bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxygen Uptake Efficiency During Cardiopulmonary Exercise Testing in Healthy Subjects
Authors: Sun Xingguo , Hansen James E 
Published: June 2021

When evaluating circulatory efficiency in transporting O2 from the lung to the metabolizing tissues in normal subjects or in patients with cardiovascular disease, the relationship of oxygen uptake (VO2, mL/min, STPD) to ventilation (VE, L/min, BTPS), i.e. oxygen uptake efficiency (OUE) has been useful for heart failure prognosis. Although it has not been normalized to the variables of age, body size, gender and fitness, OUE is often reduced in patients with cardiovascular diseases and ventilation/perfusion mismatching. To better quantify and report OUE in normal subjects and patients, we considered several VO2 and VE relationships during exercise and how the above variables influenced their values.Methods and ResultsWe studied 474 healthy adults, aged 17–78 years during increasing cycle and/or treadmill cardiopulmonary exercise at three sites, reducing the total VE by the equipment dead space ventilation. Three methods of calculation were analyzed: 1) OUE plateau (OUEP). The OUEP and OUE@AT were similar, highly reproducible, and less variable than the OUES (p<0.0001), and were unaffected by the study sites or methods of exercise. The resultant prediction equations for men are: OUEP(mL/L)=35.4–0.185xyears+0.080xcm (−2.2 for women).ConclusionsThe OUEP and OUE@AT are the preferred methods to measure circulatory efficiency.
MIP/MTMR14 is implicated in skeletal muscle aging
Authors: Brotto Leticia , Craig Robin , Hall Todd , Loghry Michael , Valdivia Hector , Nosek Thomas , Shen J , Qu C‐K , Brotto Marco 
Published: June 2021

We recently discovered a muscle‐specific inositol phosphatase (MIP/MTMR14) and demonstrated that systemic ablation of MIP induces intracellular elevation of PI(3,5)P2 in skeletal muscle cells, decreases store‐operated calcium entry, increases resting calcium, and enhances susceptibility to in vitro fatiguing stimulation after exercise (Nat Cell Biol, 2009). We also showed that PI(3,5)P2 directly binds to, activates the RyR1, and increases the open probability of the sarcoplasmic reticulum calcium channel. Here, we show that MIP expression and enzymatic activity is drastically reduced in aged compared with wild type muscles. Muscles from MIP KO animals display a combination of aging‐related muscle function changes such as reduced muscle strength, power, and activity that gradually and prematurely manifest between 12–18 months of age. We are now investigating the molecular mechanisms of MIP/PI(3,5)P2 modulation of muscle function during aging. We propose that a reduction in MIP with age is one of the factors which contribute to sarcopenia making the MIP KO a useful animal model for better understanding natural sarcopenia.Support: NIH‐TREC grant to TN, CQ, MB. American Heart Association Grant to MB.
Thyroid hormone increases rapidly the length of the AT1R mRNA poly‐A tail in cardiomyocytes
Authors: Diniz Gabriela Placoná , Bruneto Erika , da Silva Francemilson Goulart , Nunes Maria Tereza , de Chaves Maria Luiza Morais Barreto 
Published: June 2021

ObjectiveAngiotensin II type 1 receptor (AT1R) participates of thyroid hormone (TH)‐induced cardiomyocyte hypertrophy. In addition, TH modulates rapidly the AT1R expression. However, the possible mechanism involved in this response is unknown. The aim of the present study was to investigate the T3 influence in the length of the AT1R mRNA poly‐A tail in cardiomyocytes.MethodsCardiomyocytes cultures were prepared from ventricles of neonatal Wistar rats by colagenase/pancreatin method. The cells were treated with serum‐free medium (control cells) or serum‐free medium containing T3 (10nM) for 5, 10, 15 and 30 minutes. The polyadenylation of the AT1R mRNA was evaluated by Rapid Amplification of cDNAs ends ‐ poly(A) test. The results are expressed in percentage as mean±SD. Data were analyzed using one‐way analysis of variance, followed by Tukey's post hoc test. Values of P<0.05 were considered statistically significant (n=5).ResultsThe cardiomyocytes treated with T3 for 5 (157, P<0.01), 10 (172, P<0.01), 15 (167, P<0.01) and 30 minutes (140, P<0.01) showed a significant increase in the length of the AT1R mRNA poly‐A tail compared with that observed in the control cells (100%).ConclusionThese results demonstrate for the first time that T3 stimulates rapidly the polyadenylation of the AT1R mRNA, which may be contributing to the rapid increase on AT1R expression promoted by TH.
AMPK signaling pathway is downregulated by Thyroid Hormone in cardiomyocytes
Authors: Takano Ana Paula Cremasco , Diniz Gabriela Placoná , de Chaves Maria Luiza Morais Barreto 
Published: June 2021

