Integrative Physiology Research Articles

Airway Epithelium Senescence as a Driving Mechanism in COPD Pathogenesis.

Cellular senescence is a state of permanent cell cycle arrest triggered by various intrinsic and extrinsic stressors. Cellular senescence results in impaired tissue repair and remodeling, loss of physiological integrity, organ dysfunction, and changes in the secretome. The systemic accumulation of senescence cells has been observed in many age-related diseases. Likewise, cellular senescence has been implicated as a risk factor and driving mechanism in chronic obstructive pulmonary disease (COPD) pathogenesis. Airway epithelium exhibits hallmark features of senescence in COPD including activation of the p53/p21WAF1/CIP1 and p16INK4A/RB pathways, leading to cell cycle arrest. Airway epithelial senescent cells secrete an array of inflammatory mediators, the so-called senescence-associated secretory phenotype (SASP), leading to a persistent low-grade chronic inflammation in COPD. SASP further promotes senescence in an autocrine and paracrine manner, potentially contributing to the onset and progression of COPD. In addition, cellular senescence in COPD airway epithelium is associated with telomere dysfunction, DNA damage, and oxidative stress. This review discusses the potential mechanisms of airway epithelial cell senescence in COPD, the impact of cellular senescence on the development and severity of the disease, and highlights potential targets for modulating cellular senescence in airway epithelium as a potential therapeutic approach in COPD.

Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases.

Aging is a natural phenomenon characterized by a progressive decline in physiological integrity, leading to a deterioration of cognitive function and increasing the risk of suffering from chronic-degenerative diseases, including cardiovascular diseases, osteoporosis, cancer, diabetes, and neurodegeneration. Aging is considered the major risk factor for Parkinson's and Alzheimer's disease develops. Likewise, diabetes and insulin resistance constitute additional risk factors for developing neurodegenerative disorders. Currently, no treatment can effectively reverse these neurodegenerative pathologies. However, some antidiabetic drugs have opened the possibility of being used against neurodegenerative processes. In the previous framework, Vanadium species have demonstrated a notable antidiabetic effect. Our research group evaluated polyoxidovanadates such as decavanadate and metforminium-decavanadate with preventive and corrective activity on neurodegeneration in brain-specific areas from rats with metabolic syndrome. The results suggest that these polyoxidovanadates induce neuronal and cognitive restoration mechanisms. This review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the brain, constituting a therapeutic alternative for aging and neurodegenerative diseases.

Integration of physiology in a curriculum on human structure: a snapshot of the cardiovascular block.

With the gradual shift from discipline-based to competency-based medical education, the integrated curriculum has become a popular model for connecting basic science and clinical content in undergraduate medical education. Despite its popularity, there are concerns that important physiological concepts are not adequately addressed. We describe the spiral integration of physiology content in the 5-week Cardiovascular block of our Homeostasis course at the Zucker School of Medicine. We also describe our approach to incorporating physiology into an integrated, constructed response, short-answer assessment format. Our approach to spiral integration consists of rotating lab stations that highlight the distinction between normal and abnormal states, linked with appropriate clinical interventions. Physiology is at the core of integration in any curriculum and the basis of all applied fields of medicine, hence our approach is that teaching structural relationships would not be valuable without consideration of its functions, which can then be utilized in discussion of clinical presentations, imaging, and relevant pathologies. Likewise, our integrated assessments require the students to compose their answers to the questions from scratch, which creates a shift in mode of students' preparation from rote memorizations to more cognitive processing that enhances critical thinking.

Linguistic and statistical analysis of the lexical ‘Langue-Parole’ dichotomy in a restricted domain

