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At least 19 recordsLinked to original sources
PubMed1979

Conformation of Escherichia coli ribosomal protein L7/L12 in solution: hydrodynamic, spectroscopic, and conformation prediction studies.

The conformation of Escherichia coli ribosomal protein L7/L12 in solution has been studied using spectroscopic and hydrodynamic methods. Circular dichroism studies in the near-ultraviolet region reveal two bands at 262 and 268 nm originating from the tertiary conformational environment of the phenylalanyl residues. Additional characterization of the phenylalanine environment includes an intrinsic fluorescence emission spectrum arising from the phenylalanine fluorophores. Computer analysis of the far-ultraviolet circular dichroism spectrum suggests that L7/L12 contains as much as approximately 76% alpha helix. Hydrodynamic properties of L7/L12, measured with the purpose of providing relevant shape information, include the frictional coefficient ratio (1.84 +/- 0.03) and intrinsic viscosity (28 +/- 0.4 mL/g). The experimentally determined frictional coefficient (6.15 +/- 0.15 X 10(-8) has been compared with theoretical calculations of the same value employing two independent methods and assuming various dimensions for the L7/L12 dimer. Combining the experimental results from this work with those available from the literature, and using conformation predictive methods of Chou & Fasman [P. Y. Chou & G. D. Fasman (1974) Biochemistry 13, 211-222, 222-245] and of Maxfield & Scheraga (F. R. Maxfield & H. A. Scheraga (1976) Biochemistry 15, 5138-5153), several possible molecular models of the L7/L12 dimer have been constructed and critically examined. A model which is consistent with all of the available data is proposed.

Cell Fractionation↗
PubMed2026

Improving the reliability of polygenic risk score-based prediction for cardiovascular and renal complications across ancestries in type 2 diabetes using Mondrian Cross-Conformal Prediction.

Polygenic risk scores (PRS) developed in European populations often show reduced predictive performance in non-European populations, limiting their clinical utility. This lack of transferability across ancestries remains a major challenge in genomic medicine and raises concerns about health equity. We aimed to evaluate whether uncertainty-aware prediction, implemented through Mondrian Cross-Conformal Prediction, improves the performance and reliability of polygenic risk score-based predictions across ancestries for nephropathy, stroke, and myocardial infarction in individuals with type 2 diabetes in a multi-ethnic cohort. We leveraged Mondrian Cross-Conformal Prediction (MCCP), an uncertainty quantification framework, combined with logistic regression applied to a multi-polygenic risk score (multiPRS) to predict the risk of nephropathy, stroke, and myocardial infarction in individuals with type 2 diabetes. Two training frameworks were evaluated: one using 4,098 individuals with type 2 diabetes of European ancestry from the ADVANCE trial for training and 17,574 White British, 1,145 South Asian, and 749 African UK Biobank participants for testing; and another using the 17,574 White British UK Biobank participants for training and the South Asian and African participants for testing. Logistic regression provided robust baseline performance across populations. On top of this baseline, MCCP did not improve performance but added capabilities absent from probability-based stratification: for each individual, it issued a prediction together with an explicit confidence and credibility level; it allowed a tolerated error level to be set in advance and delivered prediction sets respecting it in the majority of settings; and it flagged individuals for whom no reliable prediction could be made. Applying MCCP to PRS-based prediction thus enables uncertainty-aware risk stratification and improves the reliability of risk prediction across ancestries, providing a more equitable framework for clinical use.

Female↗
PubMed1978

Conformational prediction and circular dichroism studies on ribosomal protein S4 from Escherichia coli.

The conformation of ribosomal protein S4 from Escherichia coli has been studied by circular dichroism (CD) and shown to possess unique conformation free in solution. The near ultraviolet spectrum suggests the existence of unique tertiary structural environment for the aromatic amino acid residues. The far ultraviolet spectrum gives an estimation of its secondary structure which is 32% alpha-helix and 14% beta-structure in reconstitution buffer at 25 degrees C. The conformation of S4 has been predicted from its sequence, and two models are presented here. An attempt is made to correlate these two molecular models with the available physicochemical data concerning the shape, conformation, and possible RNA binding site of protein S4.

