Physiology Commons^™

Multichannel Modulation Of Depolarizing And Repolarizing Ion Currents Increases The Positive Rate-Dependent Action Potential Prolongation, Candido Cabo

Publications and Research

Prolongation of the action potential duration (APD) could prevent reentrant arrhythmias if prolongation occurs at the fast excitation rates of tachycardia with minimal prolongation at slow excitation rates (i.e., if prolongation is positive rate-dependent). APD prolongation by current anti-arrhythmic agents is either reverse (larger APD prolongation at slow rates than at fast rates) or neutral (similar APD prolongation at slow and fast rates), which may not result in an effective anti-arrhythmic action. In this report we show that, in computer models of the human ventricular action potential, the combined modulation of both depolarizing and repolarizing ion currents results in a …

Positive Rate-Dependent Action Potential Prolongation By Modulating Potassium Ion Channels, Candido Cabo

Publications and Research

Pharmacological agents that prolong action potential duration (APD) to a larger extent at slow rates than at the fast excitation rates typical of ventricular tachycardia exhibit reverse rate dependence. Reverse rate dependence has been linked to the lack of efficacy of class III agents at preventing arrhythmias because the doses required to have an anti-arrhythmic effect at fast rates may have pro-arrhythmic effects at slow rates due to an excessive APD prolongation. In this report we show that, in computer models of the ventricular action potential, APD prolongation by accelerating phase 2 repolarization (by increasing I_Ks) and decelerating …

Threshold Concentration And Random Collision Determine The Growth Of The Huntingtin Inclusion From A Stable Core, Sen Pei, Theresa C. Swayne, Jeffrey F. Morris, Lesley Emtage

Publications and Research

The processes underlying formation and growth of unfolded protein inclusions are relevant to neurodegenerative diseases but poorly characterized in living cells. In S. cerevisiae, inclusions formed by mutant huntingtin (mHtt) have some characteristics of biomolecular condensates but the physical nature and growth mechanisms of inclusion bodies remain unclear. We have probed the relationship between concentration and inclusion growth in vivo and find that growth of mHtt inclusions in living cells is triggered at a cytoplasmic threshold concentration, while reduction in cytoplasmic mHtt causes inclusions to shrink. The growth rate is consistent with incorporation of new material through collision and coalescence. …

A Systematic Review And Meta-Analysis On The Efficacy Of Stem Cell Therapy On Bone Brittleness In Mouse Models Of Osteogenesis Imperfecta, Lauren Battle, Shoshana Yakar, Alessandra Carriero

Publications and Research

There is no cure for osteogenesis imperfecta (OI), and current treatments can only partially correct the bone phenotype. Stem cell therapy holds potential to improve bone quality and quantity in OI. Here, we conduct a systematic review and meta-analysis of published studies to investigate the efficacy of stem cell therapy to rescue bone brittleness in mouse models of OI. Identified studies included bone marrow, mesenchymal stem cells, and human fetal stem cells. Effect size of fracture incidence, maximum load, stiffness, cortical thickness, bone volume fraction, and raw engraftment rates were pooled in a random-effects meta-analysis. Cell type, cell number, injection …

Notch Signaling Represses Cone Photoreceptor Formation Through The Regulation Of Retinal Progenitor Cell States, Xueqing Chen, Mark M. Emerson

Publications and Research

Notch signaling is required to repress the formation of vertebrate cone photoreceptors and to maintain the proliferative potential of multipotent retinal progenitor cells. However, the mechanism by which Notch signaling controls these processes is unknown. Recently, restricted retinal progenitor cells with limited proliferation capacity and that preferentially generate cone photoreceptors have been identified. Thus, there are several potential steps during cone genesis that Notch signaling could act. Here we use cell type specific cis-regulatory elements to localize the primary role of Notch signaling in cone genesis to the formation of restricted retinal progenitor cells from multipotent retinal progenitor cells. Localized …

The Effect Of Fluid Flow Shear Stress And Substrate Stiffness On Yes-Associated Protein (Yap) Activity And Osteogenesis In Murine Osteosarcoma Cells, Thomas R. Coughlin, Ali Sana, Kevin Voss, Abhilash Gadi, Upal Basu-Roy, Caroline M. Curtin, Alka Mansukhani, Oran D. Kennedy

