bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the Accuracy of Physiologic and Triangular Pseudoflow Waveforms for Estimating Wave Reflection Indices in Adults
Authors: Shenouda Ninette , Stock Joseph M. , Patik Jordan C. , Chirinos Julio A. , Edwards David G. 
Published: April 2020

Central aortic pressure waveforms contain valuable prognostic information in addition to central systolic pressure. Using wave separation analysis, aortic pressure‐flow relations can be used to decompose aortic pressure waveforms into forward (Pf) and backward‐travelling (Pb) components. Pf and Pb are used to calculate reflection magnitude (RM=Pb/Pf) which is predictive of heart failure and all‐cause mortality. Aortic blood flow can be measured non‐invasively via ultrasonography or estimated using a triangular pseudoflow waveform; however, the latter can underestimate true flow and thus overestimate Pb and RM. Recently, a physiologic pseudoflow waveform has been developed that improves on the assumptions of triangulation and so may provide a more accurate estimation of wave reflection.PURPOSEThe purpose of this study was to compare estimates of Pf, Pb, and RM derived from physiologic and triangular pseudoflow waveforms relative to measured flow. We hypothesized that the physiologic waveform would provide a more accurate estimate of wave reflection indices compared to the triangular waveform.METHODSIn 75 adults (age 18–75 yrs), radial artery pressure waveforms were acquired with applanation tonometry and a generalized transfer function was used to synthesize central pressure waveforms. Aortic blood flow velocities were measured via echocardiography and estimated using physiologic (in‐house software) and triangular (SphygmoCor CvMS) pseudoflow waveforms. Pressure‐flow relations were established offline and wave separation analysis was performed. Accuracy of the physiologic and triangular‐derived estimates of Pf, Pb, and RM were assessed using 95% equivalence testing, paired t‐tests comparing the mean absolute biases, and Bland‐Altman plots.RESULTSUsing a 10% equivalence zone as the maximum acceptable difference, the physiologic and triangular pseudoflow waveforms were both comparable to the measured flow waveform in deriving Pf. However, only the physiologic waveform yielded similar estimates of Pb and RM compared to the measured waveform. Further, the physiologic waveform yielded lower mean absolute biases compared to the triangular waveform for Pf (1.7 ± 2.1 vs. 2.8 ± 2.6 mmHg, p<0.001), Pb (1.0 ± 1.1 vs. 3.3 ± 2.7 mmHg, p<0.001), and RM (3 ± 3 vs. 14 ± 13%, p<0.001). Lastly, Bland‐Altman biases were smaller, and 95% limits of agreement were narrower, for all wave reflection indices derived from the physiologic waveform than from the triangular waveform.CONCLUSIONThese data suggest that the physiologic pseudoflow waveform provides a more accurate estimate of wave reflection indices compared to the triangular waveform, and thus may offer a superior alternative when true flow cannot be measured.
Use of Conditioned Media from Electrically‐Stimulated C2C12 Myotubes to Examine the Effect of Muscle Contractile Secretions on Breast Cancer Cell Proliferation
Authors: Kump David S. , Hughes Alvysha S. , Justice Brittany , Murphy Cangela 
Published: April 2020

Background & PurposeEvidence suggests that secretions following muscle contraction may have benefits regarding breast cancer. This study aimed to examine whether conditioned media from electrically‐stimulated C2C12 myotubes would inhibit proliferation of breast cancer cells in vitro.MethodsMedia collected from electrically‐stimulated C2C12 myotubes was mixed 1:1 with fresh media and applied to either T47D subluminal type breast cancer cells or a K14TRT triple‐negative breast cancer cell line for 24 hours. Breast cancer cell proliferation was measured using the MTT method. In addition, media from electrically‐stimulated and non‐stimulated C2C12 myotubes were subjected to mass spectrometry for comparison.ResultsResults provided an inconsistent picture regarding the approach. When applied at a 1:1 ratio, the conditioned media unexpectedly accelerated the proliferation of T47D cells by more than two‐fold. When applied to K14TRT cells, one experiment demonstrated no effect, while a second showed a robust inhibition of proliferation. The disparate results are likely due to the wide natural variance in proliferation in this cell line. Mass spectrometry analysis did not yield any potential differences in secreted molecules between electrically‐stimulated and non‐stimulated media.ConclusionsThe present results suggest that further work is needed to explore the utility of media from electrically‐stimulated myotubes as a model for muscle contraction‐induced secretions and their effect on breast cancer. Future work will include a dose‐response analysis and the use of ELISA to identify potential molecules.Support or Funding InformationThis study was partially supported by a WSSU Grant from the Office of Science Initiatives. Mass spectrometry was conducted by the Wake Forest Baptist Comprehensive Cancer Center Proteomics and Metabolomics Shared Resource, which is supported by the National Cancer Institute’s Cancer Center Support Grant award number P30CA012197
Transgenerational effects following chronic circadian disturbance given to mother rats in F1 generation rats
Authors: Choi Jeonghyun , Hong Yonggeun 
Published: April 2020

