Unraveling the Membrane Topology of TMEM151A: A Step Towards Understanding its Cellular Role.

Transmembrane protein 151A (TMEM151A) has been identified as a causative gene for paroxysmal kinesigenic dyskinesia, though its molecular function remains almost completely unknown. Understanding the membrane topology of transmembrane proteins is crucial for elucidating their functions and possible interacting partners. In this study, we utilized molecular dynamics simulations, immunocytochemistry, and electron microscopy to define the topology of TMEM151A.

The Role of Virtual Reality in the Management of Football Injuries.

Injuries represent a serious concern for football players, with a significant loss in terms of sport participation and long periods of rehabilitation. According to the 2019/20 UEFA Élite Club Injury Report, the average incidence of injuries during training is 2.8 per 1000 h of training, with an average absence from training of 20 days.

Myocarditis in an FIP-Diseased Cat with FCoV M1058L Mutation: Clinical and Pathological Changes.

An 8-month-old intact male domestic shorthair cat was referred to the Emergency Service of the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Science of the University of Parma (Italy) from the Parma municipal multi-cat shelter, during the winter season (January 2023), for lethargy, anorexia, hypothermia, and hypoglycemia. At the VTH, upon cardiologic examination, an increase in heart rate, under normal blood pressure conditions, was detected. Signalment, clinical history, basal metabolic panel (BMP), ultrasound investigations, and cytological findings were all consistent with a diagnosis of feline infectious peritonitis (FIP).

Scoring Enzootic Pneumonia-like Lesions in Slaughtered Pigs: Traditional vs. Artificial-Intelligence-Based Methods.

Artificial-intelligence-based methods are regularly used in the biomedical sciences, mainly in the field of diagnostic imaging. Recently, convolutional neural networks have been trained to score pleurisy and pneumonia in slaughtered pigs. The aim of this study is to further evaluate the performance of a convolutional neural network when compared with the gold standard (i.

MEK1/2 regulate normal BCR and ABL1 tumor-suppressor functions to dictate ATO response in TKI-resistant Ph+ leukemia.

Resistance to tyrosine kinase inhibitors (TKIs) remains a clinical challenge in Ph-positive variants of chronic myeloid leukemia. We provide mechanistic insights into a previously undisclosed MEK1/2/BCR::ABL1/BCR/ABL1-driven signaling loop that may determine the efficacy of arsenic trioxide (ATO) in TKI-resistant leukemic patients. We find that activated MEK1/2 assemble into a pentameric complex with BCR::ABL1, BCR and ABL1 to induce phosphorylation of BCR and BCR::ABL1 at Tyr360 and Tyr177, and ABL1, at Thr735 and Tyr412 residues thus provoking loss of BCR's tumor-suppression functions, enhanced oncogenic activity of BCR::ABL1, cytoplasmic retention of ABL1 and consequently drug resistance.

Missense mutations in the membrane domain of PRRT2 affect its interaction with Nav1.2 voltage-gated sodium channels.

PRRT2 is a neuronal protein that controls neuronal excitability and network stability by modulating voltage-gated Na channel (Nav). PRRT2 pathogenic variants cause pleiotropic syndromes including epilepsy, paroxysmal kinesigenic dyskinesia and episodic ataxia attributable to loss-of-function pathogenetic mechanism. Based on the evidence that the transmembrane domain of PRRT2 interacts with Nav1.

Modeling PCDH19 clustering epilepsy by Neurogenin 2 induction of patient-derived induced pluripotent stem cells.

Background: Loss of function mutations in PCDH19 gene causes an X-linked, infant-onset clustering epilepsy, associated with intellectual disability and autistic features. The unique pattern of inheritance includes random X-chromosome inactivation, which leads to pathological tissue mosaicism. Females carrying PCDH19 mutations are affected, while males have a normal phenotype.

The intramembrane COOH-terminal domain of PRRT2 regulates voltage-dependent Na channels.

