What is the Limit Size of 2D Conjugated Extension on Central Units of Small Molecular Acceptors in Organic Solar Cells?

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.

Shell Modulation of Hollow Metal Sulfide Nanocomposite for Stable Potassium Storage at Room and High Temperature.

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.

Chromium Flavonoid Complexation in an Antioxidant Capacity Role.

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.

The role of optical coherence tomography angiography in moderate and advanced primary open-angle glaucoma.

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.

Effect of point mutation on structure-function correlation of hemoglobin variants, HbE and HbD Punjab.

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 ß 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 ß 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.

New Technologies for Outcome Measures in Glaucoma: Review by the European Vision Institute Special Interest Focus Group.

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.

MACUSTAR: Development and Clinical Validation of Functional, Structural, and Patient-Reported Endpoints in Intermediate Age-Related Macular Degeneration.

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.

Validation of the structure-function correlation report from the heidelberg edge perimeter and spectral-domain optical coherence tomography.

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.

Gamma crystallins of the human eye lens.

BACKGROUND: Protein crystallins co me in three types (α, ß 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.

Size matters to function: Brain volume correlates with intrinsic brain activity across healthy individuals.

A fundamental issue in neuroscience is to understand the structural substrates of neural activities. Intrinsic brain activity has been increasingly recognized as an important functional activity mode and is tightly linked with various cognitive functions. Structurally, cognitive functions have also shown a relation with brain volume/size. Therefore, an association between intrinsic brain activities and brain volume/size can be hypothesized, and brain volume/size may impact intrinsic brain activity in human brains. The present study aimed to explicitly investigate this brain structure-function relationship using two large independent cohorts of 176 and 236 young adults. Structural-MRI was performed to estimate the brain volume, and resting-state functional-MRI was applied to extract the amplitude of low-frequency fluctuations (ALFF), an imaging measure of intrinsic brain activity. Intriguingly, our results revealed a robust linear correlation between whole-brain size and ALFF. Moreover, specific brain lobes/regions, including the frontal lobe, the left middle frontal gyrus, anterior cingulate gyrus, Rolandic operculum, and insula, also showed a reliable, positive volume-ALFF correlation in the two cohorts. These findings offer direct, empirical evidence of a strong association between brain size/volume and intrinsic brain activity, as well as provide novel insight into the structural substrates of the intrinsic brain activity of the human brain.

G-quadruplexes in long non-coding RNAs and their interactions with proteins.

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.

An Overview on Mushroom Polysaccharides: Health-promoting Properties, Prebiotic and Gut Microbiota Modulation Effects and Structure-function Correlation.

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 ß-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.

Recent Progress in the Hesperetin Delivery Regimes: Significance of Pleiotropic Actions and Synergistic Anticancer Efficacy.

BACKGROUND: In the plant kingdom, flavonoids are widely distributed with multifunctional immunomodulatory actions. Hesperetin (HST) remains one of the well-studied compounds in this domain, initially perceived in citrus plants as an aglycone derivative of hesperidin (HDN). OBSERVATIONS: Natural origin, low in vivo toxicity, and pleiotropic functional essence are the foremost fascinations for HST use as an anticancer drug. However, low aqueous solubility accompanied with a prompt degradation by intestinal and hepatocellular enzymes impairs HST physiological absorption. MOTIVATION: Remedies attempted herein comprise the synthesis of derivatives and nanocarrier (NC)-mediated delivery. As the derivative synthesis aggravates the structural complexity, NC-driven HST delivery has emerged as a sustainable approach for its sustained release. Recent interest in HST has been due to its significant anticancer potential, characterized via inhibited cell division (proliferation), new blood vessel formation (angiogenesis), forceful occupation of neighboring cell's space (invasion), migration to erstwhile physiological locations (metastasis) and apoptotic induction. The sensitization of chemotherapeutic drugs (CDs) by HST is driven via stoichiometrically regulated synergistic actions. Purpose and Conclusion: This article sheds light on HST structure-function correlation and pleiotropic anticancer mechanisms, in unaided and NC-administered delivery in singular and with CDs synergy. The discussion could streamline the HST usefulness and long-term anticancer efficacy.

Structure-function correlation of retinal photoreceptors in PRPH2-associated central areolar choroidal dystrophy patients assessed by high-resolution scanning laser imaging and microperimetry.

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.

Structural insights into the molecular mechanisms of substrate recognition and hydrolysis by feruloyl esterase from Aspergillus sydowii.

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 (AsFaeE), 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 AsFaeE. AsFaeE exhibits a typical α/ß-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 AsFaeE 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 AsFaeE 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.

Prediction of Protein Function from Tertiary Structure of the Active Site in Heme Proteins by Convolutional Neural Network.

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.

Discernibility of the Interdigitation Zone (IZ), a Potential Optical Coherence Tomography (OCT) Biomarker for Visual Dysfunction in Aging.

PURPOSE: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Structure-Function Correlation and Dynamic Restructuring of Cu for Highly Efficient Electrochemical CO2 Conversion.

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 (CO2 R), still faces challenges in the improvement of electrosynthesis pathways for highly selective fuel production. In this regard, mechanistically understanding CO2 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 CO2 R catalysis on Cu was given, with the purpose of providing deep insights and guiding the future rational design of CO2 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 CO2 R were offered.

Characterization of the chimeric protein cUBC1 engineered by substituting the linker of E2-25K into UBC1 enzyme of Saccharomyces cerevisiae.

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.

Combining vascular and nerve fiber layer thickness measurements to model glaucomatous focal visual field loss.

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.