It has not been documented whether circadian disturbance of mother may influence fetal neurodevelopment. Therefore, this study aims to find the root cause of congenital neuronal defects, which is explosively increasing today, in one of the environmental factors; circadian disturbance. Female rats were randomly divided into 3 groups; L/D group with 12/12 hr light and dark cycle, LL group with 24 hr constant light, DD group with 24 hr constant dark. All subjected females were assigned to each light condition one week prior to pregnancy. Then, they were mated with males, and F1 offsprings were obtained at three weeks after the mating. The future generations were exposed exactly same light conditions. The animals in each group were randomly divided into control and melatonin‐treated subgroups. All animals were engaged in physiological, histological, and neurobehavioral analyses. LL and DD groups showed several abnormal features and decreased cecum/colon length (p<.05). Also, LL and DD groups showed lower activation of intracranial δ‐wave than L/D group showed. However, in LL and DD groups treated with melatonin improved intestinal integrity and activated intracranial δ‐wave. Axonal sprouting was evaluated by Golgi‐cox staining for identifying the abnormal neurodevelopment in all groups. The LL and DD groups showed reduction of axonal sprouting than L/D group. However, axonal branching in neuron increased in LL and DD groups treated with melatonin. In addition, neurobehavioral tests including open field test, novel objective recognition test, social interaction test, spontaneous alternation Y‐maze test, and elevated plus maze test were performed. LL and DD groups showed abnormal neurobehaviors (p<.05), whereas, melatonin treatment resulted in the normalized neurobehaviors (p<.05). In conclusion, F1 generation born from mothers exposed to chronic circadian disturbance showed abnormal neurodevelopment and neurobehaviors. Melatonin was considered as a therapeutic agent for congenital neuronal deficit.Support or Funding InformationFundings: National Research Foundation (NRF‐2017R1A2A2A01067169, NRF‐2019R1A6A3A01091422), Korea
Elevated serum melatonin under constant darkness enhances neural repair in spinal cord injury through regulation of circadian clock proteins expression
Authors: Hong Yunkyung , Jin Yunho , Park Kanghui , Hong Yonggeun 
Published: April 2020

We investigated the effects of environmental lighting conditions regulating endogenous melatonin production on neural repair, following experimental spinal cord injury (SCI). Rats were divided into three groups randomly: the SCI + L/D (12/12‐h light/dark), SCI + LL (24‐h constant light), and SCI + DD (24‐h constant dark) groups. Controlled light/dark cycle was pre‐applied 2 weeks before induction of spinal cord injury. There was a significant increase in motor recovery as well as body weight from postoperative day (POD) 7 under constant darkness. However, spontaneous elevation of endogenous melatonin in cerebrospinal fluid was seen at POD 3 in all of the SCI rats, which was enhanced in SCI + DD group. Augmented melatonin concentration under constant dark condition resulted in facilitation of neuronal differentiation as well as inhibition of primary cell death. In the rostrocaudal region, elevated endogenous melatonin concentration promoted neural remodeling in acute phase including oligodendrogenesis, excitatory synaptic formation, and axonal outgrowth. The changes were mediated via NAS‐TrkB‐AKT/ERK signal transduction co‐regulated by the circadian clock mechanism, leading to rapid motor recovery. In contrast, exposure to constant light exacerbated the inflammatory responses and neuroglial loss. These results suggest that light/dark control in the acute phase might be a considerable environmental factor for a favorable prognosis after SCI.Support or Funding InformationNational Research Foundation (NRF‐2013R1A2A2A01067169, NRF‐2015R1C1A2A01055691, NRF‐2017R1D1A1B03029565), Korea.
The implication of melatonin and Botulinum toxin type A in neural reconstruction and muscle repair after spinal cord injury
Authors: Jin Yunho , Hong Yonggeun 
Published: April 2020