Publications and Research

Osteosarcoma (OS) is an aggressive bone cancer originating in the mesenchymal lineage. Prognosis for metastatic disease is poor, with a mortality rate of approximately 40%; OS is an aggressive disease for which new treatments are needed. All bone cells are sensitive to their mechanical/ physical surroundings and changes in these surroundings can affect their behavior. However, it is not well understood how OS cells specifically respond to fluid movement, or substrate stiffness—two stimuli of relevance in the tumor microenvironment. We used cells from spontaneous OS tumors in a mouse engineered to have a bone-specific knockout of pRb-1 and p53 in …

Lighting The Way: Recent Insights Into The Structure And Regulation Of Phototropin Blue Light Receptors, Jaynee E. Hart, Kevin H. Gardner

Publications and Research

The phototropins (phots) are light-activated kinases that are critical for plant physiology and the many diverse optogenetic tools that they have inspired. Phototropins combine two bluelight- sensing Light–Oxygen–Voltage (LOV) domains (LOV1 and LOV2) and a C-terminal serine/threonine kinase domain, using the LOV domains to control the catalytic activity of the kinase. While much is known about the structure and photochemistry of the light-perceiving LOV domains, particularly in how activation of the LOV2 domain triggers the unfolding of alpha helices that communicate the light signal to the kinase domain, many questions about phot structure and mechanism remain. Recent studies have made …

Age And Sex Differences In Load-Induced Tibial Cortical Bone Surface Strain Maps, Alessandra Carriero, Behzad Javaheri, Neda Bassir Kazeruni, Andrew A. Pitsillides, Sandra J. Shefelbine

Publications and Research

Bone adapts its architecture to the applied load; however, it is still unclear how bone mechano-adaptation is coordinated and why potential for adaptation adjusts during the life course. Previous animal models have suggested strain as the mechanical stimulus for bone adaptation, but yet it is unknown how mouse cortical bone load-related strains vary with age and sex. In this study, full-field strain maps (at 1 N increments up to 12 N) on the bone surface were measured in young, adult, and old (aged 10, 22 weeks, and 20 months, respectively), male and female C57BL/6J mice with load applied using a …

Inhibition Of Mitochondrial Permeability Transition By Deletion Of The Ant Family And Cypd, Jason Karch, Michael J. Bround, Hadi Khalil, Michelle A. Sargent, Nadina Latchman, Naohiro Terada, Pablo M. Peixoto, Jeffery D. Molkentin

Publications and Research

The mitochondrial permeability transition pore (MPTP) has resisted molecular identification. The original model of the MPTP that proposed the adenine nucleotide translocator (ANT) as the inner membrane pore-forming component was challenged when mitochondria from Ant1/2 double null mouse liver still had MPTP activity. Because mice express three Ant genes, we reinvestigated whether the ANTs comprise the MPTP. Liver mitochondria from Ant1, Ant2, and Ant4 deficient mice were highly refractory to Ca2+-induced MPTP formation, and when also given cyclosporine A (CsA), the MPTP was completely inhibited. Moreover, liver mitochondria from mice with quadruple deletion of Ant1, Ant2, Ant4, and Ppif (cyclophilin …

A Critical Evaluation Of The Biological Construct Skeletal Muscle Hypertrophy: Size Matters But So Does The Measurement, Cody T. Haun, Christopher G. Vann, Brandon M. Roberts, Andrew D. Vigotsky, Brad J. Schoenfeld, Michael D. Roberts

Publications and Research

Skeletal muscle is highly adaptable and has consistently been shown to morphologically respond to exercise training. Skeletal muscle growth during periods of resistance training has traditionally been referred to as skeletal muscle hypertrophy, and this manifests as increases in muscle mass, muscle thickness, muscle area, muscle volume, and muscle fiber cross-sectional area (fCSA). Delicate electron microscopy and biochemical techniques have also been used to demonstrate that resistance exercise promotes ultrastructural adaptations within muscle fibers. Decades of research in this area of exercise physiology have promulgated a widespread hypothetical model of training-induced skeletal muscle hypertrophy; specifically, fCSA increases are accompanied by …

Spinal Control Of Locomotion: Individual Neurons, Their Circuits And Functions, Marie-Pascale Côté, Lynda M. Murray, Maria Knikou

