Biology Commons^™

Fatty Acid Oxidation And Meiotic Resumption In Mouse Oocytes, Stephen M. Downs, Jessica Odette, John Klinger

Biological Sciences Faculty Research and Publications

We have examined the potential role of fatty acid oxidation (FAO) in AMP-activated protein kinase (AMPK)-induced meiotic maturation. Etomoxir and malonyl CoA, two inhibitors of carnitine palmitoyl transferase-1 (CPT1), and thus FAO, blocked meiotic induction in dbcAMP-arrested cumulus cell-enclosed oocytes (CEO) and denuded oocytes (DO) by the AMPK activator, AICAR. C75, an activator of CPT1 and FAO, stimulated meiotic resumption in CEO and DO. This effect was insensitive to the AMPK inhibitor, compound C, indicating an action downstream of AMPK. Palmitic acid or carnitine also promoted meiotic resumption in DO in the presence of AICAR. Since C75 also suppresses the …

The Tall Fescue Turf Grass Class I Chitinase Gene Fachit1 Is Activated By Fungal Elicitors, Dehydration, Ethylene, And Mechanical Wounding, Jian Wang, Na Tian, Xuan Huang, Li Yu Chen, Michael Schläppi, Zi Qin Xu

Biological Sciences Faculty Research and Publications

The cDNA, genomic DNA, and promoter sequence of FaChit1, a class I chitinase gene from Festuca arundinacea, were isolated and characterized in the present work. The deduced amino acid sequence of FaChit1 contains the chitin binding, catalytic, and proline and glycine-rich domains characteristic for most class I chitinases, but no C-terminal extension region. FaChit1 is induced effectively by fungal elicitors, dehydration, and ethylene, but only slightly by mechanical wounding. To identify potential stress-related cis-acting elements, 5′ sequences 935, 651, and 233 bp upstream of the FaChit1 start codon were fused to the GUS reporter gene and analyzed …

Seasonal Differences In Leaf-Level Physiology Give Lianas A Competitive Advantage Over Trees In A Tropical Seasonal Forest, Zhi-Quan Cai, Stefan A. Schnitzer, Frans Bongers

Biological Sciences Faculty Research and Publications

Lianas are an important component of most tropical forests, where they vary in abundance from high in seasonal forests to low in aseasonal forests. We tested the hypothesis that the physiological ability of lianas to fix carbon (and thus grow) during seasonal drought may confer a distinct advantage in seasonal tropical forests, which may explain pan-tropical liana distributions. We compared a range of leaf-level physiological attributes of 18 co-occurring liana and 16 tree species during the wet and dry seasons in a tropical seasonal forest in Xishuangbanna, China. We found that, during the wet season, lianas had significantly higher CO …

Ic97 Is A Novel Intermediate Chain Of I1 Dynein That Interacts With Tubulin And Regulates Interdoublet Sliding, Maureen Wirschell, Chun Yang, Pinfen Yang, Laura Fox, Haru-Aki Yanagisawa, Ritsu Kamiya, George B. Witman, Mary E. Porter, Winfield S. Sale

Biological Sciences Faculty Research and Publications

Our goal is to understand the assembly and regulation of flagellar dyneins, particularly the Chlamydomonas inner arm dynein called I1 dynein. Here, we focus on the uncharacterized I1-dynein IC IC97. The IC97 gene encodes a novel IC without notable structural domains. IC97 shares homology with the murine lung adenoma susceptibility 1 (Las1) protein—a candidate tumor suppressor gene implicated in lung tumorigenesis. Multiple, independent biochemical assays determined that IC97 interacts with both α- and β-tubulin subunits within the axoneme. I1-dynein assembly mutants suggest that IC97 interacts with both the IC138 and IC140 subunits within the I1-dynein motor complex and that IC97 …

Correction For Ic97 Is A Novel Intermediate Chain Of I1 Dynein That Interacts With Tubulin And Regulates Interdoublet Sliding, Maureen Wirschell, Chun Yang, Pinfen Yang, Laura Fox, Haru-Aki Yanagisawa, Ritsu Kamiya, George B. Witman, Mary E. Porter, Winfield S. Sale