Bacterial Proteins↗
PubMed1977

Conformational prediction for snake venom toxins and laser Raman scattering of a cardiotoxin from Taiwan cobra (Naja naja atra) venom.

Secondary structure regions in snake venom toxins were predicted using the prediction method of Chou and Fasman (Chou, P. Y., and Fasman, G. D. (1974), biochemistry 13,222) and an averaging scheme assuming structural homology in each type of toxins. The results indicate that, in general, snake toxins contain only some beta-sheet regions and beta bends. The content of secondary structures thus predicted does vary to some extent. The predicted results correlate well with conclusions from physicochemical studies. Interestingly, beta-bend regions predicted for the two types of neurotoxins, short-neurotoxin-type and long-neurotoxin-type, are primarily located in the middle of disulfide loops in spite of large differences in primary sequences. Comparisons between predicted results and the crystal structure of erabutoxin b determined at 2.75 A resolution suggest that the two types of neurotoxin are both sequencely and conformationally related while cardiotoxins could have an entirely different molecular topology. The Raman spectrum of a Taiwan cobra cardiotoxin indicates that the content of beta-pleated-sheet structure could be greater than that in neurotoxins.

Amino Acid Sequence↗
PubMed1977

Prediction and conformation by synthesis of two antigenic sites in human haemoglobin by extrapolation from the known antigenic structure of sperm-whale myoglobin.

The complete antigenic structure of sperm-whale myoglobin was previously determined in our laboratory. By structural analogy with myoglobin, two regions in human haemoglobin were predicted to comprise antigenic sites. One region was on the alpha-chain [alpha-(15-23)] and the other on the beta-chain [beta-(16-23)]. These two regions were synthesized, purified and characterized, and their immunochemistry was studied. Each peptide was able specifically to bind considerable amounts of haemoglobin antibodies. In a set of homologous proteins, barring any drastic conformational or electrostatic inductive effects exerted by the substitutions, and allowing for obstruction due to subunit interaction, the determination of the antigenic structure of one protein may serve as a useful starting model for the others.

Amino Acid Sequence↗
PubMed1979

The influence of cell surface receptor clustering on the thermodynamics of ligand binding and the kinetics of its dissociation.

We show that an equilibrium model for the clustering, by divalent ligand, of homogeneous plasma membrane-bound divalent receptors that do not change conformation predicts Scatchard plots with positive second derivatives (concave up). The result is thermodynamically indistinguishable from predictions based upon receptors that are heterogeneous for ligand, or that change conformation in a negatively cooperative way when ligand binds. A more general formulation of the theory, which allows application to dissociation kinetics, predicts that the dissociation of labeled ligand is accelerated in the presence of excess cold ligand and, moreover, that the accelerated dissociation has at least two components. The theory is briefly illustrated by fitting five different sets of data, at several temperatures for two different systems, with parameter values that are well within physically meaningful ranges. The model presented is the simplest and least ad hoc explanation thus far proposed as the basis for the kinetic phenomena, and raises the possibility that the numerous experiments in which such data are observed are primarily minifestations of cell surface clustering.

Insulin↗
PubMed1976

Centrally acting emetics. 10. Rigid dopamine congeners derived from octahydrobenzo[f]quinoline.

In a study of conformational requirements for certain dopaminergic agonist molecules, a series of conformationally predictable dopamine congeners related to cis- and trans-octahydrobenzo[f]quinoline was prepared. The complexity and equivocal character of the reduction of variously substituted 4-methyl-1,2,3,4,5,6-hexahydrobenzo[f]quinolines were demonstrated and studied. It was shown that several literature methods for reduction of these systems were in error regarding the stereochemical nature of the product(s). It has been concluded that geometrically specific and predictable reductions of these hexahydrobenzo[f]quinolines seem unlikely to attain, and a plausible rationalization for this conclusion has been proposed. Pharmacologic data on the compounds prepared are consistent with our earlier proposals of a biologically significant conformation of dopamine for emesis, the pecking syndrome in pigeons, and other physiological effects.

