Growth of primary motor neurons on horizontally aligned carbon nanotube thin films and striped patterns

NASA Astrophysics Data System (ADS)

Roberts, Megan J.; Leach, Michelle K.; Bedewy, Mostafa; Meshot, Eric R.; Copic, Davor; Corey, Joseph M.; Hart, A. John

2014-06-01

Objective. Carbon nanotubes (CNTs) are attractive for use in peripheral nerve interfaces because of their unique combination of strength, flexibility, electrical conductivity and nanoscale surface texture. Here we investigated the growth of motor neurons on thin films of horizontally aligned CNTs (HACNTs). Approach. We cultured primary embryonic rat motor neurons on HACNTs and performed statistical analysis of the length and orientation of neurites. We next presented motor neurons with substrates of alternating stripes of HACNTs and SiO2. Main results. The neurons survived on HACNT substrates for up to eight days, which was the full duration of our experiments. Statistical analysis of the length and orientation of neurites indicated that the longest neurites on HACNTs tended to align with the CNT direction, although the average neurite length was similar between HACNTs and glass control substrates. We observed that when motor neurons were presented with alternating stripes of HACNTs and SiO2, the proportion of neurons on HACNTs increases over time, suggesting that neurons selectively migrate toward and adhere to the HACNT surface. Significance. The behavior of motor neurons on CNTs has not been previously investigated, and we show that aligned CNTs could provide a viable interface material to motor neurons. Combined with emerging techniques to build complex hierarchical structures of CNTs, our results suggest that organised CNTs could be incorporated into nerve grafts that use physical and electrical cues to guide regenerating axons.

Certain aspects of normal and abnormal motility of sphincter of Oddi.

PubMed

Coelho, J C; Moody, F G

1987-01-01

Applications of electromyographic and endoscopic manometric techniques in experimental and clinical studies have enhanced our knowledge of the normal physiology and motility disturbances of the sphincter of Oddi. The sphincter of Oddi has an active role in coordinating the time and rate of secretion of biliopancreatic juice into the duodenum. In the opossum, the sphincter of Oddi exhibits spontaneous contractions that migrate distally along the sphincter and expels its contents into the duodenum. Although the motor activity of the sphincter of Oddi is independent from that of the duodenum, there is a correlation between the frequency of bursts of spike potentials in the sphincter of Oddi and the migrating motor complex phases in the duodenum. Abnormal motility of the sphincter of Oddi has been reported during endoscopic manometric evaluation of patients with choledocholithiasis and sphincter of Oddi dyskinesia. Patients with common bile duct stones have an increase in the frequency of retrograde propagation of phasic waves. Elevation of basal pressure as well as an increase in the frequency and amplitude of sphincter of Oddi phasic waves and the common bile duct-duodenum gradient pressure may occur in patients with sphincter of Oddi dyskinesia. Endoscopic manometric studies of the sphincter of Oddi may become an important method to diagnose sphincter of Oddi dyskinesia.

Semaphorin 6A knockout mice display abnormalities across ethologically-based topographies of exploration and in motor learning.

PubMed

Håkansson, Kerstin; Runker, Annette E; O'Sullivan, Gerard J; Mitchell, Kevin J; Waddington, John L; O'Tuathaigh, Colm M P

2017-02-22

Semaphorins are secreted or membrane-bound proteins implicated in neurodevelopmental processes of axon guidance and cell migration. Exploratory behaviour and motor learning was examined ethologically in Semaphorin 6A (Sema6A) mutant mice. The ethogram of initial exploration in Sema6A knockout mice was characterised by increased rearing to wall with decreased sifting; over subsequent habituation, locomotion, sniffing and rearing to wall were increased, with reduced habituation of rearing seated. Rotarod analysis indicated delayed motor learning in Sema6A heterozygous mutants. Disruption to the axonal guidance and cell migration processes regulated by Sema6A is associated with topographically specific disruption to fundamental aspects of behaviour, namely the ethogram of initial exploration and subsequent habituation to the environment, and motor learning. Copyright © 2017 Elsevier B.V. All rights reserved.

Interaction between p68 RNA helicase and Ca2+-calmodulin promotes cell migration and metastasis

PubMed Central

Wang, Haizhen; Gao, Xueliang; Yang, Jenny J.; Liu, Zhi-Ren

2012-01-01

Summary p68 RNA helicase is a prototypical RNA helicase. Here we present evidence to show that, by interacting with Ca-calmodulin (CaM), p68 plays a role in cancer metastasis and cell migration. A peptide fragment that spans the IQ motif of p68 strongly inhibits cancer metastasis in two different animal models. The peptide interrupts p68 and CaM interaction and inhibits cell migration. Our results demonstrate that the p68-CaM interaction is essential for the formation of lamellipodia and filopodia in migrating cells. p68 interacts with microtubules in the presence of CaM. Our experiments show that interaction with microtubules stimulates p68 ATPase activity. Further, microtubule gliding assays demonstrate that p68, in the presence of CaM, can function as a microtubule motor. This motor activity may allow p68 to transport CaM to the leading edge of migrating cells. PMID:23322042

APC binds the Miro/Milton motor complex to stimulate transport of mitochondria to the plasma membrane.

PubMed

Mills, Kate M; Brocardo, Mariana G; Henderson, Beric R

2016-02-01

Mutations in adenomatous polyposis coli (APC) disrupt regulation of Wnt signaling, mitosis, and the cytoskeleton. We describe a new role for APC in the transport of mitochondria. Silencing of wild-type APC by small interfering RNA caused mitochondria to redistribute from the cell periphery to the perinuclear region. We identified novel APC interactions with the mitochondrial kinesin-motor complex Miro/Milton that were mediated by the APC C-terminus. Truncating mutations in APC abolished its ability to bind Miro/Milton and reduced formation of the Miro/Milton complex, correlating with disrupted mitochondrial distribution in colorectal cancer cells that could be recovered by reconstitution of wild-type APC. Using proximity ligation assays, we identified endogenous APC-Miro/Milton complexes at mitochondria, and live-cell imaging showed that loss of APC slowed the frequency of anterograde mitochondrial transport to the membrane. We propose that APC helps drive mitochondria to the membrane to supply energy for cellular processes such as directed cell migration, a process disrupted by cancer mutations. © 2016 Mills et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects.

PubMed

Willemsen, Marjolein H; Vissers, Lisenka E L; Willemsen, Michèl A A P; van Bon, Bregje W M; Kroes, Thessa; de Ligt, Joep; de Vries, Bert B; Schoots, Jeroen; Lugtenberg, Dorien; Hamel, Ben C J; van Bokhoven, Hans; Brunner, Han G; Veltman, Joris A; Kleefstra, Tjitske

2012-03-01

DYNC1H1 encodes the heavy chain protein of the cytoplasmic dynein 1 motor protein complex that plays a key role in retrograde axonal transport in neurons. Furthermore, it interacts with the LIS1 gene of which haploinsufficiency causes a severe neuronal migration disorder in humans, known as classical lissencephaly or Miller-Dieker syndrome. To describe the clinical spectrum and molecular characteristics of DYNC1H1 mutations. A family based exome sequencing approach was used to identify de novo mutations in patients with severe intellectual disability. In this report the identification of two de novo missense mutations in DYNC1H1 (p.Glu1518Lys and p.His3822Pro) in two patients with severe intellectual disability and variable neuronal migration defects is described. Since an autosomal dominant mutation in DYNC1H1 was previously identified in a family with the axonal (type 2) form of Charcot- Marie-Tooth (CMT2) disease and mutations in Dync1h1 in mice also cause impaired neuronal migration in addition to neuropathy, these data together suggest that mutations in DYNC1H1 can lead to a broad phenotypic spectrum and confirm the importance of DYNC1H1 in both central and peripheral neuronal functions.

Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control.

PubMed

Kullander, K; Croll, S D; Zimmer, M; Pan, L; McClain, J; Hughes, V; Zabski, S; DeChiara, T M; Klein, R; Yancopoulos, G D; Gale, N W

2001-04-01

Growing axons follow highly stereotypical pathways, guided by a variety of attractive and repulsive cues, before establishing specific connections with distant targets. A particularly well-known example that illustrates the complexity of axonal migration pathways involves the axonal projections of motor neurons located in the motor cortex. These projections take a complex route during which they first cross the midline, then form the corticospinal tract, and ultimately connect with motor neurons in the contralateral side of the spinal cord. These obligatory contralateral connections account for why one side of the brain controls movement on the opposing side of the body. The netrins and slits provide well-known midline signals that regulate axonal crossings at the midline. Herein we report that a member of the ephrin family, ephrin-B3, also plays a key role at the midline to regulate axonal crossing. In particular, we show that ephrin-B3 acts as the midline barrier that prevents corticospinal tract projections from recrossing when they enter the spinal gray matter. We report that in ephrin-B3(-/-) mice, corticospinal tract projections freely recross in the spinal gray matter, such that the motor cortex on one side of the brain now provides bilateral input to the spinal cord. This neuroanatomical abnormality in ephrin-B3(-/-) mice correlates with loss of unilateral motor control, yielding mice that simultaneously move their right and left limbs and thus have a peculiar hopping gait quite unlike the alternate step gait displayed by normal mice. The corticospinal and walking defects in ephrin-B3(-/-) mice resemble those recently reported for mice lacking the EphA4 receptor, which binds ephrin-B3 as well as other ephrins, suggesting that the binding of EphA4-bearing axonal processes to ephrin-B3 at the midline provides the repulsive signal that prevents corticospinal tract projections from recrossing the midline in the developing spinal cord.

Insights into the mechanisms underlying colonic motor patterns

PubMed Central

Dinning, Phil G.; Brookes, Simon J.; Costa, Marcello

2016-01-01

Abstract In recent years there have been significant technical and methodological advances in our ability to record the movements of the gastrointestinal tract. This has led to significant changes in our understanding of the different types of motor patterns that exist in the gastrointestinal tract (particularly the large intestine) and in our understanding of the mechanisms underlying their generation. Compared with other tubular smooth muscle organs, a rich variety of motor patterns occurs in the large intestine. This reflects a relatively autonomous nervous system in the gut wall, which has its own unique population of sensory neurons. Although the enteric nervous system can function independently of central neural inputs, under physiological conditions bowel motility is influenced by the CNS: if spinal pathways are disrupted, deficits in motility occur. The combination of high resolution manometry and video imaging has improved our knowledge of the range of motor patterns and provided some insight into the neural and mechanical factors underlying propulsion of contents. The neural circuits responsible for the generation of peristalsis and colonic migrating motor complexes have now been identified to lie within the myenteric plexus and do not require inputs from the mucosa or submucosal ganglia for their generation, but can be modified by their activity. This review will discuss the recent advances in our understanding of the different patterns of propagating motor activity in the large intestine of mammals and how latest technologies have led to major changes in our understanding of the mechanisms underlying their generation. PMID:26990133

Motorized Migrations: the Future or Mere Fantasy?

USGS Publications Warehouse

Ellis, D.H.; Sladen, William J. L.; Lishman, W.A.; Clegg, K.R.; Duff, J.W.; Gee, G.F.; Lewis, J.C.

2003-01-01

In 15 experiments from 1993-2002, we led cranes, geese, or swans on their first southward migration with either ultralight aircraft or vehicles on the ground. These experiments reveal that large birds can be readily trained to follow and most will return north (and south) in subsequent migrations unassisted. These techniques can now be used to teach birds new (or forgotten) migration paths. Although we are constantly improving our training techniques, we now have an operational program that can be broadly applied to those species where juveniles learn migration routes from their parents.

Lessons from the motorized migrations

USGS Publications Warehouse

Ellis, D.H.; Gee, G.F.; Clegg, K.R.; Duff, J.W.; Lishman, W.A.; Sladen, William J. L.

2001-01-01

Ten experiments have been conducted to determine if cranes can be led on migration and if those so trained will repeat migrations on their own. Results have been mixed as we have experienced the mishaps common to pilot studies. Nevertheless, we have learned many valuable lessons. Chief among these are that cranes can be led long distances behind motorized craft (air and ground), and those led over most or the entire route will return north come spring and south in fall to and from the general area of training. However, they will follow their own route. Groups transported south and flown at intervals along the route will migrate but often miss target termini. If certain protocol restrictions are followed, it is possible to make the trained cranes wild, however, the most practical way of so doing is to introduce them into a flock of wild cranes. We project that it is possible to create or restore wild migratory flocks of cranes by first leading small groups from chosen northern to southern termini.

In vivo analysis of Purkinje cell firing properties during postnatal mouse development

PubMed Central

Arancillo, Marife; White, Joshua J.; Lin, Tao; Stay, Trace L.

2014-01-01

Purkinje cell activity is essential for controlling motor behavior. During motor behavior Purkinje cells fire two types of action potentials: simple spikes that are generated intrinsically and complex spikes that are induced by climbing fiber inputs. Although the functions of these spikes are becoming clear, how they are established is still poorly understood. Here, we used in vivo electrophysiology approaches conducted in anesthetized and awake mice to record Purkinje cell activity starting from the second postnatal week of development through to adulthood. We found that the rate of complex spike firing increases sharply at 3 wk of age whereas the rate of simple spike firing gradually increases until 4 wk of age. We also found that compared with adult, the pattern of simple spike firing during development is more irregular as the cells tend to fire in bursts that are interrupted by long pauses. The regularity in simple spike firing only reached maturity at 4 wk of age. In contrast, the adult complex spike pattern was already evident by the second week of life, remaining consistent across all ages. Analyses of Purkinje cells in alert behaving mice suggested that the adult patterns are attained more than a week after the completion of key morphogenetic processes such as migration, lamination, and foliation. Purkinje cell activity is therefore dynamically sculpted throughout postnatal development, traversing several critical events that are required for circuit formation. Overall, we show that simple spike and complex spike firing develop with unique developmental trajectories. PMID:25355961

Inhibition of the proliferation and acceleration of migration of vascular endothelial cells by increased cysteine-rich motor neuron 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakashima, Yukiko; Morimoto, Mayuka; Toda, Ken-ichi

2015-07-03

Cysteine-rich motor neuron 1 (CRIM1) is upregulated only in extracellular matrix gels by angiogenic factors such as vascular endothelial growth factor (VEGF). It then plays a critical role in the tube formation of endothelial cells. In the present study, we investigated the effects of increased CRIM1 on other endothelial functions such as proliferation and migration. Knock down of CRIM1 had no effect on VEGF-induced proliferation or migration of human umbilical vein endothelial cells (HUVECs), indicating that basal CRIM1 is not involved in the proliferation or migration of endothelial cells. Stable CRIM1-overexpressing endothelial F-2 cells, termed CR1 and CR2, were constructed,more » because it was difficult to prepare monolayer HUVECs that expressed high levels of CRIM1. Proliferation was reduced and migration was accelerated in both CR1 and CR2 cells, compared with normal F-2 cells. Furthermore, the transient overexpression of CRIM1 resulted in decreased proliferation and increased migration of bovine aortic endothelial cells. In contrast, neither proliferation nor migration of COS-7 cells were changed by the overexpression of CRIM1. These results demonstrate that increased CRIM1 reduces the proliferation and accelerates the migration of endothelial cells. These CRIM1 effects might contribute to tube formation of endothelial cells. CRIM1 induced by angiogenic factors may serve as a regulator in endothelial cells to switch from proliferating cells to morphological differentiation. - Highlights: • CRIM1 was upregulated only in tubular endothelial cells, but not in monolayers. • Increased CRIM1 reduced the proliferation of endothelial cells. • Increased CRIM1 accelerated the migration of endothelial cells. • Increased CRIM1 had no effect on the proliferation or migration of COS-7 cells.« less

Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits

PubMed Central

Ramanathan, Dhakshin S.; Conner, James M.; Anilkumar, Arjun A.

2014-01-01

Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia. PMID:25505106

Factors associated with motor performance among overweight and nonoverweight Tyrolean primary school children.

PubMed

Ruedl, Gerhard; Greier, Klaus; Kirschner, Werner; Kopp, Martin

2016-01-01

The increasing prevalence of overweight and obesity among children is often associated with motor deficits. Motor performance among children partly depends on modifiable factors, for example, weight status, electronic media use, sports club participation, and on nonmodifiable factors, for example, sex, age, migration background, or socio-economic status. To evaluate factors associated with motor performance among overweight and nonoverweight Tyrolean primary school children. Height, weight, and sport motor performance of primary school children were measured using the German motor performance test DMT 6-18. In addition, children were asked about migration background, sports club participation, and electronic media use in their room. A total of 304 children (48.7% girls) with a mean age of 8.0 ± 1.2 years were tested. In total, 61 (20.1%) children were overweight or obese. Regarding motor performance, nonoverweight children showed significantly higher total z-scores (106.8 ± 5.7 vs. 102.4 ± 6.8). For the total cohort, results of the multiple linear regression analysis (R (2) = 0.20) revealed that factors male sex (β = 0.12), nonoverweight children (β = 0.28), higher school grade (β = 0.23), sports club participation (β = 0.18),and > 2 weekly lessons of physical education (β = 0.26) were associated with an increased motor performance. For nonoverweight children results of the multiple linear regression analysis (R (2) = 0.09) found that a higher school grade (β = 0.17), sports club participation (β = 0.16),and more than 2 weekly lessons of physical education (β = 0.22) were associated with an increased motor performance. For the overweight children, results of the multiple linear regression analysis (R (2) = 0 .43) showed that no migration background (β = 0.23), a higher school grade (β = 0.55), sports club participation (β = 0.33) and more than 2 weekly lessons of physical education (β = 0.48) were associated with an increased motor performance. Regarding modifiable factors, motor performance among overweight and nonoverweight children is strongly associated with a higher number of weekly lessons in physical education. Therefore, daily lessons in physical education are strongly recommended to improve motor performance especially among overweight primary school children.

Role of Netrin-1 Signaling in Nerve Regeneration

PubMed Central

Dun, Xin-Peng; Parkinson, David B.

2017-01-01

Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A–D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery. PMID:28245592

[The module "Motorik" in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Motor fitness and physical activity of children and young people].

PubMed

Opper, E; Worth, A; Wagner, M; Bös, K

2007-01-01

Motor fitness and physical activity are important aspects of a healthy development in childhood and adolescence. However, the assessment of motor fitness and physical activity is not subject to standardized criteria; furthermore, the samples investigated do not provide a representative image of the whole population. Therefore, the existing data only allow very limited statements on the state and development of motor fitness and physical activity. The "Motorik" module, as part of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), offers nationwide representative data on the motor fitness and physical activity of children and adolescents for the first time. Besides the baseline-analysis, another aim is to analyse the complex relationship between motor fitness, physical activity and health. Motor fitness, based on the systematisation of motor abilities, was assessed using a test profile. The test profile consists of 11 items measuring cardiorespiratory fitness, strength, coordination and mobility. Physical activity was assessed using a questionnaire containing 51 items on the duration, intensity and frequency of physical activity in everyday life, during leisure time, at school and in sports clubs. The above-mentioned questionnaire subtopics were supplemented by questions on the weekly prevalence of at least 60 minutes of daily physical activity, on material and local conditions, as well as on cognition and motivation for physical activity. In the years 2004 to 2006, the motor fitness and physical activity of 4,529 children and young people between the ages of 4 and 17 years was investigated on 168 sample points in the context of the "Motorik" module. Half of the children and adolescents investigated belong to the middle class, approximately 15% have a background of migration. The majority of the subjects come from small towns, about a quarter live in the city, less than 20% are settled in rural areas.

A method for multiprotein assembly in cells reveals independent action of kinesins in complex

PubMed Central

Norris, Stephen R.; Soppina, Virupakshi; Dizaji, Aslan S.; Schimert, Kristin I.; Sept, David; Cai, Dawen; Sivaramakrishnan, Sivaraj

2014-01-01

Teams of processive molecular motors are critical for intracellular transport and organization, yet coordination between motors remains poorly understood. Here, we develop a system using protein components to generate assemblies of defined spacing and composition inside cells. This system is applicable to studying macromolecular complexes in the context of cell signaling, motility, and intracellular trafficking. We use the system to study the emergent behavior of kinesin motors in teams. We find that two kinesin motors in complex act independently (do not help or hinder each other) and can alternate their activities. For complexes containing a slow kinesin-1 and fast kinesin-3 motor, the slow motor dominates motility in vitro but the fast motor can dominate on certain subpopulations of microtubules in cells. Both motors showed dynamic interactions with the complex, suggesting that motor–cargo linkages are sensitive to forces applied by the motors. We conclude that kinesin motors in complex act independently in a manner regulated by the microtubule track. PMID:25365993

Lactobacillus rhamnosus strain JB-1 reverses restraint stress-induced gut dysmotility.

PubMed

West, C; Wu, R Y; Wong, A; Stanisz, A M; Yan, R; Min, K K; Pasyk, M; McVey Neufeld, K-A; Karamat, M I; Foster, J A; Bienenstock, J; Forsythe, P; Kunze, W A

2017-01-01

Environmental stress affects the gut with dysmotility being a common consequence. Although a variety of microbes or molecules may prevent the dysmotility, none reverse the dysmotility. We have used a 1 hour restraint stress mouse model to test for treatment effects of the neuroactive microbe, L. rhamnosus JB-1 ™ . Motility of fluid-filled ex vivo gut segments in a perfusion organ bath was recorded by video and migrating motor complexes measured using spatiotemporal maps of diameter changes. Stress reduced jejunal and increased colonic propagating contractile cluster velocities and frequencies, while increasing contraction amplitudes for both. Luminal application of 10E8 cfu/mL JB-1 restored motor complex variables to unstressed levels within minutes of application. L. salivarius or Na.acetate had no treatment effects, while Na.butyrate partially reversed stress effects on colonic frequency and amplitude. Na.propionate reversed the stress effects for jejunum and colon except on jejunal amplitude. Our findings demonstrate, for the first time, a potential for certain beneficial microbes as treatment of stress-induced intestinal dysmotility and that the mechanism for restoration of function occurs within the intestine via a rapid drug-like action on the enteric nervous system. © 2016 John Wiley & Sons Ltd.

Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1.

PubMed

Kim, Edward; Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S; Anthony, Todd E; Wang, Chenran; Li, Yi E; Guan, Jun-Lin; Murphy, Geoffrey G; Zhu, Yuan

2014-12-23

Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities.

Sociocultural Influence on Obesity and Lifestyle in Children: A Study of Daily Activities, Leisure Time Behavior, Motor Skills, and Weight Status.

PubMed

Hilpert, Martin; Brockmeier, Konrad; Dordel, Sigrid; Koch, Benjamin; Weiß, Verena; Ferrari, Nina; Tokarski, Walter; Graf, Christine

2017-01-01

Juvenile overweight is increasing, and effective preventive measures are needed. After years of arbitrarily assigning these measures disregarding socioeconomic and/or cultural differences, it has become necessary to tailor interventions more specific to these target groups. Providing data for such an intervention is the objective of this study. Influencing variables on children's weight status, motor skills and lifestyle have been analyzed among 997 first graders (53.2% male) involved in the Children's Health InterventionaL Trial (CHILT). Median age was 6.9 years; 7.3% were obese, 8.8% were overweight. Children with low socioeconomic status (SES) were more likely to be obese (p = 0.029). Low SES (p ˂ 0.001), migration background (p = 0.001) and low sports activity levels (p = 0.007) contributed most to an increased consumption of television. Migration background (p = 0.003) and male gender (p < 0.001) were the strongest factors in predicting a greater consumption of computer/video games. Children with higher SES (p = 0.02), lower BMI (p = 0.035), and males (p = 0.001) performed better in motor tests. Children with a low SES and migration background were more likely to exhibit unfavorable health behavior patterns, higher BMI scores, and poorer motor skills. Interventions should integrate motivational and targeting strategies and consider cultural and educational differences to address these vulnerable groups. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

Sociocultural Influence on Obesity and Lifestyle in Children: A Study of Daily Activities, Leisure Time Behavior, Motor Skills, and Weight Status

PubMed Central

Hilpert, Martin; Brockmeier, Konrad; Dordel, Sigrid; Koch, Benjamin; Weiß, Verena; Ferrari, Nina; Tokarski, Walter; Graf, Christine

2017-01-01

Background Juvenile overweight is increasing, and effective preventive measures are needed. After years of arbitrarily assigning these measures disregarding socioeconomic and/or cultural differences, it has become necessary to tailor interventions more specific to these target groups. Providing data for such an intervention is the objective of this study. Methods Influencing variables on children's weight status, motor skills and lifestyle have been analyzed among 997 first graders (53.2% male) involved in the Children's Health InterventionaL Trial (CHILT). Results Median age was 6.9 years; 7.3% were obese, 8.8% were overweight. Children with low socioeconomic status (SES) were more likely to be obese (p = 0.029). Low SES (p ˂ 0.001), migration background (p = 0.001) and low sports activity levels (p = 0.007) contributed most to an increased consumption of television. Migration background (p = 0.003) and male gender (p < 0.001) were the strongest factors in predicting a greater consumption of computer/video games. Children with higher SES (p = 0.02), lower BMI (p = 0.035), and males (p = 0.001) performed better in motor tests. Conclusion Children with a low SES and migration background were more likely to exhibit unfavorable health behavior patterns, higher BMI scores, and poorer motor skills. Interventions should integrate motivational and targeting strategies and consider cultural and educational differences to address these vulnerable groups. PMID:28528341

Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo

PubMed Central

Law, Ah-Lai; Vehlow, Anne; Kotini, Maria; Dodgson, Lauren; Soong, Daniel; Theveneau, Eric; Bodo, Cristian; Taylor, Eleanor; Navarro, Christel; Perera, Upamali; Michael, Magdalene; Dunn, Graham A.; Bennett, Daimark; Mayor, Roberto

2013-01-01

Cell migration is essential for development, but its deregulation causes metastasis. The Scar/WAVE complex is absolutely required for lamellipodia and is a key effector in cell migration, but its regulation in vivo is enigmatic. Lamellipodin (Lpd) controls lamellipodium formation through an unknown mechanism. Here, we report that Lpd directly binds active Rac, which regulates a direct interaction between Lpd and the Scar/WAVE complex via Abi. Consequently, Lpd controls lamellipodium size, cell migration speed, and persistence via Scar/WAVE in vitro. Moreover, Lpd knockout mice display defective pigmentation because fewer migrating neural crest-derived melanoblasts reach their target during development. Consistently, Lpd regulates mesenchymal neural crest cell migration cell autonomously in Xenopus laevis via the Scar/WAVE complex. Further, Lpd’s Drosophila melanogaster orthologue Pico binds Scar, and both regulate collective epithelial border cell migration. Pico also controls directed cell protrusions of border cell clusters in a Scar-dependent manner. Taken together, Lpd is an essential, evolutionary conserved regulator of the Scar/WAVE complex during cell migration in vivo. PMID:24247431

Underlying mechanism of the cyclic migrating motor complex in Suncus murinus: a change in gastrointestinal pH is the key regulator.

PubMed

Mondal, Anupom; Koyama, Kouhei; Mikami, Takashi; Horita, Taichi; Takemi, Shota; Tsuda, Sachiko; Sakata, Ichiro; Sakai, Takafumi

2017-01-01

In the fasted gastrointestinal (GI) tract, a characteristic cyclical rhythmic migrating motor complex (MMC) occurs in an ultradian rhythm, at 90-120 min time intervals, in many species. However, the underlying mechanism directing this ultradian rhythmic MMC pattern is yet to be completely elucidated. Therefore, this study aimed to identify the possible causes or factors that involve in the occurrence of the fasting gastric contractions by using Suncus murinus a small model animal featuring almost the same rhythmic MMC as that found in humans and dogs. We observed that either intraduodenal infusion of saline at pH 8 evoked the strong gastric contraction or continuously lowering duodenal pH to 3-evoked gastric phase II-like and phase III-like contractions, and both strong contractions were essentially abolished by the intravenous administration of MA 2029 (motilin receptor antagonist) and D-Lys3-GHRP6 (ghrelin receptor antagonist) in a vagus-independent manner. Moreover, we observed that the prostaglandin E2-alpha (PGE2 - α) and serotonin type 4 (5HT4) receptors play important roles as intermediate molecules in changes in GI pH and motilin release. These results suggest a clear insight mechanism that change in the duodenal pH to alkaline condition is an essential factor for stimulating the endogenous release of motilin and governs the fasting MMC in a vagus-independent manner. Finally, we believe that the changes in duodenal pH triggered by flowing gastric acid and the release of duodenal bicarbonate through the involvement of PGE2 - α and 5HT4 receptor are the key events in the occurrence of the MMC. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Characteristics of colonic migrating motor complexes in neuronal NOS (nNOS) knockout mice.

PubMed

Spencer, Nick J

2013-01-01

It is well established that the intrinsic pacemaker mechanism that generates cyclical colonic migrating motor complexes (CMMCs) does not require endogenous nitric oxide (NO). However, pharmacological blockade of endogenous NO production potently increases the frequency of CMMCs, suggesting that endogenous NO acts normally to inhibit the CMMC pacemaker mechanism. In this study, we investigated whether mice with a life long genetic deletion of the neuronal nitric oxide synthase (nNOS) gene would show similar CMMC characteristics as wild type mice that have endogenous NO production acutely inhibited. Intracellular electrophysiological and mechanical recordings were made from circular muscle cells of isolated whole mouse colon in wild type and nNOS knockout (KO) mice at 35°C. In wild type mice, the NOS inhibitor, L-NA (100 μM) caused a significant increase in CMMC frequency and a significant depolarization of the CM layer. However, unexpectedly, the frequency of CMMCs in nNOS KO mice was not significantly different from control mice. Also, the resting membrane potential of CM cells in nNOS KO mice was not depolarized compared to controls; and the amplitude of the slow depolarization phase underlying MCs was of similar amplitude between KO and wild type offspring. These findings show that in nNOS KO mice, the major characteristics of CMMCs and their electrical correlates are, at least in adult mice, indistinguishable from wild type control offspring. One possibility why the major characteristics of CMMCs were no different between both types of mice is that nNOS KO mice may compensate for their life long deletion of the nNOS gene, and their permanent loss of neuronal NO production. In this regard, we suggest caution should be exercised when assuming that data obtained from adult nNOS KO mice can be directly extrapolated to wild type mice, that have been acutely exposed to an inhibitor of NOS.

Inverse scattering pre-stack depth imaging and it's comparison to some depth migration methods for imaging rich fault complex structure

NASA Astrophysics Data System (ADS)

Nurhandoko, Bagus Endar B.; Sukmana, Indriani; Mubarok, Syahrul; Deny, Agus; Widowati, Sri; Kurniadi, Rizal

2012-06-01

Migration is important issue for seismic imaging in complex structure. In this decade, depth imaging becomes important tools for producing accurate image in depth imaging instead of time domain imaging. The challenge of depth migration method, however, is in revealing the complex structure of subsurface. There are many methods of depth migration with their advantages and weaknesses. In this paper, we show our propose method of pre-stack depth migration based on time domain inverse scattering wave equation. Hopefully this method can be as solution for imaging complex structure in Indonesia, especially in rich thrusting fault zones. In this research, we develop a recent advance wave equation migration based on time domain inverse scattering wave which use more natural wave propagation using scattering wave. This wave equation pre-stack depth migration use time domain inverse scattering wave equation based on Helmholtz equation. To provide true amplitude recovery, an inverse of divergence procedure and recovering transmission loss are considered of pre-stack migration. Benchmarking the propose inverse scattering pre-stack depth migration with the other migration methods are also presented, i.e.: wave equation pre-stack depth migration, waveequation depth migration, and pre-stack time migration method. This inverse scattering pre-stack depth migration could image successfully the rich fault zone which consist extremely dip and resulting superior quality of seismic image. The image quality of inverse scattering migration is much better than the others migration methods.

Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration

PubMed Central

Wang, Shujie; Watanabe, Takashi; Matsuzawa, Kenji; Katsumi, Akira; Kakeno, Mai; Matsui, Toshinori; Ye, Feng; Sato, Kazuhide; Murase, Kiyoko; Sugiyama, Ikuko; Kimura, Kazushi; Mizoguchi, Akira; Ginsberg, Mark H.; Collard, John G.

2012-01-01

Migrating cells acquire front-rear polarity with a leading edge and a trailing tail for directional movement. The Rac exchange factor Tiam1 participates in polarized cell migration with the PAR complex of PAR3, PAR6, and atypical protein kinase C. However, it remains largely unknown how Tiam1 is regulated and contributes to the establishment of polarity in migrating cells. We show here that Tiam1 interacts directly with talin, which binds and activates integrins to mediate their signaling. Tiam1 accumulated at adhesions in a manner dependent on talin and the PAR complex. The interactions of talin with Tiam1 and the PAR complex were required for adhesion-induced Rac1 activation, cell spreading, and migration toward integrin substrates. Furthermore, Tiam1 acted with talin to regulate adhesion turnover. Thus, we propose that Tiam1, with the PAR complex, binds to integrins through talin and, together with the PAR complex, thereby regulates Rac1 activity and adhesion turnover for polarized migration. PMID:23071154

Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1

PubMed Central

Kim, Edward; Wang, Yuan; Kim, Sun-Jung; Bornhorst, Miriam; Jecrois, Emmanuelle S; Anthony, Todd E; Wang, Chenran; Li, Yi E; Guan, Jun-Lin; Murphy, Geoffrey G; Zhu, Yuan

2014-01-01

Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities. DOI: http://dx.doi.org/10.7554/eLife.05151.001 PMID:25535838

Variants in EXOSC9 Disrupt the RNA Exosome and Result in Cerebellar Atrophy with Spinal Motor Neuronopathy.

PubMed

Burns, David T; Donkervoort, Sandra; Müller, Juliane S; Knierim, Ellen; Bharucha-Goebel, Diana; Faqeih, Eissa Ali; Bell, Stephanie K; AlFaifi, Abdullah Y; Monies, Dorota; Millan, Francisca; Retterer, Kyle; Dyack, Sarah; MacKay, Sara; Morales-Gonzalez, Susanne; Giunta, Michele; Munro, Benjamin; Hudson, Gavin; Scavina, Mena; Baker, Laura; Massini, Tara C; Lek, Monkol; Hu, Ying; Ezzo, Daniel; AlKuraya, Fowzan S; Kang, Peter B; Griffin, Helen; Foley, A Reghan; Schuelke, Markus; Horvath, Rita; Bönnemann, Carsten G

2018-05-03

The exosome is a conserved multi-protein complex that is essential for correct RNA processing. Recessive variants in exosome components EXOSC3, EXOSC8, and RBM7 cause various constellations of pontocerebellar hypoplasia (PCH), spinal muscular atrophy (SMA), and central nervous system demyelination. Here, we report on four unrelated affected individuals with recessive variants in EXOSC9 and the effect of the variants on the function of the RNA exosome in vitro in affected individuals' fibroblasts and skeletal muscle and in vivo in zebrafish. The clinical presentation was severe, early-onset, progressive SMA-like motor neuronopathy, cerebellar atrophy, and in one affected individual, congenital fractures of the long bones. Three affected individuals of different ethnicity carried the homozygous c.41T>C (p.Leu14Pro) variant, whereas one affected individual was compound heterozygous for c.41T>C (p.Leu14Pro) and c.481C>T (p.Arg161 ∗ ). We detected reduced EXOSC9 in fibroblasts and skeletal muscle and observed a reduction of the whole multi-subunit exosome complex on blue-native polyacrylamide gel electrophoresis. RNA sequencing of fibroblasts and skeletal muscle detected significant >2-fold changes in genes involved in neuronal development and cerebellar and motor neuron degeneration, demonstrating the widespread effect of the variants. Morpholino oligonucleotide knockdown and CRISPR/Cas9-mediated mutagenesis of exosc9 in zebrafish recapitulated aspects of the human phenotype, as they have in other zebrafish models of exosomal disease. Specifically, portions of the cerebellum and hindbrain were absent, and motor neurons failed to develop and migrate properly. In summary, we show that variants in EXOSC9 result in a neurological syndrome combining cerebellar atrophy and spinal motoneuronopathy, thus expanding the list of human exosomopathies. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

X-ray-enhanced cancer cell migration requires the linker of nucleoskeleton and cytoskeleton complex.

PubMed

Imaizumi, Hiromasa; Sato, Katsutoshi; Nishihara, Asuka; Minami, Kazumasa; Koizumi, Masahiko; Matsuura, Nariaki; Hieda, Miki

2018-04-01

The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, including nuclear migration, mechanotransduction, chromatin tethering and DNA damage response. We recently showed that a nuclear envelope protein, Sad1 and UNC84 domain protein 1 (SUN1), a component of the LINC complex, has a critical function in cell migration. Although ionizing radiation activates cell migration and invasion in vivo and in vitro, the underlying molecular mechanism remains unknown. Here, we examined the involvement of the LINC complex in radiation-enhanced cell migration and invasion. A sublethal dose of X-ray radiation promoted human breast cancer MDA-MB-231 cell migration and invasion, whereas carbon ion beam radiation suppressed these processes in a dose-dependent manner. Depletion of SUN1 and SUN2 significantly suppressed X-ray-enhanced cell migration and invasion. Moreover, depletion or overexpression of each SUN1 splicing variant revealed that SUN1_888 containing 888 amino acids of SUN1 but not SUN1_916 was required for X-ray-enhanced migration and invasion. In addition, the results suggested that X-ray irradiation affected the expression level of SUN1 splicing variants and a SUN protein binding partner, nesprins. Taken together, our findings supported that the LINC complex contributed to photon-enhanced cell migration and invasion. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Cell Migration in 1D and 2D Nanofiber Microenvironments.

PubMed

Estabridis, Horacio M; Jana, Aniket; Nain, Amrinder; Odde, David J

2018-03-01

Understanding how cells migrate in fibrous environments is important in wound healing, immune function, and cancer progression. A key question is how fiber orientation and network geometry influence cell movement. Here we describe a quantitative, modeling-based approach toward identifying the mechanisms by which cells migrate in fibrous geometries having well controlled orientation. Specifically, U251 glioblastoma cells were seeded onto non-electrospinning Spinneret based tunable engineering parameters fiber substrates that consist of networks of suspended 400 nm diameter nanofibers. Cells were classified based on the local fiber geometry and cell migration dynamics observed by light microscopy. Cells were found in three distinct geometries: adhering two a single fiber, adhering to two parallel fibers, and adhering to a network of orthogonal fibers. Cells adhering to a single fiber or two parallel fibers can only move in one dimension along the fiber axis, whereas cells on a network of orthogonal fibers can move in two dimensions. We found that cells move faster and more persistently in 1D geometries than in 2D, with cell migration being faster on parallel fibers than on single fibers. To explain these behaviors mechanistically, we simulated cell migration in the three different geometries using a motor-clutch based model for cell traction forces. Using nearly identical parameter sets for each of the three cases, we found that the simulated cells naturally replicated the reduced migration in 2D relative to 1D geometries. In addition, the modestly faster 1D migration on parallel fibers relative to single fibers was captured using a correspondingly modest increase in the number of clutches to reflect increased surface area of adhesion on parallel fibers. Overall, the integrated modeling and experimental analysis shows that cell migration in response to varying fibrous geometries can be explained by a simple mechanical readout of geometry via a motor-clutch mechanism.

Geodynamic modeling of the capture and release of a plume conduit by a migrating mid-ocean ridge

NASA Astrophysics Data System (ADS)

Hall, P. S.

2011-12-01

plates over the relatively stationary, long-lived conduits of mantle plumes. However, paleomagnetic data from the Hawaii-Emperor Seamount Chain suggests that the Hawaiian hotspot moved rapidly (~40 mm/yr) between 81 - 47 Ma [Tarduno et al., 2003]. Recently, Tarduno et al. [2009] suggested that this period of rapid motion might be the surface expression of a plume conduit returning to a largely vertical orientation after having been captured and tilted as the result of being "run over" by migrating mid-ocean ridge. I report on a series of analog geodynamic experiments designed to characterize the evolution of a plume conduit as a mid-ocean ridge migrates over. Experiments were conducted in a clear acrylic tank (100 cm x 70 cm x 50 cm) filled with commercial grade high-fructose corn syrup. Plate-driven flow is modeled by dragging two sheets of Mylar film (driven by independent DC motors) in opposite directions over the surface of the fluid. Ridge migration is achieved by moving the point at which the mylar sheets diverge using a separate motor drive. Buoyant plume flow is generated using a small electrical heater placed at the bottom of the tank. Plate velocities and ridge migration rate are controlled and plume temperature monitored using LabView software. Experiments are recorded using digital video which is then analyzed using digital image analysis software to track the position and shape of the plume conduit throughout the course of the experiment. The intersection of the plume conduit with the surface of the fluid is taken as an analog for the locus of hotspot volcanism and tracked as a function of time to obtain a hotspot migration rate. Results show that the plume conduit experiences significant tilting immediately following the passage of the migrating ridge.

Prolonged Minocycline Treatment Impairs Motor Neuronal Survival and Glial Function in Organotypic Rat Spinal Cord Cultures

PubMed Central

Pinkernelle, Josephine; Fansa, Hisham; Ebmeyer, Uwe; Keilhoff, Gerburg

2013-01-01

Background Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. Methods In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM) at various time points in culture and fixed after 1 week. Results Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. Conclusions The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients. PMID:23967343

Results of the second (1996) experiment to lead cranes on migration behind a motorized ground vehicle

USGS Publications Warehouse

Ellis, D.H.; Clauss, B.; Watanabe, T.; Mykut, R.C.; Shawkey, M.; Mummert, D.P.; Sprague, D.T.; Ellis, Catherine H.; Trahan, F.B.

2001-01-01

Fourteen greater sandhill cranes (Grus canadensis tabida) were trained to follow a specially-equipped truck and 12 were led along a ca 620-km route from Camp Navajo in northern Arizona to the Buenos Aires National Wildlife Refuge near the Arizona/Mexico border. Ten survived the trek, 380 km of which were flown, although only a few cranes flew every stage of the route. Major problems during the migration were powerline collisions (ca 15, 2 fatal) and overheating (when air temperatures exceeded ca 25 C). The tenacity of the cranes in following both in 1995 and 1996 under unfavorable conditions (e.g., poor light, extreme dust, or heat) demonstrated that cranes could be led over long distances by motorized vehicles on the ground.

Neuropsychological Investigation of Motor Impairments in Autism

PubMed Central

Duffield, Tyler; Trontel, Haley; Bigler, Erin D.; Froehlich, Alyson; Prigge, Molly B.; Travers, Brittany; Green, Ryan R.; Cariello, Annahir N.; Cooperrider, Jason; Nielsen, Jared; Alexander, Andrew; Anderson, Jeffrey; Fletcher, P. Thomas; Lange, Nicholas; Zielinski, Brandon; Lainhart, Janet

2013-01-01

It is unclear how standardized neuropsychological measures of motor function relate to brain volumes of motor regions in autism spectrum disorder (ASD). An all male sample composed of 59 ASD and 30 controls (ages 5–33 years) completed three measures of motor function: strength of grip (SOG), finger tapping test (FTT), and grooved peg-board test (GPT). Likewise, all participants underwent magnetic resonance imaging with region of interest (ROI) volumes obtained to include the following regions: motor cortex (pre-central gyrus), somatosensory cortex (post-central gyrus), thalamus, basal ganglia, cerebellum and caudal middle frontal gyrus. These traditional neuropsychological measures of motor function are assumed to differ in motor complexity with GPT requiring the most followed by FTT and SOG. Performance by ASD participants on the GPT and FTT differed significantly from controls, with the largest effect size differences observed on the more complex GPT task. Differences on the SOG task between the two groups were non-significant. Since more complex motor tasks tap more complex networks, poorer GPT performance by those with ASD may reflect less efficient motor networks. There was no gross pathology observed in classic motor areas of the brain in ASD, as region of interest (ROI) volumes did not differ, but FTT was negatively related to motor cortex volume in ASD. The results suggest a hierarchical motor disruption in ASD, with difficulties evident only in more complex tasks as well as a potential anomalous size-function relation in motor cortex in ASD. PMID:23985036

Golden Eagle predation on experimental Sandhill and Whooping Cranes

USGS Publications Warehouse

Ellis, D.H.; Clegg, K.R.; Lewis, J.C.; Spaulding, E.

1999-01-01

There are very few published records of Golden Eagles preying upon cranes, especially in North America. During our experiments to lead cranes on migration behind motorized craft in the western United States, we experienced 15 attacks (four fatal) and believe many more attacks would have occurred (and more would have been fatal) without human intervention. We recognize eagle predation as an important risk to cranes especially during migration.

Fractal dimension assessment of brain white matter structural complexity post stroke in relation to upper-extremity motor function

PubMed Central

Zhang, Luduan; Butler, Andrew J.; Sun, Chang-Kai; Sahgal, Vinod; Wittenberg, George F.; Yue, Guang H.

2008-01-01

Little is known about the association between brain white matter (WM) structure and motor function in humans. This study investigated complexity of brain WM interior shape as determined by magnetic resonance imaging (MRI) and its relationship with upper-extremity (UE) motor function in patients post stroke. We hypothesized that (1) the WM complexity would decrease following stroke, and (2) higher WM complexity in non-affected cortical areas would be related to greater UE motor function. Thirty-eight stroke patients (16 with left-hemisphere lesions) underwent MRI anatomical brain scans. Fractal dimension (FD), a quantitative shape metric, was applied onto skeletonized brain WM images to evaluate WM internal structural complexity. Wolf Motor Function Test (WMFT) and Fugl-Meyer Motor Assessment (FM) scores were measured to assess motor function of the affected limb. The WM complexity was lower in the stroke-affected hemisphere. The FD was associated with better motor function in two subgroups: with left-subcortical lesions, FD values of the lesion-free areas of the left hemisphere were associated with better FM scores; with right-cortical lesions, FD values of lesion-free regions were robustly associated with better WMFT scores. These findings suggest that greater residual WM complexity is associated with less impaired UE motor function, which is more robust in patients with right-hemisphere lesions. No correlations were found between lesion volume and WMFT or FM scores. This study addressed WM complexity in stroke patients and its relationship with UE motor function. Measurement of brain WM reorganization may be a sensitive correlate of UE function in people recovering from stroke. PMID:18590710

The Hem protein mediates neuronal migration by inhibiting WAVE degradation and functions opposite of Abelson tyrosine kinase

PubMed Central

Zhu, Zengrong; Bhat, Krishna Moorthi

2011-01-01

In the nervous system, neurons form in different regions, then they migrate and occupy specific positions. We have previously shown that RP2/sib, a well-studied neuronal pair in the Drosophila ventral nerve cord (VNC), has a complex migration route. Here, we show that the Hem protein, via the WAVE complex, regulates migration of GMC-1 and its progeny RP2 neuron. In Hem or WAVE mutants, RP2 neuron either abnormally migrates, crossing the midline from one hemisegment to the contralateral hemisegment, or does not migrate at al and fail to send out its axon projection. We report that Hem regulates neuronal migration through stabilizing WAVE. Since Hem and WAVE normally form a complex, our data argues that in the absence of Hem, WAVE, which is presumably no longer in a complex, becomes susceptible to degradation. We also find that Abelson Tyrosine kinase affects RP2 migration in a similar manner as Hem and WAVE, and appears to operate via WAVE. However, while Abl negatively regulates the levels of WAVE, it regulates migration via regulating the activity of WAVE. Our results also show that during the degradation of WAVE, Hem function is opposite to that of and downstream of Abl. PMID:21726548

Ciliobrevins as tools for studying dynein motor function

PubMed Central

Roossien, Douglas H.; Miller, Kyle E.; Gallo, Gianluca

2015-01-01

Dyneins are a small class of molecular motors that bind to microtubules and walk toward their minus ends. They are essential for the transport and distribution of organelles, signaling complexes and cytoskeletal elements. In addition dyneins generate forces on microtubule arrays that power the beating of cilia and flagella, cell division, migration and growth cone motility. Classical approaches to the study of dynein function in axons involve the depletion of dynein, expression of mutant/truncated forms of the motor, or interference with accessory subunits. By necessity, these approaches require prolonged time periods for the expression or manipulation of cellular dynein levels. With the discovery of the ciliobrevins, a class of cell permeable small molecule inhibitors of dynein, it is now possible to acutely disrupt dynein both globally and locally. In this review, we briefly summarize recent work using ciliobrevins to inhibit dynein and discuss the insights ciliobrevins have provided about dynein function in various cell types with a focus on neurons. We temper this with a discussion of the need for studies that will elucidate the mechanism of action of ciliobrevin and as well as the need for experiments to further analyze the specificity of ciliobreviens for dynein. Although much remains to be learned about ciliobrevins, these small molecules are proving themselves to be valuable novel tools to assess the cellular functions of dynein. PMID:26217180

Force Exertion and Transmission in Cross-Linked Actin Networks

NASA Astrophysics Data System (ADS)

Stam, Samantha

Cells are responsive to external cues in their environment telling them to proliferate or migrate within their surrounding tissue. Sensing of cues that are mechanical in nature, such stiffness of a tissue or forces transmitted from other cells, is believed to involve the cytoskeleton of a cell. The cytoskeleton is a complex network of proteins consisting of polymers that provide structural support, motor proteins that remodel these structures, and many others. We do not yet have a complete understanding of how cytoskeletal components respond to either internal or external mechanical force and stiffness. Such an understanding should involve mechanisms by which constituent molecules, such as motor proteins, are responsive to mechanics. Additionally, physical models of how forces are transmitted through biopolymer networks are necessary. My research has focused on networks formed by the cytoskeletal filament actin and the molecular motor protein myosin II. Actin filaments form networks and bundles that form a structural framework of the cell, and myosin II slides actin filaments. In this thesis, we show that stiffness of an elastic load that opposes myosin-generated actin sliding has a very sharp effect on the myosin force output in simulations. Secondly, we show that the stiffness and connectivity of cytoskeletal filaments regulates the contractility and anisotropy of network deformations that transmit force on material length scales. Together, these results have implications for predicting and interpreting the deformations and forces in biopolymeric active materials.

Does human migration affect international trade? A complex-network perspective.

PubMed

Fagiolo, Giorgio; Mastrorillo, Marina

2014-01-01

This paper explores the relationships between international human migration and merchandise trade, using a complex-network approach. We firstly compare the topological structure of worldwide networks of human migration and bilateral trade over the period 1960-2000. Next, we ask whether the position of any pair of countries in the migration network affects their bilateral trade flows. We show that: (i) both weighted and binary versions of the networks of international migration and trade are strongly correlated; (ii) such correlations can be mostly explained by country economic/demographic size and geographical distance; and (iii) pairs of countries that are more central in the international-migration network trade more. Our findings suggest that bilateral trade between any two countries is not only affected by the presence of migrants from either countries but also by their relative embeddedness in the complex web of corridors making up the network of international human migration.

Does Human Migration Affect International Trade? A Complex-Network Perspective

PubMed Central

Fagiolo, Giorgio; Mastrorillo, Marina

2014-01-01

This paper explores the relationships between international human migration and merchandise trade using a complex-network approach. We firstly compare the topological structure of worldwide networks of human migration and bilateral trade over the period 1960–2000. Next, we ask whether pairs of countries that are more central in the migration network trade more. We show that: (i) the networks of international migration and trade are strongly correlated, and such correlation can be mostly explained by country economic/demographic size and geographical distance; (ii) centrality in the international-migration network boosts bilateral trade; (iii) intensive forms of country centrality are more trade enhancing than their extensive counterparts. Our findings suggest that bilateral trade between any two countries is not only affected by the presence of migrants from either countries, but also by their relative embeddedness in the complex web of corridors making up the network of international human migration. PMID:24828376

Action observation versus motor imagery in learning a complex motor task: a short review of literature and a kinematics study.

PubMed

Gatti, R; Tettamanti, A; Gough, P M; Riboldi, E; Marinoni, L; Buccino, G

2013-04-12

Both motor imagery and action observation have been shown to play a role in learning or re-learning complex motor tasks. According to a well accepted view they share a common neurophysiological basis in the mirror neuron system. Neurons within this system discharge when individuals perform a specific action and when they look at another individual performing the same or a motorically related action. In the present paper, after a short review of literature on the role of action observation and motor imagery in motor learning, we report the results of a kinematics study where we directly compared motor imagery and action observation in learning a novel complex motor task. This involved movement of the right hand and foot in the same angular direction (in-phase movement), while at the same time moving the left hand and foot in an opposite angular direction (anti-phase movement), all at a frequency of 1Hz. Motor learning was assessed through kinematics recording of wrists and ankles. The results showed that action observation is better than motor imagery as a strategy for learning a novel complex motor task, at least in the fast early phase of motor learning. We forward that these results may have important implications in educational activities, sport training and neurorehabilitation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Evolution and development of the mammalian cerebral cortex.

PubMed

Molnár, Zoltán; Kaas, Jon H; de Carlos, Juan A; Hevner, Robert F; Lein, Ed; Němec, Pavel

2014-01-01

Comparative developmental studies of the mammalian brain can identify key changes that can generate the diverse structures and functions of the brain. We have studied how the neocortex of early mammals became organized into functionally distinct areas, and how the current level of cortical cellular and laminar specialization arose from the simpler premammalian cortex. We demonstrate the neocortical organization in early mammals, which helps to elucidate how the large, complex human brain evolved from a long line of ancestors. The radial and tangential enlargement of the cortex was driven by changes in the patterns of cortical neurogenesis, including alterations in the proportions of distinct progenitor types. Some cortical cell populations travel to the cortex through tangential migration whereas others migrate radially. A number of recent studies have begun to characterize the chick, mouse and human and nonhuman primate cortical transcriptome to help us understand how gene expression relates to the development and anatomical and functional organization of the adult neocortex. Although all mammalian forms share the basic layout of cortical areas, the areal proportions and distributions are driven by distinct evolutionary pressures acting on sensory and motor experiences during the individual ontogenies. © 2014 S. Karger AG, Basel.

Confined Li ion migration in the silicon-graphene complex system: An ab initio investigation

NASA Astrophysics Data System (ADS)

Wang, Guoqing; Xu, Bo; Shi, Jing; Lei, Xueling; Ouyang, Chuying

2018-04-01

Silicon-Carbon complex systems play an important role in enhancing the performance of Si-based anode materials for Li ion batteries. In this work, the Li migration property of the Silicon-Graphene (Si-Gr) complex systems are investigated by using first-principles calculations. Especially, the effects of graphene coating on the migration of Li ions are discussed in detail. The distance between Si surface and graphene in the Si-Gr system significantly affects the lateral migration of Li ions. With the decrease of the distance from 4.715 to 3.844 Å, the energy barrier of Li ion migration also decreases from 0.115 to 0.067 eV, which are all lower than that of the case without graphene d(0.135 eV). However, smaller distance (3.586 Å) brings the high energy barrier (0.237 eV). Through AIMD calculations, it is found that the graphene coating in the Si-Gr complex system would result in the larger intercalation depths, more uniform distributions, and higher migration coefficients of Li ions. Further calculations of migration coefficients of Li ions at different temperature are used to obtained the activation energy for Li ions migration in the Si-Gr system, which is as low as 0.028 eV. This low activation energy shows that it is easy for Li ions migrating in the Si-Gr system. Our study provided the basically information to understand the migration mechanism of Li ions in Si-C system.

On the ultrafast charge migration and subsequent charge directed reactivity in Cl⋯N halogen-bonded clusters following vertical ionization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chandra, Sankhabrata; Bhattacharya, Atanu, E-mail: atanub@ipc.iisc.ernet.in; Periyasamy, Ganga

2015-06-28

In this article, we have presented ultrafast charge transfer dynamics through halogen bonds following vertical ionization of representative halogen bonded clusters. Subsequent hole directed reactivity of the radical cations of halogen bonded clusters is also discussed. Furthermore, we have examined effect of the halogen bond strength on the electron-electron correlation- and relaxation-driven charge migration in halogen bonded complexes. For this study, we have selected A-Cl (A represents F, OH, CN, NH{sub 2}, CF{sub 3}, and COOH substituents) molecules paired with NH{sub 3} (referred as ACl:NH{sub 3} complex): these complexes exhibit halogen bonds. To the best of our knowledge, this ismore » the first report on purely electron correlation- and relaxation-driven ultrafast (attosecond) charge migration dynamics through halogen bonds. Both density functional theory and complete active space self-consistent field theory with 6-31 + G(d, p) basis set are employed for this work. Upon vertical ionization of NCCl⋯NH{sub 3} complex, the hole is predicted to migrate from the NH{sub 3}-end to the ClCN-end of the NCCl⋯NH{sub 3} complex in approximately 0.5 fs on the D{sub 0} cationic surface. This hole migration leads to structural rearrangement of the halogen bonded complex, yielding hydrogen bonding interaction stronger than the halogen bonding interaction on the same cationic surface. Other halogen bonded complexes, such as H{sub 2}NCl:NH{sub 3}, F{sub 3}CCl:NH{sub 3}, and HOOCCl:NH{sub 3}, exhibit similar charge migration following vertical ionization. On the contrary, FCl:NH{sub 3} and HOCl:NH{sub 3} complexes do not exhibit any charge migration following vertical ionization to the D{sub 0} cation state, pointing to interesting halogen bond strength-dependent charge migration.« less

Formation of a PKCζ/β-catenin complex in endothelial cells promotes angiopoietin-1–induced collective directional migration and angiogenic sprouting

PubMed Central

Oubaha, Malika; Lin, Michelle I.; Margaron, Yoran; Filion, Dominic; Price, Emily N.; Zon, Leonard I.; Côté, Jean-François

2012-01-01

Angiogenic sprouting requires that cell-cell contacts be maintained during migration of endothelial cells. Angiopoietin-1 (Ang-1) and vascular endothelial growth factor act oppositely on endothelial cell junctions. We found that Ang-1 promotes collective and directional migration and, in contrast to VEGF, induces the formation of a complex formed of atypical protein kinase C (PKC)-ζ and β-catenin at cell-cell junctions and at the leading edge of migrating endothelial cells. This complex brings Par3, Par6, and adherens junction proteins at the front of migrating cells to locally activate Rac1 in response to Ang-1. The colocalization of PKCζ and β-catenin at leading edge along with PKCζ-dependent stabilization of cell-cell contacts promotes directed and collective endothelial cell migration. Consistent with these results, down-regulation of PKCζ in endothelial cells alters Ang-1–induced sprouting in vitro and knockdown in developing zebrafish results in intersegmental vessel defects caused by a perturbed directionality of tip cells and by loss of cell contacts between tip and stalk cells. These results reveal that PKCζ and β-catenin function in a complex at adherens junctions and at the leading edge of migrating endothelial cells to modulate collective and directional migration during angiogenesis. PMID:22936663

Matrix metalloproteinase-1 facilitates MSC migration via cleavage of IGF-2/IGFBP2 complex.

PubMed

Guan, Shou P; Lam, Alan T L; Newman, Jennifer P; Chua, Kevin L M; Kok, Catherine Y L; Chong, Siao T; Chua, Melvin L K; Lam, Paula Y P

2018-01-01

The specific mechanism underlying the tumor tropism of human mesenchymal stem cells (MSCs) for cancer is not well defined. We previously showed that the migration potential of MSCs correlated with the expression and protease activity of matrix metalloproteinase (MMP)-1. Furthermore, highly tumor-tropic MSCs expressed higher levels of MMP-1 and insulin-like growth factor (IGF)-2 than poorly migrating MSCs. In this study, we examined the functional roles of IGF-2 and MMP-1 in mediating the tumor tropism of MSCs. Exogenous addition of either recombinant IGF-2 or MMP-1 could stimulate MSC migration. The correlation between IGF-2, MMP-1 expression, and MSC migration suggests that MMP-1 may play a role in regulating MSC migration via the IGF-2 signaling cascade. High concentrations of IGF binding proteins (IGFBPs) can inhibit IGF-stimulated functions by blocking its binding to its receptors and proteolysis of IGFBP is an important mechanism for the regulation of IGF signaling. We thus hypothesized that MMP-1 acts as an IGFBP2 proteinase, resulting in the cleavage of IGF-2/IGFBP2 complex and extracellular release of free IGF-2. Indeed, our results showed that conditioned media from highly migrating MSCs, which expressed high levels of MMP-1, cleaved the IGF-2/IGFBP2 complex. Taken together, these results showed that the MMP-1 secreted by highly tumor-tropic MSCs cleaved IGF-2/IGFBP2 complex. Free IGF-2 released from the complex may facilitate MSC migration toward tumor.

The MYO6 interactome reveals adaptor complexes coordinating early endosome and cytoskeletal dynamics.

PubMed

O'Loughlin, Thomas; Masters, Thomas A; Buss, Folma

2018-04-01

The intracellular functions of myosin motors requires a number of adaptor molecules, which control cargo attachment, but also fine-tune motor activity in time and space. These motor-adaptor-cargo interactions are often weak, transient or highly regulated. To overcome these problems, we use a proximity labelling-based proteomics strategy to map the interactome of the unique minus end-directed actin motor MYO6. Detailed biochemical and functional analysis identified several distinct MYO6-adaptor modules including two complexes containing RhoGEFs: the LIFT (LARG-Induced F-actin for Tethering) complex that controls endosome positioning and motility through RHO-driven actin polymerisation; and the DISP (DOCK7-Induced Septin disPlacement) complex, a novel regulator of the septin cytoskeleton. These complexes emphasise the role of MYO6 in coordinating endosome dynamics and cytoskeletal architecture. This study provides the first in vivo interactome of a myosin motor protein and highlights the power of this approach in uncovering dynamic and functionally diverse myosin motor complexes. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Role of the import motor in insertion of transmembrane segments by the mitochondrial TIM23 complex.

PubMed

Popov-Čeleketić, Dušan; Waegemann, Karin; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

2011-06-01

The TIM23 complex mediates translocation of proteins across, and their lateral insertion into, the mitochondrial inner membrane. Translocation of proteins requires both the membrane-embedded core of the complex and its ATP-dependent import motor. Insertion of some proteins, however, occurs in the absence of ATP, questioning the need for the import motor during lateral insertion. We show here that the import motor associates with laterally inserted proteins even when its ATPase activity is not required. Furthermore, our results suggest a role for the import motor in lateral insertion. Thus, the import motor is involved in ATP-dependent translocation and ATP-independent lateral insertion.

Role of the import motor in insertion of transmembrane segments by the mitochondrial TIM23 complex

PubMed Central

Popov-Čeleketić, Dušan; Waegemann, Karin; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

2011-01-01

The TIM23 complex mediates translocation of proteins across, and their lateral insertion into, the mitochondrial inner membrane. Translocation of proteins requires both the membrane-embedded core of the complex and its ATP-dependent import motor. Insertion of some proteins, however, occurs in the absence of ATP, questioning the need for the import motor during lateral insertion. We show here that the import motor associates with laterally inserted proteins even when its ATPase activity is not required. Furthermore, our results suggest a role for the import motor in lateral insertion. Thus, the import motor is involved in ATP-dependent translocation and ATP-independent lateral insertion. PMID:21546912

Phosphoinositide Signaling Regulates the Exocyst Complex and Polarized Integrin Trafficking in Directionally Migrating Cells

PubMed Central

Thapa, Narendra; Sun, Yue; Schramp, Mark; Choi, Suyoung; Ling, Kun; Anderson, Richard A

2011-01-01

Summary Polarized delivery of signaling and adhesion molecules to the leading edge is required for directional migration of cells. Here, we describe a role for the PIP2 synthesizing enzyme, PIPKIγi2, in regulation of exocyst complex control of cell polarity and polarized integrin trafficking during migration. Loss of PIPKIγi2 impaired directional migration, formation of cell polarity, and integrin trafficking to the leading edge. Upon initiation of directional migration PIPKIγi2 via PIP2 generation controls the integration of the exocyst complex into an integrin-containing trafficking compartment(s) that requires the talin-binding ability of PIPKIγi2, and talin for integrin recruitment to the leading edge. A PIP2 requirement is further emphasized by inhibition of PIPKIγi2-regulated directional migration by an Exo70 mutant deficient in PIP2 binding. These results reveal how phosphoinositide generation orchestrates polarized trafficking of integrin in coordination with talin that links integrins to the actin cytoskeleton, processes that are required for directional migration. PMID:22264730

The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration

PubMed Central

Khatau, Shyam B.; Bloom, Ryan J.; Bajpai, Saumendra; Razafsky, David; Zang, Shu; Giri, Anjil; Wu, Pei-Hsun; Marchand, Jorge; Celedon, Alfredo; Hale, Christopher M.; Sun, Sean X.; Hodzic, Didier; Wirtz, Denis

2012-01-01

Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a minimal role in conventional 2D migration, they play a critical role in regulating the organization of a subset of actin filament bundles – the perinuclear actin cap - connected to the nucleus through Nesprin2giant and Nesprin3 in cells in 3D collagen I matrix. Actin cap fibers prolong the nucleus and mediate the formation of pseudopodial protrusions, which drive matrix traction and 3D cell migration. Disruption of LINC complexes disorganizes the actin cap, which impairs 3D cell migration. A simple mechanical model explains why LINC complexes and the perinuclear actin cap are essential in 3D migration by providing mechanical support to the formation of pseudopodial protrusions. PMID:22761994

Clinical and radiological factors related to the presence of motor deficit in lumbar disc prolapse: a prospective analysis of 70 consecutive cases with neurological deficit.

PubMed

Krishnan, Vibhu; Rajasekaran, Shanmuganathan; Aiyer, Siddharth N; Kanna, Rishi; Shetty, Ajoy Prasad

2017-10-01

To analyse the clinic-radiological factors associated with neurological deficit following lumbar disc herniation. A prospective, cross-sectional study was performed in 140 cases of micro-discectomy following lumbar disc herniation. Group 1 included 70 consecutive patients with motor deficit and group 2 (controls) included 70 patients with intact neurology. Motor deficit was defined as the occurrence of motor power ≤3/5 in L2-S1 myotomes. Multiple clinical and radiological parameters were studied between the two groups. Patients with diabetes (p 0.004), acute onset of symptoms (p 0.036), L3-4 discs (p 0.001), sequestrated discs (p 0.004), superiorly migrated discs (p 0.012) and central discs (p 0.004), greater antero-posterior disc dimension (p 0.023), primary canal stenosis (p 0.0001); and greater canal compromise (p 0.002) had a significant correlation with the development of neurological deficit. The presence of four or more of these risk factors showed a higher chance of the presence of motor deficit (sensitivity of 74%, specificity of 77%). Age, sex, previous precipitating events, severity of pain, smoking, and number of herniations levels did not affect the occurrence of deficit (p > 0.05 for all). Patients with or without bladder symptoms were similar with respect to all clinico-radiological parameters. However, the time delay since the occurrence of deficit was significantly shorter in patients with bladder involvement (p 0.001). Patients with diabetes, acute presentation, central, sequestrated and superiorly migrated discs, high lumbar disc prolapse, and greater spinal canal compromise are predisposed to the presence of motor deficit.

Kinesin-5, a mitotic microtubule-associated motor protein, modulates neuronal migration

PubMed Central

Falnikar, Aditi; Tole, Shubha; Baas, Peter W.

2011-01-01

Kinesin-5 (also called Eg5 or kif11) is a homotetrameric motor protein that functions by modulating microtubule (MT)–MT interactions. In the case of mitosis, kinesin-5 slows the rate of separation of the half-spindles. In the case of the axon, kinesin-5 limits the frequency of transport of short MTs, and also limits the rate of axonal growth. Here we show that experimental inhibition of kinesin-5 in cultured migratory neurons results in a faster but more randomly moving neuron with a shorter leading process. As is the case with axons of stationary neurons, short MT transport frequency is notably enhanced in the leading process of the migratory neuron when kinesin-5 is inhibited. Conversely, overexpression of kinesin-5, both in culture and in developing cerebral cortex, causes migration to slow and even cease. Regions of anti-parallel MT organization behind the centrosome were shown to be especially rich in kinesin-5, implicating these regions as potential sites where kinesin-5 forces may be especially relevant. We posit that kinesin-5 acts as a “brake” on MT–MT interactions that modulates the advance of the entire MT apparatus. In so doing, kinesin-5 regulates the rate and directionality of neuronal migration and possibly the cessation of migration when the neuron reaches its destination. PMID:21411631

Acetabular-epiphyseal angle and hip dislocation in cerebral palsy: a preliminary study.

PubMed

Alí-Morell, O J; Zurita-Ortega, F; Davó-Jiménez, I; Segura-Biedma, S

To relate, in non-ambulatory subjects with palsy, Reimers' migration percentage with standardized radiological measurements, including the acetabular-epiphyseal angle. Descriptive, observational and transversal study of 15 individuals with cerebral palsy at levels IV and V of the Gross Motor Function Classification System, aged between 3 and 9 years. Radiological measurements of the acetabular index, Hilgenreiner's epiphyseal angle, acetabular-epiphyseal angle, neck-shaft angle and Reimers' migration percentage of each of the hips were performed. Correlations between acetabular index, epiphyseal angle and acetabular-epiphyseal angle were obtained with respect to the Reimers migration percentage. For hips with a migration rate of 15% or less, a positive correlation was observed between acetabular and epiphyseal angles. In our population, the measurement between acetabular and epiphyseal inclination represents the highest association with the hip migration percentage. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration

PubMed Central

Elsen, Gina E.; Choi, Louis Y.; Prince, Victoria E.; Ho, Robert K.

2009-01-01

During development, Met signaling regulates a range of cellular processes including growth, differentiation, survival and migration. The Met gene encodes a tyrosine kinase receptor, which is activated by Hgf (hepatocyte growth factor) ligand. Altered regulation of human MET expression has been implicated in autism. In mouse, Met signaling has been shown to regulate cerebellum development. Since abnormalities in cerebellar structure have been reported in some autistic patients, we have used the zebrafish to address the role of Met signaling during cerebellar development and thus further our understanding of the molecular basis of autism. We find that zebrafish met is expressed in the cerebellar primordium, later localizing to the ventricular zone (VZ), with the hgf1 and hgf2 ligand genes expressed in surrounding tissues. Morpholino knockdown of either Met or its Hgf ligands leads to a significant reduction in the size of the cerebellum, primarily as a consequence of reduced proliferation. Met signaling knockdown disrupts specification of VZ-derived cell types, and also reduces granule cell numbers, due to an early effect on cerebellar proliferation and/or as an indirect consequence of loss of signals from VZ-derived cells later in development. These patterning defects preclude analysis of cerebellar neuronal migration, but we have found that Met signaling is necessary for migration of hindbrain facial motor neurons. In summary, we have described roles for Met signaling in coordinating growth and cell type specification within the developing cerebellum, and in migration of hindbrain neurons. These functions may underlie the correlation between altered MET regulation and Autism Spectrum Disorders. PMID:19732764

Distinct cortical circuit mechanisms for complex forelimb movement and motor map topography.

PubMed

Harrison, Thomas C; Ayling, Oliver G S; Murphy, Timothy H

2012-04-26

Cortical motor maps are the basis of voluntary movement, but they have proven difficult to understand in the context of their underlying neuronal circuits. We applied light-based motor mapping of Channelrhodopsin-2 mice to reveal a functional subdivision of the forelimb motor cortex based on the direction of movement evoked by brief (10 ms) pulses. Prolonged trains of electrical or optogenetic stimulation (100-500 ms) targeted to anterior or posterior subregions of motor cortex evoked reproducible complex movements of the forelimb to distinct positions in space. Blocking excitatory cortical synaptic transmission did not abolish basic motor map topography, but the site-specific expression of complex movements was lost. Our data suggest that the topography of movement maps arises from their segregated output projections, whereas complex movements evoked by prolonged stimulation require intracortical synaptic transmission. Copyright © 2012 Elsevier Inc. All rights reserved.

