Addressing Challenges in Residential Facilities: Promoting Human Rights and Recovery While Pursuing Functional Autonomy.

Objective: Italian residential facilities (RFs) aim to promote human rights and recovery for individuals with severe mental disorders. Italian RFs can be distinguished into five main types: high-intensity rehabilitation (RF1), medium-intensity rehabilitation (RF2), medium-level support (RF3.1), high-level support (RF3.

Development and validation of a new standardized measure for assessing experiences of discrimination within mental health services. A participatory research project.

Aims: People with mental disorders frequently report experiences of discrimination within mental health services, which can have significant detrimental effects on individuals' well-being and recovery. This study aimed to develop and validate a new standardized measure aiming to assess experiences of stigmatization among people with mental disorders within mental health services.

Methods: The scale was developed in Italian and tested for ease of use, comprehension, acceptability, relevance of items and response options within focus group session.

Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer's disease.

Calcium dynamics in astrocytes represent a fundamental signal that through gliotransmitter release regulates synaptic plasticity and behaviour. Here we present a longitudinal study in the PS2APP mouse model of Alzheimer's disease (AD) linking astrocyte Ca hypoactivity to memory loss. At the onset of plaque deposition, somatosensory cortical astrocytes of AD female mice exhibit a drastic reduction of Ca signaling, closely associated with decreased endoplasmic reticulum Ca concentration and reduced expression of the Ca sensor STIM1.

[Psychometric properties of the Monitoring of the Path of Rehabilitation (MPR) Form.].

Purpose: The correct placement of people with mental disorders in psychiatric residential facilities (PRF) and the monitoring of their progress in these facilities is a critical issue that has not been fully settled in the Italian system. To overcome this problem, some validated instruments are used, which mostly assess the patient's functioning/disability, while no instruments have been set up to assess functional autonomy in patients with a psychiatric disorder residents in RFs. The Verona Department of Mental Health has created the Monitoring of the Path of Rehabilitation (MPR) Form with the aim of assessing the functional autonomy of patients to admit and monitor them adequately in their residential pathways.

A New Transgenic Mouse Line for Imaging Mitochondrial Calcium Signals.

Mitochondria play a key role in cellular calcium (Ca) homeostasis. Dysfunction in the organelle Ca handling appears to be involved in several pathological conditions, ranging from neurodegenerative diseases, cardiac failure and malignant transformation. In the past years, several targeted green fluorescent protein (GFP)-based genetically encoded Ca indicators (GECIs) have been developed to study Ca dynamics inside mitochondria of living cells.

Accelerated Aging Characterizes the Early Stage of Alzheimer's Disease.

For Alzheimer's disease (AD), aging is the main risk factor, but whether cognitive impairments due to aging resemble early AD deficits is not yet defined. When working with mouse models of AD, the situation is just as complicated, because only a few studies track the progression of the disease at different ages, and most ignore how the aging process affects control mice. In this work, we addressed this problem by comparing the aging process of PS2APP (AD) and wild-type (WT) mice at the level of spontaneous brain electrical activity under anesthesia.

Performance and effectiveness of step progressive care pathways within mental health supported accommodation services in Italy.

Background: In Italy, a growing number of people with severe mental illness (SMI) require care in residential facilities (RFs), a key component of the care pathway. However, despite their development, studies about resident samples have been very few.

Aims: This study, the VALERE-REC Study (eVALuation of outcomE in Residential-use of clinical data with REsearch objeCtives) aims to identify the characteristics that increase the probability to move patients living in RFs to a more independent setting.

Generation and Characterization of a New FRET-Based Ca Sensor Targeted to the Nucleus.

Calcium (Ca) exerts a pivotal role in controlling both physiological and detrimental cellular processes. This versatility is due to the existence of a cell-specific molecular Ca toolkit and its fine subcellular compartmentalization. Study of the role of Ca in cellular physiopathology greatly benefits from tools capable of quantitatively measuring its dynamic concentration ([Ca]) simultaneously within organelles and in the cytosol to correlate localized and global [Ca] changes.

Effects of Mild Excitotoxic Stimulus on Mitochondria Ca Handling in Hippocampal Cultures of a Mouse Model of Alzheimer's Disease.

In Alzheimer's disease (AD), the molecular mechanisms involved in the neurodegeneration are still incompletely defined, though this aspect is crucial for a better understanding of the malady and for devising effective therapies. Mitochondrial dysfunctions and altered Ca signaling have long been implicated in AD, though it is debated whether these events occur early in the course of the pathology, or whether they develop at late stages of the disease and represent consequences of different alterations. Mitochondria are central to many aspects of cellular metabolism providing energy, lipids, reactive oxygen species, signaling molecules for cellular quality control, and actively shaping intracellular Ca signaling, modulating the intensity and duration of the signal itself.

PKA compartmentalization links cAMP signaling and autophagy.

Autophagy is a highly regulated degradative process crucial for maintaining cell homeostasis. This important catabolic mechanism can be nonspecific, but usually occurs with fine spatial selectivity (compartmentalization), engaging only specific subcellular sites. While the molecular machines driving autophagy are well understood, the involvement of localized signaling events in this process is not well defined.

Live Mitochondrial or Cytosolic Calcium Imaging Using Genetically-encoded Cameleon Indicator in Mammalian Cells.

Calcium (Ca) imaging aims at investigating the dynamic changes in live cells of its concentration ([Ca]) in different pathophysiological conditions. Ca is an ubiquitous and versatile intracellular signal that modulates a large variety of cellular functions thanks to a cell type-specific toolkit and a complex subcellular compartmentalization. Many Ca sensors are presently available (chemical and genetically encoded) that can be specifically targeted to different cellular compartments.

