Impact of a Structured Social Skills Training Program on Adolescents and Young Adults with Level 1 Autism.

Background/objectives: Level 1 autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by challenges in social and communication skills. Despite these difficulties, individuals with level 1 ASD often exhibit average intelligence and typical language development. Improving socialisation skills in this population requires tailored approaches that address their specific needs and include targeted strategies.

Effectiveness of Equine-Assisted Activities and Therapies for Children with Autism Spectrum Disorder: An Update.

Background/objectives: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition requiring personalised therapeutic approaches. This study evaluated the effectiveness of Equine-Assisted Activities and Therapies (EAATs) in 86 children with varying ASD severity levels (levels 1-3).

Methods: Vineland Adaptive Behaviour Scales and the Parenting Stress Index were used.

Temporal implementation of a regional referral pathway in transthyretin cardiac amyloidosis: Emilia-Romagna experience.

Aims: Transthyretin cardiac amyloidosis (ATTR-CA) is a rare and progressive cardiomyopathy caused by amyloid fibril deposition in myocardial tissue. Diagnostic challenges have historically hampered timely detection. Recent advances in noninvasive diagnostic techniques have facilitated ATTR-CA diagnosis.

Moral Agency, Rules, and Temporality in People Who Are Diagnosed With Mild Forms of Autism: In Defense of a Sentimentalist View.

The origin of moral agency is a much-debated issue. While rationalists or Kantians have argued that moral agency is rooted in reason, sentimentalists or Humeans have ascribed its origin to empathic feelings. This debate between rationalists and sentimentalists still stands with respect to persons with mental disorders, such as individuals diagnosed with mild forms of Autism Spectrum Disorder (ASD), without intellectual impairment.

Parenting Stress and Social Style in Mothers and Fathers of Children with Autism Spectrum Disorder: A Cross-Cultural Investigation in Italy and Japan.

Parents of children with autism spectrum disorder (ASD) face unique challenges, which may affect parenting functioning. However, little is known about gender and cultural variations in parenting stress and styles in these families. The aims of this study were to investigate: (1a) the differences in parenting stress and (1b) social style between Italian and Japanese mothers and fathers of children with ASD; (2) the predictive role of culture, sociodemographic, and child's characteristics on parenting stress; (3) the predictors of the social parenting style, including parenting stress dimensions.

Author Correction: Characterization of the most frequent ATP7B mutation causing Wilson disease in hepatocytes from patient induced pluripotent stem cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Unconventional secretion of α-Crystallin B requires the Autophagic pathway and is controlled by phosphorylation of its serine 59 residue.

α-Crystallin B (CRYAB or HspB5) is a chaperone member of the small heat-shock protein family that prevents aggregation of many cytosolic client proteins by means of its ATP-independent holdase activity. Surprisingly, several reports show that CRYAB exerts a protective role also extracellularly, and it has been recently demonstrated that CRYAB is secreted from human retinal pigment epithelial cells by an unconventional secretion pathway that involves multi-vesicular bodies. Here we show that autophagy is crucial for this unconventional secretion pathway and that phosphorylation at serine 59 residue regulates CRYAB secretion by inhibiting its recruitment to the autophagosomes.

An αB-Crystallin Peptide Rescues Compartmentalization and Trafficking Response to Cu Overload of ATP7B-H1069Q, the Most Frequent Cause of Wilson Disease in the Caucasian Population.

The H1069Q substitution is the most frequent mutation of the Cu transporter ATP7B that causes Wilson disease in the Caucasian population. ATP7B localizes to the Golgi complex in hepatocytes, but, in the presence of excessive Cu, it relocates to the endo-lysosomal compartment to excrete Cu via bile canaliculi. In contrast, ATP7B-H1069Q is strongly retained in the ER, does not reach the Golgi complex and fails to move to the endo-lysosomal compartment in the presence of excessive Cu, thus causing toxic Cu accumulation.

Differential phosphorylation-based regulation of αB-crystallin chaperone activity for multipass transmembrane proteins.

We have previously shown that αB-crystallin (CRYAB), a small heat shock protein (sHsp) that prevents irreversible aggregation of unfolded protein by an ATP-independent chaperone activity, plays a pivotal role in the biogenesis of multipass transmembrane proteins (TMPs) assisting their folding from the cytosolic side of the endoplasmic reticulum (ER) (D'Agostino et al., 2013). Here we present evidence, based on phosphomimetic substitutions, that the three phosphorytable serine residues at position 19, 45 and 59 of CRYAB play a different regulatory role in this novel chaperone activity: S19 and S45 have a strong inhibitory effect, either alone or in combination, while S59 has not and counteracts the inhibition caused by single phosphomimetic substitutions at S19 and S45.

Adenosine plasma level correlates with homocysteine and uric acid concentrations in patients with coronary artery disease.

The role of hyperhomocysteinemia in coronary artery disease (CAD) patients remains unclear. The present study evaluated the relationship between homocysteine (HCys), adenosine plasma concentration (APC), plasma uric acid, and CAD severity evaluated using the SYNTAX score. We also evaluated in vitro the influence of adenosine on HCys production by hepatoma cultured cells (HuH7).

Pharmacological folding chaperones act as allosteric ligands of Frizzled4.

Upon binding, ligands can chaperone their protein targets by preventing them from misfolding and aggregating. Thus, an organic molecule that works as folding chaperone for a protein might be its specific ligand, and, similarly, the chaperone potential could represent an alternative readout in a molecular screening campaign toward the identification of new hits. Here we show that small molecules selected for acting as pharmacological chaperones on a misfolded mutant of the Frizzled4 (Fz4) receptor bind and modulate wild-type Fz4, representing what are to our knowledge the first organic ligands of this until-now-undruggable GPCR.

