Cofactors facilitate bona fide prion misfolding in vitro but are not necessary for the infectivity of recombinant murine prions.

Prion diseases, particularly sporadic cases, pose a challenge due to their complex nature and heterogeneity. The underlying mechanism of the spontaneous conversion from PrPC to PrPSc, the hallmark of prion diseases, remains elusive. To shed light on this process and the involvement of cofactors, we have developed an in vitro system that faithfully mimics spontaneous prion misfolding using minimal components.

Comparing the Extent of Methionine Oxidation in the Prion and Native Conformations of PrP.

Scrapie is a prion disease of sheep and goats. Prions (PrP) replicate by inducing a natively expressed protein (PrP) to refold into the prion conformation. PrP and PrP contain a disproportionately large number of methionines.

New preclinical biomarkers for prion diseases in the cerebrospinal fluid proteome revealed by mass spectrometry.

Current diagnostic methods for prion diseases only work in late stages of the disease when neurodegeneration is irreversible. Therefore, biomarkers that can detect the disease before the onset of clinical symptoms are necessary. High-throughput discovery proteomics is of great interest in the search for such molecules.

Genetic Mechanisms Involved in Microbial Stress Responses.

The ability of living beings to deal with abrupt environmental changes is paramount for survival, and organisms have evolved a large variety of molecular mechanisms (known globally as stress responses) to buffer the harmful effects of stressors on cellular homeostasis [...

A Proteogenomic Approach to Unravel New Proteins Encoded in the (HU3) Genome.

The high-throughput proteomics data generated by increasingly more sensible mass spectrometers greatly contribute to our better understanding of molecular and cellular mechanisms operating in live beings. Nevertheless, proteomics analyses are based on accurate genomic and protein annotations, and some information may be lost if these resources are incomplete. Here, we show that most proteomics data may be recovered by interconnecting genomics and proteomics approaches (i.

The Leishmania ribosome: more than passive mRNA translating machinery.

While the central dogma of molecular biology describes how genetic information flows, gene expression is also affected by epigenetic and epitranscriptomic processes. A recent report by Rajan et al. demonstrates how pseudouridylation of a Leishmania ribosomal rRNA affects the expression of particular proteins: an example of epitranslatomic control.

Exploring the functionality and conservation of Alba proteins in Trypanosoma cruzi: A focus on biological diversity and RNA binding ability.

Trypanosoma cruzi is the causative agent of Chagas disease, as well as a trypanosomatid parasite with a complex biological cycle that requires precise mechanisms for regulating gene expression. In Trypanosomatidae, gene regulation occurs mainly at the mRNA level through the recognition of cis elements by RNA-binding proteins (RBPs). Alba family members are ubiquitous DNA/RNA-binding proteins with representatives in trypanosomatid parasites functionally related to gene expression regulation.

Datasets of Iso-Seq transcripts for decoding transcriptome complexity in four species.

The Iso-Seq technology, based on PacBio sequencing, enables the generation of high-quality, full-length transcripts, providing insights into transcriptome complexity. In this study, total RNA from promastigotes of four species ( and ) was sequenced using Single Molecule, Real-Time (SMRT) Sequencing (PacBio) methodology. The Iso-seq transcripts were categorized as either complete or truncated according to the presence or absence of the Spliced-Leader (SL) sequence at their 5'-end, respectively.

Erratum: A tetracationic porphyrin with dual anti-prion activity.

[This corrects the article DOI: 10.1016/j.isci.

Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation.

Among transmissible spongiform encephalopathies or prion diseases affecting humans, sporadic forms such as sporadic Creutzfeldt-Jakob disease are the vast majority. Unlike genetic or acquired forms of the disease, these idiopathic forms occur seemingly due to a random event of spontaneous misfolding of the cellular PrP (PrP) into the pathogenic isoform (PrP). Currently, the molecular mechanisms that trigger and drive this event, which occurs in approximately one individual per million each year, remain completely unknown.

A tetracationic porphyrin with dual anti-prion activity.

Prions are deadly infectious agents made of PrP, a misfolded variant of the cellular prion protein (PrP) which self-propagates by inducing misfolding of native PrP. PrP can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, hampering the development of effective therapies. We identified Zn(II)-BnPyP, a tetracationic porphyrin that binds to distinct domains of native PrP, eliciting a dual anti-prion effect.

Refinement of Genome Annotations in the Light of Ribosome-Protected mRNAs Fragments (Ribo-Seq Data).

Advances in next-generation sequencing methodologies have facilitated the assembly of an ever-increasing number of genomes. Gene annotations are typically conducted via specialized software, but the most accurate results require additional manual curation that incorporates insights derived from functional and bioinformatic analyses (e.g.