ObjectiveThyroid hormone (TH) modulates rapidly several signaling pathways which have been implicated in cardiac hypertrophy. In addition, the AMP‐activated protein kinase (AMPK) also plays an important role in regulating cardiac hypertrophy. The aim of the present study was to investigate the TH effect on AMPK signaling pathway in cardiomyocytes.MethodsCardiomyocytes cultures were prepared from ventricles of neonatal Wistar rats by colagenase/pancreatin method. The cells were treated with serum‐free medium (control cells) or serum‐free medium containing T3 (10nM) for 5, 10, 15 and 30 minutes. The AMPK, LKB1 and protein phosphatase 2C (PP2C) were analyzed by Western Blot. Data were presented as mean±SD and were evaluated using one‐way analysis of variance. Values of P<0.05 were considered statistically significant.ResultsThe cardiomyocytes treated with T3 for 10 and 15 minutes presented a significant decrease on AMPK (86.21±4.62 and 74.32±9.23, P<0.05) and LKB1 (65.18±5.17 and 67.43±4.92, P<0.01) phosphorylation levels, as well as on PP2C levels (77.5±5.55 and 75.21±9.83, P<0.05) in relation to control cells.ConclusionThese data demonstrate for the first time that TH modulates rapidly the AMPK signaling pathway in cardiomyocytes cultures. The possible involvement of this signaling pathway in the modulation of TH‐induced cardiomyocyte hypertrophy remains to be investigated.
Structural integration and cardiovascular effects following transplantation of endothelial progenitor cells (EPCs) into the brainstem of rats
Authors: Baquero Ana Maria Alviar , Kränkel Nicolle , Whitaker John , Dewhurst Mark , Maddedu Paolo , Paton Julian F.R. 
Published: June 2021

Our evidence indicates that brainstem endothelium is a viable target for controlling arterial pressure. Thus, we have used EPCs to target the brainstem microvasculature in vivo and assessed any effect on cardiovascular function. Bone marrow mononuclear cells from male Wistar rats were expanded for 7–15 days in conditions appropriate for the endothelial lineage. EPCs were characterized by immunofluorescence staining, flow cytometry, and using the Matrigel assay for network formation. Fluorescently tagged EPCs were injected intraparenchymally into the nucleus tractus solitarii (NTS), a region regulating arterial pressure, of male Wistar rats. Experiments were terminated 16 days post‐injection. EPCs remained at the site of injection until animals were sacrificed. During this time, EPCs migrated away from the injection site becoming closely associated with the vasculature. Peak measurements occurred between 10 to 15 days post injection and included a reduction in: systolic pressure (SP)(−7±0.5 mmHg), low frequency spectra of SP (−19%±1.0‐ indicating reduced sympathetic vasomotor tone) and heart rate (−18±4.3 beats/min). Cardiac baroreflex sensitivity increased (22%±0.8). In conclusion, EPCs remain viable for at least 16 days when transplanted into the NTS in vivo, integrate into the vascular wall and alter cardiovascular autonomic function in normotensive rats.MRC & Pfizer funded research.
Sympathetic overactivity in sinoaortic denervated C57BL mice
Authors: Rodrigues Fernanda L , Oliveira Mauro , da Silva Valdo J Dias , Salgado Helio C , Fazan Rubens 
Published: June 2021

Male C57BL mice were submitted to sinoaortic denervation (SAD), or sham surgery, implanted with catheters into femoral artery and jugular vein and let recover for 5 days. After basal recording of arterial pressure (AP) and pulse interval (PI) mice received cardiac autonomic receptor blockers methylatropine or propranolol (n=8–11 in each group). PI changes due to methylatropine or propranolol were measured as cardiac vagal and sympathetic tone, respectively. AP variability was calculated by standard deviation of successive values (SDNN) of systolic AP and PI variability determined by SDNN as well as by the square root of the mean squared differences of successive values of PI (RMSSD). Mean AP and SDNN of SAP was higher in SAD (149±3 and 10.0±0.5 mmHg) as compared to intact mice (136±2 and 6.5±0.4 mmHg). PI was similar between groups (104±3 vs 104±2 ms) while SDNN and RMSSD of PI were lower in SAD (5.4±0.7 and 2.0±0.2 ms) as compared to intact mice (8.2±0.8 and 2.7±0.3 ms). Atropine did not change PI of SAD (100±4 to 98±4 ms), while slightly decreased PI of control mice (103±2 to 96±2 ms, p<0.05). The increase in PI elicited by propranolol was marked higher in SAD (98±6 to 144±9 ms) than in intact mice (98±4 to 124±3 ms). Five days after SAD mice showed mild hypertension with marked increase in AP variability and cardiac sympathetic tone.Support: FAPESP, CNPq and CAPES.
Interaction of the effects between estrogen receptor‐alpha polymorphism and physical activity or nutrient on bone mass in Japanese young women
Authors: Kondo Hiroyo , Fujino Hidemi , Murakami Shinichiro , Takeda Isao , Ishihara Akihiko 
Published: June 2021

