Investigating Skeletal Muscle Metabolic Adaptations underlying Aerobic Fitness Gains Following High Intensity Interval Training in a Rat Model of Pulmonary Arterial Hypertension

poster abstractRationale: In patients with pulmonary arterial hypertension (PAH) a shift from oxidative to a less efficient non-oxidative (glycolytic) metabolism in skeletal muscle is believed to contribute to the reduced exercise tolerance hallmark of the disease. As seen for other cardiopulmonary diseases, exercise training (ExT) may ameliorate this “glycolytic switch” in PAH and improve exercise capacity. Previous studies in this lab showed an improved metabolic profile of skeletal muscle in PAH rats following an ExT protocol of continuous running at moderate relative intensity, 60 minutes at 75% of maximal aerobic capacity (VO2Max). High intensity interval training (HIIT) has been shown in healthy individuals as well as in patients with cardiovascular disease to promote favorable cardiac and skeletal muscle adaptations and greater improvements in aerobic capacity versus customary continuous training. This study tests the hypothesis in a PAH rat model that HIIT will result in preserved aerobic capacity and a greater attenuation of skeletal muscle glycolytic shift than that observed with continuous moderate intensity exercise. Methods: Male Sprague-Dawley rats received either monocrotaline (MCT, 40 mg/kg, s.q.) to induce PAH (n= 8), or saline, for healthy controls (n=4). After 2 wks, with MCT-induced PAH wellestablished, 6 wks of treadmill HIIT was initiated for a subset of PAH animals (PAH-ExT, n= 6) and healthy controls (CON-ExT, n=2). The HIIT runs were alternated between 2 to 3 minutes of high intensity exercise (85% VO2max reserve) and active recovery intervals between 2 to 3 minutes (10 m/min, 0 incline) VO2max was assessed at baseline, and in pre-training and post-training via analysis of expired gases during incremental treadmill running. Preliminary results: MCT-induced decrement in VO2max was attenuated by HIIT. Abundance of membrane glucose transporter Glut-1, a marker of glycolytic metabolism, is currently being evaluated in soleus cryosections with immunofluorescent staining. Findings are being compared to historical data for PAH and healthy rats from a study protocol that differed only by training approach-continuous instead of HIIT

Investigating Skeletal Muscle Metabolic Adaptations underlying Aerobic Fitness Gains following High Intensity Interval Training in a Rat Model of Pulmonary Arterial Hypertension

poster abstractRationale: In patients with pulmonary arterial hypertension (PAH) a shift from oxidative to a less efficient non-oxidative (glycolytic) metabolism in skeletal muscle is believed to contribute to the reduced exercise tolerance hallmark of the disease. As seen for other cardiopulmonary diseases, exercise training (ExT) may ameliorate this “glycolytic switch” in PAH and improve exercise capacity. Previous studies in this lab showed an improved metabolic profile of skeletal muscle in PAH rats following an ExT protocol of continuous running at moderate relative intensity, 60 minutes at 75% of maximal aerobic capacity (VO2 Max). This study tests the hypothesis in a PAH rat model that HIIT will also result in preserved aerobic capacity and attenuation of skeletal muscle glycolytic shift. Methods: Male Sprague-Dawley rats received either monocrotaline (MCT, 40 mg/kg) to induce mild PAH (n= 14), or saline, for healthy controls (n=9). After 2 wks, a 6 wkprogram of treadmill HIIT was initiated for a subset of PAH (n= 8) and healthy controls (n=6). The 30 min HIIT sessions alternated between 2 minutes at 85% VO2 max and 3 minutes at ~30% VO2 max. VO2 max was assessed at baseline, and in pre-training and post-training via analysis of expired gases. Preliminary results: MCT-induced decrement in VO2 max was attenuated by HIIT (p0.05). Western blotting of soleus homogenates for cytochromes I-V of the electron transport chain (OXPHOS), and for PGC1α, a potent stimulus for mitochondrial biogenesis, is being performed at present to further investigate potential training-induced adaptations in skeletal muscle metabolis

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Exploring gastrointestinal variables affecting drug and formulation behavior: methodologies, challenges and opportunities

Various gastrointestinal (GI) factors affect drug and formulation behavior after oral administration, including GI transfer, motility, pH and GI fluid volume and composition. An in-depth understanding of these physiological and anatomical variables is critical for a continued progress in oral drug development. In this review, different methodologies (invasive versus non-invasive) to explore the impact of physiological variables on formulation behavior in the human GI tract are presented, revealing their strengths and limitations. The techniques mentioned allow for an improved understanding of the role of following GI variables: gastric emptying (magnetic resonance imaging (MRI), scintigraphy, acetaminophen absorption technique, ultrasonography, breath test, intraluminal sampling and telemetry), motility (MRI, small intestinal/colonic manometry and telemetry), GI volume changes (MRI and ultrasonography), temperature (telemetry) and intraluminal pH (intraluminal sampling and telemetry)

Beyond Unprecedented Episode 04: Helping Small Businesses Survive – and Thrive

“Everything Must Go.” “Permanently Closed.” “Space for Rent.” These signs of the time sum up the plight of many small businesses during the COVID-19 pandemic. While the federal government’s Payroll Protection Program and the Federal Reserve’s Main Street Lending Program helped businesses across the United States in the early months of the crisis, more than 100,000 of them have closed their doors forever, according to research by Yelp. In the fourth episode of “Beyond Unprecedented”: The Post-Pandemic Economy, host Eric Talley welcomes Columbia Law Professors Lynnise E. Pantin ’03 and Tim Wu to discuss the types of assistance state and municipal lawmakers and the federal government can or should provide to keep small businesses afloat and why they are optimistic about the future for entrepreneurs.https://scholarship.law.columbia.edu/beyond_unprecedented/1004/thumbnail.jp

Beyond Unprecedented Episode 04: Helping Small Businesses Survive – and Thrive

“Everything Must Go.” “Permanently Closed.” “Space for Rent.” These signs of the time sum up the plight of many small businesses during the COVID-19 pandemic. While the federal government’s Payroll Protection Program and the Federal Reserve’s Main Street Lending Program helped businesses across the United States in the early months of the crisis, more than 100,000 of them have closed their doors forever, according to research by Yelp. In the fourth episode of “Beyond Unprecedented”: The Post-Pandemic Economy, host Eric Talley welcomes Columbia Law Professors Lynnise E. Pantin ’03 and Tim Wu to discuss the types of assistance state and municipal lawmakers and the federal government can or should provide to keep small businesses afloat and why they are optimistic about the future for entrepreneurs.https://scholarship.law.columbia.edu/beyond_unprecedented/1004/thumbnail.jp

Novel concepts in the pathophysiology and treatment of functional dyspepsia

Emerging data increasingly point towards the duodenum as a key region underlying the pathophysiology of functional dyspepsia (FD), one of the most prevalent functional GI disorders. The duodenum plays a major role in the control and coordination of gastroduodenal function. Impaired duodenal mucosal integrity and low-grade inflammation have been associated with altered neuronal signalling and systemic immune activation, and these alterations may ultimately lead to dyspeptic symptoms. Likely luminal candidates inducing the duodenal barrier defect include acid, bile, the microbiota and food antigens although no causal association with symptoms has been convincingly demonstrated. Recognition of duodenal pathology in FD will hopefully lead to the discovery of new biomarkers and therapeutic targets, allowing biologically targeted rather than symptom-based therapy. In this review, we summarise the recent advances in the diagnosis and treatment of FD with a focus on the duodenum.status: publishe

Duodenal inflammation: an emerging target for functional dyspepsia?

Introduction: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders and is classified into postprandial distress and epigastric pain syndrome. Despite the recognition of duodenal inflammation as a potential trigger of symptoms, only limited anti-inflammatory therapies exist.Areas covered: This narrative review summarizes the recent advances in the pathophysiology and treatment of FD; it identifies potential therapeutic targets and gaps in the field. An electronic literature search was conducted in Pubmed up to 31st of December 2019.Expert opinion: There is compelling evidence for the role of duodenal inflammation and the eosinophil-mast cell axis in the pathogenesis of dyspeptic symptoms. Traditional prokinetic drugs and neuromodulators target gastric dysmotility and visceral hypersensitivity but are hampered by limited efficacy and side effects. Independent of acid suppression, the anti-inflammatory action of proton pump inhibitors, which remain the first-line therapy in FD, may also explain their therapeutic effect. Other existing and newly established anti-inflammatory drugs should be investigated while trials including probiotics and selective antibiotics should examine the host microbiome and immune activation. Targeted treatments for potential causes of duodenal pathology, such as impaired permeability and dysbiosis, are likely to emerge in the future.status: publishe

Deep water formation in the North Pacific and deglacial CO2 rise

This work was supported by: a NERC studentship to JR; a NERC small grant (NE/I017240/1) to AR, GF, and JR; a NOAA/UCAR Climate and Global Change Postdoctoral Fellowship Program, administered by the University Corporation for Atmospheric Research, to JR; a NERC fellowship (NE/C00876X/2) to GF; and a DFG grant.Deep water formation in the North Atlantic and Southern Ocean is widely thought to influence deglacial CO2 rise and climate change; here we suggest that deep water formation in the North Pacific may also play an important role. We present paired radiocarbon and boron isotope data from foraminifera from sediment core MD02‐2489 at 3640 m in the North East Pacific. These show a pronounced excursion during Heinrich Stadial 1, with benthic‐planktic radiocarbon offsets dropping to ~350 years, accompanied by a decrease in benthic δ11B. We suggest that this is driven by the onset of deep convection in the North Pacific, which mixes young shallow waters to depth, old deep waters to the surface, and low‐pH water from intermediate depths into the deep ocean. This deep water formation event was likely driven by an increase in surface salinity, due to subdued atmospheric/monsoonal freshwater flux during Heinrich Stadial 1. The ability of North Pacific Deep Water (NPDW) formation to explain the excursions seen in our data is demonstrated in a series of experiments with an intermediate complexity Earth system model. These experiments also show that breakdown of stratification in the North Pacific leads to a rapid ~30 ppm increase in atmospheric CO2, along with decreases in atmospheric δ13C and Δ14C, consistent with observations of the early deglaciation. Our inference of deep water formation is based mainly on results from a single sediment core, and our boron isotope data are unavoidably sparse in the key HS1 interval, so this hypothesis merits further testing. However, we note that there is independent support for breakdown of stratification in shallower waters during this period, including a minimum in δ15N, younging in intermediate water 14C, and regional warming. We also re‐evaluate deglacial changes in North Pacific productivity and carbonate preservation in light of our new data and suggest that the regional pulse of export production observed during the Bølling‐Allerød is promoted by relatively stratified conditions, with increased light availability and a shallow, potent nutricline. Overall, our work highlights the potential of NPDW formation to play a significant and hitherto unrealized role in deglacial climate change and CO2 rise.Publisher PDFPeer reviewe