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Abstract 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 ( $$\:\kappa\:$$ ) statistic. For overall performance, RC and SAP showed 100% agreement ( $$\:\kappa\:=1$$ ) for the exclusion of VF defects (HC and preperimetric GLA) and for detection of VF defects [11 eyes of 9 GLA, ( $$\:\kappa\:=1)$$ ]. 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 ( $$\:\kappa\:=0.77,\:substantial\:agreement$$ ). For SF correspondence, RC [SAP] showed 62% [69%] pointwise agreement with OCTmacula, ( $$\:\kappa\:=0.10\:\left[0.33\right]$$ ). For macular sector-based correspondence, SF correspondence improved and reached 83% [83%] agreement, ( $$\:\kappa\:=0.57\:\left[0.57\right]$$ ). For OCTdisc sector-based analysis, SF correspondence was highest, 100% [100%] agreement, ( $$\:\kappa\:=1\:\left[1\right]$$ ). 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.

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 () statistic. For overall performance, RC and SAP showed 100% agreement () for the exclusion of VF defects (HC and preperimetric GLA) and for detection of VF defects [11 eyes of 9 GLA, ( ]. 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 (). For SF correspondence, RC [SAP] showed 62% [69%] pointwise agreement with OCTmacula, (). For macular sector-based correspondence, SF correspondence improved and reached 83% [83%] agreement, (). For OCTdisc sector-based analysis, SF correspondence was highest, 100% [100%] agreement, (). 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. [ABSTRACT FROM AUTHOR]

Purpose: High Magnification Module (HMM™, Heidelberg Engineering, Heidelberg, Germany) imaging is a novel technique, designed to visualize the retina at a cellular level. To assess the potential of HMM™‐based metrics as endpoints for future trials, we evaluated correlations between structural HMM™ cone metrics, spectral‐domain OCT (SD‐OCT, Heidelberg Engineering, Heidelberg, Germany) and retinal sensitivity on microperimetry (MP, MAIA, CenterVue, Padova, Italy) in healthy subjects and p.(Arg142Trp) PRPH2‐associated Central Areolar Choroidal Dystrophy (CACD) patients. Methods: We projected a default 10° MP grid on composite HMM™ images and performed automated cone density (CD), intercell distance (ICD) and nearest neighbour distance (NND) analysis at stimuli located at 3° and 5° retinal eccentricity. We manually measured intrasubject outer retinal thickness on SD‐OCT in absolute and relative scotomas, located outside of focal atrophy. Results: We included 15 CACD patients and five healthy subjects. We found moderate‐to‐strong correlations of HMM™ metrics and MP sensitivity at 3° eccentricity from the fovea. We found the outer retina at the locations of absolute scotomas to be statistically significant thinner (p = 0.000003, one‐sample t‐test), as the outer retinal thickness at locations of relative scotomas. Interestingly, HMM™ metrics of these areas did not differ significantly. Conclusions: We found significant correlations between structural photoreceptors metrics on HMM™ imaging and retinal sensitivity on MP in healthy subjects and CACD patients. A multimodal approach, combining SD‐OCT, MP and HMM™ imaging, allows for detailed mapping of retinal photoreceptor integrity and restitution potential, important data that could serve as biomarkers in future clinical trials. [ABSTRACT FROM AUTHOR]

The large size of K‐ion makes the pursuit of stable high‐capacity anodes for K‐ion batteries (KIBs) a formidable challenge, particularly for high temperature KIBs as the electrode instability becomes more aggravated with temperature climbing. Herein, we demonstrate that a hollow ZnS@C nanocomposite (h‐ZnS@C) with a precise shell modulation can resist electrode disintegration to enable stable high‐capacity potassium storage at room and high temperature. Based on a model electrode, we identify an interesting structure‐function correlation of the h‐ZnS@C: with an increase in the shell thickness, the cyclability increases while the rate and capacity decrease, shedding light on the design of high‐performance h‐ZnS@C anodes via engineering the shell thickness. Typically, the h‐ZnS@C anode with a shell thickness of 60 nm can deliver an impressive comprehensive performance at room temperature; the h‐ZnS@C with shell thickness increasing to 75 nm can achieve an extraordinary stability (88.6 % capacity retention over 450 cycles) with a high capacity (450 mAh g−1) and a superb rate even at an extreme temperature of 60 °C, which is much superior than those reported anodes. This contribution envisions new perspectives on rational design of functional metal sulfides composite toward high‐performance KIBs with insights into the significant structure‐function correlation. [ABSTRACT FROM AUTHOR]

Photoreceptor (PR) outer segments, retinal pigment epithelium apical processes, and inter-PR matrix contribute to the interdigitation zone (IZ) of optical coherence tomography (OCT). We hypothesize that this interface degrades over adulthood, in concert with a delay of rod mediated dark adaptation (RMDA). To explore this idea, we determined IZ discernibility and RMDA in younger and older adults. For this cross-sectional study, eyes of 20 young (20–30 years) and 40 older (≥60 years) participants with normal maculas according to the AREDS 9-step grading system underwent OCT imaging and RMDA testing at 5° superior to the fovea. Custom FIJI plugins enabled analysis for IZ discernibility at 9 eccentricities in 0.5 mm steps on one single horizontal B-scan through the fovea. Locations with discernible IZ met two criteria: visibility on B-scans and a distinct peak on a longitudinal reflectivity profile. The frequency of sites meeting both criteria was compared between both age groups and correlated with rod intercept time (RIT). The median number of locations with discernible IZ was significantly higher (foveal, 4 vs. 0, p = 0.0099; extra-foveal 6 vs. 0, p < 0.001) in eyes of young (26 ± 3 years) compared to older (73 ± 5 years) participants. For the combined young and older sample, the higher frequency of discernible IZ was correlated with shorter RIT (faster dark adaptation) (rs = –0.56, p < 0.0001). This association was significant within young eyes (rs = –0.54; p = 0.0134) and not within older eyes (rs = –0.29, p = 0.706). Results suggest that the interface between outer segments and apical processes degrades in normal aging, potentially contributing to delayed rod-mediated dark adaptation. More research is needed to verify an age-related association between IZ discernibility and rod-mediated dark adaptation. If confirmed in a large sample, IZ discernibility might prove to be a valuable biomarker and predictor for visual function in aging. [ABSTRACT FROM AUTHOR]