Statistical Mechanics of the Cytoskeleton

NASA Astrophysics Data System (ADS)

Wang, Shenshen

The mechanical integrity of eukaryotic cells along with their capability of dynamic remodeling depends on their cytoskeleton, a structural scaffold made up of a complex and dense network of filamentous proteins spanning the cytoplasm. Active force generation within the cytoskeletal networks by molecular motors is ultimately powered by the consumption of chemical energy and conversion of that energy into mechanical work. The resulting functional movements range from the collective cell migration in epithelial tissues responsible for wound healing to the changes of cell shape that occur during muscle contraction, as well as all the internal structural rearrangements essential for cell division. The role of the cytoskeleton as a dynamic versatile mesoscale "muscle", whose passive and active performance is both highly heterogeneous in space and time and intimately linked to diverse biological functions, allows it to serve as a sensitive indicator for the health and developmental state of the cell. By approaching this natural nonequilibrium many-body system from a variety of perspectives, researchers have made major progress toward understanding the cytoskeleton's unusual mechanical, dynamical and structural properties. Yet a unifying framework capable of capturing both the dynamics of active pattern formation and the emergence of spontaneous collective motion, that allows one to predict the dependence of the model's control parameters on motor properties, is still needed. In the following we construct a microscopic model and provide a theoretical framework to investigate the intricate interplay between local force generation, network architecture and collective motor action. This framework is able to accommodate both regular and heterogeneous pattern formation, as well as arrested coarsening and macroscopic contraction in a unified manner, through the notion of motor-driven effective interactions. Moreover a systematic expansion scheme combined with a variational stability analysis yields a threshold strength of motor kicking noise, below which the motorized system behaves as if it were at an effective equilibrium, but with a nontrivial effective temperature. Above the threshold, however, collective directed motion emerges spontaneously. Computer simulations support the theoretical predictions and highlight the essential role played in large-scale contraction by spatial correlation in motor kicking events.

Random intermittent search and the tug-of-war model of motor-driven transport

NASA Astrophysics Data System (ADS)

Newby, Jay; Bressloff, Paul C.

2010-04-01

We formulate the 'tug-of-war' model of microtubule cargo transport by multiple molecular motors as an intermittent random search for a hidden target. A motor complex consisting of multiple molecular motors with opposing directional preference is modeled using a discrete Markov process. The motors randomly pull each other off of the microtubule so that the state of the motor complex is determined by the number of bound motors. The tug-of-war model prescribes the state transition rates and corresponding cargo velocities in terms of experimentally measured physical parameters. We add space to the resulting Chapman-Kolmogorov (CK) equation so that we can consider delivery of the cargo to a hidden target at an unknown location along the microtubule track. The target represents some subcellular compartment such as a synapse in a neuron's dendrites, and target delivery is modeled as a simple absorption process. Using a quasi-steady-state (QSS) reduction technique we calculate analytical approximations of the mean first passage time (MFPT) to find the target. We show that there exists an optimal adenosine triphosphate (ATP) concentration that minimizes the MFPT for two different cases: (i) the motor complex is composed of equal numbers of kinesin motors bound to two different microtubules (symmetric tug-of-war model) and (ii) the motor complex is composed of different numbers of kinesin and dynein motors bound to a single microtubule (asymmetric tug-of-war model).

Using a Convection Model to Predict Altitudes of White Stork Migration Over Central Israel

NASA Astrophysics Data System (ADS)

Shamoun-Baranes, Judy; Liechti, Olivier; Yom-Tov, Yoram; Leshem, Yossi

Soaring migrants such as storks, pelicans and large birds of prey rely on thermal convection during migration. The convection model ALPTHERM was designed to predict the onset, strength, duration and depth of thermal convection for varying topographies for glider pilots, based on atmospheric conditions at midnight. We tested ALPTHERM predictions as configured for two topographies of central Israel, the Coastal Plains and the Judean and Samarian Mountains in order to predict altitudes of migrating white storks (Ciconia ciconia). Migrating flocks of white storks were tracked with a motorized glider, to measure maximum altitudes of migration during spring 2000. A significant positive correlation was found between the maximum daily altitudes of migration measured and the predicted upper boundary of thermal convection for the Coastal Plains and Samarian Mountains. Thirty-minute predictions for the Coastal Plains and Samarian Mountains correlated positively with measured maximum migration altitudes per thermal. ALPTHERM forecasts can be used to alter flight altitudes in both civil and especially military aviation and reduce the hazard of serious aircraft collisions with soaring migrants.

Intracortical Microstimulation Maps of Motor, Somatosensory, and Posterior Parietal Cortex in Tree Shrews (Tupaia belangeri) Reveal Complex Movement Representations.

PubMed

Baldwin, Mary K L; Cooke, Dylan F; Krubitzer, Leah

2017-02-01

Long-train intracortical microstimulation (LT-ICMS) is a popular method for studying the organization of motor and posterior parietal cortex (PPC) in mammals. In primates, LT-ICMS evokes both multijoint and multiple-body-part movements in primary motor, premotor, and PPC. In rodents, LT-ICMS evokes complex movements of a single limb in motor cortex. Unfortunately, very little is known about motor/PPC organization in other mammals. Tree shrews are closely related to both primates and rodents and could provide insights into the evolution of complex movement domains in primates. The present study investigated the extent of cortex in which movements could be evoked with ICMS and the characteristics of movements elicited using both short train (ST) and LT-ICMS in tree shrews. We demonstrate that LT-ICMS and ST-ICMS maps are similar, with the movements elicited with ST-ICMS being truncated versions of those elicited with LT-ICMS. In addition, LT-ICMS-evoked complex movements within motor cortex similar to those in rodents. More complex movements involving multiple body parts such as the hand and mouth were also elicited in motor cortex and PPC, as in primates. Our results suggest that complex movement networks present in PPC and motor cortex were present in mammals prior to the emergence of primates. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Transplantation of motoneurons derived from MASH1-transfected mouse ES cells reconstitutes neural networks and improves motor function in hemiplegic mice.

PubMed

Ikeda, Ritsuko; Kurokawa, Manae S; Chiba, Shunmei; Yoshikawa, Hideshi; Hashimoto, Takuo; Tadokoro, Mamoru; Suzuki, Noboru

2004-10-01

Mouse embryonic stem (ES) cells were transfected with a MASH1 expression vector and G418-resistant cells were selected. The MASH1-transfected cells became neuron-like appearance and expressed betaIIItubulin and panNCAM. Glial fibrillary acidic protein (GFAP) and galactocerebroside (GalC)-expressing cells were rarely detected. Half of the neural cells differentiated into the Islet1+ motoneuron lineage. Thus, we obtained motoneuron lineage-enriched neuronal cells by transfection of ES cells with MASH1. A hemiplegic model of mice was developed by cryogenic injury of the motor cortex, and motoneuron lineage-enriched neuronal cells were transplanted underneath the injured motor cortex neighboring the periventricular region. The motor function of the recipients was assessed by a beam walking and rotarod tests, whereby the results gradually improved, but little improvement was observed in vehicle injected control mice. We found that the grafted cells not only remained close to the implantation site, but also exhibited substantial migration, penetrating into the damaged lesion in a directed manner up to the cortical region. Grafted neuronal cells that had migrated into the cortex were elongated axon-positive for neurofilament middle chain (NFM). Synaptophysin immunostaining showed a positive staining pattern around the graft, suggesting that the transplanted neurons interacted with the recipient neurons to form a neural network. Our study suggests that the motoneuron lineage can be induced from ES cells, and grafted cells adapt to the host environment and can reconstitute a neural network to improve motor function of a paralyzed limb.

Live-cell imaging of Marburg virus-infected cells uncovers actin-dependent transport of nucleocapsids over long distances

PubMed Central

Schudt, Gordian; Kolesnikova, Larissa; Dolnik, Olga; Sodeik, Beate; Becker, Stephan

2013-01-01

Transport of large viral nucleocapsids from replication centers to assembly sites requires contributions from the host cytoskeleton via cellular adaptor and motor proteins. For the Marburg and Ebola viruses, related viruses that cause severe hemorrhagic fevers, the mechanism of nucleocapsid transport remains poorly understood. Here we developed and used live-cell imaging of fluorescently labeled viral and host proteins to characterize the dynamics and molecular requirements of nucleocapsid transport in Marburg virus-infected cells under biosafety level 4 conditions. The study showed a complex actin-based transport of nucleocapsids over long distances from the viral replication centers to the budding sites. Only after the nucleocapsids had associated with the matrix viral protein VP40 at the plasma membrane were they recruited into filopodia and cotransported with host motor myosin 10 toward the budding sites at the tip or side of the long cellular protrusions. Three different transport modes and velocities were identified: (i) Along actin filaments in the cytosol, nucleocapsids were transported at ∼200 nm/s; (ii) nucleocapsids migrated from one actin filament to another at ∼400 nm/s; and (iii) VP40-associated nucleocapsids moved inside filopodia at 100 nm/s. Unique insights into the spatiotemporal dynamics of nucleocapsids and their interaction with the cytoskeleton and motor proteins can lead to novel classes of antivirals that interfere with the trafficking and subsequent release of the Marburg virus from infected cells. PMID:23940347

Live-cell imaging of Marburg virus-infected cells uncovers actin-dependent transport of nucleocapsids over long distances.

PubMed

Schudt, Gordian; Kolesnikova, Larissa; Dolnik, Olga; Sodeik, Beate; Becker, Stephan

2013-08-27

Transport of large viral nucleocapsids from replication centers to assembly sites requires contributions from the host cytoskeleton via cellular adaptor and motor proteins. For the Marburg and Ebola viruses, related viruses that cause severe hemorrhagic fevers, the mechanism of nucleocapsid transport remains poorly understood. Here we developed and used live-cell imaging of fluorescently labeled viral and host proteins to characterize the dynamics and molecular requirements of nucleocapsid transport in Marburg virus-infected cells under biosafety level 4 conditions. The study showed a complex actin-based transport of nucleocapsids over long distances from the viral replication centers to the budding sites. Only after the nucleocapsids had associated with the matrix viral protein VP40 at the plasma membrane were they recruited into filopodia and cotransported with host motor myosin 10 toward the budding sites at the tip or side of the long cellular protrusions. Three different transport modes and velocities were identified: (i) Along actin filaments in the cytosol, nucleocapsids were transported at ∼200 nm/s; (ii) nucleocapsids migrated from one actin filament to another at ∼400 nm/s; and (iii) VP40-associated nucleocapsids moved inside filopodia at 100 nm/s. Unique insights into the spatiotemporal dynamics of nucleocapsids and their interaction with the cytoskeleton and motor proteins can lead to novel classes of antivirals that interfere with the trafficking and subsequent release of the Marburg virus from infected cells.

Potentiation of a functional autoantibody in narcolepsy by a cholinesterase inhibitor.

PubMed

Jackson, Michael W; Spencer, Nicolas J; Reed, Joanne H; Smith, Anthony J F; Gordon, Tom P

2009-12-01

We have recently reported the presence of an immunoglobulin G (IgG) autoantibody (Ab) in patients with narcolepsy with cataplexy that abolishes spontaneous colonic migrating motor complexes (CMMCs) and increases smooth muscle tension and atropine-sensitive phasic contractions in a physiological assay of an isolated colon. In this study, we used the cholinesterase inhibitor, neostigmine, to explore the mechanism of the narcoleptic IgG-mediated disruption of enteric motor function in four patients with narcolepsy with cataplexy and to identify a pharmacological mimic of the Ab. Neostigmine potentiated the narcoleptic IgG-mediated increase in smooth muscle resting tension and phasic smooth muscle contractions by an atropine-sensitive mechanism but exerted no effect on resting tension in the presence of control IgG. Decreased frequency of CMMCs mediated by IgG with anti-M3R activity was reversed by neostigmine. Therefore, a challenge with a cholinesterase inhibitor improves the specificity of the CMMC assay for narcoleptic IgG. Tetrodotoxin (TTX), a neuronal sodium channel blocker, also abolished CMMCs and increased resting tone, and a similar potentiation was observed with neostigmine; thus, TTX is a mimic of the functional effects of the narcoleptic IgG in this bioassay. These findings provide a link to pharmacological studies of canine narcolepsy and are consistent with a functional blockade of both excitatory and inhibitory motor neurons by the narcoleptic Ab, similar to the TTX mimic, presumably by binding to an autoantigenic target expressed in both populations of neurons.

Analysis of Expression Pattern and Genetic Deletion of Netrin5 in the Developing Mouse

PubMed Central

Garrett, Andrew M.; Jucius, Thomas J.; Sigaud, Liam P. R.; Tang, Fu-Lei; Xiong, Wen-Cheng; Ackerman, Susan L.; Burgess, Robert W.

2016-01-01

Boundary cap cells (BCC) are a transient, neural-crest-derived population found at the motor exit point (MEP) and dorsal root entry zone (DREZ) of the embryonic spinal cord. These cells contribute to the central/peripheral nervous system (CNS/PNS) boundary, and in their absence neurons and glia from the CNS migrate into the PNS. We found Netrin5 (Ntn5), a previously unstudied member of the netrin gene family, to be robustly expressed in BCC. We generated Ntn5 knockout mice and examined neurodevelopmental and BCC-related phenotypes. No abnormalities in cranial nerve guidance, dorsal root organization, or sensory projections were found. However, Ntn5 mutant embryos did have ectopic motor neurons (MNs) that migrated out of the ventral horn and into the motor roots. Previous studies have implicated semaphorin6A (Sema6A) in BCC signaling to plexinA2 (PlxnA2)/neuropilin2 (Nrp2) in MNs in restricting MN cell bodies to the ventral horn, particularly in the caudal spinal cord. In Ntn5 mutants, ectopic MNs are likely to be a different population, as more ectopias were found rostrally. Furthermore, ectopic MNs in Ntn5 mutants were not immunoreactive for NRP2. The netrin receptor deleted in colorectal cancer (DCC) is a potential receptor for NTN5 in MNs, as similar ectopic neurons were found in Dcc mutant mice, but not in mice deficient for other netrin receptors. Thus, Ntn5 is a novel netrin family member that is expressed in BCC, functioning to prevent MN migration out of the CNS. PMID:26858598

Mixed and Complex Mixed Migration during Armed Conflict: Multidimensional Empirical Evidence from Nepal

PubMed Central

Williams, Nathalie E.

2015-01-01

Historically, legal, policy, and academic communities largely ascribed to a dichotomy between forced and voluntary migration, creating a black and white vision that was convenient for legal and policy purposes. More recently, discussions have begun addressing the possibility of mixed migration, acknowledging that there is likely a wide continuum between forced and voluntary, and most migrants likely move with some amount of compulsion and some volition, even during armed conflict. While the mixed migration hypothesis is well-received, empirical evidence is disparate and somewhat blunt at this point. In this article, I contribute a direct theoretical and causal pathway discussion of mixed migration. I also propose the complex mixed migration hypothesis, which argues that not only do non-conflict related factors influence migration during conflict, but they do so differently than during periods of relative peace. I empirically test both hypotheses in the context of the recent armed conflict in Nepal. Using detailed survey data and event history models, results provide strong evidence for both mixed migration and complex mixed migration during conflict hypotheses. These hypotheses and evidence suggest that armed conflict might have substantial impacts on long-term population growth and change, with significant relevance in both academic and policy spheres. PMID:26366007

PCoM-DB Update: A Protein Co-Migration Database for Photosynthetic Organisms.

PubMed

Takabayashi, Atsushi; Takabayashi, Saeka; Takahashi, Kaori; Watanabe, Mai; Uchida, Hiroko; Murakami, Akio; Fujita, Tomomichi; Ikeuchi, Masahiko; Tanaka, Ayumi

2017-01-01

The identification of protein complexes is important for the understanding of protein structure and function and the regulation of cellular processes. We used blue-native PAGE and tandem mass spectrometry to identify protein complexes systematically, and built a web database, the protein co-migration database (PCoM-DB, http://pcomdb.lowtem.hokudai.ac.jp/proteins/top), to provide prediction tools for protein complexes. PCoM-DB provides migration profiles for any given protein of interest, and allows users to compare them with migration profiles of other proteins, showing the oligomeric states of proteins and thus identifying potential interaction partners. The initial version of PCoM-DB (launched in January 2013) included protein complex data for Synechocystis whole cells and Arabidopsis thaliana thylakoid membranes. Here we report PCoM-DB version 2.0, which includes new data sets and analytical tools. Additional data are included from whole cells of the pelagic marine picocyanobacterium Prochlorococcus marinus, the thermophilic cyanobacterium Thermosynechococcus elongatus, the unicellular green alga Chlamydomonas reinhardtii and the bryophyte Physcomitrella patens. The Arabidopsis protein data now include data for intact mitochondria, intact chloroplasts, chloroplast stroma and chloroplast envelopes. The new tools comprise a multiple-protein search form and a heat map viewer for protein migration profiles. Users can compare migration profiles of a protein of interest among different organelles or compare migration profiles among different proteins within the same sample. For Arabidopsis proteins, users can compare migration profiles of a protein of interest with putative homologous proteins from non-Arabidopsis organisms. The updated PCoM-DB will help researchers find novel protein complexes and estimate their evolutionary changes in the green lineage. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Bidirectional association between weight status and motor skills in adolescents : A 4-year longitudinal study.

PubMed

Greier, Klaus; Drenowatz, Clemens

2018-05-01

Despite considerable efforts the prevalence of overweight and obesity in youth remains high. Poor motor skills have been associated with increased body weight but there is still limited information on the longitudinal association of these health parameters. This study examined the prospective association between motor skills and body weight in 10- to 14-year-old youth. Body weight, height and motor skills, assessed via the German motor test 16-18 (Deutscher Motorik Test, DMT6-18), were measured in 213 middle school students (57% male) every year over a 4‑year period. Club sports participation and migration status were assessed via a questionnaire. Besides an inverse cross-sectional association between body weight and motor skills, excess body weight was associated with impaired development of motor skills (p < 0.05). Furthermore, weight loss was associated with enhanced motor development and allowed previously overweight students to catch up with their normal weight peers. High motor skills at baseline also reduced the odds of becoming overweight/obese during the observation period. These results were independent of club sports participation. There is a bidirectional, synergistic association between body weight and motor skills. Facilitating the development of motor skills in children and adolescents may therefore be a viable intervention strategy targeting weight management and physical activity in youth.

Dynamin Forms a Src Kinase–sensitive Complex with Cbl and Regulates Podosomes and Osteoclast Activity

PubMed Central

Bruzzaniti, Angela; Neff, Lynn; Sanjay, Archana; Horne, William C.; De Camilli, Pietro; Baron, Roland

2005-01-01

Podosomes are highly dynamic actin-containing adhesion structures found in osteoclasts, macrophages, and Rous sarcoma virus (RSV)-transformed fibroblasts. After integrin engagement, Pyk2 recruits Src and the adaptor protein Cbl, forming a molecular signaling complex that is critical for cell migration, and deletion of any molecule in this complex disrupts podosome ring formation and/or decreases osteoclast migration. Dynamin, a GTPase essential for endocytosis, is also involved in actin cytoskeleton remodeling and is localized to podosomes where it has a role in actin turnover. We found that dynamin colocalizes with Cbl in the actin-rich podosome belt of osteoclasts and that dynamin forms a complex with Cbl in osteoclasts and when overexpressed in 293VnR or SYF cells. The association of dynamin with Cbl in osteoclasts was decreased by Src tyrosine kinase activity and we found that destabilization of the dynamin-Cbl complex involves the recruitment of Src through the proline-rich domain of Cbl. Overexpression of dynamin increased osteoclast bone resorbing activity and migration, whereas overexpression of dynK44A decreased osteoclast resorption and migration. These studies suggest that dynamin, Cbl, and Src coordinately participate in signaling complexes that are important in the assembly and remodeling of the actin cytoskeleton, leading to changes in osteoclast adhesion, migration, and resorption. PMID:15872089

Envisioning migration: Mathematics in both experimental analysis and modeling of cell behavior

PubMed Central

Zhang, Elizabeth R.; Wu, Lani F.; Altschuler, Steven J.

2013-01-01

The complex nature of cell migration highlights the power and challenges of applying mathematics to biological studies. Mathematics may be used to create model equations that recapitulate migration, which can predict phenomena not easily uncovered by experiments or intuition alone. Alternatively, mathematics may be applied to interpreting complex data sets with better resolution—potentially empowering scientists to discern subtle patterns amid the noise and heterogeneity typical of migrating cells. Iteration between these two methods is necessary in order to reveal connections within the cell migration signaling network, as well as to understand the behavior that arises from those connections. Here, we review recent quantitative analysis and mathematical modeling approaches to the cell migration problem. PMID:23660413

Envisioning migration: mathematics in both experimental analysis and modeling of cell behavior.

PubMed

Zhang, Elizabeth R; Wu, Lani F; Altschuler, Steven J

2013-10-01

The complex nature of cell migration highlights the power and challenges of applying mathematics to biological studies. Mathematics may be used to create model equations that recapitulate migration, which can predict phenomena not easily uncovered by experiments or intuition alone. Alternatively, mathematics may be applied to interpreting complex data sets with better resolution--potentially empowering scientists to discern subtle patterns amid the noise and heterogeneity typical of migrating cells. Iteration between these two methods is necessary in order to reveal connections within the cell migration signaling network, as well as to understand the behavior that arises from those connections. Here, we review recent quantitative analysis and mathematical modeling approaches to the cell migration problem. Copyright © 2013 Elsevier Ltd. All rights reserved.

Potential involvement of kinesin-1 in the regulation of subcellular localization of Girdin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muramatsu, Aya; Enomoto, Atsushi, E-mail: enomoto@iar.nagoya-u.ac.jp; Kato, Takuya

Girdin is an actin-binding protein that has multiple functions in postnatal neural development and cancer progression. We previously showed that Girdin is a regulator of migration for neuroblasts born from neural stem cells in the subventricular zone (SVZ) and the dentate gyrus of the hippocampus in the postnatal brain. Despite a growing list of Girdin-interacting proteins, the mechanism of Girdin-mediated migration has not been fully elucidated. Girdin interacts with Disrupted-In-Schizophrenia 1 and partitioning-defective 3, both of which have been shown to interact with the kinesin microtubule motor proteins. Based on this, we have identified that Girdin also interacts with kinesin-1,more » a member of neuronal kinesin proteins. Although a direct interaction of Girdin and kinesin-1 has not been determined, it is of interest to find that Girdin loss-of-function mutant mice with the mutation of a basic amino acid residue-rich region (Basic mut mice) exhibit limited interaction with kinesin-1. Furthermore, expression of a kinesin-1 mutant with motor defects, leads to Girdin mislocalization. Finally, consistent with previous studies on the role of kinesin proteins in trafficking a cell–cell adhesion molecule N-cadherin, Basic mut mice showed an aberrant expression pattern of N-cadherin in migrating SVZ neuroblasts. These findings suggest a potential role of Girdin/kinesin-1 interaction in the regulation of neuroblast migration in the postnatal brain. - Highlights: • Girdin is a regulator of migration for neuroblasts in the postnatal brain. • Girdin interacts with kinesin-1, a member of neuronal kinesin proteins. • Girdin mutant mice showed an aberrant expression of N-cadherin in neuroblasts.« less

Anatomical basis of sun compass navigation II: the neuronal composition of the central complex of the monarch butterfly.

PubMed

Heinze, Stanley; Florman, Jeremy; Asokaraj, Surainder; El Jundi, Basil; Reppert, Steven M

2013-02-01

Each fall, eastern North American monarch butterflies in their northern range undergo a long-distance migration south to their overwintering grounds in Mexico. Migrants use a time-compensated sun compass to determine directionality during the migration. This compass system uses information extracted from sun-derived skylight cues that is compensated for time of day and ultimately transformed into the appropriate motor commands. The central complex (CX) is likely the site of the actual sun compass, because neurons in this brain region are tuned to specific skylight cues. To help illuminate the neural basis of sun compass navigation, we examined the neuronal composition of the CX and its associated brain regions. We generated a standardized version of the sun compass neuropils, providing reference volumes, as well as a common frame of reference for the registration of neuron morphologies. Volumetric comparisons between migratory and nonmigratory monarchs substantiated the proposed involvement of the CX and related brain areas in migratory behavior. Through registration of more than 55 neurons of 34 cell types, we were able to delineate the major input pathways to the CX, output pathways, and intrinsic neurons. Comparison of these neural elements with those of other species, especially the desert locust, revealed a surprising degree of conservation. From these interspecies data, we have established key components of a conserved core network of the CX, likely complemented by species-specific neurons, which together may comprise the neural substrates underlying the computations performed by the CX. Copyright © 2012 Wiley Periodicals, Inc.

Mechanical output of myosin II motors is regulated by myosin filament size and actin network mechanics

NASA Astrophysics Data System (ADS)

Stam, Samantha; Alberts, Jonathan; Gardel, Margaret; Munro, Edwin

2013-03-01

The interactions of bipolar myosin II filaments with actin arrays are a predominate means of generating forces in numerous physiological processes including muscle contraction and cell migration. However, how the spatiotemporal regulation of these forces depends on motor mechanochemistry, bipolar filament size, and local actin mechanics is unknown. Here, we simulate myosin II motors with an agent-based model in which the motors have been benchmarked against experimental measurements. Force generation occurs in two distinct regimes characterized either by stable tension maintenance or by stochastic buildup and release; transitions between these regimes occur by changes to duty ratio and myosin filament size. The time required for building force to stall scales inversely with the stiffness of a network and the actin gliding speed of a motor. Finally, myosin motors are predicted to contract a network toward stiffer regions, which is consistent with experimental observations. Our representation of myosin motors can be used to understand how their mechanical and biochemical properties influence their observed behavior in a variety of in vitro and in vivo contexts.

Performance in complex motor tasks deteriorates in hyperthermic humans.

PubMed

Piil, Jacob F; Lundbye-Jensen, Jesper; Trangmar, Steven J; Nybo, Lars

2017-01-01

Heat stress, leading to elevations in whole-body temperature, has a marked impact on both physical performance and cognition in ecological settings. Lab experiments confirm this for physically demanding activities, whereas observations are inconsistent for tasks involving cognitive processing of information or decision-making prior to responding. We hypothesized that divergences could relate to task complexity and developed a protocol consisting of 1) simple motor task [TARGET_pinch], 2) complex motor task [Visuo-motor tracking], 3) simple math task [MATH_type], 4) combined motor-math task [MATH_pinch]. Furthermore, visuo-motor tracking performance was assessed both in a separate- and a multipart protocol (complex motor tasks alternating with the three other tasks). Following familiarization, each of the 10 male subjects completed separate and multipart protocols in randomized order in the heat (40°C) or control condition (20°C) with testing at baseline (seated rest) and similar seated position, following exercise-induced hyperthermia (core temperature ∼ 39.5°C in the heat and 38.2°C in control condition). All task scores were unaffected by control exercise or passive heat exposure, but visuo-motor tracking performance was reduced by 10.7 ± 6.5% following exercise-induced hyperthermia when integrated in the multipart protocol and 4.4 ± 5.7% when tested separately (both P < 0.05 ). TARGET_pinch precision declined by 2.6 ± 1.3% ( P < 0.05 ), while no significant changes were observed for the math tasks. These results indicate that heat per se has little impact on simple motor or cognitive test performance, but complex motor performance is impaired by hyperthermia and especially so when multiple tasks are combined.

Second-chance signal transduction explains cooperative flagellar switching.

PubMed

Zot, Henry G; Hasbun, Javier E; Minh, Nguyen Van

2012-01-01

The reversal of flagellar motion (switching) results from the interaction between a switch complex of the flagellar rotor and a torque-generating stationary unit, or stator (motor unit). To explain the steeply cooperative ligand-induced switching, present models propose allosteric interactions between subunits of the rotor, but do not address the possibility of a reaction that stimulates a bidirectional motor unit to reverse direction of torque. During flagellar motion, the binding of a ligand-bound switch complex at the dwell site could excite a motor unit. The probability that another switch complex of the rotor, moving according to steady-state rotation, will reach the same dwell site before that motor unit returns to ground state will be determined by the independent decay rate of the excited-state motor unit. Here, we derive an analytical expression for the energy coupling between a switch complex and a motor unit of the stator complex of a flagellum, and demonstrate that this model accounts for the cooperative switching response without the need for allosteric interactions. The analytical result can be reproduced by simulation when (1) the motion of the rotor delivers a subsequent ligand-bound switch to the excited motor unit, thereby providing the excited motor unit with a second chance to remain excited, and (2) the outputs from multiple independent motor units are constrained to a single all-or-none event. In this proposed model, a motor unit and switch complex represent the components of a mathematically defined signal transduction mechanism in which energy coupling is driven by steady-state and is regulated by stochastic ligand binding. Mathematical derivation of the model shows the analytical function to be a general form of the Hill equation (Hill AV (1910) The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol 40: iv-vii).

Some glial progenitors in the neonatal subventricular zone migrate through the corpus callosum to the contralateral cerebral hemisphere.

PubMed

Kakita, Akiyoshi; Zerlin, Marielba; Takahashi, Hitoshi; Goldman, James E

2003-04-14

The great majority of glial cells of the mammalian forebrain are generated in the perinatal period from progenitors in the subventricular zone (SVZ). We investigated the migration of progenitors from the neonatal (postnatal day 0, P0) rat forebrain SVZ by labeling them in vivo with a green fluorescence protein (GFP) retrovirus and monitoring their movements by time-lapse video microscopy in P3 slices. We identified a small number of progenitors that migrated tangentially within the corpus callosum (CC) and crossed the midline. These cells retained a relatively uniform morphology: the leading process was extended toward the contralateral side but showed no process branching or turning away from the migratory direction. Net migration requires the elongation of the leading process and nuclear translocation, and the migrating cells in the CC showed both modes. We confirmed the presence of unmyelinated axon bundles within the P3 CC, but failed to detect any radially directed glial processes (vimentin- or GLAST-immunolabeled fibers) spanning through the CC. Confocal images showed a close proximity between neurofilament-immunolabeled axons and the leading process of the GFP-expressing progenitors in the CC. The destination of the callosal fibers was examined by applying DiI to the right cingulum; the labeled fibers ran throughout the CC and reached the left cingulate and motor areas. The distribution and final fates of the retrovirus-labeled cells were examined in P28 brains. A small proportion of the labeled cells were found in the contralateral hemisphere, where, as oligodendrocytes and astrocytes, they colonized predominantly the cortex and the underlying white matter of the cingulate and secondary motor areas. The distribution pattern appears to coincide well with the projection direction of the callosal fibers. Thus, glial progenitors migrate across the CC, presumably in conjunction with unmyelinated axons, to colonize the contralateral hemisphere. Copyright 2003 Wiley-Liss, Inc.

Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells

PubMed Central

Chabaud, Mélanie; Heuzé, Mélina L.; Bretou, Marine; Vargas, Pablo; Maiuri, Paolo; Solanes, Paola; Maurin, Mathieu; Terriac, Emmanuel; Le Berre, Maël; Lankar, Danielle; Piolot, Tristan; Adelstein, Robert S.; Zhang, Yingfan; Sixt, Michael; Jacobelli, Jordan; Bénichou, Olivier; Voituriez, Raphaël; Piel, Matthieu; Lennon-Duménil, Ana-Maria

2015-01-01

The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task. How leukocyte migration and function are coordinated is unknown. Here we show that in immature dendritic cells, which patrol their environment by engulfing extracellular material, cell migration and antigen capture are antagonistic. This antagonism results from transient enrichment of myosin IIA at the cell front, which disrupts the back-to-front gradient of the motor protein, slowing down locomotion but promoting antigen capture. We further highlight that myosin IIA enrichment at the cell front requires the MHC class II-associated invariant chain (Ii). Thus, by controlling myosin IIA localization, Ii imposes on dendritic cells an intermittent antigen capture behaviour that might facilitate environment patrolling. We propose that the requirement for myosin II in both cell migration and specific cell functions may provide a general mechanism for their coordination in time and space. PMID:26109323

Carbon-hydrogen activation of cycloalkanes by cyclopentadienylcarbonylrhodium--a lifetime enigma.

PubMed

Pitts, Amanda L; Wriglesworth, Alisdair; Sun, Xue-Zhong; Calladine, James A; Zarić, Snežana D; George, Michael W; Hall, Michael B

2014-06-18

Carbon-hydrogen bond activation reactions of four cycloalkanes (C5H10, C6H12, C7H14, and C8H16) by the Cp'Rh(CO) fragments (Cp' = η(5)-C5H5 (Cp) or η(5)-C5Me5 (Cp*)) were modeled theoretically by combining density functional and coupled cluster theories, and their reaction rates were measured by fast time-resolved infrared spectroscopy. The reaction has two steps, starting with the formation of a σ-complex intermediate, followed by oxidative addition of the C-H bond by the rhodium. A range of σ-complex stabilities among the electronically unique C-H bonds in a cycloalkane were calculated and are related to the individual strengths of the C-H bond's interactions with the Rh fragment and the steric repulsion that is incurred upon forming the specific σ-complex. The unexpectedly large increase in the lifetimes of the σ-complexes from cyclohexane to cycloheptane was predicted to be due to the large range of stabilities of the different σ-complexes found for cycloheptane. The reaction lifetimes were simulated with two mechanisms, with and without migrations among the different σ-complexes, to determine if ring migrations prior to C-H activation were influencing the rate. Both mechanisms predicted similar lifetimes for cyclopentane, cyclohexane, and, to a lesser extent, cycloheptane, suggesting ring migrations do not have a large impact on the rate of C-H activation for these cycloalkanes. For cyclooctane, the inclusion of ring migrations in the reaction mechanism led to a more accurate prediction of the lifetime, indicating that ring migrations did have an effect on the rate of C-H activation for this alkane, and that migration among the σ-complexes is faster than the C-H activation for this larger cycloalkane.

Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes

PubMed Central

Qu, Fangfei; Lorenzo, Damaris N; King, Samantha J; Brooks, Rebecca; Bear, James E; Bennett, Vann

2016-01-01

Endosomal membrane trafficking requires coordination between phosphoinositide lipids, Rab GTPases, and microtubule-based motors to dynamically determine endosome identity and promote long-range organelle transport. Here we report that ankyrin-B (AnkB), through integrating all three systems, functions as a critical node in the protein circuitry underlying polarized recycling of α5β1-integrin in mouse embryonic fibroblasts, which enables persistent fibroblast migration along fibronectin gradients. AnkB associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles in fibroblasts and binds dynactin to promote their long-range motility. We demonstrate that AnkB binds to Rab GTPase Activating Protein 1-Like (RabGAP1L) and recruits it to PI3P-positive organelles, where RabGAP1L inactivates Rab22A, and promotes polarized trafficking to the leading edge of migrating fibroblasts. We further determine that α5β1-integrin depends on an AnkB/RabGAP1L complex for polarized recycling. Our results reveal AnkB as an unexpected key element in coordinating polarized transport of α5β1-integrin and likely of other specialized endocytic cargos. DOI: http://dx.doi.org/10.7554/eLife.20417.001 PMID:27718357

Multiple intracerebroventricular injections of human umbilical cord mesenchymal stem cells delay motor neurons loss but not disease progression of SOD1G93A mice.

PubMed

Sironi, Francesca; Vallarola, Antonio; Violatto, Martina Bruna; Talamini, Laura; Freschi, Mattia; De Gioia, Roberta; Capelli, Chiara; Agostini, Azzurra; Moscatelli, Davide; Tortarolo, Massimo; Bigini, Paolo; Introna, Martino; Bendotti, Caterina

2017-12-01

Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles and Hoechst-33258 and transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated into the spinal cord after a single injection. This prompted us to assess the effect of repeated ICV injections of hUC-MSCs on disease progression in SOD1G93A mice. Although no transplanted cells migrated to the spinal cord, a partial but significant protection of motor neurons (MNs) was found in the lumbar spinal cord of hUC-MSCs-treated SOD1G93A mice, accompanied by a shift from a pro-inflammatory (IL-6, IL-1β) to anti-inflammatory (IL-4, IL-10) and neuroprotective (IGF-1) environment in the lumbar spinal cord, probably linked to the activation of p-Akt survival pathway in both motor neurons and reactive astrocytes. However, this treatment neither prevented the muscle denervation nor delayed the disease progression of mice, emphasizing the growing evidence that protecting the motor neuron perikarya is not sufficient to delay the ALS progression. Copyright © 2017. Published by Elsevier B.V.

DOE Office of Scientific and Technical Information (OSTI.GOV)

The Anh, Le, E-mail: letheanh@jaist.ac.jp; Lam, Pham Tien; Manoharan, Muruganathan

We present a first-principles study on the interstitial-mediated diffusion process of neutral phosphorus (P) atoms in a silicon crystal with the presence of mono-atomic hydrogen (H). By relaxing initial Si structures containing a P atom and an H atom, we derived four low-energy P-H-Si defect complexes whose formation energies are significantly lower than those of P-Si defect complexes. These four defect complexes are classified into two groups. In group A, an H atom is located near a Si atom, whereas in group B, an H atom is close to a P atom. We found that the H atom pairs withmore » P or Si atom and changes the nature bonding between P and Si atoms from out-of-phase conjugation to in-phase conjugation. This fact results in the lower formation energies compare to the cases without H atom. For the migration of defect complexes, we have found that P-H-Si defect complexes can migrate with low barrier energies if an H atom sticks to either P or Si atom. Group B complexes can migrate from one lattice site to another with an H atom staying close to a P atom. Group A complexes cannot migrate from one lattice site to another without a transfer of an H atom from one Si atom to another Si atom. A change in the structure of defect complexes between groups A and B during the migration results in a transfer of an H atom between P and Si atoms. The results for diffusion of group B complexes show that the presence of mono-atomic H significantly reduces the activation energy of P diffusion in a Si crystal, which is considered as a summation of formation energy and migration barrier energy, leading to the enhancement of diffusion of P atoms at low temperatures, which has been suggested by recent experimental studies.« less

The Calcium-Sensing Receptor and Integrins in Cellular Differentiation and Migration

PubMed Central

Tharmalingam, Sujeenthar; Hampson, David R.

2016-01-01

The calcium-sensing receptor (CaSR) is a widely expressed homodimeric G-protein coupled receptor structurally related to the metabotropic glutamate receptors and GPRC6A. In addition to its well characterized role in maintaining calcium homeostasis and regulating parathyroid hormone release, evidence has accumulated linking the CaSR with cellular differentiation and migration, brain development, stem cell engraftment, wound healing, and tumor growth and metastasis. Elevated expression of the CaSR in aggressive metastatic tumors has been suggested as a potential novel prognostic marker for predicting metastasis, especially to bone tissue where extracellular calcium concentrations may be sufficiently high to activate the receptor. Recent evidence supports a model whereby CaSR-mediated activation of integrins promotes cellular migration. Integrins are single transmembrane spanning heterodimeric adhesion receptors that mediate cell migration by binding to extracellular matrix proteins. The CaSR has been shown to form signaling complexes with the integrins to facilitate both the movement and differentiation of cells, such as neurons during normal brain development and tumor cells under pathological circumstances. Thus, CaSR/integrin complexes may function as a universal cell migration or homing complex. Manipulation of this complex may be of potential interest for treating metastatic cancers, and for developmental disorders pertaining to aberrant neuronal migration. PMID:27303307

Opposing effects of dopamine antagonism in a motor sequence task—tiapride increases cortical excitability and impairs motor learning

PubMed Central

Lissek, Silke; Vallana, Guido S.; Schlaffke, Lara; Lenz, Melanie; Dinse, Hubert R.; Tegenthoff, Martin

2014-01-01

The dopaminergic system is involved in learning and participates in the modulation of cortical excitability (CE). CE has been suggested as a marker of learning and use-dependent plasticity. However, results from separate studies on either motor CE or motor learning challenge this notion, suggesting opposing effects of dopaminergic modulation upon these parameters: while agonists decrease and antagonists increase CE, motor learning is enhanced by agonists and disturbed by antagonists. To examine whether this discrepancy persists when complex motor learning and motor CE are measured in the same experimental setup, we investigated the effects of dopaminergic (DA) antagonism upon both parameters and upon task-associated brain activation. Our results demonstrate that DA-antagonism has opposing effects upon motor CE and motor sequence learning. Tiapride did not alter baseline CE, but increased CE post training of a complex motor sequence while simultaneously impairing motor learning. Moreover, tiapride reduced activation in several brain regions associated with motor sequence performance, i.e., dorsolateral PFC (dlPFC), supplementary motor area (SMA), Broca's area, cingulate and caudate body. Blood-oxygenation-level-dependent (BOLD) intensity in anterior cingulate and caudate body, but not CE, correlated with performance across groups. In summary, our results do not support a concept of CE as a general marker of motor learning, since they demonstrate that a straightforward relation of increased CE and higher learning success does not apply to all instances of motor learning. At least for complex motor tasks that recruit a network of brain regions outside motor cortex, CE in primary motor cortex is probably no central determinant for learning success. PMID:24994972

Wash functions downstream of Rho1 GTPase in a subset of Drosophila immune cell developmental migrations

PubMed Central

Verboon, Jeffrey M.; Rahe, Travis K.; Rodriguez-Mesa, Evelyn; Parkhurst, Susan M.

2015-01-01

Drosophila immune cells, the hemocytes, undergo four stereotypical developmental migrations to populate the embryo, where they provide immune reconnoitering, as well as a number of non–immune-related functions necessary for proper embryogenesis. Here, we describe a role for Rho1 in one of these developmental migrations in which posteriorly located hemocytes migrate toward the head. This migration requires the interaction of Rho1 with its downstream effector Wash, a Wiskott–Aldrich syndrome family protein. Both Wash knockdown and a Rho1 transgene harboring a mutation that prevents Wash binding exhibit the same developmental migratory defect as Rho1 knockdown. Wash activates the Arp2/3 complex, whose activity is needed for this migration, whereas members of the WASH regulatory complex (SWIP, Strumpellin, and CCDC53) are not. Our results suggest a WASH complex–independent signaling pathway to regulate the cytoskeleton during a subset of hemocyte developmental migrations. PMID:25739458

Plume capture by a migrating ridge: Analog geodynamic experiments

NASA Astrophysics Data System (ADS)

Mendez, J. S.; Hall, P.

2010-12-01

Paleomagnetic data from the Hawaii-Emperor Seamount Chain (HESC) suggests that the Hawaiian hotspot moved rapidly (~40 mm/yr) between 81 - 47 Ma but has remained relatively stationary since that time. This implies that the iconic bend in the HESC may in fact reflect the transition from a period of rapid hotspot motion to a stationary state, rather than a change in motion of the Pacific plate. Tarduno et al. (2009) have suggested that this period of rapid hotspot motion might be the surface expression of a plume conduit returning to a largely vertical orientation after having been “captured” and tilted by a migrating mid-ocean ridge. We report on a series of analog fluid dynamic experiments designed to characterize the interaction between a migrating spreading center and a thermally buoyant mantle plume. Experiments were conducted in a clear acrylic tank (100 cm x 70 cm x 50 cm) filled with commercial grade high-fructose corn syrup. Plate-driven flow is modeled by dragging two sheets of Mylar film (driven by independent DC motors) in opposite directions over the surface of the fluid. Ridge migration is achieved by moving the point at which the mylar sheets diverge using a separate motor drive. Buoyant plume flow is modeled using corn syrup introduced into the bottom of the tank from an external, heated, pressurized reservoir. Small (~2 mm diameter), neutrally buoyant Delrin spheres are mixed into reservoir of plume material to aid in visualization. Plate velocities and ridge migration rate are controlled and plume temperature monitored using LabView software. Experiments are recorded using digital video which is then analyzed using digital image analysis software to track the position and shape of the plume conduit throughout the course of the experiment. The intersection of the plume conduit with the surface of the fluid is taken as an analog for the locus of hotspot volcanism and tracked as a function of time to obtain a hotspot migration rate. Experiments are scaled to the Earth's mantle through a combination of a Peclet number and a plume buoyancy number. A range of spreading rates, ridge migration rates, and plume excess temperatures representative of the Earth are considered.

Microbiota in the stomach: new insights.

PubMed

Wu, Wen Ming; Yang, Yun Sheng; Peng, Li Hua

2014-02-01

Bacteria are sparsely distributed in the stomach due to the gastric microbicidal barrier. Several innate defenses (low pH, migrating motor complex and the entero-salivary circulation of nitrate) as well as external factors (diet, Helicobacter pylori infection, proton pump inhibitors, antibiotics and stomach diseases) have been shown to influence significantly the microbiota composition in the stomach. In recent years new culture-independent technologies have allowed the investigation of the cross talk that occurs between hosts and stomach-associated microflora, which helps us to understand the role of gastric bacterial flora in the gastrointestinal microbiological system, both in physiological and pathological conditions. Here, we reviewed the literatures related to this topic and set the stage for future developments of the field. © 2013 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

The role of Sema3–Npn-1 signaling during diaphragm innervation and muscle development

PubMed Central

Huettl, Rosa-Eva; Hanuschick, Philipp; Amend, Anna-Lena; Alberton, Paolo; Aszodi, Attila; Huber, Andrea B.

2016-01-01

ABSTRACT Correct innervation of the main respiratory muscle in mammals, namely the thoracic diaphragm, is a crucial pre-requisite for the functionality of this muscle and the viability of the entire organism. Systemic impairment of Sema3A–Npn-1 (Npn-1 is also known as NRP1) signaling causes excessive branching of phrenic nerves in the diaphragm and into the central tendon region, where the majority of misguided axons innervate ectopic musculature. To elucidate whether these ectopic muscles are a result of misguidance of myoblast precursors due to the loss of Sema3A–Npn-1 signaling, we conditionally ablated Npn-1 in somatic motor neurons, which led to a similar phenotype of phrenic nerve defasciculation and, intriguingly, also formation of innervated ectopic muscles. We therefore hypothesize that ectopic myocyte fusion is caused by additional factors released by misprojecting growth cones. Slit2 and its Robo receptors are expressed by phrenic motor axons and migrating myoblasts, respectively, during innervation of the diaphragm. In vitro analyses revealed a chemoattractant effect of Slit2 on primary diaphragm myoblasts. Thus, we postulate that factors released by motor neuron growth cones have an influence on the migration properties of myoblasts during establishment of the diaphragm. PMID:27466379

Characterizing the complexity of spontaneous motor unit patterns of amyotrophic lateral sclerosis using approximate entropy

NASA Astrophysics Data System (ADS)

Zhou, Ping; Barkhaus, Paul E.; Zhang, Xu; Zev Rymer, William

2011-10-01

This paper presents a novel application of the approximate entropy (ApEn) measurement for characterizing spontaneous motor unit activity of amyotrophic lateral sclerosis (ALS) patients. High-density surface electromyography (EMG) was used to record spontaneous motor unit activity bilaterally from the thenar muscles of nine ALS subjects. Three distinct patterns of spontaneous motor unit activity (sporadic spikes, tonic spikes and high-frequency repetitive spikes) were observed. For each pattern, complexity was characterized by calculating the ApEn values of the representative signal segments. A sliding window over each segment was also introduced to quantify the dynamic changes in complexity for the different spontaneous motor unit patterns. We found that the ApEn values for the sporadic spikes were the highest, while those of the high-frequency repetitive spikes were the lowest. There is a significant difference in mean ApEn values between two arbitrary groups of the three spontaneous motor unit patterns (P < 0.001). The dynamic ApEn curve from the sliding window analysis is capable of tracking variations in EMG activity, thus providing a vivid, distinctive description for different patterns of spontaneous motor unit action potentials in terms of their complexity. These findings expand the existing knowledge of spontaneous motor unit activity in ALS beyond what was previously obtained using conventional linear methods such as firing rate or inter-spike interval statistics.

Intermanual transfer and bilateral cortical plasticity is maintained in older adults after skilled motor training with simple and complex tasks

PubMed Central

Dickins, Daina S. E.; Sale, Martin V.; Kamke, Marc R.

2015-01-01

Intermanual transfer refers to the phenomenon whereby unilateral motor training induces performance gains in both the trained limb and in the opposite, untrained limb. Evidence indicates that intermanual transfer is attenuated in older adults following training on a simple ballistic movement task, but not after training on a complex task. This study investigated whether differences in plasticity in bilateral motor cortices underlie these differential intermanual transfer effects in older adults. Twenty young (<35 years-old) and older adults (>65 years) trained on a simple (repeated ballistic thumb abduction) and complex (sequential finger-thumb opposition) task in separate sessions. Behavioral performance was used to quantify intermanual transfer between the dominant (trained) and non-dominant (untrained) hands. The amplitude of motor-evoked potentials induced by single pulse transcranial magnetic stimulation was used to investigate excitability changes in bilateral motor cortices. Contrary to predictions, both age groups exhibited performance improvements in both hands after unilateral skilled motor training with simple and complex tasks. These performance gains were accompanied by bilateral increases in cortical excitability in both groups for the simple but not the complex task. The findings suggest that advancing age does not necessarily influence the capacity for intermanual transfer after training with the dominant hand. PMID:25999856

Chronic Intestinal Pseudo-obstruction: Clinical and Manometric Characteristics in the Chilean Population

PubMed Central

de Arce, Edith Pérez; Landskron, Glauben; Hirsch, Sandra; Defilippi, Carlos; Madrid, Ana María

2017-01-01

Background/Aims Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome characterized by a failure of the propulsion of intraluminal contents and recurrent symptoms of partial bowel obstruction in the absence of mechanical obstruction. Regional variations of the intestinal compromise have been described. Intestinal manometry can indicate the pathophysiology and prognosis. Our objective is to establish the demographic and clinical characteristics of group Chilean patients and analyze the motility of the small intestine and its prognostic value. Methods Patients with symptoms of intestinal pseudo-obstruction with dilated bowel loops were included, in all of whom a manometry of the small intestine was performed using perfused catheters. Results Of the 64 patients included, 51 women (average age 41.5 ± 17.6 years), 54 primary and 10 secondary CIPO were included. Dilatation of the small intestine was the only finding in 38 patients; in the remaining, the compromise was associated with other segments, primarily the colon. Forty-nine patients underwent 65 surgeries, mainly exploratory laparotomies and colectomies. Intestinal manometry was performed on all patients; 4 “patterns” were observed: neuropathic (n = 26), myopathic (n = 3), mixed (n = 24), and a group without motor activity (n = 11). The most relevant findings were the complex migrating motor disorders and decreased frequency and propagation of contractions. The 9 patients who died had a severe myopathic compromise. Conclusions In our series, isolated small bowel compromise was the most common disorder. Neuropathic motor compromise was observed in most of the patients. Mortality was associated with severe myopathic compromise. PMID:27669829

STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo.

PubMed

Bazzi, Hisham; Soroka, Ekaterina; Alcorn, Heather L; Anderson, Kathryn V

2017-12-19

Regulated mesoderm migration is necessary for the proper morphogenesis and organ formation during embryonic development. Cell migration and its dependence on the cytoskeleton and signaling machines have been studied extensively in cultured cells; in contrast, remarkably little is known about the mechanisms that regulate mesoderm cell migration in vivo. Here, we report the identification and characterization of a mouse mutation in striatin-interacting protein 1 ( Strip1 ) that disrupts migration of the mesoderm after the gastrulation epithelial-to-mesenchymal transition (EMT). STRIP1 is a core component of the biochemically defined mammalian striatin-interacting phosphatases and kinase (STRIPAK) complexes that appear to act through regulation of protein phosphatase 2A (PP2A), but their functions in mammals in vivo have not been examined. Strip1 -null mutants arrest development at midgestation with profound disruptions in the organization of the mesoderm and its derivatives, including a complete failure of the anterior extension of axial mesoderm. Analysis of cultured mesoderm explants and mouse embryonic fibroblasts from null mutants shows that the mesoderm migration defect is correlated with decreased cell spreading, abnormal focal adhesions, changes in the organization of the actin cytoskeleton, and decreased velocity of cell migration. The results show that STRIPAK complexes are essential for cell migration and tissue morphogenesis in vivo. Copyright © 2017 the Author(s). Published by PNAS.

Oral-Motor and Motor-Speech Characteristics of Children with Autism.

ERIC Educational Resources Information Center

Adams, Lynn

1998-01-01

This study compared the oral-motor and motor-speech characteristics of four young children with autism and four nonautistic children. Three tasks requiring oral motor movements, simple syllable productions, and complex syllable productions were utilized. Significant differences were found in scores on the oral-motor movements and the…

A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development.

PubMed

Zhang, Feng; Yu, Jingwen; Yang, Tao; Xu, Dan; Chi, Zhixia; Xia, Yanheng; Xu, Zhiheng

2016-05-27

Disturbance of neuronal migration may cause various neurological disorders. Both the transforming growth factor-β (TGF-β) signaling and microcephaly-associated protein WDR62 are important for neuronal migration during brain development; however, the underlying molecular mechanisms involved remain unclear. We show here that knock-out or knockdown of Tak1 (TGFβ-activated kinase 1) and Jnk2 (c-Jun N-terminal kinase 2) perturbs neuronal migration during cortical development and that the migration defects incurred by knock-out and/or knockdown of Tβr2 (type II TGF-β receptor) or Tak1 can be partially rescued by expression of TAK1 and JNK2, respectively. Furthermore, TAK1 forms a protein complex with RAC1 and two scaffold proteins of the JNK pathway, the microcephaly-associated protein WDR62 and the RAC1-interacting protein POSH (plenty of Src homology). Components of the complex coordinate with each other in the regulation of TAK1 as well as JNK activities. We suggest that unique JNK protein complexes are involved in the diversified biological and pathological functions during brain development and pathogenesis of diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Evidence of a Cell Surface Role for Hsp90 Complex Proteins Mediating Neuroblast Migration in the Subventricular Zone.

PubMed

Miyakoshi, Leo M; Marques-Coelho, Diego; De Souza, Luiz E R; Lima, Flavia R S; Martins, Vilma R; Zanata, Silvio M; Hedin-Pereira, Cecilia

2017-01-01

In most mammalian brains, the subventricular zone (SVZ) is a germinative layer that maintains neurogenic activity throughout adulthood. Neuronal precursors arising from this region migrate through the rostral migratory stream (RMS) and reach the olfactory bulbs where they differentiate and integrate into the local circuitry. Recently, studies have shown that heat shock proteins have an important role in cancer cell migration and blocking Hsp90 function was shown to hinder cell migration in the developing cerebellum. In this work, we hypothesize that chaperone complexes may have an important function regulating migration of neuronal precursors from the subventricular zone. Proteins from the Hsp90 complex are present in the postnatal SVZ as well as in the RMS. Using an in vitro SVZ explant model, we have demonstrated the expression of Hsp90 and Hop/STI1 by migrating neuroblasts. Treatment with antibodies against Hsp90 and co-chaperone Hop/STI1, as well as Hsp90 and Hsp70 inhibitors hinder neuroblast chain migration. Time-lapse videomicroscopy analysis revealed that cell motility and average migratory speed was decreased after exposure to both antibodies and inhibitors. Antibodies recognizing Hsp90, Hsp70, and Hop/STI1 were found bound to the membranes of cells from primary SVZ cultures and biotinylation assays demonstrated that Hsp70 and Hop/STI1 could be found on the external leaflet of neuroblast membranes. The latter could also be detected in conditioned medium samples obtained from cultivated SVZ cells. Our results suggest that chaperones Hsp90, Hsp70, and co-chaperone Hop/STI1, components of the Hsp90 complex, regulate SVZ neuroblast migration in a concerted manner through an extracellular mechanism.

EphrinB3 restricts endogenous neural stem cell migration after traumatic brain injury.

PubMed

Dixon, Kirsty J; Mier, Jose; Gajavelli, Shyam; Turbic, Alisa; Bullock, Ross; Turnley, Ann M; Liebl, Daniel J

2016-11-01

Traumatic brain injury (TBI) leads to a series of pathological events that can have profound influences on motor, sensory and cognitive functions. Conversely, TBI can also stimulate neural stem/progenitor cell proliferation leading to increased numbers of neuroblasts migrating outside their restrictive neurogenic zone to areas of damage in support of tissue integrity. Unfortunately, the factors that regulate migration are poorly understood. Here, we examine whether ephrinB3 functions to restrict neuroblasts from migrating outside the subventricular zone (SVZ) and rostral migratory stream (RMS). We have previously shown that ephrinB3 is expressed in tissues surrounding these regions, including the overlying corpus callosum (CC), and is reduced after controlled cortical impact (CCI) injury. Our current study takes advantage of ephrinB3 knockout mice to examine the influences of ephrinB3 on neuroblast migration into CC and cortex tissues after CCI injury. Both injury and/or ephrinB3 deficiency led to increased neuroblast numbers and enhanced migration outside the SVZ/RMS zones. Application of soluble ephrinB3-Fc molecules reduced neuroblast migration into the CC after injury and limited neuroblast chain migration in cultured SVZ explants. Our findings suggest that ephrinB3 expression in tissues surrounding neurogenic regions functions to restrict neuroblast migration outside the RMS by limiting chain migration. Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.

Distinct roles of 1α and 1β heavy chains of the inner arm dynein I1 of Chlamydomonas flagella

PubMed Central

Toba, Shiori; Fox, Laura A.; Sakakibara, Hitoshi; Porter, Mary E.; Oiwa, Kazuhiro; Sale, Winfield S.

2011-01-01

The Chlamydomonas I1 dynein is a two-headed inner dynein arm important for the regulation of flagellar bending. Here we took advantage of mutant strains lacking either the 1α or 1β motor domain to distinguish the functional role of each motor domain. Single- particle electronic microscopic analysis confirmed that both the I1α and I1β complexes are single headed with similar ringlike, motor domain structures. Despite similarity in structure, however, the I1β complex has severalfold higher ATPase activity and microtubule gliding motility compared to the I1α complex. Moreover, in vivo measurement of microtubule sliding in axonemes revealed that the loss of the 1β motor results in a more severe impairment in motility and failure in regulation of microtubule sliding by the I1 dynein phosphoregulatory mechanism. The data indicate that each I1 motor domain is distinct in function: The I1β motor domain is an effective motor required for wild-type microtubule sliding, whereas the I1α motor domain may be responsible for local restraint of microtubule sliding. PMID:21148301

Shared and differentiated motor skill impairments in children with dyslexia and/or attention deficit disorder: From simple to complex sequential coordination

PubMed Central

Morin-Moncet, Olivier; Bélanger, Anne-Marie; Beauchamp, Miriam H.; Leonard, Gabriel

2017-01-01

Dyslexia and Attention deficit disorder (AD) are prevalent neurodevelopmental conditions in children and adolescents. They have high comorbidity rates and have both been associated with motor difficulties. Little is known, however, about what is shared or differentiated in dyslexia and AD in terms of motor abilities. Even when motor skill problems are identified, few studies have used the same measurement tools, resulting in inconstant findings. The present study assessed increasingly complex gross motor skills in children and adolescents with dyslexia, AD, and with both Dyslexia and AD. Our results suggest normal performance on simple motor-speed tests, whereas all three groups share a common impairment on unimanual and bimanual sequential motor tasks. Children in these groups generally improve with practice to the same level as normal subjects, though they make more errors. In addition, children with AD are the most impaired on complex bimanual out-of-phase movements and with manual dexterity. These latter findings are examined in light of the Multiple Deficit Model. PMID:28542319

Relations between fine motor skill and parental report of attention in young children with neurofibromatosis type 1.

PubMed

Casnar, Christy L; Janke, Kelly M; van der Fluit, Faye; Brei, Natalie G; Klein-Tasman, Bonita P

2014-01-01

Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders presenting in approximately 1 in 3,500 live births. NF1 is a highly variable condition with a large number of complications. A common complication is neuropsychological problems, including developmental delays and learning difficulties that affect as many as 60% of patients. Research has suggested that school-aged children with NF1 often have poorer fine motor skills and are at greater risk for attention difficulties than the general population. Thirty-eight children with NF1 and 23 unaffected children between the ages of 4 and 6 years, who are enrolled in a study of early development in NF1, were included in the present study. Varying levels of fine motor functioning were examined (simple to complex fine motor tasks). For children with NF1, significant difficulties were demonstrated on lab-based mid-level and complex fine motor tasks, even after controlling for nonverbal reasoning abilities, but not on simple fine motor tasks. Parental report also indicated difficulties in everyday adaptive fine motor functioning. No significant correlations were found between complex fine motor ability and attention difficulties. This study provides much needed descriptive data on the early emergence of fine motor difficulties and attention difficulties in young children with NF1.

Catalytic dimer nanomotors: continuum theory and microscopic dynamics.

PubMed

Reigh, Shang Yik; Kapral, Raymond

2015-04-28

Synthetic chemically-powered motors with various geometries have potentially new applications involving dynamics on very small scales. Self-generated concentration and fluid flow fields, which depend on geometry, play essential roles in motor dynamics. Sphere-dimer motors, comprising linked catalytic and noncatalytic spheres, display more complex versions of such fields, compared to the often-studied spherical Janus motors. By making use of analytical continuum theory and particle-based simulations we determine the concentration fields, and both the complex structure of the near-field and point-force dipole nature of the far-field behavior of the solvent velocity field that are important for studies of collective motor motion. We derive the dependence of motor velocity on geometric factors such as sphere size and dimer bond length and, thus, show how to construct motors with specific characteristics.

Diverse high-torque bacterial flagellar motors assemble wider stator rings using a conserved protein scaffold

PubMed Central

Ribardo, Deborah A.; Brennan, Caitlin A.; Ruby, Edward G.; Jensen, Grant J.; Hendrixson, David R.

2016-01-01

Although it is known that diverse bacterial flagellar motors produce different torques, the mechanism underlying torque variation is unknown. To understand this difference better, we combined genetic analyses with electron cryo-tomography subtomogram averaging to determine in situ structures of flagellar motors that produce different torques, from Campylobacter and Vibrio species. For the first time, to our knowledge, our results unambiguously locate the torque-generating stator complexes and show that diverse high-torque motors use variants of an ancestrally related family of structures to scaffold incorporation of additional stator complexes at wider radii from the axial driveshaft than in the model enteric motor. We identify the protein components of these additional scaffold structures and elucidate their sequential assembly, demonstrating that they are required for stator-complex incorporation. These proteins are widespread, suggesting that different bacteria have tailored torques to specific environments by scaffolding alternative stator placement and number. Our results quantitatively account for different motor torques, complete the assignment of the locations of the major flagellar components, and provide crucial constraints for understanding mechanisms of torque generation and the evolution of multiprotein complexes. PMID:26976588

Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis

PubMed Central

2018-01-01

Muscle morphogenesis is tightly coupled with that of motor neurons (MNs). Both MNs and muscle progenitors simultaneously explore the surrounding tissues while exchanging reciprocal signals to tune their behaviors. We previously identified the Fat1 cadherin as a regulator of muscle morphogenesis and showed that it is required in the myogenic lineage to control the polarity of progenitor migration. To expand our knowledge on how Fat1 exerts its tissue-morphogenesis regulator activity, we dissected its functions by tissue-specific genetic ablation. An emblematic example of muscle under such morphogenetic control is the cutaneous maximus (CM) muscle, a flat subcutaneous muscle in which progenitor migration is physically separated from the process of myogenic differentiation but tightly associated with elongating axons of its partner MNs. Here, we show that constitutive Fat1 disruption interferes with expansion and differentiation of the CM muscle, with its motor innervation and with specification of its associated MN pool. Fat1 is expressed in muscle progenitors, in associated mesenchymal cells, and in MN subsets, including the CM-innervating pool. We identify mesenchyme-derived connective tissue (CT) as a cell type in which Fat1 activity is required for the non–cell-autonomous control of CM muscle progenitor spreading, myogenic differentiation, motor innervation, and for motor pool specification. In parallel, Fat1 is required in MNs to promote their axonal growth and specification, indirectly influencing muscle progenitor progression. These results illustrate how Fat1 coordinates the coupling of muscular and neuronal morphogenesis by playing distinct but complementary actions in several cell types. PMID:29768404

Effect of transcranial direct current stimulation (tDCS) during complex whole body motor skill learning.

PubMed

Kaminski, Elisabeth; Hoff, Maike; Sehm, Bernhard; Taubert, Marco; Conde, Virginia; Steele, Christopher J; Villringer, Arno; Ragert, Patrick

2013-09-27

The aim of the study was to investigate tDCS effects on motor skill learning in a complex whole body dynamic balance task (DBT). We hypothesized that tDCS over the supplementary motor area (SMA), a region that is known to be involved in the control of multi-joint whole body movements, will result in polarity specific changes in DBT learning. In a randomized sham-controlled, double-blinded parallel design, we applied 20 min of tDCS over the supplementary motor area (SMA) and prefrontal cortex (PFC) while subjects performed a DBT. Anodal tDCS over SMA with the cathode placed over contralateral PFC impaired motor skill learning of the DBT compared to sham. This effect was still present on the second day of training. Reversing the polarity (cathode over SMA, anode over PFC) did not affect motor skill learning neither on the first nor on the second day of training. To better disentangle whether the impaired motor skill learning was due to a modulation of SMA or PFC, we performed an additional control experiment. Here, we applied anodal tDCS over SMA together with a larger and presumably more ineffective electrode (cathode) over PFC. Interestingly this alternative tDCS electrode setup did not affect the outcome of DBT learning. Our results provide novel evidence that a modulation of the (right) PFC seems to impair complex multi-joint motor skill learning. Hence, future studies should take the positioning of both tDCS electrodes into account when investigating complex motor skill learning. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Emerging role of ILK and ELMO2 in the integration of adhesion and migration pathways

PubMed Central

Ho, Ernest; Dagnino, Lina

2012-01-01

Integrins and their associated proteins are essential components of the cellular machinery that modulates adhesion and migration. In particular, integrin-linked kinase (ILK), which binds to the cytoplasmic tail of β1 integrins, is required for migration in a variety of cell types. We previously identified engulfment and motility 2 (ELMO2) as an ILK-binding protein in epidermal keratinocytes. Recently, we investigated the biological role of the ILK/ELMO2 complexes, and found that they exist in the cytoplasm. ILK/ELMO2 species are recruited by active RhoG to the plasma membrane, where they induce Rac1 activation and formation of lamellipodia at the leading edge of migrating cells. A large number of growth factors and cytokines induce keratinocyte migration. However, we found that formation of RhoG/ELMO2/ILK complexes occurs selectively upon stimulation by epidermal growth factor, but not by transforming growth factor-β1 or keratinocyte growth factor. Herein we discuss the relevance of these complexes to our understanding of the molecular mechanisms involved in cell migration, as well as their potential functions in morphogenesis and tissue regeneration following injury. PMID:22568984

Emerging role of ILK and ELMO2 in the integration of adhesion and migration pathways.

PubMed

Ho, Ernest; Dagnino, Lina

2012-01-01

Integrins and their associated proteins are essential components of the cellular machinery that modulates adhesion and migration. In particular, integrin-linked kinase (ILK), which binds to the cytoplasmic tail of β1 integrins, is required for migration in a variety of cell types. We previously identified engulfment and motility 2 (ELMO2) as an ILK-binding protein in epidermal keratinocytes. Recently, we investigated the biological role of the ILK/ELMO2 complexes, and found that they exist in the cytoplasm. ILK/ELMO2 species are recruited by active RhoG to the plasma membrane, where they induce Rac1 activation and formation of lamellipodia at the leading edge of migrating cells. A large number of growth factors and cytokines induce keratinocyte migration. However, we found that formation of RhoG/ELMO2/ILK complexes occurs selectively upon stimulation by epidermal growth factor, but not by transforming growth factor-β1 or keratinocyte growth factor. Herein we discuss the relevance of these complexes to our understanding of the molecular mechanisms involved in cell migration, as well as their potential functions in morphogenesis and tissue regeneration following injury.

Androgen-Induced Cell Migration: Role of Androgen Receptor/Filamin A Association

PubMed Central

Castoria, Gabriella; D'Amato, Loredana; Ciociola, Alessandra; Giovannelli, Pia; Giraldi, Tiziana; Sepe, Leandra; Paolella, Giovanni; Barone, Maria Vittoria; Migliaccio, Antimo; Auricchio, Ferdinando

2011-01-01

Background Androgen receptor (AR) controls male morphogenesis, gametogenesis and prostate growth as well as development of prostate cancer. These findings support a role for AR in cell migration and invasiveness. However, the molecular mechanism involved in AR-mediated cell migration still remains elusive. Methodology/Principal Findings Mouse embryo NIH3T3 fibroblasts and highly metastatic human fibrosarcoma HT1080 cells harbor low levels of transcriptionally incompetent AR. We now report that, through extra nuclear action, AR triggers migration of both cell types upon stimulation with physiological concentrations of the androgen R1881. We analyzed the initial events leading to androgen-induced cell migration and observed that challenging NIH3T3 cells with 10 nM R1881 rapidly induces interaction of AR with filamin A (FlnA) at cytoskeleton. AR/FlnA complex recruits integrin beta 1, thus activating its dependent cascade. Silencing of AR, FlnA and integrin beta 1 shows that this ternary complex controls focal adhesion kinase (FAK), paxillin and Rac, thereby driving cell migration. FAK-null fibroblasts migrate poorly and Rac inhibition by EHT impairs motility of androgen-treated NIH3T3 cells. Interestingly, FAK and Rac activation by androgens are independent of each other. Findings in human fibrosarcoma HT1080 cells strengthen the role of Rac in androgen signaling. The Rac inhibitor significantly impairs androgen-induced migration in these cells. A mutant AR, deleted of the sequence interacting with FlnA, fails to mediate FAK activation and paxillin tyrosine phosphorylation in androgen-stimulated cells, further reinforcing the role of AR/FlnA interaction in androgen-mediated motility. Conclusions/Significance The present report, for the first time, indicates that the extra nuclear AR/FlnA/integrin beta 1 complex is the key by which androgen activates signaling leading to cell migration. Assembly of this ternary complex may control organ development and prostate cancer metastasis. PMID:21359179

Absent movement-related cortical potentials in children with primary motor stereotypies.

PubMed

Houdayer, Elise; Walthall, Jessica; Belluscio, Beth A; Vorbach, Sherry; Singer, Harvey S; Hallett, Mark

2014-08-01

The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown, with hypotheses ranging from an arousal to a motor control disorder. Movement-related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self-initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self-paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about 1 second before the onset of a voluntary movement. Early MRCPs preceded self-paced arm movements in 8 of 10 children with motor stereotypies and in 6 of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico-striatal-thalamo-cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. © 2013 International Parkinson and Movement Disorder Society.

Absent movement-related cortical potentials in children with primary motor stereotypies

PubMed Central

Houdayer, Elise; Walthall, Jessica; Belluscio, Beth A.; Vorbach, Sherry; Singer, Harvey S.; Hallett, Mark

2013-01-01

Background The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown with hypotheses ranging from an arousal to a motor control disorder. Movement-related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self-initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Methods Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self-paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about one second before the onset of a voluntary movement. Results Early MRCPs preceded self-paced arm movements in 8 out of 10 children with motor stereotypies and in 6 out of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Conclusions Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico-striatal-thalamo-cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. PMID:24259275

Anomalous Putamen Volume in Children with Complex Motor Stereotypies

PubMed Central

Mahone, E. Mark; Crocetti, Deana; Tochen, Laura; Kline, Tina; Mostofsky, Stewart H.; Singer, Harvey S.

