3 research outputs found
Evaluation of EPAS1 variants for association with bovine congestive heart failure [version 1; peer review: 2 approved]
Background: Bovine congestive heart failure (BCHF) has become increasingly prevalent in feedlot cattle in the Western Great Plains of North America. BCHF is an untreatable complex condition involving pulmonary hypertension that culminates in right ventricular failure and death. A protein variant of hypoxia-inducible factor 2 alpha (HIF2α, encoded by the endothelial PAS domain-containing protein 1 gene, EPAS1) was previously reported to be associated with pulmonary hypertension at altitudes exceeding 2,000 m. Our aim was to evaluate EPAS1 haplotypes for association with BCHF in feedlot cattle raised at moderate altitudes (1,200 m).
Methods: Paired samples of clinical cases and unaffected controls were collected at four feedlots in Nebraska and Wyoming. Each pair (n =102) was matched for source, pen, breed type, sex, arrival date, and management conditions. Cases were identified by animal caretakers, euthanized, and diagnosis was confirmed at necropsy. Cases were derived from 30 different ranch operations, with the largest source contributing 32. Animals were tested for eight EPAS1 haplotypes encoding 36 possible different diploid combinations.
Results: The common, ancestral EPAS1 haplotype encoding HIF2α with alanine (A) at position 606 and glycine (G) at position 610 was equally frequent in cases and controls (0.67). The EPAS1 variant haplotype reported to be associated with disease (encoding threonine (T) at position 606 and serine (S) at position 610) was not enriched in cases compared with controls (0.21 and 0.25, respectively). Frequencies of other EPAS1 haplotypes (e.g., encoding Q270, L362, or G671) were each less than 0.05 overall. McNemar’s test with 45 discordant pairs showed the linked T606/S610 variant was not associated with BCHF (OR = 0.73, CI 0.38 -1.4, p-value = 0.37).
Conclusions: HIF2α polypeptide variants were not significantly associated with BCHF in feedlot cattle at moderate altitudes. Thus, a wider search is needed to identify genetic risk factors underlying this disease
Evaluation of EPAS1 variants for association with bovine congestive heart failure [version 1; peer review: 2 approved]
Background: Bovine congestive heart failure (BCHF) has become increasingly prevalent in feedlot cattle in the Western Great Plains of North America. BCHF is an untreatable complex condition involving pulmonary hypertension that culminates in right ventricular failure and death. A protein variant of hypoxia-inducible factor 2 alpha (HIF2α, encoded by the endothelial PAS domain-containing protein 1 gene, EPAS1) was previously reported to be associated with pulmonary hypertension at altitudes exceeding 2,000 m. Our aim was to evaluate EPAS1 haplotypes for association with BCHF in feedlot cattle raised at moderate altitudes (1,200 m).
Methods: Paired samples of clinical cases and unaffected controls were collected at four feedlots in Nebraska and Wyoming. Each pair (n =102) was matched for source, pen, breed type, sex, arrival date, and management conditions. Cases were identified by animal caretakers, euthanized, and diagnosis was confirmed at necropsy. Cases were derived from 30 different ranch operations, with the largest source contributing 32. Animals were tested for eight EPAS1 haplotypes encoding 36 possible different diploid combinations.
Results: The common, ancestral EPAS1 haplotype encoding HIF2α with alanine (A) at position 606 and glycine (G) at position 610 was equally frequent in cases and controls (0.67). The EPAS1 variant haplotype reported to be associated with disease (encoding threonine (T) at position 606 and serine (S) at position 610) was not enriched in cases compared with controls (0.21 and 0.25, respectively). Frequencies of other EPAS1 haplotypes (e.g., encoding Q270, L362, or G671) were each less than 0.05 overall. McNemar’s test with 45 discordant pairs showed the linked T606/S610 variant was not associated with BCHF (OR = 0.73, CI 0.38 -1.4, p-value = 0.37).
Conclusions: HIF2α polypeptide variants were not significantly associated with BCHF in feedlot cattle at moderate altitudes. Thus, a wider search is needed to identify genetic risk factors underlying this disease
Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies
Flare frequency distributions represent a key approach to addressing one of
the largest problems in solar and stellar physics: determining the mechanism
that counter-intuitively heats coronae to temperatures that are orders of
magnitude hotter than the corresponding photospheres. It is widely accepted
that the magnetic field is responsible for the heating, but there are two
competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To
date, neither can be directly observed. Nanoflares are, by definition,
extremely small, but their aggregate energy release could represent a
substantial heating mechanism, presuming they are sufficiently abundant. One
way to test this presumption is via the flare frequency distribution, which
describes how often flares of various energies occur. If the slope of the power
law fitting the flare frequency distribution is above a critical threshold,
as established in prior literature, then there should be a
sufficient abundance of nanoflares to explain coronal heating. We performed
600 case studies of solar flares, made possible by an unprecedented number
of data analysts via three semesters of an undergraduate physics laboratory
course. This allowed us to include two crucial, but nontrivial, analysis
methods: pre-flare baseline subtraction and computation of the flare energy,
which requires determining flare start and stop times. We aggregated the
results of these analyses into a statistical study to determine that . This is below the critical threshold, suggesting that Alfv\'en
waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The
Astrophysical Journal on 2023-05-09, volume 948, page 7