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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 Almacenamiento de Semillas , Proteínas de Soja , Globulinas/química , Proteínas de Almacenamiento de Semillas/química , Antígenos de Plantas/química , Proteínas de Soja/química , Relación Estructura-Actividad , Humanos , Glycine max/química , Animales , Valor NutritivoRESUMEN
Increased efforts in neuroscience seek to understand how macro-anatomical and physiological connectomes cooperatively work to generate cognitive behaviors. However, the structure-function coupling characteristics in normal aging individuals remain unclear. Here, we developed an index, the Coupling in Brain Structural connectome and Functional connectome (C-BSF) index, to quantify regional structure-function coupling in a large community-based cohort. C-BSF used diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) data from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events study (PRECISE) cohort (2007 individuals, age: 61.15 ± 6.49 years) and the Sydney Memory and Ageing Study (MAS) cohort (254 individuals, age: 83.45 ± 4.33 years). We observed that structure-function coupling was the strongest in the visual network and the weakest in the ventral attention network. We also observed that the weaker structure-function coupling was associated with increased age and worse cognitive level of the participant. Meanwhile, the structure-function coupling in the visual network was associated with the visuospatial performance and partially mediated the connections between age and the visuospatial function. This work contributes to our understanding of the underlying brain mechanisms by which aging affects cognition and also help establish early diagnosis and treatment approaches for neurological diseases in the elderly.
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The rapid detection of contaminants in water resources is vital for safeguarding the environment, where the use of eco-friendly materials for water monitoring technologies has become increasingly prioritized. In this context, the role of biocomposites in the development of a SERS sensor is reported in this study. Grafted chitosan was employed as a matrix support for Ag nanoparticles (NPs) for the surface-enhanced Raman spectroscopy (SERS). Chitosan (CS) was decorated with thiol and carboxylic acid groups by incorporating S-acetyl mercaptosuccinic anhydride (SAMSA) to yield CS-SAMSA. Then, Ag NPs were immobilized onto the CS-SAMSA (Ag@CS-SAMSA) and characterized by spectral methods (IR, Raman, NIR, solid state 13C NMR with CP-MAS, XPS, and TEM). Ag@CS-SAMSA was evaluated as a substrate for SERS, where methylene blue (MB) was used as a model dye adsorbate. The Ag@CS-SAMSA sensor demonstrated a high sensitivity (with an enhancement factor ca. 108) and reusability over three cycles, with acceptable reproducibility and storage stability. The Raman imaging revealed a large SERS effect, whereas the MB detection varied from 1-100 µM. The limits of detection (LOD) and quantitation (LOQ) of the biocomposite sensor were characterized, revealing properties that rival current state-of-the-art systems. The dye adsorption profiles were studied via SERS by fitting the isotherm results with the Hill model to yield the ΔG°ads for the adsorption process. This research demonstrates a sustainable dual-function biocomposite with tailored adsorption and sensing properties suitable for potential utility in advanced water treatment technology and environmental monitoring applications.
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Quitosano , Nanopartículas del Metal , Plata , Espectrometría Raman , Quitosano/química , Espectrometría Raman/métodos , Plata/química , Nanopartículas del Metal/química , Límite de Detección , Colorantes/química , Colorantes/análisis , Cationes/análisis , Contaminantes Químicos del Agua/análisis , Azul de Metileno/químicaRESUMEN
Tendon-bone fibrocartilaginous insertion, or enthesis, is a specialized interfacial region that connects tendon and bone, effectively transferring forces while minimizing stress concentrations. Previous studies have shown that insertion features gradient mineralization and branching fiber structure, which are believed to play critical roles in its excellent function. However, the specific structure-function relationship, particularly the effects of mineralization and structure at the mesoscale fiber level on the properties and function of insertion, remains poorly understood. In this study, we develop mesoscale computational models of the distinct fiber organization at tendon-bone insertions, capturing the branching network from tendon to interface fibers and the different mineralization scales. We specifically analyze three key descriptors: the mineralization scale of interface fibers, the mean, and relative standard deviation of the local branching angles of interface fibers. Tensile test simulations on insertion models with varying mineralization scales of interface fibers and structures are performed to mimic the primary loading condition applied to the insertion. We measure and analyze five representative mechanical properties: Young's modulus, strength, toughness, resilience, and failure strain. Our results reveal that mechanical properties are significantly influenced by the three key descriptors, with tradeoffs observed between mutually exclusive properties. For instance, strength and resilience plateau beyond a certain mineralization scale, while failure strain and Young's modulus exhibit monotonic decreasing and increasing trends, respectively. Consequently, there exists an optimal mineralization scale for toughness due to these tradeoffs. By analyzing the mesoscale deformation and failure mechanisms from simulation trajectories, we identify three fracture regimes closely related to the trends in mechanical properties, supporting the observed tradeoffs. Additionally, we examine in detail the effects of the mean and relative standard deviation of local branching angles on mechanical properties and deformation mechanisms. Overall, our study enhances the fundamental understanding of the composition-structure-function relationships at the tendon-bone insertion, complementing recent experimental studies. The mechanical insights from our work have the potential to guide the future biomimetic design of fibrillar adhesives and interfaces for joining soft and hard materials.
