Structure-function Relationships Research Articles

Zwitterionic Peptides: From Mechanism, Design Strategies to Applications.

Zwitterionic peptides, as a type of peptide composed of charged residues, are electrically neutral, which combine the advantages of zwitterionic materials and biological peptides, exhibiting hydrophilicity and programmable properties. As attractive candidates for resisting nonspecific adsorption of biomacromolecules and microorganisms, zwitterionic peptides have been applied in materials science, biomedicine, and biochemistry over the past decade. In this review, the development of zwitterionic peptides has been systematically outlined and analyzed, including their mechanisms, structure-function relationships, and design strategies. Furthermore, this review emphasizes and discusses their recent applications for developing functional coatings, biosensors, drug delivery systems, and engineering proteins. Finally, future research perspectives and challenges of zwitterionic peptides are also prospected and discussed. This review is intended to provide clarity and insight into the design and applications of zwitterionic peptides.

Synergistic Coordination Effect and Metal-Support Interaction Engineering of Single-Atom Mn-N2 Sites for Boosting Sensitive and Selective Dopamine Biosensing in Human Serum.

Coordination environment of metal atoms is core for designing high-performance single-atom catalysts (SACs), while metal-support interaction also has an important effect on structure-function relationship. Nevertheless, the interaction effect of metal-support is mostly ignored. Through synergistic regulation of coordination environment and metal-support interaction, Mn SAC with atom-dispersed Mn-N2 sites on dopamine (DA) support is synthesized for sensitive and selective DA oxidation based on theoretical calculations and experimental explorations. MnN2 presents the more optimal catalytic site for DA oxidation than other coordination conditions, enhancing sensitivity including a wide range, a low limit of detection, and particularly a very low catalytic potential. The construction of Mn-N2 active sites on DA carbon promotes the coupling between Mn metal atoms and DA support, decreasing work function, facilitating electron exchange, shortening response time, and boosting selectivity. Both the catalytic mechanism of Mn SAC toward DA and the relation construction of catalyst's structure and catalytic function are established.

Multimodal evidence for cerebellar influence on cortical development in autism: structural growth amidst functional disruption.

Despite perinatal damage to the cerebellum being one of the highest risk factors for later being diagnosed with autism spectrum disorder (ASD), it is not yet clear how the cerebellum might influence the development of cerebral cortex and whether this co-developmental process is distinct between neurotypical and ASD children. Leveraging a large structural brain MRI dataset of neurotypical children and those diagnosed with ASD, we examined whether structural variation in cerebellar tissue across individuals was correlated with neocortical variation during development, including the thalamus as a coupling factor. We found that the thalamus plays a distinct role in moderating cerebro-cerebellar structural coordination in ASD. Notably, structural coupling between cerebellum, thalamus, and neocortex was strongest in younger childhood and waned by early adolescence, mirroring a previously undescribed trajectory of behavioral development between ASD and neurotypical children. Complementary functional connectivity analyses likewise revealed atypical connectivity between cerebellum and neocortex in ASD. This relationship was particularly prominent in a model of cerebellar structure predicting functional connectivity, where ASD and neurotypical children showed divergent patterns. Interestingly, these functional-structural relationships became more prominent with age, while structural effects were most prominent earlier in childhood, and showed significant lateralization. This pattern may suggest a developmental sequence where early uncoordinated structural growth amongst regions is followed by increasingly atypical functional synchronization. These findings provide multimodal evidence in the living brain for a cerebellar diaschisis model of autism, where both increased cerebellar-cerebral structural coupling and altered functional connectivity in cerebro-cerebellar pathways contribute to the ontogeny of this neurodevelopmental disorder.

