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Microbiologically contaminated water is a significant source of infections in humans and animals, with Pseudomonas aeruginosa (PSA) being particularly concerning due to its ability to thrive in water environments and its resistance to many disinfectants. Therefore, this study investigates the adhesion potential of PSA strains on various materials used in mineral water extraction wells, focusing on hydrophobic and hydrophilic properties. Mineral water samples were collected from three wells (P-01, P-07, and P-08) within the Guarani Aquifer System and Fractured Aquifer System (SAF) in Brazil. The physicochemical properties of the water, including concentrations of Sr (strontium), Fe (iron), Si (silicon), SO42- (sulfate ions), Cl- (chloride ions), and ORP (oxidation-reduction potential), were analyzed. Results indicated higher PSA adhesion on hydrophobic materials, particularly high-density polyethylene (HDPE) and geomechanically plasticized polyvinyl chloride (PVC). Multiple correlation analyses revealed positive correlations between PSA adhesion on hydrophilic materials and Sr, Fe, Si, SO42-, and Cl- concentrations. Conversely, ORP negatively correlated with bacterial adhesion on PVC surfaces, suggesting higher ORP values reduced PSA attachment. These findings highlight the importance of water composition and material properties in influencing bacterial adhesion and potential biofilm formation in mineral water extraction systems.
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Fracture-related infection (FRI) is a devastating event, directly affecting fracture healing, impairing patient function, prolonging treatment, and increasing healthcare costs. Time plays a decisive role in prognosis, as biofilm maturation leads to the development of antibiotic resistance, potentially contributing to infection chronicity and increasing morbidity and mortality. Research exploring the association between biofilm maturation and antibiotic resistance in orthopaedics primarily addresses aspects related to quality of life and physical function; however, little exists on life-threatening conditions and mortality. Understanding the intrinsic relationship between biofilm maturation, bacterial resistance, and mortality is critical in all fields of medicine. In the herein narrative review, we summarize recent evidence regarding biofilm formation, antibiotic resistance, and infection chronicity (BARI), the three basic components of the "triangle of death" of FRI, and its implications. Preoperative, perioperative, and postoperative prevention strategies to avoid the "triangle of death" of FRI are presented and discussed. Additionally, the importance of the orthopaedic trauma surgeon in understanding new tools to combat infections related to orthopaedic devices is highlighted.
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INTRODUCTION: Candida albicans is the most common opportunistic pathogen causing fungal infections worldwide, especially in high-risk patients. Its pathogenicity is related to virulence factors gene expression, such as hyphal growth (HWP1), cell adhesion (ALS3), and protease secretion (SAP1) during infection spreading mechanisms. In recent years, an increase in non-albicans Candida infections has been reported, which may present coinfection or competitive interactions with C. albicans, potentially aggravating the patient's condition. This study aims to evaluate the expression of genes related to virulence factors of C. albicans and non-albicans Candida during planktonic stage. METHODS: C. albicans (ATCC MYA-3573) as well as with three clinical strains (C. albicans DCA53, C. tropicalis DCT6, and C. parapsilosis DCP1) isolated from blood samples, were grown in 24-well plates at 37°C for 20 h, either in monocultures or mixed cultures. Quantitative real-time polymerase chain reaction was used to evaluate the expression levels of the genes HWP1, ALS3, and SAP1 in cells collected during the planktonic stage. In addition, hyphal filamentation was observed using a Scanning Electron Microscope. RESULTS: The overexpression of HWP1 and ASL3 genes in mixed growth conditions between C. albicans and non-albicans Candida species suggests a synergistic relationship as well as an increased capacity for hyphal growth and adhesion. In contrast, C. parapsilosis versus C. tropicalis interaction shows an antagonistic relationship during mixed culture, suggesting a decreased virulence profile of C. parapsilosis during initial coinfection with C. tropicalis. CONCLUSION: The expression of HWP1, ALS3, and SAP1 genes associated with virulence factors varies under competitive conditions among species of the genus Candida during planktonic stage.
