Presenilins as hub proteins controlling the endocytic and autophagic pathways and small extracellular vesicle secretion.

Emerging evidence indicates that autophagy is tightly connected to the endocytic pathway. Here, we questioned the role of presenilins (PSENs 1 and 2), previously shown to be involved in autophagy regulation, in the secretion of small endocytic-originating extracellular vesicles known as exosomes. Indeed, while wild-type cells responded to stimuli promoting both multivesicular endosome (MVE) formation and secretion of small extracellular vesicles (sEVs) enriched in canonical exosomal proteins, PSEN-deficient cells were almost unaffected to these stimuli.

SNARE-Mediated Membrane Fusion Probed Using a Synthetic Organelle in the Living Bacterium.

Studies on the mechanisms and regulation of functional assemblies of SNARE proteins mediating membrane fusion essentially make use of recombinant proteins and artificial phospholipid bilayers. We have developed an easy-to-use in vivo system reconstituting membrane fusion in living bacteria. It relies on the formation of caveolin-dependent intracytoplasmic cisternae followed by the controlled synthesis of members of the synaptic SNARE machinery.

Understanding the Emergence of Schizophrenia in the Light of Human Evolution: New Perspectives in Genetics.

Schizophrenia is a frequent and disabling disease. The persistence of the disorder despite its harmful consequences represents an evolutionary paradox. Based on recent discoveries in genetics, scientists have formulated the "price-to-pay" hypothesis: schizophrenia would be intimately related to human evolution, particularly to brain development and human-specific higher cognitive functions.

How to facilitate the wider use of pharmacogenetic tests?

4P medicine (personalized, preventive, predictive, and participatory) is experiencing a remarkable rise, and pharmacogenetics is an essential part of it. However, several obstacles are hindering its deployment. This round table brought together a group of experts to take stock of the situation, reflecting on ways to facilitate the prescription of these tests and the dissemination of the results on a national scale.

Theory of mind in schizophrenia through a clinical liability approach: a sib-pair study.

Background: Consistent findings indicate that Theory of Mind (ToM) is impaired in schizophrenia (SZ). To investigate whether such deficits are trait- or state-dependent, we investigated if ToM is modified by clinical liability markers (such as basic symptoms and psychotic-like experiences), focusing on the analysis of unaffected siblings of individuals diagnosed with SZ.

Methods: The study included a total of 65 participants: 38 patients diagnosed with a schizophrenia-spectrum disorder and 27 healthy siblings.

Protein palmitoylation in hepatic diseases: Functional insights and therapeutic strategies.

Background: Liver pathologies represent a spectrum of conditions ranging from fatty liver to the aggressive hepatocellular carcinoma (HCC), as well as parasitic infections, which collectively pose substantial global health challenges. S-palmitoylation (commonly referred to as palmitoylation), a post-translational modification (PTM) characterized by the covalent linkage of a 16-carbon palmitic acid (PA) chain to specific cysteine residues on target proteins, plays a pivotal role in diverse cellular functions and is intimately associated with the liver's physiological and pathological states.

Aim Of Review: This study aims to elucidate how protein palmitoylation affects liver disease pathophysiology and evaluates its potential as a target for diagnostic and therapeutic interventions.

Phenotypic traits and family history in patients with 22q11.2 deletion syndrome and generalized epilepsy: A multicenter case-control study.

Objective: This study was undertaken to characterize the clinical and genetic features of patients with 22q11.2 deletion syndrome (22q11.2DS) and generalized epilepsy compared with 22q11.

GABAR-PPT1 palmitoylation homeostasis controls synaptic transmission and circuitry oscillation.

The infantile neuronal ceroid lipofuscinosis, also called CLN1 disease, is a fatal neurodegenerative disease caused by mutations in the CLN1 gene encoding palmitoyl protein thioesterase 1 (PPT1). Identifying the depalmitoylation substrates of PPT1 is crucial for understanding CLN1 disease. In this study, we found that GABAR, the critical synaptic protein essential for inhibitory neurotransmission, is a substrate of PPT1.

Effects of horticultural therapy versus handiwork on anterior cingulate cortex activity in people with chronic low back pain: A randomized, controlled, cross-over, pilot study.

To assess the efficacy of horticultural therapy (HT) on anterior cingulate cortex (ACC) activity and the changes in rumination and catastrophizing scores in individuals with chronic low back pain (LBP). We conducted a randomized, controlled, cross-over, 3-week pilot study (ClinicalTrials.gov Identifier: NCT04656158).

Potential New Expression Biomarkers for Anorexia Nervosa.

Anorexia nervosa (AN) is a psychiatric disorder with an estimated heritability of around 70%. Although the largest meta-analysis of genome-wide association studies on AN identified independent risk-conferring loci for the disorder, the molecular mechanisms underlying the genetic basis of AN remain to be elucidated. To investigate AN, we performed transcriptome profiling in peripheral blood mononuclear cells from 15 AN patients and 15 healthy controls.

