Jaw-muscle electromyography during chewing in Belanger's treeshrews (Tupaia belangeri).
Animals; Biological; Biomechanical Phenomena; Electromyography; Mastication/*physiology; Masticatory Muscles/*physiology; Models; Muscle Contraction/*physiology; Phylogeny; Time Factors; Tupaia/*physiology
We examined masseter and temporalis recruitment and firing patterns during chewing in five male Belanger's treeshrews (Tupaia belangeri), using electromyography (EMG). During chewing, the working-side masseters tend to show almost three times more scaled EMG activity than the balancing-side masseters. Similarly, the working-side temporalis muscles have more than twice the scaled EMG activity of the balancing-side temporalis. The relatively higher activity in the working-side muscles suggests that treeshrews recruit less force from their balancing-side muscles during chewing. Most of the jaw-closing muscles in treeshrews can be sorted into an early-firing or late-firing group, based on occurrence of peak activity during the chewing cycle. Specifically, the first group of jaw-closing muscles to reach peak activity consists of the working-side anterior and posterior temporalis and the balancing-side superficial masseter. The balancing-side anterior and posterior temporalis and the working-side superficial masseter peak later in the power stroke. The working-side deep masseter peaks, on average, slightly before the working-side superficial masseter. The balancing-side deep masseter typically peaks early, at about the same time as the balancing-side superficial masseter. Thus, treeshrews are unlike nonhuman anthropoids that peak their working-side deep masseters early and their balancing-side deep masseters late in the power stroke. Because in anthropoids the late firing of the balancing-side deep masseter contributes to wishboning of the symphysis, the treeshrew EMG data suggest that treeshrews do not routinely wishbone their symphyses during chewing. Based on the treeshrew EMG data, we speculate that during chewing, primitive euprimates 1) recruited more force from the working-side jaw-closing muscles as compared to the balancing-side muscles, 2) fired an early group of jaw-closing muscles followed by a second group of muscles that peaked later in the power stroke, 3) did not fire their working-side deep masseter significantly earlier than their working-side superficial masseter, and 4) did not routinely fire their balancing-side deep masseter after the working-side superficial masseter.
Vinyard Christopher J; Williams Susan H; Wall Christine E; Johnson Kirk R; Hylander William L
American journal of physical anthropology
2005
2005-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/ajpa.20176" target="_blank" rel="noreferrer noopener">10.1002/ajpa.20176</a>
Behavioral implications of ontogenetic changes in intrinsic hand and foot proportions in olive baboons (Papio Anubis).
*allometry; *early performance; *Foot/anatomy & histology/physiology; *grasping; *Hand/anatomy & histology/physiology; *locomotor development; *Papio anubis/anatomy & histology/physiology; *primate evolution; Animals; Anthropology; Female; Hand Strength/physiology; Locomotion; Male; Models; Physical; Statistical
OBJECTIVES: Relatively long digits are considered to enhance grasping performance in primates. We tested whether growth-related changes in intrinsic hand and foot proportions may have behavioral implications for growing animals, by examining whether ontogenetic changes in digital proportions are related to variation in voluntary grasping behaviors in baboons. MATERIALS AND METHODS: Longitudinal morphological and behavioral data were collected on 6 captive olive baboons (Papio anubis) as they aged from 5 to 22 months. The length of digits and metapodials, measured from radiographs, were used to calculate phalangeal indices (i.e., PIs: summed length of non-distal phalanges relative to corresponding metapodial length). We also examined the allometric scaling of digital bones relative to body mass. We observed baboon positional behaviors over a 15-day period following the radiographic sessions, quantifying the frequency of forelimb and hindlimb grasping behaviors. RESULTS: PIs for all digits declined during growth, a result of the differential scaling of metapodials (which scaled to body mass with isometry) versus phalanges (which scaled with negative allometry). The incidence of forelimb and hindlimb grasping behaviors declined with age. Though we found no relationship between forelimb grasping and hand proportions, the incidence of hindlimb grasping was directly correlated with postaxial digit PIs. DISCUSSION: Only changes in the intrinsic proportions of the pedal digits are associated with variation in grasping activity in growing baboons. This finding accords previous biomechanical and neuroanatomical studies showing distinct functional roles for the hands and feet during primate locomotion, and has important implications for reconstructing primate locomotor evolution.
Druelle Francois; Young Jesse; Berillon Gilles
American journal of physical anthropology
2018
2018-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/ajpa.23331" target="_blank" rel="noreferrer noopener">10.1002/ajpa.23331</a>
Macroevolutionary developmental biology: Embryos, fossils, and phylogenies.
*Embryo; *Fossils; *Phylogeny; Animals; Developmental Biology/*methods; embryos; evolutionary developmental biology; fossils; macroevolution; Models; Nonmammalian; phylogenetic comparative methods; Statistical; Vertebrates
The field of evolutionary developmental biology is broadly focused on identifying the genetic and developmental mechanisms underlying morphological diversity. Connecting the genotype with the phenotype means that evo-devo research often considers a wide range of evidence, from genetics and morphology to fossils. In this commentary, we provide an overview and framework for integrating fossil ontogenetic data with developmental data using phylogenetic comparative methods to test macroevolutionary hypotheses. We survey the vertebrate fossil record of preserved embryos and discuss how phylogenetic comparative methods can integrate data from developmental genetics and paleontology. Fossil embryos provide limited, yet critical, developmental data from deep time. They help constrain when developmental innovations first appeared during the history of life and also reveal the order in which related morphologies evolved. Phylogenetic comparative methods provide a powerful statistical approach that allows evo-devo researchers to infer the presence of nonpreserved developmental traits in fossil species and to detect discordant evolutionary patterns and processes across levels of biological organization.
Organ Chris L; Cooper Lisa Noelle; Hieronymus Tobin L
Developmental dynamics : an official publication of the American Association of Anatomists
2015
2015-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/dvdy.24318" target="_blank" rel="noreferrer noopener">10.1002/dvdy.24318</a>
Regulation of cholesterol and bile acid homeostasis by the cholesterol 7alpha-hydroxylase/steroid response element-binding protein 2/microRNA-33a axis in mice.
Acetyl Coenzyme A/metabolism; Animal; Animals; Bile Acids and Salts/*metabolism; Cholesterol 7-alpha-Hydroxylase/genetics/*metabolism; Cholesterol/*metabolism; Homeostasis/*physiology; Knockout; Lipid Metabolism/physiology; Liver/metabolism; Male; Messenger/metabolism; Mice; MicroRNAs/*metabolism; Models; RNA; Signal Transduction/*physiology; Sterol Regulatory Element Binding Protein 2/*metabolism; Transgenic
UNLABELLED: Bile acid synthesis not only produces physiological detergents required for intestinal nutrient absorption, but also plays a critical role in regulating hepatic and whole-body metabolic homeostasis. We recently reported that overexpression of cholesterol 7alpha-hydroxylase (CYP7A1) in the liver resulted in improved metabolic homeostasis in Cyp7a1 transgenic (Cyp7a1-tg) mice. This study further investigated the molecular links between bile acid metabolism and lipid homeostasis. Microarray gene profiling revealed that CYP7A1 overexpression led to marked activation of the steroid response element-binding protein 2 (SREBP2)-regulated cholesterol metabolic network and absence of bile acid repression of lipogenic gene expression in livers of Cyp7a1-tg mice. Interestingly, Cyp7a1-tg mice showed significantly elevated hepatic cholesterol synthesis rates, but reduced hepatic fatty acid synthesis rates, which was accompanied by increased (14) C-glucose-derived acetyl-coenzyme A incorporation into sterols for fecal excretion. Induction of SREBP2 also coinduces intronic microRNA-33a (miR-33a) in the SREBP2 gene in Cyp7a1-tg mice. Overexpression of miR-33a in the liver resulted in decreased bile acid pool, increased hepatic cholesterol content, and lowered serum cholesterol in mice. CONCLUSION: This study suggests that a CYP7A1/SREBP2/miR-33a axis plays a critical role in regulation of hepatic cholesterol, bile acid, and fatty acid synthesis. Antagonism of miR-33a may be a potential strategy to increase bile acid synthesis to maintain lipid homeostasis and prevent nonalcoholic fatty liver disease, diabetes, and obesity.
Li Tiangang; Francl Jessica M; Boehme Shannon; Chiang John Y L
Hepatology (Baltimore, Md.)
2013
2013-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/hep.26427" target="_blank" rel="noreferrer noopener">10.1002/hep.26427</a>
A novel role for Bcl-2 associated-athanogene-1 (Bag-1) in regulation of the endoplasmic reticulum stress response in mammalian chondrocytes.