2016-01-01

Introduction Complex motor stereotypies in children are repetitive, rhythmic movements that have a predictable pattern and location, seem purposeful, but serve no obvious function, tend to be prolonged, and stop with distraction, e.g., arm/hand flapping, waving. They occur in both “primary” (otherwise typically developing) and secondary conditions. These movements are best defined as habitual behaviors and therefore pathophysiologically hypothesized to reside in premotor to posterior putamen circuits. This study sought to clarify the underlying neurobiological abnormality in children with primary complex motor stereotypies using structural neuroimaging, emphasizing brain regions hypothesized to underlie these atypical behaviors. Methods High-resolution anatomical MRI images, acquired at 3.0T, were analyzed in children ages 8–12 years (20 with primary complex motor stereotypies, 20 typically developing). Frontal lobe sub-regions and striatal structures were delineated for analysis. Results Significant reductions (p=0.045) in the stereotypies group were identified in total putamen volume, but not caudate, nucleus accumbens or frontal sub-regions. There were no group differences in total cerebral volume. Conclusion Findings of a smaller putamen provide preliminary evidence suggesting the potential involvement of the habitual pathway as the underlying anatomical site in primary complex motor stereotypies. PMID:27751663

We Need More Migration Between the Sciences

NASA Astrophysics Data System (ADS)

Wiesner, Karoline

The most exciting prospects for complexity science today are in the social sciences. Migration is a good example. According to the UN 720 million people worldwide are currently internal migrants and 120 million are international migrants. How many will there be in 2030, from where and to where do they migrate, why, at what costs and what are the consequences? We require a cross-disciplinary effort involving tools from complexity science, political science, social science, environmental science, psychology, epidemiology, biochemistry, and mathematics to tackle these questions...

Leading-process actomyosin coordinates organelle positioning and adhesion receptor dynamics in radially migrating cerebellar granule neurons

DOE PAGES

Trivedi, Niraj; Ramahi, Joseph S.; Karakaya, Mahmut; ...

2014-12-02

During brain development, neurons migrate from germinal zones to their final positions to assemble neural circuits. A unique saltatory cadence involving cyclical organelle movement (e.g., centrosome motility) and leading-process actomyosin enrichment prior to nucleokinesis organizes neuronal migration. While functional evidence suggests that leading-process actomyosin is essential for centrosome motility, the role of the actin-enriched leading process in globally organizing organelle transport or traction forces remains unexplored. Our results show that myosin ii motors and F-actin dynamics are required for Golgi apparatus positioning before nucleokinesis in cerebellar granule neurons (CGNs) migrating along glial fibers. Moreover, we show that primary cilia aremore » motile organelles, localized to the leading-process F-actin-rich domain and immobilized by pharmacological inhibition of myosin ii and F-actin dynamics. Finally, leading process adhesion dynamics are dependent on myosin ii and F-actin. In conclusion, we propose that actomyosin coordinates the overall polarity of migrating CGNs by controlling asymmetric organelle positioning and cell-cell contacts as these cells move along their glial guides.« less

Leading-process actomyosin coordinates organelle positioning and adhesion receptor dynamics in radially migrating cerebellar granule neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trivedi, Niraj; Ramahi, Joseph S.; Karakaya, Mahmut

During brain development, neurons migrate from germinal zones to their final positions to assemble neural circuits. A unique saltatory cadence involving cyclical organelle movement (e.g., centrosome motility) and leading-process actomyosin enrichment prior to nucleokinesis organizes neuronal migration. While functional evidence suggests that leading-process actomyosin is essential for centrosome motility, the role of the actin-enriched leading process in globally organizing organelle transport or traction forces remains unexplored. Our results show that myosin ii motors and F-actin dynamics are required for Golgi apparatus positioning before nucleokinesis in cerebellar granule neurons (CGNs) migrating along glial fibers. Moreover, we show that primary cilia aremore » motile organelles, localized to the leading-process F-actin-rich domain and immobilized by pharmacological inhibition of myosin ii and F-actin dynamics. Finally, leading process adhesion dynamics are dependent on myosin ii and F-actin. In conclusion, we propose that actomyosin coordinates the overall polarity of migrating CGNs by controlling asymmetric organelle positioning and cell-cell contacts as these cells move along their glial guides.« less

Migration: a concept analysis from a nursing perspective.

PubMed

Freeman, Michelle; Baumann, Andrea; Blythe, Jennifer; Fisher, Anita; Akhtar-Danesh, Noori

2012-05-01

  This article is a report of a concept analysis of nurse migration.   International migration is increasing and nurse migrants are active participants in this movement. Migration is a complex term and can be examined from a range of perspectives. Analysis of nurse migration is needed to guide policy, practice and research.   A literature search was undertaken using electronic literature indexes, specific journals and websites, internet search engines and hand searches. No timeframe was placed on the search. Most literature found was published between 2001 and 2009. A sample of 80 documents met the inclusion criteria.   Walker and Avant's approach guided the analysis.   Nurse migration can be defined by five attributes: the motivation and decisions of individuals; external barriers and facilitators; freedom of choice to migrate; freedom to migrate as a human right, and dynamic movement. Antecedents of migration include the political, social, economic, legal, historical and educational forces that comprise the push and pull framework. The consequences of migration are positive or negative depending on the viewpoint and its affect on the individual and other stakeholders such as the source country, destination country, healthcare systems and the nursing profession.   This concept analysis clarified the complexities surrounding nurse migration. A nursing-specific middle-range theory was proposed to guide the understanding and study of nurse migration. © 2011 Blackwell Publishing Ltd.

Motor heuristics and embodied choices: how to choose and act.

PubMed

Raab, Markus

2017-08-01

Human performance requires choosing what to do and how to do it. The goal of this theoretical contribution is to advance understanding of how the motor and cognitive components of choices are intertwined. From a holistic perspective I extend simple heuristics that have been tested in cognitive tasks to motor tasks, coining the term motor heuristics. Similarly I extend the concept of embodied cognition, that has been tested in simple sensorimotor processes changing decisions, to complex sport behavior coining the term embodied choices. Thus both motor heuristics and embodied choices explain complex behavior such as studied in sport and exercise psychology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Slit and semaphorin signaling governed by Islet transcription factors positions motor neuron somata within the neural tube

PubMed Central

Lee, Hojae; Kim, Minkyung; Kim, Namhee; Macfarlan, Todd; Pfaff, Samuel L.; Mastick, Grant S.; Song, Mi-Ryoung

2015-01-01

Motor neurons send out axons to peripheral muscles while their cell bodies remain in the ventral spinal cord. The unique configuration of motor neurons spanning the border between the CNS and PNS has been explained by structural barriers such as boundary cap (BC) cells, basal lamina and radial glia. However, mechanisms in motor neurons that retain their position have not been addressed yet. Here we demonstrate that the Islet1 (Isl1) and Islet2 (Isl2) transcription factors, which are essential for acquisition of motor neuron identity, also contribute to restrict motor neurons within the neural tube. In mice that lack both Isl1 and Isl2, large numbers of motor neurons exited the neural tube, even prior to the appearance of BC cells at the ventral exit points. Transcriptional profiling of motor neurons derived from Isl1 null embryonic stem cells revealed that transcripts of major genes involved in repulsive mechanisms were misregulated. Particularly, expression of Neuropilin1 (Npr1) and Slit2 mRNA was diminished in Islet mutant mice, and these could be target genes of the Islet proteins. Consistent with this mechanism, Robo and Slit mutations in mice and knockdown of Npr1 and Slit2 in chick embryos caused motor neurons to migrate to the periphery. Together, our study suggests that Islet genes engage Robo-Slit and Neuropilin-Semaphorin signaling in motor neurons to retain motor somata within the CNS. PMID:25843547

Narrow-Front Loop Migration in a Population of the Common Cuckoo Cuculus canorus, as Revealed by Satellite Telemetry

PubMed Central

Willemoes, Mikkel; Strandberg, Roine; Klaassen, Raymond H. G.; Tøttrup, Anders P.; Vardanis, Yannis; Howey, Paul W.; Thorup, Kasper; Wikelski, Martin; Alerstam, Thomas

2014-01-01

Narrow migration corridors known in diurnal, social migrants such as raptors, storks and geese are thought to be caused by topographical leading line effects in combination with learning detailed routes across generations. Here, we document narrow-front migration in a nocturnal, solitary migrant, the common cuckoo Cuculus canorus, using satellite telemetry. We tracked the migration of adult cuckoos from the breeding grounds in southern Scandinavia (n = 8), to wintering sites in south-western Central Africa (n = 6) and back to the breeding grounds (n = 3). Migration patterns were very complex; in addition to the breeding and wintering sites, six different stopover sites were identified during the 16,000 km annual route that formed a large-scale clockwise loop. Despite this complexity, individuals showed surprisingly similar migration patterns, with very little variation between routes. We compared observed tracks with simulated routes based on vector orientation (with and without effects of barriers on orientation and survival). Observed distances between routes were often significantly smaller than expected if the routes were established on the basis of an innate vector orientation programme. Average distance between individuals in eastern Sahel after having migrated more than 5,000 km for example, was merely 164 km. This implies that more sophisticated inherent guiding mechanisms, possibly involving elements of intermediate goal area navigation or more elaborate external cues, are necessary to explain the complex narrow-front migration pattern observed for the cuckoos in this study. PMID:24421890

Influences of Sentence Length and Syntactic Complexity on the Speech Motor Control of Children Who Stutter

ERIC Educational Resources Information Center

MacPherson, Megan K.; Smith, Anne

2013-01-01

Purpose: To investigate the potential effects of increased sentence length and syntactic complexity on the speech motor control of children who stutter (CWS). Method: Participants repeated sentences of varied length and syntactic complexity. Kinematic measures of articulatory coordination variability and movement duration during perceptually…

Examining the Potential of Web-Based Multimedia to Support Complex Fine Motor Skill Learning: An Empirical Study

ERIC Educational Resources Information Center

Papastergiou, Marina; Pollatou, Elisana; Theofylaktou, Ioannis; Karadimou, Konstantina

2014-01-01

Research on the utilization of the Web for complex fine motor skill learning that involves whole body movements is still scarce. The aim of this study was to evaluate the impact of the introduction of a multimedia web-based learning environment, which was targeted at a rhythmic gymnastics routine consisting of eight fine motor skills, into an…

Evolution with Stochastic Fitness and Stochastic Migration

PubMed Central

Rice, Sean H.; Papadopoulos, Anthony

2009-01-01

Background Migration between local populations plays an important role in evolution - influencing local adaptation, speciation, extinction, and the maintenance of genetic variation. Like other evolutionary mechanisms, migration is a stochastic process, involving both random and deterministic elements. Many models of evolution have incorporated migration, but these have all been based on simplifying assumptions, such as low migration rate, weak selection, or large population size. We thus have no truly general and exact mathematical description of evolution that incorporates migration. Methodology/Principal Findings We derive an exact equation for directional evolution, essentially a stochastic Price equation with migration, that encompasses all processes, both deterministic and stochastic, contributing to directional change in an open population. Using this result, we show that increasing the variance in migration rates reduces the impact of migration relative to selection. This means that models that treat migration as a single parameter tend to be biassed - overestimating the relative impact of immigration. We further show that selection and migration interact in complex ways, one result being that a strategy for which fitness is negatively correlated with migration rates (high fitness when migration is low) will tend to increase in frequency, even if it has lower mean fitness than do other strategies. Finally, we derive an equation for the effective migration rate, which allows some of the complex stochastic processes that we identify to be incorporated into models with a single migration parameter. Conclusions/Significance As has previously been shown with selection, the role of migration in evolution is determined by the entire distributions of immigration and emigration rates, not just by the mean values. The interactions of stochastic migration with stochastic selection produce evolutionary processes that are invisible to deterministic evolutionary theory. PMID:19816580

CENP-C/H/I/K/M/T/W/N/L and hMis12 but not CENP-S/X participate in complex formation in the nucleoplasm of living human interphase cells outside centromeres.

PubMed

Hoischen, Christian; Yavas, Sibel; Wohland, Thorsten; Diekmann, Stephan

2018-01-01

Kinetochore proteins assemble onto centromeric chromatin and regulate DNA segregation during cell division. The inner kinetochore proteins bind centromeres while most outer kinetochore proteins assemble at centromeres during mitosis, connecting the complex to microtubules. Here, we measured the co-migration between protein pairs of the constitutive centromere associated network (CCAN) and hMis12 complexes by fluorescence cross-correlation spectroscopy (FCCS) in the nucleoplasm outside centromeres in living human interphase cells. FCCS is a method that can tell if in living cells two differently fluorescently labelled molecules migrate independently, or co-migrate and thus are part of one and the same soluble complex. We also determined the apparent dissociation constants (Kd) of the hetero-dimers CENP-T/W and CENP-S/X. We measured co-migration between CENP-K and CENP-T as well as between CENP-M and CENP-T but not between CENP-T/W and CENP-S/X. Furthermore, CENP-C co-migrated with CENP-H, and CENP-K with CENP-N as well as with CENP-L. Thus, in the nucleoplasm outside centromeres, a large fraction of the CENP-H/I/K/M proteins interact with CENP-C, CENP-N/L and CENP-T/W but not with CENP-S/X. Our FCCS analysis of the Mis12 complex showed that hMis12, Nsl1, Dsn1 and Nnf1 also form a complex outside centromeres of which at least hMis12 associated with the CENP-C/H/I/K/M/T/W/N/L complex.

Identifying future directions for subsurface hydrocarbon migration research

NASA Astrophysics Data System (ADS)

Leifer, I.; Clark, J. F.; Luyendyk, B.; Valentine, D.

Subsurface hydrocarbon migration is important for understanding the input and impacts of natural hydrocarbon seepage on the environment. Great uncertainties remain in most aspects of hydrocarbon migration, including some basic mechanisms of this four-phase flow of tar, oil, water, and gas through the complex fracture-network geometry particularly since the phases span a wide range of properties. Academic, government, and industry representatives recently attended a workshop to identify the areas of greatest need for future research in shallow hydrocarbon migration.Novel approaches such as studying temporal and spatial seepage variations and analogous geofluid systems (e.g., geysers and trickle beds) allow deductions of subsurface processes and structures that remain largely unclear. Unique complexities exist in hydrocarbon migration due to its multiphase flow and complex geometry, including in-situ biological weathering. Furthermore, many aspects of the role of hydrocarbons (positive and negative) in the environment are poorly understood, including how they enter the food chain (respiration, consumption, etc.) and “percolate” to higher trophic levels. But understanding these ecological impacts requires knowledge of the emissions' temporal and spatial variability and trajectories.

Profiles of Motor Laterality in Young Athletes' Performance of Complex Movements: Merging the MOTORLAT and PATHoops Tools

PubMed Central

Castañer, Marta; Andueza, Juan; Hileno, Raúl; Puigarnau, Silvia; Prat, Queralt; Camerino, Oleguer

2018-01-01

Laterality is a key aspect of the analysis of basic and specific motor skills. It is relevant to sports because it involves motor laterality profiles beyond left-right preference and spatial orientation of the body. The aim of this study was to obtain the laterality profiles of young athletes, taking into account the synergies between the support and precision functions of limbs and body parts in the performance of complex motor skills. We applied two instruments: (a) MOTORLAT, a motor laterality inventory comprising 30 items of basic, specific, and combined motor skills, and (b) the Precision and Agility Tapping over Hoops (PATHoops) task, in which participants had to perform a path by stepping in each of 14 hoops arranged on the floor, allowing the observation of their feet, left-right preference and spatial orientation. A total of 96 young athletes performed the PATHoops task and the 30 MOTORLAT items, allowing us to obtain data about limb dominance and spatial orientation of the body in the performance of complex motor skills. Laterality profiles were obtained by means of a cluster analysis and a correlational analysis and a contingency analysis were applied between the motor skills and spatial orientation actions performed. The results obtained using MOTORLAT show that the combined motor skills criterion (for example, turning while jumping) differentiates athletes' uses of laterality, showing a clear tendency toward mixed laterality profiles in the performance of complex movements. In the PATHoops task, the best spatial orientation strategy was “same way” (same foot and spatial wing) followed by “opposite way” (opposite foot and spatial wing), in keeping with the research assumption that actions unfolding in a horizontal direction in front of an observer's eyes are common in a variety of sports. PMID:29930527

Complex Burn Region Module (CBRM) update

NASA Technical Reports Server (NTRS)

Adams, Carl L.; Jenkins, Billy

1991-01-01

Presented here is a Complex Burn Region Module (CBRM) update for the Solid Rocket Internal Ballistics Module (SRIBM) Program for the Advanced Solid Rocket Motor (ASRM) design/performance assessments. The goal was to develop an improved version of the solid rocket internal ballistics module program that contains a diversified complex region model for motor grain design, performance prediction, and evaluation.

Effect of type of cognitive task and walking speed on cognitive-motor interference during dual-task walking.

PubMed

Patel, P; Lamar, M; Bhatt, T

2014-02-28

We aimed to determine the effect of distinctly different cognitive tasks and walking speed on cognitive-motor interference of dual-task walking. Fifteen healthy adults performed four cognitive tasks: visuomotor reaction time (VMRT) task, word list generation (WLG) task, serial subtraction (SS) task, and the Stroop (STR) task while sitting and during walking at preferred-speed (dual-task normal walking) and slow-speed (dual-task slow-speed walking). Gait speed was recorded to determine effect on walking. Motor and cognitive costs were measured. Dual-task walking had a significant effect on motor and cognitive parameters. At preferred-speed, the motor cost was lowest for the VMRT task and highest for the STR task. In contrast, the cognitive cost was highest for the VMRT task and lowest for the STR task. Dual-task slow walking resulted in increased motor cost and decreased cognitive cost only for the STR task. Results show that the motor and cognitive cost of dual-task walking depends heavily on the type and perceived complexity of the cognitive task being performed. Cognitive cost for the STR task was low irrespective of walking speed, suggesting that at preferred-speed individuals prioritize complex cognitive tasks requiring higher attentional and processing resources over walking. While performing VMRT task, individuals preferred to prioritize more complex walking task over VMRT task resulting in lesser motor cost and increased cognitive cost for VMRT task. Furthermore, slow walking can assist in diverting greater attention towards complex cognitive tasks, improving its performance while walking. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Changes in the neural control of a complex motor sequence during learning

PubMed Central

Otchy, Timothy M.; Goldberg, Jesse H.; Aronov, Dmitriy; Fee, Michale S.

2011-01-01

The acquisition of complex motor sequences often proceeds through trial-and-error learning, requiring the deliberate exploration of motor actions and the concomitant evaluation of the resulting performance. Songbirds learn their song in this manner, producing highly variable vocalizations as juveniles. As the song improves, vocal variability is gradually reduced until it is all but eliminated in adult birds. In the present study we examine how the motor program underlying such a complex motor behavior evolves during learning by recording from the robust nucleus of the arcopallium (RA), a motor cortex analog brain region. In young birds, neurons in RA exhibited highly variable firing patterns that throughout development became more precise, sparse, and bursty. We further explored how the developing motor program in RA is shaped by its two main inputs: LMAN, the output nucleus of a basal ganglia-forebrain circuit, and HVC, a premotor nucleus. Pharmacological inactivation of LMAN during singing made the song-aligned firing patterns of RA neurons adultlike in their stereotypy without dramatically affecting the spike statistics or the overall firing patterns. Removing the input from HVC, on the other hand, resulted in a complete loss of stereotypy of both the song and the underlying motor program. Thus our results show that a basal ganglia-forebrain circuit drives motor exploration required for trial-and-error learning by adding variability to the developing motor program. As learning proceeds and the motor circuits mature, the relative contribution of LMAN is reduced, allowing the premotor input from HVC to drive an increasingly stereotyped song. PMID:21543758

Anomalous Putamen Volume in Children With Complex Motor Stereotypies.

PubMed

Mahone, E Mark; Crocetti, Deana; Tochen, Laura; Kline, Tina; Mostofsky, Stewart H; Singer, Harvey S

2016-12-01

Complex motor stereotypies in children are repetitive rhythmic movements that have a predictable pattern and location, seem purposeful, but serve no obvious function, tend to be prolonged, and stop with distraction, e.g., arm or hand flapping, waving. They occur in both "primary" (otherwise typically developing) and secondary conditions. These movements are best defined as habitual behaviors and therefore pathophysiologically hypothesized to reside in premotor to posterior putamen circuits. This study sought to clarify the underlying neurobiologic abnormality in children with primary complex motor stereotypies using structural neuroimaging, emphasizing brain regions hypothesized to underlie these atypical behaviors. High-resolution anatomic magnetic resonance images, acquired at 3.0 T, were analyzed in children aged eight to twelve years (20 with primary complex motor stereotypies and 20 typically developing). Frontal lobe subregions and striatal structures were delineated for analysis. Significant reductions (P = 0.045) in the stereotypies group were identified in total putamen volume but not in caudate, nucleus accumbens, or frontal subregions. There were no group differences in total cerebral volume. Findings of a smaller putamen provide preliminary evidence suggesting the potential involvement of the habitual pathway as the underlying anatomic site in primary complex motor stereotypies. Copyright © 2016 Elsevier Inc. All rights reserved.

Perineurial Glial Plasticity and the Role of TGF-β in the Development of the Blood-Nerve Barrier.

PubMed

Morris, Angela D; Lewis, Gwendolyn M; Kucenas, Sarah

2017-05-03

Precisely orchestrated interactions between spinal motor axons and their ensheathing glia are vital for forming and maintaining functional spinal motor nerves. Following perturbations to peripheral myelinating glial cells, centrally derived oligodendrocyte progenitor cells (OPCs) ectopically exit the spinal cord and myelinate peripheral nerves in myelin with CNS characteristics. However, whether remaining peripheral ensheathing glia, such as perineurial glia, properly encase the motor nerve despite this change in glial cell and myelin composition, remains unknown. Using zebrafish mutants in which OPCs migrate out of the spinal cord and myelinate peripheral motor axons, we assayed perineurial glial development, maturation, and response to injury. Surprisingly, in the presence of OPCs, perineurial glia exited the CNS normally. However, aspects of their development, response to injury, and function were altered compared with wildtype larvae. In an effort to better understand the plasticity of perineurial glia in response to myelin perturbations, we identified transforming growth factor-β1 as a partial mediator of perineurial glial development. Together, these results demonstrate the incredible plasticity of perineurial glia in the presence of myelin perturbations. SIGNIFICANCE STATEMENT Peripheral neuropathies can result from damage or dysregulation of the insulating myelin sheath surrounding spinal motor axons, causing pain, inefficient nerve conduction, and the ectopic migration of oligodendrocyte progenitor cells (OPCs), the resident myelinating glial cell of the CNS, into the periphery. How perineurial glia, the ensheathing cells that form the protective blood-nerve barrier, are impacted by this myelin composition change is unknown. Here, we report that certain aspects of perineurial glial development and injury responses are mostly unaffected in the presence of ectopic OPCs. However, perineurial glial function is disrupted along nerves containing centrally derived myelin, demonstrating that, although perineurial glial cells display plasticity despite myelin perturbations, the blood-nerve barrier is compromised in the presence of ectopic OPCs. Copyright © 2017 the authors 0270-6474/17/374790-18$15.00/0.

Effect of intravenous amino acids on interdigestive antroduodenal motility and small bowel transit time.

PubMed

Gielkens, H A; van den Biggelaar, A; Vecht, J; Onkenhout, W; Lamers, C B; Masclee, A A

1999-02-01

Patients on total parenteral nutrition have an increased risk of developing gallstones because of gall bladder hypomotility. High dose amino acids may prevent biliary stasis by stimulating gall bladder emptying. To investigate whether intravenous amino acids also influence antroduodenal motility. Eight healthy volunteers received, on three separate occasions, intravenous saline (control), low dose amino acids (LDA), or high dose amino acids (HDA). Antroduodenal motility was recorded by perfusion manometry and duodenocaecal transit time (DCTT) using the lactulose breath hydrogen test. DCTT was significantly prolonged during LDA and HDA treatment compared with control. The interdigestive motor pattern was maintained and migrating motor complex (MMC) cycle length was significantly reduced during HDA compared with control and LDA due to a significant reduction in phase II duration. Significantly fewer phase IIIs originated in the gastric antrum during LDA and HDA compared with control. Duodenal phase II motility index was significantly reduced during HDA, but not during LDA, compared with control. Separate intravenous infusion of high doses of amino acids in healthy volunteers: (1) modulates interdigestive antroduodenal motility; (2) shortens MMC cycle length due to a reduced duration of phase II with a lower contractile incidence both in the antrum and duodenum (phase I remains unchanged whereas the effect on phase III is diverse: in the antrum phase III is suppressed and in the duodenum the frequency is increased); and (3) prolongs interdigestive DCTT.

Normal and impaired charge transport in biological systems

NASA Astrophysics Data System (ADS)

Miller, John H.; Villagrán, Martha Y. Suárez; Maric, Sladjana; Briggs, James M.

2015-03-01

We examine the physics behind some of the causes (e.g., hole migration and localization that cause incorrect base pairing in DNA) and effects (due to amino acid replacements affecting mitochondrial charge transport) of disease-implicated point mutations, with emphasis on mutations affecting mitochondrial DNA (mtDNA). First we discuss hole transport and localization in DNA, including some of our quantum mechanical modeling results, as they relate to certain mutations in cancer. Next, we give an overview of electron and proton transport in the mitochondrial electron transport chain, and how such transport can become impaired by mutations implicated in neurodegenerative diseases, cancer, and other major illnesses. In particular, we report on our molecular dynamics (MD) studies of a leucine→arginine amino acid replacement in ATP synthase, encoded by the T→G point mutation at locus 8993 of mtDNA. This mutation causes Leigh syndrome, a devastating maternally inherited neuromuscular disorder, and has been found to trigger rapid tumor growth in prostate cancer cell lines. Our MD results suggest, for the first time, that this mutation adversely affects water channels that transport protons to and from the c-ring of the rotary motor ATP synthase, thus impairing the ability of the motor to produce ATP. Finally, we discuss possible future research topics for biological physics, such as mitochondrial complex I, a large proton-pumping machine whose physics remains poorly understood.

The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled

PubMed Central

Gupta, Tripti; Kumar, Arun; Cattenoz, Pierre B.; VijayRaghavan, K; Giangrande, Angela

2016-01-01

Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination. DOI: http://dx.doi.org/10.7554/eLife.15983.001 PMID:27740455

Integrative Mechanisms of Oriented Neuronal Migration in the Developing Brain

PubMed Central

Evsyukova, Irina; Plestant, Charlotte; Anton, E.S.

2014-01-01

The emergence of functional neuronal connectivity in the developing cerebral cortex depends on neuronal migration. This process enables appropriate positioning of neurons and the emergence of neuronal identity so that the correct patterns of functional synaptic connectivity between the right types and numbers of neurons can emerge. Delineating the complexities of neuronal migration is critical to our understanding of normal cerebral cortical formation and neurodevelopmental disorders resulting from neuronal migration defects. For the most part, the integrated cell biological basis of the complex behavior of oriented neuronal migration within the developing mammalian cerebral cortex remains an enigma. This review aims to analyze the integrative mechanisms that enable neurons to sense environmental guidance cues and translate them into oriented patterns of migration toward defined areas of the cerebral cortex. We discuss how signals emanating from different domains of neurons get integrated to control distinct aspects of migratory behavior and how different types of cortical neurons coordinate their migratory activities within the developing cerebral cortex to produce functionally critical laminar organization. PMID:23937349

Simple Microfluidic Device For Studying Chemotaxis In Response To Dual Gradients

PubMed Central

Moussavi-Haramic, S. F.; Pezzi, H. M.; Huttenlocher, A.; Beebe, D. J.

2016-01-01

Chemotaxis is a fundamental biological process where complex chemotactic gradients are integrated and prioritized to guide cell migration toward specific locations. To understand the mechanisms of gradient dependent cell migration, it is important to develop in vitro models that recapitulate key attributes of the chemotactic cues present in vivo. Current in vitro tools for studying cell migration are not amenable to easily study the response of neutrophils to dual gradients. Many of these systems require external pumps and complex setups to establish and maintain the gradients. Here we report a simple yet innovative microfluidic device for studying cell migration in the presence of dual chemotactic gradients through a 3-dimensional substrate. The device is tested and validated by studying the migration of the neutrophil-like cell line PLB-985 to gradients of fMLP. Furthermore, the device is expanded and used with heparinised whole blood, whereupon neutrophils were observed to migrate from whole blood towards gradients of fMLP eliminating the need for any neutrophil purification or capture steps. PMID:25893484

Is Validation Always Valid? Cross-Cultural Complexities of Standard-Based Instruments Migrating out of Their Context

ERIC Educational Resources Information Center

Pastori, Giulia; Pagani, Valentina

2017-01-01

The international application of standard-based measures to assess ECEC quality raises crucial questions concerning the cultural complexities and the problematic validity of instruments migrating out of their cultural cradle; nevertheless the topic has received only marginal attention in the literature. This paper, which aims to address this gap,…

Age differences in the motor control of speech: An fMRI study of healthy aging.

PubMed

Tremblay, Pascale; Sato, Marc; Deschamps, Isabelle

2017-05-01

Healthy aging is associated with a decline in cognitive, executive, and motor processes that are concomitant with changes in brain activation patterns, particularly at high complexity levels. While speech production relies on all these processes, and is known to decline with age, the mechanisms that underlie these changes remain poorly understood, despite the importance of communication on everyday life. In this cross-sectional group study, we investigated age differences in the neuromotor control of speech production by combining behavioral and functional magnetic resonance imaging (fMRI) data. Twenty-seven healthy adults underwent fMRI while performing a speech production task consisting in the articulation of nonwords of different sequential and motor complexity. Results demonstrate strong age differences in movement time (MT), with longer and more variable MT in older adults. The fMRI results revealed extensive age differences in the relationship between BOLD signal and MT, within and outside the sensorimotor system. Moreover, age differences were also found in relation to sequential complexity within the motor and attentional systems, reflecting both compensatory and de-differentiation mechanisms. At very high complexity level (high motor complexity and high sequence complexity), age differences were found in both MT data and BOLD response, which increased in several sensorimotor and executive control areas. Together, these results suggest that aging of motor and executive control mechanisms may contribute to age differences in speech production. These findings highlight the importance of studying functionally relevant behavior such as speech to understand the mechanisms of human brain aging. Hum Brain Mapp 38:2751-2771, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats.

PubMed

Urakawa, S; Hida, H; Masuda, T; Misumi, S; Kim, T-S; Nishino, H

2007-02-09

Rats raised in an enriched environment (enriched rats) have been reported to show less motor dysfunction following brain lesions, but the neuronal correlates of this improvement have not been well clarified. The present study aimed to elucidate the effect of chemical brain lesions and environmental enrichment on motor function and lesion-induced neurogenesis. Three week-old, recently weaned rats were divided into two groups: one group was raised in an enriched environment and the other group was raised in a standard cage for 5 weeks. Striatal damage was induced at an age of 8 weeks by injection of the neuro-toxins 6-hydroxydopamine (6-OHDA) or quinolinic acid (QA) into the striatum, or by injection of 6-OHDA into the substantia nigra (SN), which depleted nigrostriatal dopaminergic innervation. Enriched rats showed better performance on beam walking compared with those raised in standard conditions, but both groups showed similar forelimb use asymmetry in a cylinder test. The number of bromodeoxyuridine-labeled proliferating cells in the subventricular zone was increased by a severe striatal lesion induced by QA injection 1 week after the lesion, but decreased by injection of 6-OHDA into the SN. Following induction of lesions by striatal injection of 6-OHDA or QA, the number of cells positive for doublecortin (DCX) was strongly increased in the striatum; however, there was no change in the number of DCX-positive cells following 6-OHDA injection into the SN. Environmental enrichment enhanced the increase of DCX-positive cells with migrating morphology in the dorsal striatum. In enriched rats, DCX-positive cells traversed the striatal parenchyma far from the corpus callosum and lateral ventricle. DCX-positive cells co-expressed an immature neuronal marker, polysialylated neural cell adhesion molecule, but were negative for a glial marker. These data suggest that environmental enrichment improves motor performance on beam walking and enhances neuronal migration toward a lesion area in the striatum.

Respiratory chain deficiency in aged spinal motor neurons☆

PubMed Central

Rygiel, Karolina A.; Grady, John P.; Turnbull, Doug M.

2014-01-01

Sarcopenia, muscle wasting, and strength decline with age, is an important cause of loss of mobility in the elderly individuals. The underlying mechanisms are uncertain but likely to involve defects of motor nerve, neuromuscular junction, and muscle. Loss of motor neurons with age and subsequent denervation of skeletal muscle has been recognized as one of the contributing factors. This study investigated aspects of mitochondrial biology in spinal motor neurons from elderly subjects. We found that protein components of complex I of mitochondrial respiratory chain were reduced or absent in a proportion of aged motor neurons–a phenomenon not observed in fetal tissue. Further investigation showed that complex I-deficient cells had reduced mitochondrial DNA content and smaller soma size. We propose that mitochondrial dysfunction in these motor neurons could lead to the cell loss and ultimately denervation of muscle fibers. PMID:24684792

Computational Modeling of Single-Cell Migration: The Leading Role of Extracellular Matrix Fibers

PubMed Central

Schlüter, Daniela K.; Ramis-Conde, Ignacio; Chaplain, Mark A.J.

2012-01-01

Cell migration is vitally important in a wide variety of biological contexts ranging from embryonic development and wound healing to malignant diseases such as cancer. It is a very complex process that is controlled by intracellular signaling pathways as well as the cell’s microenvironment. Due to its importance and complexity, it has been studied for many years in the biomedical sciences, and in the last 30 years it also received an increasing amount of interest from theoretical scientists and mathematical modelers. Here we propose a force-based, individual-based modeling framework that links single-cell migration with matrix fibers and cell-matrix interactions through contact guidance and matrix remodelling. With this approach, we can highlight the effect of the cell’s environment on its migration. We investigate the influence of matrix stiffness, matrix architecture, and cell speed on migration using quantitative measures that allow us to compare the results to experiments. PMID:22995486

Microtubule minus end motors kinesin-14 and dynein drive nuclear congression in parallel pathways

PubMed Central

Scheffler, Kathleen; Minnes, Refael; Fraisier, Vincent; Paoletti, Anne

2015-01-01

Microtubules (MTs) and associated motors play a central role in nuclear migration, which is crucial for diverse biological functions including cell division, polarity, and sexual reproduction. In this paper, we report a dual mechanism underlying nuclear congression during fission yeast karyogamy upon mating of haploid cells. Using microfluidic chambers for long-term imaging, we captured the precise timing of nuclear congression and identified two minus end–directed motors operating in parallel in this process. Kinesin-14 Klp2 associated with MTs may cross-link and slide antiparallel MTs emanating from the two nuclei, whereas dynein accumulating at spindle pole bodies (SPBs) may pull MTs nucleated from the opposite SPB. Klp2-dependent nuclear congression proceeds at constant speed, whereas dynein accumulation results in an increase of nuclear velocity over time. Surprisingly, the light intermediate chain Dli1, but not dynactin, is required for this previously unknown function of dynein. We conclude that efficient nuclear congression depends on the cooperation of two minus end–directed motors. PMID:25869666

Effects of glutamine on gastrointestinal motor activity in patients following gastric surgery.

PubMed

Mochiki, Erito; Ohno, Tetsuro; Yanai, Mitsuhiro; Toyomasu, Yoshitaka; Andoh, Hiroyuki; Kuwano, Hiroyuki

2011-04-01

Postoperative ileus (POI) is one of the most common complications of gastrointestinal surgery. The present study was performed to evaluate the effects of glutamine administration on POI after gastric surgery in humans. The subjects were 31 patients who underwent partial distal gastrectomy for gastric cancer and who were randomly assigned to one of two groups based on postoperative treatment: the glutamine group (3 g/day) and the control group. Manometric recording was done 12 days after surgery, and plasma glutamine concentrations were measured preoperatively and on postoperative day 12. Motor activities of the duodenum in the glutamine group were significantly greater than those of the control group in the interdigestive state. The incidence of phase III motor activity (interdigestive migrating motor contractions) in the glutamine group was significantly higher than that in the control group (60 versus 19%). The glutamine group showed a significantly smaller decrease of plasma glutamine levels compared with the control group. Glutamine could act as a motility-recovery agent after gastrectomy in humans.

A Hopping Mechanism for Cargo Transport by Molecular Motors on Crowded Microtubules

NASA Astrophysics Data System (ADS)

Goldman, Carla

2010-05-01

Most models designed to study the bidirectional movement of cargos as they are driven by molecular motors rely on the idea that motors of different polarities can be coordinated by external agents if arranged into a motor-cargo complex to perform the necessary work Gross, Hither and yon: a review of bidirectional microtubule-based transport (Gross in Phys. Biol. 1:R1-R11, 2004). Although these models have provided us with important insights into these phenomena, there are still many unanswered questions regarding the mechanisms through which the movement of the complex takes place on crowded microtubules. For example (i) how does cargo-binding affect motor motility? and in connection with that - (ii) how does the presence of other motors (and also other cargos) on the microtubule affect the motility of the motor-cargo complex? We discuss these questions from a different perspective. The movement of a cargo is conceived here as a hopping process resulting from the transference of cargo between neighboring motors. In the light of this, we examine the conditions under which cargo might display bidirectional movement even if directed by motors of a single polarity. The global properties of the model in the long-time regime are obtained by mapping the dynamics of the collection of interacting motors and cargos into an asymmetric simple exclusion process (ASEP) which can be resolved using the matrix ansatz introduced by Derrida (Derrida and Evans in Nonequilibrium Statistical Mechanics in One Dimension, pp. 277-304, 1997; Derrida et al. in J. Phys. A 26:1493-1517, 1993).

Fused cerebral organoids model interactions between brain regions.

PubMed

Bagley, Joshua A; Reumann, Daniel; Bian, Shan; Lévi-Strauss, Julie; Knoblich, Juergen A

2017-07-01

Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.

Role of coordination geometry in dictating the barrier to hydride migration in d6 square-pyramidal iridium and rhodium pincer complexes.

PubMed

Findlater, Michael; Cartwright-Sykes, Alison; White, Peter S; Schauer, Cynthia K; Brookhart, Maurice

2011-08-10

Syntheses of the olefin hydride complexes [(POCOP)M(H)(olefin)][BAr(f)(4)] (6a-M, M = Ir or Rh, olefin = C(2)H(4); 6b-M, M = Ir or Rh, olefin = C(3)H(6); POCOP = 2,6-bis(di-tert-butylphosphinito)benzene; BAr(f) = tetrakis(3,5-trifluoromethylphenyl)borate) are reported. A single-crystal X-ray structure determination of 6b-Ir shows a square-pyramidal coordination geometry for Ir, with the hydride ligand occupying the apical position. Dynamic NMR techniques were used to characterize these complexes. The rates of site exchange between the hydride and the olefinic hydrogens yielded ΔG(++) = 15.6 (6a-Ir), 16.8 (6b-Ir), 12.0 (6a-Rh), and 13.7 (6b-Rh) kcal/mol. The NMR exchange data also established that hydride migration in the propylene complexes yields exclusively the primary alkyl intermediate arising from 1,2-insertion. Unexpectedly, no averaging of the top and bottom faces of the square-pyramidal complexes is observed in the NMR spectra at high temperatures, indicating that the barrier for facial equilibration is >20 kcal/mol for both the Ir and Rh complexes. A DFT computational study was used to characterize the free energy surface for the hydride migration reactions. The classical terminal hydride complexes, [M(POCOP)(olefin)H](+), are calculated to be the global minima for both Rh and Ir, in accord with experimental results. In both the Rh ethylene and propylene complexes, the transition state for hydride migration (TS1) to form the agostic species is higher on the energy surface than the transition state for in-place rotation of the coordinated C-H bond (TS2), while for Ir, TS2 is the high point on the energy surface. Therefore, only for the case of the Rh complexes is the NMR exchange rate a direct measure of the hydride migration barrier. The trends in the experimental barriers as a function of M and olefin are in good agreement with the trends in the calculated exchange barriers. The calculated barriers for the hydride migration reaction in the Rh complexes are ∼2 kcal/mol higher than for the Ir complexes, despite the fact that the energy difference between the olefin hydride ground state and the agostic alkyl structure is ∼4 kcal/mol larger for Ir than for Rh. This feature, together with the high barrier for interchange of the top and bottom faces of the complexes, is proposed to arise from the unique coordination geometry of the agostic complexes and the strong preference for a cis-divacant octahedral geometry in four-coordinate intermediates. © 2011 American Chemical Society

Space exploration by dendritic cells requires maintenance of myosin II activity by IP3 receptor 1

PubMed Central

Solanes, Paola; Heuzé, Mélina L; Maurin, Mathieu; Bretou, Marine; Lautenschlaeger, Franziska; Maiuri, Paolo; Terriac, Emmanuel; Thoulouze, Maria-Isabel; Launay, Pierre; Piel, Matthieu; Vargas, Pablo; Lennon-Duménil, Ana-Maria

2015-01-01

Dendritic cells (DCs) patrol the interstitial space of peripheral tissues. The mechanisms that regulate their migration in such constrained environment remain unknown. We here investigated the role of calcium in immature DCs migrating in confinement. We found that they displayed calcium oscillations that were independent of extracellular calcium and more frequently observed in DCs undergoing strong speed fluctuations. In these cells, calcium spikes were associated with fast motility phases. IP3 receptors (IP3Rs) channels, which allow calcium release from the endoplasmic reticulum, were identified as required for immature DCs to migrate at fast speed. The IP3R1 isoform was further shown to specifically regulate the locomotion persistence of immature DCs, that is, their capacity to maintain directional migration. This function of IP3R1 results from its ability to control the phosphorylation levels of myosin II regulatory light chain (MLC) and the back/front polarization of the motor protein. We propose that by upholding myosin II activity, constitutive calcium release from the ER through IP3R1 maintains DC polarity during migration in confinement, facilitating the exploration of their environment. PMID:25637353

Space exploration by dendritic cells requires maintenance of myosin II activity by IP3 receptor 1.

PubMed

Solanes, Paola; Heuzé, Mélina L; Maurin, Mathieu; Bretou, Marine; Lautenschlaeger, Franziska; Maiuri, Paolo; Terriac, Emmanuel; Thoulouze, Maria-Isabel; Launay, Pierre; Piel, Matthieu; Vargas, Pablo; Lennon-Duménil, Ana-Maria

2015-03-12

Dendritic cells (DCs) patrol the interstitial space of peripheral tissues. The mechanisms that regulate their migration in such constrained environment remain unknown. We here investigated the role of calcium in immature DCs migrating in confinement. We found that they displayed calcium oscillations that were independent of extracellular calcium and more frequently observed in DCs undergoing strong speed fluctuations. In these cells, calcium spikes were associated with fast motility phases. IP₃ receptors (IP₃Rs) channels, which allow calcium release from the endoplasmic reticulum, were identified as required for immature DCs to migrate at fast speed. The IP₃R1 isoform was further shown to specifically regulate the locomotion persistence of immature DCs, that is, their capacity to maintain directional migration. This function of IP₃R1 results from its ability to control the phosphorylation levels of myosin II regulatory light chain (MLC) and the back/front polarization of the motor protein. We propose that by upholding myosin II activity, constitutive calcium release from the ER through IP₃R1 maintains DC polarity during migration in confinement, facilitating the exploration of their environment. © 2015 Institut Curie/Inserm. Published under the terms of the CC BY NC ND 4.0 license.

Acquisition of Internal Models of Motor Tasks in Children with Autism

ERIC Educational Resources Information Center

Gidley Larson, Jennifer C.; Bastian, Amy J.; Donchin, Opher; Shadmehr, Reza; Mostofsky, Stewart H.

2008-01-01

Children with autism exhibit a host of motor disorders including poor coordination, poor tool use and delayed learning of complex motor skills like riding a tricycle. Theory suggests that one of the crucial steps in motor learning is the ability to form internal models: to predict the sensory consequences of motor commands and learn from errors to…

The relationship between motor skills and cognitive skills in 4-16 year old typically developing children: A systematic review.

PubMed

van der Fels, Irene M J; Te Wierike, Sanne C M; Hartman, Esther; Elferink-Gemser, Marije T; Smith, Joanne; Visscher, Chris

2015-11-01

This review aims to give an overview of studies providing evidence for a relationship between motor and cognitive skills in typically developing children. A systematic review. PubMed, Web of Science, and PsychINFO were searched for relevant articles. A total of 21 articles were included in this study. Methodological quality was independently assessed by two reviewers. Motor and cognitive skills were divided into six categories. There was either no correlation in the literature, or insufficient evidence for or against many correlations between motor skills and cognitive skills. However, weak-to-strong evidence was found for some correlations between underlying categories of motor and cognitive skills, including complex motor skills and higher order cognitive skills. Furthermore, a stronger relationship between underlying categories of motor and cognitive skills was found in pre-pubertal children compared to pubertal children (older than 13 years). Weak-to-strong relations were found between some motor and cognitive skills. The results suggest that complex motor intervention programs can be used to stimulate both motor and higher order cognitive skills in pre-pubertal children. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

LKB1 signaling in cephalic neural crest cells is essential for vertebrate head development.

PubMed

Creuzet, Sophie E; Viallet, Jean P; Ghawitian, Maya; Torch, Sakina; Thélu, Jacques; Alrajeh, Moussab; Radu, Anca G; Bouvard, Daniel; Costagliola, Floriane; Borgne, Maïlys Le; Buchet-Poyau, Karine; Aznar, Nicolas; Buschlen, Sylvie; Hosoya, Hiroshi; Thibert, Chantal; Billaud, Marc

2016-10-15

Head development in vertebrates proceeds through a series of elaborate patterning mechanisms and cell-cell interactions involving cephalic neural crest cells (CNCC). These cells undergo extensive migration along stereotypical paths after their separation from the dorsal margins of the neural tube and they give rise to most of the craniofacial skeleton. Here, we report that the silencing of the LKB1 tumor suppressor affects the delamination of pre-migratory CNCC from the neural primordium as well as their polarization and survival, thus resulting in severe facial and brain defects. We further show that LKB1-mediated effects on the development of CNCC involve the sequential activation of the AMP-activated protein kinase (AMPK), the Rho-dependent kinase (ROCK) and the actin-based motor protein myosin II. Collectively, these results establish that the complex morphogenetic processes governing head formation critically depends on the activation of the LKB1 signaling network in CNCC. Copyright © 2016 Elsevier Inc. All rights reserved.

Hox paralog group 2 genes control the migration of mouse pontine neurons through slit-robo signaling.

PubMed

Geisen, Marc J; Di Meglio, Thomas; Pasqualetti, Massimo; Ducret, Sebastien; Brunet, Jean-François; Chedotal, Alain; Rijli, Filippo M

2008-06-10

The pontine neurons (PN) represent a major source of mossy fiber projections to the cerebellum. During mouse hindbrain development, PN migrate tangentially and sequentially along both the anteroposterior (AP) and dorsoventral (DV) axes. Unlike DV migration, which is controlled by the Netrin-1/Dcc attractive pathway, little is known about the molecular mechanisms guiding PN migration along the AP axis. Here, we show that Hoxa2 and Hoxb2 are required both intrinsically and extrinsically to maintain normal AP migration of subsets of PN, by preventing their premature ventral attraction towards the midline. Moreover, the migration defects observed in Hoxa2 and Hoxb2 mutant mice were phenocopied in compound Robo1;Robo2, Slit1;Slit2, and Robo2;Slit2 knockout animals, indicating that these guidance molecules act downstream of Hox genes to control PN migration. Indeed, using chromatin immunoprecipitation assays, we further demonstrated that Robo2 is a direct target of Hoxa2 in vivo and that maintenance of high Robo and Slit expression levels was impaired in Hoxa2 mutant mice. Lastly, the analysis of Phox2b-deficient mice indicated that the facial motor nucleus is a major Slit signaling source required to prevent premature ventral migration of PN. These findings provide novel insights into the molecular control of neuronal migration from transcription factor to regulation of guidance receptor and ligand expression. Specifically, they address the question of how exposure to multiple guidance cues along the AP and DV axes is regulated at the transcriptional level and in turn translated into stereotyped migratory responses during tangential migration of neurons in the developing mammalian brain.

Hox Paralog Group 2 Genes Control the Migration of Mouse Pontine Neurons through Slit-Robo Signaling

PubMed Central

Pasqualetti, Massimo; Ducret, Sebastien; Brunet, Jean-François; Chedotal, Alain; Rijli, Filippo M

2008-01-01

The pontine neurons (PN) represent a major source of mossy fiber projections to the cerebellum. During mouse hindbrain development, PN migrate tangentially and sequentially along both the anteroposterior (AP) and dorsoventral (DV) axes. Unlike DV migration, which is controlled by the Netrin-1/Dcc attractive pathway, little is known about the molecular mechanisms guiding PN migration along the AP axis. Here, we show that Hoxa2 and Hoxb2 are required both intrinsically and extrinsically to maintain normal AP migration of subsets of PN, by preventing their premature ventral attraction towards the midline. Moreover, the migration defects observed in Hoxa2 and Hoxb2 mutant mice were phenocopied in compound Robo1;Robo2, Slit1;Slit2, and Robo2;Slit2 knockout animals, indicating that these guidance molecules act downstream of Hox genes to control PN migration. Indeed, using chromatin immunoprecipitation assays, we further demonstrated that Robo2 is a direct target of Hoxa2 in vivo and that maintenance of high Robo and Slit expression levels was impaired in Hoxa2 mutant mice. Lastly, the analysis of Phox2b-deficient mice indicated that the facial motor nucleus is a major Slit signaling source required to prevent premature ventral migration of PN. These findings provide novel insights into the molecular control of neuronal migration from transcription factor to regulation of guidance receptor and ligand expression. Specifically, they address the question of how exposure to multiple guidance cues along the AP and DV axes is regulated at the transcriptional level and in turn translated into stereotyped migratory responses during tangential migration of neurons in the developing mammalian brain. PMID:18547144

Global migration and health: ecofeminist perspectives.

PubMed

McGuire, S

1998-12-01

Global migration is occurring at an unprecedented rate. The phenomenon of migration is complex and poorly understood by most people in countries who host immigrants. People migrate for numerous reasons related to social, economic, political, cultural, and physical environmental conditions formed by historical antecedents. Migrating people, especially vulnerable women and children, are exposed to numerous health hazards, a situation calling for a response from nursing. To respond effectively nursing needs knowledge development of global migration and health that includes the precursors to migration in addition to the postmigration experience where nurses encounter immigrants. Ecofeminist perspectives allowing for reflection on historical determinants and interlocking socioeconomic, political, and environmental conditions are used as a prism to examine global migration and health.

Modeling radionuclide migration from underground nuclear explosions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harp, Dylan Robert; Stauffer, Philip H.; Viswanathan, Hari S.

2017-03-06

The travel time of radionuclide gases to the ground surface in fracture rock depends on many complex factors. Numerical simulators are the most complete repositories of knowledge of the complex processes governing radionuclide gas migration to the ground surface allowing us to verify conceptualizations of physical processes against observations and forecast radionuclide gas travel times to the ground surface and isotopic ratios

Doxycycline reduces the migration of tuberous sclerosis complex-2 null cells - effects on RhoA-GTPase and focal adhesion kinase

PubMed Central

Ng, Ho Yin; Oliver, Brian Gregory George; Burgess, Janette Kay; Krymskaya, Vera P; Black, Judith Lee; Moir, Lyn M

2015-01-01

Lymphangioleiomyomatosis (LAM) is associated with dysfunction of the tuberous sclerosis complex (TSC) leading to enhanced cell proliferation and migration. This study aims to examine whether doxycycline, a tetracycline antibiotic, can inhibit the enhanced migration of TSC2-deficient cells, identify signalling pathways through which doxycycline works and to assess the effectiveness of combining doxycycline with rapamycin (mammalian target of rapamycin complex 1 inhibitor) in controlling cell migration, proliferation and wound closure. TSC2-positive and TSC2-negative mouse embryonic fibroblasts (MEF), 323-TSC2-positive and 323-TSC2-null MEF and Eker rat uterine leiomyoma (ELT3) cells were treated with doxycycline or rapamycin alone, or in combination. Migration, wound closure and proliferation were assessed using a transwell migration assay, time-lapse microscopy and manual cell counts respectively. RhoA-GTPase activity, phosphorylation of p70S6 kinase (p70S6K) and focal adhesion kinase (FAK) in TSC2-negative MEF treated with doxycycline were examined using ELISA and immunoblotting techniques. The enhanced migration of TSC2-null cells was reduced by doxycycline at concentrations as low as 20 pM, while the rate of wound closure was reduced at 2–59 μM. Doxycycline decreased RhoA-GTPase activity and phosphorylation of FAK in these cells but had no effect on the phosphorylation of p70S6K, ERK1/2 or AKT. Combining doxycycline with rapamycin significantly reduced the rate of wound closure at lower concentrations than achieved with either drug alone. This study shows that doxycycline inhibits TSC2-null cell migration. Thus doxycycline has potential as an anti-migratory agent in the treatment of diseases with TSC2 dysfunction. PMID:26282580

The Spatial Structure of Planform Migration - Curvature Relation of Meandering Rivers

NASA Astrophysics Data System (ADS)

Guneralp, I.; Rhoads, B. L.

2005-12-01

Planform dynamics of meandering rivers have been of fundamental interest to fluvial geomorphologists and engineers because of the intriguing complexity of these dynamics, the role of planform change in floodplain development and landscape evolution, and the economic and social consequences of bank erosion and channel migration. Improved understanding of the complex spatial structure of planform change and capacity to predict these changes are important for effective stream management, engineering and restoration. The planform characteristics of a meandering river channel are integral to its planform dynamics. Active meandering rivers continually change their positions and shapes as a consequence of hydraulic forces exerted on the channel banks and bed, but as the banks and bed change through sediment transport, so do the hydraulic forces. Thus far, this complex feedback between form and process is incompletely understood, despite the fact that the characteristics and the dynamics of meandering rivers have been studied extensively. Current theoretical models aimed at predicting planform dynamics relate rates of meander migration to local and upstream planform curvature where weighting of the influence of curvature on migration rate decays exponentially over distance. This theoretical relation, however, has not been rigorously evaluated empirically. Furthermore, although models based on exponential-weighting of curvature effects yield fairly realistic predictions of meander migration, such models are incapable of reproducing complex forms of bend development, such as double heading or compound looping. This study presents the development of a new methodology based on parametric cubic spline interpolation for the characterization of channel planform and the planform curvature of meandering rivers. The use of continuous mathematical functions overcomes the reliance on bend-averaged values or piece-wise discrete approximations of planform curvature - a major limitation of previous studies. Continuous curvature series can be related to measured rates of lateral migration to explore empirically the relationship between spatially extended curvature and local bend migration. The methodology is applied to a study reach along a highly sinuous section of the Embarras River in Illinois, USA, which contains double-headed asymmetrical loops. To identify patterns of channel planform and rates of lateral migration for a study reach along Embarrass River in central Illinois, geographical information systems analysis of historical aerial photography over a period from 1936 to 1998 was conducted. Results indicate that parametric cubic spline interpolation provides excellent characterization of the complex planforms and planform curvatures of meandering rivers. The findings also indicate that the spatial structure of migration rate-curvature relation may be more complex than a simple exponential distance-decay function. The study represents a first step toward unraveling the spatial structure of planform evolution of meandering rivers and for developing models of planform dynamics that accurately relate spatially extended patterns of channel curvature to local rates of lateral migration. Such knowledge is vital for improving the capacity to accurately predict planform change of meandering rivers.

Life without double-headed non-muscle myosin II motor proteins

PubMed Central

Betapudi, Venkaiah

2014-01-01

Non-muscle myosin II motor proteins (myosin IIA, myosin IIB, and myosin IIC) belong to a class of molecular motor proteins that are known to transduce cellular free-energy into biological work more efficiently than man-made combustion engines. Nature has given a single myosin II motor protein for lower eukaryotes and multiple for mammals but none for plants in order to provide impetus for their life. These specialized nanomachines drive cellular activities necessary for embryogenesis, organogenesis, and immunity. However, these multifunctional myosin II motor proteins are believed to go awry due to unknown reasons and contribute for the onset and progression of many autosomal-dominant disorders, cataract, deafness, infertility, cancer, kidney, neuronal, and inflammatory diseases. Many pathogens like HIV, Dengue, hepatitis C, and Lymphoma viruses as well as Salmonella and Mycobacteria are now known to take hostage of these dedicated myosin II motor proteins for their efficient pathogenesis. Even after four decades since their discovery, we still have a limited knowledge of how these motor proteins drive cell migration and cytokinesis. We need to enrich our current knowledge on these fundamental cellular processes and develop novel therapeutic strategies to fix mutated myosin II motor proteins in pathological conditions. This is the time to think how to relieve the hijacked myosins from pathogens in order to provide a renewed impetus for patients' life. Understanding how to steer these molecular motors in proliferating and differentiating stem cells will improve stem cell based-therapeutics development. Given the plethora of cellular activities non-muscle myosin motor proteins are involved in, their importance is apparent for human life. PMID:25072053

Life without double-headed non-muscle myosin II motor proteins

NASA Astrophysics Data System (ADS)

Betapudi, Venkaiah

2014-07-01

Non-muscle myosin II motor proteins (myosin IIA, myosin IIB, and myosin IIC) belong to a class of molecular motor proteins that are known to transduce cellular free-energy into biological work more efficiently than man-made combustion engines. Nature has given a single myosin II motor protein for lower eukaryotes and multiple for mammals but none for plants in order to provide impetus for their life. These specialized nanomachines drive cellular activities necessary for embryogenesis, organogenesis, and immunity. However, these multifunctional myosin II motor proteins are believed to go awry due to unknown reasons and contribute for the onset and progression of many autosomal-dominant disorders, cataract, deafness, infertility, cancer, kidney, neuronal, and inflammatory diseases. Many pathogens like HIV, Dengue, hepatitis C, and Lymphoma viruses as well as Salmonella and Mycobacteria are now known to take hostage of these dedicated myosin II motor proteins for their efficient pathogenesis. Even after four decades since their discovery, we still have a limited knowledge of how these motor proteins drive cell migration and cytokinesis. We need to enrich our current knowledge on these fundamental cellular processes and develop novel therapeutic strategies to fix mutated myosin II motor proteins in pathological conditions. This is the time to think how to relieve the hijacked myosins from pathogens in order to provide a renewed impetus for patients’ life. Understanding how to steer these molecular motors in proliferating and differentiating stem cells will improve stem cell based-therapeutics development. Given the plethora of cellular activities non-muscle myosin motor proteins are involved in, their importance is apparent for human life.

Low-Cost Robotic Assessment of Visuo-Motor Deficits in Alzheimer's Disease.

PubMed

Bartoli, Eleonora; Caso, Francesca; Magnani, Giuseppe; Baud-Bovy, Gabriel

2017-07-01

A low-cost robotic interface was used to assess the visuo-motor performance of patients with Alzheimer's disease (AD). Twenty AD patients and twenty age-matched controls participated in this work. The battery of tests included simple reaction times, position tracking, and stabilization tasks performed with both hands. The regularity, velocity, visual and haptic feedback were manipulated to vary movement complexity. Reaction times and movement tracking error were analyzed. Results show a marked group effect on a subset of conditions, in particular when the patients could not rely on the visual feedback of hand movement. The visuo-motor performance correlated with the measures of global cognitive functioning and with different memory-related abilities. Our results support the hypothesis that the ability to recall and use visuo-spatial associations might underlie the impairment in complex motor behavior that has been reported in AD patients. Importantly, the patients had preserved learning effects across sessions, which might relate to visuo-motor deficits being less evident in every-day life and clinical assessments. This robotic assessment, lasting less than 1 h, provides detailed information about the integrity of visuo-motor abilities. The data can aid the understanding of the complex pattern of deficits that characterizes this pervasive disease.

Motor-cognitive dual-task deficits in individuals with early-mid stage Huntington disease.

PubMed

Fritz, Nora E; Hamana, Katy; Kelson, Mark; Rosser, Anne; Busse, Monica; Quinn, Lori

2016-09-01

Huntington disease (HD) results in a range of cognitive and motor impairments that progress throughout the disease stages; however, little research has evaluated specific dual-task abilities in this population, and the degree to which they may be related to functional ability. The purpose of this study was to a) examine simple and complex motor-cognitive dual-task performance in individuals with HD, b) determine relationships between dual-task walking ability and disease-specific measures of motor, cognitive and functional ability, and c) examine the relationship of dual-task measures to falls in individuals with HD. Thirty-two individuals with HD were evaluated for simple and complex dual-task ability using the Walking While Talking Test. Demographics and disease-specific measures of motor, cognitive and functional ability were also obtained. Individuals with HD had impairments in simple and complex dual-task ability. Simple dual-task walking was correlated to disease-specific motor scores as well as cognitive performance, but complex dual-task walking was correlated with total functional capacity, as well as a range of cognitive measures. Number of prospective falls was moderately-strongly correlated to dual-task measures. Our results suggest that individuals with HD have impairments in cognitive-motor dual-task ability that are related to disease progression and specifically functional ability. Dual-task measures appear to evaluate a unique construct in individuals with early to mid-stage HD, and may have value in improving the prediction of falls risk in this population. Copyright © 2016 Elsevier B.V. All rights reserved.

Pressure Oscillations and Structural Vibrations in Space Shuttle RSRM and ETM-3 Motors

NASA Technical Reports Server (NTRS)

Mason, D. R.; Morstadt, R. A.; Cannon, S. M.; Gross, E. G.; Nielsen, D. B.

2004-01-01

The complex interactions between internal motor pressure oscillations resulting from vortex shedding, the motor's internal acoustic modes, and the motor's structural vibration modes were assessed for the Space Shuttle four-segment booster Reusable Solid Rocket Motor and for the five-segment engineering test motor ETM-3. Two approaches were applied 1) a predictive procedure based on numerically solving modal representations of a solid rocket motor s acoustic equations of motion and 2) a computational fluid dynamics two-dimensional axi-symmetric large eddy simulation at discrete motor burn times.

Visualization of Motor Axon Navigation and Quantification of Axon Arborization In Mouse Embryos Using Light Sheet Fluorescence Microscopy.

PubMed

Liau, Ee Shan; Yen, Ya-Ping; Chen, Jun-An

2018-05-11

Spinal motor neurons (MNs) extend their axons to communicate with their innervating targets, thereby controlling movement and complex tasks in vertebrates. Thus, it is critical to uncover the molecular mechanisms of how motor axons navigate to, arborize, and innervate their peripheral muscle targets during development and degeneration. Although transgenic Hb9::GFP mouse lines have long served to visualize motor axon trajectories during embryonic development, detailed descriptions of the full spectrum of axon terminal arborization remain incomplete due to the pattern complexity and limitations of current optical microscopy. Here, we describe an improved protocol that combines light sheet fluorescence microscopy (LSFM) and robust image analysis to qualitatively and quantitatively visualize developing motor axons. This system can be easily adopted to cross genetic mutants or MN disease models with Hb9::GFP lines, revealing novel molecular mechanisms that lead to defects in motor axon navigation and arborization.

Time-lapse microscopy and image processing for stem cell research: modeling cell migration

NASA Astrophysics Data System (ADS)

Gustavsson, Tomas; Althoff, Karin; Degerman, Johan; Olsson, Torsten; Thoreson, Ann-Catrin; Thorlin, Thorleif; Eriksson, Peter

2003-05-01

This paper presents hardware and software procedures for automated cell tracking and migration modeling. A time-lapse microscopy system equipped with a computer controllable motorized stage was developed. The performance of this stage was improved by incorporating software algorithms for stage motion displacement compensation and auto focus. The microscope is suitable for in-vitro stem cell studies and allows for multiple cell culture image sequence acquisition. This enables comparative studies concerning rate of cell splits, average cell motion velocity, cell motion as a function of cell sample density and many more. Several cell segmentation procedures are described as well as a cell tracking algorithm. Statistical methods for describing cell migration patterns are presented. In particular, the Hidden Markov Model (HMM) was investigated. Results indicate that if the cell motion can be described as a non-stationary stochastic process, then the HMM can adequately model aspects of its dynamic behavior.

Intimate partner violence and forced migration during pregnancy: Structural constraints to women's agency.

PubMed

Turan, Janet M; Hatcher, Abigail M; Romito, Patrizia; Mangone, Emily; Durojaiye, Modupeoluwa; Odero, Merab; Camlin, Carol S

2016-01-01

Little is known about migration during pregnancy related to intimate partner violence (IPV). In this paper, we examine issues of agency in relation to pregnant women's migrations in a high HIV prevalence area of Kenya. We qualitatively explored forced migration among pregnant women, using data from in-depth interviews, focus groups and IPV screening forms. To quantitatively examine migration during pregnancy, we analysed data from a prospective study of 614 pregnant women. The qualitative data revealed that women had varied responses to violence in pregnancy, with some being able to leave the marital home voluntarily as a strategy to escape violence. Others were 'sent packing' from their marital homes when they dared to exercise autonomy, in some cases related to HIV status. Quantitative analyses revealed that pregnant women who migrated were more educated, less likely to be living with a partner and had fewer children than other women. Migration among pregnant women in Kenya illustrates the complexity of understanding women's agency in the context of IPV. The findings indicate that there is not a dichotomy between 'victim' and 'agent', but rather a complex dynamic between and within pregnant women, who may sequentially or simultaneously experience aspects of victimhood and/or agentic response.

Proficiency and Linguistic Complexity Influence Speech Motor Control and Performance in Spanish Language Learners

ERIC Educational Resources Information Center

Nip, Ignatius S. B.; Blumenfeld, Henrike K.

2015-01-01

Purpose: Second-language (L2) production requires greater cognitive resources to inhibit the native language and to retrieve less robust lexical representations. The current investigation identifies how proficiency and linguistic complexity, specifically syntactic and lexical factors, influence speech motor control and performance. Method: Speech…

Conservation physiology of animal migration

PubMed Central

Lennox, Robert J.; Chapman, Jacqueline M.; Souliere, Christopher M.; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D.; Cooke, Steven J.

2016-01-01

Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains because of the complexity of biological systems, the inherently dynamic nature of the environment and the scale at which many migrations occur and associated threats operate, necessitating improved integration of physiological approaches to the conservation of migratory animals. PMID:27293751

Conservation physiology of animal migration.

PubMed

Lennox, Robert J; Chapman, Jacqueline M; Souliere, Christopher M; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D; Cooke, Steven J

2016-01-01

Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains because of the complexity of biological systems, the inherently dynamic nature of the environment and the scale at which many migrations occur and associated threats operate, necessitating improved integration of physiological approaches to the conservation of migratory animals.

Using Video Game Telemetry Data to Research Motor Chunking, Action Latencies, and Complex Cognitive-Motor Skill Learning.

PubMed

Thompson, Joseph J; McColeman, C M; Stepanova, Ekaterina R; Blair, Mark R

2017-04-01

Many theories of complex cognitive-motor skill learning are built on the notion that basic cognitive processes group actions into easy-to-perform sequences. The present work examines predictions derived from laboratory-based studies of motor chunking and motor preparation using data collected from the real-time strategy video game StarCraft 2. We examined 996,163 action sequences in the telemetry data of 3,317 players across seven levels of skill. As predicted, the latency to the first action (thought to be the beginning of a chunked sequence) is delayed relative to the other actions in the group. Other predictions, inspired by the memory drum theory of Henry and Rogers, received only weak support. Copyright © 2017 Cognitive Science Society, Inc.

Migrating Legacy Systems in the Global Merger & Acquisition Environment

ERIC Educational Resources Information Center

Katerattanakul, Pairin; Kam, Hwee-Joo; Lee, James J.; Hong, Soongoo

2009-01-01

The MetaFrame system migration project at WorldPharma, while driven by merger and acquisition, had faced complexities caused by both technical challenges and organizational issues in the climate of uncertainties. However, WorldPharma still insisted on instigating this post-merger system migration project. This project served to (1) consolidate the…

Tumor cell migration in complex microenvironments

PubMed Central

Polacheck, William J.; Zervantonakis, Ioannis K.; Kamm, Roger D.

2012-01-01

Tumor cell migration is essential for invasion and dissemination from primary solid tumors and for the establishment of lethal secondary metastases at distant organs. In vivo and in vitro models enabled identification of different factors in the tumor microenvironment that regulate tumor progression and metastasis. However, the mechanisms by which tumor cells integrate these chemical and mechanical signals from multiple sources to navigate the complex microenvironment remain poorly understood. In this review, we discuss the factors that influence tumor cell migration with a focus on the migration of transformed carcinoma cells. We provide an overview of the experimental and computational methods that allow the investigation of tumor cell migration, and we highlight the benefits and shortcomings of the various assays. We emphasize that the chemical and mechanical stimulus paradigms are not independent and that crosstalk between them motivates the development of new assays capable of applying multiple, simultaneous stimuli and imaging the cellular migratory response in real-time. These next-generation assays will more closely mimic the in vivo microenvironment to provide new insights into tumor progression, inform techniques to control tumor cell migration, and render cancer more treatable. PMID:22926411

The evolution of immunity in relation to colonization and migration.

PubMed

O'Connor, Emily A; Cornwallis, Charlie K; Hasselquist, Dennis; Nilsson, Jan-Åke; Westerdahl, Helena

2018-05-01

Colonization and migration have a crucial effect on patterns of biodiversity, with disease predicted to play an important role in these processes. However, evidence of the effect of pathogens on broad patterns of colonization and migration is limited. Here, using phylogenetic analyses of 1,311 species of Afro-Palaearctic songbirds, we show that colonization events from regions of high (sub-Saharan Africa) to low (the Palaearctic) pathogen diversity were up to 20 times more frequent than the reverse, and that migration has evolved 3 times more frequently from African- as opposed to Palaearctic-resident species. We also found that resident species that colonized the Palaearctic from Africa, as well as African species that evolved long-distance migration to breed in the Palaearctic, have reduced diversity of key immune genes associated with pathogen recognition (major histocompatibility complex class I). These results suggest that changes in the pathogen community that occur during colonization and migration shape the evolution of the immune system, potentially by adjusting the trade-off between the benefits of extensive pathogen recognition and the costs of immunopathology that result from high major histocompatibility complex class I diversity.

Passive non-linear microrheology for determining extensional viscosity

NASA Astrophysics Data System (ADS)

Hsiao, Kai-Wen; Dinic, Jelena; Ren, Yi; Sharma, Vivek; Schroeder, Charles M.

2017-12-01

Extensional viscosity is a key property of complex fluids that greatly influences the non-equilibrium behavior and processing of polymer solutions, melts, and colloidal suspensions. In this work, we use microfluidics to determine steady extensional viscosity for polymer solutions by directly observing particle migration in planar extensional flow. Tracer particles are suspended in semi-dilute solutions of DNA and polyethylene oxide, and a Stokes trap is used to confine single particles in extensional flows of polymer solutions in a cross-slot device. Particles are observed to migrate in the direction transverse to flow due to normal stresses, and particle migration is tracked and quantified using a piezo-nanopositioning stage during the microfluidic flow experiment. Particle migration trajectories are then analyzed using a second-order fluid model that accurately predicts that migration arises due to normal stress differences. Using this analytical framework, extensional viscosities can be determined from particle migration experiments, and the results are in reasonable agreement with bulk rheological measurements of extensional viscosity based on a dripping-onto-substrate method. Overall, this work demonstrates that non-equilibrium properties of complex fluids can be determined by passive yet non-linear microrheology.

