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Proteins, fundamental to cellular activities, reveal their function and evolution through their structure and sequence. CATH functional families (FunFams) are coherent clusters of protein domain sequences in which the function is conserved across their members. The increasing volume and complexity of protein data enabled by large-scale repositories like MGnify or AlphaFold Database requires more powerful approaches that can scale to the size of these new resources. In this work, we introduce MARC and FRAN, two algorithms developed to build upon and address limitations of GeMMA/FunFHMMER, our original methods developed to classify proteins with related functions using a hierarchical approach. We also present CATH-eMMA, which uses embeddings or Foldseek distances to form relationship trees from distance matrices, reducing computational demands and handling various data types effectively. CATH-eMMA offers a highly robust and much faster tool for clustering protein functions on a large scale, providing a new tool for future studies in protein function and evolution.
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Algoritmos , Bases de Dados de Proteínas , Proteínas , Proteínas/química , Proteínas/metabolismo , Análise por Conglomerados , Biologia Computacional/métodos , Domínios ProteicosRESUMO
Protein dynamics and related conformational changes are essential for their function but difficult to characterise and interpret. Amino acids in a protein behave according to their local energy landscape, which is determined by their local structural context and environmental conditions. The lowest energy state for a given residue can correspond to sharply defined conformations, e.g. in a stable helix, or can cover a wide range of conformations, e.g. in intrinsically disordered regions. A good definition of such low energy states is therefore important to describe the behaviour of a residue and how it changes with its environment. We propose a data-driven probabilistic definition of six low energy conformational states typically accessible for amino acid residues in proteins. This definition is based on solution NMR information of 1322 proteins through a combined analysis of structure ensembles with interpreted chemical shifts. We further introduce a conformational state variability parameter that captures, based on an ensemble of protein structures from molecular dynamics or other methods, how often a residue moves between these conformational states. The approach enables a different perspective on the local conformational behaviour of proteins that is complementary to their static interpretation from single structure models.
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U.S. immigration discourse has spurred interest in characterizing who illegalized immigrants are or perceived to be. What are the associated visual representations of migrant illegality? Across two studies with undergraduate and online samples (N = 686), we used face-based reverse correlation and similarity sorting to capture and compare mental representations of illegalized immigrants, native-born U.S. citizens, and documented immigrants. Documentation statuses evoked racialized imagery. Immigrant representations were dark-skinned and perceived as non-white, while citizen representations were light-skinned, evaluated positively, and perceived as white. Legality further differentiated immigrant representations: documentation conjured trustworthy representations, illegality conjured threatening representations. Participants spontaneously sorted unlabeled faces by documentation status in a spatial arrangement task. Faces' spatial similarity correlated with their similarity in pixel luminance and "American" ratings, confirming racialized distinctions. Representations of illegalized immigrants were uniquely racialized as dark-skinned un-American threats, reflecting how U.S. imperialism and colorism set conditions of possibility for existing representations of migrant illegalization.
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Racismo , Humanos , Masculino , Feminino , Adulto , Racismo/psicologia , Estados Unidos , Adulto Jovem , Emigrantes e Imigrantes/psicologia , Emigração e Imigração , Adolescente , Documentação , FaceRESUMO
The RNA recognition motif (RRM) is the most prevalent RNA binding domain in eukaryotes and is involved in most RNA metabolism processes. Single RRM domains have a limited RNA specificity and affinity and tend to be accompanied by other RNA binding domains, frequently additional RRMs that contribute to an avidity effect. Within multi-RRM proteins, the most common arrangement are tandem RRMs, with two domains connected by a variable linker. Despite their prevalence, little is known about the features that lead to specific arrangements, and especially the role of the connecting linker. In this work, we present a novel and robust way to investigate the relative domain orientation in multi-domain proteins using inter-domain vectors referenced to a stable secondary structure element. We apply this method to tandem RRM domains and cluster experimental tandem RRM structures according to their inter-domain and linker-domain contacts, and report how this correlates with their orientation. By extending our analysis to AlphaFold2 predicted structures, with particular attention to the inter-domain predicted aligned error, we identify new orientations not reported experimentally. Our analysis provides novel insights across a range of tandem RRM orientations that may help for the design of proteins with a specific RNA binding mode.
