The succession from aerobic and facultative anaerobic bacteria to obligate anaerobes in the infant gut along with the differences between the compositions of the mucosally adherent vs. luminal ...microbiota suggests that the gut microbes consume oxygen, which diffuses into the lumen from the intestinal tissue, maintaining the lumen in a deeply anaerobic state. Remarkably, measurements of luminal oxygen levels show nearly identical pO₂ (partial pressure of oxygen) profiles in conventional and germ-free mice, pointing to the existence of oxygen consumption mechanisms other than microbial respiration. In vitro experiments confirmed that the luminal contents of germ-free mice are able to chemically consume oxygen (e.g., via lipid oxidation reactions), although at rates significantly lower than those observed in the case of conventionally housed mice. For conventional mice, we also show that the taxonomic composition of the gut microbiota adherent to the gut mucosa and in the lumen throughout the length of the gut correlates with oxygen levels. At the same time, an increase in the biomass of the gut microbiota provides an explanation for the reduction of luminal oxygen in the distal vs. proximal gut. These results demonstrate how oxygen from the mammalian host is used by the gut microbiota, while both the microbes and the oxidative chemical reactions regulate luminal oxygen levels, shaping the composition of the microbial community throughout different regions of the gut.
Histone acetylation plays important roles in gene regulation, DNA replication, and the response to DNA damage, and it is frequently deregulated in tumors. We postulated that tumor cell histone ...acetylation levels are determined in part by changes in acetyl coenzyme A (acetyl-CoA) availability mediated by oncogenic metabolic reprogramming. Here, we demonstrate that acetyl-CoA is dynamically regulated by glucose availability in cancer cells and that the ratio of acetyl-CoA:coenzyme A within the nucleus modulates global histone acetylation levels. In vivo, expression of oncogenic Kras or Akt stimulates histone acetylation changes that precede tumor development. Furthermore, we show that Akt’s effects on histone acetylation are mediated through the metabolic enzyme ATP-citrate lyase and that pAkt(Ser473) levels correlate significantly with histone acetylation marks in human gliomas and prostate tumors. The data implicate acetyl-CoA metabolism as a key determinant of histone acetylation levels in cancer cells.
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•Acetyl-CoA:CoA ratio is glucose sensitive and regulates histone acetylation levels•Oncogenic AKT expression promotes elevated histone acetylation in vitro and in vivo•ACLY phosphorylation by AKT enables sustained histone acetylation in low glucose•Histone acetylation and pAKT(Ser473) levels correlate significantly in human tumors
Lee et al. show that metabolic reprogramming induced by an oncogene affects histone acetylation. Under conditions of low glucose, Akt activates the acetyl-CoA-generating enzyme ATP-citrate lyase, leading to alterations in histone acetylation marks in tumors. In vivo, oncogenic Kras or Akt expression stimulates histone acetylation changes preceding tumor development.
Abstract
Geoscience organizations shape the discipline. They influence attitudes and expectations, set standards, and provide benefits to their members. Today, racism and discrimination limit the ...participation of, and promote hostility towards, members of minoritized groups within these critical geoscience spaces. This is particularly harmful for Black, Indigenous, and other people of color in geoscience and is further exacerbated along other axes of marginalization, including disability status and gender identity. Here we present a twenty-point anti-racism plan that organizations can implement to build an inclusive, equitable and accessible geoscience community. Enacting it will combat racism, discrimination, and the harassment of all members.
Giant lobes of plasma extend approximate55degrees above and below the Galactic center, glowing in emission from gamma rays (the Fermi Bubbles) to microwaves and polarized radio waves. We use ...ultraviolet absorption-line spectra from the Hubble Space Telescope to constrain the velocity of the outflowing gas within these regions, targeting the quasar PDS 456 (scriptl b = 10degrees.4, +11degrees.2). This sightline passes through a clear biconical structure seen in hard X-ray and gamma-ray emission near the base of the northern Fermi Bubble. We report two high-velocity metal absorption components, at upsilon sub(LSR) = -235 and +250 km s super(-1), which cannot be explained by co-rotating gas in the Galactic disk or halo. Their velocities are suggestive of an origin on the front and back side of an expanding biconical outflow emanating from the Galactic center. We develop simple kinematic biconical outflow models that can explain the observed profiles with an outflow velocity of > ~900 km s super(-1) and a full opening angle of approximate110degrees (matching the X-ray bicone). This indicates Galactic center activity over the last approximate2.5-4.0 Myr, in line with age estimates of the Fermi Bubbles. The observations illustrate the use of UV spectroscopy to probe the properties of swept-up gas venting into the Fermi Bubbles.