Publications and Research

Systematic research on the physiological and anatomical characteristics of spinal cord interneurons along with their functional output has evolved for more than one century. Despite significant progress in our understanding of these networks and their role in generating and modulating movement, it has remained a challenge to elucidate the properties of the locomotor rhythm across species. Neurophysiological experimental evidence indicates similarities in the function of interneurons mediating afferent information regarding muscle stretch and loading, being affected by motor axon collaterals and those mediating presynaptic inhibition in animals and humans when their function is assessed at rest. However, significantly different muscle …

Are The Hypertrophic Adaptations To High And Low-Load Resistance Training Muscle Fiber Type Specific?, Jozo Grgic, Brad J. Schoenfeld

Publications and Research

No abstract provided.

Changes In Reach To Eat Movement Control After Intensive Training For Children With Unilateral Cerebral Palsy, Yaching Hung, Aryeh D. Spingarn

Publications and Research

Ya Ching Hung EdD. and Aryeh Spingarn EP-C, CSCS, EIM-Level 2 Queens College, City University of New York Department of Family, Nutrition, and Exercise Sciences, Changes in Reach to Eat Movement Control After Intensive Training for Children with Unilateral Cerebral Palsy. Purpose: The current study compares the effects of an intervention on children with Congenital Hemiplegia during a simple eating task using kinematic analyses. Previous studies looked at simple bimanual tasks such as opening a drawer; no studies examined the effects of intensive training on unimanual reach, grasp, and eat movement control. Methods: 20 children with Unilateral Spastic Cerebral Palsy …

Decreased Triple Network Connectivity In Patients With Recent Onset Post-Traumatic Stress Disorder After A Single Prolonged Trauma Exposure, Yang Liu, Liang Li, Baojuan Li, Na Feng, Lihong Li, Xi Zhang, Hongbing Lu, Hong Yin

Publications and Research

The triple network model provides a common framework for understanding affective and neurocognitive dysfunctions across multiple disorders, including central executive network (CEN), default mode network (DMN), and salience network (SN). Considering the effect of traumatic experience on post-traumatic stress disorder (PTSD), this study aims to explore the alteration of triple network connectivity in a specific PTSD induced by a single prolonged trauma exposure. With an arterial spin labeling sequence, three networks were first identified using independent component analysis among 10 PTSD patients and 10 healthy survivors, who experienced the same coal mining flood disaster. Then, the triple network connectivity was …

Mechanism Of Action For Rtms: A Working Hypothesis Based On Animal Studies, Thangavelu Soundara Rajan, Maria Felice Ghilardi, Hoau-Yan Wang, Emanuela Mazzon, Placido Bramanti, Domenico Restivo, Angelo Quartarone

Publications and Research

Experiments in rodents have elucidated some of the molecular mechanisms underlying repetitive transcranial magnetic stimulation (rTMS). These studies may be useful in a translational perspective so that future TMS studies in rodents can closely match human TMS protocols designed for therapeutic purposes. In the present work we will review the effects of rTMS on glutamate neurotransmission which in turn induce persistent changes in synaptic activity. In particular, we will focus on the role of NMDA and non-NMDA transmission and on the permissive role of BDNF-TrKB interaction in the rTMS induced after-effects.

Effects Of Leucine Supplementation And Resistance Training On Myopathy Of Diabetic Rats, Carlos Eduardo C. Martins, Vanessa B. De S. Lima, Brad J. Schoenfeld, Julio Tirapegui

Publications and Research

Leucine supplementation and resistance training positively influence the protein translation process and the cell signaling mTOR (mammalian target of rapamycin) pathway that regulates muscle protein balance and muscle remodeling, and thus may be therapeutic to diabetic myopathy. However, the effect of a combined intervention has not been well studied. Forty male Wistar rats were divided into five groups, control (C), diabetic control (D), diabetic + trained (DT), diabetic + L-leucine (DL), diabetic + L-leucine + trained (DLT). The supplementation of 5% leucine in chow, and resistance training were conducted for 8 weeks postweaning of rats. The extensor digitorum longus was …