Biological Sciences Faculty Research and Publications

Our goal is to understand the assembly and regulation of flagellar dyneins, particularly the Chlamydomonas inner arm dynein called I1 dynein. Here, we focus on the uncharacterized I1-dynein IC IC97. The IC97 gene encodes a novel IC without notable structural domains. IC97 shares homology with the murine lung adenoma susceptibility 1 (Las1) protein—a candidate tumor suppressor gene implicated in lung tumorigenesis. Multiple, independent biochemical assays determined that IC97 interacts with both α- and β-tubulin subunits within the axoneme. I1-dynein assembly mutants suggest that IC97 interacts with both the IC138 and IC140 subunits within the I1-dynein motor complex and that IC97 …

Srs2 Disassembles Rad51 Filaments By A Protein-Protein Interaction Triggering Atp Turnover And Dissociation Of Rad51 From Dna, Edwin Antony, Eric J. Tomko, Qi Xiao, Lumir Krejci, Timothy M. Lohman, Tom Ellenberger

Biological Sciences Faculty Research and Publications

Rad51 is a DNA recombinase functioning in the repair of DNA double-strand breaks and the generation of genetic diversity by homologous recombination (HR). In the presence of ATP, Rad51 self-assembles into an extended polymer on single-stranded DNA to catalyze strand exchange. Inappropriate HR causes genomic instability, and it is normally prevented by remodeling enzymes that antagonize the activities of Rad51 nucleoprotein filaments. In yeast, the Srs2 helicase/translocase suppresses HR by clearing Rad51 polymers from single-stranded DNA. We have examined the mechanism of disassembly of Rad51 nucleoprotein filaments by Srs2 and find that a physical interaction between Rad51 and the C-terminal …

Co2, Nitrogen, And Diversity Differentially Affect Seed Production Of Prairie Plants, J. Hillierislambers, W. S. Harpole, Stefan A. Schnitzer, D. Tilman, P. B. Reich

Biological Sciences Faculty Research and Publications

Plant species composition and diversity is often influenced by early life history stages; thus, global change could dramatically affect plant community structure by altering seed production. Unfortunately, plant reproductive responses to global change are rarely studied in field settings, making it difficult to assess this possibility. To address this issue, we quantified the effects of elevated CO₂, nitrogen deposition, and declining diversity on inflorescence production and inflorescence mass of 11 perennial grassland species in central Minnesota, USA. We analyzed these data to ask whether (1) global change differentially affects seed production of co‐occurring species; (2) seed production responses …

Liana Communities In Three Tropical Forest Types In Xishuangbanna, South-West China, Zhi-Quan Cai, Stefan A. Schnitzer, Yu-Long Zheng, Frans Bongers

Biological Sciences Faculty Research and Publications

Lianas are an important growth form in tropical forests around the world. However, they are relatively unknown in south-east Asia. We identified, measured and determined the climbing and dispersal modes for lianas in five 0.1-ha plots in three common forest types at the tropical-temperate transitional zone in Xishuangbanna, SW China, namely, montane forest, evergreen broad-leaved forest and seasonally wet forest. Liana diversity in the three forests combined was high; we found a total of 147 liana species, representing 48 families and 75 genera. The mean density of lianas was 3407 ha-1 and varied significantly between the three forests, with 445, …

Insight Into The Carboxyl Transferase Domain Mechanism Of Pyruvate Carboxylase From Rhizobium Etli, Tonya N. Zeczycki, Martin St. Maurice, Sarawut Jitrapakdee, John C. Wallace, Paul V. Attwood, W Wallace Cleland

Biological Sciences Faculty Research and Publications

The effects of mutations in the active site of the carboxyl transferase domain of Rhizobium etli pyruvate carboxylase have been determined for the forward reaction to form oxaloacetate, the reverse reaction to form MgATP, the oxamate-induced decarboxylation of oxaloacetate, the phosphorylation of MgADP by carbamoyl phosphate, and the bicarbonate-dependent ATPase reaction. Additional studies with these mutants examined the effect of pyruvate and oxamate on the reactions of the biotin carboxylase domain. From these mutagenic studies, putative roles for catalytically relevant active site residues were assigned and a more accurate description of the mechanism of the carboxyl transferase domain is presented. …

Isolation And Characterization Of A Spontaneously Immortalized Bovine Retinal Pigmented Epithelial Cell Line, Thomas E. Liggett, T. Daniel Griffiths, Elizabeth R. Gaillard

