bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Post Exercise Protein Reduce Total Protein Needs for Optimal Skeletal Muscle Responses to Resistance Training in Older Adults?
Authors: Lee Teak V , Lee Chang Woock , Gasier Heath G , Chikani Gentle , Chen Vincent , Riechman Steven E 
Published: June 2021

Purpose: Age‐related muscle and strength loss, Sarcopenia, is a significant problem in the elderly population but may be restored through adequate protein intake and resistance exercise training (RET). The amount and timing of protein consumption may potentially play an important role in skeletal muscle responses to RET. In this study, we tested the hypothesis that post‐exercise protein was sufficient to elicit the beneficial effects, with higher protein intakes unnecessary. Methods: 30 older, generally healthy men and women (age 50–69) performed 12 wks of full‐body RET. Following the sessions, subjects received a whey/egg protein supplement (0.2 g/kg lean mass). In addition, subjects were asked to complete 48 food records over 12 wks. Body composition (DEXA), 1‐RM and power tests were conducted before and after the training. Results: Mean dietary intake of protein during the 12 wks (g/kg) was significantly (P<0.01) correlated to percent change in lean mass (r=0.394). Percent change in lean mass for low (0.7 g/kg), moderate (0.9 g/kg) and high (1.1 g/kg) protein intake per day was 2.3±0.8%, 3.6±0.7%, and 5.1±0.8%, respectively. Conclusion: Contrary to our hypothesis and previous studies, variability in total daily protein intake did influence muscle gain with RET when post‐exercise protein was administered.This study was supported by the US Poultry and Egg Association.
Influence of resistance exercise on human patellar tendon structural and regulatory gene expression
Authors: Sullivan Bridget E , Carroll Chad C , Jemiolo Bozena , Trappe Scott W , Trappe Todd A 
Published: June 2021

The tendon is mainly composed of collagen surrounded by a matrix of proteoglycans that are regulated by enzymes called matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Studies have shown that acute exercise stimulates collagen turnover, but little is known about the influence exercise has on other components of the tendon. Therefore, we measured the gene expression (mRNA) levels of the tendon's main proteins (collagen type I and collagen type III), proteoglycans (decorin, biglycan, fibromodulin, and versican), and regulatory enzymes (MMP‐2, MMP‐9, MMP‐3, and TIMP‐1) at rest and following resistance exercise (RE). Patellar tendon biopsy samples were taken from six individuals (3M, 3F) before and 4h following a bout of RE (3 sets of 10 repetitions at ~70% of 1RM) and from a separate six individuals (3M, 3F) before and 24h following RE and analyzed using real‐time RT‐PCR. Collagen type I, collagen type III, and MMP‐2 mRNA levels were downregulated (p<0.05) 4h following RE, but were unchanged 24h following RE (p>0.05). The other target mRNAs remained unchanged (p>0.05) following RE. Based on these gene expression results, we speculate that acute resistance exercise stimulates both collagen type I and type III turnover in the human patellar tendon. In addition, the proteoglycans appear to be relatively refractory to a resistance exercise stimulus.NIH R01 AG020532 (TT)
Computational modelling identifies impact of subtle anatomical variation on skeletal muscle local calcium dynamics
Authors: Groenendaal Willemijn , Riel Natal van , Jeneson Jeroen , Eikelder Huub ten , Nicolay Klaas , Hilbers Peter 
Published: June 2021

Calcium is the main regulator of skeletal muscle metabolic activity. The question has been addressed whether the highly structured spatial organization of sites of Ca2+ release, uptake and action in skeletal muscle substantially impacts the dynamics of cytosolic Ca2+ handling and thereby the physiology of the cell. Hereto, the spatiotemporal dynamics of the free calcium distribution in a fast‐twitch muscle sarcomere was studied using a reaction‐diffusion computational model.The model was based on the model of Baylor and Hollingworth (J Gen Physiol. 1998 112:297–316), but was adapted to handle local calcium dynamics in mouse EDL fast twitch muscle at 35C. Furthermore, the Ca2+ mass balance was closed by adding a mathematical representation of the sarcoplasmic reticulum. Experimental calcium time courses (high time resolution, but spatially averaged) obtained under physiological conditions (35C, 125 Hz stimulation frequency) were used for model validation.The model showed that subtle changes in sarcomere microstructure influenced the local calcium concentration. Furthermore, local calcium concentration sensed by mitochondria was higher than average calcium concentration and also above the activation constant of the mitochondria, whereas the local concentration was not. Furthermore, the free Ca2+ concentration was higher at the positions with troponin C than without troponin C.
Effects of in ovo exposure to hyperoxia on chicken ductus arteriosus reactivity
Authors: Villamor Eduardo , van der Sterren Saskia , Cogolludo Angel L 
Published: June 2021