Vestibular Activation Habituates The Vasovagal Response In The Rat, Bernard Cohen, Giorgio P. Martinelli, Yongqing Xiang, Theodore Raphan, Sergei B. Yakushin

Publications and Research

Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block vasovagal syncope, this was not found in other studies. Using anesthetized, male Long–Evans rats that were highly susceptible to generation of vasovagal responses, we found that repeated activation of the vestibulosympathetic reflex (VSR) with ±2 and ±3 mA, 0.025 Hz sinusoidal galvanic vestibular stimulation (sGVS) caused incremental changes in blood pressure (BP) and heart rate (HR) that blocked further generation of vasovagal responses. Initially, BP and HR fell ≈20–50 …

Gait Changes In A Line Of Mice Artificially Selected For Longer Limbs, Leah M. Sparrow, Emily Pellattt, Sabrina S. Yu, David A. Raichlen, Herman Pontzer, Campbell Rolian

Publications and Research

In legged terrestrial locomotion, the duration of stance phase, i.e., when limbs are in contact with the substrate, is positively correlated with limb length, and negatively correlated with the metabolic cost of transport. These relationships are well documented at the interspecific level, across a broad range of body sizes and travel speeds. However, such relationships are harder to evaluate within species (i.e., where natural selection operates), largely for practical reasons, including low population variance in limb length, and the presence of confounding factors such as body mass, or training. Here, we compared spatiotemporal kinematics of gait in Longshanks, a long-legged …

Burnout And The Hypothalamic-Pituitary-Thyroid Axis: A Methodological Comment, Renzo Bianchi, Irvin Sam Schonfeld, Eric Laurent

Publications and Research

Because (a) burnout overlaps with depression and (b) depression has been associated with altered functioning of the hypothalamic-pituitary-thyroid axis changes in the activity of the HPT axis can be expected in burnout. Most probably, Guo et al.’s (2017) results are flawed by a severe form of the “healthy worker effect.”

Effects Of An 18- Week Strength, Conditioning, And Circuit Training Program On Weight Loss In A Middle Aged Adult Male, Aryeh D. Spingarn

Publications and Research

Aryeh Spingarn Queens College, City University of New York Department of Family, Nutrition, and Exercise Sciences, Effects of an 18-week strength, conditioning, and circuit training program on weight loss in a middle-aged male. Purpose: The purpose of this study was to examine the effects of a strength, conditioning, and circuit training program on weight loss in a middle age adult. Methods: The subject participated in an 18-week strength and conditioning program 2 days per week for one hour per session, totaling 2 hours of training time per week. The first 12 weeks of the program included only strength training for …

Monitoring The Progression Of Spontaneous Articular Cartilage Healing With Infrared Spectroscopy, Megan P. O'Brien, Madhuri Penmatsa, Uday Palukuru, Paul West, Xu Yang, Mathias P. G. Bostrom, Theresa Freeman, Nancy Pleshko

Publications and Research

Objective. Evaluation of early compositional changes in healing articular cartilage is critical for understanding tissue repair and for therapeutic decision-making. Fourier transform infrared imaging spectroscopy (FT-IRIS) can be used to assess the molecular composition of harvested repair tissue. Furthermore, use of an infrared fiber-optic probe (IFOP) has the potential for translation to a clinical setting to provide molecular information in situ. In the current study, we determined the feasibility of IFOP assessment of cartilage repair tissue in a rabbit model, and assessed correlations with gold-standard histology.

Design. Bilateral osteochondral defects were generated in mature white New Zealand rabbits, and …

Multidisciplinary Intensive Rehabilitation Treatment Improves Sleep Quality In Parkinson's Disease, Giuseppe Frazzitta, Roberto Maestri, Davide Ferrazzoli, Giulio Riboldazzi, Rossana Bera, Cecilia Fontanesi, Roger P. Rossi, Gianni Pezzoli, Maria Felice Ghilardi

Publications and Research

Background Sleep disturbances are among the most common non-motor symptoms of Parkinson’s disease (PD), greatly interfering with daily activities and diminishing life quality. Pharmacological treatments have not been satisfactory because of side effects and interactions with anti-parkinsonian drugs. While studies have shown that regular exercise improves sleep quality in normal aging, there is no definitive evidence in PD.

Methods In a retrospective study, we determined whether an intense physical and multidisciplinary exercise program improves sleep quality in a large group of patients with PD.