Development of new digital methods for analyzing the ‘Langue-Parole’ dichotomy is one of the most sought-after, but least researched problems of modern theoretical and applied linguistics. This determines the relevance of this study, the purpose of which is to develop a methodology for the automated linguastatistical analysis of a domain-related lexical layer in the context of the ‘Langue-Parole’ dichotomy and to apply the methodology to the Russian-language domain “Research on athlete integrative physiology” (RAIP). The study was conducted on the material of the Russian-language corpus including 56 RAIP domain texts of 300,000 wordforms in total published over the 2013-2020 period in the scientific journals “People. Sport. Medicine” (formerly “SUSU Bulletin. Series “Education, Healthcare, Physical Culture”), “Theory and Practice of Physical Culture”, etc. The key methodological approach is the ontological analysis of corpus data using statistical and linguistic modeling methods. The domain-specific language and speech are modeled by the corresponding lexicon and corpus, while the ‘Langue-Parole’ lexical dichotomy is represented by the values of the linguistic-statistical concept verbalization parameters of the domain concepts in the lexicon and corpus. The computational parameters include the indices of lexical diversity, structural complexity, conceptual syncretism, lexical structural complexity vs. conceptual syncretism correlation, and syncretical concept junction when verbalized in the corpus. The main results of the study are: 1) а methodology for analyzing domain-specific lexical dichotomy ‘Langue-Parole’, which can be ported to other domains and national languages; 2) the RAIP domain-related resources, including language-independent ontology, conceptually annotated Russian corpus, onto-lexicon, linguistic-statistical parameter values of the lexical ‘Langue-Parole’ dichotomy; and 3) tools that automate certain stages of the study.

1588-P: Translatable Modeling of Glucagon Actions in Human iPSC-Derived Hepatocytes Uniquely Predicts Differential Clinical Responses to Glucagon Analog Agonist Molecules

As the development of clinically efficacious glucagon receptor (GCGR) agonists for the treatment of metabolic diseases evolves, the challenge to identify physiologically relevant preclinical models that predict glucagon receptor actions in humans becomes ever more important. While many hepatocyte models are available, most fail to recapitulate fundamental metabolic regulatory responses to key physiologic stimuli including integration of glucagon and insulin actions that govern hepatic carbohydrate or lipid metabolism. We developed and optimized a human induced pluripotent stem cell (iPSC)-derived hepatocyte model to mimic physiologic insulin and glucagon signaling and counter-regulation of metabolic pathways. We leveraged the model to evaluate functional responses of different glucagon receptor agonist molecules to regulate carbohydrate and lipid metabolism. Unlike assays conducted in several other cell line and primary isolated hepatocyte systems, hepatic glucose output assays in the human IPSC hepatocyte model demonstrated substantial potency differences between two novel soluble glucagon analog agonists. These findings predicted differential dose-dependent blood glucose excursions in response to these agonists when administered in a single ascending dose study in healthy human volunteers. Modeling physiologic integration of insulin and glucagon signaling in a clinically translatable human iPSC hepatocyte model can advance understanding of the regulation of nutrient metabolism by glucagon receptor agonists in humans and support the development of novel therapeutic approaches to address metabolic disorders, including type 2 diabetes, obesity, and nonalcoholic fatty liver disease. Disclosure W.Roell: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Regmi: Employee; Eli Lilly and Company. C.T.Benson: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. T.Coskun: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.S.Moyers: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.Alsina-fernandez: Employee; Eli Lilly and Company. M.K.Thomas: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Integrating Foundational and Clinical Science Remotely by Combining Team-Based Learning and Simulation

Integrating foundational and clinical science in medical and other professional healthcare degree programs has been well established as a means to enhance learning. However, implementation remains challenging, and a significant gap exists in guidance for non-professional degree programs to effectively accomplish both types of integration. Additionally, many modalities described in the literature are resource-intensive, scale poorly to larger groups, and are widely inaccessible. We present an online modality combining team-based learning and a simulation-based learning experience that fosters vertical and horizontal integration of physiology, pharmacology, and clinical science. The tools utilized include a vital sign simulator, video conferencing software, and a document-sharing platform. The activity demonstrated improved knowledge comparing pre- and posttests and evidence that the activity helped students integrate physiology, pharmacology, and clinical medicine. The novel structure is effective and accessible, uses open-source software and standard equipment available to most undergraduate and graduate faculty, and is adaptable to in-person, hybrid-remote, and fully remote delivery.

Effects of physiological integration on nitrogen use efficiency of moso bamboo in homogeneous and heterogeneous environments.