Proline-rich transmembrane protein 2 (PRRT2) is the single causative gene for pleiotropic paroxysmal syndromes, including epilepsy, kinesigenic dyskinesia, episodic ataxia, and migraine. PRRT2 is a neuron-specific type-2 membrane protein with a COOH-terminal intramembrane domain and a long proline-rich NH-terminal cytoplasmic region. A large array of experimental data indicates that PRRT2 is a neuron stability gene that negatively controls intrinsic excitability by regulating surface membrane localization and biophysical properties of voltage-dependent Na channels Nav1.

An Overview of Epithelial-to-Mesenchymal Transition and Mesenchymal-to-Epithelial Transition in Canine Tumors: How Far Have We Come?

Historically, pre-clinical and clinical studies in human medicine have provided new insights, pushing forward the contemporary knowledge. The new results represented a motivation for investigators in specific fields of veterinary medicine, who addressed the same research topics from different perspectives in studies based on experimental and spontaneous animal disease models. The study of different pheno-genotypic contexts contributes to the confirmation of translational models of pathologic mechanisms.

Nipah Virus Disease: Epidemiological, Clinical, Diagnostic and Legislative Aspects of This Unpredictable Emerging Zoonosis.

Nipah virus (NiV) infection is a viral disease caused by a Henipavirus, belonging to the Paramyxoviridae family, responsible for a zoonosis. The course of the disease can be very serious and lead to death. NiV natural hosts are fruit bats (also known as megabats) belonging to the Pteropodidae family, especially those of the genus.

A Push-Pull Mechanism Between PRRT2 and β4-subunit Differentially Regulates Membrane Exposure and Biophysical Properties of NaV1.2 Sodium Channels.

Proline-rich transmembrane protein 2 (PRRT2) is a neuron-specific protein implicated in the control of neurotransmitter release and neural network stability. Accordingly, PRRT2 loss-of-function mutations associate with pleiotropic paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia, episodic ataxia, benign familial infantile seizures, and hemiplegic migraine. PRRT2 is a negative modulator of the membrane exposure and biophysical properties of Na channels Na1.

Use of the international classification of diseases (ICD)-11 method applied to veterinary forensic pathology for coding the cause and manner of death in wildlife.

The growth of human population has led, in recent years, to increasingly frequent contacts with the wild animals with which we share the territory, sometimes leading to negative interactions with them. The purpose of the study is to apply the codes contained in the 11th Revision of the International Classification of Diseases (ICD-11) method to investigate the cause and the manner of death, also to entrust the veterinarian with the task of recognizing and describing a suspected animal abuse as a sentinel indicator of violence toward humans and non-humans, thus expanding the concept of "One Health" from a forensic investigation perspective. The subjects recruited are wild mammals submitted for autopsy to the Pathology Unit of the Department of Veterinary Science, University of Parma, Italy, from 2015 to 2018.

Impact of an empiric antimicrobial therapy manual on antimicrobial usage and multidrug resistant organism trends in a large Italian teaching hospital.

Aim: To evaluate the changes in antimicrobial consumption and multidrug-resistant microorganism trends after introducing an empiric antimicrobial therapy manual to support antimicrobial stewardship.

Methods: A 4-year prospective interventional study assessed the effect of introducing an empiric antimicrobial therapy manual in medical and surgical wards during two periods: pre-intervention period (January 2015-May 2017) and post-intervention period (June 2017-December 2019). Outcomes included microorganism trends of bloodstream infections (BSI) for carbapenemase-producing bacteria (KPC), extended spectrum beta-lactamase ESBL-, meticillin-resistant (MRSA) and .

Stress in Medical Students: PRIMES, an Italian, Multicenter Cross-Sectional Study.

Medical students (MSs) are healthcare workers and must also cope with education-related stressors. This study aims to assess factors associated with perceived stress in Italian MSs. A cross-sectional study was conducted in 12 Italian medical schools (MSCs) in November 2018.