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Poly-ADP-Ribose Polymerase (PARP-1) is an overexpressed enzyme in several carcinomas; consequently, the design of PARP-1 inhibitors has acquired special attention. Hence, in the present study, three compounds (8-10) were produced through a Michael addition protocol, using phenylmethanethiol, 5-fluoro-2-mercaptobenzyl alcohol, and 4-mercaptophenylacetic acid, respectively, as nucleophiles and perezone as the substrate, expecting them to be convenient candidates that inhibit PARP-1. It is convenient to note that in the first stage of the whole study, the molecular dynamics (MD) simulations and the quantum chemistry studies of four secondary metabolites, i.e., perezone (1), perezone angelate (2), hydroxyperezone (3), and hydroxyperezone monoangelate (4), were performed, to investigate their interactions in the active site of PARP-1. Complementarily, a docking study of a set of eleven sulfur derivatives of perezone (5-15) was projected to explore novel compounds, with remarkable affinity to PARP-1. The molecules 8-10 provided the most adequate results; therefore, they were evaluated in vitro to determine their activity towards PARP-1, with 9 having the best IC50 (0.317 µM) value. Additionally, theoretical calculations were carried out using the density functional theory (DFT) with the hybrid method B3LYP with a set of base functions 6-311++G(d,p), and the reactivity properties were compared between the natural derivatives of perezone and the three synthesized compounds, and the obtained results exhibited that 9 has the best properties to bind with PARP-1. Finally, it is important to mention that 9 displays significant inhibitory activity against MDA-MB-231 and MCF-7 cells, i.e., 145.01 and 83.17 µM, respectively.
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Cicloexenos , Neoplasias , Inibidores de Poli(ADP-Ribose) Polimerases , Sesquiterpenos , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Células MCF-7 , Simulação de Dinâmica Molecular , Neoplasias/tratamento farmacológicoRESUMO
To aid the possible prevention of multidrug resistance in tumors and cause lower toxicity, a set of sixteen novel dihydropyridine carboxylic acids derivatives 3a-p were produced; thus, the activation of various ynones with triflic anhydride was performed, involving a nucleophilic addition of several bis(trimethylsilyl) ketene acetals, achieving good yields requiring easy workup. The target molecules were unequivocally characterized by common spectroscopic methods. In addition, two of the tested compounds (3a, and 3b) were selected to perform in silico studies due to the highest cytotoxic activity towards the HCT-15 cell line (7.94 ± 1.6 µM and 9.24 ± 0.9 µM, respectively). Employing theoretical calculations with density functional theory (DFT) using the B3LYP/6-311++G(d,p) showed that the molecular parameters correlate adequately with the experimental results. In contrast, predictions employing Osiris Property Explorer showed that compounds 3a and 3b present physicochemical characteristics that would likely make it an orally active drug. Moreover, the performance of Docking studies with proteins related to the apoptosis pathway allowed a proposal of which compounds could interact with PARP-1 protein. Pondering the obtained results (synthesis, in silico, and cytotoxic activity) of the target compounds, they can be judged as suitable antineoplastic agent candidates.
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Antineoplásicos , Di-Hidropiridinas , Neoplasias , Humanos , Linhagem Celular , Antineoplásicos/química , Compostos Orgânicos , Ácidos Carboxílicos/farmacologia , Di-Hidropiridinas/farmacologia , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
Faces are socially important surfaces of the body on which various meanings are attached. The widespread physiognomic belief that faces inherently contain socially predictive value is why they make a generative stimulus for perception research. However, critical problems arise in studies that simultaneously investigate faces and race. Researchers studying race and racism inadvertently engage in various research practices that transform faces with specific phenotypes into straightforward representatives of their presumed race category, thereby taking race and its phenotypic associations for granted. I argue that research practices that map race categories onto faces using bioessentialist ideas of racial phenotypes constitute a form of racecraft ideology, the dubious reasoning of which presupposes the reality of race and mystifies the causal relation between race and racism. In considering how to study racism without reifying race in face studies, this article places these practices in context, describes how they reproduce racecraft ideology and impair theoretical inferences, and then suggests counterpractices for minimizing this problem.