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Candida albicans , Proteínas Fúngicas , Fatores de Virulência , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Fatores de Virulência/genética , Candida albicans/patogenicidade , Candida albicans/genética , Virulência/genética , Hifas/genética , Regulação Fúngica da Expressão Gênica , Candidíase/microbiologia , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Plâncton/genética , Candida/patogenicidade , Candida/genética , Glicoproteínas de MembranaRESUMO
The Silurian-Devonian transition played a crucial role in the development of early terrestrial ecosystems due to the rapid diversification of early vascular plants. However, records of Pridolian plants in western Gondwana are scarce, limited to outcrops located in southern Bolivia. In this contribution, an association of fossil plants housed in the Rinconada Formation is presented. This association corresponds to primitive fossil flora with reproductive structures and sterile axes linked to basal tracheophytes. The fossil assemblage is composed of Aberlemnia caledonica, Caia langii Cooksonia cf. cambrensis, C. paranensis, C. cf. pertoni, Hostinella sp, Cf. Isidrophyton sp, Salopella marcensis, Steganoteca striata, two morphotypes of doubtful taxonomy, and graptolites colonies. The association between flora remains and graptolites, represents a parautochthonous assemblage in an inner marine platform, dominated by gravity flows. This record has paleophytogeographic importance indicating the extension of the northwest Gondwana-southern Laurusia unit to more southern areas of Gondwana. This expansion would have been favored by the post-glacial climatic improvement of the Late Silurian, together with a great radiation capacity and environmental flexibility of the flora. Furthermore, the biochron is extended of three taxa (A. caledonica, C. paranensis and Cf. Isidrophyton sp) first known from the Lochkovian, to the Pridoli.
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Fósseis , Fósseis/anatomia & histologia , Embriófitas/classificação , Embriófitas/anatomia & histologia , Ecossistema , Bolívia , Evolução Biológica , PaleontologiaRESUMO
OBJECTIVES: To evaluate the marginal integrity (MI%) and to characterize specific properties of a thermoviscous bulk-fill resin composite, two regular bulk-fill resin composites, and a non-bulk-fill resin composite. MATERIALS AND METHODS: VisCalor bulk (VBF), Filtek One Bulk Fill (OBF), and Aura Bulk Fill (ABF) were evaluated. Filtek Z250 XT (ZXT) was used as non-bulk-fill control. MI% was evaluated in standardized cylindrical cavities restored with the composites by using a 3D laser confocal microscope. The following properties were characterized: volumetric polymerization shrinkage (VS%), polymerization shrinkage stress (Pss), degree of conversion (DC%), microhardness (KHN), flexural strength (FS), and elastic modulus (EM). Data were analyzed by one-way and two-way ANOVA, and Tukey HSD post-hoc test (α = 0.05). RESULTS: VBF presented the highest MI% and the lowest VS% and Pss (p < 0.05). DC% ranged from 59.4% (OBF) to 71.0% (ZXT). ZXT and VBF presented similar and highest KHN than OBF and ABF (p < 0.05). ABF presented the lowest FS (p < 0.05). EM ranged from 5.5 GPa to 7.7 GPa, with the values of ZXT and VBF being similar and statistically higher than those of OBF and ABF (p < 0.05). CONCLUSIONS: Thermoviscous technology employed by VisCalor bulk was able to improve its mechanical behavior comparatively to regular bulk-fill resin composites and to contribute to a better marginal integrity in restorations built up in cylindrical cavities with similar geometry to a class I cavity as well. Although presenting overall better physicomechanical properties, Z250 XT presented the worst MI%. CLINICAL RELEVANCE: The marginal integrity, which is pivotal for the success of resin composite restorations, could be improved using VisCalor bulk-fill. The worst MI% presented by Z250 XT reinforces that non-bulk-fill resin composites shall not be bulk-inserted in the cavity to be restored.
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Resinas Compostas , Adaptação Marginal Dentária , Módulo de Elasticidade , Resistência à Flexão , Teste de Materiais , Polimerização , Propriedades de Superfície , Resinas Compostas/química , Dureza , Microscopia Confocal , Técnicas In Vitro , Restauração Dentária Permanente/métodos , Análise do Estresse DentárioRESUMO
This paper introduces a new latent variable probabilistic framework for representing spectral data of high spatial and spectral dimensionality, such as hyperspectral images. We use a generative Bayesian model to represent the image formation process and provide interpretable and efficient inference and learning methods. Surprisingly, our approach can be implemented with simple tools and does not require extensive training data, detailed pixel-by-pixel labeling, or significant computational resources. Numerous experiments with simulated data and real benchmark scenarios show encouraging image classification performance. These results validate the unique ability of our framework to discriminate complex hyperspectral images, irrespective of the presence of highly discriminative spectral signatures.