Structure–function relationships in proteins have been one of the crucial scientific topics in recent research. Heme proteins have diverse and pivotal biological functions. Therefore, clarifying their structure–function correlation is significant to understand their functional mechanism and is informative for various fields of science. In this study, we constructed convolutional neural network models for predicting protein functions from the tertiary structures of heme-binding sites (active sites) of heme proteins to examine the structure–function correlation. As a result, we succeeded in the classification of oxygen-binding protein (OB), oxidoreductase (OR), proteins with both functions (OB–OR), and electron transport protein (ET) with high accuracy. Although the misclassification rate for OR and ET was high, the rates between OB and ET and between OB and OR were almost zero, indicating that the prediction model works well between protein groups with quite different functions. However, predicting the function of proteins modified with amino acid mutation(s) remains a challenge. Our findings indicate a structure–function correlation in the active site of heme proteins. This study is expected to be applied to the prediction of more detailed protein functions such as catalytic reactions. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the relationship between structure and function in moderate and advanced primary open-angle glaucoma (POAG) and to determine the accuracy of structure and vasculature for discriminating moderate from advanced POAG. Methods: In this cross-sectional study, 25 eyes with moderate and 40 eyes with advanced POAG were enrolled. All eyes underwent measurement of the thickness of circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (GCC), and optical coherence tomography angiography (OCTA) of the optic nerve head (ONH) and macula. Visual field (VF) was evaluated by Swedish interactive threshold algorithm and 24–2 and 10–2 patterns. The correlation between structure and vasculature and the mean deviation (MD) of the VFs was evaluated by a partial correlation coefficient. The area under the receiver operating characteristic curve (AUC) was applied for assessing the power of variables for discrimination moderate from advanced POAG. Results: Including all eyes, whole image vessel density (wiVD) of the ONH area, and vessel density (VD) in the inferior quadrant of perifovea were the parameters with significant correlation with the mean deviation (MD) of the VF 24–2 in OCTA of the ONH and macula (r =.649 and.397; p <.05). The greatest AUCs for discriminating moderate and advanced POAG belonged to VD of the inferior hemifield of ONH area (.886; 95% CI (.805,.967)), and VD in the inferior quadrant of perifovea (.833; 95% CI (.736,.930)) without statistically significant difference (.886 Versus.833; p =.601). Conclusion: Among vascular parameters of the ONH area, wiVD had the strongest correlation with the MD of the VF 24–2 while VD of the inferior hemifield of the ONH area had the greatest AUC for discriminating moderate and advanced POAG. Vessel density in the inferior quadrant of perifovea had a significant correlation with the MD of VF 24–2 and also the greatest AUC for discriminating moderate and advanced POAG. [ABSTRACT FROM AUTHOR]

Electrochemical CO2 reduction (CO2R) represents a sustainable way to store intermittent renewable energies and produce carbon-neutral fuels, yet the energy efficiency remains a huge bottleneck owning to its sluggish kinetics and complex reaction pathways. Highly active, selective, and robust electrocatalysts are strongly demanded to accelerate CO2 conversion and deploy this technology to practical applications. In this review, we focus on single-atom catalysts (SACs), a unique category of electrocatalysts with atomically dispersed metal active sites, which have shown distinctive performances in CO2R and offer an ideal platform for in-depth mechanistic studies at the atomic level. Despite various SACs with attractive CO2R performances have been reported, the relationship between electronic/geometric structure of SACs and the corresponding electrocatalytic performance still needs to be discussed with caution. Here we take a broad overview on the recent progress in understanding the structure-function correlation of SACs in CO2R, with the purpose of providing deep insights and guiding the future rational design of SACs. First, we provide the fundamental understandings of CO2R on SACs, following different reaction pathways. Then, we describe the progresses in the development of well-defined SACs and the mechanistic studies on the influences from particular structural parameters, such as first-shell and second-sphere coordination, conductive supports and interface with a secondary catalyst. Finally, some perspectives are highlighted on the path towards efficient CO2R on SACs. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators of cellular processes, with their dysregulation linked to various disease states. Among the structural motifs in lncRNAs, RNA G-quadruplexes (rG4s) have gained increasing attention due to their diverse roles in cellular function and disease pathogenesis. This review provides an updated and comprehensive overview of rG4s in lncRNAs, elucidating their formation, interaction with proteins, and distinctive roles in cellular processes. We discuss current methodologies for experimentally probing RNA G4s, including the use of specific small molecules, biomolecular ligands and fluorescent probes. The commonly found RNA G4-interacting protein domains are summarised along with potential strategies for disrupting lncRNA G4-protein interactions from a therapeutic perspective. [Display omitted] • LncRNAs are crucial regulators of cellular processes and their dysregulation is associated with various disease conditions. • Formation of RNA G4s within lncRNAs can facilitate interactions with specific proteins thereby regulating cellular processes. • G4-interacting ligands assist in study of RNA G4-protein interactions and can serve as potential therapeutic agents. [ABSTRACT FROM AUTHOR]

(1) Background: to investigate the correlation between structural (retinal ganglion cells and retinal nerve fibers) and functional alterations analyzed point-by-point in the central 10 degrees of the visual field of patients with advanced glaucoma using Humphrey 10-2 visual field tests. (2) Methods: Single-center prospective cohort study carried on from October 2018 to February 2019 at the Croix-Rousse hospital, Lyon, France. The primary outcome measure was the point-by-point correlation between retinal sensitivity (Humphrey 10-2) and retinal ganglion cell complex (GCC) thickness. (3) Results: 29 eyes of 27 patients were examined. Of these, 15 eyes had a mean deviation (MD) less than −20 dB. There were statistically significant linear relationships between GCC thickness and 10-2 visual field sensitivity for several points in the lower part of the visual field, with lower retinal sensitivity being associated with thicker GCC layers. There were no strong linear relationships or statistically significant correlations in the other regions of the visual field. For the patients with MD < −20 dB, there were statistically significant linear relationships between GCC thickness and 10-2 visual field sensitivity for several points in the superior nasal region. Retinal sensitivity was not correlated with retinal nerve fibre layer thickness. (4) Conclusions: In this study of patients with advanced glaucoma, GCC thickness was linearly associated with 10-2 visual field sensitivity in certain regions, negatively for patients with less-severe glaucoma. The initial thickening raises questions about the apoptosis mechanism, while the thinning observed in the most severe cases is consistent with the ganglion cell death identified on visual field tests. [ABSTRACT FROM AUTHOR]

The plethora of flavonoid antioxidants in plant organisms, widespread in nature, and the appropriate metal ions known for their influence on biological processes constitute the crux of investigations toward the development of preventive metallodrugs and therapeutics in several human pathophysiologies. To that end, driven by the need to enhance the structural and (bio)chemical attributes of the flavonoid chrysin, as a metal ion complexation agent, thereby rendering it bioavailable toward oxidative stress, synthetic efforts in our lab targeted ternary Cr(III)-chrysin species in the presence of auxiliary aromatic N,N′-chelators. The crystalline metal-organic Cr(III)-chrysin-L (L = bipyridine (1) and phenanthroline (2)) compounds that arose were physicochemically characterized by elemental analysis, FT-IR, UV-Visible, ESI-MS, luminescence, and X-ray crystallography. The properties of these compounds in a solid state and in solution formulate a well-defined profile for the two species, thereby justifying their further use in biological experiments, intimately related to cellular processes on oxidative stress. Experiments in C2C12 myoblasts at the cellular level (a) focus on the antioxidant capacity of the Cr(III)-complexed flavonoids, emphasizing their distinct antiradical activity under oxidative stress conditions, and (b) exemplify the importance of structural speciation in Cr(III)-flavonoid interactions, thereby formulating correlations with the antioxidant activity of a bioavailable flavonoid toward cellular pathophysiologies, collectively supporting flavonoid introduction in new metallo-therapeutics. [ABSTRACT FROM AUTHOR]

An algorithm is applied to propose a sequence–function correlation of the transmembrane domains (TMDs) of the non-structural protein 4B (NS4B) of hepatitis C virus (HCV). The putative sequence of the TMDs is obtained using 20 available secondary structure prediction programs (SSPPs) with different lengths of the overall amino acid sequence of the protein as input. The results support the notion of four helical TMDs. Whilst the region of the first TMDs leaves room for speculation about an additional TMD, the other three TMDs are consistently predicted. Structural features and the role of each of the TMDs is proposed by applying pairwise sequence alignment using BLAST on the level (i) protein sequence alignment and consequent (ii) function-related alignment. Sequence identity with those TMDs of proteins involved in Ca-homeostasis and generation of replication vesicles, such as Nsp3 of corona viruses, murine coronavirus especially mouse hepatitis virus (MHV), middle east respiratory syndrome coronavirus (MERS), severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, are suggested. Focusing the search on those proteins in particular and their TMDs playing an active role in their mechanism of function, such as transporters, pumps, viral channel forming protein Vpu of human immunodeficiency virus type 1 (HIV-1) and mediators, suggests TMDs 2 and 4 to have functional roles in NS4B, as well as additionally TMD1 and 3 in case of vesicle formation.

