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Zika virus (ZIKV), a mosquito-borne Flavivirus of international concern, causes congenital microcephaly in newborns and Guillain-Barré syndrome in adults. ZIKV capsid (C) protein, one of three key structural proteins, is essential for viral assembly and encapsidation. In dengue virus, a closely related flavivirus, the homologous C protein interacts with host lipid systems, namely intracellular lipid droplets, for successful viral replication. Here, we investigate ZIKV C interaction with host lipid systems, showing that it binds host lipid droplets but, contrary to expected, in an unspecific manner. Contrasting with other flaviviruses, ZIKV C also does not bind very-low density-lipoproteins. Comparing with other Flavivirus, capsid proteins show that ZIKV C structure is particularly thermostable and seems to be locked into an auto-inhibitory conformation due to a disordered N-terminal, hence blocking specific interactions and supporting the experimental differences observed. Such distinct structural features must be considered when targeting capsid proteins in drug development.
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Proteínas do Capsídeo , Zika virus , Zika virus/química , Zika virus/metabolismo , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Humanos , Ligação Proteica , Modelos MolecularesRESUMO
Monitoring ocean surface temperature is critical to infer the variability of the upper layers of the ocean, from short temporal scales to climatic change scales. Analysis of the climatological trends and anomalies is fundamental to comprehend the long-term effects of climate change on marine ecosystems and coastal regions. The original data for the dataset presented was collected by the Portuguese Hydrographic Institute (Instituto Hidrográfico) using seven Ondograph and Meteo-oceanography buoys anchored offshore along the Portuguese coast to acquire ocean surface temperatures. The original raw data was pre-processed to provide averages over 3-hour periods and daily averages, and this cleaned data constitutes the provided dataset. The 3-hour temperature averages were obtained mainly between 2011 and 2015, and the daily temperature averages were obtained in intervals that vary with the considered buoy, having an average interval of 14 years per buoy. The data gathered provides a considerable temporal window, enabling the creation of data series and the implementation of data mining algorithms to develop decision support systems. Collecting data in situ makes it possible to validate simulated results obtained using approximation models. This allows for more accurate temperature readings and facilitates testing and correcting created models.
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Lynch syndrome is the most common cause of hereditary colorectal cancer. It usually develops asymptomatically until symptoms related to colorectal carcinoma appear, such as gastrointestinal bleeding, abdominal pain, and changes in bowel habits and/or stool characteristics. Oftentime, when these clinical signs and symptoms are not present, the diagnosis becomes challenging. We present the clinical case of a 69-year-old woman, adopted, with no known previous history, who presented to the emergency department with low back pain, without irradiation, that had been going on for three days, associated with inflammatory signs in the right hip region. There were no urinary or sensory alterations and no recent trauma. She was initially discharged with antibiotherapy with the diagnosis of hip cellulitis. As the symptoms continued and the inflammation spread to the right lower limb, she returned to the emergency department. A CT scan revealed an abscess (17 cm) in the right buttock, complicated by necrotizing fasciitis due to fistulization from a tumor in the right colon. She underwent an exploratory laparotomy, which identified a neoplasm of the ascending colon, adherent to the abdominal wall, in the right lumbar region. Right hemicolectomy and drainage of the right buttock/thigh abscess were performed. The histology was compatible with invasive adenocarcinoma, with high-grade dysplasia but well differentiated, pT3G1N0. The immunohistochemistry was suggestive of Lynch syndrome.
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A robust and efficient cellular response to lysosomal membrane damage prevents leakage from the lysosome lumen into the cytoplasm. This response is understood to happen through either lysosomal membrane repair or lysophagy. Here we report exocytosis as a third response mechanism to lysosomal damage, which is further potentiated when membrane repair or lysosomal degradation mechanisms are impaired. We show that Connexin43 (Cx43), a protein canonically associated with gap junctions, is recruited from the plasma membrane to damaged lysosomes, promoting their secretion and accelerating cell recovery. The effects of Cx43 on lysosome exocytosis are mediated by a reorganization of the actin cytoskeleton that increases plasma membrane fluidity and decreases cell stiffness. Furthermore, we demonstrate that Cx43 interacts with the actin nucleator Arp2, the activity of which was shown to be necessary for Cx43-mediated actin rearrangement and lysosomal exocytosis following damage. These results define a novel mechanism of lysosomal quality control whereby Cx43-mediated actin remodelling potentiates the secretion of damaged lysosomes.
