bluuebunny/crossref_metadata_2025_split huggingface dataset:
2‐ 15N Glutamine tracer overestimate rates of Arginine and Citrulline synthesis in healthy adult men
Authors: Tomlinson Christopher , Rafii Mahroukh , Ball Ronald O. , Pencharz Paul 
Published: June 2021

Recent studies have documented transfer of labeled nitrogen from 2–15N glutamine (Gln) to citrulline (Cit) and arginine (Arg) in fasting human adults. Conversely, in neonates we have shown no synthesis of Arg from glutamate. Therefore, we performed a multitracer study with 2‐15N and 1‐13C Gln given enterally to 5 healthy men fed a standardized milkshake diet. There was no difference in plasma enrichments between the two Gln tracers. 1‐13C isomers of Cit and Arg were synthesized from 1‐13C Gln. Three isomers each of Cit and Arg were synthesized from the 2‐15N Gln tracer; 2‐15N, 5‐15N and 2,5 15N2. The enrichments of these isomers of Cit and Arg expressed as atom percent excess are shown in the table.
Enrichment of Arg and Cit isomers synthesized from 1‐13C and 2‐15N Gln

1–13C
2–15N
5–15N
2,5–15N

Cit (%)
1.41
2.61,2
4.02
0.8

Arg (%)
0.141
0.41
0.8
0.1

Significantly greater enrichment was found of both 5‐15N Arg and Cit compared to 2‐15N isomers2, indicating the amino N from Gln is mostly transferred to Arg and Cit by transamination. Similarly, the enrichment of the 1‐13C isomers was significantly less than the 2‐15N isomers 1 suggesting rapid formation of α‐ketoglutarate and recycling of the nitrogen label. Our results show Gln is acting primarily as a nitrogen donor for Arg synthesis and studies using 15N label overestimate Arg synthesis rates.Grant Funding Source: CIHR
Effect of rapamycin administration in humans on the skeletal muscle protein anabolic response to essential amino acid ingestion
Authors: Dickinson Jared M , Drummond Micah J , Fry Christopher S , Glynn Erin L , Gundermann David M , Dhanani Shaheen , Volpi Elena , Rasmussen Blake B 
Published: June 2021

Nutrient ingestion, in the form of essential amino acids (EAA), has been shown to concomitantly stimulate mTORC1 signaling and muscle protein synthesis (MPS) in humans. The goal of this study was to determine whether mTORC1 activation is required for the stimulation of MPS following the ingestion of EAA in humans. Assessment of mTORC1 signaling proteins were performed on muscle biopsies from the vastus lateralis of young (22±3 yr) individuals who were administered a single oral dose of a potent mTORC1 inhibitor (rapamycin) prior to ingesting 10 g of EAA. Preliminary analyses show little or no change in the phosphorylation status of mTORC1 and key downstream effectors, S6K1 and 4E‐BP1, from basal through 1 and 2 hours post EAA ingestion (P>0.05). In contrast, ingestion of 10 g of EAA in control subjects substantially increased phosphorylation of mTORC1‐associated proteins and MPS (P<0.05). These preliminary data suggest that administration of rapamycin attenuates the mTORC1 signaling response to EAA ingestion in human skeletal muscle and, therefore, the activation of mTORC1 may be necessary to fully stimulate MPS following ingestion of EAA.Funding: NIH/NIAMS R01 AR049877 and NIA P30AG024832
A pilot study evaluating the feasibility of a summer gardening program to prevent summer weight gain in overweight adolescents
Authors: Jacquart Sarah Rose , Schoeller Dale A , Adams Alexandra K , Larson Nathan , Dennis Samuel F , LaRowe Tara L , Carrel Aaron L 
Published: June 2021

BackgroundObesity in children is a growing problem in the US. Recent data shows that children experience greater weight gain during summer months than the school year, with overweight children experiencing the greatest weight gain.MethodsThe feasibility of an 8‐week summer gardening pilot program for overweight middle school children (11–14 years) to increase physical activity and fruit and vegetable (FV) consumption was evaluated. Six subjects were recruited to participate in 3 hours of gardening activities 5 days/week. Weight, energy expenditure (EE), and FV intake were measured.ResultsProgram acceptance was evaluated using qualitative surveys and interviews. Mean weight change was −0.4 kg. Four subjects lost weight and 2 lost over 2.5 kg. Surprisingly, EE decreased. The study size was insufficient to detect significant changes; however, testing the acceptability of this type of program was essential. Qualitative data showed increased willingness to try new foods, liking at least one new food and a positive response to the program. Important logistic lessons learned were the importance of hiring a phlebotomist experienced in drawing blood from overweight children and the necessity of alternative activities to do on hot days. Future work is necessary to evaluate the effect of a larger gardening program on improving health outcomes. This research was supported by the Robert Woods Johnson Foundation.
The DIALBEST Type 2 diabetes peer counseling intervention: Process evaluation
Authors: Cruz Robert , Segura Sofia , Damio Grace , Perez‐Escamilla Rafael 
Published: June 2021

