1,223 research outputs found
Mutant DMPK 3′-UTR transcripts disrupt C2C12 myogenic differentiation by compromising MyoD
Myotonic dystrophy (DM) is caused by two similar noncoding repeat expansion mutations (DM1 and DM2). It is thought that both mutations produce pathogenic RNA molecules that accumulate in nuclear foci. The DM1 mutation is a CTG expansion in the 3′ untranslated region (3′-UTR) of dystrophia myotonica protein kinase (DMPK). In a cell culture model, mutant transcripts containing a (CUG)200 DMPK 3′-UTR disrupt C2C12 myoblast differentiation; a phenotype similar to what is observed in myoblast cultures derived from DM1 patient muscle. Here, we have used our cell culture model to investigate how the mutant 3′-UTR RNA disrupts differentiation. We show that MyoD protein levels are compromised in cells that express mutant DMPK 3′-UTR transcripts. MyoD, a transcription factor required for the differentiation of myoblasts during muscle regeneration, activates differentiation-specific genes by binding E-boxes. MyoD levels are significantly reduced in myoblasts expressing the mutant 3′-UTR RNA within the first 6 h under differentiation conditions. This reduction correlates with blunted E-box–mediated gene expression at time points that are critical for initiating differentiation. Importantly, restoring MyoD levels rescues the differentiation defect. We conclude that mutant DMPK 3′-UTR transcripts disrupt myoblast differentiation by reducing MyoD levels below a threshold required to activate the differentiation program
Naturally occurring sendai virus infection of athymic nude mice
Nude (nu/nu) mice, Balb/c derived, responded to a naturally occurring Sendai virus infection in a different manner than conventional mice. They developed a chronic debilitating disease and a persistent viral infection of the respiratory tract with intranuclear inclusion bodies in tracheal, bronchial and bronchiolar epithelial cells, laryngeal and tracheal glandular epithelium and in type I and II alveolar cells. The infection was identified by serologic and tissue culture studies, the mouse antibody production test and ultrastructural examination of pulmonary lesions. Phlebitis of pulmonary veins, suppurative rhinitis and otitis media accompanied the viral infection while some mice developed a secondary bronchopneumonia
Multiple myeloma cells Graphs and Figures inhibit adipogenesis, increase senescencerelated and inflammatory gene transcript expression, and alter metabolism in preadipocytes
Myeloma cells alter metabolism & induce senescence in adipocyte-lineage cells, suggesting that senescence-associated proteins are involved in multiple myeloma.https://knowledgeconnection.mainehealth.org/lambrew-retreat-2021/1032/thumbnail.jp
How the world's collective attention is being paid to a pandemic: COVID-19 related n-gram time series for 24 languages on Twitter
In confronting the global spread of the coronavirus disease COVID-19 pandemic
we must have coordinated medical, operational, and political responses. In all
efforts, data is crucial. Fundamentally, and in the possible absence of a
vaccine for 12 to 18 months, we need universal, well-documented testing for
both the presence of the disease as well as confirmed recovery through
serological tests for antibodies, and we need to track major socioeconomic
indices. But we also need auxiliary data of all kinds, including data related
to how populations are talking about the unfolding pandemic through news and
stories. To in part help on the social media side, we curate a set of 2000
day-scale time series of - and -grams across 24 languages on Twitter that
are most `important' for April 2020 with respect to April 2019. We determine
importance through our allotaxonometric instrument, rank-turbulence divergence.
We make some basic observations about some of the time series, including a
comparison to numbers of confirmed deaths due to COVID-19 over time. We broadly
observe across all languages a peak for the language-specific word for `virus'
in January followed by a decline through February and a recent surge through
April. The world's collective attention dropped away while the virus spread out
from China. We host the time series on Gitlab, updating them on a daily basis
while relevant. Our main intent is for other researchers to use these time
series to enhance whatever analyses that may be of use during the pandemic as
well as for retrospective investigations.Comment: 12 pages, 6 figures, 3 table
Tropical Herbivorous Phasmids, but Not Litter Snails, Alter Decomposition Rates By Modifying Litter Bacteria
Consumers can alter decomposition rates through both feces and selective feeding in many ecosystems, but these combined effects have seldom been examined in tropical ecosystems. Members of the detrital food web (litter-feeders or microbivores) should presumably have greater effects on decomposition than herbivores, members of the green food web. Using litterbag experiments within a field enclosure experiment, we determined the relative effects of common litter snails (Megalomastoma croceum) and herbivorous walking sticks (Lamponius portoricensis) on litter composition, decomposition rates, and microbes in a Puerto Rican rainforest, and whether consumer effects were altered by canopy cover presence. Although canopy presence did not alter consumers’ effects, focal organisms had unexpected influences on decomposition. Decomposition was not altered by litter snails, but herbivorous walking sticks reduced leaf decomposition by about 50% through reductions in high quality litter abundance and, consequently, lower bacterial richness and abundance. This relatively unexplored but potentially important link between tropical herbivores, detritus, and litter microbes in this forest demonstrates the need to consider autotrophic influences when examining rainforest ecosystem processes
Allotaxonometry and rank-turbulence divergence: A universal instrument for comparing complex systems
Complex systems often comprise many kinds of components which vary over many
orders of magnitude in size: Populations of cities in countries, individual and
corporate wealth in economies, species abundance in ecologies, word frequency
in natural language, and node degree in complex networks. Comparisons of
component size distributions for two complex systems---or a system with itself
at two different time points---generally employ information-theoretic
instruments, such as Jensen-Shannon divergence. We argue that these methods
lack transparency and adjustability, and should not be applied when component
probabilities are non-sensible or are problematic to estimate. Here, we
introduce `allotaxonometry' along with `rank-turbulence divergence', a tunable
instrument for comparing any two (Zipfian) ranked lists of components. We
analytically develop our rank-based divergence in a series of steps, and then
establish a rank-based allotaxonograph which pairs a map-like histogram for
rank-rank pairs with an ordered list of components according to divergence
contribution. We explore the performance of rank-turbulence divergence for a
series of distinct settings including: Language use on Twitter and in books,
species abundance, baby name popularity, market capitalization, performance in
sports, mortality causes, and job titles. We provide a series of supplementary
flipbooks which demonstrate the tunability and storytelling power of rank-based
allotaxonometry.Comment: 23 pages, 7 figures, 1 table; online appendices:
http://compstorylab.org/allotaxonometry
Decomposing the misery index: A dynamic approach
YesThe misery index (the unweighted sum of unemployment and inflation
rates) was probably the first attempt to develop a single statistic to measure the level
of a population’s economic malaise. In this letter, we develop a dynamic approach to
decompose the misery index using two basic relations of modern macroeconomics:
the expectations-augmented Phillips curve and Okun’s law. Our reformulation of the
misery index is closer in spirit to Okun’s idea. However, we are able to offer an improved
version of the index, mainly based on output and unemployment. Specifically,
this new Okun’s index measures the level of economic discomfort as a function of
three key factors: (1) the misery index in the previous period; (2) the output gap in
growth rate terms; and (3) cyclical unemployment. This dynamic approach differs
substantially from the standard one utilised to develop the misery index, and allow
us to obtain an index with five main interesting features: (1) it focuses on output,
unemployment and inflation; (2) it considers only objective variables; (3) it allows
a distinction
between short-run and long-run phenomena; (4) it places more
importance
on output and unemployment rather than inflation; and (5) it weights
recessions
more than expansions
- …