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ß-conglycinin (ß-CG) is a prominent storage protein belonging to the globulin family in soybean (Glycine max) seeds. Along with other soybean proteins, it serves as an important source of essential amino acids and high-quality nutrition. However, the digestibility and nutritional value of ß-CG are key factors affecting the nutritional profile of soy-based foods. The heterotrimeric, secondary, and quaternary structures of ß-CG, particularly the spatial arrangement of its α, α', and ß subunits, influence its functional properties. Considering these aspects, ß-CG emerges as a significant protein with diverse applications in the food and health sectors. Therefore, this review explores ß-CG's composition, structure, function, health implications, and industrial uses. Salient discussions are presented on its molecular structure, nutrition, digestibility, allergenicity, and techno-functions including emulsification, solubility, gelling, and structure-function complexities. Overall, the multifaceted potential of ß-CG in the healthcare sector and the food industry is evident.
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Antígenos de Plantas , Globulinas , Proteínas de Armazenamento de Sementes , Proteínas de Soja , Globulinas/química , Proteínas de Armazenamento de Sementes/química , Antígenos de Plantas/química , Proteínas de Soja/química , Relação Estrutura-Atividade , Humanos , Glycine max/química , Animais , Valor NutritivoRESUMO
Carrot rhamnogalacturonan-I (cRG-I) is a polydisperse polysaccharide with molecular weights of 7-250 kDa. Using size exclusion chromatography cRG-I was fractionated and pooled in fractions (PF1-6). All fractions contained the same RG-I monosaccharides and similar glycosidic linkages although in varying relative amounts. The main differences were in rhamnose substitution, arabinan- and galactan side chain length and in levels of acetylation and methyl esterification. Atomic force microscopy showed either spheric or elongated structures for cRG-I and its derived fractions. To gain insight in the structure-function relationship of cRG-I, the immunomodulatory effect of the six fractions and their saponified derivatives was assessed in vitro. All fractions, except PF2, dose-dependently stimulated TNFα, IL-6, IL-1ß, IL-8 and IL-10 production in peripheral blood mononuclear cells (PBMCs) of three healthy donors. Cytokine levels were largely influenced by the Mw and degree of esterification of the individual fractions. Notably, the highest Mw fraction (100 kDa) displayed the most potent activity, which was strongly reduced after the removal of ester residues by saponification. In contrast, the 75 kDa Mw population (PF2) proved inactive while its saponified counterpart exhibited substantial immunomodulatory activity. This confirmed the role of ester residues on the immune profile of RG-I subpopulations.
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Daucus carota , Leucócitos Mononucleares , Pectinas , Pectinas/química , Pectinas/farmacologia , Daucus carota/química , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Citocinas/metabolismo , Peso Molecular , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/químicaRESUMO
PIM-1 is a Ser/Thr kinase, which has been extensively studied as a potential target for cancer therapy due to its significant roles in various cancers, including prostate and breast cancers. Given its importance in cancer, researchers are investigating the structure of PIM-1 for pharmacological inhibition to discover therapeutic intervention. This study examines structural and conformational changes in PIM-1 across different pH using various spectroscopic and computational techniques. Spectroscopic results indicate that PIM-1 maintains its secondary and tertiary structure within the pH range of 7.0-9.0. However, protein aggregation occurs in the acidic pH range of 5.0-6.0. Additionally, kinase assays suggested that PIM-1 activity is optimal within the pH range of 7.0-9.0. Subsequently, we performed a 100â¯ns all-atom molecular dynamics (MD) simulation to see the effect of pH on PIM-1 structural stability at the molecular level. MD simulation analysis revealed that PIM-1 retains its native conformation in alkaline conditions, with some residual fluctuations in acidic conditions as well. A strong correlation was observed between our MD simulation, spectroscopic, and enzymatic activity studies. Understanding the pH-dependent structural changes of PIM-1 can provide insights into its role in disease conditions and cellular homeostasis, particularly regarding protein function under varying pH conditions.