Bone mass is strongly influenced by genetic and/or environmental factors. The estrogen receptor alpha (ESR1) is a good genetic candidate for a prime regulator of bone metabolism. The purpose of this study was to investigate the association between a PvuII or XbaI RFLP of the ESR1 polymorphisms and bone mass in Japanese young women, and the interaction with physical activity or nutrition as a lifestyle factor.Seventy healthy women (20–23 yr) were genotyped for ESR1. Bone mass was measured by quantitative ultrasound measurement. The ESR1 polymorphisms at intron I (Pvu II and Xba I) were genotyped using the PCR‐RFLP.Two major trends could be demonstrated for the ESR1 polymorphisms. Body weight, BMI and physical activity are significantly associated with bone mass in the subjects carrying CT heterozygote or TT homozygote (P<0.01). Furthermore, fish intake is significantly associated with bone mass in the subjects carrying AG heterozygote (P<0.01).These results suggest that physical activity and/or calcium intake are more important for bone mass metabolism in young women carrying T allele or AG heterozygote in estrogen receptor alpha gene, respectively.Supported by Grants‐in‐Aid for Science Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, No. 19700529.
Preparative reading improves learning in an Anatomy & Physiology course
Authors: Krontiris‐Litowitz Johanna 
Published: June 2021

Students often resist reading their textbooks, causing faculty to prepare their lectures accordingly. The question that arises is “Does preparative reading improve learning?”. This project examines the impact of pre‐class reading on student learning in a one semester Anatomy & Physiology course.In this protocol, 4 classroom quizzes were offered during the course. For 2 of the quizzes (READ) students were expected to read the textbook to learn the material for the quiz and the quiz topic was not discussed in class. For the other 2 quizzes (NOREAD) the quiz topic was discussed in class and students were expected to review lecture notes to learn the material. Student performance on 4 essay exam questions evaluated the effect of preparative reading on learning and communication.Students performed better on READ essay questions than on NOREAD questions. Mean scores on READ essay questions were higher than on NOREAD essay questions. Almost all students answered READ essay questions but 10–20% of the students did not answer NOREAD essay questions. In addition, students communicated their understanding better on READ exam questions that on NOREAD exam questions by writing longer essays, incorporating more ideas, and more clearly verbalized the relationship between their answer and the essay question.This project suggests that preparative reading can improve learning and communication of understanding.
Regulation of ameloblastin expression via gap junctional communication
Authors: Yamada Aya , Iwamoto Tsutomu , Nakamura Takashi , Fukumoto Satoshi 
Published: June 2021

Ameloblastin is a tooth‐specific glycoprotein that represents the most abundant enamel matrix protein, and plays an important role in maintaining the differentiation state of ameloblasts, serves as a cell adhesion molecule, and inhibits the proliferation of the dental epithelium. Our aim was to analyze the regulatory mechanism of ameloblastin expression via gap junctional communication using Gja1 null‐mice. Gja1 is one of the gap junctional proteins and highly expressed in tooth germ. Gja1 null‐mice showed disturbance of tooth germ, salivary gland, and lung morphogenesis, as similar to the phenotype of oculodento‐digital dysplasia. Inner dental epithelium in Gja1‐null mutants formed multiple cell layers. This phenotype was similar to that of ameloblastin mutant mice. Further, ameloblastin expression was dramatically decreased in Gja1‐null ameloblasts. TGF‐β1 administration induced ameloblastin expression in dental epithelial cell culture. On the other hand, Gap junction inhibitor 18α‐Gry and Oleamide inhibited the expression of ameloblastin induced by TGF‐β1. These results suggest that Gap junctional communication via Gja1 is important for the expression of ameloblastin and the differentiation of ameloblasts.Grant Funding Source: Ministry of Education, Culture, Sports, Science and Technology of Japan
Determination of inferior alveolar nerve position via anatomical dissection and micro‐CT: A view towards dental implants
Authors: Massey Natalie Diana , Galil Khadry , Wilson Timothy 
Published: June 2021

