bluuebunny/crossref_metadata_2025_split huggingface dataset:
Appearance of Local Abnormalities of Left Ventricular Contraction on Top of Global Diastolic Dysfunction in the Hypertensive mRen2 Rat
Authors: Csipo Tamas , Fulop Gabor Aron , Bodi Beata , Fagyas Miklos , Priksz Daniel , Juhasz Bela , Beke Livia , Hendrik Zoltan , Mehes Gabor , Olah Attila , Radovits Tamas , Merkely Bela , Granzier Henk , Papp Zoltan , Judit Barta , Toth Attila , Kovacs Arpad 
Published: November 2023

Hypertension is a major co‐morbidity of diastolic dysfunction. Appearance of systolic dysfunction on top of diastolic dysfunction further increases the risk of cardiac failure and mortality. We hypothesized that a hypertensive rat model with diastolic dysfunction can give insight into the pathomechanism of progressing human heart failure.To this end we compared 15 weeks old male rats (n=9‐9) with hypertension due to a renin transgene (mRen2, 228.9±4.9 mmHg; P<0.05) with geno‐/phentoype controls (SD, 121.3±4.4 mmHg).Invasive parameters of left ventricular (LV) active relaxation (Tau, mRen2: 16.9±0.8 ms vs. SD: 12.6±0.6 ms; P<0.05) and passive stiffness (slope of EDPVR, mRen2: 0.050±0.004 mmHg/μL vs. SD:0.040±0.002 mmHg/μL; P<0.05) confirmed diastolic dysfunction with preserved ejection fraction (EF, mRen2: 52.5±0.7% vs. SD:53.3±0.7%) in the mRen2 animals.In contrast, regional echocardiography (n=8‐8) and histology (n=5‐5) showed worse Tei index (0.78±0.04; P<0.05) and relatively higher wall thickness (0.74±0.06; P<0.05) of the LV free wall in mRen2 rats than those of the interventricular septum (0.68±0.02 and 0.54±0.03, respectively).At the cellular level, both lower Ca2+ sensitivity (pCa50) and higher troponin I (cTnI) phosphorylation of LV cardiomyocytes from the free wall and the septum (n=mean of 3‐3/4‐4 rats) suggest abnormal systolic function in the mRen2 group as compared to the control. LV heterogeneity of mRen2 rats is further supported by lower cardiomyocyte maximal Ca2+‐activated force (21.2±1.4 kN/m2), higher Ca2+ sensitivity (5.85±0.01) and phosphorylation of cTnI at Thr‐144 (1.62±0.19; P<0.05) in the free wall than those in the septum (30.0±0.6 kN/m2, 5.76±0.02 and 1.00±0.15, respectively).The local abnormalities of LV contraction on top of global diastolic dysfunction may provide a pathomechanism for the clinical progression with increasing mortality seen in human.
Angiotensin II‐mediated Proliferation of Neonatal Cardiac Fibroblasts and Role of Mitochondrial Ca2+ Uptake and Superoxide Generation
Authors: Mishra Jyotsna , Fu Deming , Jhun Bong Sook , Sheu Shey‐Shing , O‐Uchi Jin 
Published: November 2023