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The relationship between the brain's structural wiring and its dynamic activity is thought to vary regionally, implying that the mechanisms underlying structure-function coupling may differ depending on a region's position within the brain's hierarchy. To better bridge the gap between structure and function, it is crucial to identify the factors shaping this regionality, not only in terms of how static functional connectivity aligns with structure, but also regarding the time-domain variability of this interplay. Here we map structure - function coupling and its time-domain variability and relate them to the heterogeneity of the cortex. We show that these two properties split the cortical landscape into two districts anchored to the opposite ends of the brain's hierarchy. By looking at statistical relationships with layer-specific gene transcription, T1w/T2w ratio, and synaptic density, we show that macro-scale structure-function coupling may be rooted in the brain's microstructure and meso-scale laminar specialization. Finally, we demonstrate that a lower and more variable alignment of function and structure may bestow the emergence of unique functional dynamics.
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Elucidating how adaptive and maladaptive changes to the structural connectivity of brain networks influences neural synchrony, and how this structure-function coupling impacts cognition is an important question in human neuroscience. This study assesses these links in the default mode and executive control networks during resting state, a visual-motor task, and through computational modeling in the developing brain and in acquired brain injuries. Pediatric brain tumor survivors were used as an injury model as they are known to exhibit cognitive deficits, structural connectivity compromise, and perturbations in neural communication. Focusing on information processing speed to assess cognitive performance, we demonstrate that during the presence and absence of specific task demands, structural connectivity of these critical brain networks directly influences neural communication and information processing speed, and white matter compromise has an indirect adverse impact on reaction time via perturbed neural synchrony. Further, when our experimentally acquired structural connectomes simulated neural activity, the resulting functional simulations aligned with our empirical results and accurately predicted cognitive group differences. Overall, our synergistic findings further our understanding of the neural underpinnings of cognition and when it is perturbed. Further establishing alterations in structural-functional coupling as biomarkers of cognitive impairments could facilitate early intervention and monitoring of these deficits.
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The antimicrobial peptide LL-37 is a promising alternative to conventional antibiotics to combat bacteria in suspension and biofilms. Its self-assembly with polar lipids is suggested to improve its potential for therapeutic applications with higher stability against degradation and bioavailability. This study investigates the self-assembly of LL-37 with glyceryl monooleate (GMO), establishing the link between colloidal structure and antimicrobial activity. Small-angle X-ray scattering, dynamic light scattering and cryogenic transmission electron microscopy show structural transformation from dispersions of inverse bicontinuous structure (cubosomes) to multilamellar vesicles and direct rod-like mixed-micelles upon increasing the content of LL-37 in GMO. In vitro assays against planktonic and biofilm cells demonstrate that 128 µg mL-1 of GMO cubosomes have no impact on Pseudomonas aeruginosa. Still, the cubosomes reduce the Staphylococcus aureus planktonic population by ≈ 1-log after 24 h. Cylindrical micelles formed at LL-37/GMO 9/1 and 8/2 with 128 µg mL-1 LL-37 decrease the Pseudomonas aeruginosa population by 6-log. This activity is gradually abolished when LL-37 is encapsulated in vesicles or cubosomes. They also demonstrate low antibiofilm efficacy and promote the biomass of Staphylococcus aureus biofilms. These results highlight the importance of colloidal structure for therapeutic outcomes, providing insights for advanced lipid nanocarrier designs.