Hundreds of thousands of dental implants are performed each year. Precise knowledge of inferior alveolar nerve (IAN) location prior to dental implant placement is necessary to avoid complications of nerve damage such as sensory disturbances. The IAN courses anteriorly within the body of the mandible providing sensory nerve supply to the mandibular teeth. Current imaging modalities used to visualize the position of the IAN prior to dental implant placement may not be accurate. This study provides new information for locating the nerve more accurately. Micro‐CT images were acquired at a slice thickness of 154μm from 8 cadaveric mandibles. The same specimens were bisected and each hemi‐mandible was divided into 5 sections according to pre‐defined molar and pre‐molar width measurements. Superior, inferior, buccal and lingual bone distance measurements surrounding the mandibular canal were obtained by direct digital caliper measurements, and compared with corresponding μCT measurements obtained using the AMIRA segmentation and measuring software. Preliminary results suggest substantial variability in bone distance superior to the mandibular canal depending on the length of time since tooth loss. This finding highlights the importance of using an imaging modality that provides the highest spatial accuracy, when determining IAN location during the pre‐implantation stage of dental implant placement.Grant Funding Source: Internal
Papionin models for the functional relationship between the face and osseous nasopharyngeal boundaries
Authors: Pagano Anthony Santino , Yang David , Laitman Jeffrey T 
Published: June 2021

With many similarities to humans, primate models are valuable for studying the functional relationships of the upper airway. This study uses baboons and related species to test the hypothesis that extreme facial prognathism is related to tall, narrow choanae and nasopharynges. 3D landmark data were collected along the face and upper respiratory tracts of Papio, Mandrillus, and other relatively orthognathic papionins (Macaca, Cercocebus, Lophocebus). Coordinate data were subjected to Procrustes fitting, which optimally superimposes and scales sets of coordinates between individuals. This allows for direct comparison of distance, area, and volume measures. All papionins displayed marked sexual dimorphism with males possessing tall, narrow choanae, long palates, and narrow basicrania. No dimorphism was found in choanal area and nasopharyngeal depth and volume. Over ontogeny, all papionins displayed similar schedules of growth change. When pooling adult males into genera, Papio and Mandrillus possess taller, narrower choanae and nasopharynges more shallow, narrow, and voluminous (vertically) than those of other papionins (p<.05). However, in pairwise comparisons, not all species of Papio and Mandrillus were significantly (p<.05) different from the other papionin species. The results support the hypothesis and suggest that facial prognathism is related to vertical expansion of the nasopharynx.Grant Funding Source: NSF IGERT NYCEP Graduate Student Support
Evidence Based Analysis: Discussion of the relationship between prophylactic management of predisposing risk factors and non contact ACL injuries with female athletes
Authors: Bukoskey Thomas Patrick , Graves Mark , Humphreys Ryan 
Published: June 2021

ObjectiveThe purpose of this project was to determine if the number of non‐contact ACL injuries could be reduced in female soccer athletes with predisposing risk factors to an ACL injury.MethodsA peer reviewed literature search was conducted using databases such as the British Journal of Sports Medicine, Journal of the APTA, and CINATHOL. Article inclusion was based on level of evidence and key words that were related to the clinical question.ResultsFive of the 23 articles selected discussed risk factors, 9 discussed neuromuscular control, 6 discussed hyperpronation of the subtalar joint, 2 discussed anterior knee laxity, and 1 discussed male versus female athletic differences.ConclusionsA synthesis of the evidence identifying hyperpronation of the subtalar joint, anterior knee laxity, and neuromuscular control deficits as treatments to decrease the number of non‐contact ACL injuries in female athletes. The literature also suggested treatment should include prophylactic management to include Low‐Dye taping, insertion of a medial wedge orthotic, and preseason neuromuscular control‐training regime lasting six weeks. The neuromuscular training should include exercises that focused on feed forward techniques. According to the literature, these techniques were comprised of flexibility, muscular strengthening, plyometrics, core strengthening, sport related drills, and balance exercises.RelevanceThis evidence based research project reinforces anatomical concepts as the basis for treatment of non‐contact ACL injuries. Combining an understanding of the anatomy and applying the techniques identified in the literature the number of ACL injuries, amount of time lost during sport participation, and amount of health care dollars spent may be reduced for the identified population.
Flutamide does not mediate testosterone effects on BMP4 response in wild‐type rabbit bone cells
Authors: Cray James , Lensie Emily , Smalley Melissa , Finegold David , Siegel Michael , Losee Joseph , Mooney Mark , Cooper Gregory 
Published: June 2021