We analyzed the scores of PD Sleep Scale (PDSS), which was administered twice, 28 days apart, …

Family Of Flp Peptides In Caenorhabditis Elegans And Related Nematodes, Chris Li, Kyuhyung Kim

Publications and Research

Neuropeptides regulate all aspects of behavior in multicellular organisms. Because of their ability to act at long distances, neuropeptides can exert their effects beyond the conventional synaptic connections, thereby adding an intricate layer of complexity to the activity of neural networks. In the nematode Caenorhabditis elegans, a large number of neuropeptide genes that are expressed throughout the nervous system have been identified.The actions of these peptides supplement the synaptic connections of the 302 neurons, allowing for fine tuning of neural networks and increasing the ways in which behaviors can be regulated. In this review, we focus on a large …

Motor Cortex Electrical Stimulation Augments Sprouting Of The Corticospinal Tract And Promotes Recovery Of Motor Function, Jason B. Carmel, John H. Martin

Publications and Research

The corticospinal system—with its direct spinal pathway, the corticospinal tract (CST) – is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We …

The Impact Of Gut Passage By Binturongs (Arctictus Binturong) On Seed Germination, Christina P. Colon, Ahimsa Campos-Arceiz

Publications and Research

Binturongs (Arctictis binturong) are the largest of Asian civets and, due to their highly frugivorous diet, are expected to play an important role in seed dispersal processes. To study the effect of binturong gut passage on seed viability, we fed 10 captive binturongs with fruits of longan (Dimocarpus longan), papaya (Carica papaya) and chiku (Manilkara zapota), collected the seeds they defaecated, and planted these to determine seed germination rate and time. Of the defaecated seeds, 90.4% passed through binturong gut intact in under nine hours, and 99.4% passed in under 33 hours. Chiku seeds had the highest germination rate (35.7% …

Notes On The Diet Of The Malay Civet (Viverra Tangalunga) And Other Civets In Logged And Unlogged Lowland Dipterocarp Rain Forests In Sabah, Borneo, Christina P. Colon, John B. Sugau

Publications and Research

Civet diets were examined in a logged and unlogged Bornean rain forest. Malay civets (Viverra tangalunga) consumed invertebrates, fruit, rodents, insectivores, birds, snakes and lizards, and appear to show preference for centipedes and scorpions. Other civet species consumed fruit, such as figs, Connarus sp. and Annona sp., particularly in the unlogged forest, but also consumed invertebrates and vertebrates. Reduced fruit consumption observed in the logged forest may be due to lower availability and may be offset by increased consumption of invertebrates. The increased overlap in diet between Malay civets and other civets in disturbed areas may lead to …

Prediction Of Birth Weight By Cotinine Levels During Pregnancy In A Population Of African American Smokers, Ayman A.E. El-Mohandes, Michele Kiely, Marie G. Gantz, Susan M. Blake, M Nabil El-Khorazaty

Publications and Research

Objective—The goal was to investigate the association between maternal salivary cotinine levels (SCLs) and pregnancy outcome among African Americans smokers

Methods—In a randomized controlled trial conducted in 2001-2004 in Washington, D.C. 714 women (126 active smokers (18%)) were tested for SCLs at the time of recruitment and later in pregnancy. Sociodemographic health risks and pregnancy outcomes were recorded.

Results—Birth weights were significantly lower for infants born to mothers with baseline SCLs of ≥20 ng/ml compared to/ml (p=0.024), ≥50 ng/ml compared to/ml (p=0.002), ≥100 ng/ml compared to/ml (p=0.002), in bivariate analyses. In linear regression analyses adjusting for sociodemographic …

Maternal Cocaine Administration In Mice Alters Dna Methylation And Gene Expression In Hippocampal Neurons Of Neonatal And Prepubertal Offspring, Svetlana I. Novikova, Fang He, Jie Bai, Nicholas J. Cutrufello, Michael S. Lidow, Ashiwel S. Undieh

Publications and Research

Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8–19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3) or 30 (P30) days postnatum. Global DNA methylation, methylated DNA immunoprecipitation followed by CGI2 microarray profiling and bisulfite sequencing, as well as quantitative real-time RT-PCR gene expression …