Moso bamboo is one of the important clonal plants with complex underground rhizome-root system. Ramets connected by rhizome can translocate and share nitrogen (N), which may affect the nitrogen use efficiency (NUE) of moso bamboo. The aims of this study were to investigate the mechanisms of N physiological integration and its relationship with NUE of moso bamboo. A pot experiment was conducted to trace the movement of 15N between the connected ramets of moso bamboo in both homogeneous and heterogeneous N environments. Results showed that N translocation within clonal fragments of moso bamboo was detected in both homogeneous and heterogeneous environments. The intensity of physiological integration (IPI) was significantly lower in homogeneous environments than that in heterogeneous environments. 15N translocation between the connected ramtes of moso bamboo was determined by the source-sink relationship in heterogeneous environments, and the 15N allocation of the fertilized ramet was higher than that of the connected unfertilized ramet. The NUE of connected treatment was significantly higher than that of severed treatment, which suggested that physiological integration significantly improved the NUE of moso bamboo. In addition, the NUE of moso bamboo was significantly higher in heterogeneous environments than that in homogeneous environments. The contribution rate of physiological integration (CPI) on NUE in heterogeneous environments was significantly higher than that in homogenous environments. These results will provide theoretical basis for precision fertilization in moso bamboo forests.

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

Intraductal papillary mucinous neoplasm of the accessory pancreatic duct in the pancreas uncinate process: A case report.

Intraductal papillary mucinous neoplasms (IPMN) of the accessory pancreatic duct (APD) are very rare and their clinical significance is not known. Here, we describe a case of IPMN originating in a branch of the duct of APD within the uncinate process of the pancreas, which initially presented with acute pancreatitis. A 70-year-old man visited our medical center presenting with acute pancreatitis around the head and uncinate process of the pancreas. Computer tomography scans revealed the presence of a 35-mm cystic mass-like lesion within the pancreas uncinate process communicating with a branch of the APD. The patient was diagnosed with APD-IPMN in the pancreas uncinate process accompanied by acute pancreatitis. Conservative management of the acute pancreatitis relieved his symptoms, while duodenum-preserving partial pancreatic head resection (DPPHR-P) was performed to treat the APD-IPMN. Intraoperative exploration showed the presence of severe adhesions within the uncinate process of the pancreas and that the tumor's "peduncle" - a branch of the duct of APD - was saddling just at the front of the main pancreatic ducts. Thus, surgical removal of the tumor required special handling of the region between the main duct (MD) and APD to protect the integrity of the main pancreatic ducts. Finally, a 35*30*15 mm IPMN was successfully removed and the MD was preserved combined with ligation from the root of the APD of the pancreas. The drainage volume of the ventral tube increased by around 20-fold in 24 hours on the fourth day after surgery. The presence of high amylase levels in the drainage discharge (40713.5 U/L) led to the diagnosis of postoperative pancreatic fistula (POPF). The drainage volume remained high for 3 days. The patient was discharged and POPF was successfully managed through endoscopic pancreatic duct stenting. APD-IPMN in the pancreas uncinate process has its own characteristics of localized pancreatitis, and MD-preserving DPPHR-P not only protects the exocrine and endocrine functions of the pancreas, but it also protects the physiological and anatomical integrity. The appearance of POPF after DPPHR-P may be managed by endoscopic pancreatic duct stenting.

Foundations in physiology: an introductory course using the core concepts.

As one element of an extensive revision to program curriculum, the Integrative Physiology and Health Science Department at a small, private, liberal arts institution developed a novel introductory course for the major, focusing specifically on the "core concepts" of physiology. Intended to provide the initial step in explicit scaffolding for student success and, ultimately, transfer of knowledge across the curriculum, development and assessment of the first offering of the course were completed. In the fall of 2021, IPH 131: Foundations in Physiology was launched. The specific core concepts covered were as follows: causality, scientific reasoning, physics/chemistry, structure-function, homeostasis, flow-down gradients, cell membrane, energy, cell-cell communication, and interdependence/integration. To assess student learning, the Phys-MAPS (Measuring Achievement and Progress in Science for Physiology) assessment tool was administered to students during the first week of class and again in the final week of the semester. Average scores revealed significant learning gains by the end of the semester (0.497 ± 0.058 vs. 0.538 ± 0.108 correct as a proportion of the total number of questions, P = 0.0096). While a modest gain in learning outcomes, these data provide early evidence that a course specifically addressing the core concepts of physiology can be an appropriate introduction to the physiology curriculum.NEW & NOTEWORTHY This article will detail the development and implementation of an introductory course using the "core concepts." Specifics of course design, assessment, and challenges encountered will be presented for those interested in this approach.