Bayesian inference of frequency-specific functional connectivity in MEG imaging using a spectral graph model

Abstract Understanding the relationship between structural connectivity (SC) and functional connectivity (FC) of the human brain is an important goal of neuroscience. Highly detailed mathematical models of neural masses exist that can simulate the interactions between functional activity and structural wiring. These models are often complex and require intensive computation. Most importantly, they do not provide a direct or intuitive interpretation of this structure–function relationship. In this study, we employ the emerging concepts of spectral graph theory to obtain this mapping in terms of graph harmonics, which are eigenvectors of the structural graph’s Laplacian matrix. In order to imbue these harmonics with biophysical underpinnings, we leverage recent advances in parsimonious spectral graph modeling (SGM) of brain activity. Here, we show that such a model can indeed be cast in terms of graph harmonics, and can provide a closed-form prediction of FC in an arbitrary frequency band. The model requires only three global, spatially invariant parameters, yet is capable of generating rich FC patterns in different frequency bands. Only a few harmonics are sufficient to reproduce realistic FC patterns. We applied the method to predict FC obtained from pairwise magnitude coherence of source-reconstructed resting-state magnetoencephalography (MEG) recordings of 36 healthy subjects. To enable efficient model inference, we adopted a deep neural network-based Bayesian procedure called simulation-based inference. Using this tool, we were able to speedily infer not only the single most likely model parameters, but also their full posterior distributions. We also implemented several other benchmark methods relating SC to FC, including graph diffusion and coupled neural mass models. The present method was shown to give the best performance overall. Notably, we discovered that a single biophysical parameterization is capable of fitting FCs from all relevant frequency bands simultaneously, an aspect that did not receive adequate attention in prior computational studies.

Structural Determinants of Tendon Multiscale Mechanics and Their Sensitivity to Mechanical Stimulation During Development in an Embryonic Chick Model

There is an abrupt increase in the multiscale mechanical properties and load-bearing capabilities of tendon during embryonic development. While prior work has identified numerous changes that occur within the collagenous structure during this developmental period, the primary structural elements that give rise to this abrupt increase in mechanical functionality, and their mechanobiological sensitivity, remain unclear. To address this knowledge gap, we used a shear lag model along with ultrastructural imaging, biochemical/thermodynamic assays, and multiscale mechanical testing to investigate the dynamic structure-function relationships during late-stage embryonic chick development and to establish their sensitivity to mechanical stimulation. Mechanical testing and modeling suggested the rapid increase in multiscale mechanics can be explained by increases in fibril length, intrafibrillar crosslinking, and fibril area fraction. To partially test this, we inhibited collagen crosslinking during development and observed a drastic reduction in multiscale mechanical behavior that was explained by a reduction in both fibril modulus and length. Using muscle paralysis to investigate mechanosensitivity, we observed a significantly impaired multiscale mechanical response despite minimal changes in fibril diameter and fibril area fraction. Additionally, the shear lag model found a trend toward lower fibril lengths with paralysis and experimental data found decreased crosslinking and fibril modulus values following flaccid paralysis. Together, these data suggest that both intrafibrillar crosslink formation and fibril elongation are critical to the formation of load-bearing capabilities in tenogenesis and are sensitive to mechanical loading. These findings provide critical insights into the biological and structural mechanisms that give rise to tensile load-bearing soft tissue. Statement of SignificanceDespite prior work investigating the structural and mechanical changes that occur during tendon development, there has not been a comprehensive analysis of how these simultaneous changes in structure and function are connected. In this study, we performed a comprehensive battery of mechanical and structural assessments of embryonic chick tendons and input these data into a shear lag model to estimate the individual importance of each structural change to the tendon mechanical properties. Additionally, we inhibited muscle activity in the embryos to evaluate the impact of mechanical stimulation on these evolving structure-function during tendon development. These data provide insight into the primary structural elements that produce the tensile load-bearing capabilities of tendon, which will inform efforts to produce tissue engineering tendon replacements.

