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DNA Methylation Analysis Validates Organoids as a Viable Model for Studying Human Intestinal Aging.
Background & aimsThe epithelia of the intestine and colon turn over rapidly and are maintained by adult stem cells at the base of crypts. Although the small intestine and colon have distinct, well-characterized physiological functions, it remains unclear if there are fundamental regional differences in stem cell behavior or region-dependent degenerative changes during aging. Mesenchyme-free organoids provide useful tools for investigating intestinal stem cell biology in vitro and have started to be used for investigating age-related changes in stem cell function. However, it is unknown whether organoids maintain hallmarks of age in the absence of an aging niche. We tested whether stem cell-enriched organoids preserved the DNA methylation-based aging profiles associated with the tissues and crypts from which they were derived.MethodsTo address this, we used standard human methylation arrays and the human epigenetic clock as a biomarker of age to analyze in vitro-derived, 3-dimensional, stem cell-enriched intestinal organoids.ResultsWe found that human stem cell-enriched organoids maintained segmental differences in methylation patterns and that age, as measured by the epigenetic clock, also was maintained in vitro. Surprisingly, we found that stem cell-enriched organoids derived from the small intestine showed striking epigenetic age reduction relative to organoids derived from colon.ConclusionsOur data validate the use of organoids as a model for studying human intestinal aging and introduce methods that can be used when modeling aging or age-onset diseases in vitro
Mixed mode oscillations in a conceptual climate model
Much work has been done on relaxation oscillations and other simple
oscillators in conceptual climate models. However, the oscillatory patterns in
climate data are often more complicated than what can be described by such
mechanisms. This paper examines complex oscillatory behavior in climate data
through the lens of mixed-mode oscillations. As a case study, a conceptual
climate model with governing equations for global mean temperature, atmospheric
carbon, and oceanic carbon is analyzed. The nondimensionalized model is a
fast/slow system with one fast variable (corresponding to ice volume) and two
slow variables (corresponding to the two carbon stores). Geometric singular
perturbation theory is used to demonstrate the existence of a folded node
singularity. A parameter regime is found in which (singular) trajectories that
pass through the folded node are returned to the singular funnel in the
limiting case where . In this parameter regime, the model has a
stable periodic orbit of type for some . To our knowledge, it is the
first conceptual climate model demonstrated to have the capability to produce
an MMO pattern.Comment: 28 pages, 11 figure
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Imbibition dynamics of nano-particulate ink-jet drops on micro-porous media
Ink-jet printing of nano-metallic colloidal fluids on to
porous media such as coated papers has become a viable
method to produce conductive tracks for low-cost,
disposable printed electronic devices. However, the
formation of well-defined and functional tracks on an
absorbing surface is controlled by the drop imbibition
dynamics in addition to the well-studied post-impact drop
spreading behavior.
This study represents the first investigation of the realtime
imbibition of ink-jet deposited nano-Cu colloid drops
on to coated paper substrates. In addition, the same ink was
deposited on to a non-porous polymer surface as a control
substrate. By using high-speed video imaging to capture the
deposition of ink-jet drops, the time-scales of drop
spreading and imbibition were quantified and compared
with model predictions. The influences of the coating pore
size on the bulk absorption rate and nano-Cu particle
distribution have also been studied
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