In vivo exposure to hyperoxic environment modifies the in vitro vasomotor response of pulmonary and systemic vessels. We hypothesized that prenatal exposure to hyperoxia would alter the development of ductus arteriosus (DA) reactivity. Hyperoxia was induced by incubating fertilized eggs at 60% O2 from day 15 to 19 of the 21‐d incubation period. DA contractility was studied on day 19 (non‐internally‐pipped embryos) Relaxant responses were studied after precontraction with 125 mM KCl. Hyperoxia did not affect embryonic survival or growth. The contractions induced by 21% O2, KCl, the inhibitor of KV channels 4‐aminopyridine, phenylephrine, and endothelin‐1 and the relaxations induced by acetylcholine, sodium nitroprusside, forskolin, isoproterenol, and the Rho kinase inhibitor OH‐fasudil were similar in DA from embryos incubated under normoxic or hyperoxic conditions. In contrast, the membrane permeable hydroperoxide t‐butyl‐hydroperoxide (1 μM–0.1mM) induced concentration‐dependent contraction in the DA from normoxic embryos and relaxation in the DA from hyperoxic embryos. Reactive oxygen species are complex signalling molecule that produce relaxation in some vessels and contraction in others. Our results indicate that exposure to oxidant stress is capable of modifying the pattern of response of the DA to hydrogen peroxide.Supported by “Fundación de Investigación Médica Mutua Madrileña”
Thiol reducing agents provide protection and rescue for gastric glands following monochloramine‐induced injury
Authors: Tai Kaniza , Kohler Jonathan E. , Blass Amy L. , Liu Jingjing , Mathew Jeff , Soybel David I. 
Published: June 2021

Aim: Monochloramine (NH2Cl) is a thiol‐directed oxidant produced in inflamed, H. pylori‐infested gastric mucosa. We tested the hypothesis that NH2Cl‐induced death of isolated gastric glands can be reversed by thiol reducing agents such as dithiothreitol (DTT) or Lipoic Acid (LA) but not oxidant scavengers such as Vitamin C (VitC).Methods: Isolated rabbit gastric glands were incubated with Ringers solutions containing NH2Cl for 1 hour, then Ringers solution for 2 hours. Cell viability was monitored, using calcein‐AM uptake and conversion to fluorescent calcein, during exposure to NH2Cl. In some studies, DTT, LA or VitC were present throughout the entire 3 hr experiment; in others, they were present only following the 1 hr exposure to NH2Cl.Results: Exposure to NH2Cl resulted in significant (p<0.05) and dose‐dependent decreases in cell viability. Both DTT and Vitamin C were significantly protective when co‐administered with NH2Cl. Only DTT provided partial reversal of injury when given after NH2Cl. No protection was observed in response to LA, given concurrently or after exposure to NH2Cl.Conclusion: Some, but not all, thiol reducing agents protect gastric glands from NH2Cl‐induced injury by concurrent administration and can arrest and reverse injury after exposure to the oxidant. Generic oxidant scavengers can prevent, but do not reverse, injury. Funding: APS Summer Research Fellowship, NIH R01DK069929‐03
Blood Oxygen Level Dependent Magnetic Resonance Imaging and Renal Tissue Oxygenation with Successive Inhibition of Renal Sodium Transport
Authors: Warner Lizette , Haas John A. , Bolterman Rodney , Gomez Sabas , Joyner Michael J. , Romero Juan Carlos 
Published: June 2021