*Gene Expression Regulation; Animals; Apoptosis; Biological; Cell Proliferation; Chondrocytes/*metabolism/pathology; Collagen Type II/metabolism; DNA-Binding Proteins/*metabolism/physiology; Endoplasmic Reticulum/metabolism; Models; Phenotype; Rats; RNA Interference; Subcellular Fractions/metabolism; Time Factors; Transcription Factors/*metabolism/physiology; Transfection
BAG-1 (Bcl-2 associated athanogene-1) is a multifunctional protein, linking cell proliferation, cell death, protein folding, and cell stress. In vivo, BAG-1 is expressed in growth plate and articular cartilage, and the expression of BAG-1 is decreased with aging. Chondrocytes respond to endoplasmic reticulum (ER) stress with decreased expression of extracellular matrix proteins, and prolonged ER stress leads to chondrocyte apoptosis. Here we demonstrate for the first time that BAG-1 is involved in ER stress-induced apoptosis in chondrocytes. Induction of ER stress through multiple mechanisms all resulted in downregulation of BAG-1 expression. In addition, direct suppression of BAG-1 expression resulted in chondrocyte growth arrest and apoptosis, while stable overexpression of BAG-1 delayed the onset of ER stress-mediated apoptosis. In addition to regulating apoptosis, we also observed decreased expression of collagen type II in BAG-1 deficient chondrocytes. In contrast, overexpression of BAG-1 resulted in increased expression of collagen type II. Moreover, under ER stress conditions, the reduced expression of collagen type II was delayed in chondrocytes overexpressing BAG-1. These results suggest a novel role for BAG-1 in supporting viability and matrix expression of chondrocytes.
Yang Ling; McBurney Denise; Tang Shou-Ching; Carlson Sara G; Horton Walter E Jr
Journal of cellular biochemistry
2007
2007-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jcb.21328" target="_blank" rel="noreferrer noopener">10.1002/jcb.21328</a>
Activation and circuitry of uterine-cervix-related neurons in the lumbosacral dorsal root ganglia and spinal cord at parturition.
Analysis of Variance; Animals; Blotting; Cell Count/methods; Cervix Uteri/*cytology; Cyclic AMP Response Element-Binding Protein/metabolism; Estrogen Receptor alpha/metabolism; Female; Ganglia; Gene Expression Regulation/physiology; Immunohistochemistry/methods; Lumbosacral Region; Models; Nerve Net/cytology/*physiology; Neurological; Neurons/classification/*physiology; Oncogene Proteins v-fos/metabolism; Parturition/*physiology; Pregnancy; Rats; Spinal Cord/*cytology; Spinal/*cytology; Sprague-Dawley; Stilbamidines/metabolism; Time Factors; Western/methods
Stimulation of the uterine cervix at parturition activates neural circuits involving primary sensory nerves and supraspinally projecting neurons of the lumbosacral spinal cord, resulting in output of hypothalamic neurohormones. Dorsal root ganglia (DRG) and spinal neurons of these circuits are not well-characterized. The objectives of this study were to detail the activation of DRG and spinal neurons of the L6/S1 levels that are stimulated at late pregnancy, verify hypothalamic projections of activated spinal neurons, and determine whether activated neurons express estrogen receptor-alpha (ERalpha). Expression of phosphorylated cyclic-AMP response element-binding protein (PCREB) and Fos immunohistochemistry were used to "mark" activated DRG and spinal neurons, respectively. Retrograde tracing identified uterine-cervix-related and spinohypothalamic neurons. Baseline PCREB expression in the DRG increased during pregnancy and peaked during the last trimester. Some PCREB-expressing neurons contained retrograde tracer identifying them as cervix-related neurons. Fos-expressing neurons were few in spinal cords of nonpregnant and day 22 pregnant rats but were numerous in parturient animals. Some Fos-expressing neurons located in the dorsal half of the spinal cord contained retrograde tracer identifying them as spinohypothalamic neurons. Some DRG neurons expressing PCREB also expressed ERalpha, and some spinal neurons activated at parturition projected axons to the hypothalamus and expressed ERalpha. These results indicate that DRG and spinal cord neurons are activated at parturition; that those in the spinal cord are present in areas involved in autonomic and sensory processing; that some spinal neurons project axons to the hypothalamus, ostensibly part of a neuroendocrine reflex; and that sensory and spinal neurons can respond to estrogens. Moreover, some activated sensory neurons may be involved in the animal's perception of labor pain.
Puder B A; Papka R E
Journal of neuroscience research
2005
2005-12
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<a href="http://doi.org/10.1002/jnr.20690" target="_blank" rel="noreferrer noopener">10.1002/jnr.20690</a>
Promoter activity and regulation of the CYP4F2 leukotriene B(4) omega-hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2 cells.
*Gene Expression Regulation; *Promoter Regions; Amino Acid Sequence; Base Sequence; Cell Line; Cloning; Cytochrome P-450 CYP4A; Cytochrome P-450 Enzyme System/*genetics/metabolism; Cytochrome P450 Family 4; Cytoplasmic and Nuclear/metabolism; DNA; DNA Footprinting; Enzymologic; Exons; Genes; Genetic; Genetic/drug effects; Humans; Introns; Leukotriene B4/metabolism; Mixed Function Oxygenases/metabolism; Models; Molecular; Molecular Sequence Data; Peroxisome Proliferators/*metabolism; Receptors; Reporter; Retinoic Acid Receptor alpha; Retinoic Acid/metabolism; Sequence Analysis; Transcription; Transcription Factors/metabolism; Transfection; Tretinoin/*metabolism
The human liver CYP4F2 gene (Accession No. AF221943) encodes a leukotriene B(4) omega-hydroxylase that metabolizes leukotriene B(4) (LTB(4)) to a less potent proinflammatory eicosanoid, 20-OH-LTB(4). We sequenced a 6.7-kb genomic fragment of the human CYP4F2 gene that has the first five exons and 500 bp of the 5'-flanking region. The major transcription start site was found to be 49 bp upstream of the 3' end of exon 1 and the ATG translation initiation codon was located in exon 2. Besides the TATA box at -39 bp and basal transcription factor binding sites, the promoter region and 412-bp intron 1 have several putative binding sites for nuclear factors that may mediate the inflammatory response and lipid homeostasis. We found two DR1 elements in the 5' promoter, a DR2 element in intron 1, and RXR/RAR binding sites in both intron 1 and the 5' promoter. DNase I footprinting revealed three protected sequences, with the region containing two CAATT boxes at -71 and -111 bp important in CYP4F2 gene expression. Luciferase reporter assays showed that the 500-bp upstream sequence has strong promoter activity. Transient transfection experiments identified two sites in the 5' promoter and intron 1 that cooperate in gene transcription while exon 1 and a
Zhang X; Chen L; Hardwick J P
Archives of biochemistry and biophysics
2000
2000-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/abbi.2000.1836" target="_blank" rel="noreferrer noopener">10.1006/abbi.2000.1836</a>
Aspects of mineral structure in normally calcifying avian tendon.
Anatomic; Animals; Atomic Force/methods; Calcification; Collagen/chemistry/ultrastructure; Microscopy; Minerals/*chemistry; Models; Molecular; Non-programmatic; Physiologic; Tendons/*chemistry/*ultrastructure; Turkeys
Structural characteristics of normally calcifying leg tendons of the domestic turkey Meleagris gallopavo have been observed for the first time by tapping mode atomic force microscopy (TMAFM), and phase as well as corresponding topographic images were acquired to gain insight into the features of mineralizing collagen fibrils and fibers. Analysis of different regions of the tendon has yielded new information concerning the structural interrelationships in vivo between collagen fibrils and fibers and mineral crystals appearing in the form of plates and plate aggregates. TMAFM images show numerous mineralized collagen structures exhibiting characteristic periodicity (54-70 nm), organized with their respective long axes parallel to each other. In some instances, mineral plates (30-40 nm thick) are found interspersed between and in intimate contact with the mineralized collagen. The edges of such plates lie parallel to the neighboring collagen. Many of these plates appear to be aligned to form larger aggregates (475-600 nm long x 75-90 nm thick) that also retain collagen periodicity along their exposed edges. Intrinsic structural properties of the mineralizing avian tendon have not previously been described on the scale reported in this study. These data provide the first visual evidence supporting the concept that larger plates form from parallel association of smaller ones, and the data fill a gap in knowledge between macromolecular- and anatomic-scale studies of the mineralization of avian tendon and connective tissues in general. The observed organization of mineralized collagen, plates, and plate aggregates maintaining a consistently parallel nature demonstrates the means by which increasing structural complexity may be achieved in a calcified tissue over greater levels of hierarchical order.