Cardiac fibroblasts (CFs) are the major cell type in addition to cardiomyocytes in the mammalian heart, and they play a vital role in regulating normal cardiac function and adaptive cardiac remodeling during adverse clinical conditions, including fibrosis. Recent studies have revealed Angiotensin II (AngII) as a one of the principal effectors for promoting fibroblast differentiation and cardiac remodeling in the failing heart. In addition, evidences have shown that the downstream effects of AngII are mediated by elevated levels of reactive oxygen species (ROS) which have also been implicated in CF proliferation. However, the detailed signaling mechanism of ROS generation by AngII signaling in the CFs still remains unclear. We previously demonstrated in cardiac myoblast H9C2 cells that the main Ca2+ uptake mechanism, the mitochondrial Ca2+ uniporter (MCU)‐mediated mitochondrial Ca2+ overload, induces mitochondrial superoxide (mtSO) generation. Therefore, we hypothesize that Ang‐II mediated stimulation may increase mitochondrial Ca2+‐induced mtSO generation, which may further activate ROS‐dependent proliferation signaling in CFs. Using mitochondria‐targeted Ca2+ biosensor in neonatal rat CFs (NCF), we first established that AngII (≥1 μM) stimulation significantly increases the mitochondrial Ca2+ uptake in response to cytosolic Ca2+ elevation induced by the Ca2+ release from the endoplasmic reticulum (ER). Further, we also found that AngII stimulation leads to increase in the mtSO levels. We next confirmed that proliferative pathways, including ERK1/2 and p38 AT‐II were also activated in a time‐dependent manner on AngII stimulation in CFs, while the effect was abolished by pretreatment with mitochondria‐targeted antioxidant, Mito‐tempo without affecting the profiles of AngII ‐induced ER Ca2+ release and mitochondrial Ca2+ uptake. Finally, genetic inhibition of MCU function by overexpressing dominant‐negative MCU also blocked AngII‐mediated activation of proliferative pathways in CFs. In conclusion, these data suggest that MCU‐mediated mitochondrial Ca2+ accumulation induces mtSO generation and this ROS generation serves as an important regulator for the proliferative pathway in CFs under Ang II stimulation.Support or Funding Information• 14BGIA18830032 and 16SDG27260248 from AHA to J.O‐U.• Medical Research Grant (#H1403) from W.W. Smith Foundation to J.O.‐U.• NIH grant (R01 HL093671) to S.‐S.S
Green fluorescence from non‐aequorea hydrozoa Gonionemus vertens (Clinging Jellyfish)
Authors: Petroff Elena , Snitsarev Vladislav , Lopez Rafael , Bologna Paul A.X. , Gaynor John J. 
Published: November 2023

We have examined the green fluorescence of the Clinging Jellyfish, Gonionemus vertens (GV), a species that first appeared in New Jersey coastal estuaries in June, 2016. Intact specimens (0.30–0.35 g wet weight) were homogenized in 3 mL of pure water using a Kontes Glass homogenizer (Co 23; Vineland, NJ) with 10 rotational strokes and centrifuged at 16,100 × g for 10 min at 4°C (Eppendorf 5415D microcentrifuge). Two mL of the supernatant was placed in a standard 1 cm methacrylate cuvette and fluorescence was measured with a Hitachi F‐7000 spectrofluorometer at 25°C. In vitro excitation and emission maxima were λExMax = 501.4±0.2 (nm) (n=4) and λEmMax = 512.9±0.2 (nm) (n=3), respectively for the 4 individuals measured.Adult medusa of GV are relatively small and fit in a standard 1 cm spectroscopic cuvette, so we measured in vivo fluorescence of the intact individuals in sterile artificial seawater (20 ppm). When first placed in the cuvette, actively swimming GV cannot be measured; but after some time, individuals use their tentacles to cling to the inner cuvette wall and remain stationary permitting measurements. Multiple spectral scans from 450 nm to 510 nm (excitation scan) or from 510 to 570 nm (emission scan) at 240 nm/min (15 seconds per scan) were performed. In five individuals successfully measured without movements, excitation and emission maxima were λExMax = 503.9±0.4 (nm) (n=5) and λEmMax = 515.4±0.2 (nm) (n=5), respectively. t‐tests between in vitro and in vivo measurements showed a significant difference between both excitation maxima (p<0.001) and emission maxima (p<0.0001), indicating that the green fluorescence of GV is sensitive to environmental parameters.A search of the literature of green fluorescent proteins suggests that the particular excitation/emission pattern we have recorded in GV is unique and represents the shortest Stokes shift seen in nature. We plan to continue our studies on the green fluorescence of GV with a goal of isolating both the gene and protein responsible for this fluorescence through transcriptome analysis.Support or Funding InformationSokol grant to JG, VS, and EP
Neuroimmune communication between the circadian clock and tumor development in mice
Authors: Aiello Ignacio , Roman Fernanda , Fedele Malena Mul , Cerliani Belen , Richard Silvina , Chiesa Juan Jose , Golombek Diego Andrés , Paladino Natalia 
Published: November 2023

