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At least 73 records · Page 4Linked to original sources
PubMed2026

Mannheimia haemolytica strain-level diversity in cattle populations.

High-resolution genomic characterization is essential for understanding diversity, pathogenicity, and transmission dynamics of bacterial pathogens. Mannheimia haemolytica (Mh) is the most consequential bacterial agent associated with bovine respiratory disease (BRD) in cattle, as a leading cause of morbidity, mortality, and antimicrobial use. Historically, BRD pathogens, including Mh, have been studied using culture or PCR approaches that provided limited ability to characterize fine-scale genomic variation across communities. Here, we evaluated target-enriched (TE) shotgun sequencing, a culture-independent method capable of strain-level resolution within metagenomic data, for detecting and characterizing Mh in comparison with qPCR and 16S rRNA gene sequencing. Nasal swabs (10 individual and 2 composited DNA samples per pen) and environmental samples (three ropes hung on pen rails and three water bowl swabs per pen) were collected from four pens in each of five distinct cattle populations. DNA was extracted for TE sequencing to identify Mh at both species and genomic sequence variant (GSV) levels, and to characterize antimicrobial resistance genes across the bacterial communities. qPCR was performed to quantify Mh genome copies, and 16S rRNA gene sequencing was used to assess the broader respiratory microbiome. TE sequencing identified Mh in 100% of TE-tested samples and classified multiple GSVs in all but 3 of 121 samples. GSV profiles clustered within housing groups and varied across cattle populations, indicating structured strain-level diversity. In contrast, Mannheimia spp. were detected in only 47.7% of samples by 16S rRNA sequencing. These findings demonstrate that TE sequencing enables sensitive, strain-level characterization of Mh in cattle and environmental samples and reveals substantial within-population genomic diversity not captured by conventional approaches.IMPORTANCETarget-enriched shotgun sequencing enabled sensitive, strain-level detection of Mannheimia haemolytica (Mh), revealing multiple co-circulating genomic sequence variants (GSVs) within and among cattle groups. This demonstrates greater genetic variability of Mh populations in beef cattle than has been previously recognized. The clustering of GSVs within housing groups, together with the overlap between respiratory and environmental samples, is consistent with the hypothesis that contagious transmission contributes to Mh ecology. These results highlight the potential utility of composite nasal swab and environmental samples for future studies evaluating relationships between Mh genomic variation and disease risk.

Animals↗
PubMed1979

Progress report of the TUDAB project for automated cancer cell detection.

Two methods for high resolution cell image data acquisition are applied routinely. Cells are either scanned by a computer controlled fast scanning microscope photometer (SMP) or a TV-camera. The software system for digital image analysis was completely revised and implemented on the PR 330 minicomputer. The system contains codes for primary cell data acquisition, segmentation of cells, cell feature extraction and statistical cell analysis. With this system, SMP and TV scanned cell data bases of PAP stained cells in vaginal smears, grouped into several classes, have been built up. Each data base contains 34 primary features and 20 feature combinations for each cell. A linear discriminant analysis is applied routinely for cell classification. The present state of the system and its operation are described, cell features and classification results are shown, and future steps for a prescreening strategy are discussed.

Computers↗
PubMed1976

Investigations of nicandrenone--a withanolide-like aromatic plant steroid from Nicandra physaloides.

On the basis of IR, UV, ORD, NMR and high resoluted mass spectral data as well as chemical transformations, evidence for structure 1 of the D-homo-aromatic plant steroid nicandrenone from Nicandra physaloides (Solanaceae) was given. The sterochemistry of both epoxy lactol functions in this compound was established using intramolecular hydrogen bonding investigations. Biogenetical aspects are discussed.

Chemical Phenomena↗
PubMed1975

[The primary structure of a crystalline monoclonal immunoglobulin kappa-type L-chain, subgroup I (Bence-Jones protein Rei.); isolation and characterization of the tryptic peptides; the complete amino acid sequence of the protein; a contribution to the elucidation of the three-dimensional structure of antibodies, in particular their combining site (author's transl)].