Ubiquitination is an important posttranslational modification of proteins in eukaryotic cells, wherein ubiquitin molecules are conjugated to target proteins. Ubiquitination is catalyzed by the cascade of ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and ubiquitin ligase (E3). The number of E2s encoded in eukaryotes partly explains their contribution to the inherent specificity of the ubiquitin system. The ubiquitin conjugating enzyme UBC1 of Saccharomyces cerevisiae participates the degradation of short-lived and abnormal proteins. UBC1 consists of two well-defined domains separated by a long flexible linker. E2-25K, the human homolog of UBC1 is crucial to neurons and its failure leads to neurodegenerative disorders. The linker of UBC1 is of 22 amino acids, while that of E2-25K has 6 amino acids. To understand the importance of the linker, the chimeric protein, cUBC1 was constructed by substituting the linker of E2-25K in UBC1. cUBC1 shows minor changes in its secondary structure. cUBC1 expression in ubc1 deletion mutants showed no effect over growth, thermotolerance and resistance to antibiotic stress. However, survival under heat stress was enhanced with cUBC1. Western blot analysis of the enzymatic activity showed cUBC1 performed equally well as UBC1. Hence, cUBC1 demonstrates that the shorter linker increased the stability of UBC1. • E2 enzyme of yeast, UBC1 has two domains joined by a linker of twenty two residues. • E2-25k, the human homolog of UBC1 has a linker of six residues. • To study the importance of linker in UBC1 it was replaced with that of E2-25K. • The chimeric construct cUBC1 is a stable protein and can form polyubiquitin chains. • The chimeric protein cUBC1 is functional even under stress conditions. [ABSTRACT FROM AUTHOR]

We compare the focal structure–function correlation of structural measurements of peripapillary retinal nerve fiber layer thickness (RNFL‐T) using optical coherence tomography (OCT), capillary density (CD) measurements using OCT‐angiography (OCT‐A), or a combination of both, with visual field deviation (VFD) in early to advanced glaucoma. Primary open angle glaucoma patients (n = 46, mean ± SD age: 67 ± 10 years; VF mean deviation: −10.41 ± 6.76 dB) were included in this cross‐sectional study. We performed 30–2 standard automated perimetry OCT (3.5‐mm diameter ring scan) and 15°×15° OCT‐A (superficial vascular complex slab). Based on a nerve fiber trajectory model, each VF test spot was assigned to an OCT‐A wedge and an OCT ring‐sector. Two univariate linear models (Mv and Mt) using either CD‐based vascular (Mv) or RNFL‐T–based thickness information (Mt) and one multivariate model using both (Mv:t) were compared in their associations with measured focal VFD, which were higher for the multivariate model Mv:t (mean ± SD correlation coefficient: 0.710 ± 0.086) than for either nested model (0.627 ± 0.078 for Mv and 0.578 ± 0.095 for Mt). Using a focal visual field approach, the combination of RNFL‐T and CD showed better structure–function correlations than thickness or vascular information only. [ABSTRACT FROM AUTHOR]

The increasing global demand for sustainable energy sources and emerging environmental issues have pushed the development of energy conversion and storage technologies to the forefront of chemical research. Electrochemical carbon dioxide (CO2) conversion provides an attractive approach to synthesizing fuels and chemical feedstocks using renewable energy. On the path to deploying this technology, basic and applied scientific hurdles remain. Copper, as the only metal catalyst that is capable to produce C2+ fuels from CO2 reduction (CO2R), still faces challenges in the improvement of electrosynthesis pathways for highly selective fuel production. In this regard, mechanistically understanding CO2R on Cu‐based electrocatalysts, particularly identifying the structure–function correlation, is crucial. Here, a broad view of the variable structural parameters and their complex interplay in CO2R catalysis on Cu was given, with the purpose of providing deep insights and guiding the future rational design of CO2R electrocatalysts. First, this Review described the progress and recent advances in the development of well‐defined nanostructured catalysts and the mechanistic understanding on the influences from a particular structure of a catalyst, such as facet, defects, morphology, oxidation state, composition, and interface. Next, the in‐situ dynamic restructuring of Cu was presented. The importance of operando characterization methods to understand the catalyst structure‐sensitivity was also discussed. Finally, some perspectives on the future outlook for electrochemical CO2R were offered. [ABSTRACT FROM AUTHOR]

Several influential philosophers and scientists have advanced a framework, often called Neo-Cartesianism (NC), according to which animal suffering is merely apparent. Drawing upon contemporary neuroscience and philosophy of mind, Neo-Cartesians challenge the mainstream position we shall call Evolutionary Continuity (EC), the view that humans are on a nonhierarchical continuum with other species and are thus not likely to be unique in consciously experiencing negative pain affect. We argue that some Neo-Cartesians have misconstrued the underlying science or tendentiously appropriated controversial views in the philosophy of mind. We discuss recent evidence that undermines the simple neuroanatomical structure-function correlation thesis that undergirds many Neo-Cartesian arguments, has an important bearing on the recent controversy over pain in fish, and places the underlying epistemology framing the debate between NC and EC in a new light that strengthens the EC position. [ABSTRACT FROM AUTHOR]

2D conjugated extension on central units of small molecular acceptors (SMAs) has gained great successes in reaching the state-of-the-art organic photovoltaics. Whereas the limit size of 2D central planes and their dominant role in constructing 3D intermolecular packing networks are still elusive. Thus, by exploring a series of SMAs with gradually enlarged central planes, it is demonstrated that, at both single molecular and aggerated levels, there is an unexpected blue-shift for their film absorption but preferable reorganization energies, exciton lifetimes and binding energies with central planes enlarging, especially when comparing to their Y6 counterpart. More importantly, the significance of well-balanced molecular packing modes involving both central and end units is first disclosed through a systematic single crystal analysis, indicating that when the ratio of central planes area/end terminals area is no more than 3 likely provides a preferred 3D intermolecular packing network of SMAs. By exploring the limit size of 2D central planes, This work indicates that the structural profiles of ideal SMAs may require suitable central unit size together with proper heteroatom replacement instead of directly overextending 2D central planes to the maximum. These results will likely provide some guidelines for future better molecular design., (© 2024 Wiley‐VCH GmbH.)

The Green Fluorescent Protein (GFP) is a widely studied chemical system both for its large amount of applications and the complexity of the excited state proton transfer responsible of the change in the protonation state of the chromophore. A detailed investigation on the structure of the chromophore environment and the influence of chromophore form (either neutral or anionic) on it is of crucial importance to understand how these factors could potentially influence the protein function. In this study, we perform a detailed computational investigation based on the analysis of ab-initio molecular dynamics simulations, to disentangle the main structural quantities determining the fine balance in the chromophore environment. We found that specific hydrogen bonds interactions directly involving the chromophore (or not), are correlated to quantities, such as the volume of the cavity in which the chromophore is embedded and that it is importantly affected by the chromophore protonation state. The cross-correlation analysis performed on some of these hydrogen bonds and the cavity volume, demonstrates a direct correlation among them and we also identified the ones specifically involved in this correlation. We also found that specific interactions among residues far in the space are correlated, demonstrating the complexity of the chromophore environment and that many structural quantities have to be taken into account to properly describe and understand the main factors tuning the active site of the protein. From an overall evaluation of the results obtained in this work, it is shown that the residues which a priori are perceived to be spectators play instead an important role in both influencing the chromophore environment (cavity volume) and its dynamics (cross-correlations among spatially distant residues).