Daily environmental changes on Earth have imposed a selective pressure for life driving the development of circadian clock mechanisms that generate rhythms in physiological and behavioral variables, and are capable of entraining to external cues. In mammals, the clock resides in the hypothalamic suprachiasmatic nuclei (SCN), and the principal signal that adjusts its activity is the light‐dark (LD) cycle. Bidirectional interactions between the immune and the circadian systems have been under intensive study in recent years. Particularly, it has become very important the role of the circadian clock in tumor progression. According to the World Health Organization, work schedules that imply a desynchronization between the circadian system and the environmental and social factors, such as shift work, represent a risk factor for the development of cancer. Moreover, it's known that tumor growth can be regulated by genes that are part of the molecular circadian clock.Our purpose is to determine the effect of circadian desynchronization induced by chronic jet‐lag (CJL) in tumor development, focusing in the role of the immune system. We injected subcutaneously B16 cells (murine melanoma) in C57bl/6 mice housed under CJL (6 h advances every 2 days) or normal light (LD 12:12) conditions. Our results show that the tumor growth rate was significantly higher, while latency was lower under CJL condition. However, early tumor angiogenesis was not affected. In addition, tumor and liver expression of clock genes Per1–2 were decreased under CJL condition, but levels of the clock gene Bmal1 were similar under both conditions. We have also studied the proinflammatory response in the tumors of these animals at two different time points, and we found that the levels of cytokines TNF‐α, IL‐6 and IL–1β were induced during the day in animals living in normal light conditions, while the expression was similar at both time points in animals subjected to circadian desynchronization. Additionally, the spleen percentage of mature antigen‐presenting cells was decreased under CJL schedule.For the other hand, animals carrying tumors showed a decrease in the percentage of nocturnal activity and in the strength of their locotomor activity rhythms in LD conditions. We have also analyzed the mRNA levels of the chemokine Ccl2/MCP‐1 (Monocyte Chemotactic Protein‐1) and TNF‐α in the SCN of animals subjected to normal light conditions. The first one seems to increase in the SCN of animals with the tumor, while the other one was undetectable.In conclusion, here we show that the bidirectional interaction between the immune and circadian systems can be mediated by cytokines/chemokines in a murine model tumor development. We have also confirmed that circadian desynchronization can affect the development of a tumor and that the inflammatory molecules present in the tumor are over circadian control.
Hibernation: Insights from Comparative Genomics of Zapus Species
Authors: Israelsen William J. , McNulty Alyssa D. , Cong Qian 
Published: November 2023

Hibernating mammals employ unique metabolic strategies to survive harsh conditions. They become obese prior to the onset of winter, then conserve their stored energy during a long winter fast by slowing metabolism and becoming deeply hypothermic. Hibernation phenotypes may provide insights into control of metabolism and have applications in medicine, but little is known about the molecular mechanisms or genetic underpinnings of hibernation. We have begun using the meadow jumping mouse (Zapus hudsonius) as a laboratory hibernation model. We sequenced, de novo assembled, and annotated a meadow jumping mouse genome. We further generated whole genome sequences for six additional meadow jumping mice and seven western jumping mice (Zapus princeps), a closely related hibernator. Z. hudsonius uses photoperiod as the cue to initiate fall fattening, while Z. princeps ignores photoperiod and prepares for hibernation based on food availability. Preliminary comparative genomic analysis reveals a subset of ~1700 proteins that are significantly diverged between the species. These diverged proteins are enriched for genes involved in pheromone sensing and reproduction, immunity, and metabolism. Analysis of individual genes yields insights into speciation and may reveal candidate genes that explain the phenotypic differences between the two species.Support or Funding InformationWJI acknowledges support from the Sara and Frank McKnight Fund for Biochemical Research and an NIH Early Independence Award (DP5OD021365).
Effects of amaranth (Amaranthus esculantus) and canola (Brassica napus) oil supplementation on oxidative metabolism of neutrophils in patients with obesity
Authors: Dominika Kanikowska , Alina Kanikowska , Rafał Rutkowski , Małgorzata Włochal , Marian Grzymisławski , Maki Sato , Andrzej Bręborowicz , Janusz Witowski 
Published: November 2023

