Modeling Sporadic Progressive Supranuclear Palsy in 3D Midbrain Organoids: Recapitulating Disease Features for In Vitro Diagnosis and Drug Discovery.

Objective: Progressive Supranuclear Palsy (PSP) is a severe neurodegenerative disease characterized by tangles of hyperphosphorylated tau protein and tufted astrocytes. Developing treatments for PSP is challenging due to the lack of disease models reproducing its key pathological features. This study aimed to model sporadic PSP-Richardson's syndrome (PSP-RS) using multi-donor midbrain organoids (MOs).

Serum Tau Species in Progressive Supranuclear Palsy: A Pilot Study.

Background/objectives: Progressive Supranuclear Palsy (PSP) is a tauopathy showing a marked symptoms overlap with Parkinson's Disease (PD). PSP pathology suggests that tau protein might represent a valuable biomarker to distinguish between the two diseases. Here, we investigated the presence and diagnostic value of six different tau species (total tau, 4R-tau isoform, tau aggregates, p-tau202, p-tau231 and p-tau396) in serum from 13 PSP and 13 PD patients and 12 healthy controls (HCs).

Generation of hiPSCs lines from three sporadic Parkinson's disease patients.

Here, we described the generation of human induced pluripotent stem cell lines (hiPSCs) from three sporadic Parkinson's disease (sPD) patients by reprogramming of their peripheral blood mononuclear cells (PBMC).

Erythrocytic α-Synuclein in Parkinson's Disease and Progressive Supranuclear Palsy-A Pilot Study.

The current research examines the accuracy of α-synuclein in RBCs as a diagnostic biomarker for PD and PSP, despite their distinct molecular etiologies. We used ELISA to measure total, oligomeric, and p129-α-synuclein levels in erythrocytes from 8 PSP patients, 19 PD patients, and 18 healthy controls (HCs). The classification performances of RBC α-synuclein levels were investigated by receiver operator characteristic (ROC) curve.

Serum Oligomeric α-Synuclein and p-tau181 in Progressive Supranuclear Palsy and Parkinson's Disease.

Clinical differentiation of progressive supranuclear palsy (PSP) from Parkinson's disease (PD) is challenging due to overlapping phenotypes and the late onset of specific atypical signs. Therefore, easily assessable diagnostic biomarkers are highly needed. Since PD is a synucleopathy while PSP is a tauopathy, here, we investigated the clinical usefulness of serum oligomeric-α-synuclein (o-α-synuclein) and 181Thr-phosphorylated tau (p-tau181), which are considered as the most important pathological protein forms in distinguishing between these two parkinsonisms.

Unraveling the impact of ZZZ3 on the mTOR/ribosome pathway in human embryonic stem cells homeostasis.

Embryonic stem cells (ESCs) are defined as stem cells with self-renewing and differentiation capabilities. These unique properties are tightly regulated and controlled by complex genetic and molecular mechanisms, whose understanding is essential for both basic and translational research. A large number of studies have mostly focused on understanding the molecular mechanisms governing pluripotency and differentiation of ESCs, while the regulation of proliferation has received comparably less attention.

Combined blood Neurofilament light chain and third ventricle width to differentiate Progressive Supranuclear Palsy from Parkinson's Disease: A machine learning study.

Introduction: Differentiating Progressive Supranuclear Palsy (PSP) from Parkinson's Disease (PD) may be clinically challenging. In this study, we explored the performance of machine learning models based on MR imaging and blood molecular biomarkers in distinguishing between these two neurodegenerative diseases.

Methods: Twenty-eight PSP patients, 46 PD patients and 60 control subjects (HC) were consecutively enrolled in the study.

Attention to cardiac sensations enhances the heartbeat-evoked potential during exhalation.

Respiration and cardiac activity intricately interact through complex physiological mechanisms. The heartbeat-evoked potential (HEP) is an EEG fluctuation reflecting the cortical processing of cardiac signals. We recently found higher HEP amplitude during exhalation than inhalation during a task involving attention to cardiac sensations.

Ascorbic acid mitigates the impact of oxidative stress in a human model of febrile seizure and mesial temporal lobe epilepsy.

Prolonged febrile seizures (FS) in children are linked to the development of temporal lobe epilepsy (MTLE). The association between these two pathologies may be ascribed to the long-term effects that FS exert on neural stem cells, negatively affecting the generation of new neurons. Among the insults associated with FS, oxidative stress is noteworthy.

Heart is deceitful above all things: Threat expectancy induces the illusory perception of increased heartrate.

It has been suggested that our perception of the internal milieu, or the body's internal state, is shaped by our beliefs and previous knowledge about the body's expected state, rather than being solely based on actual interoceptive experiences. This study investigated whether heartbeat perception could be illusorily distorted towards prior subjective beliefs, such that threat expectations suffice to induce a misperception of heartbeat frequency. Participants were instructed to focus on their cardiac activity and report their heartbeat, either tapping along to it (Experiment 1) or silently counting (Experiment 2) while ECG was recorded.

Early categorization of social affordances during the visual encoding of bodily stimuli.

Interpersonal interactions rely on various communication channels, both verbal and non-verbal, through which information regarding one's intentions and emotions are perceived. Here, we investigated the neural correlates underlying the visual processing of hand postures conveying social affordances (i.e.

It's not always an infection: Pyoderma gangrenosum of the urogenital tract in two patients with multiple sclerosis treated with rituximab.