Rupture Mechanics of Blood Clots: Influence of Fibrin Network Structure on the Rupture Resistance

Embolization is a leading cause of mortality, yet we know little about clot rupture mechanics. Fibrin provides the main structural and mechanical stability to blood clots. Previous studies have shown that altering the concentration of coagulation activators (thrombin or tissue factor (TF)) has a significant impact on fibrin structure and viscoelastic properties, but their effects on rupture properties are mostly unknown. Toughness, which corresponds to the ability to resist rupture, is independent of viscoelastic properties. We used varying TF concentrations to alter the structure and toughness of human plasma clots. We performed single-edge notch rupture tests to examine fibrin toughness under a constant strain rate and we assessed viscoelastic mechanics using rheology. We utilized fluorescent confocal and scanning electron microscopy (SEM) to quantify the fibrin network structure under varying TF concentrations. Our results revealed that increased TF concentration resulted in increased number of fibrin fibers with a reduction in network pore size, thinner and shorter fibrin fibers. Increasing TF concentration yielded a maximum toughness at mid-TF concentration, such that fibrin diameter and number of fibers underlie a complex role in influencing the rupture resistance of blood clots, resulting in a nonmonotonic relationship between TF and toughness. A simple mechanical model, built on our findings from our Fluctuating Spring (FS) computational model, adopted to estimate the fracture toughness (critical energy release rate) as a function of TF predicts trends that are in good agreement with experiments. The differences in mechanical responses point to the importance of studying the structure-function relationships of fibrin networks, which may be predictive of the tendency for embolization. Statement of significanceFibrin, a naturally occurring biomaterial, is the main mechanical and structural scaffold of blood clots that provides the necessary strength and stability to the clot, ensuring effective stemming of bleeding. The rupture of blood clots can result in the blockage of downstream vessels thereby blocking blood flow and oxygen supply. The fibrin network structure has been shown to influence the viscoelastic mechanical properties of clots, but has not been explored for fracture mechanics. Here, we modulate the fibrin network structure by varying the concentration of Tissue Factor (TF). Interestingly, the association between TF concentration and maximum toughness of the clots is non-monotonic. The variations in mechanical responses highlight the importance of studying the structure-function relationships of fibrin networks, as these may predict the tendency for embolization.

Strain-dependent glutathionylation of fibronectin fibers impacts mechano-chemical behavior and primes an integrin switch

The extracellular matrix (ECM) is a protein polymer network that physically supports cells within a tissue. It acts as an important physical and biochemical stimulus directing cell behaviors. For fibronectin (Fn), a predominant component of the ECM, these physical and biochemical activities are inextricably linked as physical forces trigger conformational changes that impact its biochemical activity. Here, we analyze whether oxidative post-translational modifications, specifically glutathionylation, alter Fn’s mechano-chemical characteristics through stretch-dependent protein modification. ECM post-translational modifications represent a potential for time- or stimulus-dependent changes in ECM structure-function relationships that could persist over time with potentially significant impacts on cell and tissue behaviors. In this study, we show evidence that glutathionylation of Fn ECM fibers is stretch-dependent and alters Fn fiber mechanical properties with implications on the selectivity of engaging integrin receptors. These data demonstrate the existence of multimodal post-translational modification mechanisms within the ECM with high relevance to the microenvironmental regulation of downstream cell behaviors.

Exploration and Design of Carbon Dot-Based Long Afterglow Materials Using Active Machine Learning and Quantum Chemical Simulations.

Long afterglow materials based on carbon dots (CDs) have attracted extensive attention in the field of optics due to their low cost and nontoxic properties. However, the targeted synthesis of specific properties of complex and unknown structures such as CDs remains a daunting challenge. In this study, the powerful nonlinear fitting ability of machine learning was used to explore the afterglow properties of CDs. The XGBoost algorithm demonstrates high prediction accuracy in determining the optimal excitation wavelength, optimal emission wavelength, and afterglow lifetime. Using Bayesian optimization, we screened and synthesized the CDs-based long afterglow materials with the longest lifetime reported so far by a one-step microwave method. By combining quantum chemical calculations with experimental data, we revealed the structure-function relationship between CDs and their precursors through electron-hole analysis. These results show that machine learning can establish nonlinear correlations between precursors and materials with unknown structures, clarify their intrinsic relationships, simplify the material design process, and thus accelerate the development of advanced materials.