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Hepatitis E virus (HEV), species Paslahepevirus balayani, poses a global public health threat, especially in developing countries, by causing acute enterically transmitted hepatitis. HEV infects various mammalian hosts and belongs to the genus Paslahepevirus in the family Hepeviridae. While swine are recognized as the main hosts of HEV, rabbits, which can also be affected by swine HEV-3 related strains, serve as the primary reservoir for the distinct emerging and zoonotic HEV-3ra subtype. In Portugal, where the European wild rabbit is abundant, their role in HEV epidemiology remains unclear. The primary aim of the present research was to evaluate the circulation and the potential for HEV infection within these species. This study employed a molecular and longitudinal serological approach to investigate HEV in Portuguese rabbits. Among the 205 wild rabbits tested, a seroprevalence of 2.44% (95% CI: 0.80-5.60) was found, with no significant associations with age, sex, localization, or sampling dates. Seropositive animals were found in the south and center regions of the country. HEV RNA was not detected in 120 fecal samples, suggesting a natural, low level, and widespread viral circulation. The study underscores the need for further research to comprehend HEV dynamics in these species, which is crucial for assessing potential transmission risks to humans.
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Human alphaherpesvirus 1 (HSV-1) is a significantly widespread viral pathogen causing recurrent infections that are currently incurable despite available treatment protocols. Studies have highlighted the potential of antimicrobial peptides sourced from Vespula lewisii venom, particularly those belonging to the mastoparan family, as effective against HSV-1. This study aimed to demonstrate the antiviral properties of mastoparans, including mastoparan-L [I5, R8], mastoparan-MO, and [I5, R8] mastoparan, against HSV-1. Initially, Vero cell viability was assessed in the presence of these peptides, followed by the determination of antiviral activity, mechanism of action, and dose-response curves through plaque assays. Structural analyses via circular dichroism and nuclear magnetic resonance were conducted, along with evaluating membrane fluidity changes induced by [I5, R8] mastoparan using fluorescence-labeled lipid vesicles. Cytotoxic assays revealed high cell viability (>80%) at concentrations of 200 µg/mL for mastoparan-L and mastoparan-MO and 50 µg/mL for [I5, R8] mastoparan. Mastoparan-MO and [I5, R8] mastoparan exhibited over 80% HSV-1 inhibition, with up to 99% viral replication inhibition, particularly in the early infection stages. Structural analysis indicated an α-helical structure for [I5, R8] mastoparan, suggesting effective viral particle disruption before cell attachment. Mastoparans present promising prospects for HSV-1 infection control, although further investigation into their mechanisms is warranted.
