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At least 1,513 records · Page 84Linked to original sources
PubMed1997

MAP kinase in situ activation atlas during Drosophila embryogenesis.

Receptor tyrosine kinases (RTKs) and the signaling cascades that they trigger play central roles in diverse developmental processes. We describe the capacity to follow the active state of these signaling pathways in situ. This is achieved by monitoring, with a specific monoclonal antibody, the distribution of the active, dual phosphorylated form of MAP kinase (ERK). A dynamic pattern is observed during embryonic and larval phases of Drosophila development, which can be attributed, to a large extent, to the known RTKs. This specific detection has enabled us to determine the time of receptor activation, visualize gradients and boundaries of activation, and postulate the distribution of active ligands. Since the antibody was raised against the phosphorylated form of a conserved ERK peptide containing the TEY motif, this approach is applicable to a wide spectrum of multicellular organisms.

Animals↗
PubMed1978

Retained surgical swabs: possible causes for errors in x-ray detection and an atlas to assist recognition.

A swab or pack left in a patient may not be recognised on a radiograph. This will usually be due to poor observation, but errors may result from unfamiliarity with the pattern of the markers. In addition, some markers may be difficult to detect, though this usually applies only to swabs which are very small or to those produced by some continental manufacturers. It should also be realised that, in a very few hospitals, swabs which do not have an opaque marker may occasionally be used in theatre. All the X-ray detectable swabs provided by the major suppliers in the U.K. are demonstrated.

Contrast Media↗
PubMed2025

A comprehensive atlas of full-length Arabidopsis eccDNA populations identifies their genomic origins and epigenetic regulation.

Extrachromosomal circular DNA (eccDNA) has been described in several eukaryotic species and has been shown to impact phenomena as diverse as cancer and herbicide tolerance. EccDNA is thought to arise mainly through transposable element (TE) mobilization. Because studies based on short-read sequencing cannot efficiently identify full-length eccDNA forms generated from TEs, we employed the CIDER-Seq pipeline based on long-read sequencing, to obtain full-length eccDNAs from Arabidopsis. The generated eccDNA datasets identified centromeric/pericentromeric regions as hotspots of eccDNAs with several eccDNA molecules originating from Helitron and LTR TEs. To investigate the role of epigenetic marks on TE-derived eccDNA biogenesis, we studied Arabidopsis methylation mutants dcl3, rdr6, ros1, and ddm1. Contrasting the TE-suppression previously reported in the hypermethylated ros1 mutants, we identified activation of TEs in ros1, specifically of LTR/Gypsy TEs. An enrichment of LTR/Copia elements was identified in actively dividing calli and the shoot apical meristem (SAM). Uncharacterized "variable TEs" with high eccDNA and expression were identified in the SAM, including ATCOPIA58. Together, our study reveals the genomic origins of eccDNAs and delineates the link between epigenetic regulation, transposon mobilization, and eccDNA biogenesis.

Arabidopsis↗
PubMed2025

A metabolic atlas of the Klebsiella pneumoniae species complex reveals lineage-specific metabolism and capacity for intra-species co-operation.

The Klebsiella pneumoniae species complex inhabits a wide variety of hosts and environments, and is a major cause of antimicrobial resistant infections. Genomics has revealed the population comprises multiple species/sub-species and hundreds of distinct co-circulating sub-lineage (SLs) that are associated with distinct gene complements. A substantial fraction of the pan-genome is predicted to be involved in metabolic functions and hence these data are consistent with metabolic differentiation at the SL level. However, this has so far remained unsubstantiated because in the past it was not possible to explore metabolic variation at scale. Here, we used a combination of comparative genomics and high-throughput genome-scale metabolic modeling to systematically explore metabolic diversity across the K. pneumoniae species complex (n = 7,835 genomes). We simulated growth outcomes for each isolate using carbon, nitrogen, phosphorus, and sulfur sources under aerobic and anaerobic conditions (n = 1,278 conditions per isolate). We showed that the distributions of metabolic genes and growth capabilities are structured in the population, and confirmed that SLs exhibit unique metabolic profiles. In vitro co-culture experiments demonstrated reciprocal commensalistic cross-feeding between SLs, effectively extending the range of conditions supporting individual growth. We propose that these substrate specializations may promote the existence and persistence of co-circulating SLs by reducing nutrient competition and facilitating commensal interactions. Our findings have implications for understanding the eco-evolutionary dynamics of K. pneumoniae and for the design of novel strategies to prevent opportunistic infections caused by this World Health Organization priority antimicrobial resistant pathogen.