Reactive oxygen species are postulated to be involved in systemic inflammation and oxidative stress in patients with obesity. Activated polymorphonuclear neutrophils (PMNs) generate high amounts of reactive oxygen species. The aim of the study is to investigate whether amaranth oil (Amaranthus esculantus) and canola (Brassica napus) oil supplementation impacts on oxidative metabolism in patients with obesity. The hypothesis is that, owing to its lipid‐lowering and antioxidant properties, amaranth oil and canola oil will protect against oxidative stress. In the study, the effects of amaranth and canola oils on oxidative metabolism and apoptosis of neutrophils from obese individuals has been investigated. We tested 19 obese patients (aged 48.3±16 years,6 women and 13 men, BMI = 41.1 ±7.8 kg/m2, (mean ±SD)). The study adhered to basic Principles of the Declaration of Helsinki. Neutrophils were isolated and oxidant production, in response to phorbol 12‐myristate 13‐acetate, was characterized by using luminol dependent chemiluminescence (CL) and flow cytometric dichlorofluorescin oxidation assay. Neutrophils from obese individuals before treatment had a significantly higher H2O2 production and CL response compared to obese after 3 weeks of both oils supplementation (p < 0.05). This amaranth oil and canola oil exert beneficial effects in cells and may, therefore, be useful in the treatment of obesity disorders.Support or Funding Informationnone
Myometrial Response to Oxytocin Is Affected by Parity
Authors: Porta Maura , Sondgeroth Korie 
Published: November 2023

ObjectiveThe complex array of hormonal interactions that develop during pregnancy exert a profound impact in the reproductive system and in various other aspects of a woman's physiology. Some systems are permanently changed via epigenetic DNA modification, as it has been shown recently in the mammary gland (dos Santos, 2015). The aim of the present study was to investigate the hypothesis that pregnancy can affect some aspects of the uterine function, as well. Thus, we compared the response of non‐pregnant myometrium harvested from virgin and parous female rats to increasing concentrations of oxytocin, PGE2, and PGF2, which are endogenous stimulators of contractility in the uterus.MethodsVirgin and parous female non‐pregnant CD Sprague Dawley rats (Charles River Laboratories) were euthanized at 18 weeks of age (to eliminate the confounding effect of age on contractility measurements) during proestrus (to eliminated variability due to hormonal fluctuations). The uterine horns were removed and one was flash frozen for later use (ELISA), while the other was dissected into six 3×10 mm strips. These were then suspended in a tissue bath containing Krebs solution (in mM, NaCl 117, KCl 4.7, NaHCO3 25, MgCl2 1.2, KH2PO4 1.2, CaCl2 2.5, glucose 11, pH= 7.4) at 37°C and bubbled with 95% O2 and 5% CO2. Separate dose responses curves to oxytocin, PGE2, and PGF2 were generated by incremental additions of each drug to the tissue bath (10E‐10 to 10E‐5 M in all cases). After the maximal dose of stimulator, 10E‐6 M of terbutaline (beta‐2 agonist; tocolytic) was added to the system.ResultsWe found that indeed parous myometrium displays a significantly stronger response to oxytocin than its virgin counterpart (P<0.05). The EC50 of the drug for the receptor appears unchanged, but the maximal response to the drug is higher (P<0.05). Furthermore, the ability of a 10E‐6 M dose of terbutaline to inhibit activation of myometrial strips by maximal doses of oxytocin (10E‐5 M) also differs. Terbutaline inhibits 60±6% of oxytocin‐activated virgin myometrial contraction, vs. 39±5% of oxytocin‐activated parous myometrial contraction (P<0.005). Preliminary ELISA results suggest a ~30% higher expression of oxytocin receptor in non‐pregnant parous uterine tissue. No significant differences in the myometrial dose‐response relationship in virgin versus parous uterine tissue emerged in PGE2 and PGF2 treated strips.ConclusionsOur results suggest that at least in the response to oxytocin, parity affects uterine contractility. This supports the general hypothesis that some (likely epigenetic) changes occur in the uterine smooth muscle during pregnancy that persist post‐parturition.Support or Funding InformationThis study was supported by Midwestern University.
Effects of Calorie Restriction and Fiber Type on Glucose Uptake in Single Fibers from Old Rats
Authors: Wang Haiyan , Arias Edward B. , Yu Carmen S. , Verkerke Anthony R.P. , Cartee Gregory D. 
Published: November 2023