Hemoglobinopathies are examples of autosomal recessive disorders of human hemoglobin. Hemoglobin E (HbE) and Hemoglobin D Punjab (HbD Punjab) are two of the most common hemoglobin variants geographically spread across Asian continent. These two variants differ from normal human hemoglobin (HbA) at a single amino acid residue caused by the point mutation of β globin gene. The presence of the mutated amino acid residue causes perturbation in the function of both variants. However, the structure–function correlation of these variants has not been established yet. In the present study, we analyzed the conformational changes associated with oxygenation of hemoglobin variants using hydrogen/deuterium exchange-based mass spectrometry of backbone amide hydrogens of α and β globin chains in the tetrameric hemoglobin molecule. We also performed the functional assay of these variants using oxygen dissociation equilibrium curve. Compared to HbA, both variants showed reduced oxygen affinity, as reported earlier. The functional perturbations exhibited by these variants were correlated well with their structural alterations with respect to the reported changes in the residue level interactions upon oxygenation of normal hemoglobin, monitored through the hydrogen/deuterium exchange kinetics of several peptic peptides originated from the isotopically exchanged oxy and deoxy forms of HbE and HbD Punjab. [ABSTRACT FROM AUTHOR]

Mushroom polysaccharides are recognized as "biological response modifiers". Besides several bioactivities, a growing interest in their prebiotic potential has been raised due to the gut microbiota modulation potential. This review comprehensively summarizes mushroom polysaccharides' biological properties, structure-function relationship, and underlying mechanisms. It provides a recent overview of the key findings in the field (2018–2024). Key findings and limitations on structure-function correlation are discussed. Although most studies focus on β-glucans or extracts, α-glucans and chitin have gained interest. Prebiotic capacity has been associated with α-glucans and chitin, while antimicrobial and wound healing potential is attributed to chitin. However, further research is of utmost importance. Human fecal fermentation is the most reported approach to assess prebiotic potential, indicating impacts on intestinal biological, mechanical, chemical and immunological barriers. Gut microbiota dysbiosis has been directly connected with intestinal, cardiovascular, metabolic, and neurological diseases. Concerning gut microbiota modulation, animal experiments have suggested proinflammatory cytokines reduction and redox balance re-establishment. Most literature focused on the anticancer and immunomodulatory potential. However, anti-inflammatory, antimicrobial, antiviral, antidiabetic, hypocholesterolemic, antilipidemic, antioxidant, and neuroprotective properties are discussed. A significant overview of the gaps and research directions in synergistic effects, underlying mechanisms, structure-function correlation, clinical trials and scientific data is also given. [Display omitted] • Direct and gut microbiota-related effects of mushroom polysaccharides (MP)- chitin, α- and β-glucans. • Further structural research is mandatory to robust structure-function correlations. • MP promote gut metabolite production, impacting the heart, liver, and brain axis. • MP impact intestinal biological, mechanical, chemical and immunological barriers. • β-glucans exhibit a strong immunomodulating, antioxidant and metabolic regulation effect. [ABSTRACT FROM AUTHOR]

Glycation and glutathionylation are important posttranslational modifications (PTMs) of human haemoglobin that act as biomarkers of diabetes mellitus and oxidative stress. These PTMs perturb the function of normal haemoglobin. However, the structure-function correlation of these PTMs of genetically modified haemoglobin remained unexplored. Using hydrogen/deuterium exchange mass spectrometry, we studied the conformational dynamics of glycated and glutathionylated forms of two haemoglobin variants, HbE and HbD Punjab. Like glycated and glutathionylated normal haemoglobin, these PTMs of HbE were expected to have increased oxygen affinity. However, for HbD Punjab, glycation was predicted to have decreased oxygen affinity whereas glutathionylation to have increased oxygen affinity. [ABSTRACT FROM AUTHOR]