ER reorganization is remarkably induced in COS-7 cells accumulating transmembrane protein receptors not competent for export from the endoplasmic reticulum.

The newly synthesized mutant L501fsX533 Frizzled-4 form and the alpha3beta4 nicotinic acetylcholine receptor expressed in the absence of nicotine accumulate in the endoplasmic reticulum of COS-7 cells and induce the formation of large areas of smooth and highly convoluted cisternae. This results in a generalized block of the transport to the Golgi complex of newly synthesized proteins. Intriguingly, both effects happen peculiarly in COS-7 cells; HeLa, Huh-7, and HEK293 cells expressing the two receptors at similar level than COS-7 cells show normal ER and normal transport toward the plasma membrane.

Low-level laser therapy and light-emitting diode effects in the secretion of neuropeptides SP and CGRP in rat skin.

The phototherapy effects in the skin are related to biomodulation, usually to accelerate wound healing. However, there is no direct proof of the interrelation between the effects of low-level laser therapy (LLLT) and light-emitting diode (LED) in neuropeptide secretion, these substances being prematurely involved in the neurogenic inflammation phase of wound healing. This study therefore focused on investigating LLLT and LED in Calcitonin gene-related peptide (CGRP) and substance P (SP) secretion in healthy rat skin.

A disorder-to-order structural transition in the COOH-tail of Fz4 determines misfolding of the L501fsX533-Fz4 mutant.

Frizzled 4 belongs to the superfamily of G protein coupled receptors. The unstructured cytosolic tail of the receptor is essential for its activity. The mutation L501fsX533 in the fz4 gene results in a new COOH-tail of the receptor and causes a form of Familial exudative vitreoretinopathy.

The cytosolic chaperone α-crystallin B rescues folding and compartmentalization of misfolded multispan transmembrane proteins.

The α-crystallin B chain (CRYAB or HspB5) is a cytosolic chaperone belonging to the small heat shock protein family, which is known to help in the folding of cytosolic proteins. Here we show that CRYAB binds the mutant form of at least two multispan transmembrane proteins (TMPs), exerting an anti-aggregation activity. It rescues the folding of mutant Frizzled4, which is responsible for a rare autosomal dominant form of familial exudative vitreoretinopathy (Fz4-FEVR), and the mutant ATP7B Cu transporter (ATP7B-H1069Q) associated with a common form of Wilson's disease.

Familial exudative vitreoretinopathy caused by a homozygous mutation in TSPAN12 in a cystic fibrosis infant.

Familial exudative vitreoretinopathy (FEVR) is a genetic disease affecting the vascularization of the peripheral retina. The clinical manifestations are very heterogeneous, ranging from mildly affected patients, who could present no visual defects, to severe conditions which can also cause complete blindness at birth or in the first decade. FEVR can be inherited in all the three genetic forms: dominant, recessive and X-linked.

Impaired stimulation of p38α-MAPK/Vps41-HOPS by LPS from pathogenic Coxiella burnetii prevents trafficking to microbicidal phagolysosomes.

Variations in lipopolysaccharide (LPS), a bacterial outer membrane component, determine virulence of the obligate intracellular bacterium Coxiella burnetii, but the underlying mechanisms are unknown. We find that while avirulent C. burnetii LPS (avLPS) stimulates host p38α-MAPK signaling required for proper trafficking of bacteria containing compartments to lysosomes for destruction, pathogenic C.

Ligand of Numb proteins LNX1p80 and LNX2 interact with the human glycoprotein CD8α and promote its ubiquitylation and endocytosis.

E3 ubiquitin ligases give specificity to the ubiquitylation process by selectively binding substrates. Recently, their function has emerged as a crucial modulator of T-cell tolerance and immunity. However, substrates, partners and mechanism of action for most E3 ligases remain largely unknown.

In vitro effect of 470 nm LED (Light Emitting Diode) in keloid fibroblasts.

Purpose: To quantify keloid fibroblasts after irradiation with 470nm blue LED, in vitro.

Methods: Fibroblasts from keloid and adjacent skin have been obtained from 6 patients. Cells have been cultivated and maintained in DMEM culture medium.

Keloids: a new challenge for nutrition.

Keloids are the result of a dysfunctional scarring process that leads to excessive deposition of extracellular matrix in susceptible individuals, causing them physical, psychological, and social discomfort. Many studies have investigated various aspects of keloid physiopathology; however, the relationship between dietary components and keloids has not received much attention. The present literature review was conducted to examine the available evidence related to the relationships between nutrition/nutrients and keloids.

Non-coding RNAs change their expression profile after Retinoid induced differentiation of the promyelocytic cell line NB4.

Background: The importance of non-coding RNAs (ncRNAs) as fine regulators of eukaryotic gene expression has emerged by several studies focusing on microRNAs (miRNAs). miRNAs represent a newly discovered family of non coding-RNAs. They are thought to be crucial players of human hematopoiesis and related tumorigenesis and to represent a potential tool to detect the early stages of cancer.

GRASP65 and GRASP55 sequentially promote the transport of C-terminal valine-bearing cargos to and through the Golgi complex.

The Golgi matrix proteins GRASP65 and GRASP55 have recognized roles in maintaining the architecture of the Golgi complex, in mitotic progression and in unconventional protein secretion whereas, surprisingly, they have been shown to be dispensable for the transport of commonly used reporter cargo proteins along the secretory pathway. However, it is becoming increasingly clear that many trafficking machineries operate in a cargo-specific manner, thus we have investigated whether GRASPs may control the trafficking of selected classes of cargo. We have taken into consideration the C-terminal valine-bearing receptors CD8alpha and Frizzled4 that we show bind directly to the PSD95-DlgA-zo-1 (PDZ) domains of GRASP65 and GRASP55.