Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons.

Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cells were evaluated in the 0.01-1 µM range.

The Parkinson disease pain classification system: results from an international mechanism-based classification approach.

Pain is a common nonmotor symptom in patients with Parkinson disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into 3 groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities.

Assessment of Ataxia Rating Scales and Cerebellar Functional Tests: Critique and Recommendations.

Background: We assessed the clinimetric properties of ataxia rating scales and functional tests, and made recommendations regarding their use.

Methods: A systematic literature search was conducted to identify the instruments used to rate ataxia symptoms. The identified rating scales and functional ability tests were reviewed and ranked by the panel as "recommended," "suggested," or "listed" for the assessment of patients with discrete cerebellar disorders, using previously established criteria.

Implication of TRPC3 channel in gustatory perception of dietary lipids.

Aim: The pathogenesis of obesity has been associated with high intake of dietary fat, and some recent studies have explored the cellular mechanisms of oro-sensory detection of dietary fatty acids. We further assessed the role of transient receptor potential canonical (TRPC) channels in oro-sensory perception of dietary lipids.

Methods: We determined by RT-qPCR and western blotting the expression of TRPC3/6/7 channels in mouse fungiform taste bud cells (mTBC).

Reinvigorating exhausted CD8 cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy.

Immunotherapy has revolutionized the treatment of cancer in recent years and achieved overall success and long-term clinical benefit in patients with a wide variety of cancer types. However, there is still a large proportion of patients exhibiting limited or no responses to immunotherapeutic strategy, some of which were even observed with hyperprogressive disease. One major obstacle restricting the efficacy is that tumor-reactive CD8 T cells, which are central for tumor control, undergo exhaustion, and lose their ability to eliminate cancer cells after infiltrating into the strongly immunosuppressive tumor microenvironment.

Transcriptional signatures regulated by TRPC1/C4-mediated Background Ca entry after pressure-overload induced cardiac remodelling.

Aims: After summarizing current concepts for the role of TRPC cation channels in cardiac cells and in processes triggered by mechanical stimuli arising e.g. during pressure overload, we analysed the role of TRPC1 and TRPC4 for background Ca entry (BGCE) and for cardiac pressure overload induced transcriptional remodelling.

While We Wait for a Vaccine Against SARS-CoV-2, Why Not Think About Available Drugs?

At the time of reception of this article (April 2, 2020), efforts to develop a specific vaccine against SARS-Cov-2, the causative agent of the coronavirus disease 2019 (COVID-19), had just begun trial phase 1, but full validation of this and other current developments is likely to take many more months to reach completion. The ongoing pandemic constitutes a major health burden of world proportions that is also having a devastating impact on whole economies worldwide, the knock-on effects of which could be catastrophic especially in poorer countries. Alternative measures to ameliorate the impact and hamper or minimally slow down disease progression are urgently called for.

Impact of histamine H4 receptor deficiency on the modulation of T cells in a murine breast cancer model.

Background: The histamine H4 receptor (H4R) is preferentially expressed in immune cells and is a potential therapeutic target for inflammatory and autoimmune diseases. This study aimed at further exploring the role of H4R in the immunobiology of breast cancer.

Methods: We used wild type (WT) and H4R deficient mice (KO) to evaluate whether H4R genotypes show a different distribution of T cell subsets in spleens, tumours and tumour draining lymph nodes (TDLN) in a syngeneic ErbB2-positive breast cancer model developed orthotopically with LM3 cells and its impact on tumour growth.

Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPARγ signaling pathway.

Sepsis, a systemic inflammatory response syndrome (SIRS) caused by infection, is a major public health concern with limited therapeutic options. Infection disturbs the homeostasis of host, resulting in excessive inflammation and immune suppression. This has prompted the clinical use of immunomodulators to balance host response as an alternative therapeutic strategy.

GPCR-dependent biasing of GIRK channel signaling dynamics by RGS6 in mouse sinoatrial nodal cells.

How G protein-coupled receptors (GPCRs) evoke specific biological outcomes while utilizing a limited array of G proteins and effectors is poorly understood, particularly in native cell systems. Here, we examined signaling evoked by muscarinic (MR) and adenosine (AR) receptor activation in the mouse sinoatrial node (SAN), the cardiac pacemaker. MR and AR activate a shared pool of cardiac G protein-gated inwardly rectifying K (GIRK) channels in SAN cells from adult mice, but AR-GIRK responses are smaller and slower than MR-GIRK responses.

Sleep disruption in medicine students and its relationship with impaired academic performance: A systematic review and meta-analysis.

Sleep disruption severely impairs learning ability, affecting academic performance in students. This systematic review and meta-analysis aimed at assessing the prevalence of sleep disruption in medical students and its relationship with academic performance. PubMed, Web of Sciences, EBSCO and SciELO databases searches allowed to retrieve 41 papers with data about the prevalence of sleep deprivation, 20 of which also contained data on its association with academic performance.

Lack of Gα proteins in adipocytes attenuates diet-induced obesity.