The role of the antioxidant system during intense endurance exercise: lessons from migrating birds.

PubMed

Cooper-Mullin, Clara; McWilliams, Scott R

2016-12-01

During migration, birds substantially increase their metabolic rate and burn fats as fuel and yet somehow avoid succumbing to overwhelming oxidative damage. The physiological means by which vertebrates such as migrating birds can counteract an increased production of reactive species (RS) are rather limited: they can upregulate their endogenous antioxidant system and/or consume dietary antioxidants (prophylactically or therapeutically). Thus, birds can alter different components of their antioxidant system to respond to the demands of long-duration flights, but much remains to be discovered about the complexities of RS production and antioxidant protection throughout migration. Here, we use bird migration as an example to discuss how RS are produced during endurance exercise and how the complex antioxidant system can protect against cellular damage caused by RS. Understanding how a bird's antioxidant system responds during migration can lend insights into how antioxidants protect birds during other life-history stages when metabolic rate may be high, and how antioxidants protect other vertebrates from oxidative damage during endurance exercise. © 2016. Published by The Company of Biologists Ltd.

Modular assembly of chimeric phi29 packaging RNAs that support DNA packaging.

PubMed

Fang, Yun; Shu, Dan; Xiao, Feng; Guo, Peixuan; Qin, Peter Z

2008-08-08

The bacteriophage phi29 DNA packaging motor is a protein/RNA complex that can produce strong force to condense the linear-double-stranded DNA genome into a pre-formed protein capsid. The RNA component, called the packaging RNA (pRNA), utilizes magnesium-dependent inter-molecular base-pairing interactions to form ring-shaped complexes. The pRNA is a class of non-coding RNA, interacting with phi29 motor proteins to enable DNA packaging. Here, we report a two-piece chimeric pRNA construct that is fully competent in interacting with partner pRNA to form ring-shaped complexes, in packaging DNA via the motor, and in assembling infectious phi29 virions in vitro. This is the first example of a fully functional pRNA assembled using two non-covalently interacting fragments. The results support the notion of modular pRNA architecture in the phi29 packaging motor.

Modular assembly of chimeric phi29 packaging RNAs that support DNA packaging

PubMed Central

Fang, Yun; Shu, Dan; Xiao, Feng; Guo, Peixuan; Qin, Peter Z.

2008-01-01

The bacteriophage phi29 DNA packaging motor is a protein/RNA complex that can produce strong force to condense the linear-double stranded DNA genome into a pre-formed protein capsid. The RNA component, called the packaging RNA (pRNA), utilizes magnesium-dependent intermolecular base-pairing interactions to form ring-shaped complexes. The pRNA is a class of non-coding RNA, interacting with phi29 motor proteins to enable DNA packaging. Here, we report a 2-piece chimeric pRNA construct that is fully competent in interacting with partner pRNA to form ring-shaped complexes, in packaging DNA via the motor, and in assembling infectious phi29 virions in vitro. This is the first example of a fully functional pRNA assembled using two non-covalently interacting fragments. The results support the notion of modular pRNA architecture in the phi29 packaging motor. PMID:18514064

Arrested α-hydride migration activates a phosphido ligand for C–H insertion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hickey, Anne K.; Muñoz, Salvador B.; Lutz, Sean A.

Bulky tris(carbene)borate ligands provide access to high spin iron(II) phosphido complexes. The complex PhB(MesIm) 3FeP(H)Ph is thermally unstable, and we observed [PPh] group insertion into a C–H bond of the supporting ligand. An arrested α-hydride migration mechanism suggests increased nucleophilicity of the phosphorus atom facilitates [PPh] group transfer reactivity.

Autologous adipose tissue-derived stromal cells for treatment of spinal cord injury.

PubMed

Kang, Soo-Kyung; Shin, Myung-Joo; Jung, Jin Sup; Kim, Yong Geun; Kim, Cheul-Hong

2006-08-01

Isolated rat adipose tissue-derived stromal cells (rATSCs) contain pluripotent cells that can be differentiated into a variety of cell lineages, including neural cells. Recent work has shown that ATSCs can make neurosphere-like clumps and differentiate into neuron-like cells expressing neuronal markers, but their therapeutic effect is unclear. Here we report that intravenous infusion of oligodendrocyte precursor cells (OPCs) derived from rATSC autograft cells sources improve motor function in rat models of spinal cord injury (SCI). After 4-5 weeks, transplanted rATSC-OPC cells survived and migrated into the injured region of SCI very efficiently (30-35%) and migrated cells were partially differentiated into neurons and oligodendrocyte. Also, we found some of the engrafted OPCs migrated and integrated in the kidney, brain, lung, and liver through the intravenous system. Behavioral analysis revealed the locomotor functions of OPC-autografted SCI rats were significantly restored. Efficient migration of intravenously engrafted rATSC-OPCs cells into SCI lesion suggests that SCI-induced chemotaxic factors facilitate migration of rATSC-OPCs. Here, we verified that engrafted rATSCs and SCI-induced chemotaxic factors indeed play an important role in proliferation, migration, and differentiation of endogeneous spinal cord-derived neural progenitor cells in the injured region. In transplantation paradigms, the interaction between engrafted rATSC-OPCs and endogeneous spinal cord-derived neuronal progenitor cells will be important in promoting healing through fate decisions, resulting in coordinated induction of cell migration and differentiation.

F-actin cross-linking enhances the stability of force generation in disordered actomyosin networks

NASA Astrophysics Data System (ADS)

Jung, Wonyeong; Murrell, Michael P.; Kim, Taeyoon

2015-12-01

Myosin molecular motors and actin cross-linking proteins (ACPs) are known to mediate the generation and transmission of mechanical forces within the cortical F-actin cytoskeleton that drive major cellular processes such as cell division and migration. However, how motors and ACPs interact collectively over diverse timescales to modulate the time-dependent mechanical properties of the cytoskeleton remains unclear. In this study, we present a three-dimensional agent-based computational model of the cortical actomyosin network to quantitatively determine the effects of motor activity and the density and kinetics of ACPs on the accumulation and maintenance of mechanical tension within a disordered actomyosin network. We found that motors accumulate large stress quickly by behaving as temporary cross-linkers although this stress is relaxed over time unless there are sufficient passive ACPs to stabilize the network. Stabilization by ACPs helps motors to generate forces up to their maximum potential, leading to significant enhancement of the efficiency and stability of stress generation. Thus, we demonstrated that the force-dependent kinetics of ACP dissociation plays a critical role for the accumulation and sustainment of stress and the structural remodeling of networks.

Correlation analysis of motor current and chatter vibration in grinding using complex continuous wavelet coherence

NASA Astrophysics Data System (ADS)

Liu, Yao; Wang, Xiufeng; Lin, Jing; Zhao, Wei

2016-11-01

Motor current is an emerging and popular signal which can be used to detect machining chatter with its multiple advantages. To achieve accurate and reliable chatter detection using motor current, it is important to make clear the quantitative relationship between motor current and chatter vibration, which has not yet been studied clearly. In this study, complex continuous wavelet coherence, including cross wavelet transform and wavelet coherence, is applied to the correlation analysis of motor current and chatter vibration in grinding. Experimental results show that complex continuous wavelet coherence performs very well in demonstrating and quantifying the intense correlation between these two signals in frequency, amplitude and phase. When chatter occurs, clear correlations in frequency and amplitude in the chatter frequency band appear and the phase difference of current signal to vibration signal turns from random to stable. The phase lead of the most correlated chatter frequency is the largest. With the further development of chatter, the correlation grows up in intensity and expands to higher order chatter frequency band. The analyzing results confirm that there is a consistent correlation between motor current and vibration signals in the grinding chatter process. However, to achieve accurate and reliable chatter detection using motor current, the frequency response bandwidth of current loop of the feed drive system must be wide enough to response chatter effectively.

Sleep Consolidates Motor Learning of Complex Movement Sequences in Mice.

PubMed

Nagai, Hirotaka; de Vivo, Luisa; Bellesi, Michele; Ghilardi, Maria Felice; Tononi, Giulio; Cirelli, Chiara

2017-02-01

Sleep-dependent consolidation of motor learning has been extensively studied in humans, but it remains unclear why some, but not all, learned skills benefit from sleep. Here, we compared 2 different motor tasks, both requiring the mice to run on an accelerating device. In the rotarod task, mice learn to maintain balance while running on a small rod, while in the complex wheel task, mice run on an accelerating wheel with an irregular rung pattern. In the rotarod task, performance improved to the same extent after sleep or after sleep deprivation (SD). Overall, using 7 different experimental protocols (41 sleep deprived mice, 26 sleeping controls), we found large interindividual differences in the learning and consolidation of the rotarod task, but sleep before/after training did not account for this variability. By contrast, using the complex wheel, we found that sleep after training, relative to SD, led to better performance from the beginning of the retest session, and longer sleep was correlated with greater subsequent performance. As in humans, the effects of sleep showed large interindividual variability and varied between fast and slow learners, with sleep favoring the preservation of learned skills in fast learners and leading to a net offline gain in the performance in slow learners. Using Fos expression as a proxy for neuronal activation, we also found that complex wheel training engaged motor cortex and hippocampus more than the rotarod training. Sleep specifically consolidates a motor skill that requires complex movement sequences and strongly engages both motor cortex and hippocampus. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Primary complex motor stereotypies in older children and adolescents: clinical features and longitudinal follow-up.

PubMed

Oakley, Christopher; Mahone, E Mark; Morris-Berry, Christina; Kline, Tina; Singer, Harvey S

2015-04-01

Complex motor stereotypies are rhythmic, repetitive, fixed, and purposeless movements that stop with distraction. Once believed to occur only in children with autism spectrum or other developmental disorders, their presence in otherwise typically developing children (primary) has been well-established. In primary complex motor stereotypies, little information is available about the long-term outcome of these movements or existing comorbidities. Forty-nine healthy participants (31 boys), ages 9 to 20 years with primary complex motor stereotypies who were previously diagnosed at a pediatric movements disorder clinic, were identified from medical records. Parents or the young adult (if older than age 18), completed a telephone interview evaluating family history, outcome, and comorbidities including attention-deficit hyperactivity disorder, obsessive compulsive disorder, anxiety, and tics/Tourette syndrome. Standardized questionnaires assessing attention-deficit hyperactivity, obsessive compulsive disorder, and anxiety were used to validate parent report of comorbidities. Stereotypy onset occurred before age 3 years in 98%. In all but one individual, stereotypies persisted at the time of phone follow-up (follow-up range: 6.8-20.3 years). Positive family history of complex motor stereotypies was identified in 39%. Most participants (92%) had concern for at least one comorbid disorder, including parent-/patient-reported clinically elevated levels of anxiety (73%), attention-deficit hyperactivity (63%), obsessive compulsive disorder (35%), and tics/Tourette syndrome (22%). Primary motor stereotypies typically begin in early childhood and, although reduced in frequency and duration, persist at least through the teenage years. Repetitive movements are associated with a variety of comorbidities that often have a greater functional impact than the stereotypic behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Motor for High Temperature Applications

NASA Technical Reports Server (NTRS)

Roopnarine (Inventor)

2013-01-01

A high temperature motor has a stator with poles formed by wire windings, and a rotor with magnetic poles on a rotor shaft positioned coaxially within the stator. The stator and rotor are built up from stacks of magnetic-alloy laminations. The stator windings are made of high temperature magnet wire insulated with a vitreous enamel film, and the wire windings are bonded together with ceramic binder. A thin-walled cylinder is positioned coaxially between the rotor and the stator to prevent debris from the stator windings from reaching the rotor. The stator windings are wound on wire spools made of ceramic, thereby avoiding need for mica insulation and epoxy/adhesive. The stator and rotor are encased in a stator housing with rear and front end caps, and rear and front bearings for the rotor shaft are mounted on external sides of the end caps to keep debris from the motor migrating into the bearings' races.

The effect of cerebellar transplantation and enforced physical activity on motor skills and spatial learning in adult Lurcher mutant mice.

PubMed

Cendelín, Jan; Korelusová, Ivana; Vozeh, Frantisek

2009-03-01

Lurcher mutant mice represent a model of olivocerebellar degeneration. They are used to investigate cerebellar functions, consequences of cerebellar degeneration and methods of therapy influencing them. The aim of the work was to assess the effect of foetal cerebellar graft transplantation, repeated enforced physical activity and the combination of both these types of treatment on motor skills, spontaneous motor activity and spatial learning ability in adult B6CBA Lurcher mice. Foetal cerebellar grafts were applied into the cerebellum of Lurchers in the form of solid tissue pieces. Enforced motor activity was realised through rotarod training. Motor functions were examined using bar, ladder and rotarod tests. Spatial learning was tested in the Morris water maze. Spontaneous motor activity in the open field was observed. The presence of the graft was examined histologically. Enforced physical activity led to moderate improvement of some motor skills and to a significant amelioration of spatial learning ability in Lurchers. The transplantation of cerebellar tissue did not influence motor functions significantly but led to an improvement of spatial learning ability. Mutual advancement of the effects of both types of treatment was not observed. Spontaneous motor activity was influenced neither by physical activity nor by the transplantation. Physical activity did not influence the graft survival and development. Because nerve sprouting and cell migration from the graft to the host cerebellum was poor, the functional effects of the graft should be explained with regard to its trophic influence rather than with any involvement of the grafted cells into neural circuitries.

Tissue Plasminogen Activator Induction in Purkinje Neurons After Cerebellar Motor Learning

NASA Astrophysics Data System (ADS)

Seeds, Nicholas W.; Williams, Brian L.; Bickford, Paula C.

1995-12-01

The cerebellar cortex is implicated in the learning of complex motor skills. This learning may require synaptic remodeling of Purkinje cell inputs. An extracellular serine protease, tissue plasminogen activator (tPA), is involved in remodeling various nonneural tissues and is associated with developing and regenerating neurons. In situ hybridization showed that expression of tPA messenger RNA was increased in the Purkinje neurons of rats within an hour of their being trained for a complex motor task. Antibody to tPA also showed the induction of tPA protein associated with cerebellar Purkinje cells. Thus, the induction of tPA during motor learning may play a role in activity-dependent synaptic plasticity.

Perinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments

PubMed Central

Thiam, Hawa-Racine; Vargas, Pablo; Carpi, Nicolas; Crespo, Carolina Lage; Raab, Matthew; Terriac, Emmanuel; King, Megan C.; Jacobelli, Jordan; Alberts, Arthur S.; Stradal, Theresia; Lennon-Dumenil, Ana-Maria; Piel, Matthieu

2016-01-01

Cell migration has two opposite faces: although necessary for physiological processes such as immune responses, it can also have detrimental effects by enabling metastatic cells to invade new organs. In vivo, migration occurs in complex environments and often requires a high cellular deformability, a property limited by the cell nucleus. Here we show that dendritic cells, the sentinels of the immune system, possess a mechanism to pass through micrometric constrictions. This mechanism is based on a rapid Arp2/3-dependent actin nucleation around the nucleus that disrupts the nuclear lamina, the main structure limiting nuclear deformability. The cells' requirement for Arp2/3 to pass through constrictions can be relieved when nuclear stiffness is decreased by suppressing lamin A/C expression. We propose a new role for Arp2/3 in three-dimensional cell migration, allowing fast-moving cells such as leukocytes to rapidly and efficiently migrate through narrow gaps, a process probably important for their function. PMID:26975831

The role of short-term memory impairment in nonword repetition, real word repetition, and nonword decoding: A case study.

PubMed

Peter, Beate

2018-01-01

In a companion study, adults with dyslexia and adults with a probable history of childhood apraxia of speech showed evidence of difficulty with processing sequential information during nonword repetition, multisyllabic real word repetition and nonword decoding. Results suggested that some errors arose in visual encoding during nonword reading, all levels of processing but especially short-term memory storage/retrieval during nonword repetition, and motor planning and programming during complex real word repetition. To further investigate the role of short-term memory, a participant with short-term memory impairment (MI) was recruited. MI was confirmed with poor performance during a sentence repetition and three nonword repetition tasks, all of which have a high short-term memory load, whereas typical performance was observed during tests of reading, spelling, and static verbal knowledge, all with low short-term memory loads. Experimental results show error-free performance during multisyllabic real word repetition but high counts of sequence errors, especially migrations and assimilations, during nonword repetition, supporting short-term memory as a locus of sequential processing deficit during nonword repetition. Results are also consistent with the hypothesis that during complex real word repetition, short-term memory is bypassed as the word is recognized and retrieved from long-term memory prior to producing the word.

Participation of primary motor cortex area 4a in complex sensory processing: 3.0-T fMRI study.

PubMed

Terumitsu, Makoto; Ikeda, Kotaro; Kwee, Ingrid L; Nakada, Tsutomu

2009-05-06

The precise movement of human fingers requires continuous and reciprocal interaction between motor and sensory systems. Similar to other primates, there is double representation of the digits and wrists within the human primary motor cortex (M1), which are generally referred to as area 4 anterior (M1-4a) and area 4 posterior (M1-4p). In this high-field (3.0 T) functional magnetic resonance imaging (fMRI) study, we hypothesized that M1-4p is more important for initiation of motion, whereas M1-4a is important for execution of a given motion involving more complex sensoriomotor interaction. We investigated M1-4a and M1-4p activation associated with two representative motor tasks, namely, finger tapping (voluntary motion, VM) and passive finger movement accomplished by continuous pressure (passive motor, PM), and two representative sensory stimulations, namely, simple stimulation of flutter vibration (simple sensory, SS), and complex stimulation by a row of pins moving either vertically or horizontally (complex sensory, CS). Both M1-4a and M1-4p were activated in both motor tasks, VM and PM. M1-4p was not activated by either of the two sensory tasks, whereas M1-4a was activated by CS but not by SS. Analysis of the center of gravities (COG) of the activated areas showed that VM and PM moved COG towards M1-4p and 3a. SS moved COG towards somatosensory cortex Brodmann areas 1, 2, and 3b, whereas CS towards M1-4a. The result clearly showed that M1-4a represents the area of secondary motor execution, which actively participates in CS processing.

Evaluation of quasi-square wave inverter as a power source for induction motors

NASA Technical Reports Server (NTRS)

Guynes, B. V.; Haggard, R. L.; Lanier, J. R., Jr.

1977-01-01

The relative merits of quasi-square wave inverter-motor technology versus a sine wave inverter-motor system were investigated. The empirical results of several tests on various sizes of wye-wound induction motors are presented with mathematical analysis to support the conclusions of the study. It was concluded that, within the limitations presented, the quasi-square wave inverter-motor system is superior to the more complex sine wave system for most induction motor applications in space.

Asymmetrical Macromolecular Complex Formation of Lysophosphatidic Acid Receptor 2 (LPA2) Mediates Gradient Sensing in Fibroblasts*

PubMed Central

Ren, Aixia; Moon, Changsuk; Zhang, Weiqiang; Sinha, Chandrima; Yarlagadda, Sunitha; Arora, Kavisha; Wang, Xusheng; Yue, Junming; Parthasarathi, Kaushik; Heil-Chapdelaine, Rick; Tigyi, Gabor; Naren, Anjaparavanda P.

2014-01-01

Chemotactic migration of fibroblasts toward growth factors relies on their capacity to sense minute extracellular gradients and respond to spatially confined receptor-mediated signals. Currently, mechanisms underlying the gradient sensing of fibroblasts remain poorly understood. Using single-particle tracking methodology, we determined that a lysophosphatidic acid (LPA) gradient induces a spatiotemporally restricted decrease in the mobility of LPA receptor 2 (LPA2) on chemotactic fibroblasts. The onset of decreased LPA2 mobility correlates to the spatial recruitment and coupling to LPA2-interacting proteins that anchor the complex to the cytoskeleton. These localized PDZ motif-mediated macromolecular complexes of LPA2 trigger a Ca2+ puff gradient that governs gradient sensing and directional migration in response to LPA. Disruption of the PDZ motif-mediated assembly of the macromolecular complex of LPA2 disorganizes the gradient of Ca2+ puffs, disrupts gradient sensing, and reduces the directional migration of fibroblasts toward LPA. Our findings illustrate that the asymmetric macromolecular complex formation of chemoattractant receptors mediates gradient sensing and provides a new mechanistic basis for models to describe gradient sensing of fibroblasts. PMID:25542932

Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling

PubMed Central

Morgan, Mark R.; Hamidi, Hellyeh; Bass, Mark D.; Warwood, Stacey; Ballestrem, Christoph; Humphries, Martin J.

2013-01-01

Summary Precise spatiotemporal coordination of integrin adhesion complex dynamics is essential for efficient cell migration. For cells adherent to fibronectin, differential engagement of α5β1 and αVβ3 integrins is used to elicit changes in adhesion complex stability, mechanosensation, matrix assembly, and migration, but the mechanisms responsible for receptor regulation have remained largely obscure. We identify phosphorylation of the membrane-intercalated proteoglycan syndecan-4 as an essential switch controlling integrin recycling. Src phosphorylates syndecan-4 and, by driving syntenin binding, leads to suppression of Arf6 activity and recycling of αVβ3 to the plasma membrane at the expense of α5β1. The resultant elevation in αVβ3 engagement promotes stabilization of focal adhesions. Conversely, abrogation of syndecan-4 phosphorylation drives surface expression of α5β1, destabilizes adhesion complexes, and disrupts cell migration. These data identify the dynamic spatiotemporal regulation of Src-mediated syndecan-4 phosphorylation as an essential switch controlling integrin trafficking and adhesion dynamics to promote efficient cell migration. PMID:23453597

Impact of the corrin framework of vitamin B12 on the electrochemical carbon-skeleton rearrangement in comparison to an imine/oxime planar ligand; tuning selectivity in 1,2-migration of a functional group by controlling electrolysis potential.

PubMed

Tahara, Keishiro; Pan, Ling; Yamaguchi, Ryoko; Shimakoshi, Hisashi; Abe, Masaaki; Hisaeda, Yoshio

2017-10-01

Among the coenzyme B 12 -dependent enzymes, methylmalonyl-CoA mutase (MMCM) catalyzes the carbon-skeleton rearrangement reaction between R-methylmalonyl-CoA and succinyl-CoA. Diethyl 2-bromomethyl-2-phenylmalonate, an alkyl bromide substrate having two different migrating groups (phenyl and carboxylic ester groups) on the β-carbon, was applied to the electrolysis mediated by a hydrophobic vitamin B 12 model complex, heptamethyl cobyrinate perchlorate in this study. The electrolysis of the substrate at -1.0V vs. Ag-AgCl by light irradiation afforded the simple reduced product (diethyl 2-methyl-2-phenylmalonate) and the phenyl migrated product (diethyl 2-benzyl-2-phenylmalonate), as well as the electrolysis of the substrate at -1.5V vs. Ag-AgCl in the dark. The electrolysis of the substrate at -2.0V vs. Ag-AgCl afforded the carboxylic ester migrated product (diethyl phenylsuccinate) as the major product. The selectivity for the migrating group was successfully tuned by controlling the electrolysis potential. We clarified that the cathodic chemistry of the Co(III) alkylated heptamethyl cobyrinate is critical for the selectivity of the migrating group through mechanistic investigations and comparisons to the simple vitamin B 12 model complex, an imine/oxime-type cobalt complex. Copyright © 2017 Elsevier Inc. All rights reserved.

Livelihood Diversification through Migration among a Pastoral People: Contrasting Case Studies of Maasai in Northern Tanzania

PubMed Central

McCabe, J. Terrence; Smith, Nicole M.; Leslie, Paul W.; Telligman, Amy L.

2015-01-01

This paper brings together over two decades of research concerning the patterns and processes of livelihood diversification through migration among Maasai pastoralists and agro-pastoralists of northern Tanzania. Two case studies, one from the Ngorongoro Conservation Area and the other from the Simanjiro plains, jointly demonstrate the complexity of migration within a single ethnic group. We analyze the relationship between wealth and migration and examine some of the consequences of migration for building herds, expanding cultivation, and influencing political leadership. We further argue that migration in Maasai communities is becoming a cultural norm and not only a response to economic conditions. PMID:25745192

Counterintuitive migration patterns by Atlantic salmon Salmo salar smolts in a large lake.

PubMed

Honkanen, H M; Rodger, J R; Stephen, A; Adams, K; Freeman, J; Adams, C E

2018-06-21

What little is known about the seaward migration of Salmo salar smolt migration through standing waters indicates that it is both slow and results in high mortality rates, compared with riverine migration. This may be partly because smolts in lakes need to swim more actively and require more complex directional cues than they do in rivers. In this telemetry study of smolt migration through Loch Lomond, S. salar smolts made repeated movements in directions away from the outflowing river, which considerably increased migration time. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Hedgehog Is a Positive Regulator of FGF Signalling during Embryonic Tracheal Cell Migration

PubMed Central

Butí, Elisenda; Mesquita, Duarte; Araújo, Sofia J.

2014-01-01

Cell migration is a widespread and complex process that is crucial for morphogenesis and for the underlying invasion and metastasis of human cancers. During migration, cells are steered toward target sites by guidance molecules that induce cell direction and movement through complex intracellular mechanisms. The spatio-temporal regulation of the expression of these guidance molecules is of extreme importance for both normal morphogenesis and human disease. One way to achieve this precise regulation is by combinatorial inputs of different transcription factors. Here we used Drosophila melanogaster mutants with migration defects in the ganglionic branches of the tracheal system to further clarify guidance regulation during cell migration. By studying the cellular consequences of overactivated Hh signalling, using ptc mutants, we found that Hh positively regulates Bnl/FGF levels during embryonic stages. Our results show that Hh modulates cell migration non-autonomously in the tissues surrounding the action of its activity. We further demonstrate that the Hh signalling pathway regulates bnl expression via Stripe (Sr), a zinc-finger transcription factor with homology to the Early Growth Response (EGR) family of vertebrate transcription factors. We propose that Hh modulates embryonic cell migration by participating in the spatio-temporal regulation of bnl expression in a permissive mode. By doing so, we provide a molecular link between the activation of Hh signalling and increased chemotactic responses during cell migration. PMID:24651658

Hedgehog is a positive regulator of FGF signalling during embryonic tracheal cell migration.

PubMed

Butí, Elisenda; Mesquita, Duarte; Araújo, Sofia J

2014-01-01

Cell migration is a widespread and complex process that is crucial for morphogenesis and for the underlying invasion and metastasis of human cancers. During migration, cells are steered toward target sites by guidance molecules that induce cell direction and movement through complex intracellular mechanisms. The spatio-temporal regulation of the expression of these guidance molecules is of extreme importance for both normal morphogenesis and human disease. One way to achieve this precise regulation is by combinatorial inputs of different transcription factors. Here we used Drosophila melanogaster mutants with migration defects in the ganglionic branches of the tracheal system to further clarify guidance regulation during cell migration. By studying the cellular consequences of overactivated Hh signalling, using ptc mutants, we found that Hh positively regulates Bnl/FGF levels during embryonic stages. Our results show that Hh modulates cell migration non-autonomously in the tissues surrounding the action of its activity. We further demonstrate that the Hh signalling pathway regulates bnl expression via Stripe (Sr), a zinc-finger transcription factor with homology to the Early Growth Response (EGR) family of vertebrate transcription factors. We propose that Hh modulates embryonic cell migration by participating in the spatio-temporal regulation of bnl expression in a permissive mode. By doing so, we provide a molecular link between the activation of Hh signalling and increased chemotactic responses during cell migration.

Neutral endopeptidase inhibits prostate cancer cell migration by blocking focal adhesion kinase signaling.

PubMed

Sumitomo, M; Shen, R; Walburg, M; Dai, J; Geng, Y; Navarro, D; Boileau, G; Papandreou, C N; Giancotti, F G; Knudsen, B; Nanus, D M

2000-12-01

Neutral endopeptidase 24.11 (NEP, CD10) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate cancer (PC). NEP substrates such as bombesin and endothelin-1 induce cell migration. We investigated the mechanisms of NEP regulation of cell migration in PC cells, including regulation of phosphorylation on tyrosine of focal adhesion kinase (FAK). Western analyses and cell migration assays revealed an inverse correlation between NEP expression and the levels of FAK phosphorylation and cell migration in PC cell lines. Constitutively expressed NEP, recombinant NEP, and induced NEP expression using a tetracycline-repressive expression system inhibited bombesin- and endothelin-1-stimulated FAK phosphorylation and cell migration. This results from NEP-induced inhibition of neuropeptide-stimulated association of FAK with cSrc protein. Expression of a mutated catalytically inactive NEP protein also resulted in partial inhibition of FAK phosphorylation and cell migration. Coimmunoprecipitation experiments show that NEP associates with tyrosine-phosphorylated Lyn kinase, which then binds the p85 subunit of phosphatidylinositol 3-kinase (PI3-K) resulting in an NEP-Lyn-PI3-K protein complex. This complex competitively blocks FAK-PI3-K interaction, suggesting that NEP protein inhibits cell migration via a protein-protein interaction independent of its catalytic function. These experiments demonstrate that NEP can inhibit FAK phosphorylation on tyrosine and PC cell migration through multiple pathways and suggest that cell migration which contributes to invasion and metastases in PC cells can be regulated by NEP.

Neutral endopeptidase inhibits prostate cancer cell migration by blocking focal adhesion kinase signaling

PubMed Central

Sumitomo, Makoto; Shen, Ruoqian; Walburg, Marc; Dai, Jie; Geng, Yiping; Navarro, Daniel; Boileau, Guy; Papandreou, Christos N.; Giancotti, Filippo G.; Knudsen, Beatrice; Nanus, David M.

2000-01-01

Neutral endopeptidase 24.11 (NEP, CD10) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate cancer (PC). NEP substrates such as bombesin and endothelin-1 induce cell migration. We investigated the mechanisms of NEP regulation of cell migration in PC cells, including regulation of phosphorylation on tyrosine of focal adhesion kinase (FAK). Western analyses and cell migration assays revealed an inverse correlation between NEP expression and the levels of FAK phosphorylation and cell migration in PC cell lines. Constitutively expressed NEP, recombinant NEP, and induced NEP expression using a tetracycline-repressive expression system inhibited bombesin- and endothelin-1–stimulated FAK phosphorylation and cell migration. This results from NEP-induced inhibition of neuropeptide-stimulated association of FAK with cSrc protein. Expression of a mutated catalytically inactive NEP protein also resulted in partial inhibition of FAK phosphorylation and cell migration. Coimmunoprecipitation experiments show that NEP associates with tyrosine-phosphorylated Lyn kinase, which then binds the p85 subunit of phosphatidylinositol 3-kinase (PI3-K) resulting in an NEP-Lyn-PI3-K protein complex. This complex competitively blocks FAK-PI3-K interaction, suggesting that NEP protein inhibits cell migration via a protein-protein interaction independent of its catalytic function. These experiments demonstrate that NEP can inhibit FAK phosphorylation on tyrosine and PC cell migration through multiple pathways and suggest that cell migration which contributes to invasion and metastases in PC cells can be regulated by NEP. PMID:11104793

Education of Children Left Behind in Rural China*

PubMed Central

Lu, Yao

2013-01-01

Despite China’s substantial internal migration, longstanding rural-urban bifurcation has prompted many migrants to leave their children behind in rural areas. This study examines the consequences of out-migration for children’s education using longitudinal data from the China Health and Nutrition Survey (N = 885). This study takes into account the complex family migration strategies and distinguishes various types of migration in China, including different forms of parental migration as well as sibling migration. Results show that migration of siblings generates benefits for children’s education, which is particularly pronounced for girls and children at middle-school levels. But parental migration has not given children left behind a significant advantage in educational prospects as their parents had hoped. Younger children seem to be especially susceptible to the disruptive effect of parental out-migration. PMID:24163479

Inhibition by stabilization: targeting the Plasmodium falciparum aldolase-TRAP complex.

PubMed

Nemetski, Sondra Maureen; Cardozo, Timothy J; Bosch, Gundula; Weltzer, Ryan; O'Malley, Kevin; Ejigiri, Ijeoma; Kumar, Kota Arun; Buscaglia, Carlos A; Nussenzweig, Victor; Sinnis, Photini; Levitskaya, Jelena; Bosch, Jürgen

2015-08-20

Emerging resistance of the malaria parasite Plasmodium to current therapies underscores the critical importance of exploring novel strategies for disease eradication. Plasmodium species are obligate intracellular protozoan parasites. They rely on an unusual form of substrate-dependent motility for their migration on and across host-cell membranes and for host cell invasion. This peculiar motility mechanism is driven by the 'glideosome', an actin-myosin associated, macromolecular complex anchored to the inner membrane complex of the parasite. Myosin A, actin, aldolase, and thrombospondin-related anonymous protein (TRAP) constitute the molecular core of the glideosome in the sporozoite, the mosquito stage that brings the infection into mammals. Virtual library screening of a large compound library against the PfAldolase-TRAP complex was used to identify candidate compounds that stabilize and prevent the disassembly of the glideosome. The mechanism of these compounds was confirmed by biochemical, biophysical and parasitological methods. A novel inhibitory effect on the parasite was achieved by stabilizing a protein-protein interaction within the glideosome components. Compound 24 disrupts the gliding and invasive capabilities of Plasmodium parasites in in vitro parasite assays. A high-resolution, ternary X-ray crystal structure of PfAldolase-TRAP in complex with compound 24 confirms the mode of interaction and serves as a platform for future ligand optimization. This proof-of-concept study presents a novel approach to anti-malarial drug discovery and design. By strengthening a protein-protein interaction within the parasite, an avenue towards inhibiting a previously "undruggable" target is revealed and the motility motor responsible for successful invasion of host cells is rendered inactive. This study provides new insights into the malaria parasite cell invasion machinery and convincingly demonstrates that liver cell invasion is dramatically reduced by 95 % in the presence of the small molecule stabilizer compound 24.

Intimate Partner Violence and Forced Migration during Pregnancy: Structural Constraints to Women’s Agency

PubMed Central

Turan, Janet M.; Hatcher, Abigail M.; Romito, Patrizia; Mangone, Emily; Durojaiye, Modupeoluwa; Odero, Merab; Camlin, Carol S.

2015-01-01

Little is known about migration during pregnancy related to intimate partner violence (IPV). In this paper, we examine issues of agency in relation to pregnant women’s migrations in a high HIV prevalence area of Kenya. We qualitatively explored forced migration among pregnant women, using data from in-depth interviews, focus groups, and IPV screening forms. To quantitatively examine migration during pregnancy, we analyzed data from a prospective study of 614 pregnant women. The qualitative data revealed that women had varied responses to violence in pregnancy, with some being able to leave the marital home voluntarily as a strategy to escape violence. Others were ‘sent packing’ from their marital homes when they dared to exercise autonomy, in some cases related to HIV status. Quantitative analyses revealed that pregnant women who migrated were more educated, less likely to be living with a partner, and had fewer children than other women. Migration among pregnant women in Kenya illustrates the complexity of understanding women’s agency in the context of IPV. The findings indicate that there is not a dichotomy between “victim” and “agent”, but rather a complex dynamic between and within pregnant women, who may sequentially or simultaneously experience aspects of victimhood and/or agentic response. PMID:25996287

Nanomotor dynamics in a chemically oscillating medium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, Bryan, E-mail: bryan.robertson@mail.utoronto.ca; Kapral, Raymond, E-mail: rkapral@chem.utoronto.ca

2015-04-21

Synthetic nanomotors powered by chemical reactions have potential uses as cargo transport vehicles in both in vivo and in vitro applications. In many situations, motors will have to operate in out-of-equilibrium complex chemically reacting media, which supply fuel to the motors and remove the products they produce. Using molecular simulation and mean-field theory, this paper describes some of the new features that arise when a chemically powered nanomotor, operating through a diffusiophoretic mechanism, moves in an environment that supports an oscillatory chemical reaction network. It is shown how oscillations in the concentrations in chemical species in the environment give risemore » to oscillatory motor dynamics. More importantly, since the catalytic reactions on the motor that are responsible for its propulsion couple to the bulk phase reaction network, the motor can change its local environment. This process can give rise to distinctive spatiotemporal structures in reaction-diffusion media that occur as a result of active motor motion. Such locally induced nonequilibrium structure will play an important role in applications that involve motor dynamics in complex chemical media.« less

Complex interaction of sensory and motor signs and symptoms in chronic CRPS.

PubMed

Huge, Volker; Lauchart, Meike; Magerl, Walter; Beyer, Antje; Moehnle, Patrick; Kaufhold, Wibke; Schelling, Gustav; Azad, Shahnaz Christina

2011-04-29

Spontaneous pain, hyperalgesia as well as sensory abnormalities, autonomic, trophic, and motor disturbances are key features of Complex Regional Pain Syndrome (CRPS). This study was conceived to comprehensively characterize the interaction of these symptoms in 118 patients with chronic upper limb CRPS (duration of disease: 43±23 months). Disease-related stress, depression, and the degree of accompanying motor disability were likewise assessed. Stress and depression were measured by Posttraumatic Stress Symptoms Score and Center for Epidemiological Studies Depression Test. Motor disability of the affected hand was determined by Sequential Occupational Dexterity Assessment and Michigan Hand Questionnaire. Sensory changes were assessed by Quantitative Sensory Testing according to the standards of the German Research Network on Neuropathic Pain. Almost two-thirds of all patients exhibited spontaneous pain at rest. Hand force as well as hand motor function were found to be substantially impaired. Results of Quantitative Sensory Testing revealed a distinct pattern of generalized bilateral sensory loss and hyperalgesia, most prominently to blunt pressure. Patients reported substantial motor complaints confirmed by the objective motor disability testings. Interestingly, patients displayed clinically relevant levels of stress and depression. We conclude that chronic CRPS is characterized by a combination of ongoing pain, pain-related disability, stress and depression, potentially triggered by peripheral nerve/tissue damage and ensuing sensory loss. In order to consolidate the different dimensions of disturbances in chronic CRPS, we developed a model based on interaction analysis suggesting a complex hierarchical interaction of peripheral (injury/sensory loss) and central factors (pain/disability/stress/depression) predicting motor dysfunction and hyperalgesia.

Complex Interaction of Sensory and Motor Signs and Symptoms in Chronic CRPS

PubMed Central

Huge, Volker; Lauchart, Meike; Magerl, Walter; Beyer, Antje; Moehnle, Patrick; Kaufhold, Wibke; Schelling, Gustav; Azad, Shahnaz Christina

2011-01-01

Spontaneous pain, hyperalgesia as well as sensory abnormalities, autonomic, trophic, and motor disturbances are key features of Complex Regional Pain Syndrome (CRPS). This study was conceived to comprehensively characterize the interaction of these symptoms in 118 patients with chronic upper limb CRPS (duration of disease: 43±23 months). Disease-related stress, depression, and the degree of accompanying motor disability were likewise assessed. Stress and depression were measured by Posttraumatic Stress Symptoms Score and Center for Epidemiological Studies Depression Test. Motor disability of the affected hand was determined by Sequential Occupational Dexterity Assessment and Michigan Hand Questionnaire. Sensory changes were assessed by Quantitative Sensory Testing according to the standards of the German Research Network on Neuropathic Pain. Almost two-thirds of all patients exhibited spontaneous pain at rest. Hand force as well as hand motor function were found to be substantially impaired. Results of Quantitative Sensory Testing revealed a distinct pattern of generalized bilateral sensory loss and hyperalgesia, most prominently to blunt pressure. Patients reported substantial motor complaints confirmed by the objective motor disability testings. Interestingly, patients displayed clinically relevant levels of stress and depression. We conclude that chronic CRPS is characterized by a combination of ongoing pain, pain-related disability, stress and depression, potentially triggered by peripheral nerve/tissue damage and ensuing sensory loss. In order to consolidate the different dimensions of disturbances in chronic CRPS, we developed a model based on interaction analysis suggesting a complex hierarchical interaction of peripheral (injury/sensory loss) and central factors (pain/disability/stress/depression) predicting motor dysfunction and hyperalgesia. PMID:21559525

Golgi Positioning

PubMed Central

Yadav, Smita; Linstedt, Adam D.

2011-01-01

The Golgi apparatus in mammalian cells is positioned near the centrosome-based microtubule-organizing center (Fig. 1). Secretory cargo moves inward in membrane carriers for delivery to Golgi membranes in which it is processed and packaged for transport outward to the plasma membrane. Cytoplasmic dynein motor proteins (herein termed dynein) primarily mediate inward cargo carrier movement and Golgi positioning. These motors move along microtubules toward microtubule minus-ends embedded in centrosomes. Centripetal motility is controlled by a host of regulators whose precise functions remain to be determined. Significantly, a specific Golgi receptor for dynein has not been identified. This has impaired progress toward elucidation of membrane-motor-microtubule attachment in the periphery and, after inward movement, recycling of the motor for another round. Pericentrosomal positioning of the Golgi apparatus is dynamic. It is regulated during critical cellular processes such as mitosis, differentiation, cell polarization, and cell migration. Positioning is also important as it aligns the Golgi along an axis of cell polarity. In certain cell types, this promotes secretion directed to the proximal plasma membrane domain thereby maintaining specializations critical for diverse processes including wound healing, immunological synapse formation, and axon determination. PMID:21504874

Microtubule minus end motors kinesin-14 and dynein drive nuclear congression in parallel pathways.

PubMed

Scheffler, Kathleen; Minnes, Refael; Fraisier, Vincent; Paoletti, Anne; Tran, Phong T

2015-04-13

Microtubules (MTs) and associated motors play a central role in nuclear migration, which is crucial for diverse biological functions including cell division, polarity, and sexual reproduction. In this paper, we report a dual mechanism underlying nuclear congression during fission yeast karyogamy upon mating of haploid cells. Using microfluidic chambers for long-term imaging, we captured the precise timing of nuclear congression and identified two minus end-directed motors operating in parallel in this process. Kinesin-14 Klp2 associated with MTs may cross-link and slide antiparallel MTs emanating from the two nuclei, whereas dynein accumulating at spindle pole bodies (SPBs) may pull MTs nucleated from the opposite SPB. Klp2-dependent nuclear congression proceeds at constant speed, whereas dynein accumulation results in an increase of nuclear velocity over time. Surprisingly, the light intermediate chain Dli1, but not dynactin, is required for this previously unknown function of dynein. We conclude that efficient nuclear congression depends on the cooperation of two minus end-directed motors. © 2015 Scheffler et al.

A mathematical tool to generate complex whole body motor tasks and test hypotheses on underlying motor planning.

PubMed

Tagliabue, Michele; Pedrocchi, Alessandra; Pozzo, Thierry; Ferrigno, Giancarlo

2008-01-01

In spite of the complexity of human motor behavior, difficulties in mathematical modeling have restricted to rather simple movements attempts to identify the motor planning criterion used by the central nervous system. This paper presents a novel-simulation technique able to predict the "desired trajectory" corresponding to a wide range of kinematic and kinetic optimality criteria for tasks involving many degrees of freedom and the coordination between goal achievement and balance maintenance. Employment of proper time discretization, inverse dynamic methods and constrained optimization technique are combined. The application of this simulator to a planar whole body pointing movement shows its effectiveness in managing system nonlinearities and instability as well as in ensuring the anatomo-physiological feasibility of predicted motor plans. In addition, the simulator's capability to simultaneously optimize competing movement aspects represents an interesting opportunity for the motor control community, in which the coexistence of several controlled variables has been hypothesized.

Motor system evolution and the emergence of high cognitive functions.

PubMed

Mendoza, Germán; Merchant, Hugo

2014-11-01

In human and nonhuman primates, the cortical motor system comprises a collection of brain areas primarily related to motor control. Existing evidence suggests that no other mammalian group has the number, extension, and complexity of motor-related areas observed in the frontal lobe of primates. Such diversity is probably related to the wide behavioral flexibility that primates display. Indeed, recent comparative anatomical, psychophysical, and neurophysiological studies suggest that the evolution of the motor cortical areas closely correlates with the emergence of high cognitive abilities. Advances in understanding the cortical motor system have shown that these areas are also related to functions previously linked to higher-order associative areas. In addition, experimental observations have shown that the classical distinction between perceptual and motor functions is not strictly followed across cortical areas. In this paper, we review evidence suggesting that evolution of the motor system had a role in the shaping of different cognitive functions in primates. We argue that the increase in the complexity of the motor system has contributed to the emergence of new abilities observed in human and nonhuman primates, including the recognition and imitation of the actions of others, speech perception and production, and the execution and appreciation of the rhythmic structure of music. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Logical Framework for Service Migration Based Survivability

DTIC Science & Technology

2016-06-24

platforms; Service Migration Strategy Fuzzy Inference System Knowledge Base Fuzzy rules representing domain expert knowledge about implications of...service migration strategy. Our approach uses expert knowledge as linguistic reasoning rules and takes service programs damage assessment, service...programs complexity, and available network capability as input. The fuzzy inference system includes four components as shown in Figure 5: (1) a knowledge

Complex movement disorders at disease onset in childhood narcolepsy with cataplexy

PubMed Central

Pizza, Fabio; Palaia, Vincenzo; Franceschini, Christian; Poli, Francesca; Moghadam, Keivan K.; Cortelli, Pietro; Nobili, Lino; Bruni, Oliviero; Dauvilliers, Yves; Lin, Ling; Edwards, Mark J.; Mignot, Emmanuel; Bhatia, Kailash P.

2011-01-01

Narcolepsy with cataplexy is characterized by daytime sleepiness, cataplexy (sudden loss of bilateral muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. Narcolepsy with cataplexy is most often associated with human leucocyte antigen-DQB1*0602 and is caused by the loss of hypocretin-producing neurons in the hypothalamus of likely autoimmune aetiology. Noting that children with narcolepsy often display complex abnormal motor behaviours close to disease onset that do not meet the classical definition of cataplexy, we systematically analysed motor features in 39 children with narcolepsy with cataplexy in comparison with 25 age- and sex-matched healthy controls. We found that patients with narcolepsy with cataplexy displayed a complex array of ‘negative’ (hypotonia) and ‘active’ (ranging from perioral movements to dyskinetic–dystonic movements or stereotypies) motor disturbances. ‘Active’ and ‘negative’ motor scores correlated positively with the presence of hypotonic features at neurological examination and negatively with disease duration, whereas ‘negative’ motor scores also correlated negatively with age at disease onset. These observations suggest that paediatric narcolepsy with cataplexy often co-occurs with a complex movement disorder at disease onset, a phenomenon that may vanish later in the course of the disease. Further studies are warranted to assess clinical course and whether the associated movement disorder is also caused by hypocretin deficiency or by additional neurochemical abnormalities. PMID:21930661

A novel instrumented multipeg running wheel system, Step-Wheel, for monitoring and controlling complex sequential stepping in mice

PubMed Central

Nagata, Masatoshi; Yanagihara, Dai; Tomioka, Ryohei; Utsumi, Hideko; Kubota, Yasuo; Yagi, Takeshi; Graybiel, Ann M.; Yamamori, Tetsuo

2011-01-01

Motor control is critical in daily life as well as in artistic and athletic performance and thus is the subject of intense interest in neuroscience. Mouse models of movement disorders have proven valuable for many aspects of investigation, but adequate methods for analyzing complex motor control in mouse models have not been fully established. Here, we report the development of a novel running-wheel system that can be used to evoke simple and complex stepping patterns in mice. The stepping patterns are controlled by spatially organized pegs, which serve as footholds that can be arranged in adjustable, ladder-like configurations. The mice run as they drink water from a spout, providing reward, while the wheel turns at a constant speed. The stepping patterns of the mice can thus be controlled not only spatially, but also temporally. A voltage sensor to detect paw touches is attached to each peg, allowing precise registration of footfalls. We show that this device can be used to analyze patterns of complex motor coordination in mice. We further demonstrate that it is possible to measure patterns of neural activity with chronically implanted tetrodes as the mice engage in vigorous running bouts. We suggest that this instrumented multipeg running wheel (which we name the Step-Wheel System) can serve as an important tool in analyzing motor control and motor learning in mice. PMID:21525375

A novel instrumented multipeg running wheel system, Step-Wheel, for monitoring and controlling complex sequential stepping in mice.

PubMed

Kitsukawa, Takashi; Nagata, Masatoshi; Yanagihara, Dai; Tomioka, Ryohei; Utsumi, Hideko; Kubota, Yasuo; Yagi, Takeshi; Graybiel, Ann M; Yamamori, Tetsuo

2011-07-01

Motor control is critical in daily life as well as in artistic and athletic performance and thus is the subject of intense interest in neuroscience. Mouse models of movement disorders have proven valuable for many aspects of investigation, but adequate methods for analyzing complex motor control in mouse models have not been fully established. Here, we report the development of a novel running-wheel system that can be used to evoke simple and complex stepping patterns in mice. The stepping patterns are controlled by spatially organized pegs, which serve as footholds that can be arranged in adjustable, ladder-like configurations. The mice run as they drink water from a spout, providing reward, while the wheel turns at a constant speed. The stepping patterns of the mice can thus be controlled not only spatially, but also temporally. A voltage sensor to detect paw touches is attached to each peg, allowing precise registration of footfalls. We show that this device can be used to analyze patterns of complex motor coordination in mice. We further demonstrate that it is possible to measure patterns of neural activity with chronically implanted tetrodes as the mice engage in vigorous running bouts. We suggest that this instrumented multipeg running wheel (which we name the Step-Wheel System) can serve as an important tool in analyzing motor control and motor learning in mice.

Handwriting Development, Competency, and Intervention

ERIC Educational Resources Information Center

Feder, Katya P.; Majnemer, Annette

2007-01-01

Failure to attain handwriting competency during the school-age years often has far-reaching negative effects on both academic success and self-esteem. This complex occupational task has many underlying component skills that may interfere with handwriting performance. Fine motor control, bilateral and visual-motor integration, motor planning,…

Motor-driven intracellular transport powers bacterial gliding motility.

PubMed

Sun, Mingzhai; Wartel, Morgane; Cascales, Eric; Shaevitz, Joshua W; Mignot, Tâm

2011-05-03

Protein-directed intracellular transport has not been observed in bacteria despite the existence of dynamic protein localization and a complex cytoskeleton. However, protein trafficking has clear potential uses for important cellular processes such as growth, development, chromosome segregation, and motility. Conflicting models have been proposed to explain Myxococcus xanthus motility on solid surfaces, some favoring secretion engines at the rear of cells and others evoking an unknown class of molecular motors distributed along the cell body. Through a combination of fluorescence imaging, force microscopy, and genetic manipulation, we show that membrane-bound cytoplasmic complexes consisting of motor and regulatory proteins are directionally transported down the axis of a cell at constant velocity. This intracellular motion is transmitted to the exterior of the cell and converted to traction forces on the substrate. Thus, this study demonstrates the existence of a conserved class of processive intracellular motors in bacteria and shows how these motors have been adapted to produce cell motility.

Doxycycline reduces the migration of tuberous sclerosis complex-2 null cells - effects on RhoA-GTPase and focal adhesion kinase.

PubMed

Ng, Ho Yin; Oliver, Brian Gregory George; Burgess, Janette Kay; Krymskaya, Vera P; Black, Judith Lee; Moir, Lyn M

2015-11-01

Lymphangioleiomyomatosis (LAM) is associated with dysfunction of the tuberous sclerosis complex (TSC) leading to enhanced cell proliferation and migration. This study aims to examine whether doxycycline, a tetracycline antibiotic, can inhibit the enhanced migration of TSC2-deficient cells, identify signalling pathways through which doxycycline works and to assess the effectiveness of combining doxycycline with rapamycin (mammalian target of rapamycin complex 1 inhibitor) in controlling cell migration, proliferation and wound closure. TSC2-positive and TSC2-negative mouse embryonic fibroblasts (MEF), 323-TSC2-positive and 323-TSC2-null MEF and Eker rat uterine leiomyoma (ELT3) cells were treated with doxycycline or rapamycin alone, or in combination. Migration, wound closure and proliferation were assessed using a transwell migration assay, time-lapse microscopy and manual cell counts respectively. RhoA-GTPase activity, phosphorylation of p70S6 kinase (p70S6K) and focal adhesion kinase (FAK) in TSC2-negative MEF treated with doxycycline were examined using ELISA and immunoblotting techniques. The enhanced migration of TSC2-null cells was reduced by doxycycline at concentrations as low as 20 pM, while the rate of wound closure was reduced at 2-59 μM. Doxycycline decreased RhoA-GTPase activity and phosphorylation of FAK in these cells but had no effect on the phosphorylation of p70S6K, ERK1/2 or AKT. Combining doxycycline with rapamycin significantly reduced the rate of wound closure at lower concentrations than achieved with either drug alone. This study shows that doxycycline inhibits TSC2-null cell migration. Thus doxycycline has potential as an anti-migratory agent in the treatment of diseases with TSC2 dysfunction. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

A complex social-ecological disaster: Environmentally induced forced migration

PubMed Central

Rechkemmer, Andreas; O'Connor, Ashley; Rai, Abha; Decker Sparks, Jessica L.; Mudliar, Pranietha; Shultz, James M.

2016-01-01

ABSTRACT In the 21st century, global issues are increasingly characterized by inter-connectedness and complexity. Global environmental change, and climate change in particular, has become a powerful driver and catalyst of forced migration and internal displacement of people. Environmental migrants may far outnumber any other group of displaced people and refugees in the years to come. Deeper scientific integration, especially across the social sciences, is a prerequisite to tackle this issue.

A complex social-ecological disaster: Environmentally induced forced migration.

PubMed

Rechkemmer, Andreas; O'Connor, Ashley; Rai, Abha; Decker Sparks, Jessica L; Mudliar, Pranietha; Shultz, James M

2016-01-01

In the 21 st century, global issues are increasingly characterized by inter-connectedness and complexity. Global environmental change, and climate change in particular, has become a powerful driver and catalyst of forced migration and internal displacement of people. Environmental migrants may far outnumber any other group of displaced people and refugees in the years to come. Deeper scientific integration, especially across the social sciences, is a prerequisite to tackle this issue.

Lack of spacing effects during piano learning.

PubMed

Wiseheart, Melody; D'Souza, Annalise A; Chae, Jacey

2017-01-01

Spacing effects during retention of verbal information are easily obtained, and the effect size is large. Relatively little evidence exists on whether motor skill retention benefits from distributed practice, with even less evidence on complex motor skills. We taught a 17-note musical sequence on a piano to individuals without prior formal training. There were five lags between learning episodes: 0-, 1-, 5-, 10-, and 15-min. After a 5-min retention interval, participants' performance was measured using three criteria: accuracy of note playing, consistency in pressure applied to the keys, and consistency in timing. No spacing effect was found, suggesting that the effect may not always be demonstrable for complex motor skills or non-verbal abilities (timing and motor skills). Additionally, we taught short phrases from five songs, using the same set of lags and retention interval, and did not find any spacing effect for accuracy of song reproduction. Our findings indicate that although the spacing effect is one of the most robust phenomena in the memory literature (as demonstrated by verbal learning studies), the effect may vary when considered in the novel realm of complex motor skills such as piano performance.

Lack of spacing effects during piano learning

PubMed Central

D’Souza, Annalise A.; Chae, Jacey

2017-01-01

Spacing effects during retention of verbal information are easily obtained, and the effect size is large. Relatively little evidence exists on whether motor skill retention benefits from distributed practice, with even less evidence on complex motor skills. We taught a 17-note musical sequence on a piano to individuals without prior formal training. There were five lags between learning episodes: 0-, 1-, 5-, 10-, and 15-min. After a 5-min retention interval, participants’ performance was measured using three criteria: accuracy of note playing, consistency in pressure applied to the keys, and consistency in timing. No spacing effect was found, suggesting that the effect may not always be demonstrable for complex motor skills or non-verbal abilities (timing and motor skills). Additionally, we taught short phrases from five songs, using the same set of lags and retention interval, and did not find any spacing effect for accuracy of song reproduction. Our findings indicate that although the spacing effect is one of the most robust phenomena in the memory literature (as demonstrated by verbal learning studies), the effect may vary when considered in the novel realm of complex motor skills such as piano performance. PMID:28800631

Development of motor speed and associated movements from 5 to 18 years.

PubMed

Gasser, Theo; Rousson, Valentin; Caflisch, Jon; Jenni, Oskar G

2010-03-01

To study the development of motor speed and associated movements in participants aged 5 to 18 years for age, sex, and laterality. Ten motor tasks of the Zurich Neuromotor Assessment (repetitive and alternating movements of hands and feet, repetitive and sequential finger movements, the pegboard, static and dynamic balance, diadochokinesis) were administered to 593 right-handed participants (286 males, 307 females). A strong improvement with age was observed in motor speed from age 5 to 10, followed by a levelling-off between 12 and 18 years. Simple tasks and the pegboard matured early and complex tasks later. Simple tasks showed no associated movements beyond early childhood; in complex tasks associated movements persisted until early adulthood. The two sexes differed only marginally in speed, but markedly in associated movements. A significant laterality (p<0.001) in speed was found for all tasks except for static balance; the pegboard was most lateralized, and sequential finger movements least. Associated movements were lateralized only for a few complex tasks. We also noted a substantial interindividual variability. Motor speed and associated movements improve strongly in childhood, weakly in adolescence, and are both of developmental relevance. Because they correlate weakly, they provide complementary information.

Nonsomatotopic organization of the higher motor centers in octopus.

PubMed

Zullo, Letizia; Sumbre, German; Agnisola, Claudio; Flash, Tamar; Hochner, Binyamin

2009-10-13

Hyperredundant limbs with a virtually unlimited number of degrees of freedom (DOFs) pose a challenge for both biological and computational systems of motor control. In the flexible arms of the octopus, simplification strategies have evolved to reduce the number of controlled DOFs. Motor control in the octopus nervous system is hierarchically organized. A relatively small central brain integrates a huge amount of visual and tactile information from the large optic lobes and the peripheral nervous system of the arms and issues commands to lower motor centers controlling the elaborated neuromuscular system of the arms. This unique organization raises new questions on the organization of the octopus brain and whether and how it represents the rich movement repertoire. We developed a method of brain microstimulation in freely behaving animals and stimulated the higher motor centers-the basal lobes-thus inducing discrete and complex sets of movements. As stimulation strength increased, complex movements were recruited from basic components shared by different types of movement. We found no stimulation site where movements of a single arm or body part could be elicited. Discrete and complex components have no central topographical organization but are distributed over wide regions.

Disruption of self-organized actions in monkeys with progressive MPTP-induced parkinsonism. I. Effects of task complexity.

PubMed

Pessiglione, Mathias; Guehl, Dominique; Hirsch, Etienne C; Féger, Jean; Tremblay, Léon

2004-01-01

Parkinson's disease (PD) is characterized by motor symptoms, usually accompanied by cognitive deficits. The question addressed in this study is whether complexity of routine actions can exacerbate parkinsonian disorders that are often considered to be motor symptoms. To examine this question, we trained four vervet monkeys (Cercopithecus aethiops) to perform three multiple-choice retrieval tasks. In order of ascending complexity, rewards were freely available (task 1), covered with transparent sliding plaques (task 2), and covered with opaque sliding plaques cued by symbols (task 3). Thus, from task 1 to task 2 we added a motor difficulty--the recall of context-adapted movement; and from task 2 to task 3 we added a cognitive difficulty: the recall of symbol-reward associations. The more complex the task, the longer it took to learn, but after extensive training the performance was stable in all tasks, with similar retrieval durations. The monkeys then received systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections (0.3-0.4 mg/kg) every 4-7 days, until the first motor symptoms appeared. In the course of MPTP intoxication, the behavioural performance declined while the motor symptoms were absent or mild--the retrieval duration increased, and non-initiated choices and hesitations between choices became frequent. Interestingly, this decline was in proportion to task complexity, and was particularly pronounced with the cognitive difficulty. Furthermore, freezing appeared only with the cognitive difficulty. We therefore suggest that everyday cognitive difficulties may exacerbate hypokinesia (lack of initiation, abnormal slowness) and executive disorders (hesitations, freezing) in the early stages of human PD.

Actigraphically assessed activity in unipolar depression: a comparison of inpatients with and without motor retardation.

PubMed

Krane-Gartiser, Karoline; Henriksen, Tone E G; Vaaler, Arne E; Fasmer, Ole Bernt; Morken, Gunnar

2015-09-01

To compare the activity patterns of inpatients with unipolar depression, who had been divided into groups with and without motor retardation prior to actigraphy monitoring. Twenty-four-hour actigraphy recordings from 52 consecutively, acutely admitted inpatients with unipolar depression (ICD-10) were compared to recordings from 28 healthy controls. The patients, admitted between September 2011 and April 2012, were separated into 2 groups: 25 with motor retardation and 27 without motor retardation. Twenty-eight healthy controls were also included. Twenty-four-hour recordings, 9-hour daytime sequences, and 64-minute periods of continuous motor activity in the morning and evening were analyzed for mean activity, variability, and complexity. Patients with motor retardation had a reduced mean activity level (P = .04) and higher intraindividual variability, as shown by increased standard deviation (SD) (P = .003) and root mean square successive difference (RMSSD) (P = .025), during 24 hours compared to the patients without motor retardation. Both patient groups demonstrated significantly lower mean activity compared to healthy controls (P < .001) as well as higher SD (P < .02) and RMSSD (P < .001) and a higher RMSSD/SD ratio (P = .04). In the active morning period, the patients without motor retardation displayed significantly increased complexity compared to motor-retarded patients (P = .006). The patients with and without motor retardation differ in activity patterns. Findings in depressed inpatients without motor retardation closely resemble those of inpatients with mania. © Copyright 2015 Physicians Postgraduate Press, Inc.

ATP synthase--a marvellous rotary engine of the cell.

PubMed

Yoshida, M; Muneyuki, E; Hisabori, T

2001-09-01

ATP synthase can be thought of as a complex of two motors--the ATP-driven F1 motor and the proton-driven Fo motor--that rotate in opposite directions. The mechanisms by which rotation and catalysis are coupled in the working enzyme are now being unravelled on a molecular scale.

Arctic complexity: a case study on diel vertical migration of zooplankton

PubMed Central

Berge, Jørgen; Cottier, Finlo; Varpe, Øystein; Renaud, Paul E.; Falk-Petersen, Stig; Kwasniewski, Sawomir; Griffiths, Colin; Søreide, Janne E.; Johnsen, Geir; Aubert, Anais; Bjærke, Oda; Hovinen, Johanna; Jung-Madsen, Signe; Tveit, Martha; Majaneva, Sanna

2014-01-01

Diel vertical migration (DVM) of zooplankton is a global phenomenon, characteristic of both marine and limnic environments. At high latitudes, patterns of DVM have been documented, but rather little knowledge exists regarding which species perform this ecologically important behaviour. Also, in the Arctic, the vertically migrating components of the zooplankton community are usually regarded as a single sound scattering layer (SSL) performing synchronized patterns of migration directly controlled by ambient light. Here, we present evidence for hitherto unknown complexity of Arctic marine systems, where zooplankton form multiple aggregations through the water column seen via acoustics as distinct SSLs. We show that while the initiation of DVM during the autumnal equinox is light mediated, the vertical positioning of the migrants during day is linked more to the thermal characteristics of water masses than to irradiance. During night, phytoplankton biomass is shown to be the most important factor determining the vertical positioning of all migrating taxa. Further, we develop a novel way of representing acoustic data in the form of a Sound Image (SI) that enables a direct comparison of the relative importance of each potential scatterer based upon the theoretical contribution of their backscatter. Based on our comparison of locations with contrasting hydrography, we conclude that a continued warming of the Arctic is likely to result in more complex ecotones across the Arctic marine system. PMID:25221372

APC and Smad7 link TGFβ type I receptors to the microtubule system to promote cell migration

PubMed Central

Ekman, Maria; Mu, Yabing; Lee, So Young; Edlund, Sofia; Kozakai, Takaharu; Thakur, Noopur; Tran, Hoanh; Qian, Jiang; Groeden, Joanna; Heldin, Carl-Henrik; Landström, Maréne

2012-01-01

Cell migration occurs by activation of complex regulatory pathways that are spatially and temporally integrated in response to extracellular cues. Binding of adenomatous polyposis coli (APC) to the microtubule plus ends in polarized cells is regulated by glycogen synthase kinase 3β (GSK-3β). This event is crucial for establishment of cell polarity during directional migration. However, the role of APC for cellular extension in response to extracellular signals is less clear. Smad7 is a direct target gene for transforming growth factor-β (TGFβ) and is known to inhibit various TGFβ-induced responses. Here we report a new function for Smad7. We show that Smad7 and p38 mitogen–activated protein kinase together regulate the expression of APC and cell migration in prostate cancer cells in response to TGFβ stimulation. In addition, Smad7 forms a complex with APC and acts as an adaptor protein for p38 and GSK-3β kinases to facilitate local TGFβ/p38–dependent inactivation of GSK-3β, accumulation of β-catenin, and recruitment of APC to the microtubule plus end in the leading edge of migrating prostate cancer cells. Moreover, the Smad7–APC complex links the TGFβ type I receptor to the microtubule system to regulate directed cellular extension and migratory responses evoked by TGFβ. PMID:22496417

Interactive effect of acute pain and motor learning acquisition on sensorimotor integration and motor learning outcomes

PubMed Central

Dancey, Erin; Andrew, Danielle; Yielder, Paul

2016-01-01

Previous work has demonstrated differential changes in early somatosensory evoked potentials (SEPs) when motor learning acquisition occurred in the presence of acute pain; however, the learning task was insufficiently complex to determine how these underlying neurophysiological differences impacted learning acquisition and retention. To address this limitation, we have utilized a complex motor task in conjunction with SEPs. Two groups of 12 participants (n = 24) were randomly assigned to either a capsaicin (capsaicin cream) or a control (inert lotion) group. SEP amplitudes were collected at baseline, after application, and after motor learning acquisition. Participants performed a motor acquisition task followed by a pain-free retention task within 24–48 h. After motor learning acquisition, the amplitude of the N20 SEP peak significantly increased (P < 0.05) and the N24 SEP peak significantly decreased (P < 0.001) for the control group while the N18 SEP peak significantly decreased (P < 0.01) for the capsaicin group. The N30 SEP peak was significantly increased (P < 0.001) after motor learning acquisition for both groups. The P25 SEP peak decreased significantly (P < 0.05) after the application of capsaicin cream. Both groups improved in accuracy after motor learning acquisition (P < 0.001). The capsaicin group outperformed the control group before motor learning acquisition (P < 0.05) and after motor learning acquisition (P < 0.05) and approached significance at retention (P = 0.06). Improved motor learning in the presence of capsaicin provides support for the enhancement of motor learning while in acute pain. In addition, the changes in SEP peak amplitudes suggest that early SEP changes reflect neurophysiological alterations accompanying both motor learning and mild acute pain. PMID:27535371

Adaptation of the resettled Kenyah Dayak villagers to riverine environment in east Kalimantan: a preliminary report.

PubMed

Abe, T; Ohtsuka, R; Watanabe, M; Yoshida, M; Futatsuka, M

1995-06-01

The Kenyah Dayak in East Kalimantan (Indonesia), who migrated from their mountainous homeland to a riverine village in the 1940s, have subsisted on slash-and-burn rice cultivation. To cope with rapidly increasing population, the villagers have not changed their farming practice to increase land productivity but instead have exploited fields in remote riverbanks, using motorized canoes.

The spectrum of REM sleep-related episodes in children with type 1 narcolepsy.

PubMed

Antelmi, Elena; Pizza, Fabio; Vandi, Stefano; Neccia, Giulia; Ferri, Raffaele; Bruni, Oliviero; Filardi, Marco; Cantalupo, Gaetano; Liguori, Rocco; Plazzi, Giuseppe

2017-06-01

Type 1 narcolepsy is a central hypersomnia due to the loss of hypocretin-producing neurons and characterized by cataplexy, excessive daytime sleepiness, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. In children, close to the disease onset, type 1 narcolepsy has peculiar clinical features with severe cataplexy and a complex admixture of movement disorders occurring while awake. Motor dyscontrol during sleep has never been systematically investigated. Suspecting that abnormal motor control might affect also sleep, we systematically analysed motor events recorded by means of video polysomnography in 40 children with type 1 narcolepsy (20 females; mean age 11.8 ± 2.6 years) and compared these data with those recorded in 22 age- and sex-matched healthy controls. Motor events were classified as elementary movements, if brief and non-purposeful and complex behaviours, if simulating purposeful behaviours. Complex behaviours occurring during REM sleep were further classified as 'classically-defined' and 'pantomime-like' REM sleep behaviour disorder episodes, based on their duration and on their pattern (i.e. brief and vivid-energetic in the first case, longer and with subcontinuous gesturing mimicking daily life activity in the second case). Elementary movements emerging either from non-REM or REM sleep were present in both groups, even if those emerging from REM sleep were more numerous in the group of patients. Conversely, complex behaviours could be detected only in children with type 1 narcolepsy and were observed in 13 patients, with six having 'classically-defined' REM sleep behaviour disorder episodes and seven having 'pantomime-like' REM sleep behaviour disorder episodes. Complex behaviours during REM sleep tended to recur in a stereotyped fashion for several times during the night, up to be almost continuous. Patients displaying a more severe motor dyscontrol during REM sleep had also more severe motor disorder during daytime (i.e. status cataplecticus) and more complaints of disrupted nocturnal sleep and of excessive daytime sleepiness. The neurophysiological hallmark of this severe motor dyscontrol during REM sleep was a decreased atonia index. The present study reports for the first time the occurrence of a severe and peculiar motor disorder during REM sleep in paediatric type 1 narcolepsy and confirms the presence of a severe motor dyscontrol in these patients, emerging not only from wakefulness (i.e. status cataplecticus), but also from sleep (i.e. complex behaviours during REM sleep). This is probably related to the acute imbalance of the hypocretinergic system, which physiologically acts by promoting movements during wakefulness and suppressing them during sleep. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Inhibition during response preparation is sensitive to response complexity

PubMed Central

Saks, Dylan; Hoang, Timothy; Ivry, Richard B.