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The Rapid Campimetry (RC), a kinetic visual field test proved to reliably detect visual field defects within the central 10° degrees, the most crucial part for visual acuity and quality of life, affected even at very early stages of glaucoma, within a short measurement epoch, ~ 1 min. This study aims to further investigate RC correspondence with standard tests in glaucoma, namely standard automated perimetry (SAP) and optical coherence tomography (OCT) within 10° of visual field (VF). For this purpose, we included 41 participants, [21 glaucoma (GLA, mean age: 65.9 ± 12.4; 12 preperimetric eyes and 11 with VF defects) and 20 healthy controls (HC; mean age: 65.0 ± 10.3); 20 eyes]. At first, we compared the rate of detection/exclusion of VF defects in RC vs. SAP. Then, for those with VF defects (11 eyes), we investigated the 68-pointwise correspondence of 10 - 2 layout of RC and SAP. For functional and structural (SF) correspondence, pointwise correspondence of RC, SAP vs. OCTmacula [ macular ganglion cell thickness (GCL)] was also performed. Further, we compared sector-based correspondence of RC, SAP vs. OCTmacula accounting for GCL displacement at the fovea as well as sector-based correspondence with OCTdisc [peripapillary retinal nerve fiber layer thickness (pRNFL)]. Agreement estimates were reported along with Cohen Kappa ([Formula: see text]) statistic. For overall performance, RC and SAP showed 100% agreement ([Formula: see text]) for the exclusion of VF defects (HC and preperimetric GLA) and for detection of VF defects [11 eyes of 9 GLA, ([Formula: see text]]. Further, RC outperformed SAP in detection of arcuate scotomas, 7 vs. 5, respectively. Pointwise correspondence of VF defects (11 eyes), RC-SAP agreement reached 90% accuracy ([Formula: see text]). For SF correspondence, RC [SAP] showed 62% [69%] pointwise agreement with OCTmacula, ([Formula: see text]). For macular sector-based correspondence, SF correspondence improved and reached 83% [83%] agreement, ([Formula: see text]). For OCTdisc sector-based analysis, SF correspondence was highest, 100% [100%] agreement, ([Formula: see text]). Rapid Campimetry gave reproducible results in comparison to SAP and OCT with high potential as a screening VF method given its short testing duration, ~ 1 min in screening mode, and compatibility with telemedicine technologies upon future optimization and automation.
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Glaucoma , Tomografia de Coerência Óptica , Testes de Campo Visual , Campos Visuais , Humanos , Tomografia de Coerência Óptica/métodos , Testes de Campo Visual/métodos , Masculino , Feminino , Glaucoma/diagnóstico , Glaucoma/diagnóstico por imagem , Idoso , Pessoa de Meia-Idade , Células Ganglionares da Retina/patologia , Estudos de Casos e ControlesRESUMO
BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder associated with alterations in structural and functional coupling in gray matter. However, despite the detectability and modulation of brain signals in white matter, the structure-function coupling in white matter in autism remains less explored. METHODS: In this study, we investigated structural-functional coupling in white matter (WM) regions, by integrating diffusion tensor data that contain fiber orientation information from WM tracts, with functional connectivity tensor data that reflect local functional anisotropy information. Using functional and diffusion magnetic resonance images, we analyzed a cohort of 89 ASD and 63 typically developing (TD) individuals from the Autism Brain Imaging Data Exchange II (ABIDE-II). Subsequently, the associations between structural-functional coupling in WM regions and ASD severity symptoms assessed by Autism Diagnostic Observation Schedule-2 were examined via supervised machine learning in an independent test cohort of 29 ASD individuals. Furthermore, we also compared the performance of multi-model features (i.e. structural-functional coupling) with single-model features (i.e. functional or structural models alone). RESULTS: In the discovery cohort (ABIDE-II), individuals with ASD exhibited widespread reductions in structural-functional coupling in WM regions compared to TD individuals, particularly in commissural tracts (e.g. corpus callosum), association tracts (sagittal stratum), and projection tracts (e.g. internal capsule). Notably, supervised machine learning analysis in the independent test cohort revealed a significant correlation between these alterations in structural-functional coupling and ASD severity scores. Furthermore, compared to single-model features, the integration of multi-model features (i.e., structural-functional coupling) performed best in predicting ASD severity scores. CONCLUSION: This work provides novel evidence for atypical structural-functional coupling in ASD in white matter regions, further refining our understanding of the critical role of WM networks in the pathophysiology of ASD.