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Antivirais , Herpesvirus Humano 1 , Peptídeos e Proteínas de Sinalização Intercelular , Peptídeos , Venenos de Vespas , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Antivirais/farmacologia , Antivirais/química , Animais , Células Vero , Chlorocebus aethiops , Peptídeos/farmacologia , Peptídeos/química , Venenos de Vespas/farmacologia , Venenos de Vespas/química , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/química , Sobrevivência Celular/efeitos dos fármacos , Humanos , Replicação Viral/efeitos dos fármacosRESUMO
Background: Research on post-traumatic growth (PTG) and HIV is scarce and the relationship between PTG and stigma is controversial. Group psychotherapeutic interventions to facilitate PTG in clinical samples are effective but none exist to simultaneously decrease stigma in the HIV population. The main objective was to evaluate the effectiveness of an intervention in increasing PTG and decreasing stigma in HIV, as well as to explore relationships between the variables. Methods: Quasi-experimental design with a sample of 42 HIV-positive adults (M = 46.26, SD = 11.90). The experimental group (EG) was subjected to a 9-week group intervention. Instruments: CBI, PTGI-X, PSS-10, HIV stigma, emotional expression, HIV stress indicators, HIV literacy, and skills. Multiple linear regression analysis was performed to assess the relationship between the variables. Results: There was an increase in PTG and a significant decrease in stigma in all domains and subscales in the EG. Compared to the control group, stigma (t(42) = -3.040, p = 0.004) and negative self-image (W = -2.937, p = 0.003) were significant, showing the efficacy of the intervention. Discussion: The intervention demonstrated success in facilitating PTG, attesting that in order to increase PTG, personal strength, and spiritual change, it is necessary to reduce stigma and negative self-image. The research provides more information on group interventions for PTG in HIV, relationships between variables, and population-specific knowledge for professionals.
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Many factors contribute to bacterial membrane stabilization, including steric effects between lipids, membrane spontaneous curvature, and the difference in the number of neighboring molecules. This forum provides an overview of the physicochemical properties associated with membrane curvature and how this parameter can be tuned to design more effective antimicrobial peptides.
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Peptídeos Antimicrobianos , Bactérias , Membrana Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/química , Membrana Celular/metabolismo , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Antibacterianos/farmacologia , Antibacterianos/química , Lipídeos de Membrana/química , Lipídeos de Membrana/metabolismoRESUMO
Every year, millions of people suffer some form of illness associated with the consumption of contaminated food. Escherichia coli (E. coli), found in the intestines of humans and other animals, is commonly associated with various diseases, due to the existence of pathogenic strains. Strict monitoring of food products for human consumption is essential to ensure public health, but traditional cell culture-based methods are associated with long waiting times and high costs. New approaches must be developed to achieve cheap, fast, and on-site monitoring. Thus, in this work, we developed optical fiber sensors based on surface plasmon resonance. Gold and cysteamine-coated fibers were functionalized with anti-E. coli antibody and tested using E. coli suspensions with concentrations ranging from 1 cell/mL to 105 cells/mL. An average logarithmic sensitivity of 0.21 ± 0.01â nm/log(cells/mL) was obtained for three independent assays. An additional assay revealed that including molybdenum disulfide resulted in an increase of approximately 50% in sensitivity. Specificity and selectivity were also evaluated, and the sensors were used to analyze contaminated water samples, which verified their promising applicability in the aquaculture field.
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Técnicas Biossensoriais , Ressonância de Plasmônio de Superfície , Animais , Humanos , Ressonância de Plasmônio de Superfície/métodos , Escherichia coli , Fibras Ópticas , Técnicas Biossensoriais/métodos , ImunoensaioRESUMO
As a coastal state, Portugal must ensure active surveillance over its maritime area, ensuring its proper control and inspection. One of the most critical inspection activities is the fishery inspection. To protect biodiversity, we must ensure that all the ships comply with the existing safety regulations and respect the current fishing quotas. This georeferenced dataset describes the fisheries inspections done in Portuguese waters between 2015 and 2023. Since we are dealing with occurrences that may have originated some legal process to the ship's owner, we have ensured data anonymization by pre-processing the dataset to maintain its accuracy while guaranteeing no unique identifiers exist. All the pre-processing performed to ensure data consistency and accuracy is described in detail to allow a quick analysis and implementation of new algorithms. The data containing the results of these inspections can be easily analyzed to implement data mining algorithms that can efficiently retrieve more knowledge and, e.g., suggest new areas of actuation or new strategies.