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Background: Data management is fast becoming an essential part of scientific practice, driven by open science and FAIR (findable, accessible, interoperable, and reusable) data sharing requirements. Whilst data management plans (DMPs) are clear to data management experts and data stewards, understandings of their purpose and creation are often obscure to the producers of the data, which in academic environments are often PhD students. Methods: Within the RNAct EU Horizon 2020 ITN project, we engaged the 10 RNAct early-stage researchers (ESRs) in a training project aimed at formulating a DMP. To do so, we used the Data Stewardship Wizard (DSW) framework and modified the existing Life Sciences Knowledge Model into a simplified version aimed at training young scientists, with computational or experimental backgrounds, in core data management principles. We collected feedback from the ESRs during this exercise. Results: Here, we introduce our new life-sciences training DMP template for young scientists. We report and discuss our experiences as principal investigators (PIs) and ESRs during this project and address the typical difficulties that are encountered in developing and understanding a DMP. Conclusions: We found that the DS-wizard can also be an appropriate tool for DMP training, to get terminology and concepts across to researchers. A full training in addition requires an upstream step to present basic DMP concepts and a downstream step to publish a dataset in a (public) repository. Overall, the DS-Wizard tool was essential for our DMP training and we hope our efforts can be used in other projects.
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BACKGROUND: Heart valve replacement surgery with mechanical or biological prostheses entails a risk of thromboembolism and bleeding complications. OBJECTIVE: To determine the complications related to complementary anticoagulation therapy and the probability of risk. METHODS: One-hundred and sixty-three patients who underwent heart valve replacement between 2002 and 2016 with either mechanical or biological prostheses, and who received vitamin K antagonists after hospital discharge, were studied. Anticoagulation therapy was categorized into optimal and non-optimal according to INR values prior to the development of complications. Patients with comorbidities and other risk factors for thrombosis and/or bleeding were excluded. RESULTS: In total, 68.7 % of patients received mechanical prostheses, and 31.3 %, biological prostheses (p ≤ 0.001); 25.2 % experienced the complications that motivated the study (p ≤ 0.001), which were hemorrhagic in 48.8 %, thromboembolic in 26.8 %, and of both types in 24.4 % (relative risk = 4.229). Among the patients with complications, 95.1 % received mechanical prostheses, and 4.9 %, biological (p = 0.005); non-optimal INR was identified in 49.7 % (p ≤ 0.001). CONCLUSIONS: Given the high risk of thromboembolic and hemorrhagic complications, valve prostheses must be carefully chosen, and care priorities should include prevention and follow-up, especially in those patients who require anticoagulation therapy.
ANTECEDENTES: El reemplazo valvular por prótesis mecánicas o biológicas implica riesgo de tromboembolismo y complicaciones hemorrágicas. OBJETIVO: Determinar las complicaciones relacionadas con la terapia de anticoagulación complementaria y la probabilidad de riesgo en pacientes portadores de prótesis valvulares del corazón. MÉTODOS: Se estudiaron 163 pacientes entre 2002 y 2016, portadores de prótesis mecánicas y biológicas, quienes recibieron antagonistas de la vitamina K posterior al egreso hospitalario. La terapia de anticoagulación se categorizó en óptima y no óptima conforme a los valores de INR previos a las complicaciones. Fueron excluidos los pacientes con comorbilidades y otros factores de riesgo de trombosis y/o sangrado. RESULTADOS: a 68.7 % de los pacientes se les colocó prótesis mecánica y a 31.3 %, biológica (p ≤ 0.001); 25.2 % presentó las complicaciones motivo de estudio (p ≤ 0.001), hemorrágicas en 48.8 %, tromboembólicas en 26.8 % y de ambos tipos en 24.4 % (riesgo relativo = 4.229); a 95.1 % de los pacientes con complicaciones se les colocó prótesis mecánica y a 4.9 %, biológica (p = 0.005); 49.7 % presentó INR no óptimo (p ≤ 0.001). CONCLUSIONES: Ante riesgo alto de complicaciones tromboembólicas y hemorrágicas, la elección de las prótesis valvulares, la prevención y el seguimiento son prioridades, principalmente en quienes requieren terapia de anticoagulación.