An Architecture for Service Integration to Fully Support Novel Personalized Smart Tourism Offerings.

The continuous evolution of IT (information technology) technologies is radically transforming many technical areas and social aspects, also reshaping the way we behave and looking for entertainment and leisure services. In that context, tourism experiences request to enhance the level of user involvement and integration and to create an ever more personalized and connected experience, by leveraging on the differentiated tourist services and information locally present in the territory, by pushing active participation of customers, and by taking advantage of the ever-increasing presence of sensors and IoT (Internet of Things) devices deployed in many realities. However, the deep fragmentation of services and technologies adopted in tourism context characterizes the whole information provided also by customer sensing and IoTs (Internet of Things) heterogeneity and deep clashes with an effective organization of smart tourism.

A Layered Middleware for OT/IT Convergence to Empower Industry 5.0 Applications.

We are still in the midst of Industry 4.0 (I4.0), with more manufacturing lines being labeled as smart thanks to the integration of advanced ICT in Cyber-Physical Systems (CPS).

A Digital Twin Decision Support System for the Urban Facility Management Process.

The ever increasing pace of IoT deployment is opening the door to concrete implementations of smart city applications, enabling the large-scale sensing and modeling of (near-)real-time digital replicas of physical processes and environments. This digital replica could serve as the basis of a decision support system, providing insights into possible optimizations of resources in a smart city scenario. In this article, we discuss an extension of a prior work, presenting a detailed proof-of-concept implementation of a Digital Twin solution for the Urban Facility Management (UFM) process.

SARS-CoV-2 infection: efficacy of extensive vaccination of the healthcare workforce in a large Italian hospital.

Background: A prospective observational study involved 13,787 Health Care Workers (HCWs) of a large hospital to assess the effectiveness of a SARS-CoV-2 mRNA vaccine.

Methods: The daily incidence of infections was estimated from 1st October 2020 to 30th April 2021 and compared with that of the province of Turin (2.26 million).

An Emerging Role of PRRT2 in Regulating Growth Cone Morphology.

Mutations in the PRRT2 gene are the main cause for a group of paroxysmal neurological diseases including paroxysmal kinesigenic dyskinesia, episodic ataxia, benign familial infantile seizures, and hemiplegic migraine. In the mature central nervous system, the protein has both a functional and a structural role at the synapse. Indeed, PRRT2 participates in the regulation of neurotransmitter release, as well as of actin cytoskeleton dynamics during synaptogenesis.

QoS-Aware Approximate Query Processing for Smart Cities Spatial Data Streams.

Large amounts of georeferenced data streams arrive daily to stream processing systems. This is attributable to the overabundance of affordable IoT devices. In addition, interested practitioners desire to exploit Internet of Things (IoT) data streams for strategic decision-making purposes.

PRRT2 modulates presynaptic Ca influx by interacting with P/Q-type channels.

Loss-of-function mutations in proline-rich transmembrane protein-2 (PRRT2) cause paroxysmal disorders associated with defective Ca dependence of glutamatergic transmission. We find that either acute or constitutive PRRT2 deletion induces a significant decrease in the amplitude of evoked excitatory postsynaptic currents (eEPSCs) that is insensitive to extracellular Ca and associated with a reduced contribution of P/Q-type Ca channels to the EPSC amplitude. This synaptic phenotype parallels a decrease in somatic P/Q-type Ca currents due to a decreased membrane targeting of the channel with unchanged total expression levels.

Beyond COVID-19: a cross-sectional study in Italy exploring the covid collateral impacts on healthcare services.

With COVID-19, populations are facing unmet health needs due to fear of contagion, lockdown measures and overload of Healthcare services (HCS). The COCOS study aimed to investigate reduced healthcare access among Italian citizens, additionally looking for specific subgroups that will primarily need health services in the next future. A cross-sectional online survey was performed during the Italian lockdown between April and May 2020.