Establishing a Robust Nonlinear Targeted Switch for C1 Electroproduction in Atomic Alloy Cox/Pd Bimetallenes.

Establishing a targeted switch for CO2 conversion under electric drive is essential for achieving carbon-balance by enabling selective chemicals. However, engineering the topological assembly of active sites to precisely regulate the competing pathways for various intermediates has been plagued by unclear structure-function relationships. To tailor the CO/formate pathways, herein we established a robust nonlinear targeted switch with tunable active Cox sites integrated into Pd metallene, which involves Co1/Pd single-atom alloy (favoring CO) and Co2/Pd diatomic alloy (favoring formate). Transitioning from Co1/Pd to Co2/Pd atomic alloy bimetallenes resulted in a nonlinear, high-contrast flip in selectivity, surpassing 94% for CO and formate productions in both H-cell and flow cell. Furthermore, the superior selectivity and current efficiency for CO (> 80 %) and formate (> 88%) were consistently maintained at -150 mA cm-2 over continuous 200 h. Theoretical simulations and in-situ spectroscopy analyses unveiled that appropriate adjacent metal site combinations (Pd-Pd, Pd-Co and Co-Co) lead to tunable dz2 band center and a nonlinear shift in preferred adsorption configurations of intermediates, dictating the C1 pathways. Our finding reveals a desired switch in C1 selectivity and robust stability within Cox/Pd system, providing a new perspective for fine-tuning energy conversion processes through specific topological assembly.

Conformational Selection of α-Synuclein Tetramers at Biological Interfaces.

Controlling the polymorphic assemblies of α-synuclein (αS) oligomers is crucial to reroute toxic protein aggregation implicated in Parkinson's disease (PD). One potential mediator is the interaction of αS tetramers with cell membranes, which may regulate the dynamic balance between aggregation-prone disordered monomers and aggregation-resistant helical tetramers. Here, we model diverse tetramer-cell interactions and compare the structure-function relations at the supramolecular-biological interface with available experimental data. The models predict preferential interaction of compact αS tetramers with highly charged membrane surfaces, which may further stabilize this aggregation-resistant conformer. On moderately charged membranes, extended structures are preferred. In addition to surface charge, curvature influences tetramer thermodynamic stability and aggregation, with potential for selective isolation of tetramers via regio-specific interactions with strongly negatively charged micelles that screen further aggregation. Our modeling data set highlights diverse beneficial nano-bio interactions to redirect biomolecule assembly, supporting new therapeutic approaches for PD based on lipid-mediated conformational selection and inhibition.

Structure–Function Relationships and Health-Promoting Properties of the Main Nutraceuticals of the Cactus Pear (Opuntia spp.) Cladodes: A Review

Over the past decade, several studies have established a direct link between functional foods, nutraceuticals, and a reduced risk of oxidative-stress-related diseases. Nutraceuticals, which encompass a variety of bioactive molecules, exhibit both nutritional and therapeutic properties. The cactus pear (Opuntia spp.) is a plant genus with many species recognized as functional foods, largely attributed to their high content of nutraceuticals, including polyphenols, fatty acids, vitamins, amino acids, pigments, and phytosterols. These compounds of different structures and functions possess different biological activities, contributing to the health-promoting properties of cactus pear. This makes cactus pears a valuable plant for the food, cosmetic, and pharmaceutical industries. While extensive research has focused on the nutritional profile of cactus pear fruits, the cladodes have received comparatively limited attention. Notably, the nutritional composition of cladodes can exhibit considerable variability, influenced by species and growing conditions. Furthermore, although various bioactive compounds have been identified in cladodes, studies elucidating their mechanisms of action, health benefits, and potential therapeutic applications remain insufficient. Addressing these gaps is crucial for enhancing the understanding and utilization of cactus pear cladodes. This paper provides a comprehensive overview of the structure–function relationships of the main nutraceuticals found in cactus pear cladodes. It synthesizes data from recent and relevant literature to elucidate the content of these compounds in relation to species and geographical origin, while also detailing the main biological activities and health-promoting benefits associated with cactus pear cladodes.

