bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testosterone Is Not Required for The Maintenance of Muscle Mass in Fully Matured and Elderly Male Mice
Authors: Davidyan Arik , Baar Keith , Bodine Sue C 
Published: June 2021

Testosterone (T), the main androgenic hormone, is assumed to play an important role in the maintenance of skeletal muscle mass and function through its effects on satellite cell proliferation and differentiation, as well as its activation of pathways downstream of the IGF‐1 receptor and AKT. T depletion through chemical castration as a treatment for prostate cancer and the use of T to treat sarcopenia are both common practices in older humans, yet the majority of animal studies aimed at elucidating T's role in the maintenance of skeletal muscle mass are performed in young rodents under the age of 3 months. In addition, the role of T's activity in skeletal muscle health remains equivocal, with some studies showing circulating T to have great importance, while others suggest a limited or non‐significant role. Hence, the aim of this project was to characterize the phenotypic outcome of T depletion on skeletal muscle across lifespan and identify the contributing molecular pathways.To elucidate T's role on skeletal muscle throughout life, C57Bl/6 male mice were castrated at 4 different ages (1.5, 5, 12, or 24 months) and returned to normal cage activity for one month before muscle mass, protein synthesis and degradation, mTORC activity, and fiber cross sectional area were analyzed. Consistent with current literature, skeletal muscle mass reached a peak at 6 months before progressively declining (11.4% and 23.1% in the TA and gastrocnemius muscles, respectively) by 25‐months of age. In young animals, the removal of circulating T resulted in a decrease of the TA muscle mass (12.2% and 16.7% in the 1.5‐ and 5‐month old groups, respectively). Castration also slowed the growth of the gastrocnemius muscle with the 1.5‐ and 5‐month groups presenting muscles that are 9.4% and 11.6% smaller, respectively. Conversely, T depletion had no effect on muscle mass in the 12 months and 24 months groups. The decrease in cross sectional area in the absence of T in the young groups was similar to the decrease in muscle mass. Statistical analysis revealed a stronger interaction between age and treatment in the TA (P = 0.011) compared to the Gastrocnemius (P = 0.24). Together these data suggest that in skeletally immature animals, circulating T plays an important role in the regulation of muscle mass. In contrast, once muscle mass peaks and begins to decline naturally, circulating T no longer appears to affect muscle mass. Since T primarily affects skeletal maturation, it is essential that age appropriate animals are used when determining the role of T on skeletal muscle function. Specifically, studies on the anabolic effects of T need to use C57Bl/6 mice that are older than 6 months in order to translate to humans.Support or Funding InformationUC Davis Clinical and Translational Science CenterUC Davis Office of Graduate StudiesThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Lysophosphatidic acid signaling restores mislocalization of brush border proteins in MYO5B deficient mice
Authors: Kaji Izumi , Roland Joseph TE , Engevik Amy C , Goldstein Anna E , Dudeja Pradeep K , Goldenring James R 
Published: June 2021