We previously reported that a treatment of testosterone (T) and BMP4 led to decreased proliferation and differentiation in rabbit calvarial bone cells. A primary sex difference was noted; males exhibited greater differentiation for suture bone and females for non‐suture bone. Those results suggested that T decreased response for BMP4 treated cells. We hypothesized that this effect is mediated through the androgen receptor (AR). Cells were treated with the AR blocker, flutamide (F), along with T and BMP4 to determine cellular response. Calvarial cells (suture or non‐suture) from New Zealand White rabbits (N=14) were stimulated with 50ng/ml BMP4 and T (10–16 dose), with or without F treatments (10‐8, ‐10 or ‐12 dose). Proliferation and differentiation were assessed after 7 days. Differences between F treatments by dose, sex, and bone‐type were analyzed. F did not effect BMP4 alone, p>.05. The dose response was biphasic, p<.05. Non‐suture bone was more susceptible to this F‐dependent decrease in proliferation p<.05, and male derived cells exhibited a greater decrease, p<.05. F did not effect differentiation p>.05, by dose, cell type, or sex, p>.05. These results suggest the effect T has on reducing BMP4‐induced differentiation may not be mediated through the AR pathway. An alternative pathway (e.g., MAPK) should be explored for the direct effect of T on normal calvarial bone cell response.Grant Funding Source: Internal
Restorative and Compensatory Respiratory Plasticity Following Cervical Spinal Cord Injury (SCI)
Authors: Lane Michael Aron , Meyer John W. , Mercier Lynne M , Vavrousek Jennie C. , Salazar Krystal , O'steen Barbara E , Fuller David D , Reier Paul J 
Published: June 2021

Spontaneous recovery of diaphragm function ipsilateral to a complete lateral C2 hemisection (C2Hx) is an established example of “restorative respiratory plasticity”. The extent of recovered ipsilateral phrenic motoneuron activity is limited, however, and its impact on breathing has not been extensively investigated. The present study was conducted to test the hypothesis that contralateral “compensatory plasticity” plays a much greater role and is accompanied by connectivity changes associated with the contralateral phrenic circuitry.Using combined anterograde and transneuronal retrograde tracing (with biotin dextran amine (BDA) and pseudorabies virus (PRV), respectively), we recently demonstrated that cells within the medulla innervate the phrenic motoneurons (PhMNs) both directly and indirectly (via interneurons; INs). More recent experiments have revealed reduced bulbospinal inputs to PhMNs ipsilateral to injury, as well as to associated pre‐phrenic INs. PRV tracing phrenic pathways ipsilateral to injury also showed decreased IN‐PhMN connectivity. In contrast, PRV tracing of phrenic pathways contralateral to injury demonstrate some bilateral recruitment of INs at C1 which are not infected under similar labeling conditions in normal rats. These results indicate neural substrate changes that may underlie restorative versus compensatory ventilatory behavior after high cervical SCI.Grant Funding Source: NIH; Craig H. Neilsen Foundation; Anne & Oscar Lackner Chair in Neuroscience
Mass transfer is significant factor in vascular intima signaling ‐ its relevance to AMPK
Authors: Vandrangi Prashanthi , Sun Wei , Shyy John J Y , Rodgers Victor G J 
Published: June 2021

Previous literature has suggested that mechanical transduction, via shear stress, is the dominant contribution in vascular intima signaling. Cellular processes such as gene transcription, DNA replication in the disturbed flow region, and a sudden spike of ATP generation distal to plaque formation have been correlated to mechanotransduction. Here, we computationally model the significance of mass transfer relative to shear gradients on chemical species under the same experimental conditions prescribed by the work by Korenaga et al. (1997), Chiu et al. (1998), and Choi et al. (2007). The results demonstrate that mass transfer modifications of chemical species were in excellent agreement with the published observations. In addition, our experimental results showed the Ca2+ dependence for eliciting AMPK (AMP activated protein kinase) signal pathway. These results imply that the role of mechanical transduction in similar signaling may be overstated and mass transfer considerations should be carefully examined when studying triggering methods in signaling mechanisms.Grant Funding Source: CBR (Center for Bioengineering Research), UCR