Primary duodenal adenocarcinoma accounts for less than 0.5% of all gastrointestinal cancers. We report a case of duodenal adenocarcinoma with highly divergent growth patterns consisting of poorly differentiated adenocarcinoma and neuroendocrine carcinoma proven to arise as a single neoplasm of monoclonal origin, as demonstrated by microdissection-based mutational profiling. Multicomponent growth patterns, as seen in this case, can occasionally be encountered in gastrointestinal malignancies and have led to speculation about the pathogenesis. The methods used to clearly establish monoclonal origin based on the unique profiling of mutational damage can address fundamental issues related to tumor development and progression, while providing cogent clinical information. Our findings confirm the great potential for intestinal epithelial cells to differentiate along different histogenetic lines during tumor progression.
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http://dx.doi.org/10.5858/2003-127-861-PDCSDG | DOI Listing |
Sci Rep
December 2024
Department of Psychiatry and Behavioral Sciences and Weill Center for Neurosciences, University of California, San Francisco, CA, 94107, USA.
Telomere attrition is a hallmark of biological aging, contributing to cellular replicative senescence. However, few studies have examined the determinants of telomere attrition in vivo in humans. Mitochondrial Health Index (MHI), a composite marker integrating mitochondrial energy-transformation capacity and content, may be one important mediator of telomere attrition, as it could impact telomerase activity, a direct regulator of telomere maintenance.
View Article and Find Full Text PDFNat Commun
December 2024
Engineering Science and Mechanics, Penn State University, University Park, PA, USA.
Incipient ferroelectricity bridges traditional dielectrics and true ferroelectrics, enabling advanced electronic and memory devices. Firstly, we report incipient ferroelectricity in freestanding SrTiO nanomembranes integrated with monolayer MoS to create multifunctional devices, demonstrating stable ferroelectric order at low temperatures for cryogenic memory devices. Our observation includes ultra-fast polarization switching (~10 ns), low switching voltage (<6 V), over 10 years of nonvolatile retention, 100,000 endurance cycles, and 32 conductance states (5-bit memory) in SrTiO-gated MoS transistors at 15 K and up to 100 K.
View Article and Find Full Text PDFNat Commun
December 2024
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Growth differentiation factor 15, GDF15, and glucagon-like peptide-1 (GLP-1) analogues act through brainstem neurons that co-localise their receptors, GDNF-family receptor α-like (GFRAL) and GLP1R, to reduce food intake and body weight. However, their use as clinical treatments is partially hampered since both can also induce sickness-like behaviours, including aversion, that are mediated through a well-characterised pathway via the exterolateral parabrachial nucleus. Here, in mice, we describe a separate pathway downstream of GFRAL/GLP1R neurons that involves a distinct population of brain-derived neurotrophic factor (BDNF) cells in the medial nucleus of the tractus solitarius.
View Article and Find Full Text PDFEcol Lett
January 2025
U.S. Geological Survey, Fort Collins Science Center, Fort Collins, Colorado, USA.
Patterns of phytochemistry localisation in plant tissues are diverse within and across leaves. These spatial heterogeneities are important to the fitness of herbivores, but their effects on herbivore foraging and dietary experience remain elusive. We manipulated the spatial variance and clusteredness of a plant toxin in a synthetic diet landscape on which individual caterpillars fed.
View Article and Find Full Text PDFEcol Lett
January 2025
Rocky Mountain Biological Laboratory, Gothic, Colorado, USA.
It is unclear how environmental change influences standing genetic variation in wild populations. Here, we characterised environmental conditions that protect versus erode polymorphic chemical defences in Boechera stricta (Brassicaceae), a short-lived perennial wildflower. By manipulating drought and herbivory in a 4-year field experiment, we measured the effects of driver variation on vital rates of genotypes varying in defence chemistry and then assessed interacting driver effects on total fitness (estimated as each genotype's lineage growth rate, λ) using demographic models.
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