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Voltage-gated proton channel (Hv) has activity of proton transport following electrochemical gradient of proton. Hv is expressed in neutrophils and macrophages of which functions are physiologically temperature-sensitive. Hv is also expressed in human sperm cells and regulates their locomotion. H+ transport through Hv is both regulated by membrane potential and pH difference across biological membrane. It is also reported that properties of Hv such as proton conductance and gating are highly temperature-dependent. Hv consists of the N-terminal cytoplasmic domain, the voltage sensor domain (VSD), and the C-terminal coiled-coil domain, and H+ permeates through VSD voltage-dependently. The functional unit of Hv is a dimer via the interaction between C-terminal coiled-coils assembly domain. We have reported that the coiled-coil domain of Hv has the nature of dissociation around our bodily temperature and mutational change of the coiled-coil affected temperature-sensitive gating, especially its temperature threshold. The temperature-sensitive gating is assessed from two separate points: temperature threshold and temperature dependence. In this chapter, I describe physiological roles and molecular structure mechanisms of Hv by mainly focusing on thermosensitive properties.
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Activación del Canal Iónico , Canales Iónicos , Protones , Temperatura , Humanos , Canales Iónicos/metabolismo , Canales Iónicos/química , Canales Iónicos/genética , Animales , Potenciales de la Membrana/fisiología , Concentración de Iones de Hidrógeno , Dominios ProteicosRESUMEN
Structural connectivity (SC) between distant regions of the brain support synchronized function known as functional connectivity (FC) and give rise to the large-scale brain networks that enable cognition and behavior. Understanding how SC enables FC is important to understand how injuries to SC may alter brain function and cognition. Previous work evaluating whole-brain SC-FC relationships showed that SC explained FC well in unimodal visual and motor areas, but only weakly in association areas, suggesting a unimodal-heteromodal gradient organization of SC-FC coupling. However, this work was conducted in group-averaged SC/FC data. Thus, it could not account for inter-individual variability in the locations of cortical areas and white matter tracts. We evaluated the correspondence of SC and FC within three highly sampled healthy participants. For each participant, we collected 78 min of diffusion-weighted MRI for SC and 360 min of resting state fMRI for FC. We found that FC was best explained by SC in visual and motor systems, as well as in anterior and posterior cingulate regions. A unimodal-to-heteromodal gradient could not fully explain SC-FC coupling. We conclude that the SC-FC coupling of the anterior-posterior cingulate circuit is more similar to unimodal areas than to heteromodal areas.
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Encéfalo , Imagen por Resonancia Magnética , Vías Nerviosas , Humanos , Masculino , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Adulto , Femenino , Imagen por Resonancia Magnética/métodos , Vías Nerviosas/fisiología , Vías Nerviosas/diagnóstico por imagen , Mapeo Encefálico/métodos , Adulto Joven , Imagen de Difusión por Resonancia Magnética , Descanso/fisiología , Sustancia Blanca/fisiología , Sustancia Blanca/diagnóstico por imagenRESUMEN
Pyrone-2,4-dicarboxylic acid (PDC) is a valuable polymer precursor that can be derived from the microbial degradation of lignin. The key enzyme in the microbial production of PDC is CHMS dehydrogenase, which acts on the substrate 4-carboxy-2-hydroxymuconate-6-semialdehyde (CHMS). We present the crystal structure of CHMS dehydrogenase (PmdC from Comamonas testosteroni) bound to the cofactor NADP, shedding light on its three-dimensional architecture, and revealing residues responsible for binding NADP. Using a combination of structural homology, molecular docking, and quantum chemistry calculations we have predicted the binding site of CHMS. Key histidine residues in a conserved sequence are identified as crucial for binding the hydroxyl group of CHMS and facilitating dehydrogenation with NADP. Mutating these histidine residues results in a loss of enzyme activity, leading to a proposed model for the enzyme's mechanism. These findings are expected to help guide efforts in protein and metabolic engineering to enhance PDC yields in biological routes to polymer feedstock synthesis.