Glaucoma is the leading cause of irreversible blindness worldwide, with an increasing prevalence. The complexity of the disease has been a major challenge in moving the field forward with regard to both pathophysiological insight and treatment. In this context, discussing possible outcome measures in glaucoma trials is of utmost importance and clinical relevance. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "New Technologies for Outcome Measures in Retina and Glaucoma," addressing both functional and structural outcomes, as well as translational hot topics in glaucoma and retina research. In conjunction with the published literature, this review summarizes the meeting focusing on glaucoma. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • d°-Vanadate shows superior visible-light responsiveness. • Heteroatom-tuning vanadates can alter the competitive reaction pathways. • Electronic structure of vanadates interface to various reaction intermediates change. • BiVO 4 promotes the oxidation with the higher TOF (7.5 h−1) than Cu 3 V 2 O 8 (2.8 h−1). • A different KA-oil selectivity is obtained for BiVO 4 (95%) and Cu 3 V 2 O 8 (54%). Abstract Structure-function correlation constitutes a central theme in the selective photocatalytic oxidation of cyclohexane with molecular oxygen, as a result of precise tailoring band-structure towards KA-oil selectivity. Herein, we comparatively and systematically investigate the correlation among optical properties, electronic structure, and photocatalytic performance of two d°-vanadate photocatalysts (BiVO 4 and Cu 3 V 2 O 8) using theoretical calculations and experimental techniques. Results show that BiVO 4 promotes the selective oxidation pathway under visible-light irradiation with higher efficiency (TOF = 7.5 h−1, based on the molar amount of V sites) and chemoselectivity (cyclohexanone/cyclohexanol molar ratio = 3.0) than the Cu 3 V 2 O 8. Meanwhile, the photocatalytic performance of BiVO 4 demonstrates high photocatalytic selectivity towards KA-oil (95%), while Cu 3 V 2 O 8 seems to facilitate the accommodation of chlorine promoters, leading to very different chlorocyclohexane selectivity (46%). Such the distinct photocatalytic performances of BiVO 4 and Cu 3 V 2 O 8 can be ascribed to their unique electronic structures to facilitate the e−−h+ charge carriers and generation of reactive species during photoirradiation. The Bi3+ 6p states of BiVO 4 are predominant components of the conduction band minimum (CBM) and hybridize with Bi3+ 6 s , and O2− 2p and V5+ 3d orbitals at the valence band maximum (VBM); whereas the Cu2+ 3d and V5+ 3d orbitals contribute to the CBM of Cu 3 V 2 O 8 , and Cu2+ 3d , O2− 2p and V5+ 3d orbitals at the VBM. So BiVO 4 with s − p matrix elements is more effective than the Cu 3 V 2 O 8 in producing OH, h+ and H 2 O 2 , which can rapidly oxidize the C − Cl band cleavage for chlorocyclohexane intermediate to regenerate newly Cl radicals in the next cycle reactions. Heteroatom-tuning of photocatalytic performance is further supported by universal evidences from experimental results by replacing Bi or Cu of the above vanadates with Ag, La, Sr, Fe or Ti atom and the study of the electrons, holes and radicals mediated reaction pathway by scavengers, respectively. [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic assessment of glaucoma specialists with an automated structure-function correlation report combining visual field (VF) and spectral-domain optical coherence tomography (SD-OCT) imagining in subjects with glaucoma.Methods: This prospective, cross-sectional study was conducted at Wills Eye Hospital, Philadelphia, PA, USA. Subjects with glaucoma received ophthalmic examination, VF testing, and SD-OCT imaging. An automated report was generated describing structure-function correlations between the two structural elements [retinal nerve fiber layer (RNFL) and Bruch's membrane opening-minimum rim width (MRW)] and VF sectors. Three glaucoma specialists masked to the automated report and to each other identified clinically significant structure-function correlations between the VF and SD-OCT reports. Raw agreement and chance-corrected agreement (kappa statistics) between the automated report and the clinical assessments were compared.Results: A total of 53 eyes from 45 subjects with glaucoma were included in this study. The overall agreement between the automated report and clinical assessment comparing MRW and VF was good at 74.8% with a kappa of 0.62 (95% CI 0.55-0.69). Agreements for the six different MRW sections were moderate to good with kappa values ranging from 0.54 to 0.69. For mean RNFL thickness and VF comparisons, agreement between the automated report and clinical assessment was 75.4% with a kappa of 0.62 (95% CI 0.54-0.70). For different RNFL sectors, kappa values ranged from 0.47 (moderate agreement) to 0.80 (good agreement).Conclusions: This study suggests that the automated structure-function report combining results from the SD-OCT and the HEP may assist in the evaluation and management of glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: Currently, no outcome measures are clinically validated and accepted as clinical endpoints by regulatory agencies for drug development in intermediate age-related macular degeneration (iAMD). The MACUSTAR Consortium, a public-private research group funded by the European Innovative Medicines Initiative intends to close this gap. Procedures: Development of study protocol and statistical analysis plan including predictive modelling of multimodal endpoints based on a review of the literature and expert consensus. Results: This observational study consists of a cross-sectional and a longitudinal part. Functional outcome measures assessed under low contrast and low luminance have the potential to detect progression of visual deficit within iAMD and to late AMD. Structural outcome measures will be multimodal and investigate topographical relationships with function. Current patient-reported outcome measures (PROMs) are not acceptable to regulators and may not capture the functional deficit specific to iAMD with needed precision, justifying development of novel PROMs for iAMD. The total sample size will be n = 750, consisting mainly of subjects with iAMD (n = 600). Conclusions: As clinical endpoints currently accepted by regulators cannot detect functional loss or patient-relevant impact in iAMD, we will clinically validate novel candidate endpoints for iAMD. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to identify quantitatively measurable morphologic optical coherence tomography (OCT) characteristics in patients with an acute episode of central serous chorioretinopathy (CSC) and evaluate their correlation to functional and psychological variables for their use in daily clinical practice. Methods: Retinal thickness (RT), the height, area and volume of subretinal fluid (SRF)/pigment epithelium detachments were evaluated using the standardized procedures of the Vienna Reading Center. These morphologic characteristics were compared with functional variables [best‐corrected visual acuity (BCVA), contrast sensitivity (CS), retinal sensitivity/microperimetry, fixation stability], and patients' subjective handicap from CSC using the National Eye Institute 25‐item Visual Function Questionnaire (NEI VFQ‐25). Results: Data from 39 CSC patients were included in this analysis. Three different SRF height measures showed a high negative correlation (r = −0.7) to retinal sensitivity within the central 9°, which was also negatively correlated with SRF area and volume (r = −0.6). The CS score and fixation stability (fixation points within 2°) showed a moderate negative correlation (r = −0.4) with SRF height variables. Comparison of the subjective handicap with morphological characteristics in spectral‐domain (SD)‐OCT showed SRF height had the highest correlation (r = −0.4) with the subjective problems reported and overall NEI VFQ‐25 score. Conclusion: In conclusion, SRF height measured in SD‐OCT showed the best correlation with functional variables and patients' subjective handicap caused by the disease and therefore seems to be the best variable to look at in daily clinical routine. Even though area and volume also show a correlation, these cannot be so easily measured as height and are therefore not suggested for daily clinical routine. [ABSTRACT FROM AUTHOR]

The depolymerization of lignocellulosic biomass is facilitated by feruloyl esterases (FAEs), which hydrolyze ester bonds between lignin and polysaccharides. Fungal FAEs belonging to subfamily (SF) 6 release precursors such as ferulic acid derivatives, attractive for biochemical production. Among these, Aspergillus sydowii FAE (As FaeE), an SF6 FAE, exhibits remarkable activity across various substrates. In this study, we conducted X-ray crystallography and kinetic analysis to unravel the molecular mechanisms governing substrate recognition and catalysis by As FaeE. As FaeE exhibits a typical α/β -hydrolase fold, characterized by a catalytic triad of serine, aspartate, and histidine. Comparative analysis of substrate-free, ferulic acid-bound, and sinapic acid-bound forms of As FaeE suggests a conformational change in the loop covering the substrate-binding pocket upon binding. Notably, Pro158 and Phe159 within this loop cover the phenolic part of the substrate, forming three layers of planar rings. Our structure-based functional mutagenesis clarifies the roles of the residues involved in substrate binding and catalytic activity. Furthermore, distinct substrate-binding mechanisms between As FaeE and other studied FAEs are identified. This investigation offers the initial structural insights into substrate recognition by SF6 FAEs, equipping us with structural knowledge that might facilitate the design of FAE variants capable of efficiently processing a wider range of substrate sizes. • 3D structures of As FaeE in substrate-free and substrate-bound forms were revealed. • The loop covering the substrate-binding pocket plays a pivotal role in binding. • Functional roles of the residues in the substrate-binding pocket are unveiled. • Mutants with different substrate preferences were found. • SF6 FAE's preference towards monomeric hydroxycinnamates is rationally understood. [ABSTRACT FROM AUTHOR]

A new strategy to nanoengineer gold/fluorocarbon multilayer (ML) nanostructures is reported. We have investigated the morphological changes occurring at the metal−polymer interface in ML structures with varying volume fraction of gold (Au) and the kinetic growth aspect of the microscale properties of nano-sized Au in plasma polymer fluorocarbon (PPFC). Investigations were carried out at various temperatures and annealing times by means of grazing incidence small-angle and wide-angle X-ray scattering (GISAXS and GIWAXS). We have fabricated a series of MLs with varying volume fraction (0.12, 0.27, 0.38) of Au and bilayer periodicity in ML structure. They show an interesting granular structure consisting of nearly spherical nanoparticles within the polymer layer. The nanoparticle (NP) morphology changes due to the collective effects of NPs diffusion within ensembles in the in-plane vicinity and interlayer with increasing temperature. The in-plane NPs size distinctly increases with increasing temperature. The NPs become more spherical, thus reducing the surface energy. Linear growth of NPs with temperature and time shows diffusion-controlled growth of NPs in the ML structure. The structural stability of the multilayer is controlled by the volume ratio of the metal in polymer. At room temperature, UV-Vis shows a blue shift of the plasmon peak from 560 nm in ML Au/PTFE_1 to 437 nm in Au/PTFE_3. We have identified the fabrication and postdeposition annealing conditions to limit the local surface plasmon resonance (LSPR) shift from Δ λ L S P R = 180 nm (Au/PTFE_1) to Δ λ L S P R = 67 nm (Au/PTFE_3 ML)) and their optical response over a wide visible wavelength range. A variation in the dielectric constant of the polymer in presence of varying Au inclusion is found to be a possible factor affecting the LSPR frequency. Our findings may provide insights in nanoengineering of ML structure that can be useful to systematically control the growth of NPs in polymer matrix.