Functional renal oxygen consumption, VrO2 is due to tubular reabsorption of sodium (TNa) in the proximal and distal nephrons, resulting in compartments (cortex/medulla) with distinct VrO2/TNa relationships. Compartmental divisions promote non‐invasive imaging strategies like MRI, to indirectly assess tissue oxygenation, (PtO2). However, the extent to which these regional PtO2 differences are affected by successive TNa are not fully understood. The objective is to determine VrO2 and intra‐renal regional alterations in PtO2 directly and indirectly during successive TNa inhibition. It is hypothesized successive TNa inhibition is accompanied by intra‐renal regional changes in PtO2. Pigs (n=6) underwent MRI scans at baseline, furosemide and acetazolamide. Five days later, the right kidney was instrumented with PtO2 sensors (cortex/medulla). PtO2 was measured during drug infusions (identical to MRI exam). There was a decrease in VrO2, and a 40% and 30% increase in medullary and cortical PtO2 following drug infusions. There was ~25% medullary and ~20–30% cortical decrease in BOLD signal with furosemide and acetazolamide administration, respectively. This study suggests successive inhibition of TNa is accompanied by intra‐renal regional PtO2 changes and these changes are detectable with BOLD‐MRI, a non‐invasive imaging modality.Funding provided by NIH Grant (HL16496‐32), 2007 APS Porter Physiology Fellowship and the Mayo Foundation.
Lamellar body secretion in cyclically stretched rat alveolar type II cells depends on the geometry of cell‐cell interaction
Authors: Felder Edward , Appelt Daniel , Zheng Xing , Dietl Paul 
Published: June 2021

Alveolar type II cells respond to mechanical stimulation with a fusion of surfactant containing lamellar bodies (LBs) with the cell membrane. Single fusion events of LBs can be detected with the fluorescent dye FM1‐43 in vitro which was used to investigate the effect of cyclic stretch on LB exocytosis in primary rat type II cells. After cultivating the cells on an elastic growth support we used a micro‐robotic arm (kleindiek nanotechnik) that allowed us to locally stretch the underlying growth substrate and hence to apply unidirectional stretch to individual clusters of cells. Stretch of different frequencies (1, 2 and 4hz) revealed that the fusion response was inversely related to the frequency but only slighly lower (1.84Hz) in responders as compared to non‐responders (2.0Hz). Also the stretch amplitude (from 1 to 25%) did barely correlate with the number of LB fusions. Cells that responded with fusions were generally attached to more cells than the ones without response indicating cell‐cell interaction of some kind to account for the process. In cases were the position of the adjacent cells with respect to the stretch axis could precisely be defined, we found that an unsymmetric deformation rather than simple elongation of a cell cluster lead to an increased number of fusions. Latter shows that the mechanosensitive machinery of the ATII cell is able to distinguish between force patterns and we suggest cytoskeletal elements to be a key player in mediating this process.Supported by the FWF, grant P15743, the DFG, grant D1402, the Landesstiftung Baden‐Württemberg and the 6th framework of the EU, Pulmo‐Net.
Model simulation of expired CO2 from its alveolar distribution in parallel and series models
Authors: Caucha Luis Jhony , Cruz Julio Cesar , Rueda Luis Antonio 
Published: June 2021

The CO2 model of Scherer (J. Appl. Physiol. 64:1022, 1988) is here applied to the 7 regions model of Jeng et al (Ann. Biomed. Eng. 28:453, 2000). While Scherer et al ended up with an alveolar CO2 concentration of 3.1% and used a pulmonary blood flow of 100 mL/s, we applied West concept of less CO2 and blood flow at the apex. The alveolar CO2 concentrations and the pulmonary blood flow at the apex and base of the lung were: 2.6% and 4.4%; 1.2 mL/s and 41mL/s, respectively. The anatomical model of Weibel is scaled for each region The results are on the figure. Although the curves are similar, our curve shows a larger dead space and less slope of phase 3. The base of the lung contributes more to the onset of CO2 in the capnogram.Supported in part by ONG‐Centro de Enseñanza, Investigación y Servicios.
Measuring Collateral Pathways in Health via 3He MRI
Authors: Woods Jason C , Bartel Seth‐Emil , Conradi Susan H , Chang Yulin V , Yablonskiy Dmitriy A , Gierada David S , Conradi Mark S 
Published: June 2021