2015-01-01

Motor system excitability is transiently suppressed during the preparation of movement. This preparatory inhibition is hypothesized to facilitate response selection and initiation. Given that demands on selection and initiation processes increase with movement complexity, we hypothesized that complexity would influence preparatory inhibition. To test this hypothesis, we probed corticospinal excitability during a delayed-response task in which participants were cued to prepare right- or left-hand movements of varying complexity. Single-pulse transcranial magnetic stimulation was applied over right primary motor cortex to elicit motor evoked potentials (MEPs) from the first dorsal interosseous (FDI) of the left hand. MEP suppression was greater during the preparation of responses involving coordination of the FDI and adductor digiti minimi relative to easier responses involving only the FDI, independent of which hand was cued to respond. In contrast, this increased inhibition was absent when the complex responses required sequential movements of the two muscles. Moreover, complexity did not influence the level of inhibition when the response hand was fixed for the trial block, regardless of whether the complex responses were performed simultaneously or sequentially. These results suggest that preparatory inhibition contributes to response selection, possibly by suppressing extraneous movements when responses involve the simultaneous coordination of multiple effectors. PMID:25717168

Environmental Constraints Guide Migration of Malaria Parasites during Transmission

PubMed Central

Hellmann, Janina Kristin; Münter, Sylvia; Kudryashev, Mikhail; Schulz, Simon; Heiss, Kirsten; Müller, Ann-Kristin; Matuschewski, Kai; Spatz, Joachim P.; Schwarz, Ulrich S.; Frischknecht, Friedrich

2011-01-01

Migrating cells are guided in complex environments mainly by chemotaxis or structural cues presented by the surrounding tissue. During transmission of malaria, parasite motility in the skin is important for Plasmodium sporozoites to reach the blood circulation. Here we show that sporozoite migration varies in different skin environments the parasite encounters at the arbitrary sites of the mosquito bite. In order to systematically examine how sporozoite migration depends on the structure of the environment, we studied it in micro-fabricated obstacle arrays. The trajectories observed in vivo and in vitro closely resemble each other suggesting that structural constraints can be sufficient to guide Plasmodium sporozoites in complex environments. Sporozoite speed in different environments is optimized for migration and correlates with persistence length and dispersal. However, this correlation breaks down in mutant sporozoites that show adhesion impairment due to the lack of TRAP-like protein (TLP) on their surfaces. This may explain their delay in infecting the host. The flexibility of sporozoite adaption to different environments and a favorable speed for optimal dispersal ensures efficient host switching during malaria transmission. PMID:21698220

Physical assistance devices in complex motor skill learning: benefits of a self-controlled practice schedule.

PubMed

Wulf, G; Toole, T

1999-09-01

This study examines the effects of a self-controlled use of physical assistance devices on learning a complex motor skill (i.e., producing slalom-type movements on a ski simulator). Physical assistance was provided by ski poles. One group of learners (self-control) was provided with the poles whenever they requested them, whereas another (yoked) group had no influence on the pole/no-pole schedule. While there were no group differences during the practice phase (Days 1 and 2), clear group differences emerged in the retention test without poles (Day 3). The self-control group produced significantly larger amplitudes than the yoked group. These results extend previous findings by showing learning advantages of the self-controlled use of physical assistance devices in complex motor skill learning.

Iterative methods for 3D implicit finite-difference migration using the complex Padé approximation

NASA Astrophysics Data System (ADS)

Costa, Carlos A. N.; Campos, Itamara S.; Costa, Jessé C.; Neto, Francisco A.; Schleicher, Jörg; Novais, Amélia

2013-08-01

Conventional implementations of 3D finite-difference (FD) migration use splitting techniques to accelerate performance and save computational cost. However, such techniques are plagued with numerical anisotropy that jeopardises the correct positioning of dipping reflectors in the directions not used for the operator splitting. We implement 3D downward continuation FD migration without splitting using a complex Padé approximation. In this way, the numerical anisotropy is eliminated at the expense of a computationally more intensive solution of a large-band linear system. We compare the performance of the iterative stabilized biconjugate gradient (BICGSTAB) and that of the multifrontal massively parallel direct solver (MUMPS). It turns out that the use of the complex Padé approximation not only stabilizes the solution, but also acts as an effective preconditioner for the BICGSTAB algorithm, reducing the number of iterations as compared to the implementation using the real Padé expansion. As a consequence, the iterative BICGSTAB method is more efficient than the direct MUMPS method when solving a single term in the Padé expansion. The results of both algorithms, here evaluated by computing the migration impulse response in the SEG/EAGE salt model, are of comparable quality.

Spindle pole body-anchored Kar3 drives the nucleus along microtubules from another nucleus in preparation for nuclear fusion during yeast karyogamy.

PubMed

Gibeaux, Romain; Politi, Antonio Z; Nédélec, François; Antony, Claude; Knop, Michael

2013-02-01

Nuclear migration during yeast karyogamy, termed nuclear congression, is required to initiate nuclear fusion. Congression involves a specific regulation of the microtubule minus end-directed kinesin-14 motor Kar3 and a rearrangement of the cytoplasmic microtubule attachment sites at the spindle pole bodies (SPBs). However, how these elements interact to produce the forces necessary for nuclear migration is less clear. We used electron tomography, molecular genetics, quantitative imaging, and first principles modeling to investigate how cytoplasmic microtubules are organized during nuclear congression. We found that Kar3, with the help of its light chain, Cik1, is anchored during mating to the SPB component Spc72 that also serves as a nucleator and anchor for microtubules via their minus ends. Moreover, we show that no direct microtubule-microtubule interactions are required for nuclear migration. Instead, SPB-anchored Kar3 exerts the necessary pulling forces laterally on microtubules emanating from the SPB of the mating partner nucleus. Therefore, a twofold symmetrical application of the core principle that drives nuclear migration in higher cells is used in yeast to drive nuclei toward each other before nuclear fusion.

Spindle pole body-anchored Kar3 drives the nucleus along microtubules from another nucleus in preparation for nuclear fusion during yeast karyogamy

PubMed Central

Gibeaux, Romain; Politi, Antonio Z.; Nédélec, François; Antony, Claude; Knop, Michael

2013-01-01

Nuclear migration during yeast karyogamy, termed nuclear congression, is required to initiate nuclear fusion. Congression involves a specific regulation of the microtubule minus end-directed kinesin-14 motor Kar3 and a rearrangement of the cytoplasmic microtubule attachment sites at the spindle pole bodies (SPBs). However, how these elements interact to produce the forces necessary for nuclear migration is less clear. We used electron tomography, molecular genetics, quantitative imaging, and first principles modeling to investigate how cytoplasmic microtubules are organized during nuclear congression. We found that Kar3, with the help of its light chain, Cik1, is anchored during mating to the SPB component Spc72 that also serves as a nucleator and anchor for microtubules via their minus ends. Moreover, we show that no direct microtubule–microtubule interactions are required for nuclear migration. Instead, SPB-anchored Kar3 exerts the necessary pulling forces laterally on microtubules emanating from the SPB of the mating partner nucleus. Therefore, a twofold symmetrical application of the core principle that drives nuclear migration in higher cells is used in yeast to drive nuclei toward each other before nuclear fusion. PMID:23388829

Endogenous electric fields as guiding cue for cell migration

PubMed Central

Funk, Richard H. W.

2015-01-01

This review covers two topics: (1) “membrane potential of low magnitude and related electric fields (bioelectricity)” and (2) “cell migration under the guiding cue of electric fields (EF).”Membrane potentials for this “bioelectricity” arise from the segregation of charges by special molecular machines (pumps, transporters, ion channels) situated within the plasma membrane of each cell type (including eukaryotic non-neural animal cells). The arising patterns of ion gradients direct many cell- and molecular biological processes such as embryogenesis, wound healing, regeneration. Furthermore, EF are important as guiding cues for cell migration and are often overriding chemical or topographic cues. In osteoblasts, for instance, the directional information of EF is captured by charged transporters on the cell membrane and transferred into signaling mechanisms that modulate the cytoskeleton and motor proteins. This results in a persistent directional migration along an EF guiding cue. As an outlook, we discuss questions concerning the fluctuation of EF and the frequencies and mapping of the “electric” interior of the cell. Another exciting topic for further research is the modeling of field concepts for such distant, non-chemical cellular interactions. PMID:26029113

Actomyosin Pulls to Advance the Nucleus in a Migrating Tissue Cell

PubMed Central

Wu, Jun; Kent, Ian A.; Shekhar, Nandini; Chancellor, T.J.; Mendonca, Agnes; Dickinson, Richard B.; Lele, Tanmay P.

2014-01-01

The cytoskeletal forces involved in translocating the nucleus in a migrating tissue cell remain unresolved. Previous studies have variously implicated actomyosin-generated pushing or pulling forces on the nucleus, as well as pulling by nucleus-bound microtubule motors. We found that the nucleus in an isolated migrating cell can move forward without any trailing-edge detachment. When a new lamellipodium was triggered with photoactivation of Rac1, the nucleus moved toward the new lamellipodium. This forward motion required both nuclear-cytoskeletal linkages and myosin activity. Apical or basal actomyosin bundles were found not to translate with the nucleus. Although microtubules dampen fluctuations in nuclear position, they are not required for forward translocation of the nucleus during cell migration. Trailing-edge detachment and pulling with a microneedle produced motion and deformation of the nucleus suggestive of a mechanical coupling between the nucleus and the trailing edge. Significantly, decoupling the nucleus from the cytoskeleton with KASH overexpression greatly decreased the frequency of trailing-edge detachment. Collectively, these results explain how the nucleus is moved in a crawling fibroblast and raise the possibility that forces could be transmitted from the front to the back of the cell through the nucleus. PMID:24411232

Evaluation of the myoelectrical activity of the equine ileum infected with Strongylus vulgaris larvae.

PubMed

Berry, C R; Merritt, A M; Burrows, C F; Campbell, M; Drudge, J H

1986-01-01

Five weanling ponies were subjected to an intensive 6-week deworming program after which 4 Ag-AgCl bipolar electrodes were implanted surgically on the distal ileum. For 3 hours each day for 5 consecutive days, ileal myoelectrical activity was recorded from fed ponies under 3 sequential conditions: preinoculation, after oral administration of 1,000 killed Strongylus vulgaris infective larvae (3 ponies), and after oral administration of 1,000 live S vulgaris infective larvae. Recordings were analyzed for slow wave frequency, percentage duration of phases I, II, and III of the migrating myoelectrical complex (MMC), and the frequency of distinct, rapidly migrating action-potential complexes within phase 2 of the MMC. After administration of live and killed infected 3rd-stage larvae, there was a marked increase in the number of disrupted phase III complexes, and a significant (P less than 0.001) increase in the number of migrating action-potential complexes. In addition, after inoculation of live 3rd-stage larvae, there was a significant increase (P less than 0.001) in the percentage of time that the MMC was occupied by prolonged periods devoid of spike activity (phase I). The results indicate that S vulgaris larval mucosal penetration and submucosal migration can cause changes in ileal myoelectrical activity that could cause colic, and that larval antigen alone within the lumen may disrupt ileal motility.

Intermittent tremor migrations beneath Guerrero, Mexico, and implications for fault healing within the slow slip zone

NASA Astrophysics Data System (ADS)

Peng, Yajun; Rubin, Allan M.

2017-01-01

Slow slip events exhibit significant complexity in slip evolution and variations in recurrence intervals. Behavior that varies systematically with recurrence interval is likely to reflect different extents of fault healing between these events. Here we use high-resolution tremor catalogs beneath Guerrero, Mexico, to investigate the mechanics of slow slip. We observe complex tremor propagation styles, including rapid tremor migrations propagating either along the main tremor front or backward, reminiscent of those in northern Cascadia. We also find many migrations that originate well behind the front and repeatedly occupy the same source region during a tremor episode, similar to those previously reported from Shikoku, Japan. These migrations could be driven by slow slip in the surrounding regions, with recurrence intervals possibly modulated by tides. The propagation speed of these migrations decreases systematically with time since the previous migration over the same source area. Tremor amplitudes seem consistent with changes in the propagation speeds being controlled primarily by changes in the slip speeds. One interpretation is that the high propagation speeds and inferred high slip speeds during the migrations with short recurrence intervals are caused by incomplete healing within the host rock adjacent to the shear zone, which could lead to high permeability and reduced dilatant strengthening of the fault gouge. Similar processes may operate in other slow slip source regions such as Cascadia.

Molecular switch-like regulation in motor proteins.

PubMed

Tafoya, Sara; Bustamante, Carlos

2018-06-19

Motor proteins are powered by nucleotide hydrolysis and exert mechanical work to carry out many fundamental biological tasks. To ensure their correct and efficient performance, the motors' activities are allosterically regulated by additional factors that enhance or suppress their NTPase activity. Here, we review two highly conserved mechanisms of ATP hydrolysis activation and repression operating in motor proteins-the glutamate switch and the arginine finger-and their associated regulatory factors. We examine the implications of these regulatory mechanisms in proteins that are formed by multiple ATPase subunits. We argue that the regulatory mechanisms employed by motor proteins display features similar to those described in small GTPases, which require external regulatory elements, such as dissociation inhibitors, exchange factors and activating proteins, to switch the protein's function 'on' and 'off'. Likewise, similar regulatory roles are taken on by the motor's substrate, additional binding factors, and even adjacent subunits in multimeric complexes. However, in motor proteins, more than one regulatory factor and the two mechanisms described here often underlie the machine's operation. Furthermore, ATPase regulation takes place throughout the motor's cycle, which enables a more complex function than the binary 'active' and 'inactive' states.This article is part of a discussion meeting issue 'Allostery and molecular machines'. © 2018 The Author(s).

Development of magneto-rheologial fluid (MRF) based clutch for output torque control of AC motors

NASA Astrophysics Data System (ADS)

Nguyen, Q. Hung; Do, H. M. Hieu; Nguyen, V. Quoc; Nguyen, N. Diep; Le, D. Thang

2018-03-01

In industry, the AC motor is widely used because of low price, power availability, low cost maintenance. The main disadvantages of AC motors compared to DC motors are difficulty in speed and torque control, requiring expensive controllers with complex control algorithms. This is the basic limitations in the widespread adoption of AC motor systems for industrial automation. One feasible solution for AC motor control is using MRF (magneto-rheological fluid) based clutches (shortly called MR clutches) Although there have been many studies on MR clutches, most of these clutches used traditional configuration with coils wound on the middle cylindrical part and a compotator is used to supply power to the coils. Therefore, this type of MR clutches possesses many disadvantages such as high friction and unstable applied current due to commutator, complex structure which causes difficulty in manufacture, assembly, and maintenance. In addition, the bottleneck problem of magnetic field is also a challenging issue. In this research, we will develop a new type of MR clutches that overcomes the abovementioned disadvantages of traditional MR clutches and more suitable for application in controlling of AC motor. Besides, in this study, speed and torque control system for AC motors using developed MR clutches is designed and experimental validated.

Motor performance of tongue with a computer-integrated system under different levels of background physical exertion

PubMed Central

Huo, Xueliang; Johnson-Long, Ashley N.; Ghovanloo, Maysam; Shinohara, Minoru

2015-01-01

The purpose of this study was to compare the motor performance of tongue, using Tongue Drive System, to hand operation for relatively complex tasks under different levels of background physical exertion. Thirteen young able-bodied adults performed tasks that tested the accuracy and variability in tracking a sinusoidal waveform, and the performance in playing two video games that require accurate and rapid movements with cognitive processing using tongue and hand under two levels of background physical exertion. Results show additional background physical activity did not influence rapid and accurate displacement motor performance, but compromised the slow waveform tracking and shooting performances in both hand and tongue. Slow waveform tracking performance by the tongue was compromised with an additional motor or cognitive task, but with an additional motor task only for the hand. Practitioner Summary We investigated the influence of task complexity and background physical exertion on the motor performance of tongue and hand. Results indicate the task performance degrades with an additional concurrent task or physical exertion due to the limited attentional resources available for handling both the motor task and background exertion. PMID:24003900

The Beaker phenomenon and the genomic transformation of northwest Europe.

PubMed

Olalde, Iñigo; Brace, Selina; Allentoft, Morten E; Armit, Ian; Kristiansen, Kristian; Booth, Thomas; Rohland, Nadin; Mallick, Swapan; Szécsényi-Nagy, Anna; Mittnik, Alissa; Altena, Eveline; Lipson, Mark; Lazaridis, Iosif; Harper, Thomas K; Patterson, Nick; Broomandkhoshbacht, Nasreen; Diekmann, Yoan; Faltyskova, Zuzana; Fernandes, Daniel; Ferry, Matthew; Harney, Eadaoin; de Knijff, Peter; Michel, Megan; Oppenheimer, Jonas; Stewardson, Kristin; Barclay, Alistair; Alt, Kurt Werner; Liesau, Corina; Ríos, Patricia; Blasco, Concepción; Miguel, Jorge Vega; García, Roberto Menduiña; Fernández, Azucena Avilés; Bánffy, Eszter; Bernabò-Brea, Maria; Billoin, David; Bonsall, Clive; Bonsall, Laura; Allen, Tim; Büster, Lindsey; Carver, Sophie; Navarro, Laura Castells; Craig, Oliver E; Cook, Gordon T; Cunliffe, Barry; Denaire, Anthony; Dinwiddy, Kirsten Egging; Dodwell, Natasha; Ernée, Michal; Evans, Christopher; Kuchařík, Milan; Farré, Joan Francès; Fowler, Chris; Gazenbeek, Michiel; Pena, Rafael Garrido; Haber-Uriarte, María; Haduch, Elżbieta; Hey, Gill; Jowett, Nick; Knowles, Timothy; Massy, Ken; Pfrengle, Saskia; Lefranc, Philippe; Lemercier, Olivier; Lefebvre, Arnaud; Martínez, César Heras; Olmo, Virginia Galera; Ramírez, Ana Bastida; Maurandi, Joaquín Lomba; Majó, Tona; McKinley, Jacqueline I; McSweeney, Kathleen; Mende, Balázs Gusztáv; Modi, Alessandra; Kulcsár, Gabriella; Kiss, Viktória; Czene, András; Patay, Róbert; Endrődi, Anna; Köhler, Kitti; Hajdu, Tamás; Szeniczey, Tamás; Dani, János; Bernert, Zsolt; Hoole, Maya; Cheronet, Olivia; Keating, Denise; Velemínský, Petr; Dobeš, Miroslav; Candilio, Francesca; Brown, Fraser; Fernández, Raúl Flores; Herrero-Corral, Ana-Mercedes; Tusa, Sebastiano; Carnieri, Emiliano; Lentini, Luigi; Valenti, Antonella; Zanini, Alessandro; Waddington, Clive; Delibes, Germán; Guerra-Doce, Elisa; Neil, Benjamin; Brittain, Marcus; Luke, Mike; Mortimer, Richard; Desideri, Jocelyne; Besse, Marie; Brücken, Günter; Furmanek, Mirosław; Hałuszko, Agata; Mackiewicz, Maksym; Rapiński, Artur; Leach, Stephany; Soriano, Ignacio; Lillios, Katina T; Cardoso, João Luís; Pearson, Michael Parker; Włodarczak, Piotr; Price, T Douglas; Prieto, Pilar; Rey, Pierre-Jérôme; Risch, Roberto; Rojo Guerra, Manuel A; Schmitt, Aurore; Serralongue, Joël; Silva, Ana Maria; Smrčka, Václav; Vergnaud, Luc; Zilhão, João; Caramelli, David; Higham, Thomas; Thomas, Mark G; Kennett, Douglas J; Fokkens, Harry; Heyd, Volker; Sheridan, Alison; Sjögren, Karl-Göran; Stockhammer, Philipp W; Krause, Johannes; Pinhasi, Ron; Haak, Wolfgang; Barnes, Ian; Lalueza-Fox, Carles; Reich, David

2018-03-08

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.

Effects of Mirror Therapy in Stroke Patients With Complex Regional Pain Syndrome Type 1: A Randomized Controlled Study.

PubMed

Pervane Vural, Secil; Nakipoglu Yuzer, Guldal Funda; Sezgin Ozcan, Didem; Demir Ozbudak, Sibel; Ozgirgin, Nese

2016-04-01

To investigate the effects of mirror therapy on upper limb motor functions, spasticity, and pain intensity in patients with hemiplegia accompanied by complex regional pain syndrome type 1. Randomized controlled trial. Training and research hospital. Adult patients with first-time stroke and simultaneous complex regional pain syndrome type 1 of the upper extremity at the dystrophic stage (N=30). Both groups received a patient-specific conventional stroke rehabilitation program for 4 weeks, 5 d/wk, for 2 to 4 h/d. The mirror therapy group received an additional mirror therapy program for 30 min/d. We evaluated the scores of the Brunnstrom recovery stages of the arm and hand for motor recovery, wrist and hand subsections of the Fugl-Meyer Assessment (FMA) and motor items of the FIM-motor for functional status, Modified Ashworth Scale (MAS) for spasticity, and visual analog scale (VAS) for pain severity. After 4 weeks of rehabilitation, both groups had significant improvements in the FIM-motor and VAS scores compared with baseline scores. However, the scores improved more in the mirror therapy group than the control group (P<.001 and P=.03, respectively). Besides, the patients in the mirror therapy arm showed significant improvement in the Brunnstrom recovery stages and FMA scores (P<.05). No significant difference was found for MAS scores. In patients with stroke and simultaneous complex regional pain syndrome type 1, addition of mirror therapy to a conventional stroke rehabilitation program provides more improvement in motor functions of the upper limb and pain perception than conventional therapy without mirror therapy. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Tio2-dopamine complex implanted unilaterally in the caudate nucleus improves motor activity and behavior function of rats with induced hemiparkinsonism.

PubMed

Vergara-Aragón, Patricia; Domínguez-Marrufo, Leonardo Eduardo; Ibarra-Guerrero, Patricia; Hernandez-Ramírez, Heidi; Hernández-Téllez, Beatriz; López-Martínez, Irma Elena; Sánchez-Cervantes, Ivonne; Santiago-Jacinto, Patricia; García-Macedo, Jorge Alberto; Valverde-Aguilar, Guadalupe; Santiago, Julio

2011-01-01

Parkinson's disease (PD) is characterized by malfunction of dopaminergic systems, and the current symptomatic treatment is to replace lost dopamine. For investigating mechanisms of pathogenesis and alternative treatments to compensate lack of dopamine (DA) activity in PD, the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD has been useful, these animals display apomorphine-induced contralateral rotational behavior, when they are examined after lesion. The purpose of this study was to assess Titania-dopamine (TiO2-DA) complexes implanted on the caudate nucleus for diminishing motor behavior alterations of the 6-OHDA rat model. Rats with 6-OHDA unilateral lesions received TiO2 alone or TiO2-DA implants, and were tested for open field (OF) gross motor crossing and rearing behaviors, and apomorphine-induced rotation (G) behavior. TiO2 complex have no effects on rearing OF and G behaviors, and a significant reducing effect on crossing motor behavior of normal rats compared to control non-treated rats throughout 56 days of observation. Interestingly, TiO2-DA treatment significant recovered motor crossing and rearing behaviors in 6-OHDA-lesioned rats, and diminished the G behaviors during 56 days of examination. Additionally, in the 6-OHDA-lesioned rats TiO2 treatment had a moderate recovering effect only on crossing behavior compared to lesioned non treated rats. Our results suggest that continuous release of dopamine in the caudate nucleus from TiO2-DA complex is capable of reversing gross motor deficits observed in the 6-OHDA-lesioned rat model of PD. Thistype of delivery system of DA represents a promising therapy for PD in humans.

Transnational nurse migration: future directions for medical anthropological research.

PubMed

Prescott, Megan; Nichter, Mark

2014-04-01

Transnational nurse migration is a serious global health issue in which inequitably distributed shortages hinder health and development goals. This article selectively reviews the literature on nurse migration that has emerged from nursing, health planning, and the social sciences and offers productive directions for future anthropological research. The literature on global nurse migration has largely focused on push/pull economic logic and the concept of brain drain to understand the causes and effects of nurse migration. These concepts obscure political-economic, historical, and cultural factors that pattern nurse migration and influence the complex effects of nurse migration. Global nurse care chain analysis helps illuminate the numerous nodes in the production and migration of nurses, and management of this transnational process. Examples are provided from the Philippines and India to illustrate ways in which this analysis may be deepened, refined and rendered more critical by anthropological research. Copyright © 2014 Elsevier Ltd. All rights reserved.

3D cancer cell migration in a confined matrix

NASA Astrophysics Data System (ADS)

Alobaidi, Amani; Sun, Bo

Cancer cell migration is widely studied in 2D motion, which does not mimic the invasion processes in vivo. More recently, 3D cell migration studies have been performed. The ability of cancer cells to migrate within the extracellular matrix depends on the physical and biochemical features of the extracellular matrix. We present a model of cell motility in confined matrix geometry. The aim of the study is to study cancer migration in collagen matrix, as a soft tissue, to investigate their motility within the confined and surrounding collagen environment. Different collagen concentrations have been used to show the ability of these cancer cells to move through such a complex structure by measuring Cancer cell migration velocity as well as the displacement. Graduate student physics department.

Thinking, Walking, Talking: Integratory Motor and Cognitive Brain Function

PubMed Central

Leisman, Gerry; Moustafa, Ahmed A.; Shafir, Tal

2016-01-01

In this article, we argue that motor and cognitive processes are functionally related and most likely share a similar evolutionary history. This is supported by clinical and neural data showing that some brain regions integrate both motor and cognitive functions. In addition, we also argue that cognitive processes coincide with complex motor output. Further, we also review data that support the converse notion that motor processes can contribute to cognitive function, as found by many rehabilitation and aerobic exercise training programs. Support is provided for motor and cognitive processes possessing dynamic bidirectional influences on each other. PMID:27252937

Continuously Adaptive vs. Discrete Changes of Task Difficulty in the Training of a Complex Perceptual-Motor Task.

ERIC Educational Resources Information Center

Wood, Milton E.

The purpose of the effort was to determine the benefits to be derived from the adaptive training technique of automatically adjusting task difficulty as a function of a student skill during early learning of a complex perceptual motor task. A digital computer provided the task dynamics, scoring, and adaptive control of a second-order, two-axis,…

Visual Constructive and Visual-Motor Skills in Deaf Native Signers

ERIC Educational Resources Information Center

Hauser, Peter C.; Cohen, Julie; Dye, Matthew W. G.; Bavelier, Daphne

2007-01-01

Visual constructive and visual-motor skills in the deaf population were investigated by comparing performance of deaf native signers (n = 20) to that of hearing nonsigners (n = 20) on the Beery-Buktenica Developmental Test of Visual-Motor Integration, Rey-Osterrieth Complex Figure Test, Wechsler Memory Scale Visual Reproduction subtest, and…

Deliberate Laterality Practice Facilitates Sensory-Motor Processing in Developing Children

ERIC Educational Resources Information Center

Pedersen, Scott J.

2014-01-01

Background: The innate ability for typically developing children to attain developmental motor milestones early in life has been a thoroughly researched area of inquiry. Nonetheless, as children grow and are required to perform more complex motor skills in order to experience success in physical activity and sport pursuits, the range of…

Changes in Information Processing with Aging: Implications for Teaching Motor Skills.

ERIC Educational Resources Information Center

Anshel, Mark H.

Although there are marked individual differences in the effect of aging on learning and performing motor skills, there is agreement that humans process information less efficiently with advanced age. Significant decrements have been found specifically with motor tasks that are characterized as externally-paced, rapid, complex, and requiring rapid…

Light-controlled intracellular transport in Caenorhabditis elegans.

PubMed

Harterink, Martin; van Bergeijk, Petra; Allier, Calixte; de Haan, Bart; van den Heuvel, Sander; Hoogenraad, Casper C; Kapitein, Lukas C

2016-02-22

To establish and maintain their complex morphology and function, neurons and other polarized cells exploit cytoskeletal motor proteins to distribute cargoes to specific compartments. Recent studies in cultured cells have used inducible motor protein recruitment to explore how different motors contribute to polarized transport and to control the subcellular positioning of organelles. Such approaches also seem promising avenues for studying motor activity and organelle positioning within more complex cellular assemblies, but their applicability to multicellular in vivo systems has so far remained unexplored. Here, we report the development of an optogenetic organelle transport strategy in the in vivo model system Caenorhabditis elegans. We demonstrate that movement and pausing of various organelles can be achieved by recruiting the proper cytoskeletal motor protein with light. In neurons, we find that kinesin and dynein exclusively target the axon and dendrite, respectively, revealing the basic principles for polarized transport. In vivo control of motor attachment and organelle distributions will be widely useful in exploring the mechanisms that govern the dynamic morphogenesis of cells and tissues, within the context of a developing animal. Copyright © 2016 Elsevier Ltd. All rights reserved.

A novel approach to enhance ACL injury prevention programs.

PubMed

Gokeler, Alli; Seil, Romain; Kerkhoffs, Gino; Verhagen, Evert

2018-06-18

Efficacy studies have demonstrated decreased anterior cruciate ligament (ACL) injury rates for athletes participating in injury prevention programs. Typically, ACL injury prevention programs entail a combination of plyometrics, strength training, agility and balance exercises. Unfortunately, improvements of movement patterns are not sustained over time. The reason may be related to the type of instructions given during training. Encouraging athletes to consciously control knee movements during exercises may not be optimal for the acquisition of complex motor skills as needed in complex sports environments. In the motor learning domain, these types of instructions are defined as an internal attentional focus. An internal focus, on one's own movements results in a more conscious type of control that may hamper motor learning. It has been established in numerous studies that an external focus of attention facilitates motor learning more effectively due to the utilization of automatic motor control. Subsequently, the athlete has more recourses available to anticipate on situations on the field and take appropriate feed forward directed actions. The purpose of this manuscript was to present methods to optimize motor skill acquisition of athletes and elaborate on athletes' behavior.

Inhibitory motor control based on complex stopping goals relies on the same brain network as simple stopping

PubMed Central

Wessel, Jan R.; Aron, Adam R.

2014-01-01

Much research has modeled action-stopping using the stop-signal task (SST), in which an impending response has to be stopped when an explicit stop-signal occurs. A limitation of the SST is that real-world action-stopping rarely involves explicit stop-signals. Instead, the stopping-system engages when environmental features match more complex stopping goals. For example, when stepping into the street, one monitors path, velocity, size, and types of objects; and only stops if there is a vehicle approaching. Here, we developed a task in which participants compared the visual features of a multidimensional go-stimulus to a complex stopping-template, and stopped their go-response if all features matched the template. We used independent component analysis of EEG data to show that the same motor inhibition brain network that explains action-stopping in the SST also implements motor inhibition in the complex-stopping task. Furthermore, we found that partial feature overlap between go-stimulus and stopping-template lead to motor slowing, which also corresponded with greater stopping-network activity. This shows that the same brain system for action-stopping to explicit stop-signals is recruited to slow or stop behavior when stimuli match a complex stopping goal. The results imply a generalizability of the brain’s network for simple action-stopping to more ecologically valid scenarios. PMID:25270603

Breaking barriers through collaboration: the example of the Cell Migration Consortium.

PubMed

Horwitz, Alan Rick; Watson, Nikki; Parsons, J Thomas

2002-10-15

Understanding complex integrated biological processes, such as cell migration, requires interdisciplinary approaches. The Cell Migration Consortium, funded by a Large-Scale Collaborative Project Award from the National Institute of General Medical Science, develops and disseminates new technologies, data, reagents, and shared information to a wide audience. The development and operation of this Consortium may provide useful insights for those who plan similarly large-scale, interdisciplinary approaches.

Issues Related to Cleaning Complex Geometry Surfaces with ODC-Free Solvents

NASA Technical Reports Server (NTRS)

Bradford, Blake F.; Wurth, Laura A.; Nayate, Pramod D.; McCool, Alex (Technical Monitor)

2001-01-01

Implementing ozone depleting chemicals (ODC)-free solvents into full-scale reusable solid rocket motor cleaning operations has presented problems due to the low vapor pressures of the solvents. Because of slow evaporation, solvent retention is a problem on porous substrates or on surfaces with irregular geometry, such as threaded boltholes, leak check ports, and nozzle backfill joints. The new solvents are being evaluated to replace 1,1,1-trichloroethane, which readily evaporates from these surfaces. Selection of the solvents to be evaluated on full-scale hardware was made based on results of subscale tests performed with flat surface coupons, which did not manifest the problem. Test efforts have been undertaken to address concerns with the slow-evaporating solvents. These concerns include effects on materials due to long-term exposure to solvent, potential migration from bolthole threads to seal surfaces, and effects on bolt loading due to solvent retention in threads. Tests performed to date have verified that retained solvent does not affect materials or hardware performance. Process modifications have also been developed to assist drying, and these can be implemented if additional drying becomes necessary.

Effects of oxaliplatin on mouse myenteric neurons and colonic motility

PubMed Central

Wafai, Linah; Taher, Mohammadali; Jovanovska, Valentina; Bornstein, Joel C.; Dass, Crispin R.; Nurgali, Kulmira

2013-01-01

Oxaliplatin, an anti-cancer chemotherapeutic agent used for the treatment of colorectal cancer, commonly causes gastrointestinal side-effects such as constipation, diarrhoea, nausea, and vomiting. Damage to enteric neurons may underlie some of these gastrointestinal side-effects, as the enteric nervous system (ENS) controls functions of the bowel. In this study, neuronal loss and changes to the structure and immunoreactivity of myenteric neuronal nitric oxide synthase (nNOS) neurons were examined in colonic segments from mice following exposure to oxaliplatin ex vivo and following repeated intraperitoneal injections of oxaliplatin over 3 weeks in vivo, using immunohistochemistry and confocal microscopy. Significant morphological alterations and increases in the proportion of NOS-immunoreactive (IR) neurons were associated with both short-term oxaliplatin exposure and long-term oxaliplatin administration, confirming that oxaliplatin causes changes to the myenteric neurons. Long-term oxaliplatin administration induced substantial neuronal loss that was correlated with a reduction in both the frequency and propagation speed of colonic migrating motor complexes (CMMCs) in vitro. Similar changes probably produce some symptoms experienced by patients undergoing oxaliplatin treatment. PMID:23486839

Characteristics of phase 3-like activity and rebound excitation triggered by hexamethonium and atropine administration in the ovine small bowel.

PubMed

Romański, K W

2010-02-01

Administration of hexamethonium (Hx) and atropine inhibits myoelectric and motor activity and then evokes a stimulatory effect called rebound excitation (RE) in the ovine small bowel. RE has not been precisely characterized so far and it is possible that it is composed of different types of motility. This study was thus devoted to characterizing these excitatory changes in the myoelectric and motor activity of the small bowel, particularly in the duodenum in conscious sheep. These alterations occurred in response to different intravenous doses of Hx and atropine administered alone or in combinations during various phases of the migrating myoelectric or motor complex (MMC) in the fasted and non-fasted sheep. Initially two basic types of excitatory response to the cholinergic blockade were found. In the course of chronic experiments different doses of Hx and atropine evoked phase 3-like activity (unorganized phase 3 of the MMC or its fragments) alternating with the less regular RE and the duration of these changes was related to the drug dose. In the nonfasted sheep these changes were less pronounced than in the fasted animals. When the drug was given during phase 1 of the MMC, RE did not occur or was greatly reduced. Administration of Hx and atropine in the course of phase 2a and phase 2b of the MMC produced roughly similar effects. Hx triggered stronger phase 3-like activity and RE than atropine. Combinations of Hx and atropine induced an additive effect, more evident in the fasted animals. These actions of Hx and atropine, thus, appear to involve at least partly the same intramural pathways. It is concluded that Hx and atropine evoke phase 3-like activity alternating with RE as the secondary stimulatory response in conscious sheep and both these types of the intestinal motility represent two distinct motility patterns.

SK3/TRPC1/Orai1 complex regulates SOCE-dependent colon cancer cell migration: a novel opportunity to modulate anti-EGFR mAb action by the alkyl-lipid Ohmline

PubMed Central

Guéguinou, Maxime; Harnois, Thomas; Crottes, David; Uguen, Arnaud; Deliot, Nadine; Gambade, Audrey; Chantôme, Aurélie; Haelters, Jean Pierre; Jaffrès, Paul Alain; Jourdan, Marie Lise; Weber, Günther; Soriani, Olivier; Bougnoux, Philippe; Mignen, Olivier; Bourmeyster, Nicolas; Constantin, Bruno; Lecomte, Thierry

2016-01-01

Background Barely 10-20% of patients with metastatic colorectal cancer (mCRC) receive a clinical benefit from the use of anti-EGFR monoclonal antibodies (mAbs). We hypothesized that this could depends on their efficiency to reduce Store Operated Calcium Entry (SOCE) that are known to enhance cancer cells. Results In the present study, we demonstrate that SOCE promotes migration of colon cancer cell following the formation of a lipid raft ion channel complex composed of TRPC1/Orai1 and SK3 channels. Formation of this complex is stimulated by the phosphorylation of the reticular protein STIM1 by EGF and activation of the Akt pathway. Our data show that, in a positive feedback loop SOCE activates both Akt pathway and SK3 channel activity which lead to SOCE amplification. This amplification occurs through the activation of Rac1/Calpain mediated by Akt. We also show that Anti-EGFR mAbs can modulate SOCE and cancer cell migration through the Akt pathway. Interestingly, the alkyl-lipid Ohmline, which we previously showed to be an inhibitor of SK3 channel, can dissociated the lipid raft ion channel complex through decreased phosphorylation of Akt and modulation of mAbs action. Conclusions This study demonstrates that the inhibition of the SOCE-dependent colon cancer cell migration trough SK3/TRPC1/Orai1 channel complex by the alkyl-lipid Ohmline may be a novel strategy to modulate Anti-EGFR mAb action in mCRC. PMID:27102434

Functional Diversification of Motor Neuron-specific Isl1 Enhancers during Evolution

PubMed Central

Kim, Namhee; Park, Chungoo; Jeong, Yongsu; Song, Mi-Ryoung

2015-01-01

Functional diversification of motor neurons has occurred in order to selectively control the movements of different body parts including head, trunk and limbs. Here we report that transcription of Isl1, a major gene necessary for motor neuron identity, is controlled by two enhancers, CREST1 (E1) and CREST2 (E2) that allow selective gene expression of Isl1 in motor neurons. Introduction of GFP reporters into the chick neural tube revealed that E1 is active in hindbrain motor neurons and spinal cord motor neurons, whereas E2 is active in the lateral motor column (LMC) of the spinal cord, which controls the limb muscles. Genome-wide ChIP-Seq analysis combined with reporter assays showed that Phox2 and the Isl1-Lhx3 complex bind to E1 and drive hindbrain and spinal cord-specific expression of Isl1, respectively. Interestingly, Lhx3 alone was sufficient to activate E1, and this may contribute to the initiation of Isl1 expression when progenitors have just developed into motor neurons. E2 was induced by onecut 1 (OC-1) factor that permits Isl1 expression in LMCm neurons. Interestingly, the core region of E1 has been conserved in evolution, even in the lamprey, a jawless vertebrate with primitive motor neurons. All E1 sequences from lamprey to mouse responded equally well to Phox2a and the Isl1-Lhx3 complex. Conversely, E2, the enhancer for limb-innervating motor neurons, was only found in tetrapod animals. This suggests that evolutionarily-conserved enhancers permit the diversification of motor neurons. PMID:26447474

Functional Diversification of Motor Neuron-specific Isl1 Enhancers during Evolution.

PubMed

Kim, Namhee; Park, Chungoo; Jeong, Yongsu; Song, Mi-Ryoung

2015-10-01

Functional diversification of motor neurons has occurred in order to selectively control the movements of different body parts including head, trunk and limbs. Here we report that transcription of Isl1, a major gene necessary for motor neuron identity, is controlled by two enhancers, CREST1 (E1) and CREST2 (E2) that allow selective gene expression of Isl1 in motor neurons. Introduction of GFP reporters into the chick neural tube revealed that E1 is active in hindbrain motor neurons and spinal cord motor neurons, whereas E2 is active in the lateral motor column (LMC) of the spinal cord, which controls the limb muscles. Genome-wide ChIP-Seq analysis combined with reporter assays showed that Phox2 and the Isl1-Lhx3 complex bind to E1 and drive hindbrain and spinal cord-specific expression of Isl1, respectively. Interestingly, Lhx3 alone was sufficient to activate E1, and this may contribute to the initiation of Isl1 expression when progenitors have just developed into motor neurons. E2 was induced by onecut 1 (OC-1) factor that permits Isl1 expression in LMCm neurons. Interestingly, the core region of E1 has been conserved in evolution, even in the lamprey, a jawless vertebrate with primitive motor neurons. All E1 sequences from lamprey to mouse responded equally well to Phox2a and the Isl1-Lhx3 complex. Conversely, E2, the enhancer for limb-innervating motor neurons, was only found in tetrapod animals. This suggests that evolutionarily-conserved enhancers permit the diversification of motor neurons.

Multiscale Cues Drive Collective Cell Migration

NASA Astrophysics Data System (ADS)

Nam, Ki-Hwan; Kim, Peter; Wood, David K.; Kwon, Sunghoon; Provenzano, Paolo P.; Kim, Deok-Ho

2016-07-01

To investigate complex biophysical relationships driving directed cell migration, we developed a biomimetic platform that allows perturbation of microscale geometric constraints with concomitant nanoscale contact guidance architectures. This permits us to elucidate the influence, and parse out the relative contribution, of multiscale features, and define how these physical inputs are jointly processed with oncogenic signaling. We demonstrate that collective cell migration is profoundly enhanced by the addition of contract guidance cues when not otherwise constrained. However, while nanoscale cues promoted migration in all cases, microscale directed migration cues are dominant as the geometric constraint narrows, a behavior that is well explained by stochastic diffusion anisotropy modeling. Further, oncogene activation (i.e. mutant PIK3CA) resulted in profoundly increased migration where extracellular multiscale directed migration cues and intrinsic signaling synergistically conspire to greatly outperform normal cells or any extracellular guidance cues in isolation.

Borneol, a Bicyclic Monoterpene Alcohol, Reduces Nociceptive Behavior and Inflammatory Response in Mice

PubMed Central

Almeida, Jackson Roberto Guedes da Silva; Souza, Grasielly Rocha; Silva, Juliane Cabral; Saraiva, Sarah Raquel Gomes de Lima; Júnior, Raimundo Gonçalves de Oliveira; Quintans, Jullyana de Souza Siqueira; Barreto, Rosana de Souza Siqueira; Bonjardim, Leonardo Rigoldi; Cavalcanti, Sócrates Cabral de Holanda; Junior, Lucindo José Quintans

2013-01-01

Borneol, a bicyclic monoterpene, has been evaluated for antinociceptive and anti-inflammatory activities. Antinociceptive and anti-inflammatory activities were studied by measuring nociception by acetic acid, formalin, hot plate, and grip strength tests, while inflammation was prompted by carrageenan-induced peritonitis. The rotarod test was used to evaluate motor coordination. Borneol produced a significant (P < 0.01) reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice (formalin and writhing tests, resp.). When the hot plate test was conducted, borneol (in higher dose) produced an inhibition (P < 0.05) of the nociceptive behavior. Such results were unlikely to be provoked by motor abnormality. Additionally, borneol-treated mice reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. Together, our results suggest that borneol possess significant central and peripheral antinociceptive activity; it has also anti-inflammatory activity. In addition, borneol did not impair motor coordination. PMID:23710149

A Lag in Speech Motor Coordination During Sentence Production Is Associated With Stuttering Persistence in Young Children

PubMed Central

Smith, Anne; Weber, Christine

2017-01-01

Purpose The purpose of this study was to determine if indices of speech motor coordination during the production of sentences varying in sentence length and syntactic complexity were associated with stuttering persistence versus recovery in 5- to 7-year-old children. Methods We compared children with persistent stuttering (CWS-Per) with children who had recovered (CWS-Rec), and children who do not stutter (CWNS). A kinematic measure of articulatory coordination, lip aperture variability (LAVar), and overall movement duration were computed for perceptually fluent sentence productions varying in length and syntactic complexity. Results CWS-Per exhibited higher LAVar across sentence types compared to CWS-Rec and CWNS. For the participants who successfully completed the experimental paradigm, the demands of increasing sentence length and syntactic complexity did not appear to disproportionately affect the speech motor coordination of CWS-Per compared to their recovered and fluent peers. However, a subset of CWS-Per failed to produce the required number of accurate utterances. Conclusions These findings support our hypothesis that the speech motor coordination of school-age CWS-Per, on average, is less refined and less mature compared to CWS-Rec and CWNS. Childhood recovery from stuttering is characterized, in part, by overcoming an earlier occurring maturational lag in speech motor development. PMID:28056137

Drosophila hemocyte migration: an in vivo assay for directional cell migration.

PubMed

Moreira, Carolina G A; Regan, Jennifer C; Zaidman-Rémy, Anna; Jacinto, Antonio; Prag, Soren

2011-01-01

This protocol describes an in vivo assay for random and directed hemocyte migration in Drosophila. Drosophila is becoming an increasingly powerful model system for in vivo cell migration analysis, combining unique genetic tools with translucency of the embryo and pupa, which allows direct imaging and traceability of different cell types. In the assay we present here, we make use of the hemocyte response to epithelium wounding to experimentally induce a transition from random to directed migration. Time-lapse confocal microscopy of hemocyte migration in untreated conditions provides a random cell migration assay that allows identification of molecular mechanisms involved in this complex process. Upon laser-induced wounding of the thorax epithelium, a rapid chemotactic response changes hemocyte migratory behavior into a directed migration toward the wound site. This protocol provides a direct comparison of cells during both types of migration in vivo, and combined with recently developed resources such as transgenic RNAi, is ideal for forward genetic screens.

MeltMigrator: A MATLAB-based software for modeling three-dimensional melt migration and crustal thickness variations at mid-ocean ridges following a rules-based approach

NASA Astrophysics Data System (ADS)

Bai, Hailong; Montési, Laurent G. J.; Behn, Mark D.

2017-01-01

MeltMigrator is a MATLAB®-based melt migration software developed to process three-dimensional mantle temperature and velocity data from user-supplied numerical models of mid-ocean ridges, calculate melt production and melt migration trajectories in the mantle, estimate melt flux along plate boundaries, and predict crustal thickness distribution on the seafloor. MeltMigrator is also capable of calculating compositional evolution depending on the choice of petrologic melting model. Programmed in modules, MeltMigrator is highly customizable and can be expanded to a wide range of applications. We have applied it to complex mid-ocean ridge model settings, including transform faults, oblique segments, ridge migration, asymmetrical spreading, background mantle flow, and ridge-plume interaction. In this technical report, we include an example application to a segmented mid-ocean ridge. MeltMigrator is available as a supplement to this paper, and it is also available from GitHub and the University of Maryland Geodynamics Group website.

In silico Interrogation of Insect Central Complex Suggests Computational Roles for the Ellipsoid Body in Spatial Navigation.

PubMed

Fiore, Vincenzo G; Kottler, Benjamin; Gu, Xiaosi; Hirth, Frank

2017-01-01

The central complex in the insect brain is a composite of midline neuropils involved in processing sensory cues and mediating behavioral outputs to orchestrate spatial navigation. Despite recent advances, however, the neural mechanisms underlying sensory integration and motor action selections have remained largely elusive. In particular, it is not yet understood how the central complex exploits sensory inputs to realize motor functions associated with spatial navigation. Here we report an in silico interrogation of central complex-mediated spatial navigation with a special emphasis on the ellipsoid body. Based on known connectivity and function, we developed a computational model to test how the local connectome of the central complex can mediate sensorimotor integration to guide different forms of behavioral outputs. Our simulations show integration of multiple sensory sources can be effectively performed in the ellipsoid body. This processed information is used to trigger continuous sequences of action selections resulting in self-motion, obstacle avoidance and the navigation of simulated environments of varying complexity. The motor responses to perceived sensory stimuli can be stored in the neural structure of the central complex to simulate navigation relying on a collective of guidance cues, akin to sensory-driven innate or habitual behaviors. By comparing behaviors under different conditions of accessible sources of input information, we show the simulated insect computes visual inputs and body posture to estimate its position in space. Finally, we tested whether the local connectome of the central complex might also allow the flexibility required to recall an intentional behavioral sequence, among different courses of actions. Our simulations suggest that the central complex can encode combined representations of motor and spatial information to pursue a goal and thus successfully guide orientation behavior. Together, the observed computational features identify central complex circuitry, and especially the ellipsoid body, as a key neural correlate involved in spatial navigation.

In silico Interrogation of Insect Central Complex Suggests Computational Roles for the Ellipsoid Body in Spatial Navigation

PubMed Central

Fiore, Vincenzo G.; Kottler, Benjamin; Gu, Xiaosi; Hirth, Frank

2017-01-01

The central complex in the insect brain is a composite of midline neuropils involved in processing sensory cues and mediating behavioral outputs to orchestrate spatial navigation. Despite recent advances, however, the neural mechanisms underlying sensory integration and motor action selections have remained largely elusive. In particular, it is not yet understood how the central complex exploits sensory inputs to realize motor functions associated with spatial navigation. Here we report an in silico interrogation of central complex-mediated spatial navigation with a special emphasis on the ellipsoid body. Based on known connectivity and function, we developed a computational model to test how the local connectome of the central complex can mediate sensorimotor integration to guide different forms of behavioral outputs. Our simulations show integration of multiple sensory sources can be effectively performed in the ellipsoid body. This processed information is used to trigger continuous sequences of action selections resulting in self-motion, obstacle avoidance and the navigation of simulated environments of varying complexity. The motor responses to perceived sensory stimuli can be stored in the neural structure of the central complex to simulate navigation relying on a collective of guidance cues, akin to sensory-driven innate or habitual behaviors. By comparing behaviors under different conditions of accessible sources of input information, we show the simulated insect computes visual inputs and body posture to estimate its position in space. Finally, we tested whether the local connectome of the central complex might also allow the flexibility required to recall an intentional behavioral sequence, among different courses of actions. Our simulations suggest that the central complex can encode combined representations of motor and spatial information to pursue a goal and thus successfully guide orientation behavior. Together, the observed computational features identify central complex circuitry, and especially the ellipsoid body, as a key neural correlate involved in spatial navigation. PMID:28824390

Prep1.1 has essential genetic functions in hindbrain development and cranial neural crest cell differentiation.

PubMed

Deflorian, Gianluca; Tiso, Natascia; Ferretti, Elisabetta; Meyer, Dirk; Blasi, Francesco; Bortolussi, Marino; Argenton, Francesco

2004-02-01

In this study we analysed the function of the Meinox gene prep1.1 during zebrafish development. Meinox proteins form heterotrimeric complexes with Hox and Pbx members, increasing the DNA binding specificity of Hox proteins in vitro and in vivo. However, a role for a specific Meinox protein in the regulation of Hox activity in vivo has not been demonstrated. In situ hybridization showed that prep1.1 is expressed maternally and ubiquitously up to 24 hours post-fertilization (hpf), and restricted to the head from 48 hpf onwards. Morpholino-induced prep1.1 loss-of-function caused significant apoptosis in the CNS. Hindbrain segmentation and patterning was affected severely, as revealed by either loss or defective expression of several hindbrain markers (foxb1.2/mariposa, krox20, pax2.1 and pax6.1), including anteriorly expressed Hox genes (hoxb1a, hoxa2 and hoxb2), the impaired migration of facial nerve motor neurons, and the lack of reticulospinal neurons (RSNs) except Mauthner cells. Furthermore, the heads of prep1.1 morphants lacked all pharyngeal cartilages. This was not caused by the absence of neural crest cells or their impaired migration into the pharyngeal arches, as shown by expression of dlx2 and snail1, but by the inability of these cells to differentiate into chondroblasts. Our results indicate that prep1.1 has a unique genetic function in craniofacial chondrogenesis and, acting as a member of Meinox-Pbc-Hox trimers, it plays an essential role in hindbrain development.

Roles of ion transport in control of cell motility.

PubMed

Stock, Christian; Ludwig, Florian T; Hanley, Peter J; Schwab, Albrecht

2013-01-01

Cell motility is an essential feature of life. It is essential for reproduction, propagation, embryonic development, and healing processes such as wound closure and a successful immune defense. If out of control, cell motility can become life-threatening as, for example, in metastasis or autoimmune diseases. Regardless of whether ciliary/flagellar or amoeboid movement, controlled motility always requires a concerted action of ion channels and transporters, cytoskeletal elements, and signaling cascades. Ion transport across the plasma membrane contributes to cell motility by affecting the membrane potential and voltage-sensitive ion channels, by inducing local volume changes with the help of aquaporins and by modulating cytosolic Ca(2+) and H(+) concentrations. Voltage-sensitive ion channels serve as voltage detectors in electric fields thus enabling galvanotaxis; local swelling facilitates the outgrowth of protrusions at the leading edge while local shrinkage accompanies the retraction of the cell rear; the cytosolic Ca(2+) concentration exerts its main effect on cytoskeletal dynamics via motor proteins such as myosin or dynein; and both, the intracellular and the extracellular H(+) concentration modulate cell migration and adhesion by tuning the activity of enzymes and signaling molecules in the cytosol as well as the activation state of adhesion molecules at the cell surface. In addition to the actual process of ion transport, both, channels and transporters contribute to cell migration by being part of focal adhesion complexes and/or physically interacting with components of the cytoskeleton. The present article provides an overview of how the numerous ion-transport mechanisms contribute to the various modes of cell motility.

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors.

PubMed

DiGiovanna, Jack; Dominici, Nadia; Friedli, Lucia; Rigosa, Jacopo; Duis, Simone; Kreider, Julie; Beauparlant, Janine; van den Brand, Rubia; Schieppati, Marco; Micera, Silvestro; Courtine, Grégoire

2016-10-05

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor procedures. We found that the activation of hindlimb motor cortex preceded gait initiation. During overground locomotion, the motor cortex exhibited consistent neuronal population responses that were synchronized with the spatiotemporal activation of hindlimb motoneurons. Behaviors requiring enhanced muscle activity or skilled paw placement correlated with substantial adjustment in neuronal population responses. In contrast, all rats exhibited a reduction of cortical activity during more automated behavior, such as stepping on a treadmill. Despite the facultative role of the motor cortex in the production of locomotion in rats, these results show that the encoding of hindlimb features in motor cortex dynamics is comparable in rats and cats. However, the extent of motor cortex modulations appears linked to the degree of volitional engagement and complexity of the task, reemphasizing the importance of goal-directed behaviors for motor control studies, rehabilitation, and neuroprosthetics. We mapped the neuronal population responses in the hindlimb motor cortex to hindlimb kinematics and hindlimb muscle synergies across a spectrum of natural locomotion behaviors. Robust task-specific neuronal population responses revealed that the rat motor cortex displays similar modulation as other mammals during locomotion. However, the reduced motor cortex activity during more automated behaviors suggests a relationship between the degree of engagement and task complexity. This relationship emphasizes the importance of the behavioral procedure to engage the motor cortex during motor control studies, gait rehabilitation, and locomotor neuroprosthetic developments in rats. Copyright © 2016 the authors 0270-6474/16/3610440-16$15.00/0.

Field oriented control of induction motors

NASA Technical Reports Server (NTRS)

Burrows, Linda M.; Zinger, Don S.; Roth, Mary Ellen

1990-01-01

Induction motors have always been known for their simple rugged construction, but until lately were not suitable for variable speed or servo drives due to the inherent complexity of the controls. With the advent of field oriented control (FOC), however, the induction motor has become an attractive option for these types of drive systems. An FOC system which utilizes the pulse population modulation method to synthesize the motor drive frequencies is examined. This system allows for a variable voltage to frequency ratio and enables the user to have independent control of both the speed and torque of an induction motor. A second generation of the control boards were developed and tested with the next point of focus being the minimization of the size and complexity of these controls. Many options were considered with the best approach being the use of a digital signal processor (DSP) due to its inherent ability to quickly evaluate control algorithms. The present test results of the system and the status of the optimization process using a DSP are discussed.

Major Histocompatibility Complex I Expression by Motor Neurons and Its Implication in Amyotrophic Lateral Sclerosis

PubMed Central

Nardo, Giovanni; Trolese, Maria Chiara; Bendotti, Caterina

2016-01-01

Neuronal expression of major histocompatibility complex I (MHCI)-related molecules in adults and during CNS diseases is involved in the synaptic plasticity and axonal regeneration with mechanisms either dependent or independent of their immune functions. Motor neurons are highly responsive in triggering the expression of MHCI molecules during normal aging or following insults and diseases, and this has implications in the synaptic controls, axonal regeneration, and neuromuscular junction stability of these neurons. We recently reported that MHCI and immunoproteasome are strongly activated in spinal motor neurons and their peripheral motor axon in a mouse model of familial amyotrophic lateral sclerosis (ALS) during the course of the disease. This response was prominent in ALS mice with slower disease progression in which the axonal structure and function was better preserved than in fast-progressing mice. This review summarizes and discusses our observations in the light of knowledge about the possible role of MHCI in motor neurons providing additional insight into the pathophysiology of ALS. PMID:27379008

A novel technique for phase synchrony measurement from the complex motor imaginary potential of combined body and limb action

NASA Astrophysics Data System (ADS)

Zhou, Zhong-xing; Wan, Bai-kun; Ming, Dong; Qi, Hong-zhi

2010-08-01

In this study, we proposed and evaluated the use of the empirical mode decomposition (EMD) technique combined with phase synchronization analysis to investigate the human brain synchrony of the supplementary motor area (SMA) and primary motor area (M1) during complex motor imagination of combined body and limb action. We separated the EEG data of the SMA and M1 into intrinsic mode functions (IMFs) using the EMD method and determined the characteristic IMFs by power spectral density (PSD) analysis. Thereafter, the instantaneous phases of the characteristic IMFs were obtained by the Hilbert transformation, and the single-trial phase-locking value (PLV) features for brain synchrony measurement between the SMA and M1 were investigated separately. The classification performance suggests that the proposed approach is effective for phase synchronization analysis and is promising for the application of a brain-computer interface in motor nerve reconstruction of the lower limbs.

Motor-driven intracellular transport powers bacterial gliding motility

PubMed Central

Sun, Mingzhai; Wartel, Morgane; Cascales, Eric; Shaevitz, Joshua W.; Mignot, Tâm

2011-01-01

Protein-directed intracellular transport has not been observed in bacteria despite the existence of dynamic protein localization and a complex cytoskeleton. However, protein trafficking has clear potential uses for important cellular processes such as growth, development, chromosome segregation, and motility. Conflicting models have been proposed to explain Myxococcus xanthus motility on solid surfaces, some favoring secretion engines at the rear of cells and others evoking an unknown class of molecular motors distributed along the cell body. Through a combination of fluorescence imaging, force microscopy, and genetic manipulation, we show that membrane-bound cytoplasmic complexes consisting of motor and regulatory proteins are directionally transported down the axis of a cell at constant velocity. This intracellular motion is transmitted to the exterior of the cell and converted to traction forces on the substrate. Thus, this study demonstrates the existence of a conserved class of processive intracellular motors in bacteria and shows how these motors have been adapted to produce cell motility. PMID:21482768

Directionality analysis on functional magnetic resonance imaging during motor task using Granger causality.

PubMed

Anwar, A R; Muthalib, M; Perrey, S; Galka, A; Granert, O; Wolff, S; Deuschl, G; Raethjen, J; Heute, U; Muthuraman, M

2012-01-01

Directionality analysis of signals originating from different parts of brain during motor tasks has gained a lot of interest. Since brain activity can be recorded over time, methods of time series analysis can be applied to medical time series as well. Granger Causality is a method to find a causal relationship between time series. Such causality can be referred to as a directional connection and is not necessarily bidirectional. The aim of this study is to differentiate between different motor tasks on the basis of activation maps and also to understand the nature of connections present between different parts of the brain. In this paper, three different motor tasks (finger tapping, simple finger sequencing, and complex finger sequencing) are analyzed. Time series for each task were extracted from functional magnetic resonance imaging (fMRI) data, which have a very good spatial resolution and can look into the sub-cortical regions of the brain. Activation maps based on fMRI images show that, in case of complex finger sequencing, most parts of the brain are active, unlike finger tapping during which only limited regions show activity. Directionality analysis on time series extracted from contralateral motor cortex (CMC), supplementary motor area (SMA), and cerebellum (CER) show bidirectional connections between these parts of the brain. In case of simple finger sequencing and complex finger sequencing, the strongest connections originate from SMA and CMC, while connections originating from CER in either direction are the weakest ones in magnitude during all paradigms.

Management of migrating intracranial bullets: lessons learned from surviving an AK-47 bullet through the lateral brainstem.

PubMed

Rammo, Richard A; DeFazio, Michael V; Bullock, M Ross

2012-01-01

Survival after a gunshot wound (GSW) to the head is becoming more common, with an accompanying increase in spontaneous migration of these intracranial bullet fragments. This phenomenon is well described in current literature and is a potentially life-threatening delayed complication of GSW to the head. We present the case of a 17-year-old boy who survived a penetrating GSW to the cranium and cerebellum after an accident involving an AK (Automatic Kalashnikov)-47 (7.62 mm). Following initial attempts to remove the bullet and associated hematoma from the cerebellar hemisphere, intraoperative fluoroscopy revealed that the bullet had migrated to lie within the right middle cerebellar peduncle with the development of intraoperative cardiac arrhythmia. The bullet could not be retrieved without risk of damage to the superior and inferior cerebellar arteries. The patient then developed bacterial meningitis, and further imaging revealed the bullet had again migrated under the cerebellar cortex to an accessible location. The infection was treated with aggressive antibiotic therapy and the bullet was removed from the posterior fossa, thus preventing recurrence of infection and further migration. The patient regained full motor, speech, and proprioceptive function within months after injury. The potential for spontaneous migration exists with any penetrating brain injury involving a retained foreign body. When a retained intracranial foreign body is unable to be safely extracted during initial debridement, close clinical evaluation is essential and plain-film or computed tomographic imaging should be considered in order to enhance the early detection of delayed-onset life-threatening deterioration, such as meningitis and occlusion of cerebrospinal fluid drainage, because of spontaneous migration. Copyright © 2012 Elsevier Inc. All rights reserved.

Selective Effects of Motor Expertise in Mental Body Rotation Tasks: Comparing Object-Based and Perspective Transformations

ERIC Educational Resources Information Center

Steggemann, Yvonne; Engbert, Kai; Weigelt, Matthias

2011-01-01

Brain imaging studies provide strong evidence for the involvement of the human mirror system during the observation of complex movements, depending on the individual's motor expertise. Here, we ask the question whether motor expertise not only affects perception while observing movements, but also benefits perception while solving mental rotation…

Gross-Motor Skill Acquisition by Preschool Dance Students under Self-Instruction Procedures

ERIC Educational Resources Information Center

Vintere, Parsla; Hemmes, Nancy S.; Brown, Bruce L.; Poulson, Claire L.

2004-01-01

The effects of two training procedures -- (a) modeling and praise and (b) self-instruction, modeling, and praise -- on complex gross-motor chain acquisition for preschool dance class students were evaluated. Six girls participated in the study. A multiple baseline design across six gross-motor chains with a secondary group comparison for treatment…

Paliperidone-associated motor tics.

PubMed

Hsieh, Ming-Han; Chiu, Nan-Ying

2014-01-01

Paliperidone-associated motor tics. Case report. We report a 30-year-old man with schizophrenia who developed motor tics (eye blinking) after treatment of paliperidone up to 15 mg daily. Tic-like symptoms, from simple eye blinking to complex Tourette-like syndrome, may occur during paliperidone treatment, especially with high dose. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Predictive ethoinformatics reveals the complex migratory behaviour of a pelagic seabird, the Manx Shearwater

PubMed Central

Freeman, Robin; Dean, Ben; Kirk, Holly; Leonard, Kerry; Phillips, Richard A.; Perrins, Chris M.; Guilford, Tim

2013-01-01

Understanding the behaviour of animals in the wild is fundamental to conservation efforts. Advances in bio-logging technologies have offered insights into the behaviour of animals during foraging, migration and social interaction. However, broader application of these systems has been limited by device mass, cost and longevity. Here, we use information from multiple logger types to predict individual behaviour in a highly pelagic, migratory seabird, the Manx Shearwater (Puffinus puffinus). Using behavioural states resolved from GPS tracking of foraging during the breeding season, we demonstrate that individual behaviours can be accurately predicted during multi-year migrations from low cost, lightweight, salt-water immersion devices. This reveals a complex pattern of migratory stopovers: some involving high proportions of foraging, and others of rest behaviour. We use this technique to examine three consecutive years of global migrations, revealing the prominence of foraging behaviour during migration and the importance of highly productive waters during migratory stopover. PMID:23635496

The Hungry Stomach: Physiology, Disease, and Drug Development Opportunities

PubMed Central

Sanger, Gareth J.; Hellström, Per M.; Näslund, Erik

2010-01-01

During hunger, a series of high-amplitude contractions of the stomach and small intestine (phase III), which form part of a cycle of quiescence and contractions (known as the migrating motor complex, MMC), play a “housekeeping” role prior to the next meal, and may contribute toward the development of hunger. Several gastrointestinal (GI) hormones are associated with phase III MMC activity, but currently the most prominent is motilin, thought to at least partly mediate phase III contractions of the gastric MMC. Additional GI endocrine and neuronal systems play even more powerful roles in the development of hunger. In particular, the ghrelin-precursor gene is proving to have a complex physiology, giving rise to three different products: ghrelin itself, which is formed from a post-translational modification of des-acyl-ghrelin, and obestatin. The receptors acted on by des-acyl-ghrelin and by obestatin are currently unknown but both these peptides seem able to exert actions which oppose that of ghrelin, either indirectly or directly. An increased understanding of the actions of these peptides is helping to unravel a number of different eating disorders and providing opportunities for the discovery of new drugs to regulate dysfunctional gastric behaviors and appetite. To date, ghrelin and motilin receptor agonists and antagonists have been described. The most advanced are compounds which activate the ghrelin and motilin receptors which are being progressed for disorders associated with gastric hypomotility. PMID:21927604

Transoceanic migration, spatial dynamics, and population linkages of white sharks.

PubMed

Bonfil, Ramón; Meÿer, Michael; Scholl, Michael C; Johnson, Ryan; O'Brien, Shannon; Oosthuizen, Herman; Swanson, Stephan; Kotze, Deon; Paterson, Michael

2005-10-07

The large-scale spatial dynamics and population structure of marine top predators are poorly known. We present electronic tag and photographic identification data showing a complex suite of behavioral patterns in white sharks. These include coastal return migrations and the fastest known transoceanic return migration among swimming fauna, which provide direct evidence of a link between widely separated populations in South Africa and Australia. Transoceanic return migration involved a return to the original capture location, dives to depths of 980 meters, and the tolerance of water temperatures as low as 3.4 degrees C. These findings contradict previous ideas that female white sharks do not make transoceanic migrations, and they suggest natal homing behavior.

Restructuring of the labour market and the role of third world migrations in Europe.

PubMed

Pugliese, E

1993-10-01

"This paper is an analysis of the way in which the changes in the labour market and in the occupational structure in Europe affect the situation and the role of Third World migrants." Changes in European labor migration patterns since the 1960s are first analyzed. The author notes that "intra-European migrations were industrial migrations because manufacturing and building industries were the most important and growing economic activities....Present-day migrations are postindustrial migrations. Immigrants work mostly in service activities and not infrequently in the informal economy. In any case migrant workers are located in the secondary labour market. The picture is made more complex by the fact than many immigrants are alegal or illegal because of the restrictive immigration policies in European countries." excerpt

Controlled surface topography regulates collective 3D migration by epithelial-mesenchymal composite embryonic tissues.

PubMed

Song, Jiho; Shawky, Joseph H; Kim, YongTae; Hazar, Melis; LeDuc, Philip R; Sitti, Metin; Davidson, Lance A

2015-07-01

Cells in tissues encounter a range of physical cues as they migrate. Probing single cell and collective migratory responses to physically defined three-dimensional (3D) microenvironments and the factors that modulate those responses are critical to understanding how tissue migration is regulated during development, regeneration, and cancer. One key physical factor that regulates cell migration is topography. Most studies on surface topography and cell mechanics have been carried out with single migratory cells, yet little is known about the spreading and motility response of 3D complex multi-cellular tissues to topographical cues. Here, we examine the response to complex topographical cues of microsurgically isolated tissue explants composed of epithelial and mesenchymal cell layers from naturally 3D organized embryos of the aquatic frog Xenopus laevis. We control topography using fabricated micropost arrays (MPAs) and investigate the collective 3D migration of these multi-cellular systems in these MPAs. We find that the topography regulates both collective and individual cell migration and that dense MPAs reduce but do not eliminate tissue spreading. By modulating cell size through the cell cycle inhibitor Mitomycin C or the spacing of the MPAs we uncover how 3D topographical cues disrupt collective cell migration. We find surface topography can direct both single cell motility and tissue spreading, altering tissue-scale processes that enable efficient conversion of single cell motility into collective movement. Copyright © 2015 Elsevier Ltd. All rights reserved.

Conception et mise au point d'un emulateur de machine Synchrone trapezoidale a aimants permanents

NASA Astrophysics Data System (ADS)

Lessard, Francois

The development of technology leads inevitably to higher systems' complexity faced by engineers. Over time, tools are often developed in parallel with the main systems to ensure their sustainability. The work presented in this document provides a new tool for testing motor drives. In general, this project refers to active loads, which are complex dynamic loads emulated electronically with a static converter. Specifically, this document proposes and implements a system whose purpose is to recreate the behaviour of a trapezoidal permanent magnets synchronous machine. The ultimate goal is to connect a motor drive to the three terminal of the motor emulator, as it would with a real motor. The emulator's response then obtained, when subjected to disturbances of the motor drive, is ideally identical to the one of a real motor. The motor emulator led to a significant versatility of a test bench because the electrical and mechanical parameters of the application can be easily modified. The work is divided into two main parts: the static converter and real-rime. Overall, these two entities form a PHIL (Power Hardware-in-the-loop) real-time simulation. The static converter enables the exchange of real power between the drive motor and the real-time simulation. The latter gives the application the intelligence needed to interact with the motor drive in a way which the desired behaviour is recreated. The main partner of this project, Opal-RT, ensures this development. Keywords: virtual machine, PHIL, real-time simulation, electronic load

Haptic fMRI: combining functional neuroimaging with haptics for studying the brain's motor control representation.

PubMed

Menon, Samir; Brantner, Gerald; Aholt, Chris; Kay, Kendrick; Khatib, Oussama

2013-01-01

A challenging problem in motor control neuroimaging studies is the inability to perform complex human motor tasks given the Magnetic Resonance Imaging (MRI) scanner's disruptive magnetic fields and confined workspace. In this paper, we propose a novel experimental platform that combines Functional MRI (fMRI) neuroimaging, haptic virtual simulation environments, and an fMRI-compatible haptic device for real-time haptic interaction across the scanner workspace (above torso ∼ .65×.40×.20m(3)). We implement this Haptic fMRI platform with a novel haptic device, the Haptic fMRI Interface (HFI), and demonstrate its suitability for motor neuroimaging studies. HFI has three degrees-of-freedom (DOF), uses electromagnetic motors to enable high-fidelity haptic rendering (>350Hz), integrates radio frequency (RF) shields to prevent electromagnetic interference with fMRI (temporal SNR >100), and is kinematically designed to minimize currents induced by the MRI scanner's magnetic field during motor displacement (<2cm). HFI possesses uniform inertial and force transmission properties across the workspace, and has low friction (.05-.30N). HFI's RF noise levels, in addition, are within a 3 Tesla fMRI scanner's baseline noise variation (∼.85±.1%). Finally, HFI is haptically transparent and does not interfere with human motor tasks (tested for .4m reaches). By allowing fMRI experiments involving complex three-dimensional manipulation with haptic interaction, Haptic fMRI enables-for the first time-non-invasive neuroscience experiments involving interactive motor tasks, object manipulation, tactile perception, and visuo-motor integration.

SDF1 regulates leading process branching and speed of migrating interneurons

PubMed Central

Lysko, Daniel E.; Putt, Mary; Golden, Jeffrey A.