Background & AimMyosin Vb (MYO5B) is an essential trafficking protein for membrane protein recycling in gastrointestinal (GI) epithelial cells and its mutation causes the congenital diarrheal disease, microvillus inclusion disease (MVID). Our group has reported that MYO5B loss results in a decrease in the brush border localization of nutrient transporters and enzymes, but CFTR expression is maintained, causing malabsorption and secretory diarrhea in MVID patients and MYO5B KO mice. Activation of lysophosphatidic acid (LPA) receptors (LPA2 and LPA5) can inhibit CFTR and activate NHE3 in the intestinal epithelium. This study tested whether LPA treatment reverses the functional expression of apical proteins in MYO5B knockout (KO) mice.MethodsAdult tamoxifen‐induced, intestine‐specific, MYOB KO mice (VilCreERT2;Myo5bflox/flox) and littermate control mice were treated with LPA (18:1 at 1 or 3 mg/kg/day) or vehicle, orally or intraperitoneally for 4 days after a single injection of tamoxifen (2 mg/mouse, i.p.). Apical transporter activities in jejunum and ileum were measured by an Üssing chamber system and the localization of apical proteins were evaluated immunostaining with whole‐slide imaging and digital image analysis.ResultsFollowing tamoxifen injection, F‐actin‐positive inclusions appeared in the upper small intestine of VilCreERT2;Myo5bflox/flox mice and the brush border localization of phospho‐ezrin, SGLT1, NHE3, DRA, PEPT1, alkaline phosphatase, and DPPIV were lost throughout the intestine. Treatment with LPA partially restored apical localization of phospho‐ezrin, SGLT1, NHE3, alkaline phosphatase, and DPPIV particularly in villus epithelial cells. Consistent with these observations, SGLT1‐dependent short‐circuit current (Isc) was 3 times higher in LPA (3 mg/kg)‐treated jejunum and ileum than that of vehicle‐treated VilCreERT2;Myo5bflox/flox mice. LPA dose‐dependently decreased CFTR‐dependent Isc in the steady state, but had no effect on CFTR dependence in carbachol‐ and forskolin‐stimulated Isc, which was increased by MYO5B loss.ConclusionsThese results suggest that LPA signaling may modulate a MYO5B‐independent trafficking mechanism for some brush border proteins in the small intestine, demonstrating a therapeutic potential for LPA in the treatment of MVID.Support or Funding InformationSupported by The Christine Volpe FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Acute Effect of a Ketone Monoester Supplement on Metabolic Control in Individuals with Obesity
Authors: Myette‐Côté Etienne , Caldwell Hannah , Clarke Kieran , Little Jonathan P. 
Published: June 2021

OBJECTIVESTo determine whether acute ingestion of ketone monoester (KE; (R)‐3‐hydroxybutyl (R)‐3‐hydroxybutyrate) impacts plasma glucose and free fatty acid levels during a standard 75‐gram oral glucose tolerance test (OGTT) in individuals with obesity.METHODSFifteen participants (age = 47±10 years) with a body mass index > 27 kg/m2 and a waist circumference >88 cm (female) or >102 cm (male) took part in a randomized crossover study. After an overnight fast, participants consumed a KE supplement (DeltaG®; 0.45 ml/kg body weight) or taste‐matched placebo 30 minutes before completing a 2‐hour OGTT with blood samples collected every 15–30 minutes. Participants and study personnel performing laboratory analyses were blinded to condition.RESULTSKE acutely raised blood D‐beta‐hydroxybutyrate to an average concentration of 2.4±1.2 mM within 30 minutes with levels remaining elevated throughout the entire OGTT. Compared to placebo, KE significantly decreased glucose area under the curve (AUC; −11%, P = 0.002), glucose incremental area under the curve (AUC; −23%, P = 0.008) and non‐esterified fatty acid (AUC; −21%, P = 0.009). Insulin and C‐peptide levels increased significantly over the 30 minutes period prior to the OGTT (P = 0.001 and 0.003 respectively) but no differences in total AUCs were observed as compared to placebo. No significant changes in lactate or triglycerides were observed.CONCLUSIONIn conclusion, a KE supplement that acutely increased D‐beta‐hydroxybutyrate levels attenuated the glycemic response to an OGTT in individuals with obesity. The reduction in glycemic response was accompanied by a reduction in non‐esterified fatty acids. These results suggest that ketone ester supplements could have therapeutic potential in the management and prevention of metabolic diseases.Support or Funding InformationThis project was funded by a Heart and Stroke Foundation of Canada Grant‐in‐Aid. JPL is supported by a Canadian Institutes of Health Research (CIHR) New Investigator Salary Award (MSH‐141980) and a Michael Smith Foundation for Health Research (MSFHR) Scholar Award (16890).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Suppression of Copper Metabolism MURR Domain 1 (COMMD1) Prevents Myocardial Ischemic Injury in Mice
Authors: Li Chen , Wang Tao , Meng Xia , Li Kui , Peng Hongxu , Kang Y. James 
Published: June 2021