Physiological integration improves nitrogen use efficiency of moso bamboo: An isotopic (15N) assessment

Physiological integration is a means of adapting to the natural selection of moso bamboo. Connected ramets can translocate and share nitrogen (N). This phenomenon may affect the nitrogen use efficiency (NUE) of moso bamboo. The aims of this study were to investigate the characteristics of N physiological integration and its relationship with NUE of moso bamboo. We established an in-situ experiment to trace the movement of 15N between connected ramets (parent and offspring ramets) of moso bamboo in both homogeneous and heterogeneous N conditions. Results showed that 15N sharing within the clonal systems of moso bamboo was detected in both homogeneous and heterogeneous environments, and 15N translocation was bidirectional between the connected ramets. The intensity of physiological integration (IPI) was relatively low in homogeneous environments, and the connected ramets of moso bamboo were selfish. 15N translocation between the connected ramtes of moso bamboo was determined by the demand-driven source-sink relationship in heterogeneous environments, and the fertilized ramets of moso bamboo were selfish. The NUE of the connected treatment was significantly higher than that of the severed treatment, illustrating that physiological integration significantly improved the NUE of moso bamboo. Additionally, the NUE in heterogeneous environments was significantly higher than that in homogeneous environments. These results clearly demonstrate that N is readily translocated between the connected ramets of moso bamboo, particularly in heterogeneous environments, which provides reference for precision fertilization management in moso bamboo forests.

Aging-related histone modification changes in brain function.

Aging can be defined as a decline of physiological function that is more difficult to reverse, characterized by the loss of the physiological integrity of tissues, organs, and cells of an organism over time. Normal aging is associated with structural and functional changes in the brain, involving neuronal apoptosis, synaptic structure, neurotransmission, and metabolism alterations, leading to impairment in sleep, cognitive functions, memory, learning, and motor and sensory systems. Histone modification is a significant aging-related epigenetic change that influences synaptic and mitochondrial function and immune and stress responses in the brain. This review discusses the changes in histone modifications that occur during brain aging, specifically methylation and acetylation, and the associated changes in gene transcription and protein expression. We observed that genes related to synaptic and mitochondrial function are downregulated in the aging brain, while genes related to immune response and inflammatory functions are upregulated.

Editorial: Integration of development, physiology and responses to environmental change in aquatic invertebrates

Editorial: Integration of development, physiology and responses to environmental change in aquatic invertebrates

The role of the microcirculation and integrative cardiovascular physiology in the pathogenesis of ICU-acquired weakness.

Skeletal muscle dysfunction after critical illness, defined as ICU-acquired weakness (ICU-AW), is a complex and multifactorial syndrome that contributes significantly to long-term morbidity and reduced quality of life for ICU survivors and caregivers. Historically, research in this field has focused on pathological changes within the muscle itself, without much consideration for their in vivo physiological environment. Skeletal muscle has the widest range of oxygen metabolism of any organ, and regulation of oxygen supply with tissue demand is a fundamental requirement for locomotion and muscle function. During exercise, this process is exquisitely controlled and coordinated by the cardiovascular, respiratory, and autonomic systems, and also within the skeletal muscle microcirculation and mitochondria as the terminal site of oxygen exchange and utilization. This review highlights the potential contribution of the microcirculation and integrative cardiovascular physiology to the pathogenesis of ICU-AW. An overview of skeletal muscle microvascular structure and function is provided, as well as our understanding of microvascular dysfunction during the acute phase of critical illness; whether microvascular dysfunction persists after ICU discharge is currently not known. Molecular mechanisms that regulate crosstalk between endothelial cells and myocytes are discussed, including the role of the microcirculation in skeletal muscle atrophy, oxidative stress, and satellite cell biology. The concept of integrated control of oxygen delivery and utilization during exercise is introduced, with evidence of physiological dysfunction throughout the oxygen delivery pathway - from mouth to mitochondria - causing reduced exercise capacity in patients with chronic disease (e.g., heart failure, COPD). We suggest that objective and perceived weakness after critical illness represents a physiological failure of oxygen supply-demand matching - both globally throughout the body and locally within skeletal muscle. Lastly, we highlight the value of standardized cardiopulmonary exercise testing protocols for evaluating fitness in ICU survivors, and the application of near-infrared spectroscopy for directly measuring skeletal muscle oxygenation, representing potential advancements in ICU-AW research and rehabilitation.