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Lymphomas are a heterogeneous group of diseases that originate from T, B or natural killer cells. Lymphoma treatment is based on chemotherapy, radiotherapy, and monoclonal antibody (mAb) or other immunotherapies. The P-selectin glycoprotein ligand 1 (PSGL-1) is expressed at the surface of hematological malignant cells and has been shown to have a pro-oncogenic role in multiple myeloma and lymphoma. Here, we investigated the expression and therapeutic potential of PSGL-1 in T and B cell lymphomas. By flow cytometry analysis, we found that PSGL-1 was expressed in both T and B cell-derived lymphoma cell lines but generally at higher levels in T cell lymphoma cell lines. For most T and B cell-derived lymphoma cell lines, in vitro targeting with the PL1 mAb, which recognizes the PSGL-1 N-terminal extracellular region and blocks functional interactions with selectins, resulted in reduced cell viability. The PL1 mAb pro-apoptotic activity was shown to be dose-dependent, to be linked to increased ERK kinase phosphorylation, and to be dependent on the MAP kinase signaling pathway. Importantly, anti-PSGL-1 treatment of mice xenografted with the HUT-78 cutaneous T-cell lymphoma cell line resulted in decreased tumor growth, had no effect on in vivo proliferation, but increased the levels of apoptosis in tumors. Anti-PSGL-1 treatment of mice xenografted with a Burkitt lymphoma cell line that was resistant to anti-PSGL-1 treatment in vitro, had no impact on tumorigenesis. These findings show that PSGL-1 antibody targeting triggers lymphoma cell apoptosis and substantiates PSGL-1 as a potential target for lymphoma therapy.
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Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Humanos , Animais , Camundongos , Selectina-P , Ligantes , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Apoptose , CarcinogêneseRESUMO
Unmanned vehicles have become increasingly popular in the underwater domain in the last decade, as they provide better operation reliability by minimizing human involvement in most tasks. Perception of the environment is crucial for safety and other tasks, such as guidance and trajectory control, mainly when operating underwater. Mine detection is one of the riskiest operations since it involves systems that can easily damage vehicles and endanger human lives if manned. Automating mine detection from side-scan sonar images enhances safety while reducing false negatives. The collected dataset contains 1170 real sonar images taken between 2010 and 2021 using a Teledyne Marine Gavia Autonomous Underwater Vehicle (AUV), which includes enough information to classify its content objects as NOn-Mine-like BOttom Objects (NOMBO) and MIne-Like COntacts (MILCO). The dataset is annotated and can be quickly deployed for object detection, classification, or image segmentation tasks. Collecting a dataset of this type requires a significant amount of time and cost, which increases its rarity and relevance to research and industrial development.
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The successful translation of therapeutic nucleic acids (NAs) for the treatment of neurological disorders depends on their safe and efficient delivery to neural cells, in particular neurons. DNA nanostructures can be a promising NAs delivery vehicle. Nonetheless, the potential of DNA nanostructures for neuronal cell delivery of therapeutic NAs is unexplored. Here, tetrahedral DNA nanostructures (TDN) as siRNA delivery scaffolds to neuronal cells, exploring the influence of functionalization with two different reported neuronal targeting ligands: C4-3 RNA aptamer and Tet1 peptide are investigated. Nanostructures are characterized in vitro, as well as in silico using molecular dynamic simulations to better understand the overall TDN structural stability. Enhancement of neuronal cell uptake of TDN functionalized with the C4-3 Aptamer (TDN-Apt), not only in neuronal cell lines but also in primary neuronal cell cultures is demonstrated. Additionally, TDN and TDN-Apt nanostructures carrying siRNA are shown to promote silencing in a process aided by chloroquine-induced endosomal disruption. This work presents a thorough workflow for the structural and functional characterization of the proposed TDN as a nano-scaffold for neuronal delivery of therapeutic NAs and for targeting ligands evaluation, contributing to the future development of new neuronal drug delivery systems based on DNA nanostructures.
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DNA , Nanoestruturas , Neurônios , RNA Interferente Pequeno , Nanoestruturas/química , Neurônios/metabolismo , DNA/química , DNA/metabolismo , Animais , Humanos , Aptâmeros de Nucleotídeos/química , Ácidos Nucleicos/química , Simulação de Dinâmica MolecularRESUMO
This Special Issue presents five contributions covering various topics, as it would be expected for an area as comprehensive and multidisciplinary as Macromolecules [...].