These analyses include 60 participants that have completed the 12 month DIALBEST intervention that includes 17 home‐based peer counseling (PC) educational sessions in the topics of nutrition, diabetes and medication management. There were 930 PC contacts with patients with an average duration of 88 minutes per contact. The majority of sessions focused on nutrition (370) followed by diabetes complications (159). Participants evaluated the diabetes complications and food label sessions as very good/excellent (90%), the diabetes and medication management information as very good/excellent (88%), the portion size sessions as very good/excellent (85%), and the physical activity intervention as very good/excellent (83%). When asked about lifestyle changes, patients reported: eating out less (87%), eating less fast food (83%), planning their meals more (77%), being more physically active, routinely checking their feet (73%), eating lower fat foods and using food labels more (71%), as a result of their participation in DIALBEST. Funded by The Connecticut Center for Eliminating Health Disparities among Latinos (NIH‐NCMHD grant # P20MD001765).Grant Funding Source: Nutrion (ASN)
Early detection of the acute phase response in sepsis by identification of small molecule metabolites in breath and biofluids
Authors: Butz Daniel E , Cook Mark E , Porter Warren P , Assadi‐Porter Fariba 
Published: June 2021

The systemic inflammatory response associated with sepsis and septic shock causes significant morbidity and mortality in the critically ill, and early detection is critical to desirable outcomes. Septic shock is currently diagnosed using criteria such as body temperature and hypotension.This study assessed the acute phase response to an infectious insult using breath 13CO2/12CO2 ratios (delta value) combined with metabolomic biomarker fingerprinting in serum.Breath delta values drop 2–4 hours after endotoxin injection, whereas there is no breath response to dexamethasone or saline injected controls. In rat fecal peritonitis, the breath carbon delta value drops about 6 hours after injection while hypotension does not occur until 14 to 18 hours. Fingerprinting of small molecules in plasma by NMR spectroscopy indicates that concentrations of lactic acid, glucose, 2‐hydroxy‐butyrate, 3‐hydroxy‐butyrate, citrate, acetate, and ketogenic amino acids are increased. Similar metabolite profiles are exaggerated in plasma from ICU patients diagnosed with septic shock.These data indicate that metabolic perturbations are evident at a very early stage of the acute phase response, and in the peritonitis model up to 12 hours prior to onset of septic shock. These technologies can provide an early warning for sepsis and may be used as a powerful diagnostic tool.Supported by WARF and the Wisconsin Institute for Discovery.
Inhibition Of Transmethylation (TM) Leads To Histone Modifications And Plays A Critical Role In The Epigenetic Regulation Of IL‐2 Gene Expression In Primary Human CD4+ T Lymphocytes
Authors: Patil Madhuvanti , Ghare Smita , Gobejishvili Leila , Joshi‐Barve Swati , McClain Craig J , Barve Shirish 
Published: June 2021

IL‐2 is a critical lymphokine that exerts a wide spectrum of regulatory effects on the immune system. Recent work done in our laboratory has demonstrated that S‐adenosylmethionine (SAM) dependent transmethylation (TM) is essential for the function of CD4+ T lymphocytes including IL‐2 expression. SAM dependent TM impacts epigenetic changes involving histone modifications which play a key role in altering chromatin structure and transcriptional activity. The TM pathway can be significantly inhibited by the SAM metabolite S‐adenosylhomocysteine (SAH). Accordingly, the present work was carried out to examine the effect of decreased TM due to increased cellular SAH levels on IL‐2 gene expression in primary human CD4+ T cells.Decreased SAM‐dependent methylation due to an increase in cellular SAH levels was achieved by treating the cells with an SAHH inhibitor, 3‐deazaadenosine (DZA). Examination of histone modifications occurring due to decreased SAM‐dependent methylation showed a decrease in the acetylated state of histone H3 at the IL‐2 proximal promoter region which is associated with the induction of gene transcription and expression. These data strongly support the notion that histone H3 acetylation is a critical epigenetic modification that regulates IL‐2 gene expression in primary human CD4+ T cells.
Angiotensin II‐Induced Vasoconstriction in Skeletal Muscle: Effects of Aging and TNF‐α
Authors: Behnke Bradley Jon , Dominguez James M , Park Yoonjung , Delp Michael D 
Published: June 2021