Siperko L M; Landis W J
Journal of structural biology
2001
2001-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/jsbi.2001.4414" target="_blank" rel="noreferrer noopener">10.1006/jsbi.2001.4414</a>
Use of brain slices to study long-term potentiation and depression as examples of synaptic plasticity.
*Long-Term Potentiation; *Neuronal Plasticity; Animals; Brain/*physiology; Electrophysiology/methods; Glutamic Acid/physiology; In Vitro Techniques; Memory/*physiology; Models; Neurological; Synapses/*physiology; Synaptic Transmission
Brain slices have been responsible for the majority of advances in our understanding of the cellular aspects of altered synaptic strength underlying memory, long-term potentiation (LTP) and long-term depression (LTD), and increases and decreases, respectively, in synaptic strength at glutamatergic synapses. Our current understanding of LTP and LTD has come largely from studies in hippocampal slices. We consider the strengths and limitations of brain slice technology applied to this subject and conclude that they will continue to have an important role in future studies into the cellular machinery underlying changes in synaptic strength.
Teyler T J
Methods (San Diego, Calif.)
1999
1999-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/meth.1999.0764" target="_blank" rel="noreferrer noopener">10.1006/meth.1999.0764</a>
The Physiologic Impact of Unilateral Recurrent Laryngeal Nerve (RLN) Lesion on Infant Oropharyngeal and Esophageal Performance.
Animal; Animals; Aspiration; Biological; Deglutition; Deglutition – Physiology; Deglutition disorders; Deglutition Disorders – Etiology; Deglutition Disorders – Physiopathology; Deglutition Disorders/*etiology/physiopathology; Deglutition/*physiology; Disease Models; Esophagus; Esophagus – Physiopathology; Esophagus/*physiopathology; Human; Infant; Laryngeal Nerves – Injuries; Laryngeal Nerves – Physiopathology; Models; Oropharynx – Physiopathology; Oropharynx/*physiopathology; Recurrent laryngeal nerve; Recurrent Laryngeal Nerve Injuries/*complications/physiopathology; Recurrent Laryngeal Nerve/*physiopathology; Swine
Recurrent laryngeal nerve (RLN) injury in neonates, a complication of patent ductus arteriosus corrective surgery, leads to aspiration and swallowing complications. Severity of symptoms and prognosis for recovery are variable. We transected the RLN unilaterally in an infant mammalian animal model to characterize the degree and variability of dysphagia in a controlled experimental setting. We tested the hypotheses that (1) both airway protection and esophageal function would be compromised by lesion, (2) given our design, variability between multiple post-lesion trials would be minimal, and (3) variability among individuals would be minimal. Individuals' swallowing performance was assessed pre- and post-lesion using high speed VFSS. Aspiration was assessed using the Infant Mammalian Penetration-Aspiration Scale (IMPAS). Esophageal function was assessed using two measures devised for this study. Our results indicate that RLN lesion leads to increased frequency of aspiration, and increased esophageal dysfunction, with significant variation in these basic patterns at all levels. On average, aspiration worsened with time post-lesion. Within a single feeding sequence, the distribution of unsafe swallows varied. Individuals changed post-lesion either by increasing average IMPAS score, or by increasing variation in IMPAS score. Unilateral RLN transection resulted in dysphagia with both compromised airway protection and esophageal function. Despite consistent, experimentally controlled injury, significant variation in response to lesion remained. Aspiration following RLN lesion was due to more than unilateral vocal fold paralysis. We suggest that neurological variation underlies this pattern.
Gould Francois D H; Lammers Andrew R; Ohlemacher Jocelyn; Ballester Ashley; Fraley Luke; Gross Andrew; German Rebecca Z
Dysphagia
2015
2015-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00455-015-9648-8" target="_blank" rel="noreferrer noopener">10.1007/s00455-015-9648-8</a>
Animal Models for Dysphagia Studies: What Have We Learnt So Far.
*Animal models; *Deglutition; *Deglutition disorders; *Disease Models; *Pathophysiology; *Performance; Animal; Animals; Biological; Biomedical Research/*methods; Deglutition – Physiology; Deglutition Disorders – Physiopathology; Deglutition Disorders/*physiopathology; Deglutition/physiology; Humans; Medical – Methods; Models; Research
Research using animal models has contributed significantly to realizing the goal of understanding dysfunction and improving the care of patients who suffer from dysphagia. But why should other researchers and the clinicians who see patients day in and day out care about this work? Results from studies of animal models have the potential to change and grow how we think about dysphagia research and practice in general, well beyond applying specific results to human studies. Animal research provides two key contributions to our understanding of dysphagia. The first is a more complete characterization of the physiology of both normal and pathological swallow than is possible in human subjects. The second is suggesting of specific, physiological, targets for development and testing of treatment interventions to improve dysphagia outcomes.
German Rebecca Z; Crompton A W; Gould Francois D H; Thexton Allan J
Dysphagia
2017
2017-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00455-016-9778-7" target="_blank" rel="noreferrer noopener">10.1007/s00455-016-9778-7</a>
LVC Timing in Infant Pig Swallowing and the Effect of Safe Swallowing.
*Animal model; *Aspiration; *Deglutition; *Deglutition disorders; *Dysphagia; *Infant; *Laryngeal vestibule closure; *Recurrent laryngeal nerve; Animal; Animal Population Groups; Animals; Aspiration – Etiology; Aspiration/*etiology; Biological; Deglutition – Physiology; Deglutition Disorders – Etiology; Deglutition Disorders/*etiology; Deglutition/*physiology; Disease Models; Humans; Laryngeal Nerve Injuries/*complications; Laryngeal Nerves – Injuries; Larynx; Models; Newborn; Oropharynx; Pneumonia; Questionnaires; Swine
Recurrent laryngeal nerve (RLN) injury in neonates, a complication of head and neck surgeries, leads to increased aspiration risk and swallowing dysfunction. The severity of resulting sequelae range from morbidity, such as aspiration pneumonia, to mortality from infection and failure to thrive. The timing of airway protective events including laryngeal vestibule closure (LVC) is implicated in aspiration. We unilaterally transected the RLN in an infant pig model to observe changes in the timing of swallowing kinematics with lesion and aspiration. We recorded swallows using high-speed video-fluoroscopic swallow studies (VFSS) and scored them using the Infant Mammalian Penetration and Aspiration Scale (IMPAS). We hypothesized that changes would occur in swallowing kinematics (1) between RLN lesion and control animals, and (2) among safe swallows (IMPAS 1), penetration swallows (IMPAS 3), and aspiration swallows (IMPAS 7). We observed numerous changes in timing following RLN lesion in safe and unsafe swallows, suggesting pervasive changes in the coordination of oropharyngeal function. The timing of LVC, posterior tongue, and hyoid movements differed between pre- and post-lesion in safe swallows. Posterior tongue kinematics differed for post-lesion swallows with penetration. The timing and duration of LVC and posterior tongue movement differed between aspiration swallows pre- and post-lesion. After lesion, safe swallows and swallows with aspiration differed in timing of LVC, laryngeal vestibule opening, and posterior tongue and hyoid movements. The timing of thyrohyoid muscle activity varied with IMPAS, but not lesion. Further study into the pathophysiology of RLN lesion-induced swallowing dysfunction is important to developing novel therapies.
Gross Andrew; Ohlemacher Jocelyn; German Rebecca; Gould Francois
Dysphagia
2018
2018-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00455-017-9832-0" target="_blank" rel="noreferrer noopener">10.1007/s00455-017-9832-0</a>
Maturation of the Coordination Between Respiration and Deglutition with and Without Recurrent Laryngeal Nerve Lesion in an Animal Model.
*Animal model; *Deglutition; *Development; *Infant; *Recurrent laryngeal nerve; *Respiration; *Sensorimotor; Animal; Animal Population Groups; Animals; Biological; Deglutition – Physiology; Deglutition Disorders; Deglutition/*physiology; Disease Models; Humans; Laryngeal Nerves – Injuries; Laryngeal Nerves – Physiology; Larynx – Physiology; Larynx/*physiology; Models; Newborn; Questionnaires; Recurrent Laryngeal Nerve Injuries/*complications; Recurrent Laryngeal Nerve/physiology; Respiration; Swine
The timing of the occurrence of a swallow in a respiratory cycle is critical for safe swallowing, and changes with infant development. Infants with damage to the recurrent laryngeal nerve, which receives sensory information from the larynx and supplies the intrinsic muscles of the larynx, experience a significant incidence of dysphagia. Using our validated infant pig model, we determined the interaction between this nerve damage and the coordination between respiration and swallowing during postnatal development. We recorded 23 infant pigs at two ages (neonatal and older, pre-weaning) feeding on milk with barium using simultaneous high-speed videofluoroscopy and measurements of thoracic movement. With a complete linear model, we tested for changes with maturation, and whether these changes are the same in control and lesioned individuals. We found (1) the timing of swallowing and respiration coordination changes with maturation; (2) no overall effect of RLN lesion on the timing of coordination, but (3) a greater magnitude of maturational change occurs with RLN injury. We also determined that animals with no surgical intervention did not differ from animals that had surgery for marker placement and a sham procedure for nerve lesion. The coordination between respiration and swallowing changes in normal, intact individuals to provide increased airway protection prior to weaning. Further, in animals with an RLN lesion, the maturation process has a larger effect. Finally, these results suggest a high level of brainstem sensorimotor interactions with respect to these two functions.