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Staphylococcus aureus is a well-known pathogen capable of producing enterotoxins during bacterial growth in contaminated food, and the ingestion of such preformed toxins is one of the major causes of food poisoning around the world. Nowadays 33 staphylococcal enterotoxins (SEs) and SE-like toxins have been described, but nearly 95% of confirmed foodborne outbreaks are attributed to classical enterotoxins SEA, SEB, SEC, SED, and SEE. The natural habitat of S. aureus includes the skin and mucous membranes of both humans and animals, allowing the contamination of milk, its derivatives, and the processing facilities. S. aureus is well known for the ability to form biofilms in food processing environments, which contributes to its persistence and cross-contamination in food. The biocontrol of S. aureus in foods by lactic acid bacteria (LAB) and their bacteriocins has been studied for many years. Recently, LAB and their metabolites have also been explored for controlling S. aureus biofilms. LAB are used in fermented foods since in ancient times and nowadays characterized strains (or their purified bacteriocin) can be intentionally added to prolong food shelf-life and to control the growth of potentially pathogenic bacteria. Regarding the use of these microorganism and their metabolites (such as organic acids and bacteriocins) to prevent biofilm development or for biofilm removal, it is possible to conclude that a complex network behind the antagonistic activity remains poorly understood at the molecular level. The use of approaches that allow the characterization of these interactions is necessary to enhance our understanding of the mechanisms that govern the inhibitory activity of LAB against S. aureus biofilms in food processing environments.
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Biofilmes , Enterotoxinas , Microbiologia de Alimentos , Staphylococcus aureus , Staphylococcus aureus/fisiologia , Enterotoxinas/metabolismo , Humanos , Animais , Lactobacillales/fisiologia , Lactobacillales/metabolismo , Indústria de Laticínios , Bacteriocinas/metabolismo , Contaminação de Alimentos/prevenção & controle , Leite/microbiologiaRESUMO
The modes of formation and release of secretion are complex processes that occur in secretory ducts and their description has great divergence in some species. The use of modern techniques to detect hydrolytic enzymes, cytoskeleton arrangement and indicators of programmed cell death may help clarify the processes involved during the ontogeny of that gland. The goal of our study was to analyze subcellular changes during schizogenous formation and secretion production and release into the lumen in resin ducts of Kielmeyera appariciana. Our results demonstrate the participation of pectinase through the loosening of the central cells of the rosette, which subsequently split from each other through polarized growth mediated by a rearrangement of the microtubules. The resin is mainly synthesized in plastids and endoplasmic reticulum and is observed inside vesicles and small vacuoles. The secretion release is holocrine and occurs through programmed cell death related to the release of reactive oxygen species, causing cytoplasm darkening, chromatin condensation, vacuole rupture and plastid and mitochondria degeneration. Cellulase activity was identified prior to the rupture of the cell wall, causing the release of secretion into the lumen of the duct. The participation of the cytoskeleton was observed for the first time during schizogeny of ducts as well as programmed cell death as part of the process of the release of holocrine secretion. This type of secretion release may be a key innovation in Kielmeyera since it has not been observed in ducts of any other plant thus far.
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The Portezuelo Formation preserves an outstanding record of the upper Turonian - lower Coniacian. Despite the discovery of a significant quantity of sauropod fossil material from the formation, only two species have been formally described to date: Malarguesaurus florenciae and Futalognkosaurus dukei. Here we present new sauropod material mostly composed of non-articulated caudal vertebrae (MCF-PVPH 916 and 917) that belong to two titanosauriforms on the basis of the following features: anterior caudal vertebrae with procoelous-opisthoplatyan articulations, transverse processes that reach the posterior articular face of the centrum and neural spines with a transverse width of around 50% of their anteroposterior length; anterior and middle caudal vertebrae with the neural arch restricted to the anterior half of the centrum; middle caudal centra with circular cross-section. Phylogenetic analysis recovers the new material in close relation to Malarguesaurus within a monophyletic clade at the base of Somphospondyli. This clade shares large pedicel height with a vertical anterior border on the middle caudal vertebrae, a vertical orientation of the neural spines on the distalmost middle caudal vertebrae and proximalmost posterior caudal vertebrae, and subequal relative lengths of the proximal ulnar condylar processes. The specimens presented here are distinct not only from Futalognkosaurus, but also from other indeterminate titanosaurian remains from the same formation. However, there are no significant differences between the specimen MCF-PVPH 917 and Malarguesaurus, but there are differences between the posterior caudal vertebrae of MCF-PVPH 916 and Malarguesaurus, so they could be considered different species. Whilst we err on the side of caution in not naming new taxa here, the two specimens significantly expand what we know about sauropods in the Turonian-Coniacian ecosystems of Patagonia, which will continue to do so as more material is discovered.