2011-01-01

Cell migration is required for normal embryonic development, yet how cells navigate complex paths while integrating multiple guidance cues remains poorly understood. During brain development, interneurons migrate from the ventral ganglionic eminence to the cerebral cortex within several migratory streams. They must exit these streams to invade the cortical plate. While SDF1-signaling is necessary for normal interneuron stream migration, how they switch from tangential stream migration to invade the cortical plate is unknown. Here we demonstrate that SDF1-signaling reduces interneuron branching frequency by reducing cAMP levels via a Gi-signaling pathway using an in vitro mouse explant system, resulting in the maintenance of stream migration. Blocking SDF1-signaling, or increasing branching frequency, results in stream exit and cortical plate invasion in mouse brain slices. These data support a novel model to understand how migrating interneurons switch from tangential migration to invade the cortical plate in which reducing SDF1-signaling increases leading process branching and slows the migration rate, permitting migrating interneurons to sense cortically directed guidance cues. PMID:21289183

Motor Protein Myo1c Is a Podocyte Protein That Facilitates the Transport of Slit Diaphragm Protein Neph1 to the Podocyte Membrane ▿

PubMed Central

Arif, E.; Wagner, M. C.; Johnstone, D. B.; Wong, H. N.; George, B.; Pruthi, P. A.; Lazzara, M. J.; Nihalani, D.

2011-01-01

The podocyte proteins Neph1 and nephrin organize a signaling complex at the podocyte cell membrane that forms the structural framework for a functional glomerular filtration barrier. Mechanisms regulating the movement of these proteins to and from the membrane are currently unknown. This study identifies a novel interaction between Neph1 and the motor protein Myo1c, where Myo1c plays an active role in targeting Neph1 to the podocyte cell membrane. Using in vivo and in vitro experiments, we provide data supporting a direct interaction between Neph1 and Myo1c which is dynamic and actin dependent. Unlike wild-type Myo1c, the membrane localization of Neph1 was significantly reduced in podocytes expressing dominant negative Myo1c. In addition, Neph1 failed to localize at the podocyte cell membrane and cell junctions in Myo1c-depleted podocytes. We further demonstrate that similarly to Neph1, Myo1c also binds nephrin and reduces its localization at the podocyte cell membrane. A functional analysis of Myo1c knockdown cells showed defects in cell migration, as determined by a wound assay. In addition, the ability to form tight junctions was impaired in Myo1c knockdown cells, as determined by transepithelial electric resistance (TER) and bovine serum albumin (BSA) permeability assays. These results identify a novel Myo1c-dependent molecular mechanism that mediates the dynamic organization of Neph1 and nephrin at the slit diaphragm and is critical for podocyte function. PMID:21402783

Global Structure of a Three-Way Junction in a Phi29 Packaging RNA Dimer Determined Using Site-Directed Spin Labeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xiaojun; Tung, Chang-Shung; Sowa, Glenna

2012-02-08

The condensation of bacteriophage phi29 genomic DNA into its preformed procapsid requires the DNA packaging motor, which is the strongest known biological motor. The packaging motor is an intricate ring-shaped protein/RNA complex, and its function requires an RNA component called packaging RNA (pRNA). Current structural information on pRNA is limited, which hinders studies of motor function. Here, we used site-directed spin labeling to map the conformation of a pRNA three-way junction that bridges binding sites for the motor ATPase and the procapsid. The studies were carried out on a pRNA dimer, which is the simplest ring-shaped pRNA complex and servesmore » as a functional intermediate during motor assembly. Using a nucleotide-independent labeling scheme, stable nitroxide radicals were attached to eight specific pRNA sites without perturbing RNA folding and dimer formation, and a total of 17 internitroxide distances spanning the three-way junction were measured using Double Electron-Electron Resonance spectroscopy. The measured distances, together with steric chemical constraints, were used to select 3662 viable three-way junction models from a pool of 65 billion. The results reveal a similar conformation among the viable models, with two of the helices (HT and HL) adopting an acute bend. This is in contrast to a recently reported pRNA tetramer crystal structure, in which HT and HL stack onto each other linearly. The studies establish a new method for mapping global structures of complex RNA molecules, and provide information on pRNA conformation that aids investigations of phi29 packaging motor and developments of pRNA-based nanomedicine and nanomaterial.« less

Potential interactions among linguistic, autonomic, and motor factors in speech.

PubMed

Kleinow, Jennifer; Smith, Anne

2006-05-01

Though anecdotal reports link certain speech disorders to increases in autonomic arousal, few studies have described the relationship between arousal and speech processes. Additionally, it is unclear how increases in arousal may interact with other cognitive-linguistic processes to affect speech motor control. In this experiment we examine potential interactions between autonomic arousal, linguistic processing, and speech motor coordination in adults and children. Autonomic responses (heart rate, finger pulse volume, tonic skin conductance, and phasic skin conductance) were recorded simultaneously with upper and lower lip movements during speech. The lip aperture variability (LA variability index) across multiple repetitions of sentences that varied in length and syntactic complexity was calculated under low- and high-arousal conditions. High arousal conditions were elicited by performance of the Stroop color word task. Children had significantly higher lip aperture variability index values across all speaking tasks, indicating more variable speech motor coordination. Increases in syntactic complexity and utterance length were associated with increases in speech motor coordination variability in both speaker groups. There was a significant effect of Stroop task, which produced increases in autonomic arousal and increased speech motor variability in both adults and children. These results provide novel evidence that high arousal levels can influence speech motor control in both adults and children. (c) 2006 Wiley Periodicals, Inc.

The two cultures of health worker migration: a Pacific perspective.

PubMed

Connell, John

2014-09-01

Migration of health workers from relatively poor countries has been sustained for more than half a century. The rationale for migration has been linked to numerous factors relating to the economies and health systems of source and destination countries. The contemporary migration of health workers is also embedded in a longstanding and intensifying culture of migration, centred on the livelihoods of extended households, and a medical culture that is oriented to superior technology and advanced skills. This dual culture is particularly evident in small island states in the Pacific, but is apparent in other significant migrant source countries in the Caribbean, Sub-Saharan Africa and Asia. Family expectations of the benefits of migration indicate that regulating the migration and attrition of health workers necessitates more complex policies beyond those evident within health care systems alone. Copyright © 2014. Published by Elsevier Ltd.

Determinants of spring migration departure decision in a bat.

PubMed

Dechmann, Dina K N; Wikelski, M; Ellis-Soto, D; Safi, K; O'Mara, M Teague

2017-09-01

Migratory decisions in birds are closely tied to environmental cues and fat stores, but it remains unknown if the same variables trigger bat migration. To learn more about the rare phenomenon of bat migration, we studied departure decisions of female common noctules ( Nyctalus noctula ) in southern Germany. We did not find the fattening period that modulates departure decisions in birds. Female noctules departed after a regular evening foraging session, uniformly heading northeast. As the day of year increased, migratory decisions were based on the interactions among wind speed, wind direction and air pressure. As the migration season progressed, bats were likely to migrate on nights with higher air pressure and faster tail winds in the direction of travel, and also show high probability of migration on low-pressure nights with slow head winds. Common noctules thus monitor complex environmental conditions to find the optimal migration night. © 2017 The Authors.

Migration of magnetotactic bacteria in porous media.

PubMed

Rismani Yazi, Saeed; Nosrati, Reza; Stevens, Corey A; Vogel, David; Escobedo, Carlos

2018-01-01

Magnetotactic bacteria (MTB) migrate in complex porous sediments where fluid flow is ubiquitous. Here, we demonstrate that magnetotaxis enables MTB to migrate effectively through porous micromodels. Directed MTB can circumvent curved obstacles by traveling along the boundaries and pass flat obstacles by repeatedly switching between forward and backward runs. Magnetotaxis enables directed motion of MTB through heterogeneous porous media, overcoming tortuous flow fields with local velocities as high as 250  μ m s -1 . Our findings bring new insights into the migration behaviour of MTB in their natural habitats and their potential in vivo applications as microbiorobots.

Verification of the Robin and Graham classification system of hip disease in cerebral palsy using three-dimensional computed tomography.

PubMed

Gose, Shinichi; Sakai, Takashi; Shibata, Toru; Akiyama, Keisuke; Yoshikawa, Hideki; Sugamoto, Kazuomi

2011-12-01

We evaluated the validity of the Robin and Graham classification system of hip disease in cerebral palsy (CP) using three-dimensional computed tomography in young people with CP. A total of 91 hips in 91 consecutive children with bilateral spastic CP (57 males, 34 females; nine classified at Gross Motor Function Classification System level II, 42 at level III, 32 at level IV, and eight at level V; mean age 5 y 2 mo, SD 11 mo; range 2-6 y) were investigated retrospectively using anteroposterior plain radiographs and three-dimensional computed tomography (3D-CT) of the hip. The migration percentage was calculated on plain radiographs and all participants were classified into four groups according to migration percentage: grade II, migration percentage ≥ 10% but ≤ 15%, (four hips), grade III, migration percentage >15% but ≤ 30%, (20 hips); grade IV, migration percentage >30% but <100%, (63 hips); and grade V, migration percentage ≥ 100%, (four hips). The lateral opening angle and the sagittal inclination angle of the acetabulum, the neck-shaft angle, and the femoral anteversion of the femur were measured on 3D-CT. The three-dimensional quantitative evaluation indicated that there were significant differences in the lateral opening angle and the neck-shaft angle between the four groups (Kruskal-Wallis test, p ≤ 0.001). This three-dimensional evaluation supports the validation of the Robin and Graham classification system for hip disease in 2- to 7-year-olds with CP. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

"Decarbonization" of an imino N-heterocyclic carbene via triple benzyl migration from hafnium

USDA-ARS?s Scientific Manuscript database

An imino N-heterocyclic carbene underwent three sequential benzyl migrations upon reaction with tetrabenzylhafnium, resulting in complete removal of the carbene carbon from the ligand. The resulting eneamido-amidinato hafnium complex showed alkene polymerization activity comparable to that of a prec...

Definition and classification of negative motor signs in childhood.

PubMed

Sanger, Terence D; Chen, Daofen; Delgado, Mauricio R; Gaebler-Spira, Deborah; Hallett, Mark; Mink, Jonathan W

2006-11-01

In this report we describe the outcome of a consensus meeting that occurred at the National Institutes of Health in Bethesda, Maryland, March 12 through 14, 2005. The meeting brought together 39 specialists from multiple clinical and research disciplines including developmental pediatrics, neurology, neurosurgery, orthopedic surgery, physical therapy, occupational therapy, physical medicine and rehabilitation, neurophysiology, muscle physiology, motor control, and biomechanics. The purpose of the meeting was to establish terminology and definitions for 4 aspects of motor disorders that occur in children: weakness, reduced selective motor control, ataxia, and deficits of praxis. The purpose of the definitions is to assist communication between clinicians, select homogeneous groups of children for clinical research trials, facilitate the development of rating scales to assess improvement or deterioration with time, and eventually to better match individual children with specific therapies. "Weakness" is defined as the inability to generate normal voluntary force in a muscle or normal voluntary torque about a joint. "Reduced selective motor control" is defined as the impaired ability to isolate the activation of muscles in a selected pattern in response to demands of a voluntary posture or movement. "Ataxia" is defined as an inability to generate a normal or expected voluntary movement trajectory that cannot be attributed to weakness or involuntary muscle activity about the affected joints. "Apraxia" is defined as an impairment in the ability to accomplish previously learned and performed complex motor actions that is not explained by ataxia, reduced selective motor control, weakness, or involuntary motor activity. "Developmental dyspraxia" is defined as a failure to have ever acquired the ability to perform age-appropriate complex motor actions that is not explained by the presence of inadequate demonstration or practice, ataxia, reduced selective motor control, weakness, or involuntary motor activity.

Arrested 1,2-hydrogen migration from silicon to nickel upon oxidation of a three-coordinate Ni(I) silyl complex.

PubMed

Iluc, Vlad M; Hillhouse, Gregory L

2010-09-01

Reaction of the dimeric Ni(I) chloride complex [(dtbpe)NiCl](2) (1) with dimesitylsilyl potassium affords the three-coordinate Ni(I) silyl complex (dtbpe)Ni(SiHMes(2)) (2). Alternatively, 2 can be prepared by an oxidative-addition reaction of Mes(2)Si(H)OTf (Tf = CF(3)SO(3)) with the nickel(0) complex [(dtbpe)Ni](2)(mu-C(6)H(6)) (3), with (dtbpe)Ni(OTf) (4) formed as an easily separable byproduct. The one-electron oxidation of 2 by ferrocenium affords diamagnetic [(dtbpe)Ni(mu-H)SiMes(2)][BAr(F)(4)] (5), a Ni(II) complex formed by partial 1,2-H migration from silicon to nickel and featuring an unusual 3-center, 2-electron bonding motif between Ni, Si, and the bridging H. Complex 5 was also obtained from Mes(2)SiH(2) activation by the neopentyl complex salt [(dtbpe)Ni(CH(2)CMe(3))][BAr(F)(4)] (6) with elimination of neopentane.

Quantifying full phenological event distributions reveals simultaneous advances, temporal stability and delays in spring and autumn migration timing in long-distance migratory birds.

PubMed

Miles, Will T S; Bolton, Mark; Davis, Peter; Dennis, Roy; Broad, Roger; Robertson, Iain; Riddiford, Nick J; Harvey, Paul V; Riddington, Roger; Shaw, Deryk N; Parnaby, David; Reid, Jane M

2017-04-01

Phenological changes in key seasonally expressed life-history traits occurring across periods of climatic and environmental change can cause temporal mismatches between interacting species, and thereby impact population and community dynamics. However, studies quantifying long-term phenological changes have commonly only measured variation occurring in spring, measured as the first or mean dates on which focal traits or events were observed. Few studies have considered seasonally paired events spanning spring and autumn or tested the key assumption that single convenient metrics accurately capture entire event distributions. We used 60 years (1955-2014) of daily bird migration census data from Fair Isle, Scotland, to comprehensively quantify the degree to which the full distributions of spring and autumn migration timing of 13 species of long-distance migratory bird changed across a period of substantial climatic and environmental change. In most species, mean spring and autumn migration dates changed little. However, the early migration phase (≤10th percentile date) commonly got earlier, while the late migration phase (≥90th percentile date) commonly got later. Consequently, species' total migration durations typically lengthened across years. Spring and autumn migration phenologies were not consistently correlated within or between years within species and hence were not tightly coupled. Furthermore, different metrics quantifying different aspects of migration phenology within seasons were not strongly cross-correlated, meaning that no single metric adequately described the full pattern of phenological change. These analyses therefore reveal complex patterns of simultaneous advancement, temporal stability and delay in spring and autumn migration phenologies, altering species' life-history structures. Additionally, they demonstrate that this complexity is only revealed if multiple metrics encompassing entire seasonal event distributions, rather than single metrics, are used to quantify phenological change. Existing evidence of long-term phenological changes detected using only one or two metrics should consequently be interpreted cautiously because divergent changes occurring simultaneously could potentially have remained undetected. © 2016 John Wiley & Sons Ltd.

Direct migration motion estimation and mode decision to decoder for a low-complexity decoder Wyner-Ziv video coding

NASA Astrophysics Data System (ADS)

Lei, Ted Chih-Wei; Tseng, Fan-Shuo

2017-07-01

This paper addresses the problem of high-computational complexity decoding in traditional Wyner-Ziv video coding (WZVC). The key focus is the migration of two traditionally high-computationally complex encoder algorithms, namely motion estimation and mode decision. In order to reduce the computational burden in this process, the proposed architecture adopts the partial boundary matching algorithm and four flexible types of block mode decision at the decoder. This approach does away with the need for motion estimation and mode decision at the encoder. The experimental results show that the proposed padding block-based WZVC not only decreases decoder complexity to approximately one hundredth that of the state-of-the-art DISCOVER decoding but also outperforms DISCOVER codec by up to 3 to 4 dB.

Direct observation of bis(dicarbollyl)nickel conformers in solution by fluorescence spectroscopy: an approach to redox-controlled metallacarborane molecular motors.

PubMed

Safronov, Alexander V; Shlyakhtina, Natalia I; Everett, Thomas A; VanGordon, Monika R; Sevryugina, Yulia V; Jalisatgi, Satish S; Hawthorne, M Frederick

2014-10-06

As a continuation of work on metallacarborane-based molecular motors, the structures of substituted bis(dicarbollyl)nickel complexes in Ni(III) and Ni(IV) oxidation states were investigated in solution by fluorescence spectroscopy. Symmetrically positioned cage-linked pyrene molecules served as fluorescent probes to enable the observation of mixed meso-trans/dl-gauche (pyrene monomer fluorescence) and dl-cis/dl-gauche (intramolecular pyrene excimer fluorescence with residual monomer fluorescence) cage conformations of the nickelacarboranes in the Ni(III) and Ni(IV) oxidation states, respectively. The absence of energetically disfavored conformers in solution--dl-cis in the case of nickel(III) complexes and meso-trans in the case of nickel(IV)--was demonstrated based on spectroscopic data and conformer energy calculations in solution. The conformational persistence observed in solution indicates that bis(dicarbollyl)nickel complexes may provide attractive templates for building electrically driven and/or photodriven molecular motors.

Using the self-select paradigm to delineate the nature of speech motor programming.

PubMed

Wright, David L; Robin, Don A; Rhee, Jooyhun; Vaculin, Amber; Jacks, Adam; Guenther, Frank H; Fox, Peter T

2009-06-01

The authors examined the involvement of 2 speech motor programming processes identified by S. T. Klapp (1995, 2003) during the articulation of utterances differing in syllable and sequence complexity. According to S. T. Klapp, 1 process, INT, resolves the demands of the programmed unit, whereas a second process, SEQ, oversees the serial order demands of longer sequences. A modified reaction time paradigm was used to assess INT and SEQ demands. Specifically, syllable complexity was dependent on syllable structure, whereas sequence complexity involved either repeated or unique syllabi within an utterance. INT execution was slowed when articulating single syllables in the form CCCV compared to simpler CV syllables. Planning unique syllables within a multisyllabic utterance rather than repetitions of the same syllable slowed INT but not SEQ. The INT speech motor programming process, important for mental syllabary access, is sensitive to changes in both syllable structure and the number of unique syllables in an utterance.

A Model of Motor Inhibition for a Complex Skill: Baseball Batting

ERIC Educational Resources Information Center

Gray, Rob

2009-01-01

The ability to inhibit an ongoing action in response to a signal from the environment is important for many perceptual-motor actions. This paper examines a particular example of this behavior: attempting to inhibit or "check" a swing in baseball batting. A model of motor inhibition in batting is proposed. In the model there are three different…

Gendered Patterns of Migration in Rural South Africa

PubMed Central

Camlin, Carol S.; Snow, Rachel C.; Hosegood, Victoria

2013-01-01

Gender is increasingly recognized as fundamental to understanding migration processes, causes and consequences. In South Africa, it is intrinsic to the social transformations fueling high levels of internal migration and complex forms of mobility. While female migration in Africa has often been characterized as less prevalent than male migration, and primarily related to marriage, in South Africa a feminization of internal migration is underway, fueled by women’s increasing labor market participation. In this paper, we report sex differences in patterns, trends and determinants of internal migration based on data collected in a demographic surveillance system between 2001 and 2006 in rural KwaZulu-Natal. We show that women were somewhat more likely than men to undertake any migration, but sex differences in migration trends differed by migration flow, with women more likely to migrate into the area than men, and men more likely to out-migrate. Out-migration was suppressed by marriage particularly for women, but most women were not married; both men’s and women’s out-migrations were undertaken mainly for purposes of employment. Over half of female out-migrations (versus 35% of male out-migrations) were to nearby rural areas. The findings highlight the high mobility of this population and the extent to which gender is intimately related to the processes determining migration. We consider the implications of these findings for the measurement of migration and mobility, in particular for health and social policy and research among highly mobile populations in southern Africa. PMID:25332690

An advanced application of the quantitative structure-activity relationship concept in electrokinetic chromatography of metal complexes.

PubMed

Oszwałdowski, Sławomir; Timerbaev, Andrei R

2008-02-01

The relevance of the quantitative structure-activity relationship (QSAR) principle in MEKC and microemulsion EKC (MEEKC) of metal-ligand complexes was evaluated for a better understanding of analyte migration mechanism. A series of gallium chelates were applied as test solutes with available experimental migration data in order to reveal the molecular properties that govern the separation. The QSAR models operating with n-octanol-water partition coefficients or van der Waals volumes were found to be valid for estimation of the retention factors (log k') of neutral compounds when using only an aqueous MEEKC electrolyte. On the other hand, consistent approximations of log k' for both uncharged and charged complexes in either EKC mode (and also with hydro-organic BGEs) were achievable with two-parametric QSARs in which the dipole moment is additionally incorporated as a structural descriptor, reflecting the electrostatic solute-pseudostationary phase interaction. The theoretical analysis of significant molecular parameters in MEKC systems, in which the micellar BGE is modified with an organic solvent, confirmed that concomitant consideration of hydrophobic, electrostatic, and solvation factors is essential for explaining the migration behavior of neutral metal complexes.

Habitat Complexity Metrics to Guide Restoration of Large Rivers

NASA Astrophysics Data System (ADS)

Jacobson, R. B.; McElroy, B. J.; Elliott, C.; DeLonay, A.

2011-12-01

Restoration strategies on large, channelized rivers typically strive to recover lost habitat complexity, based on the assumption complexity and biophysical capacity are directly related. Although definition of links between complexity and biotic responses can be tenuous, complexity metrics have appeal because of their potential utility in quantifying habitat quality, defining reference conditions and design criteria, and measuring restoration progress. Hydroacoustic instruments provide many ways to measure complexity on large rivers, yet substantive questions remain about variables and scale of complexity that are meaningful to biota, and how complexity can be measured and monitored cost effectively. We explore these issues on the Missouri River, using the example of channel re-engineering projects that are intended to aid in recovery of the pallid sturgeon, an endangered benthic fish. We are refining understanding of what habitat complexity means for adult fish by combining hydroacoustic habitat assessments with acoustic telemetry to map locations during reproductive migrations and spawning. These data indicate that migrating sturgeon select points with relatively low velocity but adjacent to areas of high velocity (that is, with high velocity gradients); the integration of points defines pathways which minimize energy expenditures during upstream migrations of 10's to 100's of km. Complexity metrics that efficiently quantify migration potential at the reach scale are therefore directly relevant to channel restoration strategies. We are also exploring complexity as it relates to larval sturgeon dispersal. Larvae may drift for as many as 17 days (100's of km at mean velocities) before using up their yolk sac, after which they "settle" into habitats where they initiate feeding. An assumption underlying channel re-engineering is that additional channel complexity, specifically increased shallow, slow water, is necessary for early feeding and refugia. Development of complexity metrics is complicated by the fact that characteristics of channel morphology may increase complexity scores without necessarily increasing biophysical capacity for target species. For example, a cross section that samples depths and velocities across the thalweg (navigation channel) and into lentic habitat may score high on most measures of hydraulic or geomorphic complexity, but does not necessarily provide habitats beneficial to native species. Complexity measures need to be bounded by best estimates of native species requirements. In the absence of specific information, creation of habitat complexity for the sake of complexity may lead to unintended consequences, for example, lentic habitats that increase a complexity score but support invasive species. An additional practical constraint on complexity measures is the need to develop metrics that are can be deployed cost-effectively in an operational monitoring program. Design of a monitoring program requires informed choices of measurement variables, definition of reference sites, and design of sampling effort to capture spatial and temporal variability.

Phosphorylation of Tyrosine Residues 31 and 118 on Paxillin Regulates Cell Migration through an Association with Crk in Nbt-II Cells

PubMed Central

Petit, Valérie; Boyer, Brigitte; Lentz, Delphine; Turner, Christopher E.; Thiery, Jean Paul; Vallés, Ana M.

2000-01-01

Identification of signaling molecules that regulate cell migration is important for understanding fundamental processes in development and the origin of various pathological conditions. The migration of Nara Bladder Tumor II (NBT-II) cells was used to determine which signaling molecules are specifically involved in the collagen-mediated locomotion. We show here that paxillin is tyrosine phosphorylated after induction of motility on collagen. Overexpression of paxillin mutants in which tyrosine 31 and/or tyrosine 118 were replaced by phenylalanine effectively impaired cell motility. Moreover, stimulation of motility by collagen preferentially enhanced the association of paxillin with the SH2 domain of the adaptor protein CrkII. Mutations in both tyrosine 31 and 118 diminished the phosphotyrosine content of paxillin and prevented the formation of the paxillin–Crk complex, suggesting that this association is necessary for collagen-mediated NBT-II cell migration. Other responses to collagen, such as cell adhesion and spreading, were not affected by these mutations. Overexpression of wild-type paxillin or Crk could bypass the migration-deficient phenotype. Both the SH2 and the SH3 domains of CrkII are shown to play a critical role in this collagen-mediated migration. These results demonstrate the important role of the paxillin–Crk complex in the collagen-induced cell motility. PMID:10704446

Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes

PubMed Central

Clatworthy, Menna R.; Aronin, Caren E. Petrie; Mathews, Rebeccah J.; Morgan, Nicole; Smith, Kenneth G.C.; Germain, Ronald N.

2014-01-01

Antibodies are critical for defence against a variety of microbes but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). DCs are important antigen presenting cells and play a central role in inducing antigen-specific tolerance or immunity1,2. Following antigen acquisition in peripheral tissues, DCs migrate to draining lymph nodes via lymphatics to present antigen to T cells. In this study we demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC-stimulated murine and human DCs showed enhanced directional migration in a CCL19 gradient and increased CCR7 expression. Using intravital two-photon microscopy, we observed that local administration of IC resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. These observations have relevance to autoimmunity, because autoantibody-containing serum from mice and humans with SLE also increased dermal DC migration to lymph nodes in vivo, suggesting that this process may occur in lupus, potentially driving the inappropriate localisation of autoantigen-bearing DCs. PMID:25384086

Operating principles of rotary molecular motors: differences between F1 and V1 motors

PubMed Central

Yamato, Ichiro; Kakinuma, Yoshimi; Murata, Takeshi

2016-01-01

Among the many types of bioenergy-transducing machineries, F- and V-ATPases are unique bio- and nano-molecular rotary motors. The rotational catalysis of F1-ATPase has been investigated in detail, and molecular mechanisms have been proposed based on the crystal structures of the complex and on extensive single-molecule rotational observations. Recently, we obtained crystal structures of bacterial V1-ATPase (A3B3 and A3B3DF complexes) in the presence and absence of nucleotides. Based on these new structures, we present a novel model for the rotational catalysis mechanism of V1-ATPase, which is different from that of F1-ATPases. PMID:27924256

Thermal stability of isolated and complexed Ga vacancies in GaN bulk crystals

NASA Astrophysics Data System (ADS)

Saarinen, K.; Suski, T.; Grzegory, I.; Look, D. C.

2001-12-01

We have applied positron annihilation spectroscopy to show that 2-MeV electron irradiation at 300 K creates primary Ga vacancies in GaN with an introduction rate of 1 cm-1. The Ga vacancies recover in long-range migration processes at 500-600 K with an estimated migration energy of 1.5 (2) eV. Since the native Ga vacancies in as-grown GaN survive up to much higher temperatures (1300-1500 K), we conclude that they are stabilized by forming complexes with oxygen impurities. The estimated binding energy of 2.2 (4) eV of such complexes is in good agreement with the results of theoretical calculations.

Protein translocation channel of mitochondrial inner membrane and matrix-exposed import motor communicate via two-domain coupling protein.

PubMed

Banerjee, Rupa; Gladkova, Christina; Mapa, Koyeli; Witte, Gregor; Mokranjac, Dejana

2015-12-29

The majority of mitochondrial proteins are targeted to mitochondria by N-terminal presequences and use the TIM23 complex for their translocation across the mitochondrial inner membrane. During import, translocation through the channel in the inner membrane is coupled to the ATP-dependent action of an Hsp70-based import motor at the matrix face. How these two processes are coordinated remained unclear. We show here that the two domain structure of Tim44 plays a central role in this process. The N-terminal domain of Tim44 interacts with the components of the import motor, whereas its C-terminal domain interacts with the translocation channel and is in contact with translocating proteins. Our data suggest that the translocation channel and the import motor of the TIM23 complex communicate through rearrangements of the two domains of Tim44 that are stimulated by translocating proteins.

Physician Migration, Education, and Health Care

ERIC Educational Resources Information Center

Norcini, John J.; Mazmanian, Paul E.

2005-01-01

Physician migration is a complex and multifaceted phenomenon that is intimately intertwined with medical education. Imbalances in the production of physicians lead to workforce shortages and surpluses that compromise the ability to deliver adequate and equitable health care to large parts of the world's population. In this overview, we address a…

Educational Opportunity and Immigration in México: Exploring the Individual and Systemic Relationships

ERIC Educational Resources Information Center

Martínez, José Felipe; Santibanez, Lucrecia; Serván Mori, Edson E.

2013-01-01

Background/Context: Much research has investigated the complex interplay between education and migration. Education has been alternatively conceptualized as playing an important role as motivator or deterrent of future migration. This relationship, however, is often investigated in terms of coarse indicators of educational attainment. Purpose: In…

Mechanical guidance of collective cell migration and invasion

NASA Astrophysics Data System (ADS)

Trepat, Xavier

A broad range of biological processes such as morphogenesis, tissue regeneration, and cancer invasion depend on the collective migration of epithelial cells. Guidance of collective cell migration is commonly attributed to soluble or immobilized chemical gradients. I will present novel mechanisms of collective cellular guidance that are physical in origin rather than chemical. Firstly, I will focus on how the mechanical interaction between the tumor and its stroma guides cancer cell invasion. I will show that cancer associated fibroblasts exert a physical force on cancer cells that enables their collective invasion. In the second part of my talk I will focus on durotaxis, the ability of cells to follow gradients of extracellular matrix stiffness. Durotaxis is well established as a single cell phenomenon but whether it can direct the motion of cell collectives is unknown. I will show that durotaxis emerges in cell collectives even if isolated constituent cells are unable to durotax. Collective durotaxis applies to a broad variety of epithelial cell types and requires the action of myosin motors and the integrity of cell-cell junctions. Collective durotaxis is more efficient than any previous report of single cell durotaxis; it thus emerges as robust mechanism to direct collective cell migration in development and disease.eplace this text with your abstract.

In-migration and Living Conditions of Young Adolescents in Greater Johannesburg, South Africa

PubMed Central

Richter, Linda M.; Norris, Shane A.; Swart, Tanya M.; Ginsburg, Carren

2007-01-01

While migration in South Africa has been studied on a broad canvas, there have been few accounts of children's migration and the effects on living conditions and wellbeing. This article compares the access to services, housing and household amenities, and family characteristics of children born in the Greater Johannesburg metropolis with those of in-migrant children. The article also examines other indicators of child wellbeing related to parental care and schooling. In-migrant children, particularly children who have lived previously in rural areas and/or have recently migrated into the city, are significantly disadvantaged in comparison to long-term resident children in terms of parental education and occupation, housing type and ownership, access to electricity, refuse removal, water and sanitation. In-migrant children also live in households that are less likely to have amenities such as a refrigerator, television, washing machine, telephone and motor vehicle. In terms of child indicators, in-migrant children enjoy less frequent parental contact and are twice as likely to start school later than resident children. Whilst urbanisation to South Africa's metropolitan centres is generally associated with several widely recognised benefits, for children, these benefits may be tempered by the disadvantages of in-migrant families known to be associated with child wellbeing. PMID:18273401

Parabolic dune reactivation and migration at Napeague, NY, USA: Insights from aerial and GPR imagery

NASA Astrophysics Data System (ADS)

Girardi, James D.; Davis, Dan M.

2010-02-01

Observations from mapping since the 19th century and aerial imagery since 1930 have been used to study changes in the aeolian geomorphology of coastal parabolic dunes over the last ~ 170 years in the Walking Dune Field, Napeague, NY. The five large parabolic dunes of the Walking Dune Field have all migrated across, or are presently interacting with, a variably forested area that has affected their migration, stabilization and morphology. This study has concentrated on a dune with a particularly complex history of stabilization, reactivation and migration. We have correlated that dune's surface evolution, as revealed by aerial imagery, with its internal structures imaged using 200 MHz and 500 MHz Ground Penetrating Radar (GPR) surveys. Both 2D (transect) and high-resolution 3D GPR imagery image downwind dipping bedding planes which can be grouped by apparent dip angle into several discrete packages of beds that reflect distinct decadal-scale episodes of dune reactivation and growth. From aerial and high resolution GPR imagery, we document a unique mode of reactivation and migration linked to upwind dune formation and parabolic dune interactions with forest trees. This study documents how dune-dune and dune-vegetation interactions have influenced a unique mode of blowout deposition that has alternated on a decadal scale between opposite sides of a parabolic dune during reactivation and migration. The pattern of recent parabolic dune reactivation and migration in the Walking Dune Field appears to be somewhat more complex, and perhaps more sensitive to subtle environmental pressures, than an idealized growth model with uniform deposition and purely on-axis migration. This pattern, believed to be prevalent among other parabolic dunes in the Walking Dune Field, may occur also in many other places where similar observational constraints are unavailable.

Quantitative Analysis of Complex Glioma Cell Migration on Electrospun Polycaprolactone Using Time-Lapse Microscopy

PubMed Central

Johnson, Jed; Nowicki, M. Oskar; Lee, Carol H.; Chiocca, E. Antonio; Viapiano, Mariano S.; Lawler, Sean E.

2009-01-01

Malignant gliomas are the most common tumors originating within the central nervous system and account for over 15,000 deaths annually in the United States. The median survival for glioblastoma, the most common and aggressive of these tumors, is only 14 months. Therapeutic strategies targeting glioma cells migrating away from the tumor core are currently hampered by the difficulty of reproducing migration in the neural parenchyma in vitro. We utilized a tissue engineering approach to develop a physiologically relevant model of glioma cell migration. This revealed that glioma cells display dramatic differences in migration when challenged by random versus aligned electrospun poly-ɛ-caprolactone nanofibers. Cells on aligned fibers migrated at an effective velocity of 4.2 ± 0.39 μm/h compared to 0.8 ± 0.08 μm/h on random fibers, closely matching in vivo models and prior observations of glioma spread in white versus gray matter. Cells on random fibers exhibited extension along multiple fiber axes that prevented net motion; aligned fibers promoted a fusiform morphology better suited to infiltration. Time-lapse microscopy revealed that the motion of individual cells was complex and was influenced by cell cycle and local topography. Glioma stem cell–containing neurospheres seeded on random fibers did not show cell detachment and retained their original shape; on aligned fibers, cells detached and migrated in the fiber direction over a distance sixfold greater than the perpendicular direction. This chemically and physically flexible model allows time-lapse analysis of glioma cell migration while recapitulating in vivo cell morphology, potentially allowing identification of physiological mediators and pharmacological inhibitors of invasion. PMID:19199562

Electromagnetic driving units for complex microrobotic systems

NASA Astrophysics Data System (ADS)

Michel, Frank; Ehrfeld, Wolfgang; Berg, Udo; Degen, Reinhard; Schmitz, Felix

1998-10-01

Electromagnetic actuators play an important role in macroscopic robotic systems. In combination with motion transformers, like reducing gear units, angular gears or spindle-screw drives, electromagnetic motors in large product lines ensure the rotational or linear motion of robot driving units and grippers while electromagnets drive valves or part conveyors. In this paper micro actuators and miniaturized motion transformers are introduced which allow a similar development in microrobotics. An electromagnetic motor and a planetary gear box, both with a diameter of 1.9 mm, are already commercially available from the cooperation partner of IMM, the company Dr. Fritz Faulhaber GmbH in Schonaich, Germany. In addition, a motor with a diameter of 2.4 mm is in development. The motors successfully drive an angular gear and a belt drive. A linear stage with a motion range of 7 mm and an overall size as small as 5 X 3.5 X 24 mm3 has been realized involving the motor, a stationary spur gear with zero backlash and a spindle-screw drive. By the use of these commercially available elements complex microrobots can be built up cost-efficiently and rapidly. Furthermore, a batch process has been developed to produce the coils of micro actuator arrays using lithographic techniques with SU-8 resin. In applying these components, the modular construction of complex microrobotic systems becomes feasible.

Characterization of f-actin tryptophan phosphorescence in the presence and absence of tryptophan-free myosin motor domain.

PubMed

Bódis, Emöke; Strambini, Giovanni B; Gonnelli, Margherita; Málnási-Csizmadia, András; Somogyi, Béla

2004-08-01

The effect of binding the Trp-free motor domain mutant of Dictyostelium discoideum, rabbit skeletal muscle myosin S1, and tropomyosin on the dynamics and conformation of actin filaments was characterized by an analysis of steady-state tryptophan phosphorescence spectra and phosphorescence decay kinetics over a temperature range of 140-293 K. The binding of the Trp-free motor domain mutant of D. discoideum to actin caused red shifts in the phosphorescence spectrum of two internal Trp residues of actin and affected the intrinsic lifetime of each emitter, decreasing by roughly twofold the short phosphorescence lifetime components (tau(1) and tau(2)) and increasing by approximately 20% the longest component (tau(3)). The alteration of actin phosphorescence by the motor protein suggests that i), structural changes occur deep down in the core of actin and that ii), subtle changes in conformation appear also on the surface but in regions distant from the motor domain binding site. When actin formed complexes with skeletal S1, an extra phosphorescence lifetime component appeared (tau(4), twice as long as tau(3)) in the phosphorescence decay that is absent in the isolated proteins. The lack of this extra component in the analogous actin-Trp-free motor domain mutant of D. discoideum complex suggests that it should be assigned to Trps in S1 that in the complex attain a more compact local structure. Our data indicated that the binding of tropomyosin to actin filaments had no effect on the structure or flexibility of actin observable by this technique.

Complex behaviour in complex terrain - Modelling bird migration in a high resolution wind field across mountainous terrain to simulate observed patterns.

PubMed

Aurbach, Annika; Schmid, Baptiste; Liechti, Felix; Chokani, Ndaona; Abhari, Reza

2018-06-03

Crossing of large ecological barriers, such as mountains, is in terms of energy considered to be a demanding and critical step during bird migration. Besides forming a geographical barrier, mountains have a profound impact on the resulting wind flow. We use a novel framework of mathematical models to investigate the influences of wind and topography on nocturnal passerine bird behaviour, and to assess the energy costs for different flight strategies for crossing the Jura Mountains. The mathematical models include three biological models of bird behaviour: i) wind drift compensation; ii) adaptation of flight height for favourable winds; and, iii) avoidance of obstacles (cross over and/or circumvention of an obstacle following a minimum energy expenditure strategy), which are assessed separately and in combination. Further, we use a mesoscale weather model for high-resolution predictions of the wind fields. We simulate the broad front nocturnal passerine migration for autumn nights with peak migration intensities. The bird densities retrieved from a weather radar are used as the initial intensities and to specify the vertical distributions of the simulated birds. It is shown that migration over complex terrain represents the most expensive flight option in terms of energy expenditure, and wind is seen to be the main factor that influences the energy expenditure in the bird's preferred flight direction. Further, the combined effects of wind and orography lead to a high concentration of migratory birds within the favourable wind conditions of the Swiss lowlands and north of the Jura Mountains. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anticipatory activity in primary motor cortex codes memorized movement sequences.

PubMed

Lu, Xiaofeng; Ashe, James

2005-03-24

Movement sequences, defined both by the component movements and by the serial order in which they are produced, are fundamental building blocks of motor behavior. The serial order of sequence production is strongly encoded in medial motor areas. It is not known to what extent sequences are further elaborated or encoded in primary motor cortex. Here, we describe cells in the primary motor cortex of the monkey that show anticipatory activity exclusively related to a specific memorized sequence of upcoming movements. In addition, the injection of muscimol, a GABA agonist, into motor cortex resulted in an increase in the error rate during sequence production, without concomitant effects on nonsequenced motor performance. Our results challenge the role of medial motor areas in the control of well-practiced movement sequences and suggest that motor cortex contains a complete apparatus for the planning and production of this complex behavior.

Automated complex for research of electric drives control

NASA Astrophysics Data System (ADS)

Avlasko, P. V.; Antonenko, D. A.

2018-05-01

In the article, the automated complex intended for research of various control modes of electric motors including the inductor motor of double-way feed is described. As a basis of the created complex, the National Instruments platform is chosen. The operating controller built in a platform is delivered with an operating system of real-time for creation of systems of measurement and management. The software developed in the environment of LabVIEW consists of several connected modules which are in different elements of a complex. Besides the software for automated management by experimental installation, the program complex is developed for modelling of processes in the electric drive. As a result there is an opportunity to compare simulated and received experimentally transitional characteristics of the electric drive in various operating modes.

Rh-Catalyzed Intermolecular Reactions of α-Alkyl-α-Diazo Carbonyl Compounds with Selectivity over β-Hydride Migration.

PubMed

DeAngelis, Andrew; Panish, Robert; Fox, Joseph M

2016-01-19

Rh-carbenes derived from α-diazocarbonyl compounds have found broad utility across a remarkable range of reactivity, including cyclopropanation, cyclopropenation, C-H insertions, heteroatom-hydrogen insertions, and ylide forming reactions. However, in contrast to α-aryl or α-vinyl-α-diazocarbonyl compounds, the utility of α-alkyl-α-diazocarbonyl compounds had been moderated by the propensity of such compounds to undergo intramolecular β-hydride migration to give alkene products. Especially challenging had been intermolecular reactions involving α-alkyl-α-diazocarbonyl compounds. This Account discusses the historical context and prior limitations of Rh-catalyzed reactions involving α-alkyl-α-diazocarbonyl compounds. Early studies demonstrated that ligand and temperature effects could influence chemoselectivity over β-hydride migration. However, effects were modest and conflicting conclusions had been drawn about the influence of sterically demanding ligands on β-hydride migration. More recent advances have led to a more detailed understanding of the reaction conditions that can promote intermolecular reactivity in preference to β-hydride migration. In particular, the use of bulky carboxylate ligands and low reaction temperatures have been key to enabling intermolecular cyclopropenation, cyclopropanation, carbonyl ylide formation/dipolar cycloaddition, indole C-H functionalization, and intramolecular bicyclobutanation with high chemoselectivity over β-hydride migration. Cyclic α-diazocarbonyl compounds have been shown to be particularly resilient toward β-hydride migration and are the first class of compounds that can engage in intermolecular reactivity in the presence of tertiary β-hydrogens. DFT calculations were used to propose that for cyclic α-diazocarbonyl compounds, ring constraints relieve steric interaction for intermolecular reactions and thereby accelerate the rate of intermolecular reactivity relative to intramolecular β-hydride migration. Enantioselective reactions of α-alkyl-α-diazocarbonyl compounds have been developed using bimetallic N-imido-tert-leucinate-derived complexes. The most effective complexes were found by computation and X-ray crystallography to adopt a "chiral crown" conformation in which all of the imido groups are presented on one face of the paddlewheel complex in a chiral arrangement. Insight from computational studies guided the design and synthesis of a mixed ligand paddlewheel complex, Rh2(S-PTTL)3TPA, the structure of which bears similarity to the chiral crown complex Rh2(S-PTTL)4. Rh2(S-PTTL)3TPA engages substrate classes (aliphatic alkynes, silylacetylenes, α-olefins) that are especially challenging in intermolecular reactions of α-alkyl-α-diazoesters and catalyzes enantioselective cyclopropanation, cyclopropenation, and indole C-H functionalization with yields and enantioselectivities that are comparable or superior to Rh2(S-PTTL)4. The work detailed in this Account describes progress toward enabling a more general utility for α-alkyl-α-diazo compounds in Rh-catalyzed carbene reactions. Further studies on ligand design and synthesis will continue to broaden the scope of their selective reactions.

Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome.

PubMed

Chen, Byron; Hui, Jessica; Montgomery, Kelsey S; Gella, Alejandro; Bolea, Irene; Sanz, Elisenda; Palmiter, Richard D; Quintana, Albert

2017-01-01

Inability of mitochondria to generate energy leads to severe and often fatal myoencephalopathies. Among these, Leigh syndrome (LS) is one of the most common childhood mitochondrial diseases; it is characterized by hypotonia, failure to thrive, respiratory insufficiency and progressive mental and motor dysfunction, leading to early death. Basal ganglia nuclei, including the striatum, are affected in LS patients. However, neither the identity of the affected cell types in the striatum nor their contribution to the disease has been established. Here, we used a mouse model of LS lacking Ndufs4 , a mitochondrial complex I subunit, to confirm that loss of complex I, but not complex II, alters respiration in the striatum. To assess the role of striatal dysfunction in the pathology, we selectively inactivated Ndufs4 in the striatal medium spiny neurons (MSNs), which account for over 95% of striatal neurons. Our results show that lack of Ndufs4 in MSNs causes a non-fatal progressive motor impairment without affecting the cognitive function of mice. Furthermore, no inflammatory responses or neuronal loss were observed up to 6 months of age. Hence, complex I deficiency in MSNs contributes to the motor deficits observed in LS, but not to the neural degeneration, suggesting that other neuronal populations drive the plethora of clinical signs in LS.

The Gemin associates of survival motor neuron are required for motor function in Drosophila.

PubMed

Borg, Rebecca; Cauchi, Ruben J

2013-01-01

Membership of the survival motor neuron (SMN) complex extends to nine factors, including the SMN protein, the product of the spinal muscular atrophy (SMA) disease gene, Gemins 2-8 and Unrip. The best-characterised function of this macromolecular machine is the assembly of the Sm-class of uridine-rich small nuclear ribonucleoprotein (snRNP) particles and each SMN complex member has a key role during this process. So far, however, only little is known about the function of the individual Gemin components in vivo. Here, we make use of the Drosophila model organism to uncover loss-of-function phenotypes of Gemin2, Gemin3 and Gemin5, which together with SMN form the minimalistic fly SMN complex. We show that ectopic overexpression of the dead helicase Gem3(ΔN) mutant or knockdown of Gemin3 result in similar motor phenotypes, when restricted to muscle, and in combination cause lethality, hence suggesting that Gem3(ΔN) overexpression mimics a loss-of-function. Based on the localisation pattern of Gem3(ΔN), we predict that the nucleus is the primary site of the antimorphic or dominant-negative mechanism of Gem3(ΔN)-mediated interference. Interestingly, phenotypes induced by human SMN overexpression in Drosophila exhibit similarities to those induced by overexpression of Gem3(ΔN). Through enhanced knockdown we also uncover a requirement of Gemin2, Gemin3 and Gemin5 for viability and motor behaviour, including locomotion as well as flight, in muscle. Notably, in the case of Gemin3 and Gemin5, such function also depends on adequate levels of the respective protein in neurons. Overall, these findings lead us to speculate that absence of any one member is sufficient to arrest the SMN-Gemins complex function in a nucleocentric pathway, which is critical for motor function in vivo.

A novel approach to sports concussion assessment: Computerized multilimb reaction times and balance control testing.

PubMed

Vartiainen, Matti V; Holm, Anu; Lukander, Jani; Lukander, Kristian; Koskinen, Sanna; Bornstein, Robert; Hokkanen, Laura

2016-01-01

Mild traumatic brain injuries (MTBI) or concussions often result in problems with attention, executive functions, and motor control. For better identification of these diverse problems, novel approaches integrating tests of cognitive and motor functioning are needed. The aim was to characterize minor changes in motor and cognitive performance after sports-related concussions with a novel test battery, including balance tests and a computerized multilimb reaction time test. The cognitive demands of the battery gradually increase from a simple stimulus response to a complex task requiring executive attention. A total of 113 male ice hockey players (mean age = 24.6 years, SD = 5.7) were assessed before a season. During the season, nine concussed players were retested within 36 hours, four to six days after the concussion, and after the season. A control group of seven nonconcussed players from the same pool of players with comparable demographics were retested after the season. Performance was measured using a balance test and the Motor Cognitive Test battery (MotCoTe) with multilimb responses in simple reaction, choice reaction, inhibition, and conflict resolution conditions. The performance of the concussed group declined at the postconcussion assessment compared to both the baseline measurement and the nonconcussed controls. Significant changes were observed in the concussed group for the multilimb choice reaction and inhibition tests. Tapping and balance showed a similar trend, but no statistically significant difference in performance. In sports-related concussions, complex motor tests can be valuable additions in assessing the outcome and recovery. In the current study, using subtasks with varying cognitive demands, it was shown that while simple motor performance was largely unaffected, the more complex tasks induced impaired reaction times for the concussed subjects. The increased reaction times may reflect the disruption of complex and integrative cognitive function in concussions.

Loose coupling in the bacterial flagellar motor

PubMed Central

Boschert, Ryan; Adler, Frederick R.; Blair, David F.

2015-01-01

Physiological properties of the flagellar rotary motor have been taken to indicate a tightly coupled mechanism in which each revolution is driven by a fixed number of energizing ions. Measurements that would directly test the tight-coupling hypothesis have not been made. Energizing ions flow through membrane-bound complexes formed from the proteins MotA and MotB, which are anchored to the cell wall and constitute the stator. Genetic and biochemical evidence points to a “power stroke” mechanism in which the ions interact with an aspartate residue of MotB to drive conformational changes in MotA that are transmitted to the rotor protein FliG. Each stator complex contains two separate ion-binding sites, raising the question of whether the power stroke is driven by one, two, or either number of ions. Here, we describe simulations of a model in which the conformational change can be driven by either one or two ions. This loosely coupled model can account for the observed physiological properties of the motor, including those that have been taken to indicate tight coupling; it also accords with recent measurements of motor torque at high load that are harder to explain in tight-coupling models. Under loads relevant to a swimming cell, the loosely coupled motor would perform about as well as a two-proton motor and significantly better than a one-proton motor. The loosely coupled motor is predicted to be especially advantageous under conditions of diminished energy supply, or of reduced temperature, turning faster than an obligatorily two-proton motor while using fewer ions. PMID:25825730

Similarities between GCS and human motor cortex: complex movement coordination

NASA Astrophysics Data System (ADS)

Rodríguez, Jose A.; Macias, Rosa; Molgo, Jordi; Guerra, Dailos

2014-07-01

The "Gran Telescopio de Canarias" (GTC1) is an optical-infrared 10-meter segmented mirror telescope at the ORM observatory in Canary Islands (Spain). The GTC control system (GCS), the brain of the telescope, is is a distributed object & component oriented system based on RT-CORBA and it is responsible for the management and operation of the telescope, including its instrumentation. On the other hand, the Human motor cortex (HMC) is a region of the cerebrum responsible for the coordination of planning, control, and executing voluntary movements. If we analyze both systems, as far as the movement control of their mechanisms and body parts is concerned, we can find extraordinary similarities in their architectures. Both are structured in layers, and their functionalities are comparable from the movement conception until the movement action itself: In the GCS we can enumerate the Sequencer high level components, the Coordination libraries, the Control Kit library and the Device Driver library as the subsystems involved in the telescope movement control. If we look at the motor cortex, we can also enumerate the primary motor cortex, the secondary motor cortices, which include the posterior parietal cortex, the premotor cortex, and the supplementary motor area (SMA), the motor units, the sensory organs and the basal ganglia. From all these components/areas we will analyze in depth the several subcortical regions, of the the motor cortex, that are involved in organizing motor programs for complex movements and the GCS coordination framework, which is composed by a set of classes that allow to the high level components to transparently control a group of mechanisms simultaneously.

Changes in Cerebral Hemodynamics during Complex Motor Learning by Character Entry into Touch-Screen Terminals.

PubMed

Sagari, Akira; Iso, Naoki; Moriuchi, Takefumi; Ogahara, Kakuya; Kitajima, Eiji; Tanaka, Koji; Tabira, Takayuki; Higashi, Toshio

2015-01-01

Studies of cerebral hemodynamics during motor learning have mostly focused on neurorehabilitation interventions and their effectiveness. However, only a few imaging studies of motor learning and the underlying complex cognitive processes have been performed. We measured cerebral hemodynamics using near-infrared spectroscopy (NIRS) in relation to acquisition patterns of motor skills in healthy subjects using character entry into a touch-screen terminal. Twenty healthy, right-handed subjects who had no previous experience with character entry using a touch-screen terminal participated in this study. They were asked to enter the characters of a randomly formed Japanese syllabary into the touch-screen terminal. All subjects performed the task with their right thumb for 15 s alternating with 25 s of rest for 30 repetitions. Performance was calculated by subtracting the number of incorrect answers from the number of correct answers, and gains in motor skills were evaluated according to the changes in performance across cycles. Behavioral and oxygenated hemoglobin concentration changes across task cycles were analyzed using Spearman's rank correlations. Performance correlated positively with task cycle, thus confirming motor learning. Hemodynamic activation over the left sensorimotor cortex (SMC) showed a positive correlation with task cycle, whereas activations over the right prefrontal cortex (PFC) and supplementary motor area (SMA) showed negative correlations. We suggest that increases in finger momentum with motor learning are reflected in the activity of the left SMC. We further speculate that the right PFC and SMA were activated during the early phases of motor learning, and that this activity was attenuated with learning progress.

Fast social-like learning of complex behaviors based on motor motifs.

PubMed

Calvo Tapia, Carlos; Tyukin, Ivan Y; Makarov, Valeri A

2018-05-01

Social learning is widely observed in many species. Less experienced agents copy successful behaviors exhibited by more experienced individuals. Nevertheless, the dynamical mechanisms behind this process remain largely unknown. Here we assume that a complex behavior can be decomposed into a sequence of n motor motifs. Then a neural network capable of activating motor motifs in a given sequence can drive an agent. To account for (n-1)! possible sequences of motifs in a neural network, we employ the winnerless competition approach. We then consider a teacher-learner situation: one agent exhibits a complex movement, while another one aims at mimicking the teacher's behavior. Despite the huge variety of possible motif sequences we show that the learner, equipped with the provided learning model, can rewire "on the fly" its synaptic couplings in no more than (n-1) learning cycles and converge exponentially to the durations of the teacher's motifs. We validate the learning model on mobile robots. Experimental results show that the learner is indeed capable of copying the teacher's behavior composed of six motor motifs in a few learning cycles. The reported mechanism of learning is general and can be used for replicating different functions, including, for example, sound patterns or speech.

Complex analysis of neuronal spike trains of deep brain nuclei in patients with Parkinson's disease.

PubMed

Chan, Hsiao-Lung; Lin, Ming-An; Lee, Shih-Tseng; Tsai, Yu-Tai; Chao, Pei-Kuang; Wu, Tony

2010-04-05

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been used to alleviate symptoms of Parkinson's disease. During image-guided stereotactic surgery, signals from microelectrode recordings are used to distinguish the STN from adjacent areas, particularly from the substantia nigra pars reticulata (SNr). Neuronal firing patterns based on interspike intervals (ISI) are commonly used. In the present study, arrival time-based measures, including Lempel-Ziv complexity and deviation-from-Poisson index were employed. Our results revealed significant differences in the arrival time-based measures among non-motor STN, motor STN and SNr and better discrimination than the ISI-based measures. The larger deviations from the Poisson process in the SNr implied less complex dynamics of neuronal discharges. If spike classification was not used, the arrival time-based measures still produced statistical differences among STN subdivisions and SNr, but the ISI-based measures only showed significant differences between motor and non-motor STN. Arrival time-based measures are less affected by spike misclassifications, and may be used as an adjunct for the identification of the STN during microelectrode targeting. Copyright 2010 Elsevier Inc. All rights reserved.

Fast social-like learning of complex behaviors based on motor motifs

NASA Astrophysics Data System (ADS)

Calvo Tapia, Carlos; Tyukin, Ivan Y.; Makarov, Valeri A.

2018-05-01

Social learning is widely observed in many species. Less experienced agents copy successful behaviors exhibited by more experienced individuals. Nevertheless, the dynamical mechanisms behind this process remain largely unknown. Here we assume that a complex behavior can be decomposed into a sequence of n motor motifs. Then a neural network capable of activating motor motifs in a given sequence can drive an agent. To account for (n -1 )! possible sequences of motifs in a neural network, we employ the winnerless competition approach. We then consider a teacher-learner situation: one agent exhibits a complex movement, while another one aims at mimicking the teacher's behavior. Despite the huge variety of possible motif sequences we show that the learner, equipped with the provided learning model, can rewire "on the fly" its synaptic couplings in no more than (n -1 ) learning cycles and converge exponentially to the durations of the teacher's motifs. We validate the learning model on mobile robots. Experimental results show that the learner is indeed capable of copying the teacher's behavior composed of six motor motifs in a few learning cycles. The reported mechanism of learning is general and can be used for replicating different functions, including, for example, sound patterns or speech.

Bradykinesia and bradyphrenia revisited: patterns of subclinical deficit in motor speed and cognitive functioning in head-injured patients with good recovery.

PubMed

Gray, C; Cantagallo, A; Della Sala, S; Basaglia, N

1998-05-01

Twenty-four patients, showing a good clinical recovery from coma-inducing injury and coping well with the activities of everyday living, were tested, at least 1 year after trauma, on motor speed and reaction time, and given a neuropsychological examination. While the patients generally performed within the normal range on the neuropsychological tests, their motor speeds and reaction times--both simple (SRT) and complex (CRT)--were significantly slower than those of matched controls. This points to a subclinical bradykinesia. The patients' motor speed scores did not correlate significantly with any of the neuropsychological tests; nor did SRT or CRT. While the difference between simple and complex reaction time was significantly greater in the patient group, the percentage difference was not significantly different between the two groups. Collectively, these results suggest that bradykinesia and bradyphrenia do not necessarily overlap. Finally, there was no significant correlation between motor performance and severity of original injury, whether the latter was measured by number and size of lesions or by duration of post-traumatic amnesia.

Auxotonic to isometric contraction transitioning in a beating heart causes myosin step-size to down shift

PubMed Central

Sun, Xiaojing; Wang, Yihua; Ajtai, Katalin

2017-01-01

Myosin motors in cardiac ventriculum convert ATP free energy to the work of moving blood volume under pressure. The actin bound motor cyclically rotates its lever-arm/light-chain complex linking motor generated torque to the myosin filament backbone and translating actin against resisting force. Previous research showed that the unloaded in vitro motor is described with high precision by single molecule mechanical characteristics including unitary step-sizes of approximately 3, 5, and 8 nm and their relative step-frequencies of approximately 13, 50, and 37%. The 3 and 8 nm unitary step-sizes are dependent on myosin essential light chain (ELC) N-terminus actin binding. Step-size and step-frequency quantitation specifies in vitro motor function including duty-ratio, power, and strain sensitivity metrics. In vivo, motors integrated into the muscle sarcomere form the more complex and hierarchically functioning muscle machine. The goal of the research reported here is to measure single myosin step-size and step-frequency in vivo to assess how tissue integration impacts motor function. A photoactivatable GFP tags the ventriculum myosin lever-arm/light-chain complex in the beating heart of a live zebrafish embryo. Detected single GFP emission reports time-resolved myosin lever-arm orientation interpreted as step-size and step-frequency providing single myosin mechanical characteristics over the active cycle. Following step-frequency of cardiac ventriculum myosin transitioning from low to high force in relaxed to auxotonic to isometric contraction phases indicates that the imposition of resisting force during contraction causes the motor to down-shift to the 3 nm step-size accounting for >80% of all the steps in the near-isometric phase. At peak force, the ATP initiated actomyosin dissociation is the predominant strain inhibited transition in the native myosin contraction cycle. The proposed model for motor down-shifting and strain sensing involves ELC N-terminus actin binding. Overall, the approach is a unique bottom-up single molecule mechanical characterization of a hierarchically functional native muscle myosin. PMID:28423017

Neural network retuning and neural predictors of learning success associated with cello training.

PubMed

Wollman, Indiana; Penhune, Virginia; Segado, Melanie; Carpentier, Thibaut; Zatorre, Robert J

2018-06-26

The auditory and motor neural systems are closely intertwined, enabling people to carry out tasks such as playing a musical instrument whose mapping between action and sound is extremely sophisticated. While the dorsal auditory stream has been shown to mediate these audio-motor transformations, little is known about how such mapping emerges with training. Here, we use longitudinal training on a cello as a model for brain plasticity during the acquisition of specific complex skills, including continuous and many-to-one audio-motor mapping, and we investigate individual differences in learning. We trained participants with no musical background to play on a specially designed MRI-compatible cello and scanned them before and after 1 and 4 wk of training. Activation of the auditory-to-motor dorsal cortical stream emerged rapidly during the training and was similarly activated during passive listening and cello performance of trained melodies. This network activation was independent of performance accuracy and therefore appears to be a prerequisite of music playing. In contrast, greater recruitment of regions involved in auditory encoding and motor control over the training was related to better musical proficiency. Additionally, pre-supplementary motor area activity and its connectivity with the auditory cortex during passive listening before training was predictive of final training success, revealing the integrative function of this network in auditory-motor information processing. Together, these results clarify the critical role of the dorsal stream and its interaction with auditory areas in complex audio-motor learning.

Novel test of motor and other dysfunctions in mouse neurological disease models.

PubMed

Barth, Albert M I; Mody, Istvan

2014-01-15

Just like human neurological disorders, corresponding mouse models present multiple deficiencies. Estimating disease progression or potential treatment effectiveness in such models necessitates the use of time consuming and multiple tests usually requiring a large number of scarcely available genetically modified animals. Here we present a novel and simple single camera arrangement and analysis software for detailed motor function evaluation in mice walking on a wire mesh that provides complex 3D information (instantaneous position, speed, distance traveled, foot fault depth, duration, location, relationship to speed of movement, etc.). We investigated 3 groups of mice with various neurological deficits: (1) unilateral motor cortical stroke; (2) effects of moderate ethanol doses; and (3) aging (96-99 weeks old). We show that post stroke recovery can be divided into separate stages based on strikingly different characteristics of motor function deficits, some resembling the human motor neglect syndrome. Mice treated with moderate dose of alcohol and aged mice showed specific motor and exploratory deficits. Other tests rely either partially or entirely on manual video analysis introducing a significant subjective component into the analysis, and analyze a single aspect of motor function. Our novel experimental approach provides qualitatively new, complex information about motor impairments and locomotor/exploratory activity. It should be useful for the detailed characterization of a broad range of human neurological disease models in mice, and for the more accurate assessment of disease progression or treatment effectiveness. Copyright © 2013 Elsevier B.V. All rights reserved.

Gender and migration from Albania.

PubMed

Stecklov, Guy; Carletto, Calogero; Azzarri, Carlo; Davis, Benjamin

2010-11-01

This article examines the dynamics and causes of the shift in the gender composition of migration, and more particularly, in women's access to migration opportunities and decision-making. Our analysis focuses on Albania, a natural laboratory for studying international migration where out-migration was essentially nonexistent from the end of World War II to the end of the 1980s. Interest in the Albanian case is heightened because of the complex layers of inequality existing at the time when migration began: relatively low levels of inequality within the labor market and educational system-a product of the Communist era-while household relations remained heavily steeped in tradition and patriarchy. We use micro-level data from the Albania 2005 Living Standards Measurement Study, including migration histories for family members since migration began. Based on discrete-time hazard models, the analysis shows a dramatic increase in male migration and a gradual and uneven expansion of the female proportion of this international migration. Female migration, which is shown to be strongly associated with education, wealth, and social capital, appears responsive to economic incentives and constraints. Using information on the dependency of female migration to the household demographic structure as well as the sensitivity of female migration to household-level shocks, we show how household-level constraints and incentives affect male and female migration differently. Throughout this period, however, women's migration behavior appears more directly aligned with household-level factors, and there is little evidence to suggest that increased female migration signals rising behavioral independence among Albanian women.

Gender and Migration from Albania

PubMed Central

STECKLOV, GUY; CARLETTO, CALOGERO; AZZARRI, CARLO; DAVIS, BENJAMIN

2010-01-01

This article examines the dynamics and causes of the shift in the gender composition of migration, and more particularly, in women’s access to migration opportunities and decision-making. Our analysis focuses on Albania, a natural laboratory for studying international migration where out-migration was essentially nonexistent from the end of World War II to the end of the 1980s. Interest in the Albanian case is heightened because of the complex layers of inequality existing at the time when migration began: relatively low levels of inequality within the labor market and educational system—a product of the Communist era—while household relations remained heavily steeped in tradition and patriarchy. We use micro-level data from the Albania 2005 Living Standards Measurement Study, including migration histories for family members since migration began. Based on discrete-time hazard models, the analysis shows a dramatic increase in male migration and a gradual and uneven expansion of the female proportion of this international migration. Female migration, which is shown to be strongly associated with education, wealth, and social capital, appears responsive to economic incentives and constraints. Using information on the dependency of female migration to the household demographic structure as well as the sensitivity of female migration to household-level shocks, we show how household-level constraints and incentives affect male and female migration differently. Throughout this period, however, women’s migration behavior appears more directly aligned with household-level factors, and there is little evidence to suggest that increased female migration signals rising behavioral independence among Albanian women. PMID:21308565

Oligoanilines as a suppressor of polysulfide shuttling in lithium–sulfur batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Chi-Hao; Chung, Sheng-Heng; Han, Pauline

The migration of small polysulfide (LiPS) chains through the porous polymeric separators seriously jeopardizes the cycle life and energy density of lithium–sulfur (Li–S) batteries. Herein, we present a new concept in which an organic oligoaniline, amine-capped aniline trimer (ACAT), serves as an effective suppressor of the LiPS migration in Li–S cells. The strong interaction between LiPS and ACAT facilitates the formation of bulky ACAT–LiPS complexes (organoLiPS complexes), which are then size-selectively sieved by the porous polymeric separators employed in Li–S cells. Thus, the addition of ACAT significantly ameliorates the electrochemical performances of Li–S batteries due to suppressed LiPS migration. Thismore » new concept offers a viable strategy to achieve practically viable Li–S batteries.« less

Oligoanilines as a suppressor of polysulfide shuttling in lithium–sulfur batteries

DOE PAGES

Chang, Chi-Hao; Chung, Sheng-Heng; Han, Pauline; ...

2017-07-25

The migration of small polysulfide (LiPS) chains through the porous polymeric separators seriously jeopardizes the cycle life and energy density of lithium–sulfur (Li–S) batteries. Herein, we present a new concept in which an organic oligoaniline, amine-capped aniline trimer (ACAT), serves as an effective suppressor of the LiPS migration in Li–S cells. The strong interaction between LiPS and ACAT facilitates the formation of bulky ACAT–LiPS complexes (organoLiPS complexes), which are then size-selectively sieved by the porous polymeric separators employed in Li–S cells. Thus, the addition of ACAT significantly ameliorates the electrochemical performances of Li–S batteries due to suppressed LiPS migration. Thismore » new concept offers a viable strategy to achieve practically viable Li–S batteries.« less

Dissociable effects of practice variability on learning motor and timing skills.

PubMed

Caramiaux, Baptiste; Bevilacqua, Frédéric; Wanderley, Marcelo M; Palmer, Caroline

2018-01-01

Motor skill acquisition inherently depends on the way one practices the motor task. The amount of motor task variability during practice has been shown to foster transfer of the learned skill to other similar motor tasks. In addition, variability in a learning schedule, in which a task and its variations are interweaved during practice, has been shown to help the transfer of learning in motor skill acquisition. However, there is little evidence on how motor task variations and variability schedules during practice act on the acquisition of complex motor skills such as music performance, in which a performer learns both the right movements (motor skill) and the right time to perform them (timing skill). This study investigated the impact of rate (tempo) variability and the schedule of tempo change during practice on timing and motor skill acquisition. Complete novices, with no musical training, practiced a simple musical sequence on a piano keyboard at different rates. Each novice was assigned to one of four learning conditions designed to manipulate the amount of tempo variability across trials (large or small tempo set) and the schedule of tempo change (randomized or non-randomized order) during practice. At test, the novices performed the same musical sequence at a familiar tempo and at novel tempi (testing tempo transfer), as well as two novel (but related) sequences at a familiar tempo (testing spatial transfer). We found that practice conditions had little effect on learning and transfer performance of timing skill. Interestingly, practice conditions influenced motor skill learning (reduction of movement variability): lower temporal variability during practice facilitated transfer to new tempi and new sequences; non-randomized learning schedule improved transfer to new tempi and new sequences. Tempo (rate) and the sequence difficulty (spatial manipulation) affected performance variability in both timing and movement. These findings suggest that there is a dissociable effect of practice variability on learning complex skills that involve both motor and timing constraints.

Stoichiometry of DNA binding by the bacteriophage SP01-encoded type II DNA-binding protein TF1.

PubMed

Schneider, G J; Geiduschek, E P

1990-06-25

The stoichiometry of DNA binding by the bacteriophage SP01-encoded type II DNA-binding protein TF1 has been determined. 3H-Labeled TF1 was allowed to bind to a 32P-labeled DNA fragment containing a TF1 binding site. Multiple TF1-DNA complexes were resolved from each other and from unbound DNA by native gel electrophoresis. DNA-protein complexes were cut from polyacrylamide gels, and the amounts of 3H and 32P contained in each slice were measured. A ratio of 1.12 +/- 0.06 TF1 dimer/DNA molecule was calculated for the fastest-migrating TF1-DNA complex. We conclude that TF1 has a DNA-binding unit of one dimer. More slowly migrating complexes are apparently formed by serial addition of single TF1 dimers.

Postural complexity influences development in infants born preterm with brain injury: relating perception-action theory to 3 cases.

PubMed

Dusing, Stacey C; Izzo, Theresa; Thacker, Leroy R; Galloway, James Cole

2014-10-01

Perception-action theory suggests a cyclical relationship between movement and perceptual information. In this case series, changes in postural complexity were used to quantify an infant's action and perception during the development of early motor behaviors. Three infants born preterm with periventricular white matter injury were included. Longitudinal changes in postural complexity (approximate entropy of the center of pressure), head control, reaching, and global development, measured with the Test of Infant Motor Performance and the Bayley Scales of Infant and Toddler Development, were assessed every 0.5 to 3 months during the first year of life. All 3 infants demonstrated altered postural complexity and developmental delays. However, the timing of the altered postural complexity and the type of delays varied among the infants. For infant 1, reduced postural complexity or limited action while learning to control her head in the midline position may have contributed to her motor delay. However, her ability to adapt her postural complexity eventually may have supported her ability to learn from her environment, as reflected in her relative cognitive strength. For infant 2, limited early postural complexity may have negatively affected his learning through action, resulting in cognitive delay. For infant 3, an increase in postural complexity above typical levels was associated with declining neurological status. Postural complexity is proposed as a measure of perception and action in the postural control system during the development of early behaviors. An optimal, intermediate level of postural complexity supports the use of a variety of postural control strategies and enhances the perception-action cycle. Either excessive or reduced postural complexity may contribute to developmental delays in infants born preterm with white matter injury. © 2014 American Physical Therapy Association.

Life history, cognition and the evolution of complex foraging niches.

PubMed

Schuppli, Caroline; Graber, Sereina M; Isler, Karin; van Schaik, Carel P

2016-03-01

Animal species that live in complex foraging niches have, in general, improved access to energy-rich and seasonally stable food sources. Because human food procurement is uniquely complex, we ask here which conditions may have allowed species to evolve into such complex foraging niches, and also how niche complexity is related to relative brain size. To do so, we divided niche complexity into a knowledge-learning and a motor-learning dimension. Using a sample of 78 primate and 65 carnivoran species, we found that two life-history features are consistently correlated with complex niches: slow, conservative development or provisioning of offspring over extended periods of time. Both act to buffer low energy yields during periods of learning, and may thus act as limiting factors for the evolution of complex niches. Our results further showed that the knowledge and motor dimensions of niche complexity were correlated with pace of development in primates only, and with the length of provisioning in only carnivorans. Accordingly, in primates, but not carnivorans, living in a complex foraging niche requires enhanced cognitive abilities, i.e., a large brain. The patterns in these two groups of mammals show that selection favors evolution into complex niches (in either the knowledge or motor dimension) in species that either develop more slowly or provision their young for an extended period of time. These findings help to explain how humans constructed by far the most complex niche: our ancestors managed to combine slow development (as in other primates) with systematic provisioning of immatures and even adults (as in carnivorans). This study also provides strong support for the importance of ecological factors in brain size evolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

On the context-dependent nature of the contribution of the ventral premotor cortex to speech perception

PubMed Central

Tremblay, Pascale; Small, Steven L.