Bence-Jones protein Rei. was isolated from the urine of a plasmacytoma patient by precipitation with ammonium sulfate and purified by ion exchange chromatography. The determination of the molecular weight showed that the protein was present in its monomeric form. The preparation cotained a minor fraction, which consisted of the dimer of the variable parts and was characterized by its ability to crystallize. X-ray data with a resolution on the atomic level could be achieved and allowed, together with the known primary structure, the construction of a three-dimensional model, which also gave an insight into the antigen binding site. It consists of the hypervariable regions, which form a pocket 15 A in diameter lying between the two monomers at the ends of the molecules. Sequence studies were performed with tryptic peptides which were purified by chromatographic procedures and aligned in homology to other kappa-chains. The protein belongs to subgroup I on the basis of its characteristic amino acid sequence and follows a highly regular pattern of amino acid exchanges. Its sequence is in agreement with an evolutionary origin of antibody variability.

Amino Acid Sequence↗
PubMed2026

How advances in chromosome conformation capture (3C) methods are reshaping our understanding of gene regulation in hematopoiesis.

The three-dimensional organization of the DNA within the nucleus plays a key role in regulating gene expression. Over the past two decades, advances in chromosome conformation capture (3C) technologies, in tandem with other methods, have shown that the genome forms a complex structure at multiple scales. Early studies identified large-scale structures such as chromosome territories, compartments and topologically associating domains (TADs). As the resolution of 3C techniques has improved, it has become possible to identify contacts between regulatory elements in detail and more recently, it has become possible to define intricate structures within cis-regulatory elements. In this chapter, we review the development of 3C-based methodologies and discuss the strengths and limitations of the different approaches. We examine how these technologies have refined our understanding of genome organization and gene regulation. Recent high-resolution studies reveal that chromatin architecture extends beyond classical domain structures to include nanoscale organization. Integration of 3C data with super-resolution imaging and molecular dynamics simulations supports a model in which genome folding is governed by the biophysical properties of chromatin.

Animals↗
PubMed2025

Spatial transcriptomics-aided localization for single-cell transcriptomics with STALocator.

Single-cell RNA-sequencing (scRNA-seq) techniques can measure gene expression at single-cell resolution but lack spatial information. Spatial transcriptomics (ST) techniques simultaneously provide gene expression data and spatial information. However, the data quality of the spatial resolution or gene coverage is still much lower than the quality of the single-cell transcriptomics data. To this end, we develop a ST-Aided Locator for single-cell transcriptomics (STALocator) to localize single cells to corresponding ST data. Applications on simulated data showed that STALocator performed better than other localization methods. When applied to the human brain and squamous cell carcinoma data, STALocator could robustly reconstruct the relative spatial organization of critical cell populations. Moreover, STALocator could enhance gene expression patterns for Slide-seqV2 data and predict genome-wide gene expression data for fluorescence in situ hybridization (FISH) and Xenium data, leading to the identification of more spatially variable genes and more biologically relevant Gene Ontology (GO) terms compared with the raw data. A record of this paper's transparent peer review process is included in the supplemental information.

Single-Cell Analysis↗
PubMed2025

Significance in scale space for Hi-C data.

MOTIVATION: Hi-C technology has been developed to profile genome-wide chromosome conformation. So far Hi-C data have been generated from a large compendium of different cell types and different tissue types. Among different chromatin conformation units, chromatin loops were found to play a key role in gene regulation across different cell types. While many different loop calling algorithms have been developed, most loop callers identified shared loops as opposed to cell-type-specific loops. RESULTS: We propose SSSHiC, a new loop calling algorithm based on significance in scale space, which can be used to understand data at different levels of resolution. By applying SSSHiC to neuronal and glial Hi-C data, we detected more loops that are potentially engaged in cell-type-specific gene regulation. Compared with other loop callers, such as Mustache, these loops were more frequently anchored to gene promoters of cellular marker genes and had better APA scores. Therefore, our results suggest that SSSHiC can effectively capture loops that contain more gene regulatory information. AVAILABILITY AND IMPLEMENTATION: The Hi-C data used in this study can be accessed through the PsychENCODE Knowledge Portal at https://www.synapse.org/#! Synapse: syn21760712. The code utilized for Curvature SSS cited in this study is available at https://github.com/jsmarron/MarronMatlabSoftware/blob/master/Matlab9/Matlab9Combined.zip. All custom code used in this research can be found in the GitHub repository: https://github.com/jerryliu01998/HiC. The code has also been submitted to Code Ocean with the doi: 10.24433/CO.1912913.v1.