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Transtorno do Espectro Autista , Imagem de Tensor de Difusão , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/fisiopatologia , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/diagnóstico por imagem , Masculino , Feminino , Adolescente , Criança , Adulto , Adulto Jovem , Relação Estrutura-Atividade , Imageamento por Ressonância MagnéticaRESUMO
The Ca2+ sensor synaptotagmin-1 (Syt1) triggers neurotransmitter release together with the neuronal sensitive factor attachment protein receptor (SNARE) complex formed by syntaxin-1, SNAP25, and synaptobrevin. Moreover, Syt1 increases synaptic vesicle (SV) priming and impairs spontaneous vesicle release. The Syt1 C2B domain binds to the SNARE complex through a primary interface via two regions (I and II), but how exactly this interface mediates distinct functions of Syt1 and the mechanism underlying Ca2+ triggering of release are unknown. Using mutagenesis and electrophysiological experiments, we show that region II is functionally and spatially subdivided: Binding of C2B domain arginines to SNAP-25 acidic residues at one face of region II is crucial for Ca2+-evoked release but not for vesicle priming or clamping of spontaneous release, whereas other SNAP-25 and syntaxin-1 acidic residues at the other face mediate priming and clamping of spontaneous release but not evoked release. Mutations that disrupt region I impair the priming and clamping functions of Syt1 while, strikingly, mutations that enhance binding through this region increase vesicle priming and clamping of spontaneous release, but strongly inhibit evoked release and vesicle fusogenicity. These results support previous findings that the primary interface mediates the functions of Syt1 in vesicle priming and clamping of spontaneous release and, importantly, show that Ca2+ triggering of release requires a rearrangement of the primary interface involving dissociation of region I, while region II remains bound. Together with biophysical studies presented in [K. Jaczynska et al., bioRxiv [Preprint] (2024). https://doi.org/10.1101/2024.06.17.599417 (Accessed 18 June 2024)], our data suggest a model whereby this rearrangement pulls the SNARE complex to facilitate fast SV fusion.
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Cálcio , Neurotransmissores , Proteínas SNARE , Vesículas Sinápticas , Sinaptotagmina I , Sinaptotagmina I/metabolismo , Sinaptotagmina I/genética , Cálcio/metabolismo , Vesículas Sinápticas/metabolismo , Animais , Proteínas SNARE/metabolismo , Proteínas SNARE/genética , Neurotransmissores/metabolismo , Sintaxina 1/metabolismo , Sintaxina 1/genética , Proteína 25 Associada a Sinaptossoma/metabolismo , Proteína 25 Associada a Sinaptossoma/genética , Ratos , Ligação Proteica , Transmissão SinápticaRESUMO
Course-based undergraduate research experiences (CUREs) provide students with valuable opportunities to engage in research in a classroom setting, expanding access to research opportunities for undergraduates, fostering inclusive research and learning environments, and bridging the gap between the research and education communities. While scientific practices, integral to the scientific discovery process, have been widely implemented in CUREs, there have been relatively few reports emphasizing the incorporation of core biology concepts into CURE curricula. In this study, we present a CURE that integrates core biology concepts, including genetic information flow, phenotype-genotype relationships, mutations and mutants, and structure-function relationships, within the context of mutant screening and gene loci identification. The design of this laboratory course aligns with key CURE criteria, as demonstrated by data collected through the laboratory course assessment survey (LCAS). The survey of undergraduate research experiences (SURE) demonstrates students' learning gains in both course-directed skills and transferrable skills following their participation in the CURE. Additionally, concept survey data reflect students' self-perceived understanding of the aforementioned core biological concepts. Given that genetic mutant screens are central to the study of gene function in biology, we anticipate that this CURE holds potential value for educators and researchers who are interested in designing and implementing a mutant screen CURE in their classrooms. This can be accomplished through independent research or by establishing partnerships between different units or institutions.