Calcium Signaling and Mitochondrial Function in Presenilin 2 Knock-Out Mice: Looking for Any Loss-of-Function Phenotype Related to Alzheimer's Disease.

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder in which learning, memory and cognitive functions decline progressively. Familial forms of AD (FAD) are caused by mutations in amyloid precursor protein (), presenilin 1 () and presenilin 2 () genes. Presenilin 1 (PS1) and its homologue, presenilin 2 (PS2), represent, alternatively, the catalytic core of the γ-secretase complex that, by cleaving APP, produces neurotoxic amyloid beta (Aβ) peptides responsible for one of the histopathological hallmarks in AD brains, the amyloid plaques.

The basics of mitochondrial cAMP signalling: Where, when, why.

Cytosolic cAMP signalling in live cells has been extensively investigated in the past, while only in the last decade the existence of an intramitochondrial autonomous cAMP homeostatic system began to emerge. Thanks to the development of novel tools to investigate cAMP dynamics and cAMP/PKA-dependent phosphorylation within the matrix and in other mitochondrial compartments, it is now possible to address directly and in intact living cells a series of questions that until now could be addressed only by indirect approaches, in isolated organelles or through subcellular fractionation studies. In this contribution we discuss the mechanisms that regulate cAMP dynamics at the surface and inside mitochondria, and its crosstalk with organelle Ca handling.

Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks.

Presenilin-2 (PS2) is one of the three proteins that are dominantly mutated in familial Alzheimer's disease (FAD). It forms the catalytic core of the γ-secretase complex-a function shared with its homolog presenilin-1 (PS1)-the enzyme ultimately responsible of amyloid-β (Aβ) formation. Besides its enzymatic activity, PS2 is a multifunctional protein, being specifically involved, independently of γ-secretase activity, in the modulation of several cellular processes, such as Ca signalling, mitochondrial function, inter-organelle communication, and autophagy.

ORAI2 Down-Regulation Potentiates SOCE and Decreases Aβ42 Accumulation in Human Neuroglioma Cells.

Senile plaques, the hallmarks of Alzheimer's Disease (AD), are generated by the deposition of amyloid-beta (Aβ), the proteolytic product of amyloid precursor protein (APP), by β and γ-secretase. A large body of evidence points towards a role for Ca imbalances in the pathophysiology of both sporadic and familial forms of AD (FAD). A reduction in store-operated Ca entry (SOCE) is shared by numerous FAD-linked mutations, and SOCE is involved in Aβ accumulation in different model cells.

Intracellular Calcium Dysregulation by the Alzheimer's Disease-Linked Protein Presenilin 2.

Alzheimer's disease (AD) is the most common form of dementia. Even though most AD cases are sporadic, a small percentage is familial due to autosomal dominant mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes. AD mutations contribute to the generation of toxic amyloid β (Aβ) peptides and the formation of cerebral plaques, leading to the formulation of the amyloid cascade hypothesis for AD pathogenesis.

Mitochondrial communication in the context of aging.

Mitochondria constantly contribute to the cell homeostasis and this, during the lifespan of a cell, takes its toll. Indeed, the functional decline of mitochondria appears correlated to the aging of the cell. The initial idea was that excessive production of reactive oxygen species (ROS) by functionally compromised mitochondria was the causal link between the decline of the organelle functions and cellular aging.

Dampened Slow Oscillation Connectivity Anticipates Amyloid Deposition in the PS2APP Mouse Model of Alzheimer's Disease.

To fight Alzheimer's disease (AD), we should know when, where, and how brain network dysfunctions initiate. In AD mouse models, relevant information can be derived from brain electrical activity. With a multi-site linear probe, we recorded local field potentials simultaneously at the posterior-parietal cortex and hippocampus of wild-type and double transgenic AD mice, under anesthesia.

Familial Alzheimer's disease presenilin-2 mutants affect Ca homeostasis and brain network excitability.

Alzheimer's disease (AD) is the most frequent cause of dementia in the elderly. Few cases are familial (FAD), due to autosomal dominant mutations in presenilin-1 (PS1), presenilin-2 (PS2) or amyloid precursor protein (APP). The three proteins are involved in the generation of amyloid-beta (Aβ) peptides, providing genetic support to the hypothesis of Aβ pathogenicity.

New Linear Precursors of cIDPR Derivatives as Stable Analogs of cADPR: A Potent Second Messenger with Ca-Modulating Activity Isolated from Sea Urchin Eggs.

Herein, we report on the synthesis of a small set of linear precursors of an inosine analogue of cyclic ADP-ribose (cADPR), a second messenger involved in Ca mobilization from ryanodine receptor stores firstly isolated from sea urchin eggs extracts. The synthesized compounds were obtained starting from inosine and are characterized by an N1-alkyl chain replacing the "northern" ribose and a phosphate group attached at the end of the N1-alkyl chain and/or 5'-sugar positions. Preliminary Ca mobilization assays, performed on differentiated C2C12 cells, are reported as well.

Studying β and β adrenergic receptor signals in cardiac cells using FRET-based sensors.

Cyclic 3'-5' adenosine monophosphate (cAMP) is a key modulator of cardiac function. Thanks to the sophisticated organization of its pathway in distinct functional units called microdomains, cAMP is involved in the regulation of both inotropy and chronotropy as well as transcription and cardiac death. While visualization of cAMP microdomains can be achieved thanks to cAMP-sensitive FRET-based sensors, the molecular mechanisms through which cAMP-generating stimuli are coupled to distinct functional outcomes are not well understood.