Algorithms↗
PubMedDate not supplied

The effect of spatial separation of speech and noise sources on the optimal setting of the master hearing aid.

The sound fields in which hearing aid evaluations are performed with tests of speech discrimination are far from standardized. This investigation was concerned with the nature of the sound field in terms of separation of speech and noise sources as related to the optimal setting of a master hearing aid as indicated by listener performance scores on tests of speech discrimination in noise. Two sound fields were used in this investigation, one with speech and noise from the same source and another with speech and noise sources separated by 90 degrees and 45 degrees off the axis of the midsagittal plane of the listener. The repeatability of the optimal setting of the master hearing aid from one configuration to the other and the resolution available in each sound field, were of prime interest. The data indicated that the sound field configuration has no bearing on the optimal setting of the master hearing aid. The data did indicate that maximum resolution was available in the case of speech and noise from the same source.

Acoustic Stimulation↗
PubMedDate not supplied

Morphometry of the human lung: the state of the art after two decades.

This paper reviews the development of the methods for estimating morphometric parameters describing the human lung. The original work was done by light microscopy, but physiologically relevant data depend on studying the delicate structure of alveoli and capillaries by electron microscopy. Methodological improvements of recent years permitted this approach. This yielded estimates of alveolar surface which are by 80% larger than the original data; the reasons are explained by the gain in resolution. On the basis of these data, and by accounting for additional experimental information on the functional availability of gas exchanging surfaces, estimates of pulmonary diffusing capacity (DL) in the range of 90--190 ml O2 . min-1 . mmHg-1 are obtained, which compare reasonably well with physiological estimates of DL obtained under conditions of work.

Capillaries↗
PubMed2025

Genetic structuring and estimation of reproductive adults in Onchocerca volvulus: A genome-wide analysis across hosts and regions.

Genomic analysis of parasites can deepen our understanding of their transmission, population structure, and important biological characteristics. Onchocerciasis (river blindness), caused by the parasitic nematode Onchocerca volvulus, involves adult worms residing in subcutaneous nodules that produce larval-stage microfilariae (mf), which are routinely detected in the skin for diagnosis. Whole-genome studies of mf are limited; most analyses have focused on the mitochondrial genome. We conducted a genome-wide analysis with 94% median nuclear genome coverage, analyzing 171, 37, and 98 mf from 16, 3, and 5 individuals from Ghana, Liberia, and the Democratic Republic of Congo, respectively. These data were used to investigate population differentiation, estimate the number of reproductive adult worms, and analyze genetic variation across chromosomes. Population genetic analyses across hosts and countries showed that nuclear genome diversity can reveal fine-scale genetic structure, even between geographically close countries, providing more resolution than mitochondrial haplotype data. By reconstructing maternal and paternal sibships, we estimated the number of reproductively active adult filariae. Comparisons between adult worm estimates from genetic data and nodule observations showed that genetics-based estimates were higher or equal to observed worm counts in 8 out of 9 hosts for female worms and 7 out of 9 hosts for male worms. Our analysis also revealed lower-than-expected X chromosome diversity, consistent with neo-X chromosome fusions in filarial species. This study represents an important step in using nuclear genome data from mf to support onchocerciasis elimination efforts and in developing genetic tools that could inform mass drug administration programs.

Onchocerca volvulus↗
PubMed1978

The structure of oriented sphingomyelin bilayers.

X-ray diffraction from oriented bilayers of sphingomyelin gave up to 14 orders of diffraction of a lamellar repeat of 68.5 A on the merididan and up to eight reflections, including a strong reflection at 4.2 A, on the equator. The diffraction spacings did not change when the sphingomyelin bilayers were exposed to different humidities. A direct analysis of the low resolution X-ray data, using deconvolution is presented. A comparison of the Patterson functions of sphingomyelin with those of phosphatidylcholine and phosphatidylethanolamine suggests that the molecular structure of sphingomyelin in oriented bilayers resembles the structure of both phosphatidylcholine and phosphatidylethanolamine. Molecular model calculations for sphingomyelin bilayers have also been performed. Electron density profiles of sphingomyelin bilayers at resolution of about 6 A and about 2.5 A are presented. Our results indicate that the phosphorylcholine head group of sphingomyelin is in the plane of the membrane and at right angles to the hydrocarbon chains, the hydrocarbon chains are nearly parallel to each other, and there is only a limited, if any, interdigitation of the hydrocarbon chains of the adjacent sphingomyelin molecules in the bilayer.