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This study attempts to extend previous research on electrokinetic turbulence (EKT) in Oldroyd-B fluid by investigating the relationship between the Weissenberg number ( W i $Wi$ ) and the second-order velocity structure function ( S v 2 $S_v^2$ ) under applied electric fields. Inspired by Sasmal's demonstration in Sasmal (2022) of how heterogeneous zeta potentials induce turbulence above a critical W i $Wi$ , we develop a mathematical framework linking W i $Wi$ to turbulent phenomena. Our analysis incorporates recent findings on AC (Zhao & Wang, 2017) and DC (Zhao & Wang 2019) EKT, which have defined scaling laws for velocity and scalar structure functions in the forced cascade region. Our finding shows that S v 2 ( l ) â¼ λ 1 4 / 5 l 2 / 5 $S_v^2(l) \sim \lambda _1^{4/5} l^{2/5}$ and S σ 2 ( l ) â¼ λ 1 - 2 / 5 l 4 / 5 $S_\sigma ^2(l) \sim \lambda _1^{-2/5} l^{4/5}$ , for a length scale l $l$ , and W i = λ 1 u l l $Wi = \frac{\lambda _1 u_l}{l}$ , where u l = S u 2 ( l ) $u_l = \sqrt {S_u^2(l)}$ is a velocity fluctuations quantity and λ 1 $\lambda _1$ denotes the time relaxation parameter. This work establishes a positive correlation between λ 1 $\lambda _1$ and turbulent flow phenomena through a rigorous analysis of velocity structure functions, thereby offering a mathematical foundation for building the design and optimization of EKT-based microfluidic devices.
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As the site of almost all terrestrial carbon fixation, the mesophyll tissue is critical to leaf function. However, mesophyll tissue is not restricted only to leaves but also occurs in the laminar, heterotrophic organs of the floral perianth, providing a powerful test of how metabolic differences are linked to differences in tissue structure. Here, we compared mesophyll tissues of leaves and flower perianths of six species using high-resolution X-ray computed microtomography (microCT) imaging. Consistent with previous studies, stomata were nearly absent from flowers, and flowers had a significantly lower vein density compared to leaves. However, mesophyll porosity was significantly higher in flowers than in leaves, and higher mesophyll porosity was associated with more aspherical mesophyll cells. Despite these differences in cell and tissue structure between leaf and flower mesophyll, modeled intercellular airspace conductance did not differ significantly between organs, regardless of differences in stomatal density between organs. These results suggest that in addition to differences between leaves and flowers in vein and stomatal densities, the mesophyll cells and tissues inside these organs also exhibit marked differences that may allow for flowers to be relatively cheaper in terms of biomass investment per unit of flower surface area.
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The endoplasmic reticulum (ER) is organized into ordered regions enriched in cholesterol and sphingomyelin, and disordered microdomains characterized by more fluidity. Rabbit CYP1A1 and CYP1A2 localize into disordered and ordered microdomains, respectively. Previously, a CYP1A2 chimera containing the first 109 amino acids of CYP1A1 showed altered microdomain localization. The goal of this study was to identify specific residues responsible for CYP1A microdomain localization. Thus, CYP1A2 chimeras containing substitutions from homologous regions of CYP1A1 were expressed in HEK 293T/17 cells, and the localization was examined after solubilization with Brij 98. A CYP1A2 mutant with the three amino acids from CYP1A1 (VAG) at positions 27-29 of CYP1A2 was generated that showed a distribution pattern similar to those of CYP1A1/1A2 chimeras containing both the first 109 amino acids and the first 31 amino acids of CYP1A1 followed by remaining amino acids of CYP1A2. Similarly, the reciprocal substitution of three amino acids from CYP1A2 (AVR) into CYP1A1 resulted in a partial redistribution of the chimera into ordered microdomains. Molecular dynamic simulations indicate that the positive charges of the CYP1A1 and CYP1A2 linker regions between the N-termini and catalytic domains resulted in different depths of immersion of the N-termini in the membrane. The overlap of the distribution of positively charged residues in CYP1A2 (AVR) and negatively charged phospholipids was higher in the ordered than disordered microdomain. These findings identify three residues in the CYP1A N-terminus as a novel microdomain-targeting motif of the P450s and provide a mechanistic explanation for the differential microdomain localization of CYP1A.
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A major challenge in ecology is to understand how different species interact to determine ecosystem function, particularly in communities with large numbers of co-occurring species. We use a trait-based model of microbial litter decomposition to quantify how different taxa impact ecosystem function. Furthermore, we build a novel framework that highlights the interplay between taxon traits and environmental conditions, focusing on their combined influence on community interactions and ecosystem function. Our results suggest that the ecosystem impact of a taxon is driven by its resource acquisition traits and the community functional capacity, but that physiological stress amplifies the impact of both positive and negative interactions. Furthermore, net positive impacts on ecosystem function can arise even as microbes have negative pairwise interactions with other taxa. As communities shift in response to global climate change, our findings reveal the potential to predict the biogeochemical functioning of communities from taxon traits and interactions.