Comprehensive Insights into Microbial Lipases: Unveiling Structural Dynamics, Catalytic Mechanism, and Versatile Applications.

Microbial lipases (MLs) are pivotal biocatalysts in lipid biotechnology due to their diverse enzymatic properties and substrate specificity, garnering significant research attention. This comprehensive review explores the significance of MLs in biocatalysis, providing insights into their structure, catalytic domain, and oxyanion hole. The catalytic mechanism is elucidated, highlighting the molecular processes driving their efficiency. The review delves into ML sources, spanning fungi, yeasts, bacteria, and actinomycetes, followed by a discussion on classification and characterization. Emphasizing the scattered findings in the literature, the paper consolidates the latest information on ML applications across various industries, from food and pharmaceuticals to biofuel production and the paper and pulp industry. The review captures the dynamic landscape of ML research, emphasizing their structure-function relationships and practical implications across diverse sectors.

Visual Field Patterns in Optic Neuropathy

The optic nerve is susceptible to a wide variety of pathological processes. In optic neuropathy, quantitative visual field analysis using standard automated perimetry is critical in initial diagnosis, monitoring disease progression, and guiding treatment plans. While acquired visual field defects may progress rapidly, congenital visual field defects may not progress or may progress slowly. Although the most common defect in congenital or acquired optic neuropathy is the central defect, many defect types that are not pathognomonic to the disease can be seen. In ischemic optic neuropathy, which is common among optic neuropathies, arcuate defect and central defect are usually seen. In disc disorders with localized nerve damage, such as optic disc coloboma or optic pit, localized defects such as arcuate scotoma or cecocentral scotoma in which the fixation point is preserved may be observed. Papilledema causes peripapillary fluid accumulation and an enlarged blind spot in the perimetry. In compressive optic neuropathies, non-specific defects such as central and subtudinal defects may be observed, as well as quadrant defects such as hemianopsia and quadrionopsia. Studies show that the combined use of optical coherence tomography and standard automated perimetry to determine structure-function relationships improves clinical care in neuro-ophthalmic disorders.

Electrophysical cardiac remodeling at the molecular level: insights into Ryanodine Receptor activation and calcium-induced calcium release from a stochastic explicit-particle model

We present the first-ever, fully-discrete, stochastic model of triggered cardiac calcium dynamics. Using anatomically accurate subcellular cardiac myocyte geometries, we simulate the molecular players involved in calcium handling using high-resolution stochastic and explicit-particle methods at the level of an individual cardiac dyadic junction. Integrating data from multiple experimental sources, the model not only replicates the findings of traditional in silico studies and complements in vitro experimental data, but also reveals new insights into the molecular mechanisms driving cardiac dysfunction under stress and disease conditions. We improve upon older, non-discrete models using the same realistic geometry by incorporating molecular mechanisms for spontaneous, as well as triggered Calcium-Induced Calcium Release (CICR). Action potentials are used to activate L-type calcium channels (LTCCs), triggering CICR through Ryanodine receptors (RyR) on the surface of the sarcoplasmic reticulum. These improvements allow for the specific focus on the couplon: the structure-function relationship between LTCC and RyR. We investigate the electrophysical effects of normal and diseased action potentials on CICR and interrogate the effects of dyadic junction deformation through detubulation and orphaning of RyR. Our work demonstrates the importance of the electrophysical integrity of the CRU on CICR fidelity, giving insights into the molecular basis of heart disease. Finally, we provide a unique, detailed, molecular view of the CICR process using advanced rendering techniques. This easy-to-use model comes complete with tutorials and all necessary software for use and analysis so as to maximize usability and reproducibility. Our work focuses on quantifying, qualifying, and visualizing the behavior of the molecular species that underlie the function and dysfunction of subcellular cardiomyocyte systems.