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Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Tromboembolia , Humanos , Centros de Atenção Terciária , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Próteses Valvulares Cardíacas/efeitos adversos , Anticoagulantes/uso terapêutico , Hemorragia/epidemiologia , Hemorragia/etiologia , Valvas Cardíacas , Implante de Prótese de Valva Cardíaca/efeitos adversosRESUMO
Resumen Antecedentes: El reemplazo valvular por prótesis mecánicas o biológicas implica riesgo de tromboembolismo y complicaciones hemorrágicas. Objetivo: Determinar las complicaciones relacionadas con la terapia de anticoagulación complementaria y la probabilidad de riesgo en pacientes portadores de prótesis valvulares del corazón. Métodos: Se estudiaron 163 pacientes entre 2002 y 2016, portadores de prótesis mecánicas y biológicas, quienes recibieron antagonistas de la vitamina K posterior al egreso hospitalario. La terapia de anticoagulación se categorizó en óptima y no óptima conforme a los valores de INR previos a las complicaciones. Fueron excluidos los pacientes con comorbilidades y otros factores de riesgo de trombosis y/o sangrado. Resultados: a 68.7 % de los pacientes se les colocó prótesis mecánica y a 31.3 %, biológica (p ≤ 0.001); 25.2 % presentó las complicaciones motivo de estudio (p ≤ 0.001), hemorrágicas en 48.8 %, tromboembólicas en 26.8 % y de ambos tipos en 24.4 % (riesgo relativo = 4.229); a 95.1 % de los pacientes con complicaciones se les colocó prótesis mecánica y a 4.9 %, biológica (p = 0.005); 49.7 % presentó INR no óptimo (p ≤ 0.001). Conclusiones: Ante riesgo alto de complicaciones tromboembólicas y hemorrágicas, la elección de las prótesis valvulares, la prevención y el seguimiento son prioridades, principalmente en quienes requieren terapia de anticoagulación.
Abstract Background: Heart valve replacement surgery with mechanical or biological prostheses entails a risk of thromboembolism and bleeding complications. Objective: To determine the complications related to complementary anticoagulation therapy and the probability of risk. Methods: One-hundred and sixty-three patients who underwent heart valve replacement between 2002 and 2016 with either mechanical or biological prostheses, and who received vitamin K antagonists after hospital discharge, were studied. Anticoagulation therapy was categorized into optimal and non-optimal according to INR values prior to the development of complications. Patients with comorbidities and other risk factors for thrombosis and/or bleeding were excluded. Results: In total, 68.7 % of patients received mechanical prostheses, and 31.3 %, biological prostheses (p ≤ 0.001); 25.2 % experienced the complications that motivated the study (p ≤ 0.001), which were hemorrhagic in 48.8 %, thromboembolic in 26.8 %, and of both types in 24.4 % (relative risk = 4.229). Among the patients with complications, 95.1 % received mechanical prostheses, and 4.9 %, biological (p = 0.005); non-optimal INR was identified in 49.7 % (p ≤ 0.001). Conclusions: Given the high risk of thromboembolic and hemorrhagic complications, valve prostheses must be carefully chosen, and care priorities should include prevention and follow-up, especially in those patients who require anticoagulation therapy.