Biological Sciences Faculty Research and Publications

Background

The Retinal Pigmented Epithelium (RPE) is juxtaposed with the photoreceptor outer segments of the eye. The proximity of the photoreceptor cells is a prerequisite for their survival, as they depend on the RPE to remove the outer segments and are also influenced by RPE cell paracrine factors. RPE cell death can cause a progressive loss of photoreceptor function, which can diminish vision and, over time, blindness ensues. Degeneration of the retina has been shown to induce a variety of retinopathies, such as Stargardt's disease, Cone-Rod Dystrophy (CRD), Retinitis Pigmentosa (RP), Fundus Flavimaculatus (FFM), Best's disease and Age-related Macular Degeneration …

Exercise In Space: Human Skeletal Muscle After 6 Months Aboard The International Space Station, Scott A. Trappe, David Costill, Philip M. Gallagher, Andrew C. Creer, Jim R. Peters, Harlan Evans, Danny A. Riley, Robert H. Fitts

Biological Sciences Faculty Research and Publications

The aim of this investigation was to document the exercise program used by crewmembers (n = 9; 45 +/- 2 yr) while aboard the International Space Station (ISS) for 6 mo and examine its effectiveness for preserving calf muscle characteristics. Before and after spaceflight, we assessed calf muscle volume (MRI), static and dynamic calf muscle performance, and muscle fiber types (gastrocnemius and soleus). While on the ISS, crewmembers had access to a running treadmill, cycle ergometer, and resistance exercise device. The exercise regimen varied among the crewmembers with aerobic exercise performed ~5 h/wk at a moderate intensity and resistance …

Down And Out. The Functional Effects Of Silencing Calsequestrin 1 Or Deleting Both Calsequestrin Genes In Mammalian Muscle, Leandro Royer, Sandrine Pouvreau, Ying Wang, Gerhard Meissner, Jingsong Zhou, Pompeo Volpe, Alessandra Nori, Robert H. Fitts, James L. W. Bain, Feliciano Protasi, Paul D. Allen, Bjorn Knollmann, Danny R. Riley, Eduardo Rios

Biological Sciences Faculty Research and Publications

No abstract provided.

Rex1p Deficiency Leads To Accumulation Of Precursor Initiator TrnaMet And Polyadenylation Of Substrate Rnas In Saccharomyces Cerevisiae, Sarah G. Ozanick, Xuying Wang, Michael Costanzo, Renee L. Brost, Charles Boone, James T. Anderson

Biological Sciences Faculty Research and Publications

A synthetic genetic array was used to identify lethal and slow-growth phenotypes produced when a mutation in TRM6, which encodes a tRNA modification enzyme subunit, was combined with the deletion of any non-essential gene in Saccharomyces cerevisiae. We found that deletion of the REX1 gene resulted in a slow-growth phenotype in the trm6-504 strain. Previously, REX1 was shown to be involved in processing the 3′ ends of 5S rRNA and the dimeric tRNA^Arg-tRNA^Asp. In this study, we have discovered a requirement for Rex1p in processing the 3′ end of tRNA_i^Met precursors and …

Numerical Modeling Of Hemodynamics In The Thoracic Aorta And Alterations By Dacron Patch Treatment Of Aortic Coarctation, Ronak Jashwant Dholakia

Master's Theses (2009 -)

Coarctation of the aorta (CoA) is a major congenital heart disease, characterized by a severe stenosis of the proximal descending thoracic aorta. Traditionally, surgery has been the treatment of choice for CoA. Dacron patch aortoplasty gained increased popularity after its introduction in the mid-twentieth century due to its advantages over other surgical treatment methods available at the time. A major complication with Dacron patch aortoplasty has been the formation of late aneurysm with as much as 51% incidence reported in follow up studies. The change in aortic morphology and formation of aneurysms after Dacron patch surgery could lead to local …

Unique Contractile And Structural Protein Expression In Dog Ileal Inner Circular Smooth Muscle, Thomas J. Eddinger