Spinal cord is responsible for neural transmission of nerve impulses between brain and the whole body. Spinal cord injury (SCI) is caused mostly by trauma leading to motor and sensory deficits, and autonomic dysfunctions. This injury involves primary and secondary mechanisms; primary SCI is the mechanical damage to the spinal cord while secondary SCI means further prolonged insults initiated by the original damage. The therapeutic aims for SCI usually focus on the suppression of secondary SCI by means of therapeutic drugs of surgery. In this study, melatonin and Botulinum toxin type A (BTA) was exploited to accelerate the recovery of SCI. First, contribution of melatonin, which is known to have neuroprotective roles, toward the recovery from SCI through regulation of autophagy and endoplasmic reticulum (ER) stress was examined. Following SCI, muscle spasticity occurs interrupting normal functional movements. BTA was administrated to alleviate muscle spasticity for the restoration of normal movements. Melatonin was proved to protect cells from excessive autophagic cell death, and to activate ER stress response leading to the restoration of cellular homeostasis. Furthermore, dendritic branches were preserved by melatonin. Muscle degradation was suppressed following BTA injection. Furthermore, BTA injection accelerated the recovery of muscle contraction‐regulatory proteins and removal of damaged cells, and restored presynaptic homeostasis via autophagy activation. In conclusion, melatonin may result in the recovery of SCI via the regulation of autophagy and ER stress response. And, BTA was proved to draw functional recovery by alleviating muscle spasticity after SCI. In other words, melatonin or BTA could be suggested as therapeutic candidates for the recovery of SCI.Support or Funding InformationNational Research Foundation (NRF‐2017R1A2A2A01067169), Korea.
Role of Jumonji‐C Histone Demethylase in the Development of Hepatocellular Carcinoma
Authors: Jeong Do-Won , Chun Yang-Sook 
Published: April 2020

Reprogramming in lipid metabolism has received increasing recognition as a hallmark of cancer cells. In cancer cells, large demands of lipids were required to meet excessive synthesis of membranes, energy production and activation of intracellular signaling pathways during cell proliferation. To meet these demands, cancer cells express increased levels of lipogenic enzymes responsible for FAs synthesis, which is a target of crucial transcriptional regulator, sterol regulatory element binding protein 1c (SREBP1c). SREBP1c is a well‐known master transcription factor for de novo lipogenesis and is found frequently increased in many human cancers. However, the molecular mechanisms involved in the regulation of SREBP1c remain incompletely understood. In this study, we uncover the role of jumonji‐C histone demethylase (JHDM) as a repressor of SREBP1c, thereby preventing lipogenesis and proliferation of hepatocellular carcinoma (HCC) cells. JHDM directly interacts with SREBP1c at basic helix‐loop‐helix domain of SREBP1c and plant homeodomain of JHDM, promoting proteasomal degradation of SREBP1c protein. In addition, knockdown of JHDM stimulates mRNA levels of lipogenic enzymes and induces lipogenesis in HCC cells. However, JHDM‐loss‐induced lipogenesis is recovered by SREBP1c knockdown, implying that SREBP1c is crucial for the effects of JHDM toward lipogenesis. In contrast, ectopic expression of JHDM shows protective effects on oleic acid‐induced lipid accumulation in HCC cells. We also found that JHDM knockdown using si‐RNAs promotes mRNA expressions of cell cycle regulators, accompanied with enhanced cell growth, colony formation and spheroid formation. However, the effects of JHDM knockdown which promote HCC proliferation are reversed by knockdown of SREBP1c. In accordance with these data, JHDM overexpression represses cell growth in HCC cells, indicating that JHDM acts as a tumor suppressor by inhibiting SREBP1c‐mediated lipogenesis and cell cycle regulation. Overall, our findings suggest that JHDM serves as a molecular bridge between lipid metabolism and cancer development through regulation of SREBP1c and thus JHDM could be a therapeutic target in defense against HCC.Support or Funding InformationThis work was supported by grants from the National Research Foundation of Korea (2016R1A2B4013377, 2018R1A2B6007241, 2019R1A2C2083886).
Spatiotemporal Organization of Metabolic Networks in Living Cells
Authors: Kennedy Erin Laurel , Jeon Miji , Chauhan Krishna , Augustine Farhan , An Songon , Kyoung Minjoung 
Published: April 2020

Cellular metabolic networks are dynamic. Organization between membrane‐bound organelles and cytoplasmic metabolic pathways are crucial to cell survival and function. This is the case for the glucose metabolism, where cytoplasmic enzymes have been observed to form spatially organized enzyme assemblies. We have quantified the sub‐cellular organization of these glucose metabolic assemblies with the mitochondria and studied a mitochondrial‐associated population of assemblies that are functionally linked to the mitochondrial metabolism. This research was completed with a home‐built lattice light sheet microscope and other biophysical and biochemical methods, which provided crucial spatiotemporal insight into the orchestration of metabolic functions that provides a starting point to map 4D functional metabolic networks.Support or Funding InformationNIH Research Project Grant R01 GM134086, NIH Research Project Grant R01 GM125981, Research Grant R03 CA219609, Student support provided by NIH Chemistry Biology Interface Program (T32 GM066706), Student support provided by an NIGMS Initiative for Maximizing Student Development Grant (2 R25‐GM55036)
The cytosolic formate dehydrogenase FdsABG from Cupriavidus necator. Crystal structure of the FdsBG fragment which is responsible for the oxidative half‐reaction.
Authors: Blaha Gregor , Young Tynan , Niks Dimitri , Hakopian Sheron , Tam Timothy K. , Yu Xuejun , Hille Russ 
Published: April 2020