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Aflatoxin B1 (AFB1) exhibits the most potent mutagenic and carcinogenic activity among aflatoxins. For this reason, AFB1 is recognized as a human group 1 carcinogen by the International Agency of Research on Cancer. Consequently, it is essential to determine its properties and behavior in different chemical systems. The chemical properties of AFB1 can be explored using computational chemistry, which has been employed complementarily to experimental investigations. The present review includes in silico studies (semiempirical, Hartree-Fock, DFT, molecular docking, and molecular dynamics) conducted from the first computational study in 1974 to the present (2022). This work was performed, considering the following groups: (a) molecular properties of AFB1 (structural, energy, solvent effects, ground and the excited state, atomic charges, among others); (b) theoretical investigations of AFB1 (degradation, quantification, reactivity, among others); (c) molecular interactions with inorganic compounds (Ag+, Zn2+, and Mg2+); (d) molecular interactions with environmentally compounds (clays); and (e) molecular interactions with biological compounds (DNA, enzymes, cyclodextrins, glucans, among others). Accordingly, in this work, we provide to the stakeholder the knowledge of toxicity of types of AFB1-derivatives, the structure-activity relationships manifested by the bonds between AFB1 and DNA or proteins, and the types of strategies that have been employed to quantify, detect, and eliminate the AFB1 molecule.
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Aflatoxina B1 , Aflatoxinas , Humanos , Aflatoxina B1/toxicidade , Simulação de Acoplamento Molecular , Aflatoxinas/metabolismo , Relação Estrutura-Atividade , Carcinógenos , DNA/metabolismoRESUMO
RNA recognition motifs (RRM) are the most prevalent class of RNA binding domains in eucaryotes. Their RNA binding preferences have been investigated for almost two decades, and even though some RRM domains are now very well described, their RNA recognition code has remained elusive. An increasing number of experimental structures of RRM-RNA complexes has become available in recent years. Here, we perform an in-depth computational analysis to derive an RNA recognition code for canonical RRMs. We present and validate a computational scoring method to estimate the binding between an RRM and a single stranded RNA, based on structural data from a carefully curated multiple sequence alignment, which can predict RRM binding RNA sequence motifs based on the RRM protein sequence. Given the importance and prevalence of RRMs in humans and other species, this tool could help design RNA binding motifs with uses in medical or synthetic biology applications, leading towards the de novo design of RRMs with specific RNA recognition.
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Motivo de Reconhecimento de RNA , RNA , Humanos , RNA/química , Sequência de Aminoácidos , Alinhamento de Sequência , Motivos de Nucleotídeos/genética , Ligação Proteica , Sítios de LigaçãoRESUMO
Traditionally, our understanding of how proteins operate and how evolution shapes them is based on two main data sources: the overall protein fold and the protein amino acid sequence. However, a significant part of the proteome shows highly dynamic and/or structurally ambiguous behavior, which cannot be correctly represented by the traditional fixed set of static coordinates. Representing such protein behaviors remains challenging and necessarily involves a complex interpretation of conformational states, including probabilistic descriptions. Relating protein dynamics and multiple conformations to their function as well as their physiological context (e.g., post-translational modifications and subcellular localization), therefore, remains elusive for much of the proteome, with studies to investigate the effect of protein dynamics relying heavily on computational models. We here investigate the possibility of delineating three classes of protein conformational behavior: order, disorder, and ambiguity. These definitions are explored based on three different datasets, using interpretable machine learning from a set of features, from AlphaFold2 to sequence-based predictions, to understand the overlap and differences between these datasets. This forms the basis for a discussion on the current limitations in describing the behavior of dynamic and ambiguous proteins.