There is increasing evidence that oxidative stress and vascular inflammation contribute to old‐age associated vascular dysfunction. With advancing age there are elevated levels of tumor necrosis factor (TNF)‐α, which, via endothelial vasodilator impairment, may exacerbate the vasoconstrictor responses of angiotensin (ANG)‐II.PurposeTo determine whether the proinflammatory cytokine TNF‐α contributes to alterations in ANG II‐mediated vasoconstriction with aging.MethodsPegylated soluble human TNF type 1 receptor (PEG sTNF‐RI; Amgen Inc) was administered (1 mg/kg, s.c., 3x/wk) for 10 wks in eight young (4–6 mo) and seven old (22–24 mo) male Fischer 344 rats to inhibit soluble TNF‐α binding to receptors. At the end of the TNF‐α inhibition period, gastrocnemius muscle arterioles were isolated and concentration response relations to the cumulative addition of ANG II (3x10−12 to 3x10−5 M) were determined.ResultsChronic TNF‐α inhibition significantly diminished the vasoconstrictor response of arterioles from ~ 60% vasoconstriction in the old untreated animals to ~ 40% in the old treated animals. Furthermore, age‐associated differences (young vs. old) in ANG II mediated vasoconstriction were eliminated with the chronic TNF‐α inhibition.ConclusionWith old age there is an enhanced vasoconstriction to ANG II which is due, in part, to diminished endothelial function. Chronic TNF‐α inhibition eliminated age‐related differences in ANG II induced vasoconstriction which suggests that the impaired NOS signaling pathway linked to ANG II receptors with old age may be the result of a proinflammatory state.
Changes in aortic augmentation index following systemic β‐adrenergic blockade are dependent on heart rate
Authors: Allen Alexander R , Curry Timothy B. , Hart Emma C. , Charkoudian Nisha , Joyner Michael J. , Casey Darren P. 
Published: June 2021

We examined the effects of acute β‐adrenergic blockade on central artery hemodynamics and wave reflection characteristics in young healthy humans. High‐fidelity radial artery waveforms were recorded non‐invasively by applanation tonometry before and after intravenous propranolol (0.25 mg/kg bolus for 5 min followed by a maintenance infusion of 0.004/mg/kg/min for 20–30 min) in fourteen subjects (9 F/5M; 27 ± 2 years). Radial blood pressure (BP) was calibrated from the brachial BP (arterial catheter). Aortic augmentation index (AIa; a measure of amplitude and timing of arterial pressure wave reflection) and roundtrip travel time of the reflected wave to and from the periphery (Δtp; inverse of pulse wave velocity) were calculated from the generated aortic pressure waveform and are indices of central arterial stiffness. Systemic β‐blockade reduced heart rate (HR; 60 ± 2 vs. 53 ± 2 bpm, P < 0.001) and increased AIa (9.9 ± 4.3% vs. 4.3 ± 4.4%, P < 0.05), but did not alter Δtp (156 ± 4 msec vs. 152 ± 2 msec, P = 0.34). The AIa normalized to a HR of 75bpm (AIa@75) was not increased following β‐blockade (P = 0.67). Taken together, our data indicate that the increase in AIa following systemic β‐blockade is a result of a slower HR and not due to changes in β‐ mediated vascular tone.Supported by NIH K23 DK‐082424 (TBC), AHA 2170087(ECH) and CTSA RR‐024150
Commensal bacteria are required for the regeneration of damaged skeletal muscle
Authors: Matsuo Kaori , Fujita Motoo , Nagatomi Ryoichi 
Published: June 2021

Regeneration of damaged skeletal muscle requires sufficient supply of nutrients. Fully functional gut assures sufficient supplies of nutrients. Since there are strong lines of evidence that commensal bacteria support gut integrity, we hypothesized that elimination of commensal bacteria may affect muscle recovery from damage. Commensal bacteria of C57BL/6 mice were eliminated by oral administration of antibiotics. Control mice received an equivalent volume of water. Cardiotoxin (CTX) was injected to gatrocnemius muscle to induce muscle damage after the commensal elimination. On different days after CTX, mice were sacrificed and excised gastrocnemius muscle was subjected to immunohistochemical analyses. Although there was no difference in the body weight of antibiotics‐treated and control mice, muscle weight recovery was significantly impaired in antibiotics‐treated even at 20 days after CTX. Histological examination revealed regenerating myogenic cells at day 5 after CTX in both groups. Developmental MHC (dMHC) was positive up to day 7 in the control whereas in the antibody‐treated, dMHC was continuously positive even at day 20. Oral administration of LPS to antibiotics‐treated before CTX effectively restored the delayed recovery of damaged muscle.Our result suggests that components of commensal bacterial such as LPS favor the recovery of skeletal muscle from muscle damage.
Targeting of Pancreatic β‐Cells With High Specificity Using a Heterobivalent GLP‐1/Glibenclamide Ligand
Authors: Hart Nathaniel , Vagner Josef , Chung Woo Jin , Weber Craig , Limesand Sean W , De Silva Channa R , Lynch Ronald M 
Published: June 2021