(JPCM5) Transcriptome, Gene Models and Resources for an Active Curation of Gene Annotations.

is one of the causative agents of visceral leishmaniases, the most severe form of leishmaniasis. An improved assembly for the genome was published five years ago, yet delineation of its transcriptome remained to be accomplished. In this work, the transcriptome annotation was attained by a combination of both short and long RNA-seq reads.

Assembly of a Large Collection of Maxicircle Sequences and Their Usefulness for Taxonomy and Strain Typing.

Parasites of medical importance, such as and are characterized by the presence of thousands of circular DNA molecules forming a structure known as kinetoplast, within the mitochondria. The maxicircles, which are equivalent to the mitochondrial genome in other eukaryotes, have been proposed as a promising phylogenetic marker. Using whole-DNA sequencing data, it is also possible to assemble maxicircle sequences as shown here and in previous works.

The Astonishing Large Family of HSP40/DnaJ Proteins Existing in .

Abrupt environmental changes are faced by parasites during transmission from a poikilothermic insect vector to a warm-blooded host. Adaptation to harsh environmental conditions, such as nutrient deprivation, hypoxia, oxidative stress and heat shock needs to be accomplished by rapid reconfiguration of gene expression and remodeling of protein interaction networks. Chaperones play a central role in the maintenance of cellular homeostasis, and they are responsible for crucial tasks such as correct folding of nascent proteins, protein translocation across different subcellular compartments, avoiding protein aggregates and elimination of damaged proteins.

A dataset of proteins associated with mRNAs.

Post-transcriptional gene regulation in , the etiological agent of Chagas disease, plays a critical role in ensuring that the parasite successfully completes its life cycle in both of its obligate hosts: insect vector and mammals. This regulation is basically governed by RNA binding proteins (RBPs) through their interactions with -elements located in the UTRs of their mRNA targets. LYT1 gene, coding for a virulence factor of , is expressed into two isoforms: kLYT1 and mLYT1, which play different functions according to their cellular location and parasite life-cycle stages.

Impact of peripheral artery disease on prognosis after percutaneous coronary intervention: Outcomes from the multicenter prospective e-ULTIMASTER registry.

Background And Aims: Patients with peripheral artery disease (PAD) represent a high risk group, and have an increased risk of cardiovascular events and worse cardiovascular outcomes. Our aim was to study the impact of PAD among patients undergoing percutaneous coronary intervention (PCI) with a newer-generation thin-strut DES.

Methods: In this analysis of the e-ULTIMASTER registry, patients with and without known PAD undergoing PCI were compared.

Live attenuated vaccines, a favorable strategy to provide long-term immunity against protozoan diseases.

The control of diseases caused by protozoan parasites is one of the United Nations' Sustainable Development Goals. In recent years much research effort has gone into developing a new generation of live attenuated vaccines (LAVs) against malaria, Chagas disease and leishmaniasis. However, there is a bottleneck related to their biosafety, production, and distribution that slows downs further development.

Protective Efficacy in a Hamster Model of a Multivalent Vaccine for Human Visceral Leishmaniasis (MuLeVaClin) Consisting of the KMP11, LEISH-F3+, and LJL143 Antigens in Virosomes, Plus GLA-SE Adjuvant.

Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, fatal if untreated. Vaccination is the most cost-effective approach to disease control; however, to date, no vaccines against human VL have been made available. This work examines the efficacy of a novel vaccine consisting of the membrane protein KMP11, LEISH-F3+ (a recombinant fusion protein, composed of epitopes of the parasite proteins nucleoside hydrolase, sterol-24-c-methyltransferase, and cysteine protease B), and the sand fly salivary protein LJL143, in two dose ratios.

Gene Annotation and Transcriptome Delineation on a De Novo Genome Assembly for the Reference Friedlin Strain.

is the main causative agent of cutaneous leishmaniasis in humans. The Friedlin strain of this species (LmjF) was chosen when a multi-laboratory consortium undertook the objective of deciphering the first genome sequence for a parasite of the genus . The objective was successfully attained in 2005, and this represented a milestone for molecular biology studies around the world.

Variability of the Pr77 sequence of L1Tc retrotransposon among six T. cruzi strains belonging to different discrete typing units (DTUs).

All trypanosomatid genomes are colonized by non-LTR retrotransposons which exhibit a highly conserved 77-nt sequence at their 5' ends, known as the Pr77-hallmark (Pr77). The wide distribution of Pr77 is expected to be related to the gene regulation processes in these organisms as it has promoter and HDV-like ribozyme activities at the DNA and RNA levels, respectively. The identification of Pr77 hallmark-bearing retrotransposons and the study of the associations of mobile elements with relevant genes have been analyzed in the genomes of six strains of Trypanosoma cruzi belonging to different discrete typing units (DTUs) and with different geographical origins and host/vectors.