Tailoring the natural rare sugars D-tagatose and L-sorbose to produce novel functional carbohydrates

This multidisciplinary study details the biosynthesis of novel non-digestible oligosaccharides derived from rare sugars, achieved through transfructosylation of D-tagatose and L-sorbose by levansucrase from Bacillus subtilis CECT 39 (SacB). The characterization of these carbohydrates using NMR and molecular docking was instrumental in elucidating the catalytic mechanism and substrate preference of SacB. Tagatose-based oligosaccharides were higher in abundance than L-sorbose-based oligosaccharides, with the most representative structures being: β-D-Fru-(2→6)-β-D-Fru-(2→1)-D-Tag and β-D-Fru-(2→1)-D-Tag. In vitro studies demonstrated the resistance of tagatose-based oligosaccharides to intestinal digestion and their prebiotic properties, providing insights into their structure-function relationship. β-D-Fru-(2→1)-D-Tag was the most resistant structure to small-intestinal digestion after three hours (99.8% remained unaltered). This disaccharide and the commercial FOS clustered in similar branches, indicating comparable modulatory properties on human fecal microbiota, and exerted a higher bifidogenic effect than unmodified tagatose. The bioconversion of selected rare sugars into β-fructosylated species with a higher degree of polymerization emerges as an efficient strategy to enhance the bioavailability of these carbohydrates and promote their interaction with the gut microbiota. These findings open up new opportunities for tailoring natural rare sugars, like D-tagatose and L-sorbose, to produce novel biosynthesized carbohydrates with functional and structural properties desirable for use as emerging prebiotics and low-calorie sweeteners.

Uncovering malate dehydrogenase: structure, function and role in disease.

Malate dehydrogenases (MDHs) have been extensively studied since the 1960s due to their key roles in carbon metabolism and pathways such as redox balance and lipid synthesis. Recently, there has been renewed interest in these enzymes with the discovery of their role in the metabolic changes that occur during cancer and a widespread community of undergraduate teaching laboratories addressing MDH research questions, the Malate Dehydrogenase CUREs Community (MCC). This special issue describes different facets of MDH, including its physiological role, its structure-function relationships, its regulation through post-translational modifications, and perspectives on its evolutionary history. There are two human isoforms: a cytoplasmic isoform that carries out formation of NAD+ for glycolysis, and a mitochondrial isoform that plays a major role in the citric acid cycle. Although the sequences of these two isoforms vary, the structures of the enzymes are similar, and studies suggest that each isoform may form complexes with other enzymes in common pathways. Experimental and theoretical advances have helped to characterize the post-translational modifications of MDH, allowing us to ask more complex questions involving the regulation of the enzyme and substrate promiscuity in the context of cancer. Additionally, there are many unresolved questions on the role of malate dehydrogenase in other organisms, especially in parasites. The review articles in this issue seek to shed light on the latest advances in our understanding of MDH and highlight areas for future studies.

Investigating the antifungal potential of genetically modified hybrid chitinase enzymes derived from Bacillus subtilis and Serratia marcescens.

Chitinases are glycosyl hydrolase enzymes that break down chitin, an integral component of fungal cell walls. Bacteria such as Bacillus subtilis and Serratia marcescens produce chitinases with antifungal properties. In this study, we aimed to generate hybrid chitinase enzymes with enhanced antifungal activity by combining functional domains from native chitinases produced by B. subtilis and S. marcescens. Chitinase genes were cloned from both bacteria and fused together using overlap extension PCR. The hybrid constructs were expressed in E. coli and the recombinant enzymes purified. Gel electrophoresis and computational analysis confirmed the molecular weights and isoelectric points of the hybrid chitinases were intermediate between the parental enzymes. Antifungal assays demonstrated that the hybrid chitinases inhibited growth of the fungus Fusarium oxysporum significantly more than the native enzymes and also showed fungicidal activity against Candida albicans, Alternaria solani, and Rhizoctonia solani. The results indicate that hybrid bacterial chitinases are a promising approach to engineer novel antifungal proteins. This study provides insight into structure-function relationships of chitinases and strategies for generating biotherapeutics with enhanced bioactive properties. These hybrid chitinases result in a more potent and versatile antifungal agent.

