Cytosolic phospholipase A2 (cPLA2) belongs to a large family of proteins and plays a crucial role in the regulation of arachidonic acid metabolism and inflammation cascade in zebrafish (Danio rerio). ...This enzyme with a molecular weight of 85 kDa, has two distinct domains. One is the regulatory and calcium-dependent (Ca2+) domain called C2, the other is the catalytic α/β hydrolase Ca2+-independent domain, where serine and aspartic acid catalytic dyad residues are present. We investigated the interaction of malathion and their organophosphate metabolites in the cPLA2 using in silico tools. Molecular docking results showed hydrophobic interactions with the paraoxon and catalytic site residue (Ser 223). Malathion increases intracellular Ca2+ due to endoplasmic reticulum influx which in turn activities phospholipase A2 and arachidonic acid release. Molecular docking and homology modelling of proteins and ligands could be a complementary tool for ecotoxicology and environment pollution assessment.
Display omitted
•Phospholipase A2 (PLA2) is a enzyme that acts in lipid metabolism and inflammation.•The zebrafish has a PLA2 homologous to that of humans.•Malathionand their metabolites can attached to the catalytic site of zebrafish PLA2.
In the present study, we report a case of animal care, female SRD, 3 years old and 7 months old, weighing 15 kg, with clinical suspicion of fetal dystocia. He was seen in the emergency department of ...the Hospital Veterinário Universitário (HVU / UFPI), two days ago he was in labor, without expulsion of any product, with bloody vaginal discharge, prostrate and without food. However, before the physical examination was completed, the patient had a cardiorespiratory arrest and died. Thus, we opted for necropsy, which the post-mortem diagnosis revealed diaphragmatic hernia, respiratory failure and septicemia. This report highlights the importance of a thorough clinical / physical examination to establish the most correct therapy in pregnant animals that arrive for emergency care due to complications at the time of delivery, and without forgetting the importance of prenatal care in companion animals, which does not occur frequently in the veterinary clinical routine.
En el presente estudio reportamos un caso de atendimiento animal, hembra mestiza, de 3 años y 7 meses de edad, con un peso de 15 kg, con sospecha clínica de distocia fetal. Fue atendido en el servicio de urgencias del Hospital Veterinário Universitário (HVU / UFPI), se encontraba en trabajo de parto desde dos días antes, sin expulsión de ningún producto, con flujo vaginal sanguinolento, postrada y sin alimentase. Sin embargo, antes de que se completara la exploración física, el paciente sufrió un paro cardiorrespiratorio y falleció. Así, optamos por la necropsia, ya que el diagnóstico post-mortem reveló hernia diafragmática, insuficiencia respiratoria y septicemia. Este informe destaca la importancia de un examen clínico / físico minucioso para establecer la terapia más correcta en animales gestantes que llegan para atención de emergencia por complicaciones en el momento del parto, y sin olvidar la importancia del cuidado prenatal en animales de compañía, que no ocurren con frecuencia en la rutina clínica veterinaria.
No presente trabalho relata-se um caso de atendimento a animal, cadela SRD, de 3 anos e 7 meses de idade, pesando 15 Kg, com suspeita clínica de distocia fetal. Foi atendido no setor de emergência do Hospital Veterinário Universitário (HVU/UFPI), há dois dias estava em trabalho de parto, sem expulsão de nenhum produto, com secreção vaginal sanguinolenta, prostrada e sem se alimentar. Porém, antes que o exame físico se completasse a paciente apresentou uma parada cardiorrespiratória e veio a óbito. Assim, optou-se pela necropsia, que o diagnóstico post-mortem revelou hérnia diafragmática, insuficiência respiratória e septicemia. Este relato ressalta a importância de um minucioso exame clínico/físico para se estabelecer a mais correta terapêutica em animais prenhes que chegam para atendimento emergencial devido a complicações no momento do parto, e sem esquecer a importância do acompanhamento pré-natal em animais de companhia, o qual não ocorre com frequência na rotina clínica veterinária.