Bacterial toxin–antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins. We mainly explore the similar but divergent structures of type II TA proteins from 12 important pathogenic bacteria, including various aspects of protein–protein interactions. Accumulating knowledge about the structure–function correlation of TA systems from pathogenic bacteria has facilitated a novel strategy to develop antibiotic drugs that target specific pathogens. These molecules could increase the intrinsic activity of the toxin by artificially interfering with the intermolecular network of the TA systems. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the diagnostic power of the Posterior Pole Asymmetry Analysis (PPAA) from the SPECTRALIS OCT in glaucoma diagnosis and to define the correlation between the visual field sensitivity (VFS) and macular retinal thickness (MRT). Methods: 90 consecutive open-angle glaucoma patients and 23 healthy subjects were enrolled. All subjects underwent Visual Field test (Humphrey Field Analyzer, central 24-2 SITA-Standard) and SD-OCT volume scans (SPECTRALIS, Posterior Pole Asymmetry Analysis). The areas under the Receiving Operating Characteristic curve (AROC) were calculated to assess discriminating power for glaucoma, at first considering total MRT values and hemisphere MRT value and then quadrant MRT values from 16 square cells in a 8 x 8 posterior pole retinal thickness map that were averaged for a mean retinal thickness value. Structure function correlation was performed for total values, hemisphere values and for each quadrant compared to the matching central test points of the VF. Results: The AROCs ranged from 0.70 to 0.82 (p < 0.0001), with no significant differences between each other. The highest AROC observed was in inferior nasal quadrant. The VFS showed a strong correlation only with the corresponding MRT value s for quadrant analysis: Superior Temporal (r = 0.33,p = 0.0013), Superior Nasal (r = 0.43,p < 0.0001), Inferior Temporal (r = 0.57,p < 0.0001) and Inferior Nasal (r = 0.55,p < 0.0001). Conclusion: the quadrant analysis showed statistically significant structure-function correlations and may provide additional data for the diagnostic performance of SPECTRALIS OCT. [ABSTRACT FROM AUTHOR]

Introduction Rolandic epilepsy (RE) manifests during a critical phase of brain development, and has been associated with language impairments. Concordant abnormalities in structural and functional connectivity (SC and FC) have been described before. As SC and FC are under mutual influence, the current study investigates abnormalities in the SC-FC synergy in RE. Methods Twenty-two children with RE (age, mean±SD: 11.3±2.0 y) and 22 healthy controls (age 10.5±1.6 y) underwent structural, diffusion weighted, and functional MRI at 3T. The probabilistic anatomical landmarks atlas was used to parcellate the (sub)cortical gray matter. Constrained spherical deconvolution tractography and correlation of time series were used to assess SC and FC, respectively. The SC-FC correlation was assessed as a function of age for the non-zero structural connections over a range of sparsity values (0.01-0.75). A modularity analysis was performed on the mean SC network of the controls to localize potential global effects to subnetworks. SC and FC were also assessed separately using graph analysis.Results The SC-FC correlation was significantly reduced in children with RE compared to healthy controls, especially for the youngest participants. This effect was most pronounced in a left and a right centro-temporal network, as well as in a medial parietal network. Graph analysis revealed no prominent abnormalities in SC or FC network organization.Conclusion Since SC and FC converge during normal maturation, our finding of reduced SC-FC correlation illustrates impaired synergy between brain structure and function. More specifically, since this effect was most pronounced in the youngest participants, RE may represent a developmental disorder of delayed brain network maturation. The observed effects seem especially attributable to medial parietal connections, which forms an intermediate between bilateral centro-temporal modules of epileptiform activity, and bear relevance for language function.

Background Protein crystallins co me in three types (α, β and γ) and are found predominantly in the eye, and particularly in the lens, where they are packed into a compact, plastic, elastic, and transparent globule of proper refractive power range that aids in focusing incoming light on to the retina. Of these, the γ-crystallins are found largely in the nuclear region of the lens at very high concentrations (> 400 mg/ml). The connection between their structure and inter-molecular interactions and lens transparency is an issue of particular interest. Scope of review We review the origin and phylogeny of the gamma crystallins, their special structure involving the use of Greek key supersecondary structural motif, and how they aid in offering the appropriate refractive index gradient, intermolecular short range attractive interactions (aiding in packing them into a transparent ball), the role that several of the constituent amino acid residues play in this process, the thermodynamic and kinetic stability and how even single point mutations can upset this delicate balance and lead to intermolecular aggregation, forming light-scattering particles which compromise transparency. We cite several examples of this, and illustrate this by cloning, expressing, isolating and comparing the properties of the mutant protein S39C of human γS-crystallin (associated with congenital cataract-microcornea), with those of the wild type molecule. In addition, we note that human γ-crystallins are also present in other parts of the eye (e.g., retina), where their functions are yet to be understood. Major conclusions There are several ‘crucial’ residues in and around the Greek key motifs which are essential to maintain the compact architecture of the crystallin molecules. We find that a mutation that replaces even one of these residues can lead to reduction in solubility, formation of light-scattering particles and loss of transparency in the molecular assembly. General significance Such a molecular understanding of the process helps us construct the continuum of genotype–molecular structural phenotype–clinical (pathological) phenotype. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. [ABSTRACT FROM AUTHOR]

Introduction: Rolandic epilepsy (RE) manifests during a critical phase of brain development, and has been associated with language impairments. Concordant abnormalities in structural and functional connectivity (SC and FC) have been described before. As SC and FC are under mutual influence, the current study investigates abnormalities in the SC-FC synergy in RE. Methods: Twenty-two children with RE (age, mean ± SD: 11.3 ± 2.0 y) and 22 healthy controls (age 10.5 ± 1.6 y) underwent structural, diffusion weighted, and restingstate functional magnetic resonance imaging (MRI) at 3T. The probabilistic anatomical landmarks atlas was used to parcellate the (sub)cortical gray matter. Constrained spherical deconvolution tractography and correlation of time series were used to assess SC and FC, respectively. The SC-FC correlation was assessed as a function of age for the non-zero structural connections over a range of sparsity values (0.01-0.75). A modularity analysis was performed on the mean SC network of the controls to localize potential global effects to subnetworks. SC and FC were also assessed separately using graph analysis. Results: The SC-FC correlation was significantly reduced in children with RE compared to healthy controls, especially for the youngest participants. This effect was most pronounced in a left and a right centro-temporal network, as well as in a medial parietal network. Graph analysis revealed no prominent abnormalities in SC or FC network organization. Conclusion: Since SC and FC converge during normal maturation, our finding of reduced SC-FC correlation illustrates impaired synergy between brain structure and function. More specifically, since this effect was most pronounced in the youngest participants, RE may represent a developmental disorder of delayed brain network maturation. The observed effects seem especially attributable to medial parietal connections, which forms an intermediate between bilateral centro-temporal modules of epileptiform activity, and bear relevance for language function. [ABSTRACT FROM AUTHOR]