Soluble formate dehydrogenase FdsABG, is a member of the NADH dehydrogenase superfamily, which is one of the most broadly distributed family of enzymes. Unlike most members of this superfamily, formate dehydrogenase FdsABG is a cytosolic enzyme. Physiologically, the FdsABG from Cupriavidus necator oxidizes formate to CO2 by reducing NAD+ to NADH. In the process, reducing equivalents are transferred from formate to the molybdenum center of FdsA, from where they are passed through a chain of iron‐sulfur clusters to the FMN of FdsB and on to NAD+. These two steps of accepting reducing equivalents from the formate and passing them on to NAD+ are considered the reductive and oxidative half‐reactions of the formate dehydrogenase reaction. Because FdsB‐ and FdsG‐like domains are found in all NADH dehydrogenases and can perform the oxidative half reaction independent of FdsA, we embarked on a crystallographic study of FdsBG of C. necator formate dehydrogenase, with the aim of putting the oxidative half reaction of the enzyme in a structural context.Support or Funding InformationUnited States Department of Energy Grant DE‐SC0010666 (to R. H.)
Autophagy and Heat Shock Protein 70 Expression During Acute Heat Stress in Isosmotic and Hyperosmotic Conditions in Peripheral Blood Mononuclear Cells from Young Adults: Preliminary Data
Authors: Cote Melissa D. , McCormick James J. , Rutherford Maura M. , King Kelli E. , Meade Robert D. , Notley Sean R. , Akerman Ashley P. , Schmidt Madison D. , Kenny Glen P. 
Published: April 2020

Heat‐stress induced dehydration is associated with elevations in extracellular osmolality. To counteract the resultant osmotic stress, cells employ several stress response systems including the heat shock protein (HSP) and autophagy pathways. HSPs refold damaged proteins, whereas autophagy acts to degrade damaged cellular components, thereby promoting cellular survival. Accumulating evidence indicates a coordinated response between the HSP and autophagy systems, whereby both systems are activated under conditions of heat stress. However, it remains unknown whether elevated extracellular osmolality augments the HSP and autophagic response to whole‐body heat stress in humans. Thus, the purpose of this study was to examine changes in HSP (HSP70) and autophagy resulting from elevated intravascular osmolality during acute heat exposure. We hypothesized that both autophagy and HSP70 protein expression would be greater under hyperosmotic stress compared to isosmotic conditions. On separate days (separated by ~1 week), six young men (mean [SD]; 27 [5] years) received a 90‐min intravenous infusion with either isosmotic (ISO; 0.9% NaCl; 0.200 mL·kg−1·min−1) or hyperosmotic (HYP; 3.0% NaCl; 0.125 mL·kg−1·min−1) saline, followed by passive whole‐body heating to ~0.8°C above baseline esopha‐‐‐geal temperature using a water perfused suit. Serum osmolality was determined via freeze‐point depression from blood samples at baseline and at the end of passive heating. Peripheral blood mononuclear harvested at these time‐points were analyzed via Western blotting to assess changes in HSP70 protein and proteins indicative of autophagic activity including microtubule associated protein 1 light chain 3 beta‐II (LC3‐II) and p62/sequesterome‐1 (p62). All values were normalized to β‐actin and reported as fold changes relative to baseline. Data are presented as means and standard deviations (SD) and were compared between‐conditions at the end of passive heating using paired (2‐tailed) t‐tests (α=0.05). At the end of heating, serum osmolality was higher during HYP when compared to ISO (298 [SD 3] vs. 291 [SD 3]; p<0.001). During passive heating, LC3‐II was increased (2.20 [SD 2.12] vs. 1.62 [SD 1.47]; p=0.04) and p62 protein was reduced (0.47 [SD 0.33] vs. 1.20 [SD 0.56]; p=0.01) in HYP compared to ISO, indicating greater autophagic activation during HYP. Despite this, HSP70 protein was lower under HYP conditions following heating than ISO (0.72 [SD 0.24] vs. 1.20 [SD 0.19]; p=0.04). Contrary to our hypothesis, these preliminary findings indicate greater reliance on the autophagic response rather than simultaneous activation of HSP70 during acute heat exposure with super‐imposed hyperosmotic stress.Support or Funding InformationNational Science and Engineering Research Council of Canada
The Influence of Salt Loading on the Kidney Injury Biomarker Neutrophil Gelatinase‐Associated Lipocalin in Healthy Young Adults
Authors: Barnett Alex M. , Babcock Matthew C. , Watso Joseph C. , Migdal Kamila U. , Farqhuar William B. , Robinson Austin T. 
Published: April 2020