Treatment of Nondiabetic Kidney Diseases with Sodium-Glucose Cotransporter-2 Inhibitors.

Department of Medicine, University of Arizona, Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan Medical School, aAddresses for correspondence: Dr. Frank C. Brosius, University of Arizona, 1501 N. Campbell Ave, PO Box 245022, Tucson, AZ 85724, [email protected]

Gastroprotective effect of electrical spinal cord stimulation may be mediated by glucocorticoids produced in response to this stimulation

We demonstrated previously that stress-induced glucocorticoids are gastroprotective hormones but not ulcerogenic ones (Filaretova et al., 2016). Recently electrical spinal cord stimulation began to be used for both experimental studies of motor functions regulation and rehabilitation of motor functions in patients with spinal cord injury (Gerasimenko et al., 2021; Moshonkina et al., 2016). The spinal cord stimulation directed to the activation of spinal locomotor related networks affected visceral systems as well. Recently in our teamwork we have shown that the electrical spinal cord stimulation can cause an increase in blood glucocorticoid level accompanied by a gastroprotective effect (Filaretova et al., 2022). The aim of the present work was to verify the hypothesis that the gastroprotective effect of the electrical spinal cord stimulation may be mediated by glucocorticoids produced in response to this stimulation. Gastric injury was induced in anesthetized rats by prolonged gastric ischemia/reperfusion (I/R, 30 min occlusion of celiac artery followed by 3 h of reperfusion) or indomethacin administration (IM, 35 mg/kg, sc). For spinal stimulation, stainless steel wire electrodes were fixed in fasciae between T11-12 and L1–L2 vertebrae of anesthetized animals. Motor evoked responses in hindlimbs muscles to spinal stimulation were recorded. Spinal stimulation at 30 Hz was carried out with a subthreshold current for inducing muscle contractions (80% of the threshold). Sham-stimulated (control) rats were subjected to the same manipulations except for the stimulation itself. To test the participation of glucocorticoids in the gastroprotective effect of the stimulation, two approaches were used: pretreatment by the inhibitor of glucocorticoid synthesis, metyrapone (30 mg/kg, i.p.) and the antagonist of glucocorticoid receptors RU-38486 (20 mg/kg, i.p.). The concentration of corticosterone in blood plasma was determined using commercial ELISA kits. In control rats the spinal cord stimulation resulted in an increase of blood corticosterone level 1 h later. The spinal stimulation, applied 1 h before the onset of ulcerogenic stimuli, also significantly attenuated gastric erosion formation induced by I/R and IM as well. Metyrapone injected shortly before the stimulation caused a fast inhibition of corticosterone response and reversed the gastroprotective effect stimulation. The gastroprotective effect of the stimulation was also prevented by the pretreatment rats with glucocorticoid receptor antagonist RU-38486. The obtained results indicate on contribution of glucocorticoids to gastroprotective effect of spinal cord stimulation. In conclusion, the findings support the hypothesis that the gastroprotective effect of the electrical spinal cord stimulation may be mediated by glucocorticoids produced in response to this stimulation. The study was supported by the Ministry of Education and Science of the Russian Federation (agreement No. 075-15-2020-921 for the creation and development of the world-class scientific center “Pavlov Center “Integrative Physiology - to medicine, high-tech healthcare and technologies of stress resistance”). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