Abstract: The multitude of terpene carbon skeletons in plants is formed by enzymes known as terpene synthases. This review covers the monoterpene and sesquiterpene synthases presenting an up-to-date list of enzymes reported and evidence for their ability to form multiple products. The reaction mechanisms of these enzyme classes are described, and information on how terpene synthase proteins mediate catalysis is summarized. Correlations between specific amino acid motifs and terpene synthase function are described, including an analysis of the relationships between active site sequence and cyclization type and a discussion of whether specific protein features might facilitate multiple product formation. [Copyright &y& Elsevier]

Abstract: Mutations in the hydroxymethylbilane synthase (HMBS) gene are responsible for the inherited disorder of acute intermittent porphyria (AIP). AIP is diagnosed on the basis of characteristic clinical symptoms, elevated levels of urinary porphyrin precursors aminolevulinic acid (ALA) and porphobilinogen (PBG) and a decreased erythrocytic HMBS activity, although an identifiable HMBS mutation provides the ultimate proof for AIP. Six Israeli AIP families underwent biochemical and mutation analysis in order to establish an AIP diagnosis. Variability with respect to the ALA/PBG levels and HBMS activity was found among the index patients. Indeed, each family carried a unique mutation in the HMBS gene. A novel missense c.95G>C (p.R32P) was shown to be a de novo mutation in one family, along with five known mutations p.T59I, p.D178N, p.V215M, c.730_731delCT and c.982_983delCA identified in the rest of the families. Both R32P and D178N were expressed in a prokaryotic system. Recombinant p.R32P was enzymatically inactive as demonstrated by a <1% residual activity, whereas p.D178N possessed 81% of the activity of the wild type enzyme. However, the p.D178N mutant did display a shift in optimal pH and was thermo labile compared to the wild type. Among the four missense mutations, p.R32P and p.V215M had not only harmful effects on the enzyme in vitro but also were associated with high levels of ALA/PBG in patients. On the other hand, the in vitro effect of both p.T59I and p.D178N, and the impact of these mutations on the enzyme structure and function as interpreted by the 3-D structure of the Escherichia coli enzyme, were weaker than that of p.R32P and p.V215M. Concomitantly, patients carrying the p.T59I or p.D178N had normal or borderline increases in ALA/PBG concentrations although they presented characteristic clinical symptoms. These findings provided further insights into the causal relationship between HMBS mutations and AIP. [Copyright &y& Elsevier]

Amino acid sequences are known to constantly mutate and diverge unless there is a limiting condition that makes such a change deleterious. However, closer examination of the sequence and structure reveals that a few large, cryptic repeats are nevertheless sequentially conserved. This leads to the question of why only certain repeats are conserved at the sequence level. It would be interesting to find out if these sequences maintain their conservation at the three-dimensional structure level. They can play an active role in protein and nucleotide stability, thus not only ensuring proper functioning but also potentiating malfunction and disease. Therefore, insights into any aspect of the repeats - be it structure, function or evolution - would prove to be of some importance. This study aims to address the relationship between protein sequence and its three-dimensional structure, by examining if large cryptic sequence repeats have the same structure. [ABSTRACT FROM AUTHOR]

Abstract: Fourier-transform infrared spectroscopy (FT-IR) was applied to study the coordination structure of Ca2+ bound in Akazara scallop troponin C (TnC) and its site-directed mutant possessing inactivated Site IV (E142D mutant) in D2O solution. The COO− antisymmetric stretching region provides information about the coordination modes of a COO− group to a metal ion. The wild type exhibits a band at 1543cm−1 in the Ca2+-bound state, indicating that the side-chain COO− group of Glu142 (the position 12 of Site IV) serves as the ligand for Ca2+ in the bidentate coordination mode [F. Yumoto, M. Nara, H. Kagi, W. Iwasaki, T. Ojima, K. Nishita, K. Nagata, M. Tanokura, Eur. J. Biochem. 268 (2001) 6284–6290]. However, the E142D mutant showed no band around 1543cm−1 in the Ca2+-loaded state, indicating that the side-chain COO− group of Asp142 does not bind to Ca2+ in the bidentate coordination mode. This result suggests that the absence of a methylene group is critical for the Ca2+ coordination structure of Akazara scallop TnC. The Ca2+-ligand interaction at Site IV is discussed in comparison with the results of synthetic peptide analogues of Site IV of Akazara scallop TnC. [Copyright &y& Elsevier]

An atomic force microscopy (AFM) study of the shape, orientation and surface topology of RNA polymerase II supported on silanized freshly cleaved mica was made. The overall aim is to define the molecular topology of RNA polymerase II in appropriate fluids to help clarify the relationship of conformational features to biofunctionality. A Nanoscope III atomic force microscope was used in the tapping mode with oxide-sharpened (8–10 nm) Si3N4 probes in aqueous zinc chloride buffer. The main structural features observed by AFM were compared to those derived from electron-density plots based on X-ray crystallographic studies. The conformational features included a bilobal silhouette with an inverted umbrella-shaped crater connected to a reaction site. These studies provide a starting point for constructing a 3D-AFM profiling analysis of proteins such as RNA polymerase complexes. [Copyright &y& Elsevier]

The increasing global demand for sustainable energy sources and emerging environmental issues have pushed the development of energy conversion and storage technologies to the forefront of chemical research. Electrochemical carbon dioxide (CO 2 ) conversion provides an attractive approach to synthesizing fuels and chemical feedstocks using renewable energy. On the path to deploying this technology, basic and applied scientific hurdles remain. Copper, as the only metal catalyst that is capable to produce C 2+ fuels from CO 2 reduction (CO 2 R), still faces challenges in the improvement of electrosynthesis pathways for highly selective fuel production. In this regard, mechanistically understanding CO 2 R on Cu-based electrocatalysts, particularly identifying the structure-function correlation, is crucial. Here, a broad view of the variable structural parameters and their complex interplay in CO 2 R catalysis on Cu was given, with the purpose of providing deep insights and guiding the future rational design of CO 2 R electrocatalysts. First, this Review described the progress and recent advances in the development of well-defined nanostructured catalysts and the mechanistic understanding on the influences from a particular structure of a catalyst, such as facet, defects, morphology, oxidation state, composition, and interface. Next, the in-situ dynamic restructuring of Cu was presented. The importance of operando characterization methods to understand the catalyst structure-sensitivity was also discussed. Finally, some perspectives on the future outlook for electrochemical CO 2 R were offered., (© 2022 Wiley-VCH GmbH.)

