimating Power and Downtime Effects on Teletherapy Units in Low-Resource Settings.

Purpose: More than 6,500 megavoltage teletherapy units are needed worldwide, many in low-resource settings. Cobalt-60 units or linear accelerators (linacs) can fill this need. We have evaluated machine performance on the basis of patient throughput to provide insight into machine viability under various conditions in such a way that conclusions can be generalized to a vast array of clinical scenarios.

Zdhhc13-dependent Drp1 S-palmitoylation impacts brain bioenergetics, anxiety, coordination and motor skills.

Protein S-palmitoylation is a reversible post-translational modification mediated by palmitoyl acyltransferase enzymes, a group of Zn-finger DHHC-domain-containing proteins (ZDHHC). Here, for the first time, we show that Zdhhc13 plays a key role in anxiety-related behaviors and motor function, as well as brain bioenergetics, in a mouse model (luc) carrying a spontaneous Zdhhc13 recessive mutation. At 3 m of age, mutant mice displayed increased sensorimotor gating, anxiety, hypoactivity, and decreased motor coordination, compared to littermate controls.

Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis.

Phosphofructokinase 1 (PFK1) plays a critical role in glycolysis; however, its role and regulation in tumorigenesis are not well understood. Here, we demonstrate that PFK1 platelet isoform (PFKP) is the predominant PFK1 isoform in human glioblastoma cells and its expression correlates with total PFK activity. We show that PFKP is overexpressed in human glioblastoma specimens due to an increased stability, which is induced by AKT activation resulting from phosphatase and tensin homologue (PTEN) loss and EGFR-dependent PI3K activation.

The inhibition of the kynurenine pathway prevents behavioral disturbances and oxidative stress in the brain of adult rats subjected to an animal model of schizophrenia.

Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of oxidative stress and also in the pathophysiology of schizophrenia. The aim of this study was to use a pharmacological animal model of schizophrenia induced by ketamine to investigate if KP inhibitors could protect the brains of Wistar rats against oxidative stress and behavioral changes. Ketamine, injected at the dose of 25mg/kg, increased spontaneous locomotor activity.

Contrasting effects of an Mdm2 functional polymorphism on tumor phenotypes.

MDM2, an E3 ubiquitin ligase, is a potent inhibitor of the p53 tumor suppressor and is elevated in many human cancers that retain wild-type p53. MDM2 SNP309G is a functional polymorphism that results in elevated levels of MDM2 (due to enhanced SP1 binding to the MDM2 promoter) thus decreasing p53 activity. Mdm2 mice are more prone to spontaneous tumor formation than Mdm2 mice, providing direct evidence for the impact of this SNP in tumor development.

Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis.

Background: Circular RNAs (circRNAs) are RNA transcripts that are widespread in the eukaryotic genome. Recent evidence indicates that circRNAs play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs encode functional proteins remains elusive, although translation of several circRNAs was recently reported.

Vitamin B Reduces Neurochemical and Long-Term Cognitive Alterations After Polymicrobial Sepsis: Involvement of the Kynurenine Pathway Modulation.

Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B (vit B) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway.

Preparation and fabrication of a full-scale, sagittal-sliced, 3D-printed, patient-specific radiotherapy phantom.

Purpose: Patient-specific 3D-printed phantoms have many potential applications, both research and clinical. However, they have been limited in size and complexity because of the small size of most commercially available 3D printers as well as material warping concerns. We aimed to overcome these limitations by developing and testing an effective 3D printing workflow to fabricate a large patient-specific radiotherapy phantom with minimal warping errors.

Antimanic activity of minocycline in a GBR12909-induced model of mania in mice: Possible role of antioxidant and neurotrophic mechanisms.

Background: Mania/hypomania is the cardinal feature of bipolar disorder. Recently, single administration of the dopamine transporter (DAT) inhibitor, GBR12909, was related to mania-like alterations. In the present study we aimed at testing behavioral and brain oxidant/neurotrophic alterations induced by the repeated administration of GBR12909 and its prevention/reversal by the mood stabilizing drugs, lithium (Li) and valproate (VAL) as well as by the neuroprotective drug, minocycline (Mino).

Chitosan Nanoparticles for miRNA Delivery.

RNA interference techniques represent a promising strategy for therapeutic applications. In addition to small interfering RNA-based approaches, which have been widely studied and translated into clinical investigations, microRNA-based approaches are attractive owing to their "one hit, multiple targets" concept. To overcome challenges with in vivo delivery of microRNAs related to stability, cellular uptake, and specific delivery, our group has developed and characterized chitosan nanoparticles for nucleotide delivery.

The impact of chronic mild stress on long-term depressive behavior in rats which have survived sepsis.

The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30).

Development of a Monte Carlo multiple source model for inclusion in a dose calculation auditing tool.

Purpose: The Imaging and Radiation Oncology Core Houston (IROC-H) (formerly the Radiological Physics Center) has reported varying levels of agreement in their anthropomorphic phantom audits. There is reason to believe one source of error in this observed disagreement is the accuracy of the dose calculation algorithms and heterogeneity corrections used. To audit this component of the radiotherapy treatment process, an independent dose calculation tool is needed.

Rapid monoisotopic cisplatin based barcoding for multiplexed mass cytometry.

Mass cytometry presents an exceptional opportunity to interrogate the biology of highly heterogeneous cell populations, owing to the ability to collect highly parametric proteomic data at a single cell level. However, sample-to-sample variability, due to antibody staining and/or instrument sensitivity, can introduce substantial artifacts into the data, which can in turn lead to erroneous conclusions. This variability can be eliminated by sample barcoding which enables samples to be pooled, stained and run simultaneously.

Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1.

Aberrant activation of the Hedgehog (Hh) signaling pathway drives the tumorigenesis of multiple cancers. In this study, we screened a panel of deubiquitinases that may regulate the Hh pathway. We find that deubiquitinase USP48 activates Gli-dependent transcription by stabilizing Gli1 protein.

Lithium ameliorates sleep deprivation-induced mania-like behavior, hypothalamic-pituitary-adrenal (HPA) axis alterations, oxidative stress and elevations of cytokine concentrations in the brain and serum of mice.

Objectives: The goal of the present study was to investigate the effects of lithium administration on behavior, oxidative stress parameters and cytokine levels in the periphery and brain of mice subjected to an animal model of mania induced by paradoxical sleep deprivation (PSD).

Methods: Male C57 mice were treated with saline or lithium for 7 days. The sleep deprivation protocol started on the 5th day during for the last 36 hours of the treatment period.

Alpha-lipoic acid attenuates acute neuroinflammation and long-term cognitive impairment after polymicrobial sepsis.

Sepsis is a complication of an infection which imbalance the normal regulation of several organ systems, including the central nervous system (CNS). Evidence points towards inflammation and oxidative stress as major steps associated with brain dysfunction in sepsis. Thus, we investigated the α-lipoic acid (ALA) effect as an important antioxidant compound on brain dysfunction in rats.

Zika Virus as an Emerging Neuropathogen: Mechanisms of Neurovirulence and Neuro-Immune Interactions.

Zika virus (ZIKV) is an emerging arbovirus of the genus Flaviviridae, which causes a febrile illness and has spread from across the Pacific to the Americas in a short timeframe. Convincing evidence has implicated the ZIKV to incident cases of neonatal microcephaly and a set of neurodevelopmental abnormalities referred to as the congenital Zika virus syndrome. In addition, emerging data points to an association with the ZIKV and the development of the so-called Guillain-Barre syndrome, an acute autoimmune polyneuropathy.