Klebsiella pneumoniae↗
PubMed2024

A genetic atlas for the butterflies of continental Canada and United States.

Multi-locus genetic data for phylogeographic studies is generally limited in geographic and taxonomic scope as most studies only examine a few related species. The strong adoption of DNA barcoding has generated large datasets of mtDNA COI sequences. This work examines the butterfly fauna of Canada and United States based on 13,236 COI barcode records derived from 619 species. It compiles i) geographic maps depicting the spatial distribution of haplotypes, ii) haplotype networks (minimum spanning trees), and iii) standard indices of genetic diversity such as nucleotide diversity (π), haplotype richness (H), and a measure of spatial genetic structure (GST). High intraspecific genetic diversity and marked spatial structure were observed in the northwestern and southern North America, as well as in proximity to mountain chains. While species generally displayed concordance between genetic diversity and spatial structure, some revealed incongruence between these two metrics. Interestingly, most species falling in this category shared their barcode sequences with one at least other species. Aside from revealing large-scale phylogeographic patterns and shedding light on the processes underlying these patterns, this work also exposed cases of potential synonymy and hybridization.

Animals↗
PubMed2026

Shared genetic basis and spatial cellular atlas of psoriasis and metabolic syndrome.

BACKGROUND: Psoriasis (PS) and metabolic syndrome (MetS) frequently co-occur. Characterizing their shared genetic architecture and spatially enriched cellular populations may clarify the context of their co-occurrence and generate hypotheses for functional validation. METHODS: We integrated genome-wide association study (GWAS) summary statistics for PS, MetS, and five related components with spatially resolved single-cell transcriptomic data. Global and local genetic correlations were assessed using linkage disequilibrium score regression, genetic covariance analysis, high-definition likelihood, and local analysis of variant association. A bivariate causal mixture model quantified polygenic overlap. Conditional/conjunctional false discovery rate and composite-null pleiotropy analyses identified shared susceptibility loci. Finally, gsMap evaluated trait-associated enrichment across annotated embryonic tissues at single-cell resolution. RESULTS: Genetic approaches identified significant genome-wide correlations and polygenic sharing between PS, MetS, and its components. Local and cross-trait analyses identified region-specific signals and cross-validated shared loci. gsMap revealed trait-specific tissue enrichment. PS showed the strongest enrichment in the epidermis (pCauchy = 1.0573 × 10  - ⁴), adipose tissue (pCauchy = 1.5366 × 10 - ⁴), and liver (pCauchy = 1.0167 × 10 - ³). Across MetS, FBG, HDL-C, hypertension, and TG, enriched regions mainly involved the liver, adipose tissue, and epidermis. WC enrichment was predominantly observed in adipose tissue (pCauchy = 1.7823 × 10 - ⁴), with no significant liver or epidermal enrichment. CONCLUSION: Integrating GWAS with single-cell transcriptomic and spatial information characterized shared genetic architecture between PS and MetS-related phenotypes and their spatial enrichment patterns. These findings provide a framework for generating testable hypotheses about comorbidity biology and guiding future functional and clinical validation.

Psoriasis↗
PubMedDate not supplied

Wrangling prescription drug benefits: a conversation with Express Scripts' Barrett Toan. Interview by Robert F. Atlas.

Express Scripts, one of the three largest U.S. pharmacy benefit management (PBM) firms, has had one chief executive officer since its founding in the late 1980s. As Barrett Toan prepares to retire (he will remain as nonexecutive chairman), his company and other PBMs have moved onto center stage. The recent surge in drug spending has spawned great interest in PBMs' role, as well as controversy over PBMs' business practices. Implementation of the new Medicare prescription drug benefit depends heavily upon the capabilities that PBMs offer. Toan discusses these matters, plus expectations for the future of his industry-particularly opportunities associated with electronic prescribing.

Humans↗
PubMed2004

Defining a molecular atlas of the hippocampus using DNA microarrays and high-throughput in situ hybridization.