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Estudos Interdisciplinares , Portugal , Substâncias MacromolecularesRESUMO
The existence of encrypted fragments with antimicrobial activity in human proteins has been thoroughly demonstrated in the literature. Recently, algorithms for the large-scale identification of these segments in whole proteomes were developed, and the pervasiveness of this phenomenon was stated. These algorithms typically mine encrypted cationic and amphiphilic segments of proteins, which, when synthesized as individual polypeptide sequences, exert antimicrobial activity by membrane disruption. In the present report, the human reference proteome was submitted to the software kamal for the uncovering of protein segments that correspond to putative intragenic antimicrobial peptides (IAPs). The assessment of the identity of these segments, frequency, functional classes of parent proteins, structural relevance, and evolutionary conservation of amino acid residues within their corresponding proteins was conducted in silico. Additionally, the antimicrobial and anticancer activity of six selected synthetic peptides was evaluated. Our results indicate that cationic and amphiphilic segments can be found in 2% of all human proteins, but are more common in transmembrane and peripheral membrane proteins. These segments are surface-exposed basic patches whose amino acid residues present similar conservation scores to other residues with similar solvent accessibility. Moreover, the antimicrobial and anticancer activity of the synthetic putative IAP sequences was irrespective to whether these are associated to membranes in the cellular setting. Our study discusses these findings in light of the current understanding of encrypted peptide sequences, offering some insights into the relevance of these segments to the organism in the context of their harboring proteins or as separate polypeptide sequences.
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Anti-Infecciosos , Proteoma , Humanos , Proteoma/genética , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Sequência de Aminoácidos , AminoácidosRESUMO
Resumo: A proatividade e o capital psicológico (PsyCap) são construtos associados às virtudes psicológicas, recursos despertados por fatores individuais e organizacionais, que podem maximizar resultados. Este estudo visou investigar qualitativamente os determinantes e aspectos que podem estimular o PsyCap e a proatividade, a partir da perspectiva de trabalhadores de duas empresas brasileiras. A pesquisa foi realizada por meio de entrevistas semiestruturadas com uma amostra de 26 funcionários. Os resultados revelaram determinantes comuns para a proatividade e o PsyCap, dentre eles a aprendizagem formal e informal, o feedback, a felicidade, a persistência, a curiosidade, os desafios e a estratégia. Foram observados alguns consequentes positivos, como euforia, alegria, realização, entusiasmo, engajamento e gratidão. Notou-se também que a ausência de proatividade e níveis baixos de PsyCap podem desencadear reações negativas, como indignação, tristeza, procrastinação, paralisação, desequilíbrio e frustração. Esses resultados sugerem que intervenções focadas no desenvolvimento da proatividade e do PsyCap podem ser essenciais para potencializar o bem-estar individual e resultados positivos nas organizações.
Abstract: Proactivity and psychological capital (PsyCap) are concepts associated with psychological virtues, resources awakened from individual and organizational factors, which can maximize results. This study aimed to investigate qualitatively the determinants and aspects that can stimulate PsyCap and proactivity, from the perspective of workers of two Brazilian businesses. The research was carried out with semi-structured interviews with a sample of 26 employees. The results revealed common determinants for proactivity and PsyCap, among them formal and informal learning, feedback, happiness, persistence, curiosity, challenges, and strategy. Some positive consequences were observed, such as euphoria, joy, fulfillment, enthusiasm, engagement, and gratitude. Also note that the absence of proactivity and low levels of PsyCap could trigger negative reactions, such as indignation, sadness, procrastination, paralysis, imbalance, and frustration. These results suggest that interventions focused on the development of proactivity and PsyCap can be essential to enhance individual well-being and positive results in organizations.