Previous studies demonstrated that myocardial ischemia causes copper (Cu) reduction and Cu metabolism MURR domain 1 (COMMD1) protein accumulation in the ischemic infarct myocardium. Since COMMD1 is involved in the export of Cu from several types of cells, the present study was undertaken to test the hypothesis that the accumulation of COMMD1 is responsible for Cu reduction in the ischemic heart, thus worsening myocardial ischemic injury. We generated a tamoxifen‐induced, cardiac‐specific COMMD1 knockout mouse model (Myh6‐creER COMMD1flox/flox) to examine the alterations in Cu status and myocardial function in mice subjected to ischemic insult. Six‐week‐old, male Myh6‐creER COMMD1flox/flox and littermate control mice were injected intraperitoneally with tamoxifen for two weeks and subsequently subjected to left anterior descending (LAD) coronary artery ligation or sham operation. Cardiac function was determined by echocardiography on the seventh day after the operation. Histological examinations including hematoxylin and eosin stain (HE) and sirius red (SR) staining were performed to visualize the differences in infracted area, myocardial cell death, and fibrosis. The results showed that in the absence of COMMD1, ischemia‐induced reduction of Cu concentrations in the heart was alleviated, and the declines in both ejection fraction (EF) and fractional shortening (FS) were significantly suppressed. These changes were accompanied by the reduction in the infarct size, cell death, and fibrosis in the COMMD1‐deficient heart. These results thus suggest that COMMD1 plays a critical role in the pathogenesis of ischemic heart disease, and deletion of COMMD1 leads to suppression of myocardial ischemic injury.Support or Funding InformationScientific research funds of West China Hospital of Sichuan UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Iron Deficiency Induces Faster Sickling Kinetics in Transgenic Sickle Mice
Authors: Almashjary Majed , Brooks Steven , Dunkelberger Emily , Castro Oswaldo , Eaton William , Ackerman Hans 
Published: June 2021

Sickle cell disease (SCD) is caused by polymerization of deoxygenated hemoglobin‐S (HbS) within the red blood cell (RBC). The kinetics of hemoglobin polymerization are dependent on the intra‐erythrocytic concentration of HbS; specifically, the time from deoxygenation to polymerization is inversely related to HbS concentration30. We hypothesized that iron‐deficient erythropoiesis would produce RBCs with decreased intracellular Hb concentration and prolonged sickling times which would reduce the severity of SCD.To interrogate this hypothesis, we studied Townes mice that express humanized alpha globin, gamma globin, and either beta‐S (Townes‐SCD) or normal beta globin (Townes‐Control). RBCs from these Townes‐SCD mice have similar sickling kinetics to RBCs from human volunteers with SCD. To induce iron deficiency, we fed mice either an iron‐restricted diet (3 ppm iron) or iron‐normal diet (48 ppm iron) introduced at the time of weaning. After two months on the experimental diets, we measured RBC parameters using an Advia 2120 hematology analyzer and measured in vitro RBC sickling kinetics at 3% oxygen. Analysis of RBC parameters revealed that SCD mice on the iron‐restricted diet had lower hematocrit (32% vs 42.2%, P <0.0001), and there were trends toward lower hemoglobin, mean corpuscular volume, mean cell hemoglobin, and mean corpuscular hemoglobin concentration. Surprisingly, the in vitro sickling kinetic assay showed a significantly shortened time to 50% sickled in the Iron Restricted group (t50: 96.6 vs 136.5 min., p<0.0001).At this two‐month time point, this study provides insights into the hematologic changes that occur during the initial onset of iron deficiency anemia in Townes‐SCD mice. We were surprised to find that the rate of sickling increased in the iron‐restricted mice; however, at two months of iron deficient diet, we have yet to see a substantial fall in the MCHC, a major determinant of the sickling delay time. Furthermore, these mice may have experienced compensatory changes in the red cell that adversely affected sickling such as a decrease in hemoglobin F levels, or a shift in the Hb‐ O2 dissociation curve that favors releasing oxygen at lower partial pressures. To address these questions, we will investigate the hemoglobin composition and the oxygen dissociation curve at the remaining four‐ and six‐month timepoints. We aim to determine the intermediate and long‐term potential of iron deficiency to delay sickling and reduce the severity of organ damage in the context of SCD. This may inform a strategy of optimizing iron intake as a potential treatment for SCD.Support or Funding InformationSupport from NIAID Intramural funding and NIH Division of Veterinary ResourcesScholarship Award from the Saudi Arabian Cultural Mission (SACM)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chromatin Regulation of Tumor Responses to Immune Checkpoint Blockade
Authors: Shi Yang 
Published: June 2021