The Togaviridae family comprises a large and diverse group of viruses responsible for recurrent outbreaks in humans. Within this family, the Chikungunya virus (CHIKV) is an important Alphavirus in ...terms of morbidity, mortality, and economic impact on humans in different regions of the world. The objective of this study was to perform an IgG epitope recognition of the CHIKV’s structural proteins E2 and E3 using linear synthetic peptides recognized by serum from patients in the convalescence phase of infection. The serum samples used were collected in the state of Sergipe, Brazil in 2016. Based on the results obtained using immunoinformatic predictions, synthetic B-cell peptides corresponding to the epitopes of structural proteins E2 and E3 of the CHIKV were analyzed by the indirect peptide ELISA technique. Protein E2 was the main target of the immune response, and three conserved peptides, corresponding to peptides P3 and P4 located at Domain A and P5 at the end of Domain B, were identified. The peptides P4 and P5 were the most reactive and specific among the 11 epitopes analyzed and showed potential for use in serological diagnostic trials and development and/or improvement of the Chikungunya virus diagnosis and vaccine design.
Zika virus (ZIKV) was recognised as a zoonotic pathogen in Africa and southeastern Asia. Human infections were infrequently reported until 2007, when the first known epidemic occurred in Micronesia. ...After 2013, the Asian lineage of ZIKV spread along the Pacific Islands and Americas, causing severe outbreaks with millions of human infections. The recent human infections of ZIKV were also associated with severe complications, such as an increase in cases of Guillain-Barre syndrome and the emergence of congenital Zika syndrome.
To better understand the recent and rapid expansion of ZIKV, as well as the presentation of novel complications, we compared the genetic differences between the African sylvatic lineage and the Asian epidemic lineage that caused the recent massive outbreaks.
The epidemic lineages have significant codon adaptation in NS1 gene to translate these proteins in human and Aedes aegypti mosquito cells compared to the African zoonotic lineage. Accordingly, a Brazilian epidemic isolate (ZBR) produced more NS1 protein than the MR766 African lineage (ZAF) did, as indicated by proteomic data from infections of neuron progenitor cells-derived neurospheres. Although ZBR replicated more efficiently in these cells, the differences observed in the stoichiometry of ZIKV proteins were not exclusively explained by the differences in viral replication between the lineages.
Our findings suggest that natural, silent translational selection in the second half of 20th century could have improved the fitness of Asian ZIKV lineage in human and mosquito cells.
Chikungunya virus (CHIKV) is an arbovirus (Togaviridae family, Alphavirus genus) that was first identified in 1953 in Tanzania. In 2014, the Asian and East/Central/South/African (ECSA) genotypes were ...identified in Brazil, although the genotype that spread the most in the following years across the Brazilian territory was the ECSA. The clinical symptoms associated with the infection caused by CHIKV include mainly fever, myalgia, headache, and arthralgia. In infections caused by other arboviruses (such as the ones caused by Dengue and West Nile viruses), changes in biochemical markers are often observed. This study aims to evaluate the biochemical markers profile of kidney and liver injury in acute patients infected with CHIKV. Two groups of correlations were found between the variables analyzed, namely, one between liver enzymes (r = 0.91), and another for kidney markers (r = 0.54–0.66). A significant elevation in the percentage of altered creatinine in CHIKV‐infected patients was observed, followed by uric acid and AST. Altogether, in 8 different comparisons, it was possible to observe statistically significant differences between the levels of the markers when compared to the manifestation of symptoms (presence and absence). These noticeable changes in marker measurements could potentially be connected to the range of clinical symptoms seen in the disease.
Display omitted
•The Red Queen Hypothesis in virus-host interactions; viruses adapt proteins, hosts alter receptors.•Mutual adaptation shapes receptor interactions, informing disease unpredictability ...and interventions.•The article utilizes phylogenetics, modeling, and dynamics, focusing on Brazilian Dengue strains.•Viral quasispecies explores mutational space elegantly,linking genotype mutations to phenotype variations.•Energetic decomposition analyses identifies critical amino acids, highlighting Phe 313 in DC-SIGN interactions.