Pancreatic β‐cell dysfunction, and subsequent loss of β‐cell mass underlies the development of Diabetes Mellitus. The ability to monitor β‐cell mass in vivo is limited because the endocrine pancreas comprises less than 5% of the total pancreatic mass requiring highly specific β‐cell targeting agents; new targeting agents will require at least 100X higher specificity than previously tested agents. We previously demonstrated that multivalent ligands (MVL) composed of two different receptor binding moieties that crosslink multiple receptors, increase the specificity of binding to cells that express only the complimentary receptor pair. To test this approach for use in β‐cell specific targeting, we synthesized a ligand composed of Glucagon‐like Peptide 1 and Glibenclamide (Glb, Sulfonylurea Receptor 1ligand). Using rt‐PCR, expression of these surface receptors was demonstrated in a β‐cell line βTC3, while the ductal cell line PANC1 was shown to express only SUR1. The divalent GLP‐1/Glb binds βTC3 cells at concentrations at least 50 fold lower than required for binding to PANC1cells. The MVL rapidly is internalized from the cell surface (within 2–3 min) after binding via endocytosis. Our findings indicate that the GLP‐1/Glb MVL has increased affinity and specificity for β‐cells, and therefore provides a basis for developing high specificity targeting agents to monitor β‐cell mass.Supported by: Juvenile Diabetes Research Foundation, and the Arizona Biomedical Research Commission
Female gender and estrous cycle‐dependent estrogen regulation of intestinal secretion and KCNQ1 channel function via membrane estrogen receptors
Authors: O'Mahony Fiona , Thomas Warren , Harvey Brian J. 
Published: June 2021

Estradiol (E2) produces a female‐gender specific anti‐secretory response in rat distal colon which is mediated by rapid phosporylation (via PKCδ and PKA) and inactivation of KCNQ1 channels (1). The anti‐secretory action of E2 is sustained although the activation of the signalling protein kinases is transient. E2 (10nM) caused a rapid (<5min) PKCδ dependent decrease in KCNQ1 channel current and a latent (>30min) reduction in KCNQ1 channel density at the basolateral membrane of colonic crypt cells. E2 decreased secretion during the estrus, metaestrus and diestrus stages with only weak inhibition in the proestrus stage. The expression levels of PKCδ and PKA fluctuated throughout the estrous cycle and correlated with the potency of the anti‐secretory effect of E2. The expression of PKCδ and PKA were up‐regulated by E2 at a transcriptional level via a PKCδ‐MAPK‐CREB regulated pathway indicating a genomic priming of the anti‐secretory response. PKCδ was activated by the membrane impermeant E2‐BSA and this response was inhibited by the ER antagonist ICI 182,780. The 66kDa ERα was present at the plasma membrane in female colonic crypts and in lower abundance in male tissue. The study demonstrates an interdependent relationship between both rapid and genomic E2 anti‐secretory responses mediated by ERα.Funded by the Higher Education Authority of Ireland PRTLI NBIP Cycle 4.
Clonal Analysis of Myofibroblast Differentiation
Authors: Chukwuma Sarah , Vaughan Melville 
Published: June 2021

The objective of this study was to observe the growth and transition of the fibroblast cell into a myofibroblast. Fibroblasts make up the cells that maintain the dermis of skin, and slowly transform into the intermediary stage of the protomyofibroblast and finally the myofibroblast. We have observed cultured cells from tissue containing a mixed population of fibroblasts and myofibroblasts. Myofibroblasts are evident in normal wound healing due to the contraction effect of stress fibers. Alpha‐smooth muscle actin is an identifying protein found in stress fibers of these highly contractile cells that participate in normal wound healing. Protomyofibroblasts are made up of the necessary stress fibers that contain beta and gamma‐cytoplasmic actins, yet lack alpha‐smooth muscle actin to become a complete myofibroblast. After making an informative conclusion that fibroblasts are not genetically programmed to become myofibroblasts based on earlier experiments of isolating single cells and growing clonal populations, we wanted to observe this transition phase and determine the factors affecting the completion of this transition and inhibiting the protomyofibroblasts from becoming myofibroblasts. CT4hT cells were cultivated to isolate the protomyofibroblast cells, the phenotype is then induced with TGF‐beta, a transforming growth factor, and then grown in clonal populations.Grant Funding Source: NSF SureStep/UCO Research & Grants
Virtual pelvic anatomy simulator improved medical student comprehension of pelvic anatomy
Authors: Hassinger James Peyton , Dozois Eric J , Holubar Stefan D , Pawlina Wojciech , Pendlimari Rajesh , Fidler Jeff L , Holmes David R , Robb Richard A 
Published: June 2021