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Dinossauros , Fósseis , Filogenia , Animais , Dinossauros/anatomia & histologia , Argentina , Coluna Vertebral/anatomia & histologia , BiodiversidadeRESUMO
Background: The chromosome 1p32p31 deletion syndrome is a contiguous gene disorder with a variable phenotype characterized by brain malformations with or without urinary tract defects, besides neurodevelopmental delay and dysmorphisms. An expanded phenotype was proposed based on additional findings, including one previous report of a patient presenting with moyamoya disease. Case Presentation: The authors report a patient presenting with early neurodevelopmental delay, hydrocephalus, renal malformation, and dysmorphisms. After presenting with a sudden choreic movement disorder, the neuroimaging investigation revealed an ischemic stroke, moyamoya disease, and bilateral incomplete hippocampal inversion. Chromosomal microarray analysis revealed a deletion of 13.2 Mb at 1p31.3p32.2, compatible with the contiguous gene syndrome caused by microdeletions of this region. Discussion/Conclusion: This is the second report of a patient who developed Moyamoya disease and the first to describe bilateral incomplete hippocampal inversion in this microdeletion syndrome.
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BACKGROUND: Unenlagiine paravians are among the most relevant Gondwanan theropod dinosaur clades for understanding the origin of birds, yet their fossil record remains incomplete, with most taxa being represented by fragmentary material and/or separated by lengthy temporal gaps, frustrating attempts to characterize unenlagiine evolution. RESULTS AND CONCLUSIONS: Here we describe Diuqin lechiguanae gen. et sp. nov., a new unenlagiine taxon from the Upper Cretaceous (Santonian) Bajo de la Carpa Formation of the Neuquén Basin of Neuquén Province in northern Patagonia, Argentina that fills a substantial stratigraphic gap in the fossil record of these theropods. Although known only from a very incomplete postcranial skeleton, the preserved bones of Diuqin differ from corresponding elements in other unenlagiines, justifying the erection of the new taxon. Moreover, in several morphological aspects, the humerus of Diuqin appears intermediate between those of geologically older unenlagiines from the Neuquén Basin (e.g., Unenlagia spp. from the Turonian-Coniacian Portezuelo Formation) and that of the stratigraphically younger, larger-bodied Austroraptor cabazai from the Campanian-Maastrichtian Allen Formation. Consequently, the morphology of the new taxon appears to indicate a transitional stage in unenlagiine evolution. Phylogenetic analysis recovers Diuqin as a paravian with multiple plausible systematic positions, but the strongest affinity is with Unenlagiinae. The humerus of the new form exhibits subcircular punctures near its distal end that are interpreted as feeding traces most likely left by a conical-toothed crocodyliform, mammal, or theropod, the latter potentially corresponding to a megaraptorid or another unenlagiine individual. Thus, in addition to filling important morphological and temporal gaps in unenlagiine evolutionary history, the new taxon also offers information relating to the paleoecology of these theropods.
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Dinossauros , Fósseis , Argentina , Animais , Dinossauros/anatomia & histologia , Dinossauros/classificação , Filogenia , Evolução BiológicaRESUMO
This work analyzes the effect of wall geometry when a reaction-diffusion system is confined to a narrow channel. In particular, we study the entropy production density in the reversible Gray-Scott system. Using an effective diffusion equation that considers modifications by the channel characteristics, we find that the entropy density changes its value but not its qualitative behavior, which helps explore the structure-formation space.