Resumen: La proactividad y el capital psicológico (PsyCap) son constructos asociados a las virtudes psicológicas, recursos que pueden ser despertados por factores individuales y organizacionales para maximizar los resultados. Este estudio tuvo como objetivo investigar cualitativamente los determinantes y aspectos que pueden despertar el PsyCap y la proactividad desde la perspectiva de los trabajadores de dos empresas brasileñas. Este estudio se realizó mediante entrevistas semiestructuradas en una muestra de 26 empleados. Los resultados revelaron determinantes comunes para la proactividad y el PsyCap, entre ellos, el aprendizaje formal e informal, la retroalimentación, la felicidad, la persistencia, la curiosidad, los desafíos y la estrategia. Se observaron algunas consecuencias positivas, como euforia, alegría, logro, entusiasmo, compromiso y gratitud. También se señaló que la ausencia de proactividad y los bajos niveles del PsyCap pueden desencadenar reacciones negativas, como indignación, tristeza, procrastinación, parálisis, desequilibrio y frustración. Estos resultados sugieren que las intervenciones centradas en el desarrollo de la proactividad y del PsyCap pueden ser esenciales para mejorar el bienestar individual y los resultados positivos en las organizaciones.
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Erythrocytes play a fundamental role in oxygen delivery to tissues and binding to inflammatory mediators. Evidences suggest that dysregulated erythrocyte function could contribute to the pathophysiology of several neurodegenerative diseases. We aimed to evaluate changes in morphological, biomechanical, and biophysical properties of erythrocytes from amyotrophic lateral sclerosis (ALS) patients, as new areas of study in this disease. Blood samples were collected from ALS patients, comparing with healthy volunteers. Erythrocytes were assessed using atomic force microscopy (AFM) and zeta potential analysis. The patients' motor and respiratory functions were evaluated using the revised ALS Functional Rating Scale (ALSFRS-R) and percentage of forced vital capacity (%FVC). Patient survival was also assessed. Erythrocyte surface roughness was significantly smoother in ALS patients, and this parameter was a predictor of faster decline in ALSFRS-R scores. ALS patients exhibited higher erythrocyte stiffness, as indicated by reduced AFM tip penetration depth, which predicted a faster ALSFRS-R score and respiratory subscore decay. A lower negative charge on the erythrocyte membrane was predictor of a faster ALSFRS-R and FVC decline. Additionally, a larger erythrocyte surface area was an independent predictor of lower survival. These changes in morphological and biophysical membrane properties of ALS patients' erythrocytes, lead to increased cell stiffness and morphological variations. We speculate that these changes might precipitate motoneurons dysfunction and accelerate disease progression. Further studies should explore the molecular alterations related to these observations. Our findings may contribute to dissect the complex interplay between respiratory function, tissue hypoxia, progression rate, and survival in ALS.
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Esclerose Lateral Amiotrófica , Eritrócitos , Microscopia de Força Atômica , Humanos , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/mortalidade , Esclerose Lateral Amiotrófica/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Eritrócitos/metabolismo , Eritrócitos/patologia , Idoso , Propriedades de Superfície , Membrana Eritrocítica/metabolismo , Adulto , Capacidade Vital , Progressão da DoençaRESUMO
Piracy has been a global concern and a threat to the safety of people performing maritime trade around the globe. Since ancient times maritime piracy has been a common practice that, unfortunately, has not ended in the current days. A georeferenced dataset providing the position, meteorologic conditions, and a description of the occurrence can provide essential information for analyzing this global phenomenon. The dataset focuses on the Gulf of Guinea (GoG) as an area dominated by corruption and weak supervision capacity by the local authorities. The time interval considered in this paper is between 2010 and 2021. Using this simple dataset, it is possible to analyze attributes such as when the piracy occurred or if the illegal activity involved deaths or kidnapping. The accuracy of the data was guaranteed by cross-referencing data sources, so we have 595 pirate attacks accurately described. This dataset can easily be used for data mining, allowing further analysis of the patterns and trends of pirate attacks in the GoG over time.