Violacein-Induced Chaperone System Collapse Underlies Multistage Antiplasmodial Activity

Antimalarial drugs with novel modes of action and wide therapeutic potential are needed to pave the way for malaria eradication. Violacein is a natural compound known for its biological activity against cancer cells and several pathogens, including the malaria parasite, Plasmodium falciparum (Pf). Herein, using chemical genomic profiling (CGP), we found that violacein affects protein homeostasis. Mechanistically, violacein binds Pf chaperones, PfHsp90 and PfHsp70-1, compromising the latter's ATPase and chaperone activities. Additionally, violacein-treated parasites exhibited increased protein unfolding and proteasomal degradation. The uncoupling of the parasite stress response reflects the multistage growth inhibitory effect promoted by violacein. Despite evidence of proteotoxic stress, violacein did not inhibit global protein synthesis via UPR activation - a process that is highly dependent on chaperones, in agreement with the notion of a violacein-induced proteostasis collapse. Our data highlight the importance of a functioning chaperone-proteasome system for parasite development and differentiation. Thus, a violacein-like small molecule might provide a good scaffold for development of a novel probe for examining the molecular chaperone network and/or antiplasmodial drug design.publishersversionpublishe

Catálogo Taxonômico da Fauna do Brasil: setting the baseline knowledge on the animal diversity in Brazil

The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others

Structural, functional characterization and thermal stability of human proteins HspA5 and HspA8: a comparative approach

As proteínas de choque térmico (Hsps) são componentes importantes do controle de qualidade proteico celular (PQC), atuando na síntese, enovelamento, transporte de proteínas e marcação de proteínas para degradação. O componente central no PQC é a família Hsp70, que consiste em chaperonas moleculares altamente conservadas, ubíquas e ATP-dependentes. Estas chaperonas podem assumir diferentes conformações que são reguladas por sua associação dinâmica com os nucleotídeos adenosina (ATP e ADP), bem como por sua interação com co-chaperonas e proteínas-clientes. Nos seres humanos existem várias proteínas Hsp70, sendo a maioria delas encontrada no citoplasma, enquanto outras são específicas de organelas. O objetivo deste trabalho foi caracterizar estruturalmente e funcionalmente as proteínas Hsp70 humanas citossólica (HspA8) e do retículo endoplasmático (HspA5), por meio de metodologias similares. Para tal, as proteínas hHsp70 recombinantes foram expressas, purificadas e então caracterizadas quanto à estrutura, estabilidade e função por meio de testes biofísicos. Os resultados mostram que as proteínas HspA5 e HspA8 foram produzidas em suas formas enoveladas, com conteúdo de estrutura secundária majoritário em hélices-? e como monômeros levemente alongados em solução. Tais Hsp70 apresentaram estabilidades química e térmica similares, contudo foram observadas duas transições térmicas para a HspA5 e três para a HspA8, indicando diferenças estruturais que resultam em estabilidades térmicas distintas. A presença de nucleotídeos adenosina causou alterações nos conteúdos de estrutura secundária e terciária em ambas as proteínas, os quais também causaram a estabilização térmica das hHsp70. A presença dos íons Ca2+ e Mg2+ favoreceu a ligação das hHsp70 aos nucleotídeos ATP e ADP de formas distintas, e diferentemente da HspA5, a proteína HspA8 interagiu com o Ca2+ mesmo na ausência dos nucleotídeos. Um processo termodinamicamente regido por entalpia e entropia foi observado para a interação dos nucleotídeos adenosina com as proteínas HspA5 e HspA8. As hHsp70 apresentaram atividade ATPásica similar e relativamente baixa, contudo a afinidade da HspA5 pelo ATP foi maior do que a da HspA8. Adicionalmente, as proteínas HspA5 e HspA8 foram eficazes na prevenção da agregação de proteínas-clientes modelo, apresentando diferentes especificidades. Em suma os dados obtidos demonstram que, embora compartilhem 66% de identidade, as proteínas humanas HspA5 e HspA8 apresentam peculiaridades estruturais e funcionais, enriquecendo, portanto, o conhecimento acerca de tais macromoléculas.Heat shock proteins (Hsps) are important components of cell protein quality control (PQC), acting on protein synthesis, folding, traffic and degradation. The central component in the PQC is the Hsp70 family, which consists of highly conserved, ubiquitous and ATP-dependent molecular chaperones. These chaperones can assume different conformations that are regulated by their dynamic association with the adenosine nucleotides (ATP and ADP), as well as by their interaction with co-chaperones and client proteins. In humans there are several Hsp70 proteins, most of which are found in the cytoplasm, while others are specific for organelles. The objective of this work was to structurally and functionally characterize the cytosolic (HspA8) and endoplasmic reticulum (HspA5) human Hsp70 proteins, using similar methodologies. For this, the recombinant hHsp70 proteins were expressed, purified and then characterized for structure, stability and function by means of biophysical tests. The results show that the HspA5 and HspA8 proteins were produced in their folded form, with secondary structure content rich in ?-helices and as slightly elongated monomers in solution. Such Hsp70 showed similar chemical and thermal stability, however two thermal transitions (Tm) were observed for HspA5 and three for HspA8, indicating structural differences that result in distinct thermal stability. Changes in secondary and tertiary structure were observed in the proteins under study in the presence of nucleotides, which also caused the thermal stabilization of hHsp70. The presence of Ca2+ and Mg2+ ions favored the binding of hHsp70 to ATP and ADP nucleotides in different ways, and unlike HspA5, the HspA8 protein interacted with Ca2+ even in the absence of nucleotides. A process thermodynamically governed by enthalpy and entropy was observed for the interaction of the adenosine nucleotides with the HspA5 and HspA8 proteins. hHsp70 showed similar and relatively low ATP activity, however the affinity of HspA5 for ATP was higher than that of HspA8. Additionally, the HspA5 and HspA8 proteins were effective in preventing the aggregation of model client proteins, with different specificities. In summary, the data obtained demonstrate that, although they share 66% of identity, the human proteins HspA5 and HspA8 present structural and functional peculiarities, thus enriching the knowledge about such macromolecules

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data

NEOTROPICAL CARNIVORES: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data