Mathematics↗
PubMed2025

Nanoscale Epigenetic Profiling of Colorectal Cancer Cell-Derived Exosomes via Single-Vesicle Nanoscopy.

Exosomes play critical roles in cancer diagnosis and treatment as they carry molecular information that reflects the epigenetic state of their parent cells. For the first time, nanoscale epigenetic profiling of individual exosomes derived from colorectal cancer cell lines is demonstrated via photo-induced force microscopy (PiFM). Exosomes from three cell lines with distinct CpG island methylator phenotype (CIMP) status are analyzed at the single-vesicle level. The nano-IR method provides simultaneous high-resolution topographical and spectroscopic data, revealing detailed vibrational signatures that distinguish CIMP-high (HCT116 and HT29) exosomes from CIMP-negative (SW480) ones. Notably, exosomes from CIMP-high cells exhibit red-shifted amide I and nucleic acid region compared to those from CIMP-negative cells, a shift attributed to increased 5-methylcytosine (5mC) modifications, as verified by quantum chemical calculations. Furthermore, these measurements reveal heterogeneity among individual exosomes, suggesting the presence of distinct subpopulations with unique epigenetic profiles, demonstrating the importance of single-vesicle resolution to detect molecular variations that remain obscured in ensemble studies. These findings present the potential of PiFM-based single-vesicle analysis to identify epigenetic markers in exosomes, laying the groundwork for its application in refined cancer diagnostics and targeted therapeutic strategies.

Humans↗
PubMed2026

Development of Genome-Derived InDel Markers and Genetic Diversity Analysis of Caragana acanthophylla in Xinjiang, China.

Caragana acanthophylla Kom. is an ecologically important drought-tolerant shrub in Xinjiang, China, but species-specific molecular markers for germplasm characterization remain limited. We sampled 93 individuals from 11 localities representing the currently known distribution of C. acanthophylla in Xinjiang. Three individuals per locality (33 in total) were whole-genome resequenced, yielding 2,873,410 high-quality SNPs and 5,679,915 InDels. Genome-wide SNP-based PCA and genetic relationship analysis provided an independent high-resolution assessment of the 33 resequenced individuals. From 34 candidate primer pairs, eight polymorphic InDel markers with stable amplification and clear genotyping profiles were retained and applied to all 93 individuals. The SNP dataset revealed clear regional differentiation and finer locality-associated relationships. Analysis of the same 33 individuals with the eight InDel loci recovered part of this broad pattern, particularly the differentiation of the western YL materials, but showed lower fine-scale resolution. Across all 93 individuals, the InDel panel revealed moderate to low marker-level genetic diversity and detectable regional differentiation. AMOVA attributed 67.00% of the variation to differences among the 11 original sampling localities, while the five exploratory analytical groups showed a similar among-group component (68.37%). The Mantel correlation detected across all 93 individuals (r = 0.801, p < 0.001) disappeared after YL was excluded (r = -0.032, p = 0.724), indicating that the overall spatial signal was largely driven by the geographic separation of YL. These results support the eight-marker panel as a practical, low-cost tool for preliminary germplasm characterization and broader sample screening, while genome-wide SNP data provide substantially greater resolution for population-level inference.

Caragana acanthophylla↗
PubMed2026

3D Proteomics: Structural, Functional, Chemical and Biomarker Discovery Proteomics With LiP-MS.

Protein structural dynamics drive changes in protein function, making the capture of such dynamics essential for interrogating biological systems. Here we review limited proteolysis coupled to mass spectrometry (LiP-MS), a structural and chemical proteomics method that uses changes in susceptibility to protease cleavage to profile proteome-wide protein structural changes within complex biological samples. In the decade since its development, LiP-MS has become a broadly used structural proteomics method, with peptide-level resolution. It has identified drug targets, delineated altered cellular pathways in response to complex perturbations, revealed structural information on otherwise challenging protein targets, and demonstrated the new concept of structural biomarkers of disease. Because LiP-MS simultaneously probes numerous types of molecular events, such as molecular binding, changes in enzyme activity, chemical modifications, allosteric conformational changes, aggregation, and unfolding, it supports a new proteomics workflow which we term 3D proteomics. This workflow enables the detection of specific functional sites within proteins that are altered upon perturbation, thereby guiding the generation of molecular hypotheses. Further, by globally profiling structural in addition to protein abundance changes, LiP-MS has proven able to greatly increase the information content of functional proteomics screens. In sum, LiP-MS has supported the development of a novel conceptual framework for generating, visualizing, and interpreting structural proteomics data with peptide level resolution, thereby comprehensively probing biological systems. Here we survey the applications of LiP-MS, discuss methodological variants developed by us and others, and describe the use of this new type of omics readout for structural, functional, chemical, and biomarker discovery proteomics.