Given curricular time constraints, the complex relationships of pelvic viscera can be difficult for students to master. We developed an interactive 3‐dimensional virtual pelvic model using high‐resolution 3‐Telsa magnetic resonance and 64‐slice computed tomographic datasets of a healthy male. The aim of this study was to determine if use of this curricular adjunct was associated with improved comprehension of pelvic anatomy as measured by a 33 item test. The software was distributed to 47 first year medical students during their 3‐day pelvic anatomy curriculum. Forty students (85%) completed the test. Students used the software for a median of 15 (interquartile range [IQR] 10 – 22) minutes; total minutes studying pelvic anatomy was 240 (IQR 125 – 525) minutes. Minutes of software use was strongly associated with the total study time (p<0.0001). On univariate analysis, pelvic anatomy test scores were associated with both minutes of software use (p=0.05) and total study time (p=0.04). On multivariate analysis both software use (p=0.12) and total study time (p=0.08) trended towards significant association with test scores. Most students used the software alongside books to aid in initial spatial orientation to the pelvis. Virtual anatomy software can be a valuable, effective adjunct to traditional anatomy education. Source of funding: Mayo Foundation for Medical Education and Research.Grant Funding Source: Source of funding: Mayo Foundation for Medical Education and Research.
How Dental Students are taught the Anatomical Sciences: Survey results from North American basic science course directors
Authors: Lambert H Wayne , Gould Douglas J. , Burk Dorothy T. , Lee Lisa M. J. , Atsas Stavros , Hutchins Bob 
Published: June 2021

Members of the Anatomical Sciences Section of the American Dental Education Association (ADEA) surveyed North American course directors to assess how undergraduate dental students are taught the anatomical sciences. Web‐based surveys were sent to faculty members charged with teaching anatomy, neuroanatomy, histology, and embryology in the US and Canada. The completed anatomy and neuroanatomy surveys received 100% and 98.5% response rates from the 67 dental schools, respectively. The ongoing embryology and histology survey has had 53 (79.1%) schools respond.The results of these surveys indicate, amongst other things, that: 1) reliance upon medical school faculty and facilities is high; 2) emphasis on clinical topics has increased; 3) a general trend for a decrease in student contact hours is ongoing; 4) the use of computer‐assisted instruction (CAI) tools has increased; 5) a disparity in the number of contact hours reported for anatomical science courses exists among institutions; 6) a pattern of increased use of integrated curricula among dental schools has emerged; and 7) the experience levels of faculty indicate a future need for young faculty competent at teaching in the anatomical sciences.
Identification of novel regulatory domains in the yeast Snf2 protein
Authors: Sen Payel , Ghosh Sujana , Pugh Frank , Bartholomew Blaine 
Published: June 2021

The yeast SWI/SNF complex is a 1MDa multisubunit chromatin remodeler that uses ATP to alter chromatin structure for global transcription regulation. The ATPase‐helicase domain of the catalytic subunit Snf2 has been studied extensively but there has been little focus on regions outside this domain. This study identifies four domains outside the ATPase‐helicase domain that regulate catalytic activity, one of which also plays a role in targeting the complex for recruitment. Deletion of the first sixty amino acids (ΔN, 1–60) and the double AT‐hook (ΔAT, 1446–1530) decrease the rate of remodeling without much effect on ATP hydrolysis whereas deletion of spacer (1312–1444) and QLQ (239–527) show a severe defect in ATP hydrolysis. ΔN and ΔAT reduce remodeling efficiency by 13 and 29 fold respectively compared to WT, an extent that far exceeds their defect in ATP hydrolysis that is only 2.5 and 3.2 fold. Thus ΔN and ΔAT uncouple ATP hydrolysis from remodeling. The defects conferred by deletion of these domains are validated in vivo by growth assays and genome‐wide expression profiling. Biochemical characterization of complexes harboring point mutations in 9 amino acids conserved from yeast to humans in the spacer domain revealed moderate to severe remodeling defects. This study identifies novel, physiologically relevant domains and residues in Snf2 that regulate its targeting and catalytic function.NIH (GM48413)