2011-01-01

What is the nature of the interface between speech perception and production, where auditory and motor representations converge? One set of explanations suggests that during perception, the motor circuits involved in producing a perceived action are in some way enacting the action without actually causing movement (covert simulation) or sending along the motor information to be used to predict its sensory consequences (i.e., efference copy). Other accounts either reject entirely the involvement of motor representations in perception, or explain their role as being more supportive than integral, and not employing the identical circuits used in production. Using fMRI, we investigated whether there are brain regions that are conjointly active for both speech perception and production, and whether these regions are sensitive to articulatory (syllabic) complexity during both processes, which is predicted by a covert simulation account. A group of healthy young adults (1) observed a female speaker produce a set of familiar words (perception), and (2) observed and then repeated the words (production). There were two types of words, varying in articulatory complexity, as measured by the presence or absence of consonant clusters. The simple words contained no consonant cluster (e.g. “palace”), while the complex words contained one to three consonant clusters (e.g. “planet”). Results indicate that the left ventral premotor cortex (PMv) was significantly active during speech perception and speech production but that activation in this region was scaled to articulatory complexity only during speech production, revealing an incompletely specified efferent motor signal during speech perception. The right planum temporal (PT) was also active during speech perception and speech production, and activation in this region was scaled to articulatory complexity during both production and perception. These findings are discussed in the context of current theories theory of speech perception, with particular attention to accounts that include an explanatory role for mirror neurons. PMID:21664275

Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover.

PubMed

Bustamante, Juanita; Karadayian, Analia G; Lores-Arnaiz, Silvia; Cutrera, Rodolfo A

2012-08-01

Ethanol has been known to affect various behavioral parameters in experimental animals, even several hours after ethanol (EtOH) is absent from blood circulation, in the period known as hangover. The aim of this study was to assess the effects of acute ethanol hangover on motor performance in association with the brain cortex energetic metabolism. Evaluation of motor performance and brain cortex mitochondrial function during alcohol hangover was performed in mice 6 hours after a high ethanol dose (hangover onset). Animals were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Ethanol hangover group showed a bad motor performance compared with control animals (p < .05). Oxygen uptake in brain cortex mitochondria from hangover animals showed a 34% decrease in the respiratory control rate as compared with the control group. Mitochondrial complex activities were decreased being the complex I-III the less affected by the hangover condition; complex II-III was markedly decreased by ethanol hangover showing 50% less activity than controls. Complex IV was 42% decreased as compared with control animals. Hydrogen peroxide production was 51% increased in brain cortex mitochondria from the hangover group, as compared with the control animals. Quantification of the mitochondrial transmembrane potential indicated that ethanol injected animals presented 17% less ability to maintain the polarized condition as compared with controls. These results indicate that a clear decrease in proton motive force occurs in brain cortex mitochondria during hangover conditions. We can conclude that a decreased motor performance observed in the hangover group of animals could be associated with brain cortex mitochondrial dysfunction and the resulting impairment of its energetic metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

Child Migration and Academic Performance: The Case of Basic Education in Ghana

ERIC Educational Resources Information Center

Tamanja, Emmanuel Makabu J.

2016-01-01

The nexus between migration and academic performance is complex and difficult to extricate. Not only are there several factors affecting academic performance, but also many of these factors are confounding, making it difficult to identify and isolate in order to address. Furthermore, the discourse appears silent on the nexus between child…

The Geographical Mobility of Women in "Dual Career" Households: Determinants and Consequences.

ERIC Educational Resources Information Center

Brzeskwinski, Janina

This paper investigates occupational characteristics influencing a household's migration propensity. The study was based on the premise that earlier studies have not done justice to the complexity of male/female influences on family migration. The hypothesis was that the geographical mobility of 'dual career' families will be determined by the…

The Reconstruction of Parenting after Migration: A Perspective from Cultural Translation

ERIC Educational Resources Information Center

de Haan, Mariette

2011-01-01

Migration induces complex processes of human transformation that are usually not reflected in theories that describe these changes. In most theories regarding these transformations, the implicit assumption is that immigrants undergo a transition to the culture of the mainstream population according to a modernization perspective. Based on a review…

Modulating EGFR Signaling by Targeting the Deacetylase HDAC6-Hsp90 Complex in Breast Tumors

DTIC Science & Technology

2007-06-01

concomitant increase in 4 directed cell migration (15). Analysis of fibroblasts derived from WAVE2 knockout mice 5 demonstrates deficiency in ruffle...Takenawa. 2003. Differential 1 roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for 2 fibroblast cell migration. Dev Cell 5:595

New views on the neural crest epithelial-mesenchymal transition and neuroepithelial interkinetic nuclear migration

PubMed Central

Erickson, Carol A

2009-01-01

By developing a technique for imaging the avian neural crest epithelial-mesenchymal transition (EMT), we have discovered cellular behaviors that challenge current thinking on this important developmental event, including the probability that complete disassembly of the adherens junctions may not control whether or not a neural epithelial cell undergoes an EMT. Further, neural crest cells can adopt multiple modes of cell motility in order to emigrate from the neuroepithelium. We also gained insights into interkinetic nuclear migration (INM). For example, the movement of the nucleus from the basal to apical domain may not require microtubule motors nor an intact nuclear envelope, and the nucleus does not always need to reach the apical surface in order for cytokinesis to occur. These studies illustrate the value of live-cell imaging to elucidate cellular processes. PMID:20195454

Sequential actin-based pushing forces drive meiosis I chromosome migration and symmetry breaking in oocytes.

PubMed

Yi, Kexi; Rubinstein, Boris; Unruh, Jay R; Guo, Fengli; Slaughter, Brian D; Li, Rong

2013-03-04

Polar body extrusion during oocyte maturation is critically dependent on asymmetric positioning of the meiotic spindle, which is established through migration of the meiosis I (MI) spindle/chromosomes from the oocyte interior to a subcortical location. In this study, we show that MI chromosome migration is biphasic and driven by consecutive actin-based pushing forces regulated by two actin nucleators, Fmn2, a formin family protein, and the Arp2/3 complex. Fmn2 was recruited to endoplasmic reticulum structures surrounding the MI spindle, where it nucleated actin filaments to initiate an initially slow and poorly directed motion of the spindle away from the cell center. A fast and highly directed second migration phase was driven by actin-mediated cytoplasmic streaming and occurred as the chromosomes reach a sufficient proximity to the cortex to activate the Arp2/3 complex. We propose that decisive symmetry breaking in mouse oocytes results from Fmn2-mediated perturbation of spindle position and the positive feedback loop between chromosome signal-induced Arp2/3 activation and Arp2/3-orchestrated cytoplasmic streaming that transports the chromosomes.

Sequential actin-based pushing forces drive meiosis I chromosome migration and symmetry breaking in oocytes

PubMed Central

Yi, Kexi; Rubinstein, Boris; Unruh, Jay R.; Guo, Fengli; Slaughter, Brian D.

2013-01-01

Polar body extrusion during oocyte maturation is critically dependent on asymmetric positioning of the meiotic spindle, which is established through migration of the meiosis I (MI) spindle/chromosomes from the oocyte interior to a subcortical location. In this study, we show that MI chromosome migration is biphasic and driven by consecutive actin-based pushing forces regulated by two actin nucleators, Fmn2, a formin family protein, and the Arp2/3 complex. Fmn2 was recruited to endoplasmic reticulum structures surrounding the MI spindle, where it nucleated actin filaments to initiate an initially slow and poorly directed motion of the spindle away from the cell center. A fast and highly directed second migration phase was driven by actin-mediated cytoplasmic streaming and occurred as the chromosomes reach a sufficient proximity to the cortex to activate the Arp2/3 complex. We propose that decisive symmetry breaking in mouse oocytes results from Fmn2-mediated perturbation of spindle position and the positive feedback loop between chromosome signal-induced Arp2/3 activation and Arp2/3-orchestrated cytoplasmic streaming that transports the chromosomes. PMID:23439682

A family affair: A Ral-exocyst-centered network links Ras, Rac, Rho signaling to control cell migration.

PubMed

Zago, Giulia; Biondini, Marco; Camonis, Jacques; Parrini, Maria Carla

2017-05-12

Cell migration is central to many developmental, physiologic and pathological processes, including cancer progression. The Ral GTPases (RalA and RalB) which act down-stream the Ras oncogenes, are key players in the coordination between membrane trafficking and actin polymerization. A major direct effector of Ral, the exocyst complex, works in polarized exocytosis and is at the center of multiple protein-protein interactions that support cell migration by promoting protrusion formation, front-rear polarization, and extra-cellular matrix degradation. In this review we describe the recent advancements in deciphering the molecular mechanisms underlying this role of Ral via exocyst on cell migration. Among others, we will discuss the recently identified cross-talk between Ral and Rac1 pathways: exocyst binds to a negative regulator (the RacGAP SH3BP1) and to the major effector (the Wave Regulatory Complex, WRC) of Rac1, the master regulator of protrusions. Next challenge will be to better characterize the dynamics in space and in time of these molecular interplays, to better understand the pleiotropic functions of Ral in both normal and cancer cells.

A Molecular Smart Surface for Spatio-Temporal Studies of Cell Mobility

PubMed Central

Lee, Eun-ju; Luo, Wei; Chan, Eugene W. L.; Yousaf, Muhammad N.

2015-01-01

Active migration in both healthy and malignant cells requires the integration of information derived from soluble signaling molecules with positional information gained from interactions with the extracellular matrix and with other cells. How a cell responds and moves involves complex signaling cascades that guide the directional functions of the cytoskeleton as well as the synthesis and release of proteases that facilitate movement through tissues. The biochemical events of the signaling cascades occur in a spatially and temporally coordinated manner then dynamically shape the cytoskeleton in specific subcellular regions. Therefore, cell migration and invasion involve a precise but constantly changing subcellular nano-architecture. A multidisciplinary effort that combines new surface chemistry and cell biological tools is required to understand the reorganization of cytoskeleton triggered by complex signaling during migration. Here we generate a class of model substrates that modulate the dynamic environment for a variety of cell adhesion and migration experiments. In particular, we use these dynamic substrates to probe in real-time how the interplay between the population of cells, the initial pattern geometry, ligand density, ligand affinity and integrin composition affects cell migration and growth. Whole genome microarray analysis indicates that several classes of genes ranging from signal transduction to cytoskeletal reorganization are differentially regulated depending on the nature of the surface conditions. PMID:26030281

Identification of a rhythmic firing pattern in the enteric nervous system that generates rhythmic electrical activity in smooth muscle.

PubMed

Spencer, Nick J; Hibberd, Timothy J; Travis, Lee; Wiklendt, Lukasz; Costa, Marcello; Hu, Hongzhen; Brookes, Simon J; Wattchow, David A; Dinning, Phil G; Keating, Damien J; Sorensen, Julian

2018-05-28

The enteric nervous system (ENS) contains millions of neurons essential for organization of motor behaviour of the intestine. It is well established the large intestine requires ENS activity to drive propulsive motor behaviours. However, the firing pattern of the ENS underlying propagating neurogenic contractions of the large intestine remains unknown. To identify this, we used high resolution neuronal imaging with electrophysiology from neighbouring smooth muscle. Myoelectric activity underlying propagating neurogenic contractions along murine large intestine (referred to as colonic migrating motor complexes, CMMCs) consisted of prolonged bursts of rhythmic depolarizations at a frequency of ∼2 Hz. Temporal coordination of this activity in the smooth muscle over large spatial fields (∼7mm, longitudinally) was dependent on the ENS. During quiescent periods between neurogenic contractions, recordings from large populations of enteric neurons, in mice of either sex, revealed ongoing activity. The onset of neurogenic contractions was characterized by the emergence of temporally synchronized activity across large populations of excitatory and inhibitory neurons. This neuronal firing pattern was rhythmic and temporally synchronized across large numbers of ganglia at ∼2 Hz. ENS activation preceded smooth muscle depolarization, indicating rhythmic depolarizations in smooth muscle were controlled by firing of enteric neurons. The cyclical emergence of temporally coordinated firing of large populations of enteric neurons represents a unique neural motor pattern outside the central nervous system. This is the first direct observation of rhythmic firing in the ENS underlying rhythmic electrical depolarizations in smooth muscle. The pattern of neuronal activity we identified underlies the generation of CMMCs. SIGNIFICANCE STATEMENT How the enteric nervous system (ENS) generates neurogenic contractions of smooth muscle in the gastrointestinal (GI) tract has been a long-standing mystery in vertebrates. It is well known that myogenic pacemaker cells exist in the GI-tract (called Interstitial cells of Cajal, ICC) that generate rhythmic myogenic contractions. However, the mechanisms underlying the generation of rhythmic neurogenic contractions of smooth muscle in the GI-tract remains unknown. We developed a high resolution neuronal imaging method with electrophysiology to address this issue. This technique revealed a novel pattern of rhythmic coordinated neuronal firing in the ENS that has never been identified. Rhythmic neuronal firing in the ENS was found to generate rhythmic neurogenic depolarizations in smooth muscle that underlie contraction of the GI-tract. Copyright © 2018 the authors.

Interhemispheric Control of Unilateral Movement

PubMed Central

Beaulé, Vincent; Tremblay, Sara; Théoret, Hugo

2012-01-01

To perform strictly unilateral movements, the brain relies on a large cortical and subcortical network. This network enables healthy adults to perform complex unimanual motor tasks without the activation of contralateral muscles. However, mirror movements (involuntary movements in ipsilateral muscles that can accompany intended movement) can be seen in healthy individuals if a task is complex or fatiguing, in childhood, and with increasing age. Lateralization of movement depends on complex interhemispheric communication between cortical (i.e., dorsal premotor cortex, supplementary motor area) and subcortical (i.e., basal ganglia) areas, probably coursing through the corpus callosum (CC). Here, we will focus on transcallosal interhemispheric inhibition (IHI), which facilitates complex unilateral movements and appears to play an important role in handedness, pathological conditions such as Parkinson's disease, and stroke recovery. PMID:23304559

Overview of 10 inch Diameter HTPB Hybrid Motor Testing with Liquid Oxygen at Stennis Space Center

NASA Technical Reports Server (NTRS)

Knowles, Timothy E.; Kearney, Darren; Roberts, Ryan

2005-01-01

To further explore the operation of hybrid rocket motors and to demonstrate the performance characteristics of the motor design Lockheed Martin funded research on a series of 10 inch diameter hybrid motors that produce less than 10 klbf sea level thrust. This test series was given the name "Hybrid Technology Test Program." These motors were fired in the existing test stand at the SSC E-3 complex Cell 1. The fuel and oxidizer for these 10 inch diameter motors are HTPB and LO2, respectively. The original goal of the testing was to verify that the predicted performance matched the actual performance of these 10 inch motors (ref. figure 1) and then confirm that the motors performed acceptably. For this element of testing horizontally fired hybrid motors will be tested using LO2 supplied from the existing facility 100 gallon LO2 tank that is pressurized with facility GN2. The thrust produced by the motor will be measured by a Lockheed Martin supplied load cell.

Contained rocket motor burn demonstrations in X-tunnel: Final report for the DoD/DOE Joint Demilitarization Technology Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

S. W. Allendorf; B. W. Bellow; R. f. Boehm

Three low-pressure rocket motor propellant burn tests were performed in a large, sealed test chamber located at the X-tunnel complex on the Department of Energy's Nevada Test Site in the period May--June 1997. NIKE rocket motors containing double base propellant were used in two tests (two and four motors, respectively), and the third test used two improved HAWK rocket motors containing composite propellant. The preliminary containment safety calculations, the crack and burn procedures used in each test, and the results of various measurements made during and after each test are all summarized and collected in this document.

Research on Attribute Reduction in Hoisting Motor State Recognition of Quayside Container Crane

NASA Astrophysics Data System (ADS)

Li, F.; Tang, G.; Hu, X.

2017-07-01

In view of too many attributes in hoisting motor state recognition of quayside container crane. Attribute reduction method based on discernibility matrix is introduced to attribute reduction of lifting motor state information table. A method of attribute reduction based on the combination of rough set and genetic algorithm is proposed to deal with the hoisting motor state decision table. Under the condition that the information system's decision-making ability is unchanged, the redundant attribute is deleted. Which reduces the complexity and computation of the recognition process of the hoisting motor. It is possible to realize the fast state recognition.

A validated finite element model of a soft artificial muscle motor

NASA Astrophysics Data System (ADS)

Tse, Tony Chun H.; O'Brien, Benjamin; McKay, Thomas; Anderson, Iain A.

2011-04-01

The Biomimetics Laboratory has developed a soft artificial muscle motor based on Dielectric Elastomers. The motor, 'Flexidrive', is light-weight and has low system complexity. It works by gripping and turning a shaft with a soft gear, like we would with our fingers. The motor's performance depends on many factors, such as actuation waveform, electrode patterning, geometries and contact tribology between the shaft and gear. We have developed a finite element model (FEM) of the motor as a study and design tool. Contact interaction was integrated with previous material and electromechanical coupling models in ABAQUS. The model was experimentally validated through a shape and blocked force analysis.

Hsp90 C-Terminal Inhibitors Exhibit Antimigratory Activity by Disrupting the Hsp90α/Aha1 Complex in PC3-MM2 Cells

PubMed Central

2015-01-01

Human Hsp90 isoforms are molecular chaperones that are often up-regulated in malignances and represent a primary target for Hsp90 inhibitors undergoing clinical evaluation. Hsp90α is a stress-inducible isoform of Hsp90 that plays a significant role in apoptosis and metastasis. Though Hsp90α is secreted into the extracellular space under metastatic conditions, its role in cancer biology is poorly understood. We report that Hsp90α associates with the Aha1 co-chaperone and found this complex to localize in secretory vesicles and at the leading edge of migrating cells. Knockdown of Hsp90α resulted in a defect in cell migration. The functional role of Hsp90α/Aha1 was studied by treating the cells with various novobiocin-based Hsp90 C-terminal inhibitors. These inhibitors disrupted the Hsp90α/Aha1 complex, caused a cytoplasmic redistribution of Hsp90α and Aha1, and decreased cell migration. Structure–function studies determined that disruption of Hsp90α/Aha1 association and inhibition of cell migration correlated with the presence of a benzamide side chain, since an acetamide substituted analog was less effective. Our results show that disruption of Hsp90α/Aha1 interactions with novobiocin-based Hsp90 C-terminal inhibitors may limit the metastatic potential of tumors. PMID:25402753

Social Justice and Mobility in Coastal Louisiana, USA.

PubMed

Colten, Craig E; Simms, Jessica R Z; Grismore, Audrey A; Hemmerling, Scott A

2018-02-01

Louisiana faces extensive coastal land loss which threatens the livelihoods of marginalized populations. These groups have endured extreme disruptive events in the past and have survived in the region by relying on several resilient practices, including mobility. Facing environmental changes that will be wrought by deliberate coastal restoration programs, elderly residents are resisting migration while younger residents continue a decades-long inland migration. Interviews and historical records illustrate a complex intersection of resilient practices and environmental migration. The process underway conflicts to some extent with prevailing concepts in environmental migration most notably deviating from established migration patterns. In terms of social justice, selective out-migration of younger adults leaves a more vulnerable population behind, but also provides a supplementary source of income and social links to inland locales. Organized resistance to restoration projects represents a social justice response to programs that threaten the resource-based livelihoods of coastal residents while offering protection to safer inland urban residents.

AMF/PGI transactivates the MMP-3 gene through the activation of Src-RhoA-phosphatidylinositol 3-kinase signaling to induce hepatoma cell migration.

PubMed

Shih, Wen-Ling; Liao, Ming-Huei; Yu, Feng-Ling; Lin, Ping-Yuan; Hsu, Hsue-Yin; Chiu, Shu-Jun

2008-11-08

We have previously shown that AMF/PGI induces hepatoma cell migration through the induction of MMP-3. This work investigates how AMF/PGI activates the MMP-3 gene. We demonstrated that AMF/PGI transactivates the MMP-3 gene promoter through AP-1. The transactivation and induction of cell migration effect of AMF/PGI directly correlates with its enzymatic activity. Various analyses showed that AMF/PGI stimulated the Src-RhoA-PI3-kinase signaling pathway, and these three signaling molecules could form a complex. Our results demonstrate a new mechanism of AMF/PGI-induced cell migration and a link between Src-RhoA-PI3-kinase, AP-1, MMP-3 and hepatoma cell migration.

Improving TOGAF ADM 9.1 Migration Planning Phase by ITIL V3 Service Transition

NASA Astrophysics Data System (ADS)

Hanum Harani, Nisa; Akhmad Arman, Arry; Maulana Awangga, Rolly

2018-04-01

Modification planning of business transformation involving technological utilization required a system of transition and migration planning process. Planning of system migration activity is the most important. The migration process is including complex elements such as business re-engineering, transition scheme mapping, data transformation, application development, individual involvement by computer and trial interaction. TOGAF ADM is the framework and method of enterprise architecture implementation. TOGAF ADM provides a manual refer to the architecture and migration planning. The planning includes an implementation solution, in this case, IT solution, but when the solution becomes an IT operational planning, TOGAF could not handle it. This paper presents a new model framework detail transitions process of integration between TOGAF and ITIL. We evaluated our models in field study inside a private university.

A MAPK-Driven Feedback Loop Suppresses Rac Activity to Promote RhoA-Driven Cancer Cell Invasion

PubMed Central

Hetmanski, Joseph H. R.; Zindy, Egor; Schwartz, Jean-Marc; Caswell, Patrick T.

2016-01-01

Cell migration in 3D microenvironments is fundamental to development, homeostasis and the pathobiology of diseases such as cancer. Rab-coupling protein (RCP) dependent co-trafficking of α5β1 and EGFR1 promotes cancer cell invasion into fibronectin (FN) containing extracellular matrix (ECM), by potentiating EGFR1 signalling at the front of invasive cells. This promotes a switch in RhoGTPase signalling to inhibit Rac1 and activate a RhoA-ROCK-Formin homology domain-containing 3 (FHOD3) pathway and generate filopodial actin-spike protrusions which drive invasion. To further understand the signalling network that drives RCP-driven invasive migration, we generated a Boolean logical model based on existing network pathways/models, where each node can be interrogated by computational simulation. The model predicted an unanticipated feedback loop, whereby Raf/MEK/ERK signalling maintains suppression of Rac1 by inhibiting the Rac-activating Sos1-Eps8-Abi1 complex, allowing RhoA activity to predominate in invasive protrusions. MEK inhibition was sufficient to promote lamellipodia formation and oppose filopodial actin-spike formation, and led to activation of Rac and inactivation of RhoA at the leading edge of cells moving in 3D matrix. Furthermore, MEK inhibition abrogated RCP/α5β1/EGFR1-driven invasive migration. However, upon knockdown of Eps8 (to suppress the Sos1-Abi1-Eps8 complex), MEK inhibition had no effect on RhoGTPase activity and did not oppose invasive migration, suggesting that MEK-ERK signalling suppresses the Rac-activating Sos1-Abi1-Eps8 complex to maintain RhoA activity and promote filopodial actin-spike formation and invasive migration. Our study highlights the predictive potential of mathematical modelling approaches, and demonstrates that a simple intervention (MEK-inhibition) could be of therapeutic benefit in preventing invasive migration and metastasis. PMID:27138333

Experimenting with theoretical motor neuroscience.

PubMed

Ajemian, Robert; Hogan, Neville

2010-11-01

Motor neuroscience is well over 100 years old, with seminal work such as G. T. Fritz and E. Hitzig's discovery of motor cortex occurring in 1870. Theoretical motor neuroscience has been ongoing for at least the last 50 years. How mature a scientific discipline is motor neuroscience? Are experimentalists and theoreticians working together productively to help the field progress? This article addresses these questions by advancing the following theses. Motor neuroscience remains at a descriptive stage due to the incredible complexity of the problem to be solved. The proliferation of models--and distinct modeling camps--stems from the absence of unifying conceptual constructs. To advance the field, theoreticians must rely more heavily on the concept of falsification by producing models that lend themselves to clear experimental testing.

A soft and dexterous motor

NASA Astrophysics Data System (ADS)

Anderson, Iain A.; Tse, Tony Chun Hin; Inamura, Tokushu; O'Brien, Benjamin M.; McKay, Thomas; Gisby, Todd

2011-03-01

We present a soft, bearing-free artificial muscle motor that cannot only turn a shaft but also grip and reposition it through a flexible gear. The bearing-free operation provides a foundation for low complexity soft machines, with multiple degree-of-freedom actuation, that can act simultaneously as motors and manipulators. The mechanism also enables an artificial muscle controlled gear change. Future work will include self-sensing feedback for precision, multidegree-of-freedom operation.

Virtual Reality As a Training Tool to Treat Physical Inactivity in Children.

PubMed

Kiefer, Adam W; Pincus, David; Richardson, Michael J; Myer, Gregory D

2017-01-01

Lack of adequate physical activity in children is an epidemic that can result in obesity and other poor health outcomes across the lifespan. Physical activity interventions focused on motor skill competence continue to be developed, but some interventions, such as neuromuscular training (NMT), may be limited in how early they can be implemented due to dependence on the child's level of cognitive and perceptual-motor development. Early implementation of motor-rich activities that support motor skill development in children is critical for the development of healthy levels of physical activity that carry through into adulthood. Virtual reality (VR) training may be beneficial in this regard. VR training, when grounded in an information-based theory of perceptual-motor behavior that modifies the visual information in the virtual world, can promote early development of motor skills in youth akin to more natural, real-world development as opposed to strictly formalized training. This approach can be tailored to the individual child and training scenarios can increase in complexity as the child develops. Ultimately, training in VR may help serve as a precursor to "real-world" NMT, and once the child reaches the appropriate training age can also augment more complex NMT regimens performed outside of the virtual environment.

Virtual Reality As a Training Tool to Treat Physical Inactivity in Children

PubMed Central

Kiefer, Adam W.; Pincus, David; Richardson, Michael J.; Myer, Gregory D.

2017-01-01

Lack of adequate physical activity in children is an epidemic that can result in obesity and other poor health outcomes across the lifespan. Physical activity interventions focused on motor skill competence continue to be developed, but some interventions, such as neuromuscular training (NMT), may be limited in how early they can be implemented due to dependence on the child’s level of cognitive and perceptual-motor development. Early implementation of motor-rich activities that support motor skill development in children is critical for the development of healthy levels of physical activity that carry through into adulthood. Virtual reality (VR) training may be beneficial in this regard. VR training, when grounded in an information-based theory of perceptual-motor behavior that modifies the visual information in the virtual world, can promote early development of motor skills in youth akin to more natural, real-world development as opposed to strictly formalized training. This approach can be tailored to the individual child and training scenarios can increase in complexity as the child develops. Ultimately, training in VR may help serve as a precursor to “real-world” NMT, and once the child reaches the appropriate training age can also augment more complex NMT regimens performed outside of the virtual environment. PMID:29376045

Research and simulation of the decoupling transformation in AC motor vector control

NASA Astrophysics Data System (ADS)

He, Jiaojiao; Zhao, Zhongjie; Liu, Ken; Zhang, Yongping; Yao, Tuozhong

2018-04-01

Permanent magnet synchronous motor (PMSM) is a nonlinear, strong coupling, multivariable complex object, and transformation decoupling can solve the coupling problem of permanent magnet synchronous motor. This paper gives a permanent magnet synchronous motor (PMSM) mathematical model, introduces the permanent magnet synchronous motor vector control coordinate transformation in the process of modal matrix inductance matrix transform through the matrix related knowledge of different coordinates of diagonalization, which makes the coupling between the independent, realize the control of motor current and excitation the torque current coupling separation, and derived the coordinate transformation matrix, the thought to solve the coupling problem of AC motor. Finally, in the Matlab/Simulink environment, through the establishment and combination between the PMSM ontology, coordinate conversion module, built the simulation model of permanent magnet synchronous motor vector control, introduces the model of each part, and analyzed the simulation results.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Cheng-hu; Cao, Guo-Fan; Jiang, Qin, E-mail: Jqin710@vip.sina.com

Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-addedmore » active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.« less

Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration.

PubMed

Suetsugu, Shiro; Yamazaki, Daisuke; Kurisu, Shusaku; Takenawa, Tadaomi

2003-10-01

Cell migration is driven by actin polymerization at the leading edge of lamellipodia, where WASP family verprolin-homologous proteins (WAVEs) activate Arp2/3 complex. When fibroblasts are stimulated with PDGF, formation of peripheral ruffles precedes that of dorsal ruffles in lamellipodia. Here, we show that WAVE2 deficiency impairs peripheral ruffle formation and WAVE1 deficiency impairs dorsal ruffle formation. During directed cell migration in the absence of extracellular matrix (ECM), cells migrate with peripheral ruffles at the leading edge and WAVE2, but not WAVE1, is essential. In contrast, both WAVE1 and WAVE2 are essential for invading migration into ECM, suggesting that the leading edge in ECM has characteristics of both ruffles. WAVE1 is colocalized with ECM-degrading enzyme MMP-2 in dorsal ruffles, and WAVE1-, but not WAVE2-, dependent migration requires MMP activity. Thus, WAVE2 is essential for leading edge extension for directed migration in general and WAVE1 is essential in MMP-dependent migration in ECM.

Integration of motor proteins - towards an ATP fueled soft actuator.

PubMed

Kakugo, Akira; Shikinaka, Kazuhiro; Gong, Jian Ping

2008-09-01

We present a soft bio-machine constructed from biological motors (actin/myosin). We have found that chemically cross-linked polymer-actin complex gel filaments can move on myosin coated surfaces with a velocity as high as that of native F-actin, by coupling to ATP hydrolysis. Additionally, it is shown that the velocity of polymer-actin complex gel depends on the species of polycations binding to the F-actins. Since the design of functional actuators of well-defined size and morphology is important, the structural behavior of polymer-actin complexes has been investigated. Our results show that the morphology and growth size of polymer-actin complex can be controlled by changes in the electrostatic interactions between F-actins and polycations. Our results indicate that bio actuators with desired shapes can be created by using a polymer-actin complex.

Formation of VP-Zn complexes in bulk InP(Zn) by migration of P vacancies from the (110) surface

NASA Astrophysics Data System (ADS)

Slotte, J.; Saarinen, K.; Ebert, Ph.

2006-05-01

We apply a combination of positron annihilation spectroscopy and scanning tunneling microscopy to show that thermally generated P vacancies diffuse from the InP surface toward the bulk. The defect observed in the bulk can be identified as a complex consisting of a P vacancy and a Zn impurity. We infer that this pair is formed when the diffusing positive P vacancy is trapped at the Zn dopant. A rough estimate for the migration energy of the P vacancy results in a value of 1.3eV .

The E3 ubiquitin ligase NEDD4 mediates cell migration signaling of EGFR in lung cancer cells.

PubMed

Shao, Genbao; Wang, Ranran; Sun, Aiqin; Wei, Jing; Peng, Ke; Dai, Qian; Yang, Wannian; Lin, Qiong

2018-02-19

EGFR-dependent cell migration plays an important role in lung cancer progression. Our previous study observed that the HECT E3 ubiquitin ligase NEDD4 is significantly correlated with tumor metastasis and required for migration and invasion signaling of EGFR in gastric cancer cells. However, how NEDD4 promotes the EGFR-dependent lung cancer cell migration is unknown. This study is to elucidate the mechanism by which NEDD4 mediates the EGFR lung cancer migration signaling. Lentiviral vector-loaded NEDD4 shRNA was used to deplete endogenous NEDD4 in lung cancer cell lines. Effects of the NEDD4 knockdown on the EGFR-dependent or independent lung cancer cell migration were determined using the wound-healing and transwell assays. Association of NEDD4 with activated EGFR was assayed by co-immunoprecipitation. Co-expression of NEDD4 with EGFR or PTEN was determined by immunohistochemical (IHC) staining in 63 lung adenocarcinoma tissue samples. Effects of NEDD4 ectopic expression or knockdown on PTEN ubiquitination and down-regulation, AKT activation and lysosomal secretion were examined using the GST-Uba pulldown assay, immunoblotting, immunofluorescent staining and a human cathepsin B ELISA assay respectively. The specific cathepsin B inhibitor CA-074Me was used for assessing the role of cathepsin B in lung cancer cell migration. Knockdown of NEDD4 significantly reduced EGF-stimulated cell migration in non-small cell lung carcinoma (NSCLC) cells. Co-immunoprecipitation assay found that NEDD4 is associated with EGFR complex upon EGF stimulation, and IHC staining indicates that NEDD4 is co-expressed with EGFR in lung adenocarcinoma tumor tissues, suggesting that NEDD4 might mediate lung cancer cell migration by interaction with the EGFR signaling complex. Interestingly, NEDD4 promotes the EGF-induced cathepsin B secretion, possibly through lysosomal exocytosis, as overexpression of the ligase-dead mutant of NEDD4 impedes lysosomal secretion, and knockdown of NEDD4 significantly reduced extracellular amount of cathepsin B induced by EGF. Consistent with the role of NEDD4, cathepsin B is pivotal for both basal and the EGF-stimulated lung cancer cell migration. Our studies propose a novel mechanism underlying the EGFR-promoted lung cancer cell migration that is mediated by NEDD4 through regulation of cathepsin B secretion. NEDD4 mediates the EGFR lung cancer cell migration signaling through promoting lysosomal secretion of cathepsin B.

Prosthetic avian vocal organ controlled by a freely behaving bird based on a low dimensional model of the biomechanical periphery.

PubMed

Arneodo, Ezequiel M; Perl, Yonatan Sanz; Goller, Franz; Mindlin, Gabriel B

2012-01-01

Because of the parallels found with human language production and acquisition, birdsong is an ideal animal model to study general mechanisms underlying complex, learned motor behavior. The rich and diverse vocalizations of songbirds emerge as a result of the interaction between a pattern generator in the brain and a highly nontrivial nonlinear periphery. Much of the complexity of this vocal behavior has been understood by studying the physics of the avian vocal organ, particularly the syrinx. A mathematical model describing the complex periphery as a nonlinear dynamical system leads to the conclusion that nontrivial behavior emerges even when the organ is commanded by simple motor instructions: smooth paths in a low dimensional parameter space. An analysis of the model provides insight into which parameters are responsible for generating a rich variety of diverse vocalizations, and what the physiological meaning of these parameters is. By recording the physiological motor instructions elicited by a spontaneously singing muted bird and computing the model on a Digital Signal Processor in real-time, we produce realistic synthetic vocalizations that replace the bird's own auditory feedback. In this way, we build a bio-prosthetic avian vocal organ driven by a freely behaving bird via its physiologically coded motor commands. Since it is based on a low-dimensional nonlinear mathematical model of the peripheral effector, the emulation of the motor behavior requires light computation, in such a way that our bio-prosthetic device can be implemented on a portable platform.

Efficient Endocytic Uptake and Maturation in Drosophila Oocytes Requires Dynamitin/p50

PubMed Central

Liu, Guojun; Sanghavi, Paulomi; Bollinger, Kathryn E.; Perry, Libby; Marshall, Brendan; Roon, Penny; Tanaka, Tsubasa; Nakamura, Akira; Gonsalvez, Graydon B.

2015-01-01

Dynactin is a multi-subunit complex that functions as a regulator of the Dynein motor. A central component of this complex is Dynamitin/p50 (Dmn). Dmn is required for endosome motility in mammalian cell lines. However, the extent to which Dmn participates in the sorting of cargo via the endosomal system is unknown. In this study, we examined the endocytic role of Dmn using the Drosophila melanogaster oocyte as a model. Yolk proteins are internalized into the oocyte via clathrin-mediated endocytosis, trafficked through the endocytic pathway, and stored in condensed yolk granules. Oocytes that were depleted of Dmn contained fewer yolk granules than controls. In addition, these oocytes accumulated numerous endocytic intermediate structures. Particularly prominent were enlarged endosomes that were relatively devoid of Yolk proteins. Ultrastructural and genetic analyses indicate that the endocytic intermediates are produced downstream of Rab5. Similar phenotypes were observed upon depleting Dynein heavy chain (Dhc) or Lis1. Dhc is the motor subunit of the Dynein complex and Lis1 is a regulator of Dynein activity. We therefore propose that Dmn performs its function in endocytosis via the Dynein motor. Consistent with a role for Dynein in endocytosis, the motor colocalized with the endocytic machinery at the oocyte cortex in an endocytosis-dependent manner. Our results suggest a model whereby endocytic activity recruits Dynein to the oocyte cortex. The motor along with its regulators, Dynactin and Lis1, functions to ensure efficient endocytic uptake and maturation. PMID:26265702

Studies of a new hybrid taxon in the Artemisia tridentata (Asteraceae: Anthemideae) complex

Treesearch

Heather D. Garrison; Leila M. Shultz; E. Durant McArthur

2013-01-01

Members of the Artemisia tridentata complex (ASTERACEAE: Anthemideae: Artemisia subgen. Tridentatae) have adapted to changing environmental conditions through geographic migration, introgression, and hybridization. These processes have resulted in morphologic and genetic variation. A presumed hybrid ("Bonneville" big sagebrush) of the complex occurs in the...

A system level model for preliminary design of a space propulsion solid rocket motor

NASA Astrophysics Data System (ADS)

Schumacher, Daniel M.

Preliminary design of space propulsion solid rocket motors entails a combination of components and subsystems. Expert design tools exist to find near optimal performance of subsystems and components. Conversely, there is no system level preliminary design process for space propulsion solid rocket motors that is capable of synthesizing customer requirements into a high utility design for the customer. The preliminary design process for space propulsion solid rocket motors typically builds on existing designs and pursues feasible rather than the most favorable design. Classical optimization is an extremely challenging method when dealing with the complex behavior of an integrated system. The complexity and combinations of system configurations make the number of the design parameters that are traded off unreasonable when manual techniques are used. Existing multi-disciplinary optimization approaches generally address estimating ratios and correlations rather than utilizing mathematical models. The developed system level model utilizes the Genetic Algorithm to perform the necessary population searches to efficiently replace the human iterations required during a typical solid rocket motor preliminary design. This research augments, automates, and increases the fidelity of the existing preliminary design process for space propulsion solid rocket motors. The system level aspect of this preliminary design process, and the ability to synthesize space propulsion solid rocket motor requirements into a near optimal design, is achievable. The process of developing the motor performance estimate and the system level model of a space propulsion solid rocket motor is described in detail. The results of this research indicate that the model is valid for use and able to manage a very large number of variable inputs and constraints towards the pursuit of the best possible design.

Neutrophils establish rapid and robust WAVE complex polarity in an actin-dependent fashion.

PubMed

Millius, Arthur; Dandekar, Sheel N; Houk, Andrew R; Weiner, Orion D

2009-02-10

Asymmetric intracellular signals enable cells to migrate in response to external cues. The multiprotein WAVE (also known as SCAR or WASF) complex activates the actin-nucleating Arp2/3 complex [1-4] and localizes to propagating "waves," which direct actin assembly during neutrophil migration [5, 6]. Here, we observe similar WAVE complex dynamics in other mammalian cells and analyze WAVE complex dynamics during establishment of neutrophil polarity. Earlier models proposed that spatially biased generation [7] or selection of protrusions [8] enables chemotaxis. These models require existing morphological polarity to control protrusions. We show that spatially biased generation and selection of WAVE complex recruitment also occur in morphologically unpolarized neutrophils during development of their first protrusions. Additionally, several mechanisms limit WAVE complex recruitment during polarization and movement: Intrinsic cues restrict WAVE complex distribution during establishment of polarity, and asymmetric intracellular signals constrain it in morphologically polarized cells. External gradients can overcome both intrinsic biases and control WAVE complex localization. After latrunculin-mediated inhibition of actin polymerization, addition and removal of agonist gradients globally recruits and releases the WAVE complex from the membrane. Under these conditions, the WAVE complex no longer polarizes, despite the presence of strong external gradients. Thus, actin polymer and the WAVE complex reciprocally interact during polarization.

Using the Self-Select Paradigm to Delineate the Nature of Speech Motor Programming

PubMed Central

Wright, David L.; Robin, Don A.; Rhee, Jooyhun; Vaculin, Amber; Jacks, Adam; Guenther, Frank H.; Fox, Peter T.

2015-01-01

Purpose The authors examined the involvement of 2 speech motor programming processes identified by S. T. Klapp (1995, 2003) during the articulation of utterances differing in syllable and sequence complexity. According to S. T. Klapp, 1 process, INT, resolves the demands of the programmed unit, whereas a second process, SEQ, oversees the serial order demands of longer sequences. Method A modified reaction time paradigm was used to assess INT and SEQ demands. Specifically, syllable complexity was dependent on syllable structure, whereas sequence complexity involved either repeated or unique syllabi within an utterance. Results INT execution was slowed when articulating single syllables in the form CCCV compared to simpler CV syllables. Planning unique syllables within a multisyllabic utterance rather than repetitions of the same syllable slowed INT but not SEQ. Conclusions The INT speech motor programming process, important for mental syllabary access, is sensitive to changes in both syllable structure and the number of unique syllables in an utterance. PMID:19474396

Self-organized adaptation of a simple neural circuit enables complex robot behaviour

NASA Astrophysics Data System (ADS)

Steingrube, Silke; Timme, Marc; Wörgötter, Florentin; Manoonpong, Poramate

2010-03-01

Controlling sensori-motor systems in higher animals or complex robots is a challenging combinatorial problem, because many sensory signals need to be simultaneously coordinated into a broad behavioural spectrum. To rapidly interact with the environment, this control needs to be fast and adaptive. Present robotic solutions operate with limited autonomy and are mostly restricted to few behavioural patterns. Here we introduce chaos control as a new strategy to generate complex behaviour of an autonomous robot. In the presented system, 18 sensors drive 18 motors by means of a simple neural control circuit, thereby generating 11 basic behavioural patterns (for example, orienting, taxis, self-protection and various gaits) and their combinations. The control signal quickly and reversibly adapts to new situations and also enables learning and synaptic long-term storage of behaviourally useful motor responses. Thus, such neural control provides a powerful yet simple way to self-organize versatile behaviours in autonomous agents with many degrees of freedom.

Global spatio-temporal patterns in human migration: a complex network perspective.

PubMed

Davis, Kyle F; D'Odorico, Paolo; Laio, Francesco; Ridolfi, Luca

2013-01-01

Migration is a powerful adaptive strategy for humans to navigate hardship and pursue a better quality of life. As a universal vehicle facilitating exchanges of ideas, culture, money and goods, international migration is a major contributor to globalization. Consisting of countries linked by multiple connections of human movements, global migration constitutes a network. Despite the important role of human migration in connecting various communities in different parts of the world, the topology and behavior of the international migration network and its changes through time remain poorly understood. Here we show that the global human migration network became more interconnected during the latter half of the twentieth century and that migrant destination choice partly reflects colonial and postcolonial histories, language, religion, and distances. From 1960 to 2000 we found a steady increase in network transitivity (i.e. connectivity between nodes connected to the same node), a decrease in average path length and an upward shift in degree distribution, all of which strengthened the 'small-world' behavior of the migration network. Furthermore, we found that distinct groups of countries preferentially interact to form migration communities based largely on historical, cultural and economic factors.

Climate Variability and Inter-Provincial Migration in South America, 1970-2011

PubMed Central

Thiede, Brian; Gray, Clark; Mueller, Valerie

2016-01-01

We examine the effect of climate variability on human migration in South America. Our analyses draw on over 21 million observations of adults aged 15-40 from 25 censuses conducted in eight South American countries. Addressing limitations associated with methodological diversity among prior studies, we apply a common analytic approach and uniform definitions of migration and climate across all countries. We estimate the effects of climate variability on migration overall and also investigate heterogeneity across sex, age, and socioeconomic groups, across countries, and across historical climate conditions. We also disaggregate migration by the rural/urban status of destination. We find that exposure to monthly temperature shocks has the most consistent effects on migration relative to monthly rainfall shocks and gradual changes in climate over multi-year periods. We also find evidence of heterogeneity across demographic groups and countries. Analyses that disaggregate migration by the rural/urban status of destination suggest that much of the climate-related inter-province migration is directed toward urban areas. Overall, our results underscore the complexity of environment-migration linkages and challenge simplistic narratives that envision a linear and monolithic migratory response to changing climates. PMID:28413264

Learning from HIV: exploring migration and health in South Africa.

PubMed

Vearey, Joanna

2012-01-01

Southern Africa is associated with high HIV prevalence and diverse population movements, including temporary, circular movements between rural and urban areas within countries (internal migration), and movements across borders (international migration). Whilst most migration in southern Africa is associated with the search for improved livelihood opportunities in urban areas a small--but significant--number of people are forced to migrate to escape persecution or civil war. This paper utilises recent empirical studies conducted in South Africa to explore linkages between migration into urban areas and health, focusing on HIV. It is shown that the relationship between migration and HIV is complex; that both internal and international migrants move to urban areas for reasons other than healthcare seeking; and that most migratory movements into urban areas involve the positive selection of healthy individuals. Whilst healthy migration has economic benefits for rural sending households, the data uncovers an important process of return migration (internally or across borders) in times of sickness, with the burden of care placed on the rural, sending household. There is an urgent need for a comprehensive response that maintains the health of migrants in urban areas, and provides support to rural areas in times of sickness.

Climate Variability and Inter-Provincial Migration in South America, 1970-2011.

PubMed

Thiede, Brian; Gray, Clark; Mueller, Valerie

2016-11-01

We examine the effect of climate variability on human migration in South America. Our analyses draw on over 21 million observations of adults aged 15-40 from 25 censuses conducted in eight South American countries. Addressing limitations associated with methodological diversity among prior studies, we apply a common analytic approach and uniform definitions of migration and climate across all countries. We estimate the effects of climate variability on migration overall and also investigate heterogeneity across sex, age, and socioeconomic groups, across countries, and across historical climate conditions. We also disaggregate migration by the rural/urban status of destination. We find that exposure to monthly temperature shocks has the most consistent effects on migration relative to monthly rainfall shocks and gradual changes in climate over multi-year periods. We also find evidence of heterogeneity across demographic groups and countries. Analyses that disaggregate migration by the rural/urban status of destination suggest that much of the climate-related inter-province migration is directed toward urban areas. Overall, our results underscore the complexity of environment-migration linkages and challenge simplistic narratives that envision a linear and monolithic migratory response to changing climates.

Dysregulation of chromatin remodelling complexes in amyotrophic lateral sclerosis.

PubMed

Tibshirani, Michael; Zhao, Beibei; Gentil, Benoit J; Minotti, Sandra; Marques, Christine; Keith, Julia; Rogaeva, Ekaterina; Zinman, Lorne; Rouaux, Caroline; Robertson, Janice; Durham, Heather D

2017-11-01

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with paralysis resulting from dysfunction and loss of motor neurons. A common neuropathological finding is attrition of motor neuron dendrites, which make central connections vital to motor control. The chromatin remodelling complex, neuronal Brahma-related gene 1 (Brg1)-associated factor complex (nBAF), is critical for neuronal differentiation, dendritic extension and synaptic function. We have identified loss of the crucial nBAF subunits Brg1, Brg1-associated factor 53b and calcium responsive transactivator in cultured motor neurons expressing FUS or TAR-DNA Binding Protein 43 (TDP-43) mutants linked to familial ALS. When plasmids encoding wild-type or mutant human FUS or TDP-43 were expressed in motor neurons of dissociated spinal cord cultures prepared from E13 mice, mutant proteins in particular accumulated in the cytoplasm. Immunolabelling of nBAF subunits was reduced in proportion to loss of nuclear FUS or TDP-43 and depletion of Brg1 was associated with nuclear retention of Brg1 mRNA. Dendritic attrition (loss of intermediate and terminal dendritic branches) occurred in motor neurons expressing mutant, but not wild-type, FUS or TDP-43. This attrition was delayed by ectopic over-expression of Brg1 and was reproduced by inhibiting Brg1 activity either through genetic manipulation or treatment with the chemical inhibitor, (E)-1-(2-Hydroxyphenyl)-3-((1R, 4R)-5-(pyridin-2-yl)-2, 5-diazabicyclo[2.2.1]heptan-2-yl)prop-2-en-1-one, demonstrating the importance of Brg1 to maintenance of dendritic architecture. Loss of nBAF subunits was also documented in spinal motor neurons in autopsy tissue from familial amyotrophic sclerosis (chromosome 9 open reading frame 72 with G4C2 nucleotide expansion) and from sporadic cases with no identified mutation, pointing to dysfunction of nBAF chromatin remodelling in multiple forms of ALS. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Apoptosis of Limb Innervating Motor Neurons and Erosion of Motor Pool Identity Upon Lineage Specific Dicer Inactivation

PubMed Central

Chen, Jun-An; Wichterle, Hynek

2012-01-01

Diversification of mammalian spinal motor neurons into hundreds of subtypes is critical for the maintenance of body posture and coordination of complex movements. Motor neuron differentiation is controlled by extrinsic signals that regulate intrinsic genetic programs specifying and consolidating motor neuron subtype identity. While transcription factors have been recognized as principal regulators of the intrinsic program, the role of posttranscriptional regulations has not been systematically tested. MicroRNAs produced by Dicer mediated cleavage of RNA hairpins contribute to gene regulation by posttranscriptional silencing. Here we used Olig2-cre conditional deletion of Dicer gene in motor neuron progenitors to examine effects of miRNA biogenesis disruption on postmitotic spinal motor neurons. We report that despite the initial increase in the number of motor neuron progenitors, disruption of Dicer function results in a loss of many limb- and sympathetic ganglia-innervating spinal motor neurons. Furthermore, it leads to defects in motor pool identity specification. Thus, our results indicate that miRNAs are an integral part of the genetic program controlling motor neuron survival and acquisition of subtype specific properties. PMID:22629237

Mice with genetic deletion of the heparin-binding growth factor midkine exhibit early preclinical features of Parkinson's disease.

PubMed

Prediger, Rui D S; Rojas-Mayorquin, Argelia E; Aguiar, Aderbal S; Chevarin, Caroline; Mongeau, Raymond; Hamon, Michel; Lanfumey, Laurence; Del Bel, Elaine; Muramatsu, Hisako; Courty, José; Raisman-Vozari, Rita

2011-08-01

There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD) begin many years before the appearance of the characteristic motor symptoms and that impairments in olfactory, cognitive and motor functions are associated with time-dependent disruption of dopaminergic neurotransmission in different brain areas. Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in many biological processes in the central nervous system such as cell migration, neurogenesis and tissue repair. The abnormal midkine expression may be associated with neurochemical dysfunction in the dopaminergic system and cognitive impairments in rodents. Here, we employed adult midkine knockout mice (Mdk(-/-)) to further investigate the relevance of midkine in dopaminergic neurotransmission and in olfactory, cognitive and motor functions. Mdk(/-) mice displayed pronounced impairments in their olfactory discrimination ability and short-term social recognition memory with no gross motor alterations. Moreover, the genetic deletion of midkine decreased the expression of the enzyme tyrosine hydroxylase in the substantia nigra reducing partially the levels of dopamine and its metabolites in the olfactory bulb and striatum of mice. These findings indicate that the genetic deletion of midkine causes a partial loss of dopaminergic neurons and depletion of dopamine, resulting in olfactory and memory deficits with no major motor impairments. Therefore, Mdk(-/-) mice may represent a promising animal model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

Plasticity and alterations of trunk motor cortex following spinal cord injury and non-stepping robot and treadmill training.

PubMed

Oza, Chintan S; Giszter, Simon F

2014-06-01

Spinal cord injury (SCI) induces significant reorganization in the sensorimotor cortex. Trunk motor control is crucial for postural stability and propulsion after low thoracic SCI and several rehabilitative strategies are aimed at trunk stability and control. However little is known about the effect of SCI and rehabilitation training on trunk motor representations and their plasticity in the cortex. Here, we used intracortical microstimulation to examine the motor cortex representations of the trunk in relation to other representations in three groups of chronic adult complete low thoracic SCI rats: chronic untrained, treadmill trained (but 'non-stepping') and robot assisted treadmill trained (but 'non-stepping') and compared with a group of normal rats. Our results demonstrate extensive and significant reorganization of the trunk motor cortex after chronic adult SCI which includes (1) expansion and rostral displacement of trunk motor representations in the cortex, with the greatest significant increase observed for rostral (to injury) trunk, and slight but significant increase of motor representation for caudal (to injury) trunk at low thoracic levels in all spinalized rats; (2) significant changes in coactivation and the synergy representation (or map overlap) between different trunk muscles and between trunk and forelimb. No significant differences were observed between the groups of transected rats for the majority of the comparisons. However, (3) the treadmill and robot-treadmill trained groups of rats showed a further small but significant rostral migration of the trunk representations, beyond the shift caused by transection alone. We conclude that SCI induces a significant reorganization of the trunk motor cortex, which is not qualitatively altered by non-stepping treadmill training or non-stepping robot assisted treadmill training, but is shifted further from normal topography by the training. This shift may potentially make subsequent rehabilitation with stepping longer or less successful. Copyright © 2014 Elsevier Inc. All rights reserved.

New insights into sucking, swallowing and breathing central generators: A complexity analysis of rhythmic motor behaviors.

PubMed

Samson, Nathalie; Praud, Jean-Paul; Quenet, Brigitte; Similowski, Thomas; Straus, Christian

2017-01-18

Sucking, swallowing and breathing are dynamic motor behaviors. Breathing displays features of chaos-like dynamics, in particular nonlinearity and complexity, which take their source in the automatic command of breathing. In contrast, buccal/gill ventilation in amphibians is one of the rare motor behaviors that do not display nonlinear complexity. This study aimed at assessing whether sucking and swallowing would also follow nonlinear complex dynamics in the newborn lamb. Breathing movements were recorded before, during and after bottle-feeding. Sucking pressure and the integrated EMG of the thyroartenoid muscle, as an index of swallowing, were recorded during bottle-feeding. Nonlinear complexity of the whole signals was assessed through the calculation of the noise limit value (NL). Breathing and swallowing always exhibited chaos-like dynamics. The NL of breathing did not change significantly before, during or after bottle-feeding. On the other hand, sucking inconsistently and significantly less frequently than breathing exhibited a chaos-like dynamics. Therefore, the central pattern generator (CPG) that drives sucking may be functionally different from the breathing CPG. Furthermore, the analogy between buccal/gill ventilation and sucking suggests that the latter may take its phylogenetic origin in the gill ventilation CPG of the common ancestor of extant amphibians and mammals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Recruitment of prefrontal-striatal circuit in response to skilled motor challenge.

PubMed

Guo, Yumei; Wang, Zhuo; Prathap, Sandhya; Holschneider, Daniel P

2017-12-13

A variety of physical fitness regimens have been shown to improve cognition, including executive function, yet our understanding of which parameters of motor training are important in optimizing outcomes remains limited. We used functional brain mapping to compare the ability of two motor challenges to acutely recruit the prefrontal-striatal circuit. The two motor tasks - walking in a complex running wheel with irregularly spaced rungs or walking in a running wheel with a smooth internal surface - differed only in the extent of skill required for their execution. Cerebral perfusion was mapped in rats by intravenous injection of [C]-iodoantipyrine during walking in either a motorized complex wheel or in a simple wheel. Regional cerebral blood flow (rCBF) was quantified by whole-brain autoradiography and analyzed in three-dimensional reconstructed brains by statistical parametric mapping and seed-based functional connectivity. Skilled or simple walking compared with rest, increased rCBF in regions of the motor circuit, somatosensory and visual cortex, as well as the hippocampus. Significantly greater rCBF increases were noted during skilled walking than for simple walking. Skilled walking, unlike simple walking or the resting condition, was associated with a significant positive functional connectivity in the prefrontal-striatal circuit (prelimbic cortex-dorsomedial striatum) and greater negative functional connectivity in the prefrontal-hippocampal circuit. Our findings suggest that the level of skill of a motor training task determines the extent of functional recruitment of the prefrontal-corticostriatal circuit, with implications for a new approach in neurorehabilitation that uses circuit-specific neuroplasticity to improve motor and cognitive functions.

Sensory-Motor Networks Involved in Speech Production and Motor Control: An fMRI Study

PubMed Central

Behroozmand, Roozbeh; Shebek, Rachel; Hansen, Daniel R.; Oya, Hiroyuki; Robin, Donald A.; Howard, Matthew A.; Greenlee, Jeremy D.W.

2015-01-01

Speaking is one of the most complex motor behaviors developed to facilitate human communication. The underlying neural mechanisms of speech involve sensory-motor interactions that incorporate feedback information for online monitoring and control of produced speech sounds. In the present study, we adopted an auditory feedback pitch perturbation paradigm and combined it with functional magnetic resonance imaging (fMRI) recordings in order to identify brain areas involved in speech production and motor control. Subjects underwent fMRI scanning while they produced a steady vowel sound /a/ (speaking) or listened to the playback of their own vowel production (playback). During each condition, the auditory feedback from vowel production was either normal (no perturbation) or perturbed by an upward (+600 cents) pitch shift stimulus randomly. Analysis of BOLD responses during speaking (with and without shift) vs. rest revealed activation of a complex network including bilateral superior temporal gyrus (STG), Heschl's gyrus, precentral gyrus, supplementary motor area (SMA), Rolandic operculum, postcentral gyrus and right inferior frontal gyrus (IFG). Performance correlation analysis showed that the subjects produced compensatory vocal responses that significantly correlated with BOLD response increases in bilateral STG and left precentral gyrus. However, during playback, the activation network was limited to cortical auditory areas including bilateral STG and Heschl's gyrus. Moreover, the contrast between speaking vs. playback highlighted a distinct functional network that included bilateral precentral gyrus, SMA, IFG, postcentral gyrus and insula. These findings suggest that speech motor control involves feedback error detection in sensory (e.g. auditory) cortices that subsequently activate motor-related areas for the adjustment of speech parameters during speaking. PMID:25623499

Self-monitoring in the cerebral cortex: Neural responses to small pitch shifts in auditory feedback during speech production.

PubMed

Franken, Matthias K; Eisner, Frank; Acheson, Daniel J; McQueen, James M; Hagoort, Peter; Schoffelen, Jan-Mathijs

2018-06-21

Speaking is a complex motor skill which requires near instantaneous integration of sensory and motor-related information. Current theory hypothesizes a complex interplay between motor and auditory processes during speech production, involving the online comparison of the speech output with an internally generated forward model. To examine the neural correlates of this intricate interplay between sensory and motor processes, the current study uses altered auditory feedback (AAF) in combination with magnetoencephalography (MEG). Participants vocalized the vowel/e/and heard auditory feedback that was temporarily pitch-shifted by only 25 cents, while neural activity was recorded with MEG. As a control condition, participants also heard the recordings of the same auditory feedback that they heard in the first half of the experiment, now without vocalizing. The participants were not aware of any perturbation of the auditory feedback. We found auditory cortical areas responded more strongly to the pitch shifts during vocalization. In addition, auditory feedback perturbation resulted in spectral power increases in the θ and lower β bands, predominantly in sensorimotor areas. These results are in line with current models of speech production, suggesting auditory cortical areas are involved in an active comparison between a forward model's prediction and the actual sensory input. Subsequently, these areas interact with motor areas to generate a motor response. Furthermore, the results suggest that θ and β power increases support auditory-motor interaction, motor error detection and/or sensory prediction processing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Mitomycin C retardation of corneal fibroblast migration via sustained dephosphorylation of paxillin at tyrosine 118.

PubMed

Chen, Tsan-Chi; Lai, Chien-Hsueh; Chang, Jie-Ling; Chang, Shu-Wen

2012-03-21

To investigate how mitomycin C (MMC) modulates corneal fibroblast migration and its molecular mechanisms in the wound healing process. After treatment with 0 and 0.2 mg · mL(-1) MMC for 5 minutes, effect of MMC on cell migration of human corneal fibroblasts (HCFs) was examined with a cell migration assay. Both focal adhesion kinase (FAK) and paxillin (PXN) expressions in HCFs were analyzed by semiquantitative real-time PCR, immunoblotting, and immunofluorescence confocal microscopy. Using gene silencing or gene overexpression with lentiviral-based pseudovirion infection, the phosphorylation level of FAK, PXN, and mutated PXNs at tyrosine sites 31 (Y31F-EGFP) and 118 (Y118F-EGFP) were verified in HCFs. MMC retarded HCF migration at 1 and 2 days posttreatment (dpt). MMC reduced levels of FAK transcript and FAK protein, but increased both transcript and protein expression of PXN at 1 and 2 dpt. Furthermore, MMC upregulated FAK-pY397, which subsequently enhanced PXN-pY31 in a dose-dependent manner at 1 dpt. Concurrently, MMC downregulated PXN-pY118 at 1 dpt. However, MMC treatment resulted in dephosphorylation of FAK-pY397, PXN-pY31, and PXN-pY118 at 2 dpt. The FAK/PXN complex in MMC-treated HCFs was detected at focal adhesion sites more than at the leading edge at 1 and 2 dpt, contributing to retardation of HCF migration. Y118F-EGFP-expressing HCFs exhibited lower mobility than that of PXN-EGFP- or Y31F-EGFP-expressing HCFs. The sustained PXN-pY118 dephosphorylation resulted in steadfastness of an incompletely active FAK/PXN complex at focal adhesion sites and played a pivotal role in MMC-retarded HCF migration.

Latino Immigrant Youth Living in a Nontraditional Migration City: A Social-Ecological Examination of the Complexities of Stress and Resilience

ERIC Educational Resources Information Center

DeJonckheere, Melissa J.; Vaughn, Lisa M.; Jacquez, Farrah

2017-01-01

Latino immigrant children represent the fastest-growing population in the United States and families are frequently residing outside of the traditional migration destinations. These cities lack the infrastructure and resources to provide culturally relevant services and bilingual education that supports these youth. Following a social-ecological…

Protein translocation channel of mitochondrial inner membrane and matrix-exposed import motor communicate via two-domain coupling protein

PubMed Central

Banerjee, Rupa; Gladkova, Christina; Mapa, Koyeli; Witte, Gregor; Mokranjac, Dejana

2015-01-01

The majority of mitochondrial proteins are targeted to mitochondria by N-terminal presequences and use the TIM23 complex for their translocation across the mitochondrial inner membrane. During import, translocation through the channel in the inner membrane is coupled to the ATP-dependent action of an Hsp70-based import motor at the matrix face. How these two processes are coordinated remained unclear. We show here that the two domain structure of Tim44 plays a central role in this process. The N-terminal domain of Tim44 interacts with the components of the import motor, whereas its C-terminal domain interacts with the translocation channel and is in contact with translocating proteins. Our data suggest that the translocation channel and the import motor of the TIM23 complex communicate through rearrangements of the two domains of Tim44 that are stimulated by translocating proteins. DOI: http://dx.doi.org/10.7554/eLife.11897.001 PMID:26714107

Sensorimotor Integration by Corticospinal System

PubMed Central

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior. PMID:27013985

Sensorimotor Integration by Corticospinal System.

PubMed

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior.

A bio-hybrid DNA rotor-stator nanoengine that moves along predefined tracks

NASA Astrophysics Data System (ADS)

Valero, Julián; Pal, Nibedita; Dhakal, Soma; Walter, Nils G.; Famulok, Michael

2018-06-01

Biological motors are highly complex protein assemblies that generate linear or rotary motion, powered by chemical energy. Synthetic motors based on DNA nanostructures, bio-hybrid designs or synthetic organic chemistry have been assembled. However, unidirectionally rotating biomimetic wheel motors with rotor-stator units that consume chemical energy are elusive. Here, we report a bio-hybrid nanoengine consisting of a catalytic stator that unidirectionally rotates an interlocked DNA wheel, powered by NTP hydrolysis. The engine consists of an engineered T7 RNA polymerase (T7RNAP-ZIF) attached to a dsDNA nanoring that is catenated to a rigid rotating dsDNA wheel. The wheel motor produces long, repetitive RNA transcripts that remain attached to the engine and are used to guide its movement along predefined ssDNA tracks arranged on a DNA nanotube. The simplicity of the design renders this walking nanoengine adaptable to other biological nanoarchitectures, facilitating the construction of complex bio-hybrid structures that achieve NTP-driven locomotion.

Spinal muscular atrophy: Selective motor neuron loss and global defect in the assembly of ribonucleoproteins.

PubMed

Beattie, Christine E; Kolb, Stephen J

2018-08-15

Spinal muscular atrophy is caused by deletions or mutations in the SMN1 gene that result in reduced expression of the SMN protein. The SMN protein is an essential molecular chaperone that is required for the biogenesis of multiple ribonucleoprotein (RNP) complexes including spliceosomal small nuclear RNPs (snRNPs). Reductions in SMN expression result in a reduced abundance of snRNPs and to downstream RNA splicing alterations. SMN is also present in axons and dendrites and appears to have important roles in the formation of neuronal mRNA-protein complexes during development or neuronal repair. Thus, SMA is an exemplar, selective motor neuron disorder that is caused by defects in fundamental RNA processing events. A detailed molecular understanding of how motor neurons fail, and why other neurons do not, in SMA will yield important principals about motor neuron maintenance and neuronal specificity in neurodegenerative diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

How can surgical training benefit from theories of skilled motor development, musical skill acquisition and performance psychology?

PubMed

McCaskie, Andrew W; Kenny, Dianna T; Deshmukh, Sandeep

2011-05-02

Trainee surgeons must acquire expert status in the context of reduced hours, reduced operating room time and the need to learn complex skills involving screen-mediated techniques, computers and robotics. Ever more sophisticated surgical simulation strategies have been helpful in providing surgeons with the opportunity to practise, but not all of these strategies are widely available. Similarities in the motor skills required in skilled musical performance and surgery suggest that models of music learning, and particularly skilled motor development, may be applicable in training surgeons. More attention should be paid to factors associated with optimal arousal and optimal performance in surgical training - lessons learned from helping anxious musicians optimise performance and manage anxiety may also be transferable to trainee surgeons. The ways in which the trainee surgeon moves from novice to expert need to be better understood so that this process can be expedited using current knowledge in other disciplines requiring the performance of complex fine motor tasks with high cognitive load under pressure.

A bio-hybrid DNA rotor-stator nanoengine that moves along predefined tracks.

PubMed

Valero, Julián; Pal, Nibedita; Dhakal, Soma; Walter, Nils G; Famulok, Michael

2018-06-01

Biological motors are highly complex protein assemblies that generate linear or rotary motion, powered by chemical energy. Synthetic motors based on DNA nanostructures, bio-hybrid designs or synthetic organic chemistry have been assembled. However, unidirectionally rotating biomimetic wheel motors with rotor-stator units that consume chemical energy are elusive. Here, we report a bio-hybrid nanoengine consisting of a catalytic stator that unidirectionally rotates an interlocked DNA wheel, powered by NTP hydrolysis. The engine consists of an engineered T7 RNA polymerase (T7RNAP-ZIF) attached to a dsDNA nanoring that is catenated to a rigid rotating dsDNA wheel. The wheel motor produces long, repetitive RNA transcripts that remain attached to the engine and are used to guide its movement along predefined ssDNA tracks arranged on a DNA nanotube. The simplicity of the design renders this walking nanoengine adaptable to other biological nanoarchitectures, facilitating the construction of complex bio-hybrid structures that achieve NTP-driven locomotion.

Matrikine and matricellular regulators of EGF Receptor signaling on cancer cell migration and invasion

PubMed Central

Grahovac, Jelena; Wells, Alan

2014-01-01

SYNOPSIS Cancer invasion is a complex process requiring, among other events, extensive remodeling of the extracellular matrix including deposition of pro-migratory and pro-proliferative moieties. In recent years it has been described that while invading through matrices cancer cells can change shape and adapt their migration strategies depending on the microenvironmental context. Although intracellular signaling pathways governing the mesenchymal to amoeboid migration shift and vice versa have been mostly elucidated, the extracellular signals promoting these shifts are largely unknown. In this review we summarize findings that point to matrikines that bind specifically to the EGF receptor as matricellular molecules that enable cancer cell migrational plasticity and promote invasion. PMID:24247562

Hemispheric Lateralization of Motor Thresholds in Relation to Stuttering

PubMed Central

Alm, Per A.; Karlsson, Ragnhild; Sundberg, Madeleine; Axelson, Hans W.

2013-01-01

Stuttering is a complex speech disorder. Previous studies indicate a tendency towards elevated motor threshold for the left hemisphere, as measured using transcranial magnetic stimulation (TMS). This may reflect a monohemispheric motor system impairment. The purpose of the study was to investigate the relative side-to-side difference (asymmetry) and the absolute levels of motor threshold for the hand area, using TMS in adults who stutter (n = 15) and in controls (n = 15). In accordance with the hypothesis, the groups differed significantly regarding the relative side-to-side difference of finger motor threshold (p = 0.0026), with the stuttering group showing higher motor threshold of the left hemisphere in relation to the right. Also the absolute level of the finger motor threshold for the left hemisphere differed between the groups (p = 0.049). The obtained results, together with previous investigations, provide support for the hypothesis that stuttering tends to be related to left hemisphere motor impairment, and possibly to a dysfunctional state of bilateral speech motor control. PMID:24146930

Voltage-Gated Potassium Channel Antibodies in Slow-Progression Motor Neuron Disease.

PubMed

Godani, Massimiliano; Zoccarato, Marco; Beronio, Alessandro; Zuliani, Luigi; Benedetti, Luana; Giometto, Bruno; Del Sette, Massimo; Raggio, Elisa; Baldi, Roberta; Vincent, Angela

2017-01-01

The spectrum of autoimmune neurological diseases associated with voltage-gated potassium channel (VGKC)-complex antibodies (Abs) ranges from peripheral nerve disorders to limbic encephalitis. Recently, low titers of VGKC-complex Abs have also been reported in neurodegenerative disorders, but their clinical relevance is unknown. The aim of the study was to explore the prevalence of VGKC-complex Abs in slow-progression motor neuron disease (MND). We compared 11 patients affected by slow-progression MND with 9 patients presenting typical progression illness. Sera were tested for VGKC-complex Abs by radioimmunoassay. The distribution of VGKC-complex Abs was analyzed with the Mann-Whitney U test. The statistical analysis showed a significant difference between the mean values in the study and control groups. A case with long-survival MND harboring VGKC-complex Abs and treated with intravenous immunoglobulins is described. Although VGKC-complex Abs are not likely to be pathogenic, these results could reflect the coexistence of an immunological activation in patients with slow disease progression. © 2016 S. Karger AG, Basel.

Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells

PubMed Central

Mukhtar, Eiman; Adhami, Vaqar Mustafa; Sechi, Mario; Mukhtar, Hasan

2015-01-01

Microtubule targeting based therapies have revolutionized cancer treatment; however, resistance and side effects remain a major limitation. Therefore, novel strategies that can overcome these limitations are urgently needed. We made a novel discovery that fisetin, a hydroxyflavone, is a microtubule stabilizing agent. Fisetin binds to tubulin and stabilizes microtubules with binding characteristics far superior than paclitaxel. Surface plasmon resonance and computational docking studies suggested that fisetin binds to β-tubulin with superior affinity compared to paclitaxel. Fisetin treatment of human prostate cancer cells resulted in robust up-regulation of microtubule associated proteins (MAP)-2 and -4. In addition, fisetin treated cells were enriched in α-tubulin acetylation, an indication of stabilization of microtubules. Fisetin significantly inhibited PCa cell proliferation, migration, and invasion. Nudc, a protein associated with microtubule motor dynein/dynactin complex that regulates microtubule dynamics, was inhibited with fisetin treatment. Further, fisetin treatment of a P-glycoprotein overexpressing multidrug-resistant cancer cell line NCI/ADR-RES inhibited the viability and colony formation. Our results offer in vitro proof-of-concept for fisetin as a microtubule targeting agent. We suggest that fisetin could be developed as an adjuvant for treatment of prostate and other cancer types. PMID:26235140

Top3-Rmi1 dissolve Rad51-mediated D-loops by a topoisomerase-based mechanism

PubMed Central

Fasching, Clare L.; Cejka, Petr; Kowalczykowski, Stephen C.; Heyer, Wolf-Dietrich

2015-01-01

Summary The displacement loop (D-loop) is the DNA strand invasion product formed during homologous recombination. Disruption of nascent D-loops represents a mechanism of anti-recombination. During Synthesis-Dependent Strand Annealing D-loop disruption after extension of the invading strand is an integral step of the pathway and ensures a non-crossover outcome. The proteins implicated in D-loop disruption are DNA motor proteins/helicases acting by migrating DNA junctions. Here we report an unanticipated mechanism of D-loop dissolution mediated by DNA topoisomerase 3 (Top3) and dependent on its catalytic activity. D-loop dissolution catalyzed by yeast Top3 is highly specific for yeast Rad51/Rad54-mediated D-loops, whereas protein-free D-loops or D-loop mediated by bacterial RecA protein or human RAD51/RAD54 resist dissolution. Also the human Topoisomerase IIIα-RMI1–RMI2 complex is capable of dissolving D-loops. Consistent with genetic data, we suggest that the extreme growth defect and hyper-recombination phenotype of Top3-deficient yeast cells is in part a result of unprocessed D-loops. PMID:25699708

Requirement of kinesin-mediated membrane transport of WAVE2 along microtubules for lamellipodia formation promoted by hepatocyte growth factor.

PubMed

Takahashi, Kazuhide; Suzuki, Katsuo

2008-07-01

Lamellipodia formation necessary for epithelial cell migration and invasion is accomplished by rearrangement of the actin cytoskeleton at the leading edge through membrane transport of WAVE2. However, how WAVE2 is transported to the cell periphery where lamellipodia are formed remains to be established. We report here that hepatocyte growth factor (HGF) promoted lamellipodia formation and intracellular transport of WAVE2 to the cell periphery, depending on Rac1 activity, in MDA-MB-231 human breast cancer cells. Immunoblot analyses indicating the coimmunoprecipitation of WAVE2 with kinesin heavy chain KIF5B, one of the motor proteins, and IQGAP1 suggest that KIF5B and IQGAP1 formed a complex with WAVE2 in serum-starved cells and increased in their amount after HGF stimulation. Both downregulation of KIF5B by the small interfering RNA and depolymerization of microtubules with nocodazole abrogated the HGF-induced lamellipodia formation and WAVE2 transport. Therefore, we propose here that the promotion of lamellipodia formation by HGF in MDA-MB-231 cells is Rac1-dependent and requires KIF5B-mediated transport of WAVE2 and IQGAP1 to the cell periphery along microtubules.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spiller, R.C.; Brown, M.L.; Phillips, S.F.

Emptying of the terminal ileum was assessed in 15 healthy humans by injecting technetium 99m-diethyltriaminopentaacetic acid into the bowel through a multilumen orocolonic tube. The subsequent arrival of isotope in the colon was quantified by gamma-scintigraphy and colonic filling curves were obtained. Studies were performed during fasting (n = 5) cnd 2.5 h after either a low residue meal (n = 5) or a meal made high in residue (n = 5) by adding 4 g of guar. The time for 50% of the isotope to reach the colon (T50) was significantly accelerated after both meals, being 72 +/- 15more » min for the high residue meal and 62 +/- 8 min for the low residue meal, compared with 183 +/- 37 min (p less than 0.01) in the 5 fasting subjects. Although the addition of guar did not alter T50 significantly, it did cause a significant fall in the rate of colonic filling, implying increased isotope dilution. Delay at the ileocolonic junction, as shown by plateaus in the middle of the colonic filling curves, was uncommon. Hold-up was significant in only 2 of 10 postprandial and 2 of 5 fasting studies. Rates of ileocolonic transit could not be related to either a mean ileal motility index or the occurrence of specific ileal motor patterns immediately proximal to the ileocolonic junction. Fasting ileocolonic transit was characteristically erratic but could not be related to interdigestive migrating motor complexes, which were rarely observed in the last 60 cm of ileum. We conclude that ileocolonic transit in humans is related to the rate at which material accumulates in the ileum, being rapid postprandially and slow and erratic during fasting. This method yields consistent results and could be used to define further factors that influence ileocolonic inflow.« less

Effect of Error Augmentation on Brain Activation and Motor Learning of a Complex Locomotor Task

PubMed Central

Marchal-Crespo, Laura; Michels, Lars; Jaeger, Lukas; López-Olóriz, Jorge; Riener, Robert

2017-01-01

Up to date, the functional gains obtained after robot-aided gait rehabilitation training are limited. Error augmenting strategies have a great potential to enhance motor learning of simple motor tasks. However, little is known about the effect of these error modulating strategies on complex tasks, such as relearning to walk after a neurologic accident. Additionally, neuroimaging evaluation of brain regions involved in learning processes could provide valuable information on behavioral outcomes. We investigated the effect of robotic training strategies that augment errors—error amplification and random force disturbance—and training without perturbations on brain activation and motor learning of a complex locomotor task. Thirty-four healthy subjects performed the experiment with a robotic stepper (MARCOS) in a 1.5 T MR scanner. The task consisted in tracking a Lissajous figure presented on a display by coordinating the legs in a gait-like movement pattern. Behavioral results showed that training without perturbations enhanced motor learning in initially less skilled subjects, while error amplification benefited better-skilled subjects. Training with error amplification, however, hampered transfer of learning. Randomly disturbing forces induced learning and promoted transfer in all subjects, probably because the unexpected forces increased subjects' attention. Functional MRI revealed main effects of training strategy and skill level during training. A main effect of training strategy was seen in brain regions typically associated with motor control and learning, such as, the basal ganglia, cerebellum, intraparietal sulcus, and angular gyrus. Especially, random disturbance and no perturbation lead to stronger brain activation in similar brain regions than error amplification. Skill-level related effects were observed in the IPS, in parts of the superior parietal lobe (SPL), i.e., precuneus, and temporal cortex. These neuroimaging findings indicate that gait-like motor learning depends on interplay between subcortical, cerebellar, and fronto-parietal brain regions. An interesting observation was the low activation observed in the brain's reward system after training with error amplification compared to training without perturbations. Our results suggest that to enhance learning of a locomotor task, errors should be augmented based on subjects' skill level. The impacts of these strategies on motor learning, brain activation, and motivation in neurological patients need further investigation. PMID:29021739

Invariant principles of speech motor control that are not language-specific.

PubMed

Chakraborty, Rahul

2012-12-01

Bilingual speakers must learn to modify their speech motor control mechanism based on the linguistic parameters and rules specified by the target language. This study examines if there are aspects of speech motor control which remain invariant regardless of the first (L1) and second (L2) language targets. Based on the age of academic exposure and proficiency in L2, 21 Bengali-English bilingual participants were classified into high (n = 11) and low (n = 10) L2 (English) proficiency groups. Using the Optotrak 3020 motion sensitive camera system, the lips and jaw movements were recorded while participants produced Bengali (L1) and English (L2) sentences. Based on kinematic analyses of the lip and jaw movements, two different variability measures (i.e., lip aperture and lower lip/jaw complex) were computed for English and Bengali sentences. Analyses demonstrated that the two groups of bilingual speakers produced lip aperture complexes (a higher order synergy) that were more consistent in co-ordination than were the lower lip/jaw complexes (a lower order synergy). Similar findings were reported earlier in monolingual English speakers by Smith and Zelaznik. Thus, this hierarchical organization may be viewed as a fundamental principle of speech motor control, since it is maintained even in bilingual speakers.

Cytoskeletal motor-driven active self-assembly in in vitro systems

DOE PAGES

Lam, A. T.; VanDelinder, V.; Kabir, A. M. R.; ...

2015-11-11

Molecular motor-driven self-assembly has been an active area of soft matter research for the past decade. Because molecular motors transform chemical energy into mechanical work, systems which employ molecular motors to drive self-assembly processes are able to overcome kinetic and thermodynamic limits on assembly time, size, complexity, and structure. Here, we review the progress in elucidating and demonstrating the rules and capabilities of motor-driven active self-assembly. Lastly, we focus on the types of structures created and the degree of control realized over these structures, and discuss the next steps necessary to achieve the full potential of this assembly mode whichmore » complements robotic manipulation and passive self-assembly.« less

Control of octopus arm extension by a peripheral motor program.

PubMed

Sumbre, G; Gutfreund, Y; Fiorito, G; Flash, T; Hochner, B

2001-09-07

For goal-directed arm movements, the nervous system generates a sequence of motor commands that bring the arm toward the target. Control of the octopus arm is especially complex because the arm can be moved in any direction, with a virtually infinite number of degrees of freedom. Here we show that arm extensions can be evoked mechanically or electrically in arms whose connection with the brain has been severed. These extensions show kinematic features that are almost identical to normal behavior, suggesting that the basic motor program for voluntary movement is embedded within the neural circuitry of the arm itself. Such peripheral motor programs represent considerable simplification in the motor control of this highly redundant appendage.

The Representation of Motor (Inter)action, States of Action, and Learning: Three Perspectives on Motor Learning by Way of Imagery and Execution

PubMed Central

Frank, Cornelia; Schack, Thomas

2017-01-01

Learning in intelligent systems is a result of direct and indirect interaction with the environment. While humans can learn by way of different states of (inter)action such as the execution or the imagery of an action, their unique potential to induce brain- and mind-related changes in the motor action system is still being debated. The systematic repetition of different states of action (e.g., physical and/or mental practice) and their contribution to the learning of complex motor actions has traditionally been approached by way of performance improvements. More recently, approaches highlighting the role of action representation in the learning of complex motor actions have evolved and may provide additional insight into the learning process. In the present perspective paper, we build on brain-related findings and sketch recent research on learning by way of imagery and execution from a hierarchical, perceptual-cognitive approach to motor control and learning. These findings provide insights into the learning of intelligent systems from a perceptual-cognitive, representation-based perspective and as such add to our current understanding of action representation in memory and its changes with practice. Future research should build bridges between approaches in order to more thoroughly understand functional changes throughout the learning process and to facilitate motor learning, which may have particular importance for cognitive systems research in robotics, rehabilitation, and sports. PMID:28588510

Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex

PubMed Central

Nebl, Thomas; Prieto, Judith Helena; Kapp, Eugene; Smith, Brian J.; Williams, Melanie J.; Yates, John R.; Cowman, Alan F.; Tonkin, Christopher J.

2011-01-01

Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+-dependent phosphorylation patterns on three of its components - GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component. PMID:21980283

New Developments in Understanding the Complexity of Human Speech Production.

PubMed

Simonyan, Kristina; Ackermann, Hermann; Chang, Edward F; Greenlee, Jeremy D

2016-11-09

Speech is one of the most unique features of human communication. Our ability to articulate our thoughts by means of speech production depends critically on the integrity of the motor cortex. Long thought to be a low-order brain region, exciting work in the past years is overturning this notion. Here, we highlight some of major experimental advances in speech motor control research and discuss the emerging findings about the complexity of speech motocortical organization and its large-scale networks. This review summarizes the talks presented at a symposium at the Annual Meeting of the Society of Neuroscience; it does not represent a comprehensive review of contemporary literature in the broader field of speech motor control. Copyright © 2016 the authors 0270-6474/16/3611440-09$15.00/0.

Impact of Discrete Corrections in a Modular Approach for Trajectory Generation in Quadruped Robots

NASA Astrophysics Data System (ADS)

Pinto, Carla M. A.; Santos, Cristina P.; Rocha, Diana; Matos, Vítor

2011-09-01

Online generation of trajectories in robots is a very complex task that involves the combination of different types of movements, i.e., distinct motor primitives. The later are used to model complex behaviors in robots, such as locomotion in irregular terrain and obstacle avoidance. In this paper, we consider two motor primitives: rhythmic and discrete. We study the effect on the robots' gaits of superimposing the two motor primitives, considering two distinct types of coupling. Additionally, we simulate two scenarios, where the discrete primitive is inserted in all of the four limbs, or is inserted in ipsilateral pairs of limbs. Numerical results show that amplitude and frequency of the periodic solutions, corresponding to the gaits trot and pace, are almost constant for diffusive and synaptic couplings.

Nonlinear analysis of dynamic signature

NASA Astrophysics Data System (ADS)

Rashidi, S.; Fallah, A.; Towhidkhah, F.

2013-12-01

Signature is a long trained motor skill resulting in well combination of segments like strokes and loops. It is a physical manifestation of complex motor processes. The problem, generally stated, is that how relative simplicity in behavior emerges from considerable complexity of perception-action system that produces behavior within an infinitely variable biomechanical and environmental context. To solve this problem, we present evidences which indicate that motor control dynamic in signing process is a chaotic process. This chaotic dynamic may explain a richer array of time series behavior in motor skill of signature. Nonlinear analysis is a powerful approach and suitable tool which seeks for characterizing dynamical systems through concepts such as fractal dimension and Lyapunov exponent. As a result, they can be analyzed in both horizontal and vertical for time series of position and velocity. We observed from the results that noninteger values for the correlation dimension indicates low dimensional deterministic dynamics. This result could be confirmed by using surrogate data tests. We have also used time series to calculate the largest Lyapunov exponent and obtain a positive value. These results constitute significant evidence that signature data are outcome of chaos in a nonlinear dynamical system of motor control.

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2014-09-01

810. 22. Plow EB, Carey JR, Nudo RJ, Pascual-Leone A (2009) Invasive cortical stimulation to promote recovery of function after stroke: A critical...stimulation of the motor cortex enhances pro- genitor cell migration in the adult rat brain. Exp Brain Res 231(2):165–177. 28. Edwardson MA, Lucas TH, Carey ...The screws and rod were further secured with dental acrylic (all animals). In both the ADS and OLS groups, a hybrid, 16-channel, single-shank, chronic

Results of an experiment to lead cranes on migration behind motorized ground vehicles

USGS Publications Warehouse

Ellis, D.H.; Clauss, B.; Watanabe, T.; Mykut, R.C.; Kinloch, M.; Ellis, Catherine H.; Urbanek, Richard P.; Stahlecker, Dale W.

1997-01-01

Ten greater sandhill cranes (Grus canadensis tabida), trained to enter and ride in a specially equipped truck, were transported at 80? days of age from their rearing site at Patuxent Wildlife Research Center (Patuxent), Maryland, to a reintroduction site located within the species? former breeding range in northern Arizona. After 5 additional weeks of training, these juvenile cranes were led south ca 600 km to a wintering area on the Arizona/Mexico border. Nine of the 10 survived the trek, 495 km of which was flown, although only a few cranes flew every stage of the route. Their longest flight was 77 km. Major problems during the migration were power line collisions (three, one fatal), eagle attacks (none fatal), and overheating (when air temperatures exceeded ca 25?C). All cranes that entered training quickly learned to follow the truck, and their tenacity when following under unfavorable conditions (e.g., poor light, extreme dust, or heat) showed that cranes could consistently be led over long distances. We cannot predict if the cranes will retrace their route unassisted when adults, but 2 cranes returned 130 km to the starting point of the migration after the flock was scattered by an eagle during our migration south. Three other cranes were recovered 55 km from the attack site and on course toward the starting point.

Multidisciplinary Interventions in Motor Neuron Disease

PubMed Central

Williams, U. E.; Philip-Ephraim, E. E.; Oparah, S. K.

2014-01-01

Motor neuron disease is a neurodegenerative disease characterized by loss of upper motor neuron in the motor cortex and lower motor neurons in the brain stem and spinal cord. Death occurs 2–4 years after the onset of the disease. A complex interplay of cellular processes such as mitochondrial dysfunction, oxidative stress, excitotoxicity, and impaired axonal transport are proposed pathogenetic processes underlying neuronal cell loss. Currently evidence exists for the use of riluzole as a disease modifying drug; multidisciplinary team care approach to patient management; noninvasive ventilation for respiratory management; botulinum toxin B for sialorrhoea treatment; palliative care throughout the course of the disease; and Modafinil use for fatigue treatment. Further research is needed in management of dysphagia, bronchial secretion, pseudobulbar affect, spasticity, cramps, insomnia, cognitive impairment, and communication in motor neuron disease. PMID:26317009

Neural correlates in the processing of phoneme-level complexity in vowel production.

PubMed

Park, Haeil; Iverson, Gregory K; Park, Hae-Jeong

2011-12-01

We investigated how articulatory complexity at the phoneme level is manifested neurobiologically in an overt production task. fMRI images were acquired from young Korean-speaking adults as they pronounced bisyllabic pseudowords in which we manipulated phonological complexity defined in terms of vowel duration and instability (viz., COMPLEX: /tiɯi/ > MID-COMPLEX: /tiye/ > SIMPLE: /tii/). Increased activity in the left inferior frontal gyrus (Brodmann Areas (BA) 44 and 47), supplementary motor area and anterior insula was observed for the articulation of COMPLEX sequences relative to MID-COMPLEX; this was the case with the articulation of MID-COMPLEX relative to SIMPLE, except that the pars orbitalis (BA 47) was dominantly identified in the Broca's area. The differentiation indicates that phonological complexity is reflected in the neural processing of distinct phonemic representations, both by recruiting brain regions associated with retrieval of phonological information from memory and via articulatory rehearsal for the production of COMPLEX vowels. In addition, the finding that increased complexity engages greater areas of the brain suggests that brain activation can be a neurobiological measure of articulo-phonological complexity, complementing, if not substituting for, biomechanical measurements of speech motor activity. 2011 Elsevier Inc. All rights reserved.

Motor Tics, Tourette Syndrome, and Learning Disabilities.

ERIC Educational Resources Information Center

Lerer, Robert J.

1987-01-01

Complex motor tics associated with vocal tics indicate a high likelihood of Tourette syndrome; children with this syndrome may also have learning disabilities and attentional disorders. Individuals may be treated with stimulant drugs which may precipitate or exacerbate tics. Pharmacotherapy is available for management of tics and attentional…

Waving of filaments induced by molecular motors

NASA Astrophysics Data System (ADS)

de Canio, Gabriele; Lauga, Eric; Goldstein, Raymond E.

2017-11-01

In many cellular phenomena, for example cytoplasmic streaming, molecular motors translocate along microtubules carrying cargoes which entrain fluid. The piconewton forces that motors produce can be sufficient to bend or buckle the filaments. When large numbers of such forced filaments interact through the surrounding fluid, as in particular stages of oocyte development in Drosophila melanogaster, complex dynamics are observed, but the mechanism underlying them has remained unclear. By using a combination of theory and numerical simulations, we study a simplified microtubules-molecular motor system in a viscous fluid and show that it can capture the wave-like filament motion dynamics observed in experiments.

Actin and microtubule-based cytoskeletal cues direct polarized targeting of proteins in neurons

PubMed Central

Arnold, Don B.

2010-01-01

Neuronal proteins are transported to either the axon or dendrites through the action of kinesin motors; however understanding of how cytoskeletal elements steer these cargo-motor complexes to one compartment or the other has remained elusive. Three recent developments, the discovery of an actin-based filter within the axon initial segment, the identification of the pivotal role played by myosin motors in dendritic targeting, and the determination of the properties of a kinesin motor that cause it to prefer axonal to dendritic microtubules, have now provided a structural framework for understanding polarized targeting in neurons. PMID:19671926

State Identification of Hoisting Motors Based on Association Rules for Quayside Container Crane

NASA Astrophysics Data System (ADS)

Li, Q. Z.; Gang, T.; Pan, H. Y.; Xiong, H.

2017-07-01

Quay container crane hoisting motor is a complex system, and the characteristics of long-term evolution and change of running status of there is a rule, and use it. Through association rules analysis, this paper introduced the similarity in association rules, and quay container crane hoisting motor status identification. Finally validated by an example, some rules change amplitude is small, regular monitoring, not easy to find, but it is precisely because of these small changes led to mechanical failure. Therefore, using the association rules change in monitoring the motor status has the very strong practical significance.

Molecular motor traffic: From biological nanomachines to macroscopic transport

NASA Astrophysics Data System (ADS)

Lipowsky, Reinhard; Chai, Yan; Klumpp, Stefan; Liepelt, Steffen; Müller, Melanie J. I.

2006-12-01

All cells of animals and plants contain complex transport systems based on molecular motors which walk along cytoskeletal filaments. These motors are rather small and have a size of 20-100 nm but are able to pull vesicles, organelles and other types of cargo over large distances, from micrometers up to meters. There are several families of motors: kinesins, dyneins, and myosins. Most of these motors have two heads which are used as legs and perform discrete steps along the filaments. Several aspects of the motor behavior will be discussed: motor cycles of two-headed motors; walks of single motors or cargo particles which consist of directed movements interrupted by random, diffusive motion; cargo transport through tube-like compartments; active diffusion of cargo particles in slab-like compartments; cooperative transport of cargo by several motors which may be uni- or bi-directional; and systems with many interacting motors that exhibit traffic jams, self-organized density and flux patterns, and traffic phase transitions far from equilibrium. It is necessary to understand these traffic phenomena in a quantitative manner in order to construct and optimize biomimetic transport systems based on motors and filaments with many possible applications in bioengineering, pharmacology, and medicine.

Multipathing Via Three Parameter Common Image Gathers (CIGs) From Reverse Time Migration

NASA Astrophysics Data System (ADS)

Ostadhassan, M.; Zhang, X.

2015-12-01

A noteworthy problem for seismic exploration is effects of multipathing (both wanted or unwanted) caused by subsurface complex structures. We show that reverse time migration (RTM) combined with a unified, systematic three parameter framework that flexibly handles multipathing can be accomplished by adding one more dimension (image time) to the angle domain common image gather (ADCIG) data. RTM is widely used to generate prestack depth migration images. When using the cross-correlation image condition in 2D prestack migration in RTM, the usual practice is to sum over all the migration time steps. Thus all possible wave types and paths automatically contribute to the resulting image, including destructive wave interferences, phase shifts, and other distortions. One reason is that multipath (prismatic wave) contributions are not properly sorted and mapped in the ADCIGs. Also, multipath arrivals usually have different instantaneous attributes (amplitude, phase and frequency), and if not separated, the amplitudes and phases in the final prestack image will not stack coherently across sources. A prismatic path satisfies an image time for it's unique path; Cavalca and Lailly (2005) show that RTM images with multipaths can provide more complete target information in complex geology, as multipaths usually have different incident angles and amplitudes compared to primary reflections. If the image time slices within a cross-correlation common-source migration are saved for each image time, this three-parameter (incident angle, depth, image time) volume can be post-processed to generate separate, or composite, images of any desired subset of the migrated data. Images can by displayed for primary contributions, any combination of primary and multipath contributions (with or without artifacts), or various projections, including the conventional ADCIG (angle vs depth) plane. Examples show that signal from the true structure can be separated from artifacts caused by multiple arrivals when they have different image times. This improves the quality of images and benefits migration velocity analysis (MVA) and amplitude variation with angle (AVA) inversion.

Submarine gas seepage in a mixed contractional and shear deformation regime: Cases from the Hikurangi oblique-subduction margin

NASA Astrophysics Data System (ADS)

Plaza-Faverola, Andreia; Pecher, Ingo; Crutchley, Gareth; Barnes, Philip M.; Bünz, Stefan; Golding, Thomas; Klaeschen, Dirk; Papenberg, Cord; Bialas, Joerg

2014-02-01

Gas seepage from marine sediments has implications for understanding feedbacks between the global carbon reservoir, seabed ecology, and climate change. Although the relationship between hydrates, gas chimneys, and seafloor seepage is well established, the nature of fluid sources and plumbing mechanisms controlling fluid escape into the hydrate zone and up to the seafloor remain one of the least understood components of fluid migration systems. In this study, we present the analysis of new three-dimensional high-resolution seismic data acquired to investigate fluid migration systems sustaining active seafloor seepage at Omakere Ridge, on the Hikurangi subduction margin, New Zealand. The analysis reveals at high resolution, complex overprinting fault structures (i.e., protothrusts, normal faults from flexural extension, and shallow (<1 km) arrays of oblique shear structures) implicated in fluid migration within the gas hydrate stability zone in an area of 2 × 7 km. In addition to fluid migration systems sustaining seafloor seepage on both sides of a central thrust fault, the data show seismic evidence for subseafloor gas-rich fluid accumulation associated with proto-thrusts and extensional faults. In these latter systems fluid pressure dissipation through time has been favored, hindering the development of gas chimneys. We discuss the elements of the distinct fluid migration systems and the influence that a complex partitioning of stress may have on the evolution of fluid flow systems in active subduction margins.

Quantitative analysis of random migration of cells using time-lapse video microscopy.

PubMed

Jain, Prachi; Worthylake, Rebecca A; Alahari, Suresh K

2012-05-13

Cell migration is a dynamic process, which is important for embryonic development, tissue repair, immune system function, and tumor invasion (1, 2). During directional migration, cells move rapidly in response to an extracellular chemotactic signal, or in response to intrinsic cues (3) provided by the basic motility machinery. Random migration occurs when a cell possesses low intrinsic directionality, allowing the cells to explore their local environment. Cell migration is a complex process, in the initial response cell undergoes polarization and extends protrusions in the direction of migration (2). Traditional methods to measure migration such as the Boyden chamber migration assay is an easy method to measure chemotaxis in vitro, which allows measuring migration as an end point result. However, this approach neither allows measurement of individual migration parameters, nor does it allow to visualization of morphological changes that cell undergoes during migration. Here, we present a method that allows us to monitor migrating cells in real time using video - time lapse microscopy. Since cell migration and invasion are hallmarks of cancer, this method will be applicable in studying cancer cell migration and invasion in vitro. Random migration of platelets has been considered as one of the parameters of platelet function (4), hence this method could also be helpful in studying platelet functions. This assay has the advantage of being rapid, reliable, reproducible, and does not require optimization of cell numbers. In order to maintain physiologically suitable conditions for cells, the microscope is equipped with CO(2) supply and temperature thermostat. Cell movement is monitored by taking pictures using a camera fitted to the microscope at regular intervals. Cell migration can be calculated by measuring average speed and average displacement, which is calculated by Slidebook software.

IQGAP1 Interacts with Components of the Slit Diaphragm Complex in Podocytes and Is Involved in Podocyte Migration and Permeability In Vitro

PubMed Central

Rigothier, Claire; Auguste, Patrick; Welsh, Gavin I.; Lepreux, Sébastien; Deminière, Colette; Mathieson, Peter W.; Saleem, Moin A.; Ripoche, Jean; Combe, Christian

2012-01-01

IQGAP1 is a scaffold protein that interacts with proteins of the cytoskeleton and the intercellular adhesion complex. In podocytes, IQGAP1 is associated with nephrin in the glomerular slit diaphragm (SD) complex, but its role remains ill-defined. In this work, we investigated the interaction of IQGAP1 with the cytoskeleton and SD proteins in podocytes in culture, and its role in podocyte migration and permeability. Expression, localization, and interactions between IQGAP1 and SD or cytoskeletal proteins were determined in cultured human podocytes by Western blot (WB), immunocytolocalization (IC), immunoprecipitation (IP), and In situ Proximity Ligation assay (IsPL). Involvement of IQGAP1 in migration and permeability was also assessed. IQGAP1 expression in normal kidney biopsies was studied by immunohistochemistry. IQGAP1 expression by podocytes increased during their in vitro differentiation. IC, IP, and IsPL experiments showed colocalizations and/or interactions between IQGAP1 and SD proteins (nephrin, MAGI-1, CD2AP, NCK 1/2, podocin), podocalyxin, and cytoskeletal proteins (α-actinin-4). IQGAP1 silencing decreased podocyte migration and increased the permeability of a podocyte layer. Immunohistochemistry on normal human kidney confirmed IQGAP1 expression in podocytes and distal tubular epithelial cells and also showed an expression in glomerular parietal epithelial cells. In summary, our results suggest that IQGAP1, through its interaction with components of SD and cytoskeletal proteins, is involved in podocyte barrier properties. PMID:22662192

Cognitive-motor interference during fine and gross motor tasks in children with Developmental Coordination Disorder (DCD).

PubMed

Schott, Nadja; El-Rajab, Inaam; Klotzbier, Thomas

2016-10-01

While typically developing children produce relatively automatized postural control processes, children with DCD seem to exhibit an automatization deficit. Dual tasks with various cognitive loads seem to be an effective way to assess the automatic deficit hypothesis. The aims of the study were: (1) to examine the effect of a concurrent cognitive task on fine and gross motor tasks in children with DCD, and (2) to determine whether the effect varied with different difficulty levels of the concurrent task. We examined dual-task performance (Trail-Making-Test, Trail-Walking-Test) in 20 children with DCD and 39 typically developing children. Based on the idea of the Trail-Making-Test, participants walked along a fixed pathway, following a prescribed path, delineated by target markers of (1) increasing sequential numbers, and (2) increasing sequential numbers and letters. The motor and cognitive dual-task effects (DTE) were calculated for each task. Regardless of the cognitive task, children with DCD performed equally well in fine and gross motor tasks, and were slower in the dual task conditions than under single task-conditions, compared with children without DCD. Increased cognitive task complexity resulted in slow trail walking as well as slower trail tracing. The motor interference for the gross motor tasks was least for the simplest conditions and greatest for the complex conditions and was more pronounced in children with DCD. Cognitive interference was low irrespective of the motor task. Children with DCD show a different approach to allocation of cognitive resources, and have difficulties making motor skills automatic. The latter notion is consistent with impaired cerebellar function and the "automatization deficit hypothesis", suggesting that any deficit in the automatization process will appear if conscious monitoring of the motor skill is made more difficult by integrating another task requiring attentional resources. Copyright © 2016 Elsevier Ltd. All rights reserved.

Delta II JPSS-1 Solid Rocket Motor Hoist and Mate

NASA Image and Video Library

2016-07-19

The United Launch Alliance/Orbital ATK Delta II solid rocket motor arrives at Space Launch Complex 2 at Vandenberg Air Force Base in California. Technicians and engineers lift and mate the solid rocket motor to a Delta II rocket in preparation for launch of the Joint Polar Satellite System-1 (JPSS-1) later this year. JPSS, a next-generation environmental satellite system, is a collaborative program between the National Oceanic and Atmospheric Administration (NOAA) and NASA.

Delta II JPSS-1 Solid Rocket Motor (SRM) Installation

NASA Image and Video Library

2017-04-04

The United Launch Alliance/Orbital ATK Delta II solid rocket motor arrives at Space Launch Complex 2 at Vandenberg Air Force Base in California. Technicians and engineers lift and mate the solid rocket motor to a Delta II rocket in preparation for launch of the Joint Polar Satellite System-1 (JPSS-1) later this year. JPSS, a next-generation environmental satellite system, is a collaborative program between the National Oceanic and Atmospheric Administration (NOAA) and NASA.

SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration.

PubMed

Sundararajan, Lakshmi; Norris, Megan L; Lundquist, Erik A

2015-05-28

The Q neuroblasts in Caenorhabditis elegans display left-right asymmetry in their migration, with QR and descendants on the right migrating anteriorly, and QL and descendants on the left migrating posteriorly. Initial QR and QL migration is controlled by the transmembrane receptors UNC-40/DCC, PTP-3/LAR, and the Fat-like cadherin CDH-4. After initial migration, QL responds to an EGL-20/Wnt signal that drives continued posterior migration by activating MAB-5/Hox activity in QL but not QR. QR expresses the transmembrane protein MIG-13, which is repressed by MAB-5 in QL and which drives anterior migration of QR descendants. A screen for new Q descendant AQR and PQR migration mutations identified mig-13 as well as hse-5, the gene encoding the glucuronyl C5-epimerase enzyme, which catalyzes epimerization of glucuronic acid to iduronic acid in the heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs). Of five C. elegans HSPGs, we found that only SDN-1/Syndecan affected Q migrations. sdn-1 mutants showed QR descendant AQR anterior migration defects, and weaker QL descendant PQR migration defects. hse-5 affected initial Q migration, whereas sdn-1 did not. sdn-1 and hse-5 acted redundantly in AQR and PQR migration, but not initial Q migration, suggesting the involvement of other HSPGs in Q migration. Cell-specific expression studies indicated that SDN-1 can act in QR to promote anterior migration. Genetic interactions between sdn-1, mig-13, and mab-5 suggest that MIG-13 and SDN-1 act in parallel to promote anterior AQR migration and that SDN-1 also controls posterior migration. Together, our results indicate previously unappreciated complexity in the role of multiple signaling pathways and inherent left-right asymmetry in the control of Q neuroblast descendant migration. Copyright © 2015 Sundararajan et al.

SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration

PubMed Central

Sundararajan, Lakshmi; Norris, Megan L.; Lundquist, Erik A.

2015-01-01

The Q neuroblasts in Caenorhabditis elegans display left-right asymmetry in their migration, with QR and descendants on the right migrating anteriorly, and QL and descendants on the left migrating posteriorly. Initial QR and QL migration is controlled by the transmembrane receptors UNC-40/DCC, PTP-3/LAR, and the Fat-like cadherin CDH-4. After initial migration, QL responds to an EGL-20/Wnt signal that drives continued posterior migration by activating MAB-5/Hox activity in QL but not QR. QR expresses the transmembrane protein MIG-13, which is repressed by MAB-5 in QL and which drives anterior migration of QR descendants. A screen for new Q descendant AQR and PQR migration mutations identified mig-13 as well as hse-5, the gene encoding the glucuronyl C5-epimerase enzyme, which catalyzes epimerization of glucuronic acid to iduronic acid in the heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs). Of five C. elegans HSPGs, we found that only SDN-1/Syndecan affected Q migrations. sdn-1 mutants showed QR descendant AQR anterior migration defects, and weaker QL descendant PQR migration defects. hse-5 affected initial Q migration, whereas sdn-1 did not. sdn-1 and hse-5 acted redundantly in AQR and PQR migration, but not initial Q migration, suggesting the involvement of other HSPGs in Q migration. Cell-specific expression studies indicated that SDN-1 can act in QR to promote anterior migration. Genetic interactions between sdn-1, mig-13, and mab-5 suggest that MIG-13 and SDN-1 act in parallel to promote anterior AQR migration and that SDN-1 also controls posterior migration. Together, our results indicate previously unappreciated complexity in the role of multiple signaling pathways and inherent left-right asymmetry in the control of Q neuroblast descendant migration. PMID:26022293

Coming out and Coming Back: Rural Gay Migration and the City

ERIC Educational Resources Information Center

Annes, Alexis; Redlin, Meredith

2012-01-01

This research focuses on the complex meaning and role of the city in American and French rural gay men's imaginary and life experience. It explores how gay men who grew up in the country build their sense of self through back-and-forth movement from rural to urban spaces. Therefore, it questions traditional gay migration studies, which have often…

Evaluation of mirrored muscle activity in patients with Complex Regional Pain Syndrome.

PubMed

Bank, Paulina J M; Peper, C Lieke E; Marinus, Johan; Beek, Peter J; van Hilten, Jacobus J

2014-10-01

Motor dysfunction in Complex Regional Pain Syndrome (CRPS) has been associated with bilateral changes in central motor processing, suggesting abnormal coupling between the affected and unaffected limb. We evaluated the occurrence of involuntary muscle activity in a limb during voluntary movements of the contralateral limb (i.e., mirror activity) in unilaterally affected patients to examine disinhibition of contralateral motor activity in CRPS. Mirror activity was examined during unimanual rhythmic flexion-extension movements of the wrist through in-depth analysis of electromyography recordings from the passive arm in 20 CRPS patients and 40 controls. The number of mirror-epochs was comparable for both arms in both CRPS patients and controls. Mirror-epochs in the affected arm of patients were comparable to those in controls. Mirror-epochs in the unaffected arm were shorter and showed less resemblance (in terms of rhythm and timing) to activity of the homologous muscle in the moving arm compared to mirror-epochs in controls. No evidence for disinhibition of contralateral motor activity was found during unimanual movement. Although motor dysfunction in CRPS has been associated with bilateral changes in cortical motor processing, the present findings argue against disinhibition of interhemispheric projections to homologous muscles in the contralateral limb during unimanual movement. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Xylose Migration During Tandem Mass Spectrometry of N-Linked Glycans

NASA Astrophysics Data System (ADS)

Hecht, Elizabeth S.; Loziuk, Philip L.; Muddiman, David C.

2017-04-01

Understanding the rearrangement of gas-phase ions via tandem mass spectrometry is critical to improving manual and automated interpretation of complex datasets. N-glycan analysis may be carried out under collision induced (CID) or higher energy collision dissociation (HCD), which favors cleavage at the glycosidic bond. However, fucose migration has been observed in tandem MS, leading to the formation of new bonds over four saccharide units away. In the following work, we report the second instance of saccharide migration ever to occur for N-glycans. Using horseradish peroxidase as a standard, the beta-1,2 xylose was observed to migrate from a hexose to a glucosamine residue on the (Xyl)Man3GlcNac2 glycan. This investigation was followed up in a complex N-linked glycan mixture derived from stem differentiating xylem tissue, and the rearranged product ion was observed for 75% of the glycans. Rearrangement was not favored in isomeric glycans with a core or antennae fucose and unobserved in glycans predicted to have a permanent core-fucose modification. As the first empirical observation of this rearrangement, this work warrants dissemination so it may be searched in de novo sequencing glycan workflows.

The nucleus is an intracellular propagator of tensile forces in NIH 3T3 fibroblasts

PubMed Central

Alam, Samer G.; Lovett, David; Kim, Dae In; Roux, Kyle J.; Dickinson, Richard B.; Lele, Tanmay P.

2015-01-01

ABSTRACT Nuclear positioning is a crucial cell function, but how a migrating cell positions its nucleus is not understood. Using traction-force microscopy, we found that the position of the nucleus in migrating fibroblasts closely coincided with the center point of the traction-force balance, called the point of maximum tension (PMT). Positioning of the nucleus close to the PMT required nucleus–cytoskeleton connections through linker of nucleoskeleton-to-cytoskeleton (LINC) complexes. Although the nucleus briefly lagged behind the PMT following spontaneous detachment of the uropod during migration, the nucleus quickly repositioned to the PMT within a few minutes. Moreover, traction-generating spontaneous protrusions deformed the nearby nucleus surface to pull the nuclear centroid toward the new PMT, and subsequent retraction of these protrusions relaxed the nuclear deformation and restored the nucleus to its original position. We propose that the protruding or retracting cell boundary transmits a force to the surface of the nucleus through the intervening cytoskeletal network connected by the LINC complexes, and that these forces help to position the nucleus centrally and allow the nucleus to efficiently propagate traction forces across the length of the cell during migration. PMID:25908852

Skill Acquisition in Physical Education: A Speculative Perspective

ERIC Educational Resources Information Center

Smith, Wayne W.

2011-01-01

How we learn motor skills has always been of interest to physical educators. Contemporary conceptual frameworks about motor skill learning draw from earlier behavioral and cognitive psychology learning theories. As a point of departure this paper foregrounds complexity theorizing, arguing that skill is contingent upon the performer's physical and…

Multiple Sensory-Motor Pathways Lead to Coordinated Visual Attention

ERIC Educational Resources Information Center

Yu, Chen; Smith, Linda B.

2017-01-01

Joint attention has been extensively studied in the developmental literature because of overwhelming evidence that the ability to socially coordinate visual attention to an object is essential to healthy developmental outcomes, including language learning. The goal of this study was to understand the complex system of sensory-motor behaviors that…

The Influence of Syllable Onset Complexity and Syllable Frequency on Speech Motor Control

ERIC Educational Resources Information Center

Riecker, Axel; Brendel, Bettina; Ziegler, Wolfram; Erb, Michael; Ackermann, Hermann

2008-01-01

Functional imaging studies have delineated a "minimal network for overt speech production," encompassing mesiofrontal structures (supplementary motor area, anterior cingulate gyrus), bilateral pre- and postcentral convolutions, extending rostrally into posterior parts of the inferior frontal gyrus (IFG) of the language-dominant hemisphere, left…

126. MOTOR CONTROL CENTER 1 (MCC1), FACING NORTH IN ROW ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

126. MOTOR CONTROL CENTER 1 (MCC-1), FACING NORTH IN ROW OF ELECTRICAL CABINETS JUST SOUTH OF TRANSFORMER SUBSTATION CABINETS IN TRANSFORMER ROOM (112), LSB (BLDG. 770) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Sleep-Dependent Learning and Motor-Skill Complexity

ERIC Educational Resources Information Center

Kuriyama, Kenichi; Stickgold, Robert; Walker, Matthew P.

2004-01-01

Learning of a procedural motor-skill task is known to progress through a series of unique memory stages. Performance initially improves during training, and continues to improve, without further rehearsal, across subsequent periods of sleep. Here, we investigate how this delayed sleep-dependent learning is affected when the task characteristics…

Immediate Effect of Alcohol on Voice Tremor Parameters and Speech Motor Control

ERIC Educational Resources Information Center

Krishnan, Gayathri; Ghosh, Vipin

2017-01-01

The complex neuro-muscular interplay of speech subsystems is susceptible to alcohol intoxication. Published reports have studied language formulation and fundamental frequency measures pre- and post-intoxication. This study aimed at tapping the speech motor control measure using rate, consistency, and accuracy measures of diadochokinesis and…

Spatial distribution of filament elasticity determines the migratory behaviors of a cell

PubMed Central

Harn, Hans I-Chen; Hsu, Chao-Kai; Wang, Yang-Kao; Huang, Yi-Wei; Chiu, Wen-Tai; Lin, Hsi-Hui; Cheng, Chao-Min; Tang, Ming-Jer

2016-01-01

ABSTRACT Any cellular response leading to morphological changes is highly tuned to balance the force generated from structural reorganization, provided by actin cytoskeleton. Actin filaments serve as the backbone of intracellular force, and transduce external mechanical signal via focal adhesion complex into the cell. During migration, cells not only undergo molecular changes but also rapid mechanical modulation. Here we focus on determining, the role of spatial distribution of mechanical changes of actin filaments in epithelial, mesenchymal, fibrotic and cancer cells with non-migration, directional migration, and non-directional migration behaviors using the atomic force microscopy. We found 1) non-migratory cells only generated one type of filament elasticity, 2) cells generating spatially distributed two types of filament elasticity showed directional migration, and 3) pathologic cells that autonomously generated two types of filament elasticity without spatial distribution were actively migrating non-directionally. The demonstration of spatial regulation of filament elasticity of different cell types at the nano-scale highlights the coupling of cytoskeletal function with physical characters at the sub-cellular level, and provides new research directions for migration related disease. PMID:26919488

Functional Coordination of WAVE and WASP in C. elegans Neuroblast Migration.

PubMed

Zhu, Zhiwen; Chai, Yongping; Jiang, Yuxiang; Li, Wenjing; Hu, Huifang; Li, Wei; Wu, Jia-Wei; Wang, Zhi-Xin; Huang, Shanjin; Ou, Guangshuo

2016-10-24

Directional cell migration is critical for metazoan development. We define two molecular pathways that activate the Arp2/3 complex during neuroblast migration in Caenorhabditis elegans. The transmembrane protein MIG-13/Lrp12 is linked to the Arp2/3 nucleation-promoting factors WAVE or WASP through direct interactions with ABL-1 or SEM-5/Grb2, respectively. WAVE mutations partially impaired F-actin organization and decelerated cell migration, and WASP mutations did not inhibit cell migration but enhanced migration defects in WAVE-deficient cells. Purified SEM-5 and MIG-2 synergistically stimulated the F-actin branching activity of WASP-Arp2/3 in vitro. In GFP knockin animals, WAVE and WASP were largely organized into separate clusters at the leading edge, and the amount of WASP was less than WAVE but could be elevated by WAVE mutations. Our results indicate that the MIG-13-WAVE pathway provides the major force for directional cell motility, whereas MIG-13-WASP partially compensates for its loss, underscoring their coordinated activities in facilitating robust cell migration. Copyright © 2016 Elsevier Inc. All rights reserved.

A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the CNS.

PubMed

Amodeo, Valeria; A, Deli; Betts, Joanne; Bartesaghi, Stefano; Zhang, Ying; Richard-Londt, Angela; Ellis, Matthew; Roshani, Rozita; Vouri, Mikaella; Galavotti, Sara; Oberndorfer, Sarah; Leite, Ana Paula; Mackay, Alan; Lampada, Aikaterini; Stratford, Eva Wessel; Li, Ningning; Dinsdale, David; Grimwade, David; Jones, Chris; Nicotera, Pierluigi; Michod, David; Brandner, Sebastian; Salomoni, Paolo

2017-07-11

Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain. The PML pro-migratory role is active also in transformed mouse NPCs and in human primary GBM cells. In both normal and neoplastic settings, PML controls cell migration via Polycomb repressive complex 2 (PRC2)-mediated repression of Slits, key regulators of axon guidance. Finally, a PML/SLIT1 axis regulates sensitivity to the PML-targeting drug arsenic trioxide in primary GBM cells. Taken together, these findings uncover a drug-targetable molecular axis controlling cell migration in both normal and neoplastic cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Migrants, refugees and insecurity. Current threats to peace?

PubMed

Lohrmann, R

2000-01-01

Since the early 1980s, international migration has moved beyond humanitarian, economic development, labor market and societal integration concerns, raising complex interactive security implications for governments of migrant sending, receiving and transit countries, as well as for multilateral bodies. This article examines the effects of international migration on varied understandings and perceptions of international security. It discusses why international migration has come to be perceived as a security issue, both in industrialized and developing countries. Questions are raised on the migration-security nexus and the way in which the concepts "security" and "migration" are used. The real and perceived impacts of international migration upon national and regional security, both in industrialized and developing countries, are analyzed. The policies developed by governments and multilateral agencies since the mid-1980s to mitigate the destabilizing effects of certain kinds of international population movement and human displacement are examined. The conclusions stress the need for the establishment of a comprehensive framework of international cooperation among origin and receiving countries and international organizations to address the destabilizing implications of international migration.

Prestack depth migration for complex 2D structure using phase-screen propagators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, P.; Huang, Lian-Jie; Burch, C.

1997-11-01

We present results for the phase-screen propagator method applied to prestack depth migration of the Marmousi synthetic data set. The data were migrated as individual common-shot records and the resulting partial images were superposed to obtain the final complete Image. Tests were performed to determine the minimum number of frequency components required to achieve the best quality image and this in turn provided estimates of the minimum computing time. Running on a single processor SUN SPARC Ultra I, high quality images were obtained in as little as 8.7 CPU hours and adequate images were obtained in as little as 4.4more » CPU hours. Different methods were tested for choosing the reference velocity used for the background phase-shift operation and for defining the slowness perturbation screens. Although the depths of some of the steeply dipping, high-contrast features were shifted slightly the overall image quality was fairly insensitive to the choice of the reference velocity. Our jests show the phase-screen method to be a reliable and fast algorithm for imaging complex geologic structures, at least for complex 2D synthetic data where the velocity model is known.« less

Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria.

PubMed

Popov-Celeketić, Dusan; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

2008-05-21

The TIM23 (translocase of the mitochondrial inner membrane) complex mediates translocation of preproteins across and their insertion into the mitochondrial inner membrane. How the translocase mediates sorting of preproteins into the two different subcompartments is poorly understood. In particular, it is not clear whether association of two operationally defined parts of the translocase, the membrane-integrated part and the import motor, depends on the activity state of the translocase. We established conditions to in vivo trap the TIM23 complex in different translocation modes. Membrane-integrated part of the complex and import motor were always found in one complex irrespective of whether an arrested preprotein was present or not. Instead, we detected different conformations of the complex in response to the presence and, importantly, the type of preprotein being translocated. Two non-essential subunits of the complex, Tim21 and Pam17, modulate its activity in an antagonistic manner. Our data demonstrate that the TIM23 complex acts as a single structural and functional entity that is actively remodelled to sort preproteins into different mitochondrial subcompartments.

Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria

PubMed Central

Popov-Čeleketić, Dus̆an; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

2008-01-01

The TIM23 (translocase of the mitochondrial inner membrane) complex mediates translocation of preproteins across and their insertion into the mitochondrial inner membrane. How the translocase mediates sorting of preproteins into the two different subcompartments is poorly understood. In particular, it is not clear whether association of two operationally defined parts of the translocase, the membrane-integrated part and the import motor, depends on the activity state of the translocase. We established conditions to in vivo trap the TIM23 complex in different translocation modes. Membrane-integrated part of the complex and import motor were always found in one complex irrespective of whether an arrested preprotein was present or not. Instead, we detected different conformations of the complex in response to the presence and, importantly, the type of preprotein being translocated. Two non-essential subunits of the complex, Tim21 and Pam17, modulate its activity in an antagonistic manner. Our data demonstrate that the TIM23 complex acts as a single structural and functional entity that is actively remodelled to sort preproteins into different mitochondrial subcompartments. PMID:18418384

Research Techniques Made Simple: Analysis of Collective Cell Migration Using the Wound Healing Assay.

PubMed

Grada, Ayman; Otero-Vinas, Marta; Prieto-Castrillo, Francisco; Obagi, Zaidal; Falanga, Vincent

2017-02-01

Collective cell migration is a hallmark of wound repair, cancer invasion and metastasis, immune responses, angiogenesis, and embryonic morphogenesis. Wound healing is a complex cellular and biochemical process necessary to restore structurally damaged tissue. It involves dynamic interactions and crosstalk between various cell types, interaction with extracellular matrix molecules, and regulated production of soluble mediators and cytokines. In cutaneous wound healing, skin cells migrate from the wound edges into the wound to restore skin integrity. Analysis of cell migration in vitro is a useful assay to quantify alterations in cell migratory capacity in response to experimental manipulations. Although several methods exist to study cell migration (such as Boyden chamber assay, barrier assays, and microfluidics-based assays), in this short report we will explain the wound healing assay, also known as the "in vitro scratch assay" as a simple, versatile, and cost-effective method to study collective cell migration and wound healing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Migration and mental health: An interface

PubMed Central

Virupaksha, H. G.; Kumar, Ashok; Nirmala, Bergai Parthsarathy

2014-01-01

Migration is a universal phenomenon, which existed with the subsistence of the human beings on earth. People migrate from one place to another for several reasons, but the goal or main reason behind changing the residence would be improving their living conditions or to escape from debts and poverty. Migration is also a social phenomenon which influences human life and the environment around. Hence, migration has a great impact on any geographical area and it is known as one of the three basic components of population growth of any particular region (the other two are, mortality and fertility). Migration involves certain phases to go through; hence, it is a process. Many times, lack of preparedness, difficulties in adjusting to the new environment, the complexity of the local system, language difficulties, cultural disparities and adverse experiences would cause distress to the migrants. Moreover subsequently it has a negative impact on mental well-being of such population. Due to globalization, modernization, improved technologies and developments in all the sectors, the migration and its impact on human well-being is a contemporary issue; hence, here is an attempt to understand the migration and its impact on the mental health of the migrants based on the studies conducted around. PMID:25097389

Emerging migration flows in a changing climate in dryland Africa

NASA Astrophysics Data System (ADS)

Kniveton, Dominic R.; Smith, Christopher D.; Black, Richard

2012-06-01

Fears of the movement of large numbers of people as a result of changes in the environment were first voiced in the 1980s (ref. ). Nearly thirty years later the numbers likely to migrate as a result of the impacts of climate change are still, at best, guesswork. Owing to the high prevalence of rainfed agriculture, many livelihoods in sub-Saharan African drylands are particularly vulnerable to changes in climate. One commonly adopted response strategy used by populations to deal with the resulting livelihood stress is migration. Here, we use an agent-based model developed around the theory of planned behaviour to explore how climate and demographic change, defined by the ENSEMBLES project and the United Nations Statistics Division of the Department of Economic and Social Affairs, combine to influence migration within and from Burkina Faso. The emergent migration patterns modelled support framing the nexus of climate change and migration as a complex adaptive system. Using this conceptual framework, we show that the extent of climate-change-related migration is likely to be highly nonlinear and the extent of this nonlinearity is dependent on population growth; therefore supporting migration policy interventions based on both demographic and climate change adaptation.

Migration and depressive symptoms in migrant-sending areas: findings from the survey of internal migration and health in China.

PubMed

Lu, Yao; Hu, Peifeng; Treiman, Donald J

2012-08-01

China has experienced large-scale internal migration and growing mental health disorders. Limited research has examined the relationship between the two processes. We examined the association between labor out-migration and depressive symptoms of family members left behind in migrant-sending areas. We conducted a multistage probability sample survey of Chinese adults in 2008 ("Internal Migration and Health in China"), including 787 people in rural migrant-sending areas. To study whether adults in out-migrant households were more likely to experience depressive symptoms (CES-D) than were adults in non-migrant households, we used multivariate regressions and adjusted for a wide range of confounding factors and for the complex sampling design. Adults in households with labor out-migrants were more likely to report depressive symptoms than those in households without out-migrants, presumably a result of the absence of family members. However, monetary remittances from labor migrants buffered the mental health costs of out-migration. Labor out-migration has important consequences for the mental health in migrant-sending communities. There is an urgent need to address the psychological costs of migration and to promote regular remittances.

Beyond greener pastures: exploring contexts surrounding Filipino nurse migration in Canada through oral history.

PubMed

Ronquillo, Charlene; Boschma, Geertje; Wong, Sabrina T; Quiney, Linda

2011-09-01

The history of immigrant Filipino nurses in Canada has received little attention, yet Canada is a major receiving country of a growing number of Filipino migrants and incorporates Filipino immigrant nurses into its healthcare workforce at a steady rate. This study aims to look beyond the traditional economic and policy analysis perspectives of global migration and beyond the push and pull factors commonly discussed in the migration literature. Through oral history, this study explores biographical histories of nine Filipino immigrant nurses currently working in British Columbia and Alberta, Canada. Narratives reveal the instrumental role of the deeply embedded culture of migration in the Philippines in influencing Filipino nurses to migrate. Additionally, the stories illustrate the weight of cultural pressures and societal constructs these nurses faced that first colored their decision to pursue a career in nursing and ultimately to pursue emigration. Oral history is a powerful tool for examining migration history and sheds light on nuances of experience that might otherwise be neglected. This study explores the complex connections between various factors motivating Filipino nurse migration, the decision-making process, and other pre-migration experiences. © 2011 Blackwell Publishing Ltd.

Modal Survey of ETM-3, A 5-Segment Derivative of the Space Shuttle Solid Rocket Booster

NASA Technical Reports Server (NTRS)

Nielsen, D.; Townsend, J.; Kappus, K.; Driskill, T.; Torres, I.; Parks, R.

2005-01-01

The complex interactions between internal motor generated pressure oscillations and motor structural vibration modes associated with the static test configuration of a Reusable Solid Rocket Motor have potential to generate significant dynamic thrust loads in the 5-segment configuration (Engineering Test Motor 3). Finite element model load predictions for worst-case conditions were generated based on extrapolation of a previously correlated 4-segment motor model. A modal survey was performed on the largest rocket motor to date, Engineering Test Motor #3 (ETM-3), to provide data for finite element model correlation and validation of model generated design loads. The modal survey preparation included pretest analyses to determine an efficient analysis set selection using the Effective Independence Method and test simulations to assure critical test stand component loads did not exceed design limits. Historical Reusable Solid Rocket Motor modal testing, ETM-3 test analysis model development and pre-test loads analyses, as well as test execution, and a comparison of results to pre-test predictions are discussed.

Global thermal analysis of air-air cooled motor based on thermal network

NASA Astrophysics Data System (ADS)

Hu, Tian; Leng, Xue; Shen, Li; Liu, Haidong

2018-02-01

The air-air cooled motors with high efficiency, large starting torque, strong overload capacity, low noise, small vibration and other characteristics, are widely used in different department of national industry, but its cooling structure is complex, it requires the motor thermal management technology should be high. The thermal network method is a common method to calculate the temperature field of the motor, it has the advantages of small computation time and short time consuming, it can save a lot of time in the initial design phase of the motor. The domain analysis of air-air cooled motor and its cooler was based on thermal network method, the combined thermal network model was based, the main components of motor internal and external cooler temperature were calculated and analyzed, and the temperature rise test results were compared to verify the correctness of the combined thermal network model, the calculation method can satisfy the need of engineering design, and provide a reference for the initial and optimum design of the motor.

Downregulation of ROCK2 through nanocomplex sensitizes the cytotoxic effect of temozolomide in U251 glioma cells.

PubMed

Wen, Xiaojun; Huang, Amin; Liu, Zhonglin; Liu, Yunyun; Hu, Jingyang; Liu, Jun; Shuai, Xintao

2014-01-01

Rho-associated coiled-coil kinase 2 (ROCK2) is an attractive therapeutic target because it is overexpressed in many malignancies, including glioma. Therefore, we designed the current study to determine whether the downregulation of ROCK2 would sensitize the cytotoxic effect of temozolomide (TMZ) in U251 cells. Glycol-polyethyleneimine (PEG-PEI) was used to deliver siROCK2 to U251 cells, and the physical characteristics of the PEG-PEI/siROCK2 complex (referred to as the siROCK2 complex) were investigated. The transfection efficiency and cell uptake were determined by flow cytometry (FCM) and confocal laser microscopy (CLSM), respectively. U251 cells were then treated with 100 μM TMZ, siROCK2 complexes or their combination. The apoptosis rate and cell migration were measured by FCM and wound-healing assay, respectively. The levels of Bax, Bcl-2, cleaved caspase-3, MMP-2, and MMP-9 were detected to analyze the degrees of apoptosis and migration. Our results revealed that the characteristics of the siROCK2 complexes depended closely on the N/P ratios. PEG-PEI served as a good vector for siROCK2 and exhibited low cytotoxicity toward U251 cells. The CLSM assay showed that the siROCK2 complexes were successfully uptaken and that both the protein and mRNA levels of ROCK2 were significantly suppressed. Furthermore, the combination treatment induced a higher apoptosis rate and markedly increased the gap distance of U251 cells in the wound-healing assay. Levels of the proapoptotic proteins Bax and cleaved caspase-3 were significantly increased, whereas levels of the antiapoptotic protein Bcl-2 and the migration-related proteins MMP-2 and MMP-9 were significantly reduced by the combination treatment compared with either treatment alone. In conclusion, our results demonstrate that the combination of TMZ and siROCK2 effectively induces apoptosis and inhibits the migration of U251 cells. Therefore, the combination of TMZ and siROCK2 complex is a potential therapeutic approach for human glioma.

Downregulation of ROCK2 through Nanocomplex Sensitizes the Cytotoxic Effect of Temozolomide in U251 Glioma Cells

PubMed Central

Liu, Yunyun; Hu, Jingyang; Liu, Jun; Shuai, Xintao

2014-01-01

Objective Rho-associated coiled-coil kinase 2 (ROCK2) is an attractive therapeutic target because it is overexpressed in many malignancies, including glioma. Therefore, we designed the current study to determine whether the downregulation of ROCK2 would sensitize the cytotoxic effect of temozolomide (TMZ) in U251 cells. Methods Glycol-polyethyleneimine (PEG-PEI) was used to deliver siROCK2 to U251 cells, and the physical characteristics of the PEG-PEI/siROCK2 complex (referred to as the siROCK2 complex) were investigated. The transfection efficiency and cell uptake were determined by flow cytometry (FCM) and confocal laser microscopy (CLSM), respectively. U251 cells were then treated with 100 μM TMZ, siROCK2 complexes or their combination. The apoptosis rate and cell migration were measured by FCM and wound-healing assay, respectively. The levels of Bax, Bcl-2, cleaved caspase-3, MMP-2, and MMP-9 were detected to analyze the degrees of apoptosis and migration. Results Our results revealed that the characteristics of the siROCK2 complexes depended closely on the N/P ratios. PEG-PEI served as a good vector for siROCK2 and exhibited low cytotoxicity toward U251 cells. The CLSM assay showed that the siROCK2 complexes were successfully uptaken and that both the protein and mRNA levels of ROCK2 were significantly suppressed. Furthermore, the combination treatment induced a higher apoptosis rate and markedly increased the gap distance of U251 cells in the wound-healing assay. Levels of the proapoptotic proteins Bax and cleaved caspase-3 were significantly increased, whereas levels of the antiapoptotic protein Bcl-2 and the migration-related proteins MMP-2 and MMP-9 were significantly reduced by the combination treatment compared with either treatment alone. Conclusions In conclusion, our results demonstrate that the combination of TMZ and siROCK2 effectively induces apoptosis and inhibits the migration of U251 cells. Therefore, the combination of TMZ and siROCK2 complex is a potential therapeutic approach for human glioma. PMID:24642531

Structure of the active form of human origin recognition complex and its ATPase motor module

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tocilj, Ante; On, Kin Fan; Yuan, Zuanning

Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of the active form of human ORC determined by X-ray crystallography and cryo-electron microscopy. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes. A second lobe contains the ORC2/3 subunits. The complex is organized as a double-layered shallow corkscrew, with the AAA+ and AAA+-like domains forming one layer, and the winged-helix domains (WHDs) forming a topmore » layer. CDC6 fits easily between ORC1 and ORC2, completing the ring and the DNA-binding channel, forming an additional ATP hydrolysis site. Analysis of the ATPase activity of the complex provides a basis for understanding ORC activity as well as molecular defects observed in Meier-Gorlin Syndrome mutations.« less

A multicenter examination and strategic revisions of the Yale Global Tic Severity Scale.

PubMed

McGuire, Joseph F; Piacentini, John; Storch, Eric A; Murphy, Tanya K; Ricketts, Emily J; Woods, Douglas W; Walkup, John W; Peterson, Alan L; Wilhelm, Sabine; Lewin, Adam B; McCracken, James T; Leckman, James F; Scahill, Lawrence

2018-05-08

To examine the internal consistency and distribution of the Yale Global Tic Severity Scale (YGTSS) scores to inform modification of the measure. This cross-sectional study included 617 participants with a tic disorder (516 children and 101 adults), who completed an age-appropriate diagnostic interview and the YGTSS to evaluate tic symptom severity. The distributions of scores on YGTSS dimensions were evaluated for normality and skewness. For dimensions that were skewed across motor and phonic tics, a modified Delphi consensus process was used to revise selected anchor points. Children and adults had similar clinical characteristics, including tic symptom severity. All participants were examined together. Strong internal consistency was identified for the YGTSS Motor Tic score (α = 0.80), YGTSS Phonic Tic score (α = 0.87), and YGTSS Total Tic score (α = 0.82). The YGTSS Total Tic and Impairment scores exhibited relatively normal distributions. Several subscales and individual item scales departed from a normal distribution. Higher scores were more often used on the Motor Tic Number, Frequency, and Intensity dimensions and the Phonic Tic Frequency dimension. By contrast, lower scores were more often used on Motor Tic Complexity and Interference, and Phonic Tic Number, Intensity, Complexity, and Interference. The YGTSS exhibits good internal consistency across children and adults. The parallel findings across Motor and Phonic Frequency, Complexity, and Interference dimensions prompted minor revisions to the anchor point description to promote use of the full range of scores in each dimension. Specific minor revisions to the YGTSS Phonic Tic Symptom Checklist were also proposed. © 2018 American Academy of Neurology.

Prosthetic Avian Vocal Organ Controlled by a Freely Behaving Bird Based on a Low Dimensional Model of the Biomechanical Periphery

PubMed Central

Arneodo, Ezequiel M.; Perl, Yonatan Sanz; Goller, Franz; Mindlin, Gabriel B.

2012-01-01

Because of the parallels found with human language production and acquisition, birdsong is an ideal animal model to study general mechanisms underlying complex, learned motor behavior. The rich and diverse vocalizations of songbirds emerge as a result of the interaction between a pattern generator in the brain and a highly nontrivial nonlinear periphery. Much of the complexity of this vocal behavior has been understood by studying the physics of the avian vocal organ, particularly the syrinx. A mathematical model describing the complex periphery as a nonlinear dynamical system leads to the conclusion that nontrivial behavior emerges even when the organ is commanded by simple motor instructions: smooth paths in a low dimensional parameter space. An analysis of the model provides insight into which parameters are responsible for generating a rich variety of diverse vocalizations, and what the physiological meaning of these parameters is. By recording the physiological motor instructions elicited by a spontaneously singing muted bird and computing the model on a Digital Signal Processor in real-time, we produce realistic synthetic vocalizations that replace the bird's own auditory feedback. In this way, we build a bio-prosthetic avian vocal organ driven by a freely behaving bird via its physiologically coded motor commands. Since it is based on a low-dimensional nonlinear mathematical model of the peripheral effector, the emulation of the motor behavior requires light computation, in such a way that our bio-prosthetic device can be implemented on a portable platform. PMID:22761555

Detection of Ludic Patterns in Two Triadic Motor Games and Differences in Decision Complexity

PubMed Central

Aguilar, Miguel Pic; Navarro-Adelantado, Vicente; Jonsson, Gudberg K.

2018-01-01

The triad is a particular structure in which an ambivalent social relationship takes place. This work is focused on the search of behavioral regularities in the practice of motor games in triad, which is a little known field. For the detection of behavioral patterns not visible to the naked eye, we use Theme. A chasing games model was followed, with rules, and in two different structures (A↔B↔C↔A and A → B → C → A) on four class groups (two for each structure), for a total of 84, 12, and 13 year old secondary school students, 37 girls (44%) and 47 boys (56%). The aim was to examine if the players' behavior, in relation to the triad structure, matches with any ludic behavior patterns. An observational methodology was applied, with a nomothetic, punctual and multidimensional design. The intra and inter-evaluative correlation coefficients and the generalizability theory ensured the quality of the data. A mixed behavioral role system was used (four criteria and 15 categories), and the pattern detection software Theme was applied to detect temporal regularities in the order of event occurrences. The results show that time location of motor responses in triad games was not random. In the “maze” game we detected more complex ludic patterns than the “three fields” game, which might be explained by means of structural determinants such as circulation. This research points out the decisional complexity in motor games, and it confirms the differences among triads from the point of view of motor communication. PMID:29354084

A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis.

PubMed

Zhao, Zhong; Lange, Dale J; Voustianiouk, Andrei; MacGrogan, Donal; Ho, Lap; Suh, Jason; Humala, Nelson; Thiyagarajan, Meenakshisundaram; Wang, Jun; Pasinetti, Giulio M

2006-04-03

The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization. SOD1-G93A transgenic ALS mice were fed a ketogenic diet (KD) based on known formulations for humans. Motor performance, longevity, and motor neuron counts were measured in treated and disease controls. Because mitochondrial dysfunction plays a central role in neuronal cell death in ALS, we also studied the effect that the principal ketone body, D-beta-3 hydroxybutyrate (DBH), has on mitochondrial ATP generation and neuroprotection. Blood ketones were > 3.5 times higher in KD fed animals compared to controls. KD fed mice lost 50% of baseline motor performance 25 days later than disease controls. KD animals weighed 4.6 g more than disease control animals at study endpoint; the interaction between diet and change in weight was significant (p = 0.047). In spinal cord sections obtained at the study endpoint, there were more motor neurons in KD fed animals (p = 0.030). DBH prevented rotenone mediated inhibition of mitochondrial complex I but not malonate inhibition of complex II. Rotenone neurotoxicity in SMI-32 immunopositive motor neurons was also inhibited by DBH. This is the first study showing that diet, specifically a KD, alters the progression of the clinical and biological manifestations of the G93A SOD1 transgenic mouse model of ALS. These effects may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain.

Impact of density-dependent migration flows on epidemic outbreaks in heterogeneous metapopulations

NASA Astrophysics Data System (ADS)

Ripoll, J.; Avinyó, A.; Pellicer, M.; Saldaña, J.

2015-08-01

We investigate the role of migration patterns on the spread of epidemics in complex networks. We enhance the SIS-diffusion model on metapopulations to a nonlinear diffusion. Specifically, individuals move randomly over the network but at a rate depending on the population of the departure patch. In the absence of epidemics, the migration-driven equilibrium is described by quantifying the total number of individuals living in heavily or lightly populated areas. Our analytical approach reveals that strengthening the migration from populous areas contains the infection at the early stage of the epidemic. Moreover, depending on the exponent of the nonlinear diffusion rate, epidemic outbreaks do not always occur in the most populated areas as one might expect.

Characterization of oxygen vacancies and their migration in Ba-doped Pb(Zr0.52Ti0.48)O3 ferroelectrics

NASA Astrophysics Data System (ADS)

Zhang, M. F.; Wang, Y.; Wang, K. F.; Zhu, J. S.; Liu, J.-M.

2009-03-01

We investigate in detail the migration kinetics of oxygen vacancies (OVs) in Ba-doped Pb(Zr0.52Ti0.48)O3 (PZT) ferroelectrics by complex impedance spectroscopy. The temperature dependent dc-electrical conductivity σdc suggests that Ba doping into PZT can lower significantly the density of OVs, leading to the distinctly decreased σdc and slightly enhanced activation energy U for the migration of OVs, thus benefiting the polarization fatigue resistance. Furthermore, the polarization fluctuation induced by the relaxation of OVs is reduced by the Ba doping. The Cole-Cole fitting to the dielectric loss manifests strong correlation among OVs, and the migration of OVs appears to be a collective behavior.

Cerebellar contributions to motor timing: a PET study of auditory and visual rhythm reproduction.

PubMed

Penhune, V B; Zattore, R J; Evans, A C

1998-11-01

The perception and production of temporal patterns, or rhythms, is important for both music and speech. However, the way in which the human brain achieves accurate timing of perceptual input and motor output is as yet little understood. Central control of both motor timing and perceptual timing across modalities has been linked to both the cerebellum and the basal ganglia (BG). The present study was designed to test the hypothesized central control of temporal processing and to examine the roles of the cerebellum, BG, and sensory association areas. In this positron emission tomography (PET) activation paradigm, subjects reproduced rhythms of increasing temporal complexity that were presented separately in the auditory and visual modalities. The results provide support for a supramodal contribution of the lateral cerebellar cortex and cerebellar vermis to the production of a timed motor response, particularly when it is complex and/or novel. The results also give partial support to the involvement of BG structures in motor timing, although this may be more directly related to implementation of the motor response than to timing per se. Finally, sensory association areas and the ventrolateral frontal cortex were found to be involved in modality-specific encoding and retrieval of the temporal stimuli. Taken together, these results point to the participation of a number of neural structures in the production of a timed motor response from an external stimulus. The role of the cerebellum in timing is conceptualized not as a clock or counter but simply as