Proteomics↗
PubMed2025

Prediction of Australian wheat genotype by environment interactions and mega-environments.

Latent environmental effects of genotype by environment interactions could be predicted from observed environmental covariates. Predictions into the wider target population of environments revealed greater insights. Wheat is grown across a diverse range of environments in Australia with contrasting environmental constraints. Targeted breeding to optimise genotypes in target environments is hindered by large and ubiquitous genotype by environment interactions (GEI). Common GEI in multi-environment trial experiments, which sample the target population of environments, can be efficiently modelled using latent environmental effects from factor analytic mixed models. However, generalised prediction into the full target population of environments is difficult without a clear link to observed environmental covariates (ECs) that are defined from high-resolution weather and soil data. Here, we used a large wheat multi-environment trial dataset and demonstrated that latent environmental effects can be associated with and predicted from observed ECs. We found GEI-based environment classes could be defined by combinations of key ECs. Prediction of main and latent effects in a wider set of environments covering the full TPE across the Australian grain belt over 13&#xa0;years revealed the complex trends of environmental effects and GEI over regional scales demonstrating high year-to-year variability. Regional environment types often shifted year-to-year. Cross-validation of forward genomic prediction into untested year environments demonstrated that increased accuracy is possible if estimated genetic effects are also accurate and ECs of new environments are known. These findings may guide Australian wheat breeders to better target specifically adapted material to mega-environments defined by static GEI while also considering broad adaptability and non-static GEI resulting from year-to-year variability.

Triticum↗
PubMed1978

The effect of cholesterol on the structure of phosphatidylcholine bilayers.

The effect of cholesterol on the structure of phosphatidylcholine bilayer was investigated by X-ray diffraction methods. Electron density profiles at 5 A resolution along with chain tilt and chain packing parameters were obtained and compared for phosphatidylcholine/cholesterol bilayers and for pure phosphatidylcholine bilayers in both the gel and liquid crystalline states. The cholesterol in the bilayers was localized by noting the position of discrete elevations in the electron density profiles. Cholesterol can either increase or decrease the width of the bilayer depending on the physical state and chain length of the lipid before the introduction of cholesterol. For saturated phosphatidylcholines containing 12--16 carbons per chain, cholesterol increases the width of the bilayer as it removes the chain tilt from gel state lipids or increases the trans conformations of the chains for liquid crystalline lipids. However, cholesterol reduces the width of 18 carbon chain bilayers below the phase transition temperature as the long phospholipid chains must deform or kink to accomodate the significantly shorter cholesterol molecule. Although cholesterol has a marked effect on hydrocarbon chain organization, it was found that, within the resolution limits of the data, the phosphatidylcholine head group conformation is unchanged by the addition of cholesterol to the bilayer. The head group is oriented parallel to the plane of the bilayer for phosphatidylcholine in the gel and liquid crystalline states and this orientation is not changed by the addition of cholesterol.

Cholesterol↗
PubMed1977

Instrumentation trends in nuclear medicine.

Nuclear medicine instrumentation requires use of various configurations of photon detectors for the purpose of in vivo and in vitro measurements of flow and metabolism. Computed tomography has solved a previous limitation of an ambiguous volume of interest intrinsic to projection images. Selection of instruments involves first, a definition of the medical problem to be solved; then an evaluation of the following characteristics of the candidate instruments: sensitivity, spatial resolution, saturation performance, dead time, uniformity of resolution, uniformity of sensitivity, data processing capabilities, and cost. New developments include dynamic imaging in transverse section with either single photon or positron annihilation photons, and whole-body quantitative imaging of sequential changes in radiopharmaceutical concentration.

Evaluation Studies as Topic↗