Cognitive impairment in the schizophrenia spectrum: exploring the relationships of the g-factor with sociodemography, psychopathology, neurodevelopment, and genetics.

Background: Cognitive impairment constitutes a prevailing issue in the schizophrenia spectrum, severely impacting patients' functional outcomes. A global cognitive score, sensitive to the stages of the spectrum, would benefit the exploration of potential factors involved in the cognitive decline.

Methods: First, we performed principal component analysis on cognitive scores from 768 individuals across the schizophrenia spectrum, including first-degree relatives of patients, individuals at ultra-high risk, who had a first-episode psychosis, and chronic schizophrenia patients, alongside 124 healthy controls.

Impact of minimal self disorders on naturalistic episodic memory in first-episode psychosis and parallels in healthy individuals with schizotypal traits.

Background: Self-disorders constitute a core feature of the schizophrenia spectrum, including early stages such as first-episode psychosis (FEP). These disorders impact the minimal Self, or bodily self-consciousness, which refers to the basic, pre-reflective sense of embodied experience. The minimal Self is intrinsically linked to episodic memory, which captures specific past experiences of the Self.

"The zipper technique"-a zip/unzip manoeuvre for thrombectomy in a giant coiled thrombotic aneurysm - how i do it.

Background: In GTA, exposing the neck is challenging, and temporary clipping is often not feasible, increasing the risk of intraoperative bleeding.

Method: An aneurysmotomy with a continuous lock on one side and a clip on the other is performed and functions as a "zipper." During thrombectomy, if bleeding occurs, the zipper closes for temporary clipping.

A Genetic Bridge Between Medicine and Neurodiversity for Autism.

Autism represents a large spectrum of diverse individuals with varying underlying genetic architectures and needs. For some individuals, a single de novo or ultrarare genetic variant has a large effect on the intensity of specific dimensions of the phenotype, while, for others, a combination of thousands of variants commonly found in the general population are involved. The variants with large impact are found in up to 30% of autistic individuals presenting with intellectual disability, significant speech delay, motor delay, and/or seizures.

MRI-Proven Incident Ischemia: A New Marker of Disease Progression in Small Vessel Diseases.

Background: In ischemic cerebral small vessel diseases (cSVD), recurrent ischemic stroke is rare (2%-3% per year). Because acute ischemia may not always lead to stroke in cSVD due to the small size of lesions, acute stroke may not reliably reflect ischemic activity or the risk of further clinical worsening, as both incident lacunes and incidental diffusion-weighted imaging-positive lesions can occur without stroke symptoms. We aimed to evaluate the total ischemic activity by measuring the incidence of magnetic resonance imaging (MRI)-proven incident ischemia, independent of the presence of stroke symptoms in a large cohort of cSVD.

Zdhhc1 deficiency mitigates foam cell formation and atherosclerosis by inhibiting PI3K-Akt-mTOR signaling pathway through facilitating the nuclear translocation of p110α.

Monocyte-to-macrophage differentiation and subsequent foam cell formation are key processes that contribute to plaque build-up during the progression of atherosclerotic lesions. Palmitoylation enzymes are known to play pivotal roles in the development and progression of inflammatory diseases. However, their specific impact on atherosclerosis development remains unclear.

Early-onset anorexia nervosa: a scoping review and management guidelines.

Background: Anorexia nervosa (AN) is a serious multifactorial eating disorder characterized by insufficient nutritional intake to maintain a minimum normal weight for one's age and height, a fear of gaining weight and a distorted body image. It affects mainly adolescents, but a decreased age at diagnosis has been reported, leading to the definition of a rare form of AN called early-onset or prepubertal anorexia nervosa (EOAN; ORPHA 525738), with reported epidemiological and clinical specificity. Current knowledge and specific treatments for this particular condition remain scarce.

NEDD4L contributes to ferroptosis and cell growth inhibition in esophageal squamous cell carcinoma by facilitating xCT ubiquitination.

The oncogene xCT plays an indispensable role in tumor growth by protecting cancer cells from oxidative stress and ferroptosis. Emerging evidence indicated xCT function is tightly controlled by posttranslational modifications, especially ubiquitination. However, it still remains unclear what specific regulatory mechanism of xCT by ubiquitin ligases in human cancers.

Phenotypic and epigenetic heterogeneity in FGFR2-fused glial and glioneuronal tumours.

Aims: FGFR-fused central nervous system (CNS) tumours are rare and are usually within the glioneuronal and neuronal tumours or the paediatric-type diffuse low-grade glioma spectrum. Among this spectrum, FGFR2 fusion has been documented in tumours classified by DNA-methylation profiling as polymorphous low-grade neuroepithelial tumours of the young (PLNTY), a recently described tumour type. However, FGFR2 fusions have also been reported in glioneuronal tumours, highlighting the overlapping diagnostic criteria and challenges.