First Author Highlights

AnnouncementFirst Author HighlightsPublished Online:19 May 2023https://doi.org/10.1152/ajprenal.2023.324.5.AUMoreSectionsPDF (362 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations DANIELLE L. KIRKMANDepartment of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, Virginia, United StatesFigure 1.Danielle KirkmanDownload figureDownload PowerPointDanielle Kirkman is an Assistant Professor in the Department of Kinesiology and Health Sciences at Virginia Commonwealth University. She received her PhD in Clinical Exercise Physiology from Bangor University in Wales before completing her postdoctoral fellowship in vascular physiology at the University of Delaware. Her research is focused on applied, integrative physiology at the nexus of cardiovascular and renal health. As an exercise physiologist by training, a large body of her work has investigated the cardiovascular and metabolic effects of exercise in patients across the spectrum of kidney diseases. In her spare time, she enjoys the outdoors [Photo: Fig. 1].https://doi.org/10.1152/ajprenal.00046.2023FERNANDO MARMOLNorthwestern University Feinberg School of Medicine, Chicago, Illinois, United StatesFigure 2.Fernando MarmolDownload figureDownload PowerPointFernando Marmol is a research scholar at Northwestern University in Chicago, IL, mentored by Dr. Daniel Batlle. He is an International Medical Graduate MD from Ecuador. His research interests focus on acid-base and electrolyte disorders as well as angiotensin-converting enzyme 2 and its potential therapeutic use. Like Dr. Batlle, he is a fan of the soccer team Barcelona FC. Away from the laboratory bench, he loves practicing basketball, soccer, and cycling. He is pursuing becoming a nephrologist [Photo: Fig. 2].https://doi.org/10.1152/ajprenal.00312.2022LINDSEY A. RAMIREZDepartment of Physiology, Medical College of Georgia at Augusta University, Augusta, Georgia, United StatesFigure 3.Lindsey RamirezDownload figureDownload PowerPointLindsey Ramirez completed her PhD in Physiology at Augusta University under the mentorship of Jennifer Sullivan. In 2022, she successfully defended with distinction. In her doctoral laboratory, she studied the role of inflammation in mediating high-fat diet-induced changes in adiposity and blood pressure. Currently, she is a postdoctoral fellow in the laboratory of Elizabeth Glover at the University of Illinois in Chicago, IL. In her current role, she is investigating the neural mechanisms that mediate aversion to ethanol. She enjoys learning about true crime, collecting rocks, and various crafts such as sewing, knitting, and crocheting [Photo: Fig. 3].https://doi.org/10.1152/ajprenal.00308.2022YU TAODepartment of Physiology and Anatomy, University of North Texas Health Science Center, Texas, United StatesFigure 4.Yu TaoDownload figureDownload PowerPointYu Tao is a PhD student in the Integrative Physiology Department in the University of North Texas Health Science Center, mentored by Dr. Rong Ma. She got her MS from Wuhan University, China. Her research focused on the podocyte and mesangial cell physiology in diabetic kidney disease. She enjoys cooking, baking, and hiking in her spare time [Photo: Fig. 4].https://doi.org/10.1152/ajprenal.00297.2022This article has no references to display. Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Related ArticlesCall for Papers: Exercise and the kidneys in health and disease 27 Apr 2023American Journal of Physiology-Renal PhysiologyFecal ammonium in mice with CKD: gastrointestinal sequestration by sodium zirconium cyclosilicate 02 May 2023American Journal of Physiology-Renal PhysiologyPerinatal intermittent hypoxia increases early susceptibility to ANG II-induced hypertension in adult male but not in female Sprague–Dawley rats 27 Apr 2023American Journal of Physiology-Renal PhysiologyStore-operated Ca2+ entry inhibition ameliorates high glucose and ANG II-induced podocyte apoptosis and mitochondrial damage 27 Apr 2023American Journal of Physiology-Renal Physiology More from this issue > Volume 324Issue 5May 2023Pages i-ii Crossmark Copyright & PermissionsCopyright © 2023 the American Physiological Society.https://doi.org/10.1152/ajprenal.2023.324.5.AUPubMed37204405History Published online 19 May 2023 Published in print 1 May 2023 Metrics

Mitochondrial Ca2+ dynamics differ between the left and right ventricles in murine and porcine hearts