Ballester Ashley; Gould Francois; Bond Laura; Stricklen Bethany; Ohlemacher Jocelyn; Gross Andrew; DeLozier Katherine R; Buddington Randall; Buddington Karyl; Danos Nicole; German Rebecca
Dysphagia
2018
2018-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00455-018-9881-z" target="_blank" rel="noreferrer noopener">10.1007/s00455-018-9881-z</a>
Increased transperitoneal bacterial translocation in laparoscopic surgery.
*Bacterial Translocation; *Laparoscopy; Animal; Animals; Artificial/*adverse effects/methods; Carbon Dioxide/administration & dosage; Escherichia coli Infections/*microbiology; Escherichia coli/isolation & purification/physiology; Gases; Helium/administration & dosage; Insufflation/adverse effects; Male; Models; Peritonitis/*microbiology; Pneumoperitoneum; Pressure; Rats; Sprague-Dawley
BACKGROUND: The indications for laparoscopic surgery have expanded to include diseases possibly associated with peritonitis such as appendicitis, perforated peptic ulcers, and diverticulitis. The safety of carbon dioxide (CO2) pneumoperitoneum in the presence of peritonitis has not been proved. Our previous investigations demonstrated increased bacteremia associated with CO2 insufflation. In effort to clarify the relative effects of intraabdominal pressure and type of gas, this study was designed to measure bacterial translocation with different gases at different pressures of pneumoperitoneum. METHODS: For this study, 110 rats were given intraperitoneal bacterial innoculations with Escherichia coli and equally divided into five groups of 20 animals each. The study groups included a control group with no pneumoperitoneum administered (n = 30), insufflation at a commonly used pressure of 14 mmHg with helium (n = 20) and CO2 (n = 20), and low insufflation at 3 mmHg with helium (n = 20) and CO2 (n = 20) in an effort to minimize influences related to pressure. Blood cultures were checked at 15-min intervals for the first 45 min, then hourly thereafter for a total of 165 min after peritoneal inoculation with 2 x 10(7) E. coli. RESULTS: There is increased risk of bacterial translocation in comparing groups that underwent pneumoperitoneum with those that did not in the rat peritonitis model. Furthermore, these findings are dependent on the presence or absence of gas, but not necessarily on the type of gas used for insufflation. In the low-pressure groups of both gases (helium and CO2), bacterial translocation was significantly increased, as compared with the control group. Low pressure also was associated with increased bacterial translocation, as compared with high pressure, but beyond 30 min of insufflation, no significant differences were apparent. CONCLUSIONS: The risk of bacterial translocation in the E. coli rat peritonitis model is increased with insufflation using CO2 or helium, and this effect is more significant at lower pressures (3 mmHg) than at higher pressures (14 mmHg). However, no clinically applicable conclusions regarding the relative effects from type of gas or insufflation pressures could be confirmed.
Horattas M C; Haller N; Ricchiuti D
Surgical endoscopy
2003
2003-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00464-001-8289-1" target="_blank" rel="noreferrer noopener">10.1007/s00464-001-8289-1</a>
Activation of heterotrimeric G-proteins independent of a G-protein coupled receptor and the implications for signal processing.
*Signal Transduction; Animals; Biological; G-Protein-Coupled/*metabolism; Heterotrimeric GTP-Binding Proteins/*metabolism; Humans; Models; Receptors
Heterotrimeric G-proteins are key transducers for signal transfer from outside the cell, mediating signals emanating from cell-surface G-protein coupled receptors (GPCR). Many, if not all, subtypes of heterotrimeric G-proteins are also regulated by accessory proteins that influence guanine nucleotide binding, guanosine triphosphate (GTP) hydrolysis, or subunit interactions. One subgroup of such accessory proteins (activators of G-protein signaling; AGS proteins) refer to a functionally defined group of proteins that activate selected G-protein signaring systems in the absence of classical G-protein coupled receptors. AGS and related proteins provide unexpected insights into the regulation of the
Cismowski M J; Lanier S M
Reviews of physiology, biochemistry and pharmacology
2005
1905-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s10254-005-0042-z" target="_blank" rel="noreferrer noopener">10.1007/s10254-005-0042-z</a>
Uncovering the hidden medical curriculum through a pedagogy of discomfort.
*Curriculum; *Decision Making; *Physician-Patient Relations; Adult; Education; Female; Humans; Medical; Models; Psychological; Undergraduate/*methods
What lies beneath the formal or overt curriculum may impair students' professional growth and development, including their ability to foster genuine relationships with patients and others, and may contribute to the inadvertent, often negative attitudes, beliefs, and behaviors expressed by medical students and witnessed by educators within and external to the classroom environment. To understand the impact a hidden medical curriculum has on both students and educators, I look at one particular model often used in medical education–the physician-patient relationship. I show how this therapeutic relationship ought to be understood through a pedagogy of discomfort, a model developed by Megan Boler (Feeling Power; Emotions and Education, 1999), as a way to uncover the hidden curriculum as it engages students in a collective, critical discourse through which their sense of self in relation to others becomes the groundwork for their professional and moral development. Understanding the physician-patient relationship through a pedagogy of discomfort also teachers students how to critically think about the different values and beliefs held by physicians and patients and how to begin to recognize themselves as physicians in relation to their patients and others.
Aultman Julie M
Advances in health sciences education : theory and practice
2005
2005-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s10459-004-4455-2" target="_blank" rel="noreferrer noopener">10.1007/s10459-004-4455-2</a>
Crisis Intervention Team (CIT) programs in rural communities: a focus group study.
Cooperative Behavior; Criminal Law/organization & administration; Crisis Intervention; Crisis Intervention/*organization & administration; Descriptive Statistics; Focus Groups; Human; Humans; Interprofessional Relations; Mental Health Personnel; Mental Health Services/*organization & administration; Models; National Alliance for the Mentally Ill; Organizational; Police; Program Development; Program Evaluation; Psychiatric Emergencies; Qualitative Research; Rural Health; Rural Health Services/*organization & administration
The Crisis Intervention Teams model (CIT) was originally developed as an urban model for police officers responding to calls about persons experiencing a mental illness crisis. Literature suggests that there is reason to believe that there may be unique challenges to adapting this model in rural settings. This study attempts to better understand these unique challenges. Thematic analysis of focus group interviews revealed that there were both external and internal barriers to developing CIT in their respective communities. Some of these barriers were a consequence of working in small communities and working within small police departments. Participants actively overcame these barriers through the realization that CIT was needed in their community, through collaborative efforts across disciplines, and through the involvement of mental health advocacy groups. These results indicate that CIT can be successfully implemented in rural communities.
Skubby David; Bonfine Natalie; Novisky Meghan; Munetz Mark R; Ritter Christian
Community mental health journal
2013
2013-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s10597-012-9517-y" target="_blank" rel="noreferrer noopener">10.1007/s10597-012-9517-y</a>
An Engagement Intervention for Young Adults with Serious Mental Health Conditions.
*Decision Making; *Mental Health Services; *Models; ADULTS – Mental health; Decision Making; DECISION making; FEASIBILITY studies; HEALTH services administration; Human; Humans; INFORMATION processing; MATHEMATICAL models; Mental Disorders – Therapy; Mental Disorders/*therapy; Mental Health; MENTAL health; Mental Health Services; MENTAL health services; MENTAL illness treatment; Models; Qualitative Research; QUALITATIVE research; Qualitative Studies; Theoretical; THEORY; Young Adult
Young adults with serious mental health conditions (SMHCs) often do not engage continuously with mental health services, and there are few engagement interventions designed for them. This qualitative study presents a blueprint for conceptualizing and developing an engagement intervention designed for young adults with SMHCs. The blueprint includes the following activities: (1) establishing a strong theoretical basis, (2) designing an initial manual based on previous research and practice, (3) systematically examining feedback on the manual from stakeholders, and (4) examining the feasibility, acceptability, and implementation demands of the intervention. Interviews, group discussions, and journaling were utilized to collect information from young adult participant-researchers, intervention facilitators (i.e., recovery role models and clinicians), and additional stakeholders (e.g., clinic staff and administrators) (N = 43). Analyses were performed with multiple coders using constant comparative methods. Results revealed critical information to improve the intervention, while also suggesting that the engagement intervention for young adults with SMHCs has promise.