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Tetrahydrofolate and its derivatives participate in one-carbon transfer reactions in all organisms. The cellular form of tetrahydrofolate (THF) is modified by multiple glutamate residues and polyglutamylation plays a key role in organellar and cellular folate homeostasis. In addition, polyglutamylation of THF is known to increase the binding affinity to enzymes in the folate cycle, many of which can utilize polyglutamylated THF as a substrate. Here, we use X-ray crystallography to provide a high-resolution view of interactions between the enzyme serine hydroxymethyltransferase (SHMT), which provides one carbon precursors for the folate cycle, and a polyglutamylated form of THF. Our 1.7 Å crystal structure of soybean SHMT8 in complex with diglutamylated 5-formyl-THF reveals, for the first time, a structural rearrangement of a loop at the entrance to the folate binding site accompanied by the formation of novel specific interactions between the enzyme and the diglutamyl tail of the ligand. Biochemical assays show that additional glutamate moieties on the folate ligand increase both enzyme stability and binding affinity. Together these studies provide new information on SHMT structure and function and inform the design of anti-folate agents.
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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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Antiinflamatorios , Colitis , Sulfato de Dextran , Fructanos , Ajo , Microbioma Gastrointestinal , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/patología , Ajo/química , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Fructanos/farmacología , Fructanos/química , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo , Relación Estructura-Actividad , Citocinas/metabolismo , Ratones Endogámicos C57BL , Peso Molecular , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Zinc (Zn) deficiency is a global problem disorder affecting both crops and humans. Herein, modified functional carbon nanodots (MFCNs) with various structures and characteristics were developed to regulate tomato yields and Zn migration in plant-soil systems affected by Zn deficiency through structure-function relationships. Sulfur-doped FCNs (S-FCNs), nitrogen-doped FCNs (N-FCNs), and nitrogensulfur co-doped FCNs (N,S-FCNs) were hydrothermally modified using FCNs as precursors. Their regulatory effects on tomatoes growing in Zn-deficient alkaline soils were studied in pot culture experiments. Specifically, 8 mg kg-1 of FCNs and S-FCNs improved tomato yields by 132 % and 108 %, respectively, compared with the control. However, N-FCNs and N,S-FCNs showed no significant effect on yield compared with the control (P < 0.05). Moreover, the application of FCNs or S-FCNs significantly improved fruit quality and nutritional value, including Zn content (by 26.3 % and 22.0 %, respectively) and naturally occurring antioxidants (by 3.37- and 2.08-fold for lycopene, 1.31- and 1.18-fold for flavonoids, and 2.28- and 1.89-fold for phenolics, respectively; P < 0.05). Although N-FCNs and N,S-FCNs increased Zn contents, they inhibited the synthesis of naturally occurring antioxidants in fruits. Zn bioaccessibility, uptake, and transportation in plant-soil systems were regulated by MFCNs through both direct and indirect mechanisms, including ionic reactions, plant physiology, and environmental effects. MFCNs regulated plant tolerance to Zn deficiency not only by affecting root activity, redox homeostasis, micronutrient balance, chelator synthesis, genetic expression, and plant photosynthesis but also by influencing rhizosphere soil properties and the microbial environment. Based on their dual role as "plant growth regulators" and "soil conditioners", MFCNs may have general applicability in agriculture. This study highlights the behavior of MFCNs in plant-soil systems, providing innovative nanotools for enhancing Zn availability, crop stress resistance and environmental preservation in sustainable agriculture.