The major tissue for insulin‐stimulated glucose disposal is skeletal muscle. Calorie restriction (CR; reducing calorie intake by ~40% below ad libitum) can increase glucose uptake by insulin‐stimulated muscle. Skeletal muscle is comprised of multiple, heterogeneous fiber types, and the efficacy of CR for enhancing insulin‐stimulated glucose uptake across all fiber types is uncertain. The conventional approach to evaluate possible fiber type differences has been to measure glucose uptake by multiple muscles or regions of muscles with differing fiber type profiles. However, tissue analyses cannot resolve fiber type differences in glucose uptake at the cellular level because: 1) whole muscles include multiple fiber types; 2) apparently no rodent muscle has been identified that is mostly comprised of type IIX fibers; 3) measurement of glucose uptake by fibers expressing multiple myosin heavy chain isoforms (i.e., hybrid fibers) requires single fiber analysis; and 4) various cell types (including neural, vascular, and adipose cells) contribute to glucose uptake determined in muscle tissue samples. The limitations of muscle tissue analysis motivated us to recently develop and validate the first method to determine both glucose uptake and fiber type in a single rat skeletal muscle fiber. We used this method in the current study with the primary aim to determine in 23–26 months‐old rats the effects of chronic CR (60% of ad libitum, AL, initiated at 14 weeks‐old) and fiber type on insulin‐stimulated glucose uptake by single fibers of diverse fiber types. Isolated epitrochlearis muscles from AL and CR rats were incubated with [3H]‐2‐deoxyglucose ± 1.8nMinsulin. Glucose uptake and fiber type (based on myosin heavy chain expression) were determined for single fibers dissected from the muscles. We also determined CR‐effects on the abundance of hexokinase II (a key enzyme that favors greater glucose uptake by catalyzing the conversion of glucose to glucose 6‐phosphate) in single fibers by immunoblotting. We found in single fibers from CR compared to AL rats: 1) significantly greater insulin‐stimulated glucose uptake by type I, IIA, IIB, IIBX and IIX fibers (P<0.01 for I, IIA and IIB; P<0.001 for IIBX and IIX); and 2) unaltered hexokinase II abundance in each fiber type. These observations revealed at the cellular level that long‐term CR by older rats enhanced insulin‐stimulated glucose uptake in rat epitrochlearis muscle regardless of fiber type and independent of elevated hexokinase II protein content.Support or Funding InformationThis work was supported by a grant from the National Institute on Aging at the National Institutes of Health (grant number AG10026) to GDC.
Prior Treatment with the AMPK Activator AICAR Induces Subsequently Enhanced Glucose Uptake in Isolated Skeletal Muscles from Old Rats
Authors: Oki Kentaro , Arias Edward B , Cartee Gregory D 
Published: November 2023

Prior treatment of isolated skeletal muscles from young rats (≤4 months‐old) to the 5′ adenosine monophosphate‐activated protein kinase (AMPK) activator 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICAR) in the presence of serum can induce elevated insulin‐stimulated glucose uptake (GU) several hours after of removal of the muscles from AICAR and serum. Previous research did not determine if both AICAR and serum were required for the observed effect on insulin‐dependent GU, or if incubation with either was sufficient. Earlier research also has not evaluated the effects of prior AICAR incubation with and without serum on the GU of muscles from older rats. Accordingly, we examined the separate and combined effects of AICAR and serum on subsequent insulin‐independent and insulin‐dependent GU in skeletal muscles from aged rats (23–24 month old; n=20). Both epitrochlearis muscles from each rat were dissected and split into two separate muscle strips. Each muscle strip underwent a four‐step incubation. During step 1 (60 minutes), one muscle strip from each animal was incubated with: Krebs‐Henseleit Buffer (KHB) alone, KHB with AICAR, serum alone, or serum with AICAR. During step 2 (180 minutes), all muscle strips were incubated with KHB. During steps 3 (30 minutes) and 4 (20 minutes), all 4 strips from 10 rats were incubated without insulin, and all 4 strips from the remaining 10 rats were incubated with insulin. During step 4, muscle strips were incubated with radiolabeled 3‐O‐methyl‐D‐glucose and the same insulin concentration as the previous step. Repeated measures analysis of variance (RM ANOVA) in the basal (no insulin) group indicated a significant interaction (serum × AICAR) for insulin‐independent GU. In the insulin group, RM ANOVA revealed a significant main effect of AICAR on insulin‐dependent GU without a significant main effect of serum or significant serum × AICAR interaction. Our working hypothesis is that the elevated insulin‐independent GU after combined AICAR and serum incubation is secondary to subsequently elevated phosphorylation of TBC1D1 on Ser237 (an AMPK‐phosphosite), and the AICAR‐induced elevation of insulin‐dependent GU is secondary to subsequently elevated phosphorylation of TBC1D4 on Ser711 (an AMPK phosphosite) and Thr642 (an Akt‐phosphosite).Support or Funding InformationNIA Training Grant AG 000114 and NIA R01 AG10026 (GDC)