Biological Sciences Faculty Research and Publications

This study was designed to test the hypothesis that there is heterogeneous expression of contractile and structural proteins between the smooth muscle cells (SMCs) in the inner and outer circular muscle (ICM and OCM) layers of the ileum. Immunohistochemical staining and quantitation of fresh frozen sections of the dog ileum was performed using protein specific antibodies. Smooth muscle (SM) SMA myosin heavy chain (MHC), α- and γ-SM actin, and vinculin all show greater expression in the ICM relative to the OCM. SMB MHC and fibronectin show the opposite pattern, with greater expression in the OCM relative to the ICM. Differences …

Adverse Effects Of Chronic Circadian Desynchronization In Animals In A "Challenging" Environment, Fabian Preuss, Tueming Tang, Aaron D. Laposky, Deanna M. Arble, Ali Keshavarzian, Fred W. Turek

Biological Sciences Faculty Research and Publications

Continuous disruption of circadian rhythms, as seen in human shift workers, has been associated with the development of a number of adverse mental and physiological conditions. However, scientific evidence linking circadian disruption to overall health, particularly in animal models, is not well documented. In this study, we have demonstrated that exposing C57BL/6J mice to 12-h phase shifts every 5 days for 3 mo had no effect on body weight or intestinal physiology. However, when animals were further challenged with dextran sodium sulfate to induce colitis, chronic shifting of the light-dark cycle led to a dramatic increase in the progression of …

Phylogeography Of The Bigeye Chub Hybopsis Amblops (Teleostei: Cypriniformes): Early Pleistocene Diversification And Post‐Glacial Range Expansion, Peter B. Berendzen, Tony Gamble, Andrew M. Simons

Biological Sciences Faculty Research and Publications

The bigeye chub, Hybopsis amblops, is a member of the Central Highlands ichthyofauna of eastern North America. Phylogenetic analyses of the H. amblops species group based on a 1059 bp fragment of the mitochondrial DNA cytochrome b gene did not recover a monophyletic group. The inclusion of Hybopsis hypsinotus in the species complex is questionable. Within H. amblops, five strongly supported clades were identified; two clades containing haplotypes from the Ozark Highlands and three clades containing haplotypes from the Eastern Highlands and previously glaciated regions of the Ohio and Wabash River drainages. Estimates of the timing of divergence …

The Yeast Aac2 Protein Exists In Physical Association With The Cytochrome Bc1-Cox Supercomplex And The Tim23 Machinery, Mary Kathryn Dienhart, Rosemary A. Stuart

Biological Sciences Faculty Research and Publications

The ADP/ATP carrier (AAC) proteins play a central role in cellular metabolism as they facilitate the exchange of ADP and ATP across the mitochondrial inner membrane. We present evidence here that in yeast (Saccharomyces cerevisiae) mitochondria the abundant Aac2 isoform exists in physical association with the cytochrome c reductase (cytochrome bc₁)-cytochrome c oxidase (COX) supercomplex and its associated TIM23 machinery. Using a His-tagged Aac2 derivative and affinity purification studies, we also demonstrate here that the Aac2 isoform can be affinity-purified with other AAC proteins. Copurification of the Aac2 protein with the TIM23 machinery can occur independently …

Limited Native Plant Regeneration In Novel, Exotic-Dominated Forests On Hawai’I, Joseph Mascaro, Kristen K. Becklund, R. Flint Hughes, Stefan A. Schnitzer

Biological Sciences Faculty Research and Publications

Ecological invasions are a major driver of global environmental change. When invasions are frequent and prolonged, exotic species can become dominant and ultimately create novel ecosystem types. These ecosystems are now widespread globally. Recent evidence from Puerto Rico suggests that exotic-dominated forests can provide suitable regeneration sites for native species and promote native species abundance, but this pattern has been little explored elsewhere. We surveyed 46 sites in Hawai’i to determine whether native species occurred in the understories of exotic-dominated forests. Native trees smaller than 10 cm in diameter were absent in 28 of the 46 sites and rare in …

Blunted Cystine–Glutamate Antiporter Function In The Nucleus Accumbens Promotes Cocaine-Induced Drug Seeking, Kristen S. Kau, Aric Madayag, John R. Mantsch, Mark D. Grier, Omer Abdulhameed, David A. Baker