Recent studies have shown that chromatin regulators impact tumor cell immunogenicity and immune cell functions, thus impacting responses of tumors to the immune system. We have been using genetic tools to identify chromatin regulators that control tumor responses to the immune system, with the ultimate goal of identifying small molecules which would work together with checkpoint inhibitors to curtail cancers.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Connecting variation in the gut microbiome with susceptibility to vascular disease
Authors: Rey Federico 
Published: June 2021

The human distal gut harbors complex, diverse and dynamic microbial communities that are shaped by diet and host factors. These communities provide the host with a vast range of functions such as digestion of complex dietary components, production of vitamins, and maturation of the immune system. Dietary components such as complex plant polysaccharides (e.g., fiber) which are not absorbed in the proximal intestine reach the distal gut where they boost the growth of many intestinal bacteria, which in turn release metabolites that modulate host epigenetic programing and health. Because of the large variation in gut microbiota composition among individuals these microbial communities represent an important and differential factor that can modulate the nutritional value of food., with increased representation of butyrate‐producing microbes proposed as one of the potential mediators. I will illustrate approaches focusing on our recent studies aimed at defining the interrelationships between diet, gut microbiome variation, host epigenetic regulation and atherosclerosis.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Rare Bilateral Variation of the Posterior Intercostal Arteries
Authors: Sehi Daniel , Wallace Nolan , Daly Daniel , Martin John , Tan Yun 
Published: June 2021

BackgroundThe thoracic aorta usually gives off the 3rd to 11th pairs of posterior intercostal arteries (PIA) and 1 pair of subcostal arteries. The first two pairs of PIA typically originate via the highest intercostal artery via the costocervical trunk of the subclavian artery. The PIA supply blood to the intercostal spaces, spinal cord and spinal nerve roots.A bilateral branching anomaly in multiple PIA were observed in an 81 year‐old male cadaver during routine dissection. The thoracic aorta gave rise to asymmetrical common PIA trunks at different levels on both sides. Five common PIA trunks were found arising from the thoracic aorta and a descending branch of the right vertebral artery was also observed. Two common PIA trunks were observed on the right side branching from the thoracic aorta. The first common PIA trunk supplied the 4th through 7th intercostal spaces while the second common PIA supplied the 10th and 11th intercostal spaces. The 8th and 9th PIAs were direct branches off the thoracic aorta as normal. Three common PIA trunks were observed on the left side originating from the thoracic aorta. The first common trunk supplied the 3rd through 5th intercostal spaces. The second supplied the 6th and 7th intercostal spaces. The third trunk was observed to supply the 11th intercostal space as well as the subcostal region. Another vascular variation observed included a branch from the right vertebral artery that descended inferiorly and dorsally toward the first four ribs through the right costotransverse foramen. This descending branch of the vertebral artery gave off branches to supply the second, third, and fourth intercostal spaces on the right side. While common trunks of PIA have been reported to be highly prevalent, there are normally 1–2 common trunks found in a typical thorax. Thus, a cadaver that displays up to 5 common trunks of PIA in a singular thorax is a rare occurrence. Also anomalous is the presentation of a direct branch of the vertebral artery that courses dorsal to ribs while supplying several intercostal spaces. Understanding such anomalies has important clinical implications to interventional radiologists during thoracic cavity procedures as well as spine and thoracic surgeries.Support or Funding InformationCenter for Anatomical Science and Education, Department of Surgery, Saint Louis University School of MedicineThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Estimation of Stature from the Sternal Length in American White Population Using Linear Regression Equation: A Preliminary Cadaveric Study
Authors: Zavurov Gabriel , Malhis Camillia , Sims Taylor , Gupta Anupam , Walia Jasmit , Khalid Kanza , Ambati Sudhir , Lobo Stany 
Published: June 2021