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Alzheimer's disease (AD) is a neurodegenerative condition characterized by cognitive and functional impairments. The investigation of AD has focused on the formation of senile plaques, composed mainly by amyloid ß (Aß) peptide, and neurofibrillary tangles (NFTs) in the brain. Senile plaques and NFTs cause the excessive recruitment and activation of microglia, thus generating neuroinflammation and neuronal damage. Among the risk factors for the development of AD, diabetes has increasingly attracted attention. Hyperglycemia, the fundamental characteristic of diabetes, is involved in several mechanisms that give rise to microglial overactivation, resulting in neuronal damage and cognitive impairment. Indeed, various studies have identified the correlation between diabetes and AD. The aim of this review is to describe various mechanisms of the hyperglycemia-induced overactivation of microglia, which leads to neuroinflammation and neuronal damage and consequently contributes to the pathology of AD. The disruption of the regulation of microglial activity by hyperglycemia occurs through many mechanisms, including a greater production of reactive oxygen species (ROS) and glycation end products (AGEs), and a decrease in the elimination of Aß. The future direction of research on the relation between hyperglycemia and AD is addressed, such as the importance of determining whether the hyperglycemia-induced harmful effects on microglial activity can be reversed or attenuated if blood glucose returns to a normal level.
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Doença de Alzheimer , Hiperglicemia , Humanos , Doença de Alzheimer/patologia , Microglia/patologia , Peptídeos beta-Amiloides , Placa Amiloide/complicações , Placa Amiloide/patologia , Espécies Reativas de Oxigênio , Glicemia , Hiperglicemia/complicaçõesRESUMO
The coordination of one and two aflatoxin B1 (AFB1, a potent carcinogen) molecules with chlorophyll a (chl a) was studied at a theoretical level. Calculations were performed using the M06-2X method in conjunction with the 6-311G(d,p) basis set, in both gas and water phases. The molecular electrostatic potential map shows the chemical activity of various sites of the AFB1 and chl a molecules. The energy difference between molecular orbitals of AFB1 and chl a allowed for the establishment of an intermolecular interaction. A charge transfer from AFB1 to the central cation of chl a was shown. The energies of the optimized structures for chl a show two configurations, unfolded and folded, with a difference of 15.41 kcal/mol. Chl a appeared axially coordinated to the plane (α-down or ß-up) of the porphyrin moiety, either with the oxygen atom of the ketonic group, or with the oxygen atom of the lactone moiety of AFB1. The complexes of maximum stability were chl a 1-α-E-AFB1 and chl a 2-ß-E-AFB1, at -36.4 and -39.2 kcal/mol, respectively. Additionally, with two AFB1 molecules were chl a 1-D-2AFB1 and chl a 2-E-2AFB1, at -60.0 and -64.8 kcal/mol, respectively. Finally, biosorbents containing chlorophyll could improve AFB1 adsorption.
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Aflatoxina B1 , Clorofila , Aflatoxina B1/química , Carcinógenos , Clorofila A , OxigênioRESUMO
Glioblastoma multiforme (GBM) represents the most malignant type of astrocytoma, with a life expectancy of two years. It has been shown that Poly (ADP-ribose) polymerase 1 (PARP-1) protein is over-expressed in GBM cells, while its expression in healthy tissue is low. In addition, perezone, a phyto-compound, is a PARP-1 inhibitor with anti-neoplastic activity. As a consequence, in the present study, both in vitro and computational evaluations of perezone and its chemically related compound, perezone angelate, as anti-GBM agents were performed. Hence, the anti-proliferative assay showed that perezone angelate induces higher cytotoxicity in the GBM cell line (U373 IC50 = 6.44 µM) than perezone (U373 IC50 = 51.20 µM) by induction of apoptosis. In addition, perezone angelate showed low cytotoxic activity in rat glial cells (IC50 = 173.66 µM). PARP-1 inhibitory activity (IC50 = 5.25 µM) and oxidative stress induction by perezone angelate were corroborated employing in vitro studies. In the other hand, the performed docking studies allowed explaining the PARP-1 inhibitory activity of perezone angelate, and ADMET studies showed its probability to permeate cell membranes and the blood-brain barrier, which is an essential characteristic of drugs to treat neurological diseases. Finally, it is essential to highlight that the results confirm perezone angelate as a potential anti-GBM agent.