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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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Purpose: We compared pulmonary function indices and quantitative CT parameters of airway remodeling, air trapping, and emphysema in asthmatic patients and patients with COPD and asthma-COPD overlap (ACO) and explored their relationships with airflow limitation. Patients and Methods: Patients with asthma (n=48), COPD (n=52), and ACO (n=30) and controls (n=54) who completed pulmonary function tests and HRCT scans were retrospectively enrolled in our study. Quantitative CT analysis software was used to assess emphysema (LAA%), airway wall dimensions (wall area (WA), luminal area (LA), and wall area percentage (WA%)), and air trapping ((relative volume change of -860 HU to -950 HU (RVC-860 to-950) and the expiration-to-inspiration ratio of the mean lung density (MLDE/I))). Differences in pulmonary function and HRCT parameters were compared among the groups. Spearman correlation analysis and regression analysis were utilized to explore structureâfunction relationships. Results: The LAA% in COPD and ACO patients was significantly greater than that in asthmatic patients and controls. The WA% and WA in COPD and ACO patients were greater than those in controls, whereas the WA% and LA between asthmatic patients and controls reached statistical significance. The RVC-860 to -950 levels decreased in the following order: ACO, COPD, and asthma. RVC-860 to -950 independently predicted FEV1% in asthmatic patients; LAA% and MLDE/I in COPD patients; and LAA%, WA% and RVC-860 to -950 in ACO patients. Conclusion: Comparable emphysema was observed in patients with COPD and ACO but not in asthmatic patients. All patients exhibited proximal airway remodeling. The bronchi were thickened outward in COPD and ACO patients but are thickened inward in asthmatic patients. Furthermore, air trapping in ACO patients was the most severe among all the groups. Indirect lung densitometry measurements might be more predictive of the degree of airflow limitation than direct airway measurements in obstructive airway diseases.
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Remodelación de las Vías Aéreas (Respiratorias) , Síndrome de Superposición de la Enfermedad Pulmonar Obstructiva Crónica-Asmática , Asma , Pulmón , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Masculino , Femenino , Persona de Mediana Edad , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Estudios Retrospectivos , Asma/fisiopatología , Asma/diagnóstico por imagen , Asma/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Anciano , Enfisema Pulmonar/fisiopatología , Enfisema Pulmonar/diagnóstico por imagen , Volumen Espiratorio Forzado , Síndrome de Superposición de la Enfermedad Pulmonar Obstructiva Crónica-Asmática/fisiopatología , Síndrome de Superposición de la Enfermedad Pulmonar Obstructiva Crónica-Asmática/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Capacidad Vital , Pruebas de Función Respiratoria , Tomografía Computarizada MultidetectorRESUMEN
Introduction: This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.
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Tight junctions play a pivotal role in the functional integrity of the human body by forming barriers that compartmentalize tissues and protect the body from external threats. Essential components of tight junctions are the transmembrane claudin proteins, which can polymerize into tight junction strands and meshworks. This study delves into the structural determinants of claudin polymerization, utilizing the close homology yet strong difference in polymerization capacity between claudin-3 and claudin-4. Through a combination of sequence alignment and structural modeling, critical residues in the second extracellular segment are pinpointed. Molecular dynamics simulations provide insights into the interactions of and the conformational changes induced by the identified extracellular segment 2 residues. Live-STED imaging demonstrates that introduction of these residues from claudin-3 into claudin-4 significantly enhances polymerization in non-epithelial cells. In tight junction-deficient epithelial cells, mutated claudin-4 not only influences tight junction morphology but also partially restores barrier function. Understanding the structural basis of claudin polymerization is crucial, as it offers insights into the dynamic nature of tight junctions. This knowledge could be applied to targeted therapeutic interventions, offering insight to repair or prevent barrier defects associated with pathological conditions, or introduce temporary barrier openings during drug delivery.
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Flavobacterium strains exert a substantial influence on roots and leaves of plants. However, there is still limited understanding of how the specific interactions between Flavobacterium and their plant hosts are and how these bacteria thrive in this competitive environment. A crucial step in understanding Flavobacterium - plant interactions is to unravel the structure of bacterial envelope components and the molecular features that facilitate initial contact with the host environment. Here, we have revealed structure and properties of the exopolysaccharides (EPS) produced by Flavobacterium sp. Root935. Chemical analyses revealed a complex and interesting branched heptasaccharidic repeating unit, containing a variety of sugar moieties, including Rha, Fuc, GlcN, Fuc4N, Gal, Man and QuiN and an important and extended substitution pattern, including acetyl and lactyl groups. Additionally, conformational analysis using molecular dynamics simulation showed an extended hydrophobic interface and a distinctly elongated, left-handed helicoidal arrangement. Furthermore, properties of the saccharide chain, and likely the huge substitution pattern prevented interaction and recognition by host lectins and possessed a low immunogenic potential, highlighting a potential role of Flavobacterium sp. Root935 in plant-microbial crosstalk.