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Global warming is changing precipitation patterns, particularly harming communities in low-and-middle income countries (LMICs). Whilst the long-term effects of being exposed to rainfall shocks early in life on school-achievement tests are well-established, there is little population-based evidence from LMICs on the mechanisms through which these shocks operate. Executive functions (EFs) are key for children's learning abilities. This paper analyses the effects of early exposure to rainfall shocks on four foundational cognitive skills (FCSs), including EFs that have been found to be key predictors of educational success. These skills were measured via a series of tablet-based tasks administered in Peru as part of the Young Lives longitudinal study (YLS). We combine the YLS data with gridded data on monthly precipitation to generate monthly, community-level rainfall shock estimates. The key identification strategy relies on temporary climatic shocks being uncorrelated with other latent determinants of FCSs development. Our results show significant negative effects of early life exposure to rainfall shocks on EFs-especially, on working memory-measured in later childhood. We also find evidence of rainfall shocks decreasing households' abilities to invest in human capital, which may affect both FCSs and domain-specific test scores. Finally, there is suggestive, but not conclusive, evidence that a conditional-cash-transfer program providing poor households with additional financial resources might partially offset the effects of the rainfall shocks.
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Cognição , Função Executiva , Chuva , Humanos , Peru , Masculino , Feminino , Estudos Longitudinais , Criança , Fatores Socioeconômicos , Memória de Curto Prazo , Pré-Escolar , Adolescente , Aquecimento GlobalRESUMO
Paepalanthus is a diverse genus characteristic of the campos rupestres, a megadiverse vegetation found on mountaintops of mainly quartzitic mountain ranges of central-eastern Brazil. Recent efforts on prospecting the biodiversity of Serra do Padre Ângelo, a small mountain complex in eastern Minas Gerais, yielded several new plant and animal species, highlighting the urgency of conservation actions towards this still unprotected area. Here, we describe yet another new species found in the campos rupestres of these mountains, Paepalanthusmagnus, a mountaintop microendemic species morphologically similar to taxa found in the Espinhaço Range, over 200 km distant, a biogeographic pattern shared by several other species. The affinities of the new species are discussed, and we provide illustrations, photographs, and SEM photomicrographs of the seed. We also discuss the conservation status of the species, which is preliminarily assessed as Critically Endangered, reinforcing the urgent need to address the conservation of the unique biodiversity of Serra do Padre Ângelo.
ResumoPaepalanthus é um gênero característico dos campos rupestres, uma vegetação megadiversa encontrada no topo de montanhas de cadeias montanhosas, principalmente quartzíticas, do centro-leste do Brasil. Esforços recentes de inventariar a biodiversidade da Serra do Padre Ângelo, um pequeno complexo montanhoso no leste de Minas Gerais, resultaram na descoberta de várias novas espécies de plantas e animais, destacando a urgência de ações de conservação para esta área ainda não protegida. Aqui, descrevemos mais uma nova espécie encontrada nos campos rupestres dessas montanhas, Paepalanthusmagnus, uma espécie microendêmica, morfologicamente semelhante a táxons encontrados na Serra do Espinhaço, a mais de 200 km de distância, um padrão biogeográfico repetido por várias outras espécies. As afinidades da nova espécie são discutidas e fornecemos ilustrações, fotografias da planta e de microscopia eletrônica de varredura (MEV) da semente. Também discutimos o status de conservação da espécie, que é preliminarmente avaliada como Criticamente Em Perigo, reforçando a necessidade urgente de abordar a conservação da biodiversidade única da Serra do Padre Ângelo.
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AIMS: Pyometra and cystitis caused by Escherichia coli are common diseases identified in canine or feline females. The origin of pyometra infection remains uncertain, and effective prevention strategies for this disease are still unknown. This study aimed to provide a phenotypic characterization, including antimicrobial resistance and virulence profiles, of endometrial pathogenic (EnPEC) and uropathogenic (UPEC) E. coli strains isolated simultaneously from the same animal. METHODS AND RESULTS: Sixteen E. coli strains, from eight different animals, were analyzed in this study. The antimicrobial susceptibility profile of EnPEC and UPEC strains was determined using the disc diffusion method, which showed a similar susceptibility profile among strains (EnPEC and UPEC) from the same animal. The virulence profile of the strains was assessed through biofilm formation, as well as serum resistance abilities. EnPEC and UPEC strains from the same animal exhibited slight variations in their virulence and antimicrobial resistance capabilities. Overall, most of the strain pairs showed a high similarity in their ability to establish biofilms and survive in serum complement activity. CONCLUSIONS: Overall, strains of E. coli isolated from both pyometra and cystitis in the same animal, despite presenting distinct clinical diseases, exhibit a wide phenotypic similarity, suggesting a common origin for the strains.
