The alpha-synuclein oligomers activate nuclear factor of activated T-cell (NFAT) modulating synaptic homeostasis and apoptosis.

Background: Soluble oligomeric forms of alpha-synuclein (aSyn-O) are believed to be one of the main toxic species in Parkinson's disease (PD) leading to degeneration. aSyn-O can induce Ca influx, over activating downstream pathways leading to PD phenotype. Calcineurin (CN), a phosphatase regulated by Ca levels, activates NFAT transcription factors that are involved in the regulation of neuronal plasticity, growth, and survival.

Connection between MHC class II binding and aggregation propensity: The antigenic peptide 10 of as a benchmark study.

The aggregation of epitopes that are also able to bind major histocompatibility complex (MHC) alleles raises questions around the potential connection between the formation of epitope aggregates and their affinities to MHC receptors. We first performed a general bioinformatic assessment over a public dataset of MHC class II epitopes, finding that higher experimental binding correlates with higher aggregation-propensity predictors. We then focused on the case of P10, an epitope used as a vaccine candidate against that aggregates into amyloid fibrils.

The same strain leading to different clinical outcomes: The enigma behind the canine leptospirosis.

Canine leptospirosis is a worldwide zoonosis, varying from asymptomatic and chronic infections to clinical acute disease. In many parts of the world Leptospira interrogans serogroup Icterohaemorrhagiae strains have great epidemiological importance, being the most prevalent on dogs. The present study aims to characterize and compare strains/sequences belonging to the serogroup Icterohaemorrhagiae recovered from clinically ill and asymptomatic dogs.

Peptides derived from gp43, the most antigenic protein from Paracoccidioides brasiliensis, form amyloid fibrils in vitro: implications for vaccine development.

Fungal infection is an important health problem in Latin America, and in Brazil in particular. Paracoccidioides (mainly P. brasiliensis and P.

Disease-associated mutations impacting BC-loop flexibility trigger long-range transthyretin tetramer destabilization and aggregation.

Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant disease characterized by the extracellular deposition of the transport protein transthyretin (TTR) as amyloid fibrils. Despite the progress achieved in recent years, understanding why different TTR residue substitutions lead to different clinical manifestations remains elusive. Here, we studied the molecular basis of disease-causing missense mutations affecting residues R34 and K35.

Pentameric Thiophene as a Probe to Monitor EGCG's Remodeling Activity of Mature Amyloid Fibrils: Overcoming Signal Artifacts of Thioflavin T.

Thioflavin T fluorescence is a gold standard probe for the detection of amyloid fibrils. Herein, we showed that mature amyloid fibrils incubated with polyphenol epigallocatechin gallate (EGCG) present a fast reduction of the thioflavin T fluorescence, which is not related to remodeling activity. We propose the use of the pentameric thiophene fluorescence for monitoring the polyphenol remodeling activity.

Padded Headgear does not Reduce the Incidence of Match Concussions in Professional Men's Rugby Union: A Case-control Study of 417 Cases.

Concussion is the most common match injury in rugby union. Some players wear padded headgear, but whether this protects against concussion is unclear. In professional male rugby union players, we examined: (i) the association between the use of headgear and match concussion injury incidence, and (ii) whether wearing headgear influenced time to return to play following concussion.

Rugby union referees' physical and physiological demands across different competitive levels.

Background: The purpose of this study was to compare the match demands of officiating 15-a-side rugby union at different competitive levels.

Methods: Data was collected using Global Navigation Satellite Systems from 21 referees during 82 competitive rugby union matches across three different competitive levels: 1) professional; 2) semi-professional; 3) amateur.

Results: Compared with referees at the professional and semi-professional levels, referees at the amateur level covered less total distance (P=0.

Physical Demands of Refereeing Rugby Sevens Matches at Different Competitive Levels.

Sant'Anna, RT, Roberts, SP, Moore, LJ, and Stokes, KA. Physical demands of refereeing rugby sevens matches at different competitive levels. J Strength Cond Res 35(11): 3164-3169, 2021-The aim of this study was to compare the physical demands of officiating across different competitive levels in rugby sevens.

Discovering Putative Prion-Like Proteins in : A Computational and Experimental Analysis.

