Endothelial Cell-Derived Soluble CD200 Determines the Ability of Immune Cells to Cross the Blood-Brain Barrier.

The infiltration of immune cells into the central nervous system mediates the development of autoimmune neuroinflammatory diseases. We previously showed that the loss of either Fabp5 or calnexin causes resistance to the induction of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Here we show that brain endothelial cells lacking either Fabp5 or calnexin have an increased abundance of cell surface CD200 and soluble CD200 (sCD200) as well as decreased T-cell adhesion.

Student pharmacists' perceptions of a NAPLEX preparation module in the pharmacy curriculum at one United States college of pharmacy.

Background And Purpose: To investigate final-year student pharmacists' experiences of a new module for North American Pharmacist Licensure Examination® (NAPLEX®) preparation at one college of pharmacy in the United States.

Educational Activity And Setting: All student pharmacists enrolled in a new Spring 2023 module for NAPLEX preparation (n = 118) were invited to complete an electronic questionnaire and participate in a semi-structured interview. The questionnaire investigated the perceived helpfulness, grading, importance, prioritization, structure, and timing of the module in the curriculum, as well as assignment choices, confidence building, and time management using a six-point Likert scale.

Elevated external temperature affects cell ultrastructure and heat shock proteins (HSPs) in Paramacrobiotus experimentalis Kaczmarek, Mioduchowska, Poprawa, & Roszkowska, 2020.

Increasing temperature influences the habitats of various organisms, including microscopic invertebrates. To gain insight into temperature-dependent changes in tardigrades, we isolated storage cells exposed to various temperatures and conducted biochemical and ultrastructural analysis in active and tun-state Paramacrobiotus experimentalis Kaczmarek, Mioduchowska, Poprawa, & Roszkowska, 2020. The abundance of heat shock proteins (HSPs) and ultrastructure of the storage cells were examined at different temperatures (20 °C, 30 °C, 35 °C, 37 °C, 40 °C, and 42 °C) in storage cells isolated from active specimens of Pam.

Calreticulin and the Heart.

Calreticulin is an endoplasmic Ca binding protein and molecular chaperone. As a cardiac embryonic gene, calreticulin is essential for heart development. The protein supports Ca-dependent signaling events that are critical to cardiomyocyte differentiation and cardiogenesis.

The Fabp5/calnexin complex is a prerequisite for sensitization of mice to experimental autoimmune encephalomyelitis.

We previously showed that calnexin (Canx)-deficient mice are desensitized to experimental autoimmune encephalomyelitis (EAE) induction, a model that is frequently used to study inflammatory demyelinating diseases, due to increased resistance of the blood-brain barrier to immune cell transmigration. We also discovered that Fabp5, an abundant cytoplasmic lipid-binding protein found in brain endothelial cells, makes protein-protein contact with the cytoplasmic C-tail domain of Canx. Remarkably, both Canx-deficient and Fabp5-deficient mice commonly manifest resistance to EAE induction.

Selective enhancement of cardiomyocyte efficiency results in a pernicious heart condition.

Transgenic mice with selective induction of calreticulin transgene expression in cardiomyocytes (CardiacCRT+) were analyzed. CardiacCRT+ cardiomyocytes showed increased contractility and Ca2+ transients. Yet, in vivo assessment of cardiac performance, and ischemic tolerance of CardiacCRT+ mice demonstrated right ventricle dilation and reduced cardiac output, increased QT interval and decreased P amplitude.

Tauroursodeoxycholic acid attenuates cyclosporine-induced renal fibrogenesis in the mouse model.

Chronic exposure to cyclosporine causes nephrotoxicity and organ damage. Here we show that cyclosporine nephrotoxicity in vivo is associated with the activation of the unfolded protein response (UPR) pathway to initiate tissue fibrosis. We demonstrate that cyclosporine therapy activated the IRE1α branch of the unfolded protein response (UPR) and stimulated the TGFβ1 signaling pathway in the kidneys of male mice.

Calnexin is necessary for T cell transmigration into the central nervous system.

In multiple sclerosis (MS), a demyelinating inflammatory disease of the CNS, and its animal model (experimental autoimmune encephalomyelitis; EAE), circulating immune cells gain access to the CNS across the blood-brain barrier to cause inflammation, myelin destruction, and neuronal damage. Here, we discovered that calnexin, an ER chaperone, is highly abundant in human brain endothelial cells of MS patients. Conversely, mice lacking calnexin exhibited resistance to EAE induction, no evidence of immune cell infiltration into the CNS, and no induction of inflammation markers within the CNS.

Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes.

Aims/hypothesis: A new class of treatments termed bioelectronic medicines are now emerging that aim to target individual nerve fibres or specific brain circuits in pathological conditions to repair lost function and reinstate a healthy balance. Carotid sinus nerve (CSN) denervation has been shown to improve glucose homeostasis in insulin-resistant and glucose-intolerant rats; however, these positive effects from surgery appear to diminish over time and are heavily caveated by the severe adverse effects associated with permanent loss of chemosensory function. Herein we characterise the ability of a novel bioelectronic application, classified as kilohertz frequency alternating current (KHFAC) modulation, to suppress neural signals within the CSN of rodents.

Development and feasibility of a child obesity prevention intervention in general practice: the Healthy 4 Life pilot study.

Aim: Approximately 20% of Australian pre-school children are overweight. Primary care providers have a crucial role in identifying children at risk of unhealthy weight gain and to offer advice and suggestions to parents. The Healthy 4 Life pilot study aimed to develop and test the feasibility of a practice nurse (PN)-led brief intervention into a healthy kid's check in general practice.

Child obesity prevention in primary health care: investigating practice nurse roles, attitudes and current practices.

Aim: Overweight and obesity affects approximately 20% of Australian pre-schoolers. The general practice nurse (PN) workforce has increased in recent years; however, little is known of PN capacity and potential to provide routine advice for the prevention of child obesity. This mixed methods pilot study aims to explore the current practices, attitudes, confidence and training needs of Australian PNs surrounding child obesity prevention in the general practice setting.

Calreticulin induces dilated cardiomyopathy.

Background: Calreticulin, a Ca(2+)-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart.

Progression and variability of TNBS colitis-associated inflammation in rats assessed by contrast-enhanced and T2-weighted MRI.

Background: A common feature of preclinical models of colitis is that the time-course, magnitude, and persistence of inflammation vary considerably within the experimental animal group. Accordingly, noninvasive, serial quantification of colonic inflammation could advantageously guide dosing regimens and assess drug efficacy, thus enhancing the value of colitis models in research. This investigation using magnetic resonance imaging (MRI) was therefore undertaken to objectively determine inflammatory progression, variability, and response to therapy associated with trinitrobenzene sulfonic acid (TNBS)-induced colitis in Wistar rats.