Munson Michelle R; Cole Andrea; Jaccard James; Kranke Derrick; Farkas Kathleen; Frese Fred J 3rd
The journal of behavioral health services & research
2016
2016-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s11414-014-9424-9" target="_blank" rel="noreferrer noopener">10.1007/s11414-014-9424-9</a>
Exploring the Role of YouTube in Disseminating Psychoeducation.
*Models; China – Ethnology; China/ethnology; Communication; Educational; Human; Humans; Mental health; Mental Health – Education; Mental Health/*education; Models; Schizophrenia; Social media; Social Media – Utilization; Social Media/*statistics & numerical data; Social Stigma; Stigma; United States; Video Recording/*trends; Videorecording – Trends; Young Adult
OBJECTIVE: Social media can bridge the gap between health care and ethnic minorities over cultural barriers. This study explores the role of YouTube in delivering schizophrenia education to individuals in the USA who are also fluent in Chinese. METHODS: Three psychoeducational YouTube videos related to schizophrenia were uploaded. Data were collected for a 12-month period, and results were analyzed using descriptive statistics. RESULTS: The videos recorded 4935 views with a total viewing time of 35,614 min. The first-episode psychosis video had the most number of views and shares, and the longest total watch time and average view duration. The targeted age group (\textless 34 years old) comprised about half of the total views and had a 14.4% longer average view duration compared to the overall average. CONCLUSION: YouTube is a useful tool that delivers schizophrenia education to Chinese-speaking individuals in the USA. It may also help alleviate the negative stigma regarding schizophrenia and other mental health issues.
Lam Nikki Hei Tong; Tsiang John Ta-Hsiang; Woo Benjamin K P
Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry
2017
2017-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s40596-017-0835-9" target="_blank" rel="noreferrer noopener">10.1007/s40596-017-0835-9</a>
Synaptic plasticity in the hippocampal slice: functional consequences.
Animals; Calcium Channels/physiology; Hippocampus/*physiology; Long-Term Potentiation/physiology; Models; N-Methyl-D-Aspartate/physiology; Neurological; Neuronal Plasticity/*physiology; Receptors; Synapses/*physiology
There are 3 known forms of synaptic plasticity at CNS synapses: long-term potentiation (LTP) mediated by NMDA receptor activation, LTP mediated by voltage-dependent calcium channel (VDCC) activation, and long-term depression (LTD) mediated by the NMDA receptor. All 3 forms of synaptic plasticity can be observed in hippocampal CAl cells, all are induced by afferent activation, all involve Ca2+ influx, and all activate Ca(2+)-dependent mechanisms. We consider the functional consequences of the presence of 3, sometime opposing, forms of synaptic plasticity at the same synapse. We suggest that the 2 forms of LTP have different consequences for the synapse. We postulate that the co-existence of potentiating and depressing capabilities influences the network processing capabilities of neural networks.
Teyler T J; Cavus I; Coussens C
Journal of neuroscience methods
1995
1995-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0165-0270(94)00188-m" target="_blank" rel="noreferrer noopener">10.1016/0165-0270(94)00188-m</a>
Structure-activity relationships of pentacycloundecylamines at the
Amines/chemical synthesis/chemistry/*pharmacology; Animals; Brain/drug effects; Dizocilpine Maleate/pharmacology; Excitatory Amino Acid Antagonists/*pharmacology; Inbred ICR; Ion Channels; Male; Mice; Models; Molecular; N-Methyl-D-Aspartate/*antagonists & inhibitors; Phencyclidine/analogs & derivatives; Piperidines/pharmacology; Radioligand Assay; Receptors; Structure-Activity Relationship; Synaptosomes/*drug effects; Thiophenes/pharmacology
Prompted by our interest in neuroprotective agents with multiple mechanisms of action, we assessed the structure-activity relationship of a series of pentacycloundecylamine derivatives previously shown to have both L-type calcium channel blocking activity and N-methyl-d-aspartate receptor (NMDAR) antagonistic activity. We utilized a functional assay to measure NMDAR channel block using (45)Ca(2+) influx into synaptoneurosomes. The cage amine
Geldenhuys Werner J; Malan Sarel F; Bloomquist Jeffrey R; Van der Schyf Cornelis J
Bioorganic & medicinal chemistry
2007
2007-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bmc.2006.09.060" target="_blank" rel="noreferrer noopener">10.1016/j.bmc.2006.09.060</a>
3D-QSAR and docking studies on transforming growth factor (TGF)-beta receptor 1 antagonists.
Models; Molecular; Quantitative Structure-Activity Relationship; Receptors; Transforming Growth Factor beta/*antagonists & inhibitors
The transforming growth factor-beta (TGF-beta) is part of a family of cytokines which regulate various signaling pathways such as cell development, growth, and tissue injury. Although several studies have been published describing the synthesis of small compounds which inhibit the receptor of TGF-beta, especially the subtype 1 receptor (TGBR1) kinase, no 3D-quantitiative structure-activity relationship study has been published. Here we describe the development of a comparative molecular field analysis (CoMFA) model which yielded a partial least squares statistical cross validated r(2) of \textgreater0.3. CoMFA maps agree with docking studies and pharmacophore analysis that hydrogen bonding is important for binding to ALK-5. These studies could enable the medicinal chemist to develop novel inhibitors which can be used in glaucoma filtration surgery.
Geldenhuys Werner J; Nakamura Hiroshi
Bioorganic & medicinal chemistry letters
2010
2010-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bmcl.2010.01.140" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2010.01.140</a>
3-D-QSAR and docking studies on the neuronal choline transporter.
Binding Sites; Blood-Brain Barrier/metabolism; Computer Simulation; Membrane Transport Proteins/*chemistry/metabolism; Models; Molecular; Neurons/*metabolism; Quantitative Structure-Activity Relationship; Quaternary Ammonium Compounds/chemistry
The high affinity neuronal choline transporter (CHT1) is responsible for the uptake of choline into the pre-synaptic terminal of cholinergic neurons. Considering our past experience with modeling the blood-brain barrier choline transporter (BBBCHT) as drug delivery vector to the CNS, we investigated the
Geldenhuys Werner J; Allen David D; Lockman Paul R
Bioorganic & medicinal chemistry letters
2010
2010-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bmcl.2010.06.090" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2010.06.090</a>
Identification of novel monoamine oxidase B inhibitors by structure-based virtual screening.
Models; Molecular; Monoamine Oxidase Inhibitors/chemistry/*pharmacology; Monoamine Oxidase/*drug effects; Structure-Activity Relationship
Parkinson's disease is a severe debilitating neurodegenerative disorder. Recently, it was shown that the peroxisome proliferating-activator receptor-gamma agonist pioglitazone protected mice from
Geldenhuys Werner J; Darvesh Altaf S; Funk Max O; Van der Schyf Cornelis J; Carroll Richard T
Bioorganic & medicinal chemistry letters
2010
2010-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bmcl.2010.06.128" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2010.06.128</a>
Structure-activity relationship and docking studies of thiazolidinedione-type compounds with monoamine oxidase B.
Animals; Humans; Inbred C57BL; Male; Mice; Models; Molecular; Molecular Structure; Monoamine Oxidase Inhibitors/chemical synthesis/chemistry/*pharmacology; Monoamine Oxidase/*metabolism; Stereoisomerism; Structure-Activity Relationship; Thiazolidinediones/chemical synthesis/chemistry/*pharmacology
The neuroprotective activity of pioglitazone and rosiglitazone in the MPTP parkinsonian mouse prompted us to evaluate a set of thiazolidinedione (TZD) type compounds for monoamine oxidase A and B inhibition activity. These compounds were able to inhibit MAO-B over several log units of magnitude (82 nM to 600 muM). Initial structure-activity relationship studies identified key areas to modify the aromatic substituted TZD compounds. Primarily, substitutions on the aromatic group and the TZD nitrogen were key areas where activity was enhanced within this group of compounds.
Carroll Richard T; Dluzen Dean E; Stinnett Hilary; Awale Prabha S; Funk Max O; Geldenhuys Werner J
Bioorganic & medicinal chemistry letters
2011
2011-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bmcl.2011.06.060" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2011.06.060</a>
3D-Quantitative structure-activity relationship and docking studies of the tachykinin NK3 receptor.