PurposeThe kidneys play a critical role in blood pressure (BP) regulation. In hypertensive patients and in rodent models, long‐term high dietary sodium (Na+) causes a reduction in kidney function (reduced glomerular filtration rate; GFR). Rodent studies demonstrate that high dietary Na+ increases levels of novel kidney injury biomarkers, independent of changes in BP and GFR. However, it is unclear if short‐term high Na+ increases kidney injury biomarkers in healthy humans. Therefore, we tested the hypothesis that short‐term high Na+ intake increases urinary excretion of the novel kidney injury marker Neutrophil Gelatinase‐Associated Lipocalin (NGAL) in healthy, young adults.MethodsTwenty participants (12 M/8 F; age: 24±4 years; BMI: 23.1±0.6 kg/m2; BP: 112 ±10/64 ±9 mmHg, mean ± SD) participated in a double‐blind, placebo‐controlled, randomized, crossover study. For 10‐days, participants were asked to consume a 2,300 mg/day Na+ diet and supplement with salt (3,900 mg/day of Na+) or placebo (dextrose) capsules. The conditions were separated by at least two weeks and female participants were tested during the placebo phase of their oral contraceptive cycle. Participants collected their urine for the final 24 hours of each supplementation period to assess urine flow rate, and Na+ excretion to verify diet adherence. Brachial BP was measured after at least five minutes of rest. We measured urine and serum creatinine (kinetic modification via the Jaffe reaction) to estimate GFR via creatinine clearance. We used enzyme‐linked immunosorbent assays (Toronto Bioscience) to measure urinary NGAL. Statistical analysis included paired t‐tests and Wilcoxon matched‐pairs signed rank tests.ResultsCompared to placebo, Na+ supplementation increased urinary Na+ excretion (139.9±68.4 vs. 282.5±69.8 mmol/24 hours, p<0.01) but there was no difference in mean arterial BP (77±7 vs. 77±6 mmHg, p=0.64). Serum creatinine concentrations (0.78±0.12 vs. 0.77±0.09 mg/dL, p=0.55) were not different between conditions. However, compared to placebo, Na+ supplementation increased creatinine clearance (110.5±32.9 vs. 145.0±24.9 mL/min, p<0.01) and increased urinary NGAL excretion indexed to urine flow rate (16.9±21.9 vs. 28.4±36.1 ng/min, p=0.02).DiscussionOur preliminary data suggests that salt loading does not alter serum creatinine concentration but increases creatinine clearance and urinary excretion of the kidney injury marker NGAL in healthy young adults.Support or Funding InformationFundingSupported by NIH grants R01HL128388 and K01HL147998, and ACSM Foundation Doctoral Student Research Grant 17‐00521
In vitro and in vivo characterisation of structure‐based nucleosome binding peptides
Authors: Teles Kaian Amorim , Fernandes Vinicius , Torres Isabel , Leite Manuela , Lobbia Vincenzo , Honorato Rodrigo , Lopes-de-Oliveira Paulo , Van Ingen Hugo , Grisolia Cesar , Treptow Werner , Santos Guilherme Martins 
Published: April 2020

The modulation of chromatin is orchestrated by Nucleosome Binding Proteins (NBPs). The nucleosome surface has been hypothesized as a therapeutic target due to its capacity to modulate chromatin architecture. Herein, we evaluated if Nucleosome Binding Peptides (NBPeps) would be able to occupy the nucleosome surface directly, thereby modulating chromatin status and influencing phenotypic outcomes. To understand how the nucleosome structure is affected by NBPeps, we performed biochemical assays indicating that distinct NBPeps present differential actions on the nucleosome structure despite binding to similar target regions on the nucleosome. Cellbased assays and animal models demonstrated that the NBPeps penetrate the cell and have specific effects on cell physiology and phenotypic outcome, suggesting that NBPeps might have important therapeutic implications.Support or Funding InformationThis work has been supported by CNPq for KT,VF and IT fellowships, Fap‐DF grant number 04/2017 for GS, iNEXT grant number 6756, funded by the Horizon 2020 programme of the European Union, for HI.