Biomedical Sciences Faculty Research and Publications

Repeated cocaine alters glutamate neurotransmission, in part, by reducing cystine–glutamate exchange via system x_c−, which maintains glutamate levels and receptor stimulation in the extrasynaptic compartment. In the present study, we undertook two approaches to determine the significance of plasticity involving system x_c−. First, we examined whether the cysteine prodrug N-acetylcysteine attenuates cocaine-primed reinstatement by targeting system x_c−. Rats were trained to self-administer cocaine (1 mg/kg/200 μl, i.v.) under extended access conditions (6 h/day). After extinction training, cocaine (10 mg/kg, i.p.) primed reinstatement was assessed in rats pretreated with N-acetylcysteine (0–60 mg/kg, i.p.) in the …

Vibration Causes Acute Vascular Injury In A Two-Step Process: Vasoconstriction And Vacuole Disruption, Sandya R. Govindaraju, James L. W. Bain, Thomas J. Eddinger, Danny A. Riley

Biological Sciences Faculty Research and Publications

Hand–arm vibration syndrome is a vasospastic and neurodegenerative occupational disease. In the current study, the mechanism of vibration- induced vascular smooth muscle cell (SMC) injury was examined in a rat-tail vibration model. Tails of male Sprague Dawley rats were vibrated continuously for 4 hr at 60 Hz, 49 m/s2 with or without general anesthesia. Ventral tail arteries were aldehyde fixed and embedded in epoxy resin to enable morphological analysis. Vibration without anesthesia caused vasoconstriction and vacuoles in the SMC. Anesthetizing rats during vibration prevented vasoconstriction and vacuole formation. Exposing tail arteries in situ to 1 mM norepinephrine (NE) for 15 …

Cellular And Synaptic Actions Of Acetylcholine In The Lamprey Spinal Cord, Katharina A. Quinlan, James T. Buchanan

Biological Sciences Faculty Research and Publications

This study investigated cellular and synaptic mechanisms of cholinergic neuromodulation in the in vitro lamprey spinal cord. Most spinal neurons tested responded to local application of acetylcholine (ACh) with depolarization and decreased input resistance. The depolarization persisted in the presence of either tetrodotoxin or muscarinic antagonist scopolamine and was abolished with nicotinic antagonist mecamylamine, indicating a direct depolarization through nicotinic ACh receptors. Local application of muscarinic ACh agonists modulated synaptic strength in the spinal cord by decreasing the amplitude of unitary excitatory and inhibitory postsynaptic potentials. The postsynaptic response to direct application of glutamate was unchanged by muscarinic agonists, suggesting …

Weak Competition Among Tropical Tree Seedlings: Implications For Species Coexistence, C.E. Timothy Paine, Kyle E. Harms, Stefan A. Schnitzer, Walter P. Carson

Biological Sciences Faculty Research and Publications

The intensity of competition among forest tree seedlings is poorly understood, but has important ramifications for their recruitment and for the maintenance of species diversity. Intense competition among seedlings could allow competitively dominant species to exclude subordinate species. Alternatively, the low density and small stature of forest tree seedlings could preclude intense interseedling competition. In this case, other processes, such as size‐asymmetric competition with adults, interactions with consumers, or neutral dynamics would prevail as those structuring the forest understory. We tested the intensity of, and potential for, intraspecific competition among tree seedlings of three species (Brosimum alicastrum, Matisia …

Cloning Of The Neurodegeneration Gene Drop-Dead And Characterization Of Additional Phenotypes Of Its Mutation, Edward M. Blumenthal

Biological Sciences Faculty Research and Publications

Mutations in the Drosophila gene drop-dead (drd) result in early adult lethality and neurodegeneration, but the molecular identity of the drd gene and its mechanism of action are not known. This paper describes the characterization of a new X-linked recessive adult-lethal mutation, originally called lot's wife (lwf¹) but subsequently identified as an allele of drd (drd^lwf); drd^lwf mutants die within two weeks of eclosion. Through mapping and complementation, the drd gene has been identified as CG33968, which encodes a putative integral membrane protein of unknown function. The drd^lwf allele is associated …

Species Limits And Phylogeography Of North American Cricket Frogs (Acris: Hylidae), Tony Gamble, Peter B. Berendzen, H. Bradley Shaffer, David E. Starkey, Andrew M. Simons