*Quantitative Structure-Activity Relationship; Binding Sites; Computer Simulation; Drug Design; Humans; Ligands; Models; Molecular; Neurokinin-3/*chemistry/metabolism; Protein Structure; Quinolines/chemistry; Receptors; Tertiary
The tachykinin NK(3) receptor (NK(3)R) is a novel drug target for schizophrenia and drug abuse. Since few non-peptide antagonists of this G protein-coupled receptor are available, we have initiated this study to gain a better understanding of the structure-activity relationships of NK(3) antagonist compounds. We developed a 3D comparative molecular similarity index analysis (CoMSIA) model that gave cross-validated PLS values with q(2) \textgreater0.5 which were validated using a test set. We also describe the development of a homology model of the NK(3)R. The model was then used to develop a pharmacophore for docked ligands. This pharmacophore showed two aromatic, two hydrogen donor and one acceptor/aromatic points. These data will be useful for future structure-based drug discovery of ligands for the NK(3)R.
Geldenhuys Werner J; Simmons Mark A
Bioorganic & medicinal chemistry letters
2011
2011-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bmcl.2011.10.014" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2011.10.014</a>
A scaffold hopping approach to identify novel monoamine oxidase B inhibitors.
*Monoamine Oxidase/chemistry/metabolism; Benzofurans/chemistry/pharmacology; Enzyme Activation/drug effects; Flavonoids/chemistry/pharmacology; Humans; Inhibitory Concentration 50; Models; Molecular; Molecular Structure; Monoamine Oxidase Inhibitors/*chemistry/*pharmacology; Protein Binding/drug effects; Small Molecule Libraries; Structure-Activity Relationship
Monoamine oxidase B (MAO-B) inhibitors are used to treat Parkinson's disease. In this study, we searched for novel MAO-B inhibitors using a scaffold hopping approach based on our experience with the thiazolidinedione (TZD) class of compounds as MAO-B inhibitors. Several novel compounds were identified, with potencies in the low nanomolar and low micromolar range. We also found that derivatives of the natural product sulfuretin are potent MAO-A and MAO-B inhibitors.
Geldenhuys Werner J; Funk Max O; Van der Schyf Cornelis J; Carroll Richard T
Bioorganic & medicinal chemistry letters
2012
2012-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bmcl.2011.12.056" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2011.12.056</a>
Vanadium in the detection, prevention and treatment of cancer: the in vivo evidence.
10-Dimethyl-1; 2-benzanthracene; 9; Animal; Animals; Biological; Breast Neoplasms – Chemically Induced; Breast Neoplasms – Diagnosis; Breast Neoplasms – Drug Therapy; Cell Division – Drug Effects; Cell Division/drug effects; Disease Models; Experimental/chemically induced/diagnosis/drug therapy; Experimental/drug therapy/pathology; Female; Glioblastoma/drug therapy; Glioma – Drug Therapy; Heterologous; Humans; Hydrocarbons; Male; Mammary Neoplasms; Metals; Metals – Diagnostic Use; Metals – Therapeutic Use; Models; Neoplasm Staging; Neoplasm Transplantation; Neoplasms; Neoplasms – Diagnosis; Neoplasms – Drug Therapy; Neoplasms – Pathology; Neoplasms – Prevention and Control; Neoplasms/*diagnosis/drug therapy/prevention & control; Organometallic Compounds – Therapeutic Use; Organometallic Compounds/therapeutic use; Rats; Trace Elements – Diagnostic Use; Trace Elements – Therapeutic Use; Trace Elements/therapeutic use; Transplantation; Vanadium Compounds; Vanadium Compounds – Therapeutic Use; Vanadium Compounds/therapeutic use/toxicity; Vanadium/*therapeutic use/toxicity; Xenografts
Vanadium, a dietary micronutrient, is yet to be established as an essential part of the human diet. Over the past century, several biological effects of vanadium, such as insulin-mimetic action as well as amelioration of hyperlipidemia and hypertension, have been discovered. This transition element is known to influence a battery of enzymatic systems, namely phosphatases, ATPases, peroxidases, ribonucleases, protein kinases and oxidoreductases. Multiple biochemical and molecular actions of vanadium have been implicated in its inhibitory effects on various tumor cells of human origin. Successful in vitro studies over the past few decades have advanced the anticancer research on vanadium into the preclinical stage. Vanadium in several animal cancer models provides protection against all stages of carcinogenesis–initiation, promotion, and progression. This review focuses on the current advances in cancer prevention and treatment as well as early detection by vanadium compounds in preclinical animal models while pointing to possible mechanisms of such diverse beneficial effects. Clinical pharmacokinetic and potential toxicity studies on vanadium are also highlighted in this review. Supporting and challenging evidence as well as future directions of vanadium research exploring the possibility of using this dietary agent for detection, prevention and treatment of human cancers are critically discussed.
Bishayee Anupam; Waghray Abhijeet; Patel Mehool A; Chatterjee Malay
Cancer letters
2010
2010-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.canlet.2010.01.030" target="_blank" rel="noreferrer noopener">10.1016/j.canlet.2010.01.030</a>
The role of type I interferons and other cytokines in dermatomyositis.
Autoantibodies/immunology; Biological; Cytokines; Dermatomyositis; Dermatomyositis/*immunology/physiopathology/therapy; Humans; Inflammatory myopathy; Interferon Type I/*metabolism; Models; Pathogenesis; Signal Transduction; Type I interferons
Much work has been done to unveil the mechanisms behind the pathogenesis of dermatomyositis (DM) - mainly those involving certain pathogenic cytokines, termed "pathokines" as the principal cytokines involved. Recently, it has become clear that a group of cytokines known as type I interferons (IFN-Is) play a significant role in the development of DM. We review the literature published between 1946 and 2014 using an Ovid Medline database search to provide an update on the role of IFN-Is and other cytokines in the pathogenesis of DM. We provide information about the genes and proteins induced by IFN-Is and potential mechanisms by which these downstream products relate to clinical disease activity. We also explore findings of other autoimmune phenomena that may contribute to disease onset and activity including T-helper 17 (Th17) cells and associated interleukins, as well as autoantibodies. Finally, we provide a brief update on current treatment options for DM as well as some new immunomodulatory treatment modalities in development.
Arshanapalli Ashish; Shah Mihir; Veerula Vindhya; Somani Ally-Khan
Cytokine
2015
2015-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.cyto.2014.11.026" target="_blank" rel="noreferrer noopener">10.1016/j.cyto.2014.11.026</a>
The role of the N-terminal and mid-region residues of substance P in regulating functional selectivity at the tachykinin NK1 receptor.
Amino Acid Sequence; Animals; Binding; Calcium Signaling/physiology; CHO Cells; Competitive/drug effects; Cricetinae; Cricetulus; Dose-Response Relationship; Drug; Iodine Radioisotopes; Ligands; Models; Molecular; Molecular Sequence Data; Neurokinin-1/chemistry/drug effects/*metabolism; Rats; Receptors; Substance P/chemistry/drug effects/*physiology
Previous studies have shown that tachykinin peptide ligands of the tachykinin NK1 receptor exhibit functional selectivity with respect to signal activation and desensitization. The differences are most dramatic between the naturally occurring peptides substance P (RPKPQQFFGLM-NH2) and ranatachykinin C (HNPASFIGLM-NH2). To understand the structural features of the peptides that underlie these differences, four peptide analogs have been designed and tested. The analogs were designed to assess the major structural differences between substance P and ranatachykinin C, including the role of the N-terminal Arg and the substitution of the mid-region Glns with Ala and Ser (Q5 replaced with A and/or Q6 replaced with S). Receptor binding, receptor activation of intracellular calcium fluxes, and receptor desensitization of the rat tachykinin NK1 receptor were quantified for each ligand. All of the peptides bound to the rat tachykinin NK1 receptor with high affinity, produced robust calcium signal activation, and led to agonist-induced receptor desensitization. It was found that deletion of the N-terminal Arg of substance P or replacement of either or both Q5 and Q6 altered the functional selectivity of substance P based on the relationship of receptor binding to receptor activation and activation to desensitization. When considered in light of our previously published nuclear magnetic resonance structure data, the data presented herein suggest that the one, five and six positions of the substance P backbone are key structural residues that govern the relative degree of tachykinin peptide-mediated receptor signaling and desensitization.
Perrine Shane A; Beard Debbie J; Young John K; Simmons Mark A
European journal of pharmacology
2008
2008-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.ejphar.2008.06.097" target="_blank" rel="noreferrer noopener">10.1016/j.ejphar.2008.06.097</a>
Protein thiyl radical mediates S-glutathionylation of complex I.