Purpose: To investigate the functional associations of intraretinal fluid (IRF) and subretinal fluid (SRF) volumes at baseline and after the loading dose as well as fluid change after the first injection with best-corrected visual acuity (BCVA) in patients with neovascular age-related macular degeneration (nAMD) who received an anti-VEGF treatment over 24 months., Design: Post hoc analysis of a phase III, randomized, multicenter trial in which ranibizumab was administered monthly or in a pro re nata regimen (HARBOR)., Participants: Study eyes of 1094 treatment-naïve patients with nAMD., Methods: IRF and SRF volumes were segmented automatically on monthly spectral domain OCT images. Fluid volumes and changes thereof were included as covariates into longitudinal mixed-effects models, which modeled BCVA trajectories., Main Outcome Measures: BCVA estimates corresponding to baseline, follow-up, and persistent IRF/SRF volumes after the loading dose; BCVA estimates of change in fluid volumes after the first injection; and marginal and conditional R 2 ., Results: Analysis of 22 494 volumetric scans revealed that foveal IRF consistently shows a negative correlation with BCVA at baseline and subsequent visits (-3.23 and -4.32 letters/100 nL, respectively). After the first injection, BCVA increased by +2.13 letters/100 nL decrease in foveal IRF. Persistent IRF was associated with lower baseline BCVA and less improvement. Foveal SRF correlated with better BCVA at baseline and subsequent visits (+6.52 and +1.42 letters/100 nL, respectively). After the first injection, SRF decrease was associated with significant vision gain (+5.88 letters/100 nL). Foveal fluid correlated more with BCVA than parafoveal IRF/SRF., Conclusions: Although IRF consistently correlates with decreased function and recovery throughout therapy, SRF is associated with a more pronounced functional improvement. Moreover, SRF resolution provides increased benefit. Fluid-function correlation represents an essential base for the development of personalized treatment regimens, optimizing functional outcomes, and reducing treatment burden., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Both acute cardiac rejection and acute idiopathic myocarditis may present with similar clinical signs, including heart failure. Morphologically, both may be defined as an inflammatory infiltrate (predominantly T lymphocytes) of the myocardium causing injury to adjacent myocytes. In both cases, the diffuse inflammatory infiltrate involves the endocardium, myocardium and pericardium. The morphological sequence of progression is similar. Acute rejection appears to be a good morphological model of myocarditis. From the acute rejection model it is known that myocardial damage must be diffuse and with considerable necrosis before heart failure occurs. It follows that patients suspected of having myocarditis and presenting in heart failure would be expected to have the equivalent of ‘moderate rejection’ and not a small focus of inflammatory cells on which the endomyocardial biopsy diagnosis of myocarditis is sometimes made. Such focal myocarditis may result in a clinical presentation of arrhythmias, but should not cause florid heart failure. If heart failure is present, other causes for it should be sought before a diagnosis of myocarditis is made. [ABSTRACT FROM PUBLISHER]

The extraglomerular mesangial cell field was studied by morphometric techniques in volume expanded and volume depleted rats. The volume density of the extraglomerular mesangial interstitium was found to be significantly different between the two conditions, 16.9±3.7% in volume depletion and 29.0±4.1% in volume expansion. No difference in the volume density of the peritubular interstitium could be detected under the same conditions. These findings are interpreted as indicating a specific sensitivity of the extraglomerular mesangial interstitium to changes in body fluid content, a phenomenon which may play a role in the mechanism of resetting the tubulo-glomerular feedback control. [ABSTRACT FROM AUTHOR]

Topological features extracted from X-ray CT data are used to distinguish different material lots: Grain Count (GC), Internal Boundary Surface Area (BSA) • Novel quantitative summarization of X-ray CT data for material microstructure. • Method uses new developments in scalar field topology and Morse complex theory. • Enables systematic tracking of process- and age-related changes in materials. • Algorithm involves structure recognition over multiple resolution levels. • Analysis reveals strong density-dependence of aging and performance trends. X-ray computed tomography (CT) is an established non-destructive tool for 3D imaging of multiphasic composites. Numerous applications of X-ray CT in medical diagnosis and materials characterization have been reported, many involving field-specific innovations in the imaging technology itself. Yet, quantitative summarization to link image features to properties of interest has been rare. We address this issue by employing state-of-the-art technics in scalar field topology for the summarization of X-ray CT images of an example biphasic system. By varying processing-parameters we create different microstructures, evolve them through accelerated thermal aging, CT-image them pre- and post-aged, and demonstrate the ability of our image summarization method to systematically track process- and age-related changes, which can often be very subtle. A novel aspect of the algorithm involves recognition over multiple resolution levels, which provides deeper insight into the pattern relationship between grain-like features and their neighbors. The method is general, adaptable to diverse image reconstruction methods and materials systems, and particularly useful in applications where practical constraints on the sample-size limits the reliable use of more complex models, e.g., convolutional neural networks. [ABSTRACT FROM AUTHOR]

Conjugated polymers (CPs) are unique in their synthetic challenges to tailor their chemical, electronic, and processing properties while identifying significant structure-to-property correlations. Over the past half century chemists have worked towards synthesizing more complex and solution processable conjugated polymers while approaching structural perfection. These efforts aim to maximize their beneficial properties such as high charge mobilities, impressive absorption and emission signals, as well as the ability to stabilize charges, among others. Yet, chemists have only scratched the surface of these characteristics, and new synthetic approaches continue to elevate the field of conjugated polymers. The processability of CPs is no longer solely dependent on adding solubilizing chains to the macromolecules, but can be achieved through polymerizing soluble derivatives that can undergo post-polymerization modification resulting in the desired CPs. New step-growth and chain-growth polymerization techniques have been discovered to provide control over polymerization of CPs to manipulate their molecular weight and molecular weight distribution, in addition to producing new "donor-acceptor" copolymers that have enhanced electronic and photophysical properties. Additionally, graphene nanoribbons can be synthesized with atomic precision along their edges to control their charge transport properties, and even their ability to create spins along their periphery for potential use in spintronics. New vapor-phase polymerization techniques have made it possible to create thin films of poorly soluble polymers without the need for toxic solvents, and recent breakthroughs in aryl-aryl couplings have eliminated the need for toxic and expensive reagents. Furthermore, strides have been made to bridge electrodes in organic devices with either small molecules or CPs in attempts of achieving single molecule devices, while chemists have also pursued expanding CPs into the second dimension in an effort to improve their charge carrier mobilities. In honor of Staudinger's 100th anniversary of identifying the field of polymer chemistry this article will outline how the synthetic evolution of conjugated polymers has resulted in the aforementioned properties, among others, and how these materials have opened the door for many state-of-the-art applications. [ABSTRACT FROM AUTHOR]

A new strategy to nanoengineer gold/fluorocarbon multilayer (ML) nanostructures is reported. We have investigated the morphological changes occurring at the metal–polymer interface in ML structures with varying volume fraction of gold (Au) and the kinetic growth aspect of the microscale properties of nano-sized Au in plasma polymer fluorocarbon (PPFC). Investigations were carried out at various temperatures and annealing times by means of grazing incidence small-angle and wide-angle X-ray scattering (GISAXS and GIWAXS). We have fabricated a series of MLs with varying volume fraction (0.12, 0.27, 0.38) of Au and bilayer periodicity in ML structure. They show an interesting granular structure consisting of nearly spherical nanoparticles within the polymer layer. The nanoparticle (NP) morphology changes due to the collective effects of NPs diffusion within ensembles in the in-plane vicinity and interlayer with increasing temperature. The in-plane NPs size distinctly increases with increasing temperature. The NPs become more spherical, thus reducing the surface energy. Linear growth of NPs with temperature and time shows diffusion-controlled growth of NPs in the ML structure. The structural stability of the multilayer is controlled by the volume ratio of the metal in polymer. At room temperature, UV-Vis shows a blue shift of the plasmon peak from 560 nm in ML Au/PTFE_1 to 437 nm in Au/PTFE_3. We have identified the fabrication and postdeposition annealing conditions to limit the local surface plasmon resonance (LSPR) shift from Δ λ L S P R = 180 nm (Au/PTFE_1) to Δ λ L S P R = 67 nm (Au/PTFE_3 ML)) and their optical response over a wide visible wavelength range. A variation in the dielectric constant of the polymer in presence of varying Au inclusion is found to be a possible factor affecting the LSPR frequency. Our findings may provide insights in nanoengineering of ML structure that can be useful to systematically control the growth of NPs in polymer matrix. [ABSTRACT FROM AUTHOR]