Biological Sciences Faculty Research and Publications

Cricket frogs are widely distributed across the eastern United States and two species, the northern cricket frog (Acris crepitans) and the southern cricket frog (A. gryllus) are currently recognized. We generated a phylogenetic hypothesis for Acris using fragments of nuclear and mitochondrial genes in separate and combined phylogenetic analyses. We also used distance methods and fixation indices to evaluate species limits within the genus and the validity of currently recognized subspecies of A. crepitans. The distributions of existing A. crepitans subspecies, defined by morphology and call types, do not match the distributions of evolutionary lineages recovered using …

Out Of The Blue: A Novel, Trans‐Atlantic Clade Of Geckos (Gekkota, Squamata), Tony Gamble, Aaron M. Bauer, Eli Greenbaum, Todd R. Jackman

Biological Sciences Faculty Research and Publications

Phylogenetic relationships among gekkotan lizards were estimated from five nuclear protein-coding genes in separate and combined analyses using maximum parsimony, maximum likelihood and Bayesian analyses. All analyses recovered a monophyletic trans-Atlantic gecko clade (Phyllodactylidae) consisting of the genera Asaccus, Haemodracon, Homonota, Phyllodactylus, Phyllopezus, Ptyodactylus, Tarentola and Thecadactylus. No other phylogenetic or taxonomic hypotheses have proposed linking these genera, which have been consistently grouped with other taxa outside of the clade. In this paper, we determine the relationships of this new clade to other major gekkotan groups, evaluate previous phylogenetic hypotheses regarding constituent members of this novel clade, and critically …

Contribution Of Cystine-Glutamate Antiporters To The Psychotomimetic Effects Of Phencyclidine, David A. Baker, Aric Madayag, Lars V. Kristiansen, James H. Meador-Woodruff, Vahram Haroutunian, Ilangovan Raju

Biological Sciences Faculty Research and Publications

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect …

Requirement Of A Plasmid-Encoded Catalase For Survival Of Rhizobium Etli Cfn42 In A Polyphenol-Rich Environment, Alejandro García-De Los Santos, Erika López, Ciro A. Cubillas, K. Dale Noel, Susana Brom, David Romero

Biological Sciences Faculty Research and Publications

Nitrogen-fixing bacteria collectively called rhizobia are adapted to live in polyphenol-rich environments. The mechanisms that allow these bacteria to overcome toxic concentrations of plant polyphenols have not been clearly elucidated. We used a crude extract of polyphenols released from the seed coat of the black bean to simulate a polyphenol-rich environment and analyze the response of the bean-nodulating strain Rhizobium etli CFN42. Our results showed that the viability of the wild type as well as that of derivative strains cured of plasmids p42a, p42b, p42c, and p42d or lacking 200 kb of plasmid p42e was not affected in this environment. …

Supplemental Protocol For Liana Censuses, Stefan A. Schnitzer, Suzanne Rutishauser, Salomón Aguilar

Biological Sciences Faculty Research and Publications

Lianas affect many aspects of tropical forest dynamics and thus the study of their ecology is critical for a comprehensive understanding of tropical forest ecology. Recently, we initiated a complete census of all lianas ≥1 cm diameter in the 50 ha forest dynamics plot on Barro Colorado Island, Panama using the census protocol developed by Gerwing et al. [Gerwing, J.J., Schnitzer, S.A., Burnham, R.J., Bongers, F., Chave, J., DeWalt, S.J., Ewango, C.E.N., Foster, R., Kenfack, D., Martinez-Ramos, M., Parren, M., Parthasarathy, N., Perez-Salicrup, D.R., Putz, F.E., Thomas, D.W., 2006. A standard protocol for liana censuses. Biotropica 38, 256–261]. This protocol …

The Cross-Bridge Cycle And Skeletal Muscle Fatigue, Robert H. Fitts

Biological Sciences Faculty Research and Publications

The functional correlates of fatigue observed in both animals and humans during exercise include a decline in peak force (P₀), maximal velocity, and peak power. Establishing the extent to which these deleterious functional changes result from direct effects on the myofilaments is facilitated through understanding the molecular mechanisms of the cross-bridge cycle. With actin-myosin binding, the cross-bridge transitions from a weakly bound low-force state to a strongly bound high-force state. Low pH reduces the number of high-force cross bridges in fast fibers, and the force per cross bridge in both fast and slow fibers. The former is thought …