Objectives: Typically, obesity results from an inappropriate balance between energy uptake from nutrient consumption and burning of calories, which leads to a pathological increase in fat mass. Obesity is a major cause of insulin resistance and diabetes. Inhibitory G proteins (Gα) form a subfamily that is involved in the regulation of adipose tissue function.

Pleiotropic effects of statins on brain cells.

Starting with cholesterol homeostasis, the first part of the review addresses various aspects of cholesterol metabolism in neuronal and glial cells and the mutual crosstalk between the two cell types, particularly the transport of cholesterol from its site of synthesis to its target loci in neuronal cells, discussing the multiple mechanistic aspects and transporter systems involved. Statins are next analyzed from the point of view of their chemical structure and its impingement on their pharmacological properties and permeability through cell membranes and the blood-brain barrier in particular. The following section then discusses the transcriptional effects of statins and the changes they induce in brain cell genes associated with a variety of processes, including cell growth, signaling and trafficking, uptake and synthesis of cholesterol.

RNA-seq analysis reveals TRPC genes to impact an unexpected number of metabolic and regulatory pathways.

The seven-member transient receptor potential canonical genes (TRPC1-7) encode cation channels linked to several human diseases. There is little understanding of the participation of each TRPC in each pathology, considering functional redundancy. Also, most of the inhibitors available are not specific.

Identification and characterization of human PEIG-1/GPRC5A as a 12-O-tetradecanoyl phorbol-13-acetate (TPA) and PKC-induced gene.

Homo sapiens orphan G protein-coupling receptor PEIG-1 was first cloned and characterized by applying differential display to T84 colonic carcinoma cells incubated in the presence of phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (GenBank AF506289.1). Later, Lotan's laboratory found the same gene product in response to retinoic acid analogues, naming it with the symbol RAIG1.

Analysis of Mrgprb2 Receptor-Evoked Ca Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice.

Mast cells are a heterogeneous group of immune cells. The simplest and commonly accepted classification divides them in two groups according to their protease content. We have compared the action of diverse secretagogues on bone marrow derived (BMMC) and peritoneal (PMC) mast cells which represent classical models of mucosal and connective tissue type mast cells in mice.

TRPC1 participates in the HSV-1 infection process by facilitating viral entry.

Mammalian transient receptor potential (TRP) channels are major components of Ca signaling pathways and control a diversity of physiological functions. Here, we report a specific role for TRPC1 in the entry of herpes simplex virus type 1 (HSV-1) into cells. HSV-1-induced Ca release and entry were dependent on Orai1, STIM1, and TRPC1.

Subjective time estimation in Antarctica: The impact of extreme environments and isolation on a time production task.

Interval timing measures time estimation in the seconds-to-minutes range. Antarctica provides a real-world context to study the effect of extreme photoperiods and isolation on time perception. The aim of this study was to explore interval timing as a cognitive measure in the crew of Belgrano II Argentine Antarctic Station.

Melatonin protects the retina from experimental nonexudative age-related macular degeneration in mice.

Nonexudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. Currently, there are no available treatments for NE-AMD. We have developed a NE-AMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks.

Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson's Disease Animal Models from a Molecular Signaling Perspective.

Despite the fact that astrocytes are the most abundant glial cells, critical for brain function, few studies have dealt with their possible role in neurodegenerative diseases like Parkinson's disease (PD). This article explores relevant evidence on the involvement of astrocytes in experimental PD neurodegeneration from a molecular signaling perspective. For a long time, astrocytic proliferation was merely considered a byproduct of neuroinflammation, but by the time being, it is clear that astrocytic dysfunction plays a far more important role in PD pathophysiology.

Sleep misalignment and circadian rhythm impairment in long-haul bus drivers under a two-up operations system.

Objectives: The objective of the study was to describe working and sleep conditions and to assess how sleep opportunities are associated with obtained sleep and alertness, in a sample of long-haul bus drivers working with a two-up operations system.

Methods: Measures of subjective sleep and sleepiness, actigraphy, circadian temperature rhythm, and psychomotor vigilance tasks were obtained from a sample of 122 drivers from Argentina. Variables were compared between high and low fatigue risk groups, which were formed using a median split of a fatigue risk score.

Measurement Invariance of the Prosocial Behavior Scale in Three Hispanic Countries (Argentina, Spain, and Peru).

In a growing context of multiculturalism, prosocial behavior is important to build effective social exchange and service orientation among university students. The present study investigates prosocial behavior from a psychometric approach, to obtain evidence of the internal structure of the prosocial behavior scale (PS), in 737 young people enrolled at universities in Argentina (207), Spain (310), and Peru (220). First, the clarity of the items was explored in the three countries; second, possible irrelevant patterns of response, such as the careless and extreme responses, were evaluated; third, the non-parametric Mokken methodology was applied to identify the basic properties of the scale score; fourth, the structural equation modeling (SEM) methodology was used to identify the properties of the internal structure (dimensionality, tau-equivalence) of the latent construct; fifth, the measurement invariance according to sex (intra-equivalence) and country (inter-equivalence) was examined with the SEM methodology and other complementary strategies.