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Ecossistema , Interações Microbianas , Estresse Fisiológico , Mudança Climática , Modelos BiológicosRESUMO
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a naturally occurring genetic defense system in bacteria and archaea. It is comprised of a series of DNA sequence repeats with spacers derived from previous exposures to plasmid or phage. Further understanding and applications of CRISPR system have revolutionized our capacity for gene or genome editing of prokaryotes and eukaryotes. The CRISPR systems are classified into 3 distinct types: type I, type II, and type III, each of which possesses an associated signature protein, Cas3, Cas9, and Cas10, respectively. As the CRISPR loci originated from earlier independent exposures of foreign genetic elements, it is likely that their associated signature proteins may have evolved rapidly. Also, their functional domain structures might have experienced different selective pressures, and therefore, they have differentially diverged in their amino acid sequences. We employed genomic, phylogenetic, and structure-function constraint analyses to reveal the evolutionary distribution, phylogenetic relationship, and structure-function constraints of Cas3, Cas9, and Cas10 proteins. Results reveal that all 3 Cas-associated proteins are highly represented in the phyla Bacteroidetes, Firmicutes, and Proteobacteria, including both pathogenic and non-pathogenic species. Genomic analysis of homologous proteins demonstrates that the proteins share 30% to 50% amino acid identity; therefore, they are low to moderately conserved and evolved rapidly. Phylogenetic analysis shows that 3 proteins originated monophyletically; however, the evolution rates were different among different branches of the clades. Furthermore, structure-function constraint analysis reveals that both Cas3 and Cas9 proteins experiences low to moderate levels of negative selection, and several protein domains of Cas3 and Cas9 proteins are highly conserved. To the contrary, most protein domains of Cas10 proteins experience neutral or positive selection, which supports rapid genetic divergence and less structure-function constraints.
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Ginkgo biloba, a deciduous tree from the Ginkgoaceae family, is widely cultivated globally. In China, it predominantly grows in the eastern and southern regions. The leaves can be harvested multiple times throughout the growing season, presenting a significant resource potential. Ginkgo biloba leaves are considered as a living fossil with both medicinal and edible properties in traditional Chinese medicine. Polysaccharides, the primary bioactive compounds in these leaves, exhibit numerous biological activities, including antioxidant, antitumor, anti-inflammatory, immunoregulatory activity, antidepressant effects, hepatoprotective, hypoglycemic activity and hair-growth promoting effect. This review highlights the advancements in the extraction separation purification, structural elucidation, and functional analysis of polysaccharides derived from Ginkgo biloba leaves over the past decade, aiming to provide valuable insights for future development and commercialization of Ginkgo biloba leave polysaccharides.
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SUMMARYThe discovery of bacterial efflux pumps significantly advanced our understanding of how bacteria can resist cytotoxic compounds that they encounter. Within the structurally and functionally distinct families of efflux pumps, those of the Resistance-Nodulation-Division (RND) superfamily are noteworthy for their ability to reduce the intracellular concentration of structurally diverse antimicrobials. RND systems are possessed by many Gram-negative bacteria, including those causing serious human disease, and frequently contribute to resistance to multiple antibiotics. Herein, we review the current literature on the structure-function relationships of representative transporter proteins of tripartite RND efflux pumps of clinically important pathogens. We emphasize their contribution to bacterial resistance to clinically used antibiotics, host defense antimicrobials and other biocides, as well as highlighting structural similarities and differences among efflux transporters that help bacteria survive in the face of antimicrobials. Furthermore, we discuss technical advances that have facilitated and advanced efflux pump research and suggest future areas of investigation that will advance antimicrobial development efforts.