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Flavobacterium , Polisacáridos Bacterianos , Flavobacterium/química , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/aislamiento & purificación , Simulación de Dinámica Molecular , Raíces de Plantas/microbiología , Raíces de Plantas/químicaRESUMEN
ELO-like elongase is a condensing enzyme elongating long chain fatty acids in eukaryotes. Eranthis hyemalis ELO-like elongase (EhELO1) is the first higher plant ELO-type elongase that is highly active in elongating a wide range of polyunsaturated fatty acids (PUFAs) and some monounsaturated fatty acids (MUFAs). This study attempted using domain swapping and site-directed mutagenesis of EhELO1 and EhELO2, a close homologue of EhELO1 but with no apparent elongase activity, to elucidate the structural determinants critical for catalytic activity and substrate specificity. Domain swapping analysis of the two showed that subdomain B in the C-terminal half of EhELO1 is essential for MUFA elongation while subdomain C in the C-terminal half of EhELO1 is essential for both PUFA and MUFA elongations, implying these regions are critical in defining the architecture of the substrate tunnel for substrate specificity. Site-directed mutagenesis showed that the glycine at position 220 in the subdomain C plays a key role in differentiating the function of the two elongases. In addition, valine at 161 and cysteine at 165 in subdomain A also play critical roles in defining the architecture of the deep substrate tunnel, thereby contributing significantly to the acceptance of, and interaction with primer substrates.
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Acetiltransferasas , Elongasas de Ácidos Grasos , Mutagénesis Sitio-Dirigida , Elongasas de Ácidos Grasos/metabolismo , Elongasas de Ácidos Grasos/genética , Especificidad por Sustrato , Acetiltransferasas/metabolismo , Acetiltransferasas/genética , Acetiltransferasas/química , Ácidos Grasos Insaturados/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Secuencia de Aminoácidos , Ácidos Grasos/metabolismo , Modelos MolecularesRESUMEN
The diverse class of plant diterpenoid metabolites serves important functions in mediating growth, chemical defence, and ecological adaptation. In major monocot crops, such as maize (Zea mays), rice (Oryza sativa), and barley (Hordeum vulgare), diterpenoids function as core components of biotic and abiotic stress resilience. Switchgrass (Panicum virgatum) is a perennial grass valued as a stress-resilient biofuel model crop. Previously we identified an unusually large diterpene synthase family that produces both common and species-specific diterpenoids, several of which accumulate in response to abiotic stress. Here, we report discovery and functional characterization of a previously unrecognized monofunctional class I diterpene synthase (PvKSL1) via in vivo co-expression assays with different copalyl pyrophosphate (CPP) isomers, structural and mutagenesis studies, as well as genomic and transcriptomic analyses. In particular, PvKSL1 converts ent-CPP into ent-abietadiene, ent-palustradiene, ent-levopimaradiene, and ent-neoabietadiene via a 13-hydroxy-8(14)-ent-abietene intermediate. Notably, although featuring a distinct ent-stereochemistry, this product profile is near-identical to bifunctional (+)-levopimaradiene/abietadiene synthases occurring in conifer trees. PvKSL1 has three of four active site residues previously shown to control (+)-levopimaradiene/abietadiene synthase catalytic specificity. However, mutagenesis studies suggest a distinct catalytic mechanism in PvKSL1. Genome localization of PvKSL1 distant from other diterpene synthases, and its phylogenetic distinctiveness from known abietane-forming diterpene synthases, support an independent evolution of PvKSL1 activity. Albeit at low levels, PvKSL1 gene expression predominantly in roots suggests a role of diterpenoid formation in belowground tissue. Together, these findings expand the known chemical and functional space of diterpenoid metabolism in monocot crops.