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Biofilmes , Doenças do Gato , Cistite , Infecções por Escherichia coli , Escherichia coli , Testes de Sensibilidade Microbiana , Fenótipo , Piometra , Animais , Cistite/microbiologia , Cistite/veterinária , Piometra/microbiologia , Piometra/veterinária , Feminino , Gatos , Cães , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Doenças do Gato/microbiologia , Biofilmes/crescimento & desenvolvimento , Virulência , Antibacterianos/farmacologia , Doenças do Cão/microbiologia , Escherichia coli Uropatogênica/isolamento & purificação , Escherichia coli Uropatogênica/patogenicidade , Farmacorresistência BacterianaRESUMO
The study of thirty-two shed crowns from the Portezuelo Formation (middle Turonian-late Coniacian) at the Sierra del Portezuelo locality, reveals six distinct tooth morphotypes identified through cladistic, discriminant, and cluster analyses. Two morphotypes were identified as belonging to Megaraptoridae, three to Abelisauridae, one to Abelisauroidea, and one to Alvarezsauridae. Additionally, two of the morphotypes exhibit a combination of dental features typically found in megaraptorid and abelisauridtheropods. These results suggest a greater diversity of theropods in the original ecosystem than previously thought, including the presence of a second morphotype of megaraptorid and alvarezsaurid previously undocumented in this formation. Furthermore, the existence of Morphotype 6 indicates the potential coexistence of medium-sized abelisauroids alongside larger abelisaurids in the same ecosystem. These findings underscore the importance of future expeditions to the Sierra del Portezuelo locality to further our understanding of these previously unknown theropod species.
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Fósseis , Dente , Animais , Dente/anatomia & histologia , Biodiversidade , Argentina , FilogeniaRESUMO
Ephedroid macrofossils have been widely documented in Cretaceous deposits, including numerous from the Lower Cretaceous Yixian Formation of NE China. However, few ephedroid macrofossils have been reported from South America. Herein, we describe a new plant of the family Ephedraceae, Arlenea delicata gen. et sp. nov., from the Lower Cretaceous Crato Formation of the Araripe Basin, Northeast Brazil, based on the vegetative and reproductive structures. It has the typical morphological characteristics of ephedroid plants, including fertile reproductive branches, opposite phyllotaxy, terminal female cones, a sympodial branching system, longitudinally striated internodes, and swollen nodes. Our new finding is unusual in having inner chlamydosperms subtended by two pairs of bracts, reproductive units connected to branches through swollen receptacles and a smooth seed surface. This new ephedroid taxon from the Crato Formation increases our understanding of plant diversity of this group during the Early Cretaceous. Furthermore, the general morphology (fleshy bracts and enlarged receptacles) of this new fossil discovery indicates that seeds of this plant may have been dispersed by animals such as pterosaurs (mainly the Tapejaridae) and birds (Enantiornithes and Ornituromorpha). If true, this would explain the cosmopolitan distribution of Ephedraceae in the Lower Cretaceous.
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Vertebrate hippocampal formation is central to conversations on the comparative analysis of spatial cognition, especially in light of variation found in different vertebrate classes. Assuming the medial pallium (MP) of extant amphibians resembles the hippocampal formation (HF) of ancestral stem tetrapods, we propose that the HF of modern amniotes began with a MP characterized by a relatively undifferentiated cytoarchitecture, more direct thalamic/olfactory sensory inputs, and a more generalized role in associative learning-memory processes. As such, hippocampal evolution in amniotes, especially mammals, can be seen as progressing toward a cytoarchitecture with well-defined subdivisions, regional connectivity, and a functional specialization supporting map-like representations of space. We then summarize a growing literature on amphibian spatial cognition and its underlying brain organization. Emphasizing the MP/HF, we highlight that further research into amphibian spatial cognition would provide novel insight into the role of the HF in spatial memory processes, and their supporting neural mechanisms. A more complete reconstruction of hippocampal evolution would benefit from additional research on non-mammalian vertebrates, with amphibians being of particular interest.
