Search results for "Mission"

Exosomes in semen: opportunities as a new tool in prostate cancer diagnosis

2017

Abstract: Prostate cancer (PCa) is the most common cancer in men. Nowadays, it is diagnosed through the test of serum prostate-specific antigen (PSA) and rectal examination; however, there is still debate about the PSA-based diagnosis. Seminal fluid (SF), contains a high concentration of subcellular lipid-bound microparticles, traditionally termed "prostasomes", that are extracellular vesicles (EVs) released into the extracellular space by prostate gland's epithelial cells. These vesicles, first described in 1982 promote motility of sperm cells, regulation of sperm cell capacitation, acrosome reaction and immune suppression within the female reproductive tract. It was demonstrated that pros…

Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum

2018

The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A(2A) receptor (A(2A)R) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A(2A)R and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A(2A)R-CB1R heteromeric complexes. However, th…

2021

Brain homeostasis is the dynamic equilibrium whereby physiological parameters are kept actively within a specific range. The homeostatic range is not fixed and may change throughout the individual's lifespan, or may be transiently modified in the presence of severe perturbations. The endocannabinoid system has emerged as a safeguard of homeostasis, e.g., it modulates neurotransmission and protects neurons from prolonged or excessively strong activation. We used genetically engineered mouse lines that lack the cannabinoid type-1 receptor (CB1) either in dorsal telencephalic glutamatergic or in forebrain GABAergic neurons to create new allostatic states, resulting from alterations in the exci…

Localization of the cannabinoid type-1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus

2018

Astroglial type‐1 cannabinoid (CB1) receptors are involved in synaptic transmission, plasticity and behavior by interfering with the so‐called tripartite synapse formed by pre‐ and post‐synaptic neuronal elements and surrounding astrocyte processes. However, little is known concerning the subcellular distribution of astroglial CB1 receptors. In particular, brain CB1 receptors are mostly localized at cells' plasmalemma, but recent evidence indicates their functional presence in mitochondrial membranes. Whether CB1 receptors are present in astroglial mitochondria has remained unknown. To investigate this issue, we included conditional knock‐out mice lacking astroglial CB1 receptor expression …

Autism Related Neuroligin-4 Knockout Impairs Intracortical Processing but not Sensory Inputs in Mouse Barrel Cortex

2016

Neuroligin-4 (Nlgn4) is a cell adhesion protein that regulates synapse organization and function. Mutations in human NLGN4 are among the causes of autism spectrum disorders. In mouse, Nlgn4 knockout (KO) perturbs GABAergic synaptic transmission and oscillatory activity in hippocampus, and causes social interaction deficits. The complex profile of cellular and circuit changes that are caused by Nlgn4-KO is still only partly understood. Using Nlgn4-KO mice, we found that Nlgn4-KO increases the power in the alpha frequency band of spontaneous network activity in the barrel cortex under urethane anesthesia in vivo. Nlgn4-KO did not affect single-whisker-induced local field potentials, but suppr…

General Aspects of Metal Ions as Signaling Agents in Health and Disease

2020

This review focuses on the current knowledge on the involvement of metal ions in signaling processes within the cell, in both physiological and pathological conditions. The first section is devoted to the recent discoveries on magnesium and calcium-dependent signal transduction—the most recognized signaling agents among metals. The following sections then describe signaling pathways where zinc, copper, and iron play a key role. There are many systems in which changes in intra- and extra-cellular zinc and copper concentrations have been linked to important downstream events, especially in nervous signal transduction. Iron signaling is mostly related with its homeostasis. However, it is also …

Direct estrogen receptor (ER) / HER family crosstalk mediating sensitivity to lumretuzumab and pertuzumab in ER+ breast cancer.

2017

Bidirectional cross talk between members of the human epidermal growth factor family of receptors (HER) and the estrogen receptor (ER) is believed to underlie resistance mechanisms that develop in response to treatment with anti-HER agents and endocrine therapy. We investigated the interaction between HER2, HER3 and the ER in vitro using human embryonic kidney cells transfected with human HER2, HER3, and ERα. We also investigated the additive efficacy of combination regimens consisting of anti-HER3 (lumretuzumab), anti-HER2 (pertuzumab), and endocrine (fulvestrant) therapy in vivo. Our data show that both HER2 and HER3 can directly complex with the ER and can mediate phosphorylation of the …

Long Term Culture of the A549 Cancer Cell Line Promotes Multilamellar Body Formation and Differentiation towards an Alveolar Type II Pneumocyte Pheno…

2016

Pulmonary research requires models that represent the physiology of alveolar epithelium but concerns with reproducibility, consistency and the technical and ethical challenges of using primary or stem cells has resulted in widespread use of continuous cancer or other immortalized cell lines. The A549 'alveolar' cell line has been available for over four decades but there is an inconsistent view as to its suitability as an appropriate model for primary alveolar type II (ATII) cells. Since most work with A549 cells involves short term culture of proliferating cells, we postulated that culture conditions that reduced proliferation of the cancer cells would promote a more differentiated ATII ce…

Visualizing In Vitro Type I Collagen Fibrillogenesis by Transmission Electron Microscopy

2017

Techniques and protocols for the in vitro formation of collagen type I fibrils and the extensive biochemical variation of the fibrillogenesis conditions are presented. In all cases, the incubation and fibrillogenesis product can be readily monitored by transmission electron microscopic study of negatively stained specimens. Representative TEM data is presented and discussed within the context of the products of the fibrillogenesis protocols, from which the extensive biochemical and structural possibilities of this integrated approach can be appreciated.

Environmental Tobacco Smoke During the Early Postnatal Period of Mice Interferes With Brain 18 F-FDG Uptake From Infancy to Early Adulthood – A Longi…

2020

Exposure to environmental tobacco smoke (ETS) is associated with high morbidity and mortality, mainly in childhood. Our aim was to evaluate the effects of postnatal ETS exposure in the brain 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) uptake of mice by positron emission tomography (PET) neuroimaging in a longitudinal study. C57BL/6J mice were exposed to ETS that was generated from 3R4F cigarettes from postnatal day 3 (P3) to P14. PET analyses were performed in male and female mice during infancy (P15), adolescence (P35), and adulthood (P65). We observed that ETS exposure decreased 18F-FDG uptake in the whole brain, both left and right hemispheres, and frontal cortex in both male and female i…