The purpose of this study was to examine the impact of combined cardiorespiratory fitness and waist-to-height ratio in the form of a fit-fat index on incident diabetes risk. Additionally, the ...independent predictive performance of cardiorespiratory fitness, waist-to-height ratio, and body mass index also were estimated and compared.
This was a prospective cohort study of 10,381 men who had a normal electrocardiogram and no history of major chronic disease at baseline from 1979 to 2005. Random survival forest models and traditional Cox proportional hazards models were used to predict diabetes at 5-, 10-, and 15-year incidence horizons.
Overall, 4.8% of the participants developed diabetes. Receiver operating characteristic curve analyses for incidence risk demonstrated good discrimination using random survival forest models across fitness and fatness measures; Cox models were poor to fair. The differences between fitness and fatness measures across horizons were clinically negligible. Smoothed random survival forest estimates demonstrated the impact of each fitness and fatness measure on incident diabetes was intuitive and graded.
Although fitness and fatness measures showed a similar discriminative ability in predicting incident diabetes, unique to the study was the ability of the fit-fat index to demonstrate a better indication of incident risk when compared to fitness or fatness alone. A single index combining cardiorespiratory fitness and waist-to-height ratio may be more useful because it can indicate improvements in either or both of the measures.
Eustachian tube dysfunction (ETD) is a common medical issue, occurring in at least 1% of the adult population. Patients suffering from ET dysfunction typically present with complaints of hearing loss ...or sensation of pressure or plugged ear, which can lead to impaired quality of life. Over time ETD can result in conductive hearing loss or choleastatoma formation. Effective theraputic options for ET dysfunction are few. Eustachian tube balloon dilation is a novel surgical technique being used to treat ETD. The aim of our study is to objectively measure the success of Eustachian tube balloon dilation by comparing pre and post-operative middle ear pressures using tympanometric testing.
RA retrospective chart review was preformed on all patients who underwent balloon dilation of the Eustachian tube by authors NC or MB from 2010 to 2014. Pre and post-operative tympanograms were analyzed and categorized based on type (Type A, Type B, Type C). Success was defined by an improvement in tympanogram type: Type B or C to Type A, or Type B to type C. Pre and post-operative tympanograms were further analyzed using middle ear pressure values. Follow-up ranged from 3 to 15 months.
Twenty-five ears (18 patients) were included in the study. Overall 36% of ears had improvement in tympanogram type, and 32% had normalization of tympanogram post-operatively. The Jerger tympanogram type improved significantly following the procedure (p = 0.04). Patients also had statistically significant improvement in measured middle ear pressure post-operatively (P = 0.003).
The natural history of Eustachian tube dysfunction is poorly understood, and evidence for current treatments are limited. Eustachian tube balloon dilation is a safe procedure, and produces significant improvement in tympanogram values up to 15 months post-operatively. Further refinement of patient selection and standardization of technique is required to optimize the effect of this therapy. Longterm follow-up data will clarify the persistence of the effect.
Objective
There is limited evidence on the reliability of video‐based physical examinations. We aimed to evaluate the safety of a remote physician‐directed abdominal examination using tablet‐based ...video.
Methods
This was a prospective observational pilot study of patients >19 years old presenting with abdominal pain to an academic emergency department July 9, 2021–December 21, 2021. In addition to usual care, patients had a tablet video‐based telehealth history and examination by an emergency physician who was otherwise not involved in the visit. Both telehealth and in‐person clinicians were asked about the patient's need for abdominal imaging (yes/no). Thirty‐day chart review searched for subsequent ED visits, hospitalizations, and procedures. Our primary outcome was agreement between telehealth and in‐person clinicians on imaging need. Our secondary outcome was potentially missed imaging by the telehealth physicians leading to morbidity or mortality. We used descriptive and bivariate analyses to examine characteristics associated with disagreement on imaging needs.
Results
Fifty‐six patients were enrolled; the median age was 43 years (interquartile range: 27–59), 31 (55%) were female. The telehealth and in‐person clinicians agreed on the need for imaging in 42 (75%) of the patients (95% confidence interval CI: 62%–86%), with moderate agreement with Cohen's kappa ((k = 0.41, 95% CI: 0.15–0.67). For study patients who had a procedure within 24 hours of ED arrival (n = 3, 5.4%, 95% CI: 1.1%–14.9%) or within 30 days (n = 7, 12.5%, 95% CI: 5.2%–24.1%), neither telehealth physicians nor in‐person clinicians missed timely imaging.
Conclusion
In this pilot study, telehealth physicians and in‐person clinicians agreed on the need for imaging for the majority of patients with abdominal pain. Importantly, telehealth physicians did not miss the identification of imaging needs for patients requiring urgent or emergent surgery.
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