B-cell depleting therapies such as rituximab and ocrelizumab are widely used for the treatment of Multiple Sclerosis but have increased risks of adverse reactions compared to earlier MS therapies. One rarely reported reaction is pyoderma gangrenosum (PG), an inflammatory, ulcerative, skin disease of unclear etiology. Here we describe a male and female patient, each with Relapsing-Remitting Multiple Sclerosis, and both of whom developed PG while on rituximab.

Insights into the Genetic Profile of Two Siblings Affected by Unverricht-Lundborg Disease Using Patient-Derived hiPSCs.

Unverricht-Lundborg disease (ULD), also known as progressive myoclonic epilepsy 1 (EPM1), is a rare autosomal recessive neurodegenerative disorder characterized by a complex symptomatology that includes action- and stimulus-sensitive myoclonus and tonic-clonic seizures. The main cause of the onset and development of ULD is a repeat expansion of a dodecamer sequence localized in the promoter region of the gene encoding cystatin B (CSTB), an inhibitor of lysosomal proteases. Although this is the predominant mutation found in most patients, the physio-pathological mechanisms underlying the disease complexity remain largely unknown.

Brain-heart interactions are modulated across the respiratory cycle via interoceptive attention.

Respiration and heartbeat continuously interact within the living organism at many different levels, representing two of the main oscillatory rhythms of the body and providing major sources of interoceptive information to the brain. Despite the modulatory effect of respiration on exteroception and cognition has been recently established in humans, its role in shaping interoceptive perception has been scarcely investigated so far. In two independent studies, we investigated the effect of spontaneous breathing on cardiac interoception by assessing the Heartbeat Evoked Potential (HEP) in healthy humans.

Microfluidics for 3D Cell and Tissue Cultures: Microfabricative and Ethical Aspects Updates.

The necessity to improve in vitro cell screening assays is becoming ever more important. Pharmaceutical companies, research laboratories and hospitals require technologies that help to speed up conventional screening and therapeutic procedures to produce more data in a short time in a realistic and reliable manner. The design of new solutions for test biomaterials and active molecules is one of the urgent problems of preclinical screening and the limited correlation between in vitro and in vivo data remains one of the major issues.

Human iPSC Modeling of Genetic Febrile Seizure Reveals Aberrant Molecular and Physiological Features Underlying an Impaired Neuronal Activity.

Mutations in SCN1A gene, encoding the voltage-gated sodium channel (VGSC) NaV1.1, are widely recognized as a leading cause of genetic febrile seizures (FS), due to the decrease in the Na+ current density, mainly affecting the inhibitory neuronal transmission. Here, we generated induced pluripotent stem cells (iPSCs)-derived neurons (idNs) from a patient belonging to a genetically well-characterized Italian family, carrying the c.

Direct Visualization and Identification of Membrane Voltage-Gated Sodium Channels from Human iPSC-Derived Neurons by Multiple Imaging and Light Enhanced Spectroscopy.

In this study, transmission electron microscopy atomic force microscopy, and surface enhanced Raman spectroscopy are combined through a direct imaging approach, to gather structural and chemical information of complex molecular systems such as ion channels in their original plasma membrane. Customized microfabricated sample holder allows to characterize Na channels embedded in the original plasma membrane extracted from neuronal cells that are derived from healthy human induced pluripotent stem cells. The identification of the channels is accomplished by using two different approaches, one of them widely used in cryo-EM (the particle analysis method) and the other based on a novel Zernike Polynomial expansion of the images bitmap.

Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors.

Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host-graft crosstalk remains elusive. Here, by combining lineage tracing and single-cell transcriptomics in injured non-human primate heart biomimics, we uncover the coordinated action modes of human progenitor-mediated muscle repair.

Uncovering the Metabolic and Stress Responses of Human Embryonic Stem Cells to Gene Silencing.

Embryonic stem cells (ESCs) are pluripotent cells with indefinite self-renewal ability and differentiation properties. To function properly and maintain genomic stability, ESCs need to be endowed with an efficient repair system as well as effective redox homeostasis. In this study, we investigated different aspects involved in ESCs' response to iron accumulation following stable knockdown of the ferritin heavy chain (FTH1) gene, which encodes for a major iron storage protein with ferroxidase activity.

Generation of human induced pluripotent stem cell lines (UNIMGi003-A and UNIMGi004-A) from two Italian siblings affected by Unverricht-Lundborg disease.

Unverricht-Lundborg disease (ULD) is an inherited form of progressive myoclonus epilepsy caused by mutations in the gene encoding Cystatin B (CSTB), an inhibitor of lysosomal proteases. The most common mutation described in ULD patients is an unstable expansion of a dodecamer sequence located in the CSTB gene promoter. This expansion is causative of the downregulation of CSTB gene expression and, consequently, of its inhibitory activity.

Deciphering the Role of Wnt and Rho Signaling Pathway in iPSC-Derived ARVC Cardiomyocytes by In Silico Mathematical Modeling.

Arrhythmogenic Right Ventricular cardiomyopathy (ARVC) is an inherited cardiac muscle disease linked to genetic deficiency in components of the desmosomes. The disease is characterized by progressive fibro-fatty replacement of the right ventricle, which acts as a substrate for arrhythmias and sudden cardiac death. The molecular mechanisms underpinning ARVC are largely unknown.

Generation of iPSC lines from two patients affected by febrile seizure due to inherited missense mutation in SCN1A gene.

Here, we described the generation of human induced pluripotent stem cell lines (hiPSCs) from fibroblasts isolated by punch biopsies of two siblings carrying inherited mutation (c.434 T > C) in the SCN1A gene, encoding for the neuronal voltage gated sodium channel Na1.1.