The hippocampus consists of a series of cytoarchitecturally discrete subregions that can be distinguished from one another on the basis of morphology, connectivity, and electrophysiological properties. To understand the molecular underpinnings for these differences, DNA microarrays were used to find genes predicted to be enriched in subregions CA1, CA3, and the dentate gyrus, and >100 of these genes were subsequently analyzed using in situ hybridization to obtain cellular-level localization of their transcripts. The most striking commonality among the resulting patterns of gene expression is the extent to which cytoarchitectural boundaries within the hippocampus are respected, although the complexity of these patterns could not have been predicted on the basis of the microarray data alone. Among those genes with expression that can be characterized as "restricted" to neurons in one or more subregions of the hippocampus are a number of signal transduction molecules, transcription factors, calcium-binding proteins, and carbohydrate-modifying enzymes. These results suggest that important determinants of the unique identities of adult hippocampal neurons are differential signal transduction, regulation of gene expression, calcium homeostasis, and the maintenance of a unique extracellular milieu. Furthermore, the extremely high correlation between microarray data and in situ expression demonstrates the great utility of using DNA microarrays to genetically profile discrete brain regions.

Animals↗
PubMedDate not supplied

[Research protocol for the mortality atlas of the provincial capitals of Andalusia and Catalonia (AMCAC Project)].

The aim of this work is to make known the multicentric project AMCAC, whose objective is to describe the geographical distribution of mortality from all causes in census groups of the provincial capitals of Andalusia and Catalonia during 1992-2002 and 1994-2000 respectively, and to study the relationship between the sociodemographic characteristics of the census groups and mortality. This is an ecological study in which the analytical unit is the census group. The data correspond to 298,731 individuals (152,913 men and 145,818 women) who died during the study periods in the towns of Almeria, Barcelona, Cadiz, Cordoba, Girona, Granada, Huelva, Jaen, Lleida, Malaga, Seville and Tarragona during the study periods. The dependent variable is the number of deaths observed per census group. The independent variables are the percentage of unemployment, illiteracy and manual workers. Estimation of the moderated relative risk and the study of the associations among the sociodemographic characteristics of the census groups and the mortality will be done for each town and each sex using the Besag-York-Mollie model. Dissemination of the results will help to improve and broaden knowledge about the population's health, and will provide an important starting point to establish the influence of contextual variables on the health of urban populations.

Algorithms↗
PubMed2003

Atlas of the embryonic brain in the pygmy squid, Idiosepius paradoxus.

Gross structural changes and neuropil formation in the brain during development were described in Idiosepius paradoxus, a sepioid that we chose as a model cephalopod. The brain originates in 4 pairs of ectodermal placodes, which occur separately in the embryonic surface undergoing epiboly. In the final period of epiboly, neuroblasts internalize from the placodes and gather into 4 pairs of ganglionic masses. The ganglionic masses assemble into a ring-like cluster encircling the inner yolk and the foregut anlage, gradually integrated into the 4 domains of a massive brain, a subesophageal mass (SBM), a supraesophageal mass (SPM), and a pair of optic lobes. In the early brain, neuropil forms a framework composed of a longitudinal ladder lying in the SBM, and a transverse arch standing on the lateral sides of the SBM and crossing the SPM. Differentiation of brain lobes proceeds from ventral to dorsal along this framework; first the magnocellular lobes and the posterior pedal lobe appear first in the SBM, the other lobes in the SBM and the basal lobes follow in the proximal region of the SPM, and the accessory lobes develop last in the most dorsal zone of the SPM. In the hatchlings, the brain lobes show almost the same arrangement as in the adults, but the accessory lobes, particularly the vertical lobe, are much smaller than those in the adults. Comparison of the present results with those in the teuthoid and the octopod indicates that developmental sequences of the brain are highly conserved in the coleoid cephalopods.

Animals↗
PubMed1975

Scanning electron microscopy of the ventricular system in normal and hydrocephalic rabbits. Preliminary report and atlas.

The author used the scanning electron microscope to study the ependyma in six control rabbits and six rabbits made hydrocephalic by infusion of silicone oil into the cisterna magna. The ependymal lining of the third ventricle, head of the caudate nucleus, superior angle of the caudate, and atrium of the lateral ventricle was examined. In the hydrocephalic animals, clusters of cilia emanating from the ependyma over periventricular white matter become separated; the author believes this is secondary to ingrowth of new ependymal cell processes covered with microvilli. The addition of these cells to the ependymal surface permits ventricular dilatation without ependymal disruption and provides more surface containing microvilli, presumably capable of increased transventricular fluid transfer. No such changes occur over gray matter masses since their surfaces are not deformed by moderate ventricular dilatation. The morphological alterations in the ependyma that occur in moderate hydrocephalus do not appear to be simply manifestations of ependymal destruction but rather suggest a modification in its function from that of a surface capable of propelling cerebrospinal fluid to one capable of increased transfer of transventricular fluid. As hydrocephalus progresses, compensation may fail because of the relative decrease in microvilli so that the cell surface provides a less efficient mechanism for absorption.

Animals↗