IntroductionThere has been recent interest in the use of 3He diffusion MRI because of the close correlations of the imaging measure with tissue morphometry. The long‐range diffusion coefficient (LRDC) has been shown to be a measure of collateral pathways in emphysema, but little is known of the role of collaterals in the LRDC in health. A recent publication attempted to explain the LRDC by simulations within single lung acini, without collateral pathways.MethodsWe measured the LRDC of 3He ex‐vivo in 4 human donor lungs that were rejected for transplantation and in 3 pig lungs, which are known to have greatly reduced collateral ventilation. We also simulated the interacinar diffusion of 3He (at 2‐cm diffusion distances) via the diffusion equation in a strictly branching model of human lung with no collateral pathways. (Airway radii, lengths, and branching angles were taken from detailed, morphometric literature.)ResultsLRDC in pig lungs (0.004 cm2/s) was 4x lower than in the human lungs (0.022 cm2/s), implying that collateral pathways can play a significant role in the measurements. The robustly tested simulations revealed a surprisingly low LRDC (24x lower than the measured value), implying that diffusion via the airway tree alone (no collaterals) cannot account for the measured value in healthy lung. A surprisingly small number of 5‐μ pores is shown to account for the discrepancy.
Estrogens modulate intracellular Ca2+ in human airway smooth muscle
Authors: Townsend Elizabeth A , Thompson Michael A , Pabelick Christina M , Prakash YS 
Published: June 2021

Asthma is a disease characterized by airway hyperresponsiveness and inflammation. One‐third of pregnant women with pre‐existing disease experience a decrease in symptoms during the third trimester, when estrogen levels are highest. Previous studies have shown that estrogens relax vascular smooth muscle, however, little is known about estrogen effects on airway smooth muscle (ASM). We tested the hypothesis that estrogen modulates human ASM contractility. Western blot analysis and immunohistochemical studies showed the presence of both full‐length and truncated isoforms of ERα and β. Furthermore, ER isoforms were localized to caveolae. Caveolin‐1 siRNA downregulated ERα isoform in human ASM. Exposure to the pro‐inflammatory cytokine TNFα substantially increased ERα expression in ASM. In fura‐2 loaded human ASM cells, acute exposure to biologically‐active 17β‐estradiol decreased the intracellular Ca2+ response to contractile agonists such as histamine and bradykinin; this effect was blunted by the ER antagonist ICI 182, 780. Overall, these data suggest that estrogens may have a bronchodilatory effect. Accordingly, increased ER expression with airway inflammation may actually be protective during pregnancy in that bronchodilation resulting from higher estrogen levels (acting via ERs) may alleviate the increased ASM contractility of asthma.Supported by the Mayo Graduate School and NIH grant UL1RR024150‐01(Mayo Clinic CTSA awards to YSP and CMP)
Integrating Teaching and Research at the Post‐doctoral level: The Fellowships in Research and Science Teaching (FIRST) Program
Authors: Holzman Jennifer L. , Brommer Chad L. , Eisen Arri , Haynes J. K. , Eaton Douglas C. 
Published: June 2021

The Fellowships in Research and Science Teaching (FIRST) program presents post‐doctoral fellows with a unique experience that combines research and teaching in preparation for positions in academia. FIRST fellows participate in a traditional, mentored research setting at a consortium institution (Emory, Morehouse School of Medicine, and the Atlanta University Center), and as AUC teachers – at Spelman or Morehouse Colleges, or Clark Atlanta University. The complementation of these two critical aspects of academic life allows fellows to be trained in teaching pedagogies and techniques, and to gain hands‐on mentored experiences in the classroom, while balancing the demands of a research program. By receiving comprehensive feedback about their teaching, fellows can improve their teaching skills during their time in the program, setting them up for successful teaching jobs in the future. Fellows also participate in workshops and seminars, as well as continue to publish their research and present their work at national meetings. Of the 52 fellows that have completed the program, 65% have obtained jobs at a diversity of academic institutions, and continue to be active and innovative in both their research and teaching endeavors. Furthermore, FIRST fellows have exhibited success obtaining extramural funding (80%) at four times the rate of other NIH grant applicants.Funded by: NIH, NIGMH K12‐GM00680‐06
Dissection in the UNAM_Mexico City
Authors: Herrera Patricia M 
Published: June 2021