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Neoplasias Encefálicas , Glioblastoma , Sesquiterpenos , Animais , Apoptose , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioblastoma/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Ratos , Sesquiterpenos/farmacologiaRESUMO
The introduction of biomedical HIV prevention methods, such as pre-exposure prophylaxis (PrEP), holds the potential to overcome the serodivide. We investigated the attitudes of PrEP users towards having sex with partners living with HIV. PrEP users in the Netherlands were recruited online and completed three questionnaires over a period of six months. We investigated changes over time in feelings of fear of HIV, comfort, and attitudes towards condom use when having sex with men living with HIV (MLHIV). A majority of PrEP users in our sample (up to 71.6%) had sex with MLHIV. Feeling comfortable to have sex with MLHIV did not change over time, but was already at a high level at T1. Most importantly, feeling safe not to use condoms with HIV-positive partners significantly increased, and did so in a rather short period of time after the onset of PrEP use (3-6 months). Taken together, the findings suggest that that PrEP may contribute to decreasing the serodivide between MSM rather quickly after the onset of PrEP use.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Fármacos Anti-HIV/uso terapêutico , Preservativos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Sexo Seguro , Parceiros SexuaisRESUMO
Next to its benefits for HIV prevention, PrEP may have psychosocial benefits relating to improved quality of sex life. The aim of the current study was to investigate the onset of changes in the quality of sex life and sexual pleasure of PrEP users in the first months of commencing PrEP use. Moreover, we investigated what factors were related to the quality of sex life of PrEP users. We recruited 145 participants via the Dutch PrEP-advocacy website PrEPnu.nl, and they received follow-up questionnaires after three and six months. We found that PrEP users reported an increase in the quality of their sex life, which was related to reduced fear of HIV since they started using PrEP but not to decreased condom use. PrEP users were more interested in experimenting with sex practices, but they did not always feel more desirable as a sex partner because of PrEP use. Health-care providers and health promotion campaigns could emphasize the positive effects of PrEP on the quality of sex life, in addition to the HIV-preventive effects of PrEP, to decrease PrEP stigma and increase PrEP uptake.
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Infecções por HIV , Profilaxia Pré-Exposição , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Homossexualidade Masculina/psicologia , Humanos , Masculino , Países Baixos , Prazer , Comportamento SexualRESUMO
This chapter covers a sesquiterpene quinone, commonly named perezone. This molecule is documented as the first secondary metabolite isolated in crystalline form in the New World in 1852. An introduction, with its structure, the IUPAC nomenclature, and the most recent physical and spectroscopic characterizations are firstly described initially. Alongside this, a timeline and scheme with summarized information of the history of this molecule is given including the "Códice Badiano de la Cruz, 1552, highlighting the year of its isolation culminating with information up to 2005. Subsequently, in a chronological order the most recent advances of the target molecule are included and organized in subsections covering the last 15-year period 2006-2020. Finally, recently submitted contributions from the laboratory of the authors are described. It is important to note that the details provided highlight the importance and relevance of perezone.
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Sesquiterpenos , QuinonasRESUMO
We provide integrated protein sequence-based predictions via https://bio2byte.be/b2btools/. The aim of our predictions is to identify the biophysical behaviour or features of proteins that are not readily captured by structural biology and/or molecular dynamics approaches. Upload of a FASTA file or text input of a sequence provides integrated predictions from DynaMine backbone and side-chain dynamics, conformational propensities, and derived EFoldMine early folding, DisoMine disorder, and Agmata ß-sheet aggregation. These predictions, several of which were previously not available online, capture 'emergent' properties of proteins, i.e. the inherent biophysical propensities encoded in their sequence, rather than context-dependent behaviour (e.g. final folded state). In addition, upload of a multiple sequence alignment (MSA) in a variety of formats enables exploration of the biophysical variation observed in homologous proteins. The associated plots indicate the biophysical limits of functionally relevant protein behaviour, with unusual residues flagged by a Gaussian mixture model analysis. The prediction results are available as JSON or CSV files and directly accessible via an API. Online visualisation is available as interactive plots, with brief explanations and tutorial pages included. The server and API employ an email-free token-based system that can be used to anonymously access previously generated results.