*Oxidative Stress; Amino Acid Motifs; Amino Acid Sequence; Animals; Binding Sites; Cattle; Cell Line; Cyclic N-Oxides/chemistry/pharmacology; Cysteine/chemistry/*metabolism; Electron Transport Complex I/chemistry/*metabolism; Free Radical Scavengers/chemistry/pharmacology; Free Radicals/chemistry/*metabolism; Glutathione/chemistry/*metabolism; Heart/enzymology/metabolism; Mice; Mitochondria; Models; Molecular; Molecular Sequence Data; Muscle Cells/drug effects/metabolism; Onium Compounds/pharmacology; Peptide Fragments/chemistry; Peptide Mapping; Protein; Rats; Rotenone/pharmacology; Structural Homology; Superoxides/metabolism
Complex I is a critical site of O(2)(*-) production and the major host of reactive protein thiols in mitochondria. In response to oxidative stress, complex I protein thiols at the 51- and 75-kDa subunits are reversibly
Kang Patrick T; Zhang Liwen; Chen Chwen-Lih; Chen Jingfeng; Green Kari B; Chen Yeong-Renn
Free radical biology & medicine
2012
2012-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.freeradbiomed.2012.05.025" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2012.05.025</a>
Prepulse inhibition of the acoustic startle reflex vs. auditory brainstem response for hearing assessment.
*Audiometric functions; *Hearing loss; *Mouse; *Permanent threshold shift; *Sound exposure; *Temporary threshold shift; Acoustic Stimulation/*methods; Animal; Animals; Audiometry; Auditory; Auditory Threshold/*physiology; Brain Stem/*physiology; Evoked Potentials; Hearing; Inbred CBA; Male; Mice; Models; Noise; Prepulse Inhibition/*physiology; Pure-Tone/*methods; Reflex; Startle/*physiology
The high prevalence of noise-induced and age-related hearing loss in the general population has warranted the use of animal models to study the etiology of these pathologies. Quick and accurate auditory threshold determination is a prerequisite for experimental manipulations targeting hearing loss in animal models. The standard auditory brainstem response (ABR) measurement is fairly quick and translational across species, but is limited by the need for anesthesia and a lack of perceptual assessment. The goal of this study was to develop a new method of hearing assessment utilizing prepulse inhibition (PPI) of the acoustic startle reflex, a commonly used tool that measures detection thresholds in awake animals, and can be performed on multiple animals simultaneously. We found that in control mice PPI audiometric functions are similar to both ABR and traditional operant conditioning audiograms. The hearing thresholds assessed with PPI audiometry in sound exposed mice were also similar to those detected by ABR thresholds one day after exposure. However, three months after exposure PPI threshold shifts were still evident at and near the frequency of exposure whereas ABR thresholds recovered to the pre-exposed level. In contrast, PPI audiometry and ABR wave one amplitudes detected similar losses. PPI audiometry provides a high throughput automated behavioral screening tool of hearing in awake animals. Overall, PPI audiometry and ABR assessments of the auditory system are robust techniques with distinct advantages and limitations, which when combined, can provide ample information about the functionality of the auditory system.
Longenecker R J; Alghamdi F; Rosen M J; Galazyuk A V
Hearing research
2016
2016-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.heares.2016.06.006" target="_blank" rel="noreferrer noopener">10.1016/j.heares.2016.06.006</a>
Police officer perceptions of the impact of Crisis Intervention Team (CIT) programs.
*Attitude; *Crisis Intervention; *Mentally Ill Persons; *Police; *Professional Competence; Adult; Attitude; Crisis Intervention; Crisis intervention team; Familiarity with mental illness; Female; Human; Humans; Law Enforcement; Male; Management; Middle Age; Middle Aged; Models; Officer confidence; Organizational; Police; Professional Competence; Psychiatric Patients; Social Control
The Crisis Intervention Team (CIT) program is an approach for law enforcement officers to safely response to individuals who are experiencing a mental health crisis. Research must identify the components of CIT that are instrumental to the overall effectiveness of the program. For instance, recent studies report that CIT may have a transformative effect on officers' attitudes by increasing exposure to and familiarity with mental illness. This study explores this possibility further by examining 57 CIT officers' experiences with mental illness and attitudes about CIT. Specifically, we assessed how personal and professional exposure to mental illness associates with officers' perceptions about CIT generally, as well as with opinions about the officers' confidence in their abilities and the perceived effectiveness of the police department in responding to individuals in mental health crisis. Our findings indicate that CIT is rated very positively by officers. We found that officers' attitudes about the impact of CIT on improving overall safety, accessibility of services, officer skills and techniques, and the preparedness of officers to handle calls involving persons with mental illness are positively associated with officers' confidence in their abilities or with officers' perceptions of overall departmental effectiveness. There is further evidence that personal contact with individuals with mental illness affects the relationship between attitudes that CIT impacts overall safety and perceived departmental effectiveness. The results of this exploratory study underscore the importance of CIT officers' perceptions of key elements of CIT and the role of exposure to mental illness in examining program effectiveness.
Bonfine Natalie; Ritter Christian; Munetz Mark R
International journal of law and psychiatry
2014
2014-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.ijlp.2014.02.004" target="_blank" rel="noreferrer noopener">10.1016/j.ijlp.2014.02.004</a>
Hematologic counts as predictors of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.
*Blood Cell Count; *Inflammation; *Intracranial vasospasm; *Subarachnoid hemorrhage; *Transcranial Doppler sonography; Anemia/blood/diagnosis; Brain Ischemia/blood/complications/*diagnosis/epidemiology; Cerebrovascular Circulation/physiology; Critical Care; Databases; Doppler; Factual; Female; Humans; Leukocytosis/blood/diagnosis; Logistic Models; Male; Middle Aged; Models; Odds Ratio; Ohio/epidemiology; Sensitivity and Specificity; Subarachnoid Hemorrhage/*complications/diagnostic imaging; Theoretical; Transcranial; Ultrasonography
PURPOSE: Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality, but currently no single clinical method or ancillary test can reliably predict which subset of patients will develop delayed cerebral ischemia (DCI). The aim of this study was to find hematologic derangements and clinical factors present during the first 7 days after bleeding that could help identify patients at risk for development of DCI. MATERIALS AND METHODS: Databank analysis of patients with SAH admitted between 2010 and 2012 in a single center. Data from demographics, imaging, laboratory, and clinical factors were collected. Statistical testing was conducted to test for association to the outcome, and multivariate logistic regression was used to design a predictive model. RESULTS: Of 55 patients, 14 developed DCI (25%). Anemia and leukocytosis on the third day after bleeding were significantly correlated with the outcome (for anemia: P\textless.032; confidence interval, 1.12-15.16; odds ratio, 4.12; for leukocytosis: P\textless.046; confidence interval, 1.03-26.13; odds ratio, 5.18). Anemia and leukocytosis were still statistically significant after adjustment for age, sex, modified Fisher scale, and Hunt-Hess scale. CONCLUSION: The presence of leukocytosis and anemia during the third day after SAH was statistically correlated with the occurrence of DCI.
Da Silva Ivan Rocha Ferreira; Gomes Joao Antonio; Wachsman Ari; de Freitas Gabriel Rodriguez; Provencio Jose Javier
Journal of critical care
2017
2017-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.jcrc.2016.09.011" target="_blank" rel="noreferrer noopener">10.1016/j.jcrc.2016.09.011</a>
Ontogeny of limb force distribution in squirrel monkeys (Saimiri boliviensis): insights into the mechanical bases of primate hind limb dominance.
*Locomotion; Age Factors; Animals; Biological; Biomechanical Phenomena; Female; Leg/anatomy & histology/*growth & development/*physiology; Models; Saimiri/anatomy & histology/*growth & development/*physiology; Videotape Recording; Weight-Bearing
The distribution of peak vertical forces between the forelimbs and the hind limbs is one of the key traits distinguishing primate quadrupedal locomotion from that of other mammals. Whereas most mammals generate greater peak vertical forelimb forces, primates generate greater peak vertical hind limb forces. At the ultimate level, hind limb dominance in limb force distribution is typically interpreted as an adaptation to facilitate fine-branch arboreality. However, the proximate biomechanical bases for primate limb force distribution remain controversial. Three models have been previously proposed. The Center of Mass (COM) Position model attributes primates' unique mode of limb loading to differences in the position of the whole-body COM relative to the hands and feet. The Active Weight Shift model asserts that primates actively redistribute body weight to their hind limbs by pitching the trunk up via the activation of hind limb retractor muscles. Finally, the Limb Compliance model argues that primates selectively mitigate forelimb forces by maintaining a compliant forelimb and a flat shoulder trajectory. Here, a detailed dataset of ontogenetic changes in morphology and locomotor mechanics in Bolivian squirrel monkeys (Saimiri boliviensis) was employed as a model system to evaluate each of these proposed models in turn. Over the first 10 months of life, squirrel monkeys transitioned from forelimb dominant infants to hind limb dominant juveniles, a change that was precipitated by decreases in peak vertical forelimb forces and increases in peak vertical hind limb forces. Results provided some support for all three of the models, although the COM Position and Active Weight Shift models were most strongly supported by the data. Overall, this study suggests that primates may use a variety of biomechanical strategies to achieve hind limb dominance in limb force distribution.