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The hippocampus is a central modulator of the HPA-axis, impacting the regulation of stress on brain structure, function, and behavior. The current study assessed whether three different types of 3 months mental Training Modules geared towards nurturing (a) attention-based mindfulness, (b) socio-affective, or (c) socio-cognitive skills may impact hippocampal organization by reducing stress. We evaluated mental training-induced changes in hippocampal subfield volume and intrinsic functional connectivity, by combining longitudinal structural and resting-state fMRI connectivity analysis in 332 healthy adults. We related these changes to changes in diurnal and chronic cortisol levels. We observed increases in bilateral cornu ammonis volume (CA1-3) following the 3 months compassion-based module targeting socio-affective skills (Affect module), as compared to socio-cognitive skills (Perspective module) or a waitlist cohort with no training intervention. Structural changes were paralleled by relative increases in functional connectivity of CA1-3 when fostering socio-affective as compared to socio-cognitive skills. Furthermore, training-induced changes in CA1-3 structure and function consistently correlated with reductions in cortisol output. Notably, using a multivariate approach, we found that other subfields that did not show group-level changes also contributed to changes in cortisol levels. Overall, we provide a link between a socio-emotional behavioural intervention, changes in hippocampal subfield structure and function, and reductions in cortisol in healthy adults.
Too much stress is harmful to the brain and overall health, as it can lead to chronically high levels of the stress hormone cortisol. The part of the brain that regulates memory and emotions, called the hippocampus, is especially sensitive to stress because it has a high number of receptors that bind to cortisol. This connection may explain why stress can lead to memory lapses or strong emotions. Studies have shown that mental training exercises, such as mindfulness and meditation, may change the structure of the brain and reduce stress. However, the results from these experiments have been mixed due to the variation in mental practices used by different programs. Here, Valk, Engert et al. set out to find how distinct types of mental training affect the brain, focusing on the hippocampus and cortisol levels. The team used various magnetic resonance imaging techniques to study the hippocampus of 322 healthy adult volunteers who had undergone three months of mental training. The relationship between mental training, hippocampus size, and stress levels was complex when studying the results of each individual. However, when the results were grouped together, it revealed that volunteers who underwent training to increase empathy and compassion experienced expansion in parts of their hippocampus. As these areas of the brain increased in size, these individuals experienced corresponding reductions in cortisol levels. But volunteers who underwent mental training focused on attention or developing perspective did not experience such increases. These findings suggest that mental training to increase empathy and compassion alters brain structure and lowers cortisol levels. Future studies may explain how this happens, which could lead to improved mental training programs for mitigating stress.
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Hipocampo , Hidrocortisona , Imagen por Resonancia Magnética , Humanos , Hidrocortisona/metabolismo , Masculino , Femenino , Hipocampo/fisiología , Adulto , Adulto Joven , Atención Plena , Ritmo Circadiano/fisiología , Estrés PsicológicoRESUMEN
We have approached the construction of an artificial enzyme by employing a robust protein scaffold, lactococcal multidrug resistance regulator, LmrR, providing a structured secondary and outer coordination spheres around a molecular rhodium complex, [RhI(PEt2NglyPEt2)2]-. Previously, we demonstrated a 2-3 fold increase in activity for one Rh-LmrR construct by introducing positive charge in the secondary coordination sphere. In this study, a series of variants was made through site-directed mutagenesis where the negative charge is located in the secondary sphere or outer coordination sphere, with additional variants made with increasingly negative charge in the outer coordination sphere while keeping a positive charge in the secondary sphere. Placing a negative charge in the secondary or outer coordination sphere demonstrates decreased activity by a factor of two compared to the wild-type Rh-LmrR. Interestingly, addition of positive charge in the secondary sphere, with the negatively charged outer coordination sphere restores activity. Vibrational and NMR spectroscopy suggest minimal changes to the electronic density at the rhodium center, regardless of inclusion of a negative or positive charge in the secondary sphere, suggesting another mechanism is impacting catalytic activity, explored in the discussion.
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Dióxido de Carbono , Rodio , Rodio/química , Hidrogenación , Dióxido de Carbono/química , Dióxido de Carbono/metabolismo , Biocatálisis , Modelos Moleculares , Catálisis , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Complejos de Coordinación/química , Complejos de Coordinación/metabolismoRESUMEN
The most severe form of malaria, caused by infection with Plasmodium falciparum parasites, continues to be an important cause of human suffering and poverty. The P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of clonally variant antigens, which mediates the adhesion of infected erythrocytes to the vascular endothelium in various tissues and organs, is a central component of the pathogenesis of the disease and a key target of the acquired immune response to malaria. Much new knowledge has accumulated since we published a systematic overview of the PfEMP1 family almost ten years ago. In this chapter, we therefore aim to summarize research progress since 2015 on the structure, function, regulation etc. of this key protein family of arguably the most important human parasite. Recent insights regarding PfEMP1-specific immune responses and PfEMP1-specific vaccination against malaria, as well as an outlook for the coming years are also covered.