Anatomy dissection is being questioned all over the World. In the UNAM in Mexico City we still have the possibility of obtaining cadavers and we endorse the practice of dissection. In the past the dissection of regions was separated from the actual themes that were covered in class. We have proposed for the past 5 years to dissect exactly the same region that has been covered in the lectures. We divide the 40 student group into 4 groups each responsible for the dissection of a corpse. They rotate the different roles and have to finish finding the elements presented to them in a check list. They are examined precisely in the identification of those elements that represent the core knowledge of the Anatomy Course.We compare the results obtained by those groups with the grades of the groups that dissect regions unrelated to the class topics.The results show that there is a statistically significant difference at p= 0.5We conclude that dissecting is important to the learning of anatomy.
Targeting the Enoyl‐Reductase Enzyme (FabI): Modern Drug Discovery Effects to Combat Tularemia
Authors: LU HAO , amEnde Chris , Boyne Melissa , Luckner Sylvia , Slayden Richard , Kisker Caroline , Tonge Peter J. 
Published: June 2021

Francisella tularensis is a highly virulent and contagious gram‐negativeintracellular bacterium that causes the disease tularemia in mammals. The high infectivity and the ability of the bacteriumto survive for weeks in a cool, moist environment have raisedthe possibility that this organism can be exploited deliberatelyas a potential biological weapon. Fatty acid synthesis (FAS) is essential for bacterial viability and it has also been validatedas an attractive target for the discovery of novel antibacterials.We have successfully cloned, overexpressed and purified the F. tularensis FAS enoyl reductase enzyme FabI (ftuFabI) and fully characterized the reaction mechanism through steady‐state kinetics. Based on the 2.5Å resolution crystal structure we firstly resolved and pre‐steady state kinetics, a two‐step mechanism coupled to ordering of the active site loop was proposed for inhibition of the enzyme by triclosan. We also identified a series of diphenyl ethers which are subnanomolar inhibitors of the enzyme and that inhibit bacterial growth with MIC90 values as low as 0.09 μg/ml. One of these promising compounds is active in a mouse model of tularemia infection.
Targeting the Dimerization of EGFR
Authors: Yang Rob , Pike Linda , Marshall Garland 
Published: June 2021

It is estimated that one in eight American women will develop breast cancer in her lifetime and a significant number of these cases are due to misregulation of the epidermal growth factor receptor, EGFR. Current drugs based on antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) show promising yet highly variable clinical efficacy. Recent advancements in EGFR‐signaling suggest that these therapeutic limitations are due to underestimation of a complex system that relies on receptor dimerization. Here we report a class of small‐molecule inhibitors that target and disrupt the dimerization in living cells, which contrasts the traditional strategies of developing mAb‐ and TKI‐based inhibitors. Our approach is a top‐down protocol that combines in silico high‐throughput screen of a compound library and in vitro biochemical assays that experimentally test the putative candidates. Several compounds were identified as potent and specific inhibitor against the activation of EGFR in living cells. The discovery, and the on‐going characterization, of these inhibitors offer an alternative class of EGFR‐inhibitors and could serve as the building blocks of novel therapeutics against breast cancer.NIH grant GM68460
Immunosuppressive drug FTY720 sensitizes prostate cancer cells to radiotherapy by inhibition of sphingosine kinase‐1.
Authors: Pshezhetskiy Dmitry , Bohler Torsten , Doumerc Nicolas , Golzio Muriel , Brinkmann Volker , Waxman Jonathan , Malavaud Bernard , Cuvillier Olivier 
Published: June 2021

A sphingolipid analogue FTY720 is a novel immunosuppressive drug – an agonist of sphingosine 1‐phosphate (S1P) receptors. Recently we identified S1P as a therapy target in prostate cancer. In the current study we have demonstrated that FTY720 can radiosensitize prostate cancer in cell and animal models.FTY720 has induced apoptosis in several hormone‐ and radio‐resistant prostate cancer cell lines. FTY720 treatment induced a sustained inhibition of prosurvival sphingosine kinase‐1 (SK1) and a decrease in the intracellular S1P content. Enforced expression of SK1 in prostate cancer cells rendered them resistant to FTY720. In vitro sub‐lethal concentrations of FTY720 have dramatically sensitized PC‐3 cells to radiotherapy in p53‐independent manner.Mice orthotopically engrafted with fluorescent PC‐3 cells were treated with FTY720 with or without ã‐Irradiation. FTY720 has demonstrated a synergy with ã‐irradiation significantly reducing tumor size, angiogenesis and formation of micrometastases as demonstrated by fluorescent in vivo imaging.In conclusion, FTY720 can sensitize prostate cancer cells to radiotherapy both in vitro and in vivo, through inhibition of SK1 and modification of intracellular levels of lipid second messengers.