Prions are a singular subset of proteins able to switch between a soluble conformation and a self-perpetuating amyloid state. Traditionally associated with neurodegenerative diseases, increasing evidence indicates that organisms exploit prion-like mechanisms for beneficial purposes. The ability to transit between conformations is encoded in the so-called prion domains, long disordered regions usually enriched in glutamine/asparagine residues.

Environmental and genetic factors support the dissociation between α-synuclein aggregation and toxicity.

Synucleinopathies are a group of progressive disorders characterized by the abnormal aggregation and accumulation of α-synuclein (aSyn), an abundant neuronal protein that can adopt different conformations and biological properties. Recently, aSyn pathology was shown to spread between neurons in a prion-like manner. Proteins like aSyn that exhibit self-propagating capacity appear to be able to adopt different stable conformational states, known as protein strains, which can be modulated both by environmental and by protein-intrinsic factors.

Characterization of Amyloid Cores in Prion Domains.

Amyloids consist of repetitions of a specific polypeptide chain in a regular cross-β-sheet conformation. Amyloid propensity is largely determined by the protein sequence, the aggregation process being nucleated by specific and short segments. Prions are special amyloids that become self-perpetuating after aggregation.

Aerobic power and field test results of amateur 15-a-side rugby union players.

Background: The aim of the present study was to verify whether it is possible to predict aerobic power in amateur 15-a-side rugby union players through the Yo-Yo Intermittent Recovery Test Level 1 (Yo-Yo IRT1) and the 5-meter Multiple Shuttle Test (5-m MST).

Methods: Forty-two amateur players - 22 forwards and 20 backs - were evaluated in three phases: 1) maximum treadmill test in the laboratory; 2) field test set by a drawing in the first phase; and 3) second field test. Descriptive, comparison, correlation, regression and level of agreement analyses were performed.

Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity.

Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological TTR aggregation. Native state stabilizers are promising drugs to treat TTR amyloidoses.

Amyloid properties of the leader peptide of variant B cystatin C: implications for Alzheimer and macular degeneration.

Variant B (VB) of cystatin C has a mutation in its signal peptide (A25T), which interferes with its processing leading to reduced secretion and partial retention in the vicinity of the mitochondria. There are genetic evidences of the association of VB with Alzheimer's disease (AD) and age-related macular degeneration (AMD). Here, we investigated aggregation and amyloid propensities of unprocessed VB combining computational and in vitro studies.

Mammalian prion protein (PrP) forms conformationally different amyloid intracellular aggregates in bacteria.

Background: An increasing number of proteins are being shown to assemble into amyloid structures that lead to pathological states. Among them, mammalian prions outstand due to their ability to transmit the pathogenic conformation, becoming thus infectious. The structural conversion of the cellular prion protein (PrP(C)), into its misfolded pathogenic form (PrP(Sc)) is the central event of prion-driven pathologies.

The importance of a gatekeeper residue on the aggregation of transthyretin: implications for transthyretin-related amyloidoses.

Protein aggregation into β-sheet-enriched amyloid fibrils is associated with an increasing number of human disorders. The adoption of such amyloid conformations seems to constitute a generic property of polypeptide chains. Therefore, during evolution, proteins have adopted negative design strategies to diminish their intrinsic propensity to aggregate, including enrichment of gatekeeper charged residues at the flanks of hydrophobic aggregation-prone segments.

Inhibition of human transthyretin aggregation by non-steroidal anti-inflammatory compounds: a structural and thermodynamic analysis.

Transthyretin (TTR) is a homotetrameric protein that circulates in plasma and cerebral spinal fluid (CSF) whose aggregation into amyloid fibrils has been associated with at least two different amyloid diseases: senile systemic amyloidosis (SSA) and familial amyloid polyneuropathy (FAP). In SSA aggregates are composed of WT-TTR, while in FAP more than 100 already-described variants have been found in deposits. Until now, TTR-related diseases have been untreatable, although a new drug called Tafamidis has been approved only in Europe to specifically treat V30M patients.

[Surgical myocardial revascularization in young patients].

Purpose: To determine early and late results of surgical myocardial revascularization (SMR) in young patients.

Methods: We studied retrospectively 73 patients aging less than 40 years and submitted to SMR between 1975 and 1989. The method used was patient card review and thelephone contact with the patient or his physician.