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Antibacterianos , Proteínas de Bactérias , Bactérias Gram-Negativas , Proteínas de Membrana Transportadoras , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/química , Humanos , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Relação Estrutura-Atividade , Farmacorresistência Bacteriana , Bactérias/metabolismo , Bactérias/efeitos dos fármacosRESUMO
Fungi are ubiquitous in the environment and play a key role in the decomposition and recycling of nutrients. On the one hand, their special properties are a great asset for the agricultural and industrial sector, as they are used as source of nutrients, producers of enzymes, pigments, flavorings, and biocontrol agents, and in food processing, bio-remediation and plant growth promotion. On the other hand, they pose a serious challenge to our lives and the environment, as they are responsible for fungal infections in plants, animals and humans. Although host immunity opposes invading pathogens, certain factors favor the manifestation of fungal diseases. The prevalence of fungal infections is on the rise, and there is an alarming increase in the resistance of fungal pathogens to approved drugs. The limited number of antimycotics, the obstacles encountered in the development of new drugs due to the poor tolerability of antifungal agents in patients, the limited number of unique antifungal targets, and the low species specificity contribute to the gradual depletion of the antifungal pipeline and newly discovered antifungal drugs are rare. Promising candidates as next-generation therapeutics are antimicrobial proteins and peptides (AMPs) produced by numerous prokaryotic and eukaryotic organisms belonging to all kingdom classes. Importantly, filamentous fungi from the order Eurotiales have been shown to be a rich source of AMPs with specific antifungal activity. A growing number of published studies reflects the efforts made in the search for new antifungal proteins and peptides (AFPs), their efficacy, species specificity and applicability. In this review, we discuss important aspects related to fungi, their impact on our life and issues involved in treating fungal infections in plants, animals and humans. We specifically highlight the potential of AFPs from Eurotiales as promising alternative antifungal therapeutics. This article provides insight into the structural features, mode of action, and progress made toward their potential application in a clinical and agricultural setting. It also identifies the challenges that must be overcome in order to develop AFPs into therapeutics.
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The present study identified the protective effects of garlic oligo/poly-saccharides of different chain lengths against dextran sulfate sodium (DSS)-induced colitis in mice and elucidated the structure-function relationships. The results showed that oral intake of garlic oligo/poly-saccharides decreased disease activity index, reduced colon shortening and spleen enlargement, and ameliorated pathological damage in the mouse colon. The dysregulation of colonic pro/anti-inflammatory cytokines was significantly alleviated, accompanied by up-regulated antioxidant enzymes, blocked TLR4-MyD88-NF-κB signaling pathway, enhanced intestinal barrier integrity, and restored SCFA production. Garlic oligo/poly-saccharides also reversed gut microbiota dysbiosis in colitic mice by expanding beneficial bacteria and suppressing the growth of harmful bacteria. High-molecular-weight polysaccharides exhibited stronger alleviating effects on DSS-induced colitic symptoms in mice than low-molecular-weight oligo/poly-saccharides did, probably due to their greater ability to be fermented in the colon. Taken together, this study demonstrated the anti-inflammatory effects of garlic oligo/poly-saccharides and revealed that high-molecular-weight polysaccharide fractions were more effective in alleviating DSS-induced colitis.
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Anti-Inflamatórios , Colite , Sulfato de Dextrana , Frutanos , Alho , Microbioma Gastrointestinal , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Alho/química , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Frutanos/farmacologia , Frutanos/química , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Relação Estrutura-Atividade , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Peso Molecular , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
A novel artificial peroxidase has been developed for the efficient degradation of the non-steroidal anti-inflammatory drug meloxicam by combining computer simulation and genetic engineering techniques. The results showed that the artificial peroxidase was able to completely degrade meloxicam within 90 s, with a degradation rate of 100 %, which was much higher than that of natural lacquer (46 %). The reaction time of the artificial enzyme was significantly shorter than that of natural peroxidase (10 min) and laccase (48 h). Further studies showed that the amino acid arrangement of the active site of the protein plays an important role in the catalytic performance. The degradation pathway of meloxicam was revealed using UPLC-MS analysis. In vitro toxicity assay showed complete disappearance of toxicity after meloxicam degradation. Therefore, the biocatalytic system proved to be an effective route for the green degradation of meloxicam with important application potential.