The Red Queen Hypothesis (RQH), derived from Lewis Carroll's “Through the Looking-Glass”, postulates that organisms must continually adapt in response to each other to maintain relative fitness. Within the context of host-pathogen interactions, the RQH implies an evolutionary arms race, wherein viruses evolve to exploit hosts and hosts evolve to resist viral invasion. This study delves into the dynamics of the RQH in the context of virus-cell interactions, specifically focusing on virus receptors and cell receptors. We observed multiple virus-host systems and noted patterns of co-evolution. As viruses evolved receptor-binding proteins to effectively engage with cell receptors, cells countered by altering their receptor genes. This ongoing mutual adaptation cycle has influenced the molecular intricacies of receptor-ligand interactions. Our data supports the RQH as a driving force behind the diversification and specialization of both viral and host cell receptors. Understanding this co-evolutionary dance offers insights into the unpredictability of emerging viral diseases and potential therapeutic interventions. Future research is crucial to dissect the nuanced molecular changes and the broader ecological consequences of this ever-evolving battle. Here, we combine phylogenetic inferences, structural modeling, and molecular dynamics analyses to describe the epidemiological characteristics of major Brazilian DENV strains that circulated from 1990 to 2022 from a combined perspective, thus providing us with a more detailed picture on the dynamics of such interactions over time.
The development of pharmacological agents for the treatment of Alzheimer's Disease (AD) is very relevant since this is the most common type of dementia. The inhibition of acetylcholinesterase (AChE) ...is important to increase the low levels of acetylcholine (ACh) neurotransmitter observed in sick people, which is associated with the memory loss. In this work, a new guanylhydrazone was designed and synthesized as an AChE inhibitor. This new compound was compared to tacrine and other guanylhydrazones. All of them were studied by molecular docking and tested in vitro as AChE inhibitors by Ellman's test and Fig-NMR method. A high inhibition of AChE by the new compound was observed, showing that this compound has great potential for the treatment of AD.
The Spike protein's structure of the SARS-CoV-2 provides a unique opportunity to consider perturbations at the atomic level. We used the cryo-electron microscopy structure of the open conformation of ...the Spike protein to assess the impact of the mutations observed in the variants of concern at the molecular level. Molecular dynamics were subsequently performed with both the wt and the mutated forms to compare the flexibility and variation data for each residue of the three-dimensional fluctuations in the region associated with each alpha carbon. Additionally, protein-protein docking was used to investigate the interaction of each mutated profile with the ACE-2 receptor. After the molecular dynamics, the results show that the mutations increased the stability of the trimeric protein, with greater stability observed in the Gamma variant harboring the 10 characteristic mutations. The results of molecular dynamics, as shown by RMSF demonstrated for the residues that comprise the binding domain receptor (RBD), exhibited a reduction in flexibility, which was more pronounced in the Gamma variant. Finally, protein-protein docking experiments revealed an increase in the number of hydrophobic interactions and hydrogen bonds in the Gamma variant against the ACE-2 receptor, as opposed to the other variants. Taken together, these in silico experiments suggest that the evolution of the mutations favored the increased stability of Spike protein while potentially improving its interaction with the ACE-2 receptor, which in turn may indicate putative structural outcomes of the selection of these mutations in the convergent adaptive evolution as it has been observed for SARS-CoV-2.
Communicated by Ramaswamy H. Sarma
Zika virus (ZIKV) and dengue virus (DENV) share a lot of similarities being both phylogenetically closely related, share the same insect vector passage for reaching the host, affinity for the same ...carbohydrate receptor domains (CRDs), indicating feasible competition between them on the natural field. Here, we prospected interactions of both envelope proteins with a DC-SIGN, a transmembrane c-type lectine receptor with the most implicated CRD with the Flavivirus infection presents on dendritic cells involved in viruses replication processes into the host, and among rares CRD receptors susceptible to interacting with a broad of subtypes of DENV. Protein-protein docking procedures produced structures for molecular dynamics experiments, suggesting the most energetically favorable complex. The difference found in the deltaG results prompted the experimentation with molecular dynamics. To investigate further specific residues involved with such interactions we produced a decomposition analysis using molecular dynamics of the docked proteins evaluated afterward with the Generalized Born Surface Area method. Solvent-accessible surface area (SASA) analysis for both showed very similar but with a slight reduction for ZIKV_E, which agreed with residues SASA analysis highlighting regions more exposed in the ZIVK protein than in DENV. Despite residues PHE313 is reponsible for most of the interactions with the envelope of these arboviruses, ZIKV interacted with this residue in DC-SIGN with lower energies and using more interactions with not expexted residues GLU241 and ARG386. Taken together these results suggest better competitive interaction of ZIKV with the DC-SIGN receptor, particularly in the CRD portion.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