Upcycling of polyethylene waste to biodegradable adhesive and coating via Baeyer-Villiger reaction: a new view on oxidation-fracture mechanism and structure-function relationship

Non-biodegradable polyethylene waste accumulates in large quantities in the environment posing a serious threat to the survival of creatures. Meanwhile, polyethylene suffers from inherent polarity limitations that curtails its application scope. Oxidation is an efficient approach of upcycling waste polyethylene through introduction of hydrophilic functional groups (such as -COOH, -OH), yet often at the expense of their original hydrophobicity. Herein, the hydrophobic ester groups, were introduced via Baeyer-Villiger oxidation to ingeniously balance the contradiction among hydrophobicity, interfacial forces and sustainability of polyethylene oxidation products. A tandem conversion mechanism among the oxidative groups was proposed while the decrease in molecular weight and branching degree was clarified to be a result of β-scissions occurring the branches during the oxidation. Meanwhile, the effect of oxidation degree and molecular weight on interfacial forces was revealed. The excellent hydrophobicity and corrosion resistance of the oxidized polyethylene coating can be attributed to the low content of carboxyl/hydroxyl groups, rich hydrophobic ester groups and the retained long carbon chain structure. Besides, the introduced ester groups and lower molecular weight also provided the oxidation products with potential biodegradability. This work provided a new insight on the Baeyer-Villiger oxidation of polyethylene and the potential for upcycling of polyethylene waste into sustainable materials.

Quantitative assessment of the nanoanatomy of the contractile vacuole complex in Trypanosoma cruzi.

Trypanosoma cruzi uses various mechanisms to cope with osmotic fluctuations during infection, including the remodeling of organelles such as the contractile vacuole complex (CVC). Little is known about the morphological changes of the CVC during pulsation cycles occurring upon osmotic stress. Here, we investigated the structure-function relationship between the CVC and the flagellar pocket domain where fluid discharge takes place-the adhesion plaque-during the CVC pulsation cycle. Using TcrPDEC2 and TcVps34 overexpressing mutants, known to have low and high efficiency for osmotic responses, we described a structural phenotype for the CVC that matches their corresponding physiological responses. Quantitative tomography provided data on the volume of the CVC and spongiome connections. Changes in the adhesion plaque during the pulsation cycle were also quantified and a dense filamentous network was observed. Together, the results suggest that the adhesion plaque mediates fluid discharge from the central vacuole, revealing new aspects of the osmoregulatory system in T. cruzi.

Comprehensive review on ethnomedicinal, phytochemistry and pharmacological profile of.

Ficus religiosa L. (F. religiosa) or sacred fig is a large perennial tree belonging to the family Moraceae or mulberry family. Though the tree has pan-tropical distribution but originally it is indigenous to the Indian subcontinent and Indochina region. Popularly the tree is named "Pepal or bodhi tree". Traditionally, it is practiced for the treatment of asthma, nose bleeding, heart disorders, diabetes, wound healing, ear problems, constipation, hyperlipidemia, gonorrhea, ulcers and infectious disorders. Chemical analysis demonstrated the presence of numerous bioactives including tannins, phenols, saponins, sugars, alkaloids, methionine, terpenoids, flavonoids, glycosides, proteins, separated amino acids, essential and volatile oils and steroids etc., which are probably responsible for its diverse pharmacological actions. The present work is an attempt to compile up-to-date comprehensive information on F. religiosa that covers its taxonomy, ethnomedicinal importance, phytochemistry, pharmacological attributes and clinical trials. Keeping in mind the various health attributes of F. religiosa, future research can be aimed at in-depth elucidation of the structure-function relationship and multifactorial signalings pathways.