Young Jesse W
Journal of human evolution
2012
2012-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.jhevol.2012.01.003" target="_blank" rel="noreferrer noopener">10.1016/j.jhevol.2012.01.003</a>
Professional judgments about advance care planning with community-dwelling consumers.
*Attitude of Health Personnel; *Decision Making; *Health Care Surveys; Advance Care Planning; Advance Care Planning/organization & administration/*statistics & numerical data; Attitude of Health Personnel; Consumer Behavior/*statistics & numerical data; Consumer Satisfaction – Statistics and Numerical Data; Decision Making; Human; Humans; Management; Midwestern United States; Models; Organizational; Patient Satisfaction – Statistics and Numerical Data; Patient Satisfaction/*statistics & numerical data; Population Surveillance; Questionnaires; Randomized Controlled Trials; Surveys; Surveys and Questionnaires
CONTEXT: There is limited research on how community-based long-term care (CBLTC) providers' personal characteristics and attitudes affect their decisions to initiate advance care planning (ACP) conversations with consumers. OBJECTIVES: To examine judgments by CBLTC providers as to whether a consumer was in need of ACP and to compare the relative influence of situational features of the consumer with the influence of personal characteristics of the CBLTC provider. METHODS: Factorial surveys with vignettes with randomly assigned situational features of a hypothetical consumer were obtained from 182 CBLTC providers at three Area Agencies on Aging located in the Midwestern U.S. Measures included the consumer's situational features, such as demographics, diagnosis, pain level, level of functioning, and caregiver involvement. Personal characteristics of the CBLTC provider included demographics, discipline, past experience with ACP, and attitudes toward ACP. RESULTS: Hierarchical linear models indicated that most variability in ACP decisions was the result of differences among CBLTC providers (64%) rather than consumers' situational features. Positive decisions to discuss ACP were associated with consumers who needed assistance with legal issues and had a cancer diagnosis; these variables explained 8% of the vignette level variance. Significant personal characteristics of the CBLTC provider included a nursing background, less direct contact with consumers, past experience with ACP, and positive attitudes toward ACP; these variables explained 41% of the person-level variance. CONCLUSION: This study shows the lack of normative consensus about ACP and highlights the need for consistent educational programs regarding the role of the CBLTC provider in the ACP process.
Baughman Kristin R; Ludwick Ruth E; Merolla David M; Palmisano Barbara; Hazelett Susan; Winchell Janice; Hewit Michael
Journal of pain and symptom management
2012
2012-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.jpainsymman.2011.03.023" target="_blank" rel="noreferrer noopener">10.1016/j.jpainsymman.2011.03.023</a>
Neural processing of target distance by echolocating bats: functional roles of the auditory midbrain.
Animals; Auditory Cortex/physiology; Auditory Pathways/*physiology; Auditory Perception/*physiology; Brain Mapping/psychology; Chiroptera/*physiology; Echolocation/*physiology; Inferior Colliculi/*physiology; Models; Neurological; Neurons/physiology
Using their biological sonar, bats estimate distance to avoid obstacles and capture moving prey. The primary distance cue is the delay between the bat's emitted echolocation pulse and the return of an echo. The mustached bat's auditory midbrain (inferior colliculus, IC) is crucial to the analysis of pulse-echo delay. IC neurons are selective for certain delays between frequency modulated (FM) elements of the pulse and echo. One role of the IC is to create these "delay-tuned", "FM-FM" response properties through a series of spectro-temporal integrative interactions. A second major role of the midbrain is to project target distance information to many parts of the brain. Pathways through auditory thalamus undergo radical reorganization to create highly ordered maps of pulse-echo delay in auditory cortex, likely contributing to perceptual features of target distance analysis. FM-FM neurons in IC also project strongly to pre-motor centers including the pretectum and the pontine nuclei. These pathways may contribute to rapid adjustments in flight, body position, and sonar vocalizations that occur as a bat closes in on a target.
Wenstrup Jeffrey J; Portfors Christine V
Neuroscience and biobehavioral reviews
2011
2011-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neubiorev.2010.12.015" target="_blank" rel="noreferrer noopener">10.1016/j.neubiorev.2010.12.015</a>
Non-receptor activators of heterotrimeric G-protein signaling (AGS proteins).
*Signal Transduction; Animals; Biological; G-Protein-Coupled/*metabolism; Heterotrimeric GTP-Binding Proteins/*metabolism; Humans; Models; Receptors
G-protein coupled receptor (GPCR) signaling represents one of the most conserved and ubiquitous means in mammalian cells for transferring information across the plasma membrane to the intracellular environment. Heterotrimeric G-protein subunits play key roles in transducing these signals, and intracellular regulators influencing the activation state and interaction of these subunits regulate the extent and duration of GPCR signaling. One class of intracellular regulator, the non-receptor activators of G-protein signaling (or AGS proteins), are the major focus of this review. AGS proteins provide a basis for understanding the function of heterotrimeric G-proteins in both GPCR-driven and GPCR independent cellular signaling pathways.
Cismowski Mary J
Seminars in cell & developmental biology
2006
2006-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.semcdb.2006.03.003" target="_blank" rel="noreferrer noopener">10.1016/j.semcdb.2006.03.003</a>
Non-fibrillar collagens: key mediators of post-infarction cardiac remodeling?
Animals; Biological; Humans; Matrix Metalloproteinases/metabolism; Models; Myocardial Infarction/*metabolism/physiopathology; Myocardium/metabolism/pathology; Non-Fibrillar Collagens/*metabolism; Wound Healing/physiology
Cardiac remodeling is accelerated during pathological conditions and several anabolic and catabolic regulators work in concert to repair the myocardium and maintain its functionality. The fibroblasts play a major role in this process via collagen deposition as well as supplying the degradative matrix metalloproteinases. During the more acute responses to a myocardial infarction (MI) the heart relies on a more aggressive wound healing sequence that includes the myofibroblasts, specialized secretory cells necessary for infarct scar formation and thus, rescue of the myocardium. The activated fibroblasts and myofibroblasts deposit large amounts of fibrillar collagen during the post-MI wound healing phase, type I and III collagen are the most abundant collagens in the heart and they maintain the structural integrity under normal and disease states. While collagen I and III have been the traditional focus of the myocardial matrix, recent studies have suggested that the non-fibrillar collagens (types IV and VI) are also deposited during pathological wound healing and may play key roles in myofibroblast differentiation and organization of the fibrillar collagen network. This review highlights the potential roles of the non-fibrillar collagens and how they work in concert with the fibrillar collagens in mediating myocardial remodeling.
Shamhart Patricia E; Meszaros J Gary
Journal of molecular and cellular cardiology
2010
2010-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.yjmcc.2009.06.017" target="_blank" rel="noreferrer noopener">10.1016/j.yjmcc.2009.06.017</a>
Sperry's concept of mind as an emergent property of brain function and its implications for the future of humankind.
*Forecasting; *Humanism; *Psychophysiology; Biological; Brain/physiology; Conscience; Humans; Models; Psychology/trends
Sperry's proposal that subjective experience plays a major role in brain function and in the emergence of mind, consciousness and human values represent a challenge to behaviorism as the dominant force in psychology. Mind is viewed as an emergent property of the brain, generated from and dependent upon neural activity, but nonetheless separate from it. Macrodeterministic factors result in the evolution of human values, which represent a critical key to world change. Two major conferences resulted from Sperry's challenge to the scientific community. The Trieste Conference led to a 'Declaration of Human Responsibilities', presently under consideration by the United Nations as a corollary to the 'Declaration of Human Rights'. The Japan Conference inspired work toward a Network University of the Green World, in which computer networking will support international communication in areas of environmental concern.
Voneida T J
Neuropsychologia
1998
1998-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0028-3932(98)00061-x" target="_blank" rel="noreferrer noopener">10.1016/s0028-3932(98)00061-x</a>