Despite their differences in metabolism, mechanics, and developmental origin, the right ventricle (RV) is often assumed to function similarly to the left ventricle (LV). Specifically, though Ca 2+ transport into mitochondria is well established to play a crucial role in matching cardiac energy production to demand, little is known regarding whether mitochondrial Ca 2+ (mtCa 2+ ) handling is distinct in the RV and LV. Our objective was to test the hypothesis that the regulation of mtCa 2+ differs in the RV and LV. By isolating mitochondria from RV and LV free wall tissues from wild-type mice and healthy pigs, we compared several parameters indicative of Ca 2+ -regulated mitochondrial function. Basal mtCa 2+ levels were higher in RV mitochondria than in LV mitochondria. When successive boluses of Ca 2+ were administered to isolated mitochondria, RV mitochondria took up fewer Ca 2+ boluses, showing lower Ca 2+ retention capacity. RV mitochondria displayed relatively more protein carbonylation, suggesting oxidative stress. Interestingly, ATP production rate was higher in RV mitochondria relative to LV mitochondria; however, only LV mitochondria exhibited an increase in ATP production rate in the presence of Ca 2+ . We also compared the protein expression of the subunits of the mitochondrial Ca 2+ uniporter complex (MCUC) and the mitochondrial Na+/Ca 2+ exchanger (NCLX) and found that levels of the MCUC subunit Essential MCU Regulator (EMRE) and NCLX were higher in the LV than the RV, potentially facilitating more dynamic Ca 2+ transport in and out of LV mitochondria. Collectively, these data suggest that mtCa 2+ is calibrated to higher but more static levels in the RV, whereas in the LV basal mtCa 2+ is lower to ensure dynamic range for physiological stimuli to increase mitochondrial bioenergetics, corresponding to the larger changes in workload experienced by the LV. This study was supported by the National Institutes of Health (1K22HL137901 to Julia C. Liu) and by the Department of Integrative Biology and Physiology (to Jae Hwi Sung). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

ИННОВАЦИОННОЕ ЦИФРОВОЕ ПРИЛОЖЕНИЕ ПО ЭСТЕТИЧЕСКОЙ РЕСТАВРАЦИИ ФРОНТАЛЬНОЙ ГРУППЫ ЗУБОВ «COLORDENT»

The article describes the process of creating an interactive mobile application "ColorDent" for dentists. ColorDent is a mobile application equipped with systematic parameters for detecting defects in tooth hard tissues for further restoration, differentiation of structural forms and selection of the color palette of dental elements of a particular patient in order to qualitatively carry out the restoration process of the frontal group of teeth with the choice of filling material of a specific manufacturer. It is focused on the selection of the required color of the filling material according to the standard “Vita” scale, based on the database of dental photographs of persons with the physiological integrity of the hard tissues of the frontal group of teeth uploaded into it, as well as with their defects of various etiologies. The application will allow specialists to freely navigate among all color palettes of filling materials in a short period of time and achieve the highest aesthetic indicators in the restoration industry. This digital platform will allow a novice dentist to achieve the highest results at the restoration and remain competitive against the background of his experienced colleagues. Analogs of the created application are Color Tooth, Tooth Color Free, iSmileStudio, Ips e.max shade navigatioapp. The application developed by us has a number of advantages related to optimizing the selection of a color palette, reducing the time for selecting restoration material for a specific clinical case, and the economic availability of the application.

The Olfactory Bulb in Companion Animals-Anatomy, Physiology, and Clinical Importance.

The Olfactory Bulb is a component of the Olfactory System, in which it plays an essential role as an interface between the peripheral components and the cerebral cortex responsible for olfactory interpretation and discrimination. It is in this element that the first selective integration of olfactory stimuli occurs through a complex cell interaction that forwards the received olfactory information to higher cortical centers. Considering its position in the organizational hierarchy of the olfactory system, it is now known that changes in the Olfactory Bulb can lead to olfactory abnormalities. Through imaging techniques, it was possible to establish relationships between the occurrence of changes secondary to brain aging and senility, neurodegenerative diseases, head trauma, and infectious diseases with a decrease in the size of the Olfactory Bulb and in olfactory acuity. In companion animals, this relationship has also been identified, with observations of relations between the cranial conformation, the disposition, size, and shape of the Olfactory Bulb, and the occurrence of structural alterations associated with diseases with different etiologies. However, greater difficulty in quantitatively assessing olfactory acuity in animals and a manifestly smaller number of studies dedicated to this topic maintain a lack of concrete and unequivocal results in this field of veterinary sciences. The aim of this work is to revisit the Olfactory Bulb in companion animals in all its dimensions, review its anatomy and histological characteristics, physiological integration in the olfactory system, importance as a potential early indicator of the establishment of specific pathologies, as well as techniques of imaging evaluation for its in vivo clinical exploration.