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Anfíbios , Cognição , Animais , Anfíbios/fisiologia , Cognição/fisiologia , Telencéfalo/fisiologia , Telencéfalo/anatomia & histologia , Hipocampo/fisiologia , Evolução Biológica , Percepção Espacial/fisiologiaRESUMO
BACKGROUND: Extensive antifungal drug use has enhanced fungal resistance, resulting in persistent mycoses. Combining antifungal plant extracts/compounds with these drugs offers good alternatives to increase the activity of both partners, minimize side effects, and overcome drug resistance. In our previous study, Phytolacca tetramera berries extracts demonstrated activity against Candida spp., correlating with the amount of the main constituent phytolaccoside B and its genin, phytolaccagenin. The extracts and phytolaccagenin altered the fungal plasma membrane by binding to ergosterol, whereas phytolaccoside B increased chitin synthase activity. However, the presence of triterpenoid saponins in Phytolacca spp. has been linked to acute toxicity in humans. PURPOSE: This study aimed to evaluate combinations of P. tetramera berries extracts, phytolaccoside B and phytolaccagenin, together with commercial antifungals [amphotericin B, fluconazole, itraconazole, posaconazole, and caspofungin] against Candida albicans and Candida glabrata, to find synergistic effects with multi-target actions, in which the doses of both partners are reduced, and therefore their toxicity. Additionally, we intended to explore their anti-virulence capacity, thereby hindering the development of drug-resistant strains. METHODS: The effects of these combinations were evaluated using both the checkerboard and isobologram methods. Fractional Inhibitory Concentration Index and Dose Reduction Index were calculated to interpret the combination results. To confirm the multi-target effect, studies on mechanisms of action of synergistic mixtures were performed using ergosterol-binding and quantification assays. The ability to inhibit Candida virulence factors, including biofilm formation and eradication from inert surfaces, was also evaluated. Quantification of active markers was performed using a validated UHPLC-ESI-MS method. RESULTS: Eight synergistic combinations of P. tetramera extracts or phytolaccagenin (but not phytolaccoside B) with itraconazole or posaconazole were obtained against C. albicans, including a resistant strain. These mixtures acted by binding to ergosterol, decreasing its whole content, and inhibiting Candida biofilm formation in 96-well microplates and feeding tubes in vitro, but were unable to eradicate preformed biofilms. CONCLUSIONS: This study demonstrated the synergistic and anti-virulence effects of P. tetramera berries extracts and phytolaccagenin with antifungal drugs against Candida spp., providing novel treatment avenues for fungal infections with reduced doses of both natural products and commercial antifungals, thereby mitigating potential human toxicity concerns.
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Antifúngicos , Candida albicans , Sinergismo Farmacológico , Frutas , Testes de Sensibilidade Microbiana , Phytolacca , Extratos Vegetais , Antifúngicos/farmacologia , Antifúngicos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Frutas/química , Candida albicans/efeitos dos fármacos , Phytolacca/química , Candida glabrata/efeitos dos fármacos , Saponinas/farmacologia , Candida/efeitos dos fármacosRESUMO
AIMS: Enterococcus faecalis (E. faecalis) is a leading cause of nosocomial infection and presents a wide spectrum of antibiotic resistance, being vancomycin-resistant Enterococcus (VRE) one of the most relevant. Synthetic antimicrobial peptides (SAMPs) are currently a promising option to overcome antimicrobial resistance. Thus, the purpose of this study was to assess the effect of eight SAMPs against vancomycin-resistant E. faecalis, as well as to investigate their mechanism of action and synergy with conventional antibiotics. METHODS AND RESULTS: Here, eight SAMPs, Mo-CBP3-PepI, Mo-CBP3-PepII, Mo-CBP3-PepIII, RcAlb-PepI, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA, were tested for antibacterial activity in vitro against E. faecalis (ATCC® 51299) through broth microdilution. A maximum of 48% of E. faecalis growth inhibition was achieved by treatment with SAMPs alone. However, when these peptides were combined with the antibiotic chloramphenicol, assessed by checkerboard method, the inhibition increased to 55%-76% of inhibition, two to three-folds of increase if compared to the effects of the compounds alone. Microscopic analysis showed that E. faecalis cells treated with a combination of SAMPs and chloramphenicol resulted in bacterial membrane damage. The biofilm inhibition maximum was 22% for SAMPs alone, when combined with chloramphenicol, the maximum increased to 33%. CONCLUSIONS: SAMPs and their combination with chloramphenicol demonstrate antibacterial activity against E. faecalis, possibly by inducing bacterial membrane damage.