Animals↗
PubMed1977

Conformation studies of biologically active fragments of bovine growth hormone.

Conformations of bovine growth hormone active fragments were studied using far ultraviolet circular dichroism and intrinsic fluorescence emission spectroscopy. The small fragment, A-II (segment 96-133 of bovine growth hormone), undergoes a helix to random coil structural transition between pH 5 and 10 (pKa = 7.15). At pH9, the random coil state of A-II reverts back to helix conformation as ionic strength increases from 0.01 to 1. The A-II fluorophore, Tyr-110, is quenched by a neighboring carboxyl group of Glu-111, but is only slightly affected by the secondary structural transition. The large fragment, A-I (segments 1-95 and 134-191, connected via a disulfide linkage, of bovine growth hormone), is a rigidly structured molecule with a large amount of beta-sheet structure. Trp-86 of A-I was found to reside in an aromatic and hydrophobic amino acid cluster which is only destroyed by a high concentration of denaturant. Based on the primary sequence of bovine growth hormone, conformation predictions were made using the Chou-Fasman method ((1974) Biochemistry 13, 222). Bovine growth hormone helical structures are predicted to be in segments 10-34, 66-87, 111-127, and 186-191, beta-Sheet structures are predicted to be in segments 45-54, 90-94, 101-105, 136-142, 161-165, and 174-179. Tetrapeptides 37-40, 41-44, 60-63, 129-132, 146-149, and 156-159 were predicted to be beta turns. The prediction scheme confirmed several spectroscopic observations, but it did not completely explain the behavior of bovine growth hormone peptide fragments.

Amino Acid Sequence↗
PubMed2026

GiantHost: a domain-adaptive and uncertainty-aware framework for giant virus host prediction.

MOTIVATION: Nucleocytoplasmic large DNA viruses (NCLDVs) play crucial roles in global ecosystems. Although metagenomics has vastly accelerated the discovery of novel NCLDVs, predicting their hosts from fragmented contigs remains a critical bottleneck, with no dedicated end-to-end computational tools currently available. Addressing this gap requires overcoming three fundamental challenges: the extreme scarcity of labeled reference genomes, the severe domain shift between laboratory isolates and diverse environmental metagenomes, and the inability of traditional deterministic models to quantify prediction uncertainty-a crucial requirement for reliable ecological profiling where novel, divergent viruses are prevalent. RESULTS: We present GiantHost, the first NCLDV host prediction tool with domain adaptation and uncertainlty awareness. GiantHost employs a dual-tower neural network to integrate dense genome traits and sparse GVOG profiles, allowing better integration of heterogeneous features. To overcome label scarcity and domain shift, we leverage 1400 environmental viral genomes (GVMAGs) via semi-supervised multi-task learning and Domain Adversarial Neural Networks (DANN), effectively bridging the distributional gap between RefSeq and environmental data. Additionally, GiantHost incorporates Conformal Prediction (CP) to output statistically guaranteed prediction sets rather than overconfident single labels. Evaluated under rigorous genome-level cross-validation, GiantHost demonstrates robust predictive power. Applied to the Tara Ocean dataset, GiantHost successfully captured the vertical stratification of NCLDV hosts-revealing a depth-dependent decline of phytoplankton-infecting viruses and a relative enrichment of Amoebozoa-infecting viruses in the mesopelagic zone. AVAILABILITY: The source code of GiantHost is available via: https://github.com/FuchuanQu/GiantHost.

Giant Viruses↗
PubMed2026

Isolation and identification of a highly oncogenic subgroup J avian leukosis virus strain from Chinese black chickens.

Avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, is a highly contagious pathogen that induces myelocytomas, hemangiomas, and other neoplastic diseases in chickens. Recently, ALV-J infection in Chinese local chicken breeds has increased, with enhanced pathogenicity, posing a severe threat to the local poultry industry. In March 2024, a tumor outbreak occurred on a Chinese black chicken farm in Heze City, China, causing lethargy, emaciation, and tumorigenesis in the eyes and legs of affected chickens. Necropsy revealed extensive yellow-white neoplasms disseminated across the sternum, ribs, vertebrae, and visceral organs. Pathological examinations revealed multiple tumor types, including myelocytomas, hemangiomas, fibromas, and reticulosarcomas in the affected chickens. In this study, nine ALV-J isolates were isolated and designated HZ0319-1 to HZ0319-9. All isolates possessed an identical full-genome length of 7,687 bp and exhibited high nucleotide sequence similarity, ranging from 99.8% to 99.9%, suggesting that they were closely related variants from the same outbreak. Nucleotide sequence analysis identified unique deletions and mutations in the gag, pol, and gp85 genes, leading to predicted conformational changes in the P2, P10, and SU proteins. In addition, HZ0319 showed deletions in the r-TM region and a large 125-nt deletion in the E element of the 3' untranslated region, leaving only a short conserved fragment. The representative isolate HZ0319-1 showed stronger replication capacity than the reference strain NX0101 in DF-1 cells. In experimentally infected chicks, HZ0319-1 induced myelocytomas and hemangiomas and produced high viral load in multiple tissues. Notably, viral load analysis revealed that the liver showed the highest viral load at 1 day of age, whereas most other tissues reached peak viral load at 21 days of age, suggesting early hepatic replication followed by systemic dissemination. Furthermore, HZ0319-1infection significantly upregulated tumor-related host genes, including p53, c-Myc, c-Fos, and ZIC1, in tumor-associated tissues. These results demonstrate that the HZ0319-1 isolate has enhanced tumorigenicity and replication ability. Nucleotide mutations and deletions in both coding and non-coding regions of the viral genome may alter the viral tissue tropism and oncogenic potential. This study provides novel insights into the molecular characteristics and pathogenicity of ALV-J in local Chinese chickens, and provides a foundation for the prevention and eradication of ALV-J in the local poultry industry.

Avian leukosis virus subgroup J↗
PubMed2025

Multi-criteria decision making and its application to in silico discovery of vaccine candidates for Toxoplasma gondii.

Vaccine discovery against eukaryotic parasites is not trivial and few exist. Reverse vaccinology is an in silico vaccine discovery approach, designed to identify vaccine candidates from the thousands of protein sequences encoded by a target genome. Previously, we produced the Vacceed bioinformatics pipeline for identification of parasite membrane and excreted/secreted proteins that were likely be exposed to the hosts immune system. More recently, we improved upon machine learning as the final decision-making process to identify parasite proteins that induce a protective response in an animal model. Subsequently, we combined Vacceed with metrics on B and T cell epitope types to produce a new in silico discovery workflow. In this study we extend this in silico workflow to the developability of proteins as vaccines by the incorporation of metrics on the physicochemical properties of proteins. To demonstrate this process, every Toxoplasma gondii protein was ranked in its capacity to provide exposure to the immune system (Vacceed exposure score), presence of epitopes and solubility characteristics by several multicriteria decision making (MCDM) tools (such as TOPSIS, VIKOR and MABAC). A consensus rank was subsequently generated from the results of these tools using a variety of aggregate ranking methods. Levels of uncertainty in the aggregate protein rankings was assessed by conformal interval prediction in association with a machine learning model. Several of the top ranked proteins identified by this approach were novel, uncharacterized membrane transporters or proteins associated with RNA metabolism. In conclusion, MCDM automated the decision making using well known algorithms while conformal prediction intervals varied significantly across the 8000+ proteins of T. gondii. Highly ranked proteins (e.g. the top 100) typically generated low prediction intervals, providing high levels of confidence in their ranks.

Toxoplasma↗
PubMed1979

Acridine araphanes: a new class of probe molecules for biological systems.

The bis-acridine ring system forms the basis for new biophysical probes of novel stereochemistry. Spectral data indicate that certain alkylene bridged bis-9-aminoacridines have a parallel plane conformation of predictable interplane distance. The parallel plane conformation is independent of solvent and thus is different from nucleic acid systems. This stable conformation allows these compounds to be used as sensitive "rulers" for describing binding site geometry in cholinergic enzymes and in the delineation of the mechanism of allosteric control in acetylcholinesterase.

Acetylcholinesterase↗
PubMed1975

Analysis of the conformation of polypeptides : the combined use of energy computations and nuclear magnetic resonance studies.

This review surveys current approaches to the problem of determining the solution conformation of polypeptides. The basic principles of energy computations are described. The utility, problems, and limitations of various theoretical methods are summarized: conformational energy mapping, energy minimization, scanning of selected local conformations, statistical predictive schemes. The need for combining the calculations with experimental studies is pointed out. The information content of various physico-chemical methods is compared for this purpose. The analysis of nmr coupling constants is discussed in more detail. In combination with energy computations, it can furnish specific information on local aspects of the conformation. Examples of such combined studies on small peptides are summarized.

Angiotensin II↗
PubMed1975

Molecular conformation of bovine A1 basic protein, a coiling macromolecule in aqueous solution.

Aqueous solutions of bovine A1 protein, the major component of the basic protein fraction of myelin, were studied by small angle X-ray diffraction. The experimentally determined molecular weight, 17,800, is within 3% of that corresponding to the amino acid sequence, 18, 395, and the radius of gyration was found to be 46.3 A. No equivalent scattering particle of uniform electron density could be found which was compatible with all parameters evaluated from the diffraction measurements. The possibility of a coiled shape was therefore investigated using a worm-like chain model. This yielded a contour length of 439 A and a persistence length of 15.7 A. The radius of gyration of this model chain, 47.1 A, is in quite reasonable accord with the experimental value. The latter, after correction for excluded volume effects and finite chain length, yields for the characteristic ratio, ro2/nplp-2, 5.4. This may be compared with the value, 6.1, obtained after applying a correction for finite chain length to the viscosity data given by Tanford et al. for 12 proteins in 6 M guanidine hydrochloride and 0.1 M beta-mercaptoethanol. These two experimental values fall in the expected order, since the 15% glycine content of the A1 protein is considerably higher than the average for other proteins, which is about 8%. The corresponding values predicted from conformational calculations by Miller et al. for random copolymers of the L-alanine-glycine type are 5.9 (18% glycine) and 7.0 (8% glycine). We conclude that the A1 protein exists predominately, if not exclusively, as a random coil in aqueous solution.

Animals↗
PubMed2026

Insights from expert panels on the EU clinical evaluation consultation procedure.

BACKGROUND: The Clinical Evaluation Consultation Procedure (CECP) under the EU Medical Device Regulation aims to strengthen and harmonize the assessment of high-risk medical devices. This review summarizes early insights from expert panels to support improved clinical evaluation practices. RESEARCH DESIGN AND METHODS: This review analyses 34 expert panel opinions derived from 281 CECP submissions between April 2021 and December 2025. Statements from opinions were systematically extracted, de-duplicated, and grouped into thematic categories, with independent review and validation. The analysis focuses on common challenges found during the consultation procedure of the expert panels on the content of the clinical assessment in relation to clinical evidence, benefit-risk assessment, intended purpose alignment, and post-market clinical follow-up planning. RESULTS: Expert panel findings highlight recurrent issues in the sufficiency, consistency, and transparency of clinical evidence, underscoring the need for improved standardization and clearer guidance. CONCLUSIONS: Strengthening documentation quality and alignment across stakeholders will enhance the robustness, efficiency, and predictability of conformity assessments for high-risk medical devices.

Humans↗