ObjectiveTo estimate stature from the sternal length in American white population using linear regression equation.RationaleThere is an extensive study to correlate the stature from long bones and sternum in the literature in the Asian continent population. However these studies are sporadic for white and Hispanic American population. In this study we used regression analysis to address the reliability of sternal length for estimation of stature in White American population.Material and MethodsThis preliminary research project was conducted at Touro College of Osteopathic Medicine during the academic year 2018–2019 and 21 female and 14 male cadavers from the Department of Anatomy were used for the study. The research project was approved by the Institutional research committee. Cadavers with any noticeable physical anomaly affecting the stature were excluded from the study. The age and ethnicity of the cadavers were obtained by the departmental records. Stature was measured using a steel tape from Heel to Vertex. After the reflexion of the skin, the length of the sternum was measured from incisura angularis to mesoxiphoid point using a digital Vernier Caliper. Regression equations were derived using SPSS statistical software.ResultsRegression equation for female: Y= 135.039 + (0.146) X where Y= stature and X= length of the sternum. Regression equation for male: Y=141.603 + (0.17) X where Y= stature and X= length of the sternum. The SD was 13.88, 16.21 and P value was 0.18, 0.12 respectively for females and males.ConclusionBased on the calculations and the P value, we concluded that the length of the sternum is not a reliable factor for stature estimation for American white population. Forensic importance of these findings and its comparison with existing literature will be discussed.Support or Funding InformationNAThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Environmental Radio‐Toxins as Possible Radio‐biomarkers for Diseases of the CNS
Authors: Lykken Glenn I. , Momcilovic Berislav , Traudt Jon , Ward Thomas E. 
Published: June 2021

A hypothesis is presented identifying environmental radon (EnRn) progeny as a radio‐biomarker of use in studies of the brain and central nervous system (CNS) diseases such as Alzheimer's (AD) and Parkinson's (PD). The long‐lived environmental radon progeny, Pb‐210/Po‐210, in air and soil is a common radio‐biomarker in plants and animals. Hydrocarbon combustion in power plants and internal combustion engines produce copious quantities of ultrafine carbon particles that entrain heavy metals such as Pb‐210 found in air of the combustion process. The UFP's laden with Pb‐210 are readily taken up in the lungs and transported by the blood throughout the body including the brain and CNS. The more numerous small UFP's (<10nm) can be transferred across the blood‐brain and cellular barriers into cells where Pb‐210 is permanently deposited. The Pb+2 ions can mimic Ca+2 in brain and CNS cellular action potential systems providing a pathway into the cells and producing deleterious biochemical effects, additionally with radioactive Pb‐210 there are cellular radiation effects. Within the context of the proposed hypothesis data of diseased brain tissues containing Pb‐210/Po‐210 showed selective deposition in the brain proteins in AD and brain lipids in PD, with increased Po‐210 in MS colon tissueSupport or Funding InformationThis abstract is an end result of over 40 years of collaborative studies of environment radon progeny in humans. Collaboration among scientists from academia, government and private industry is noted.The support programs are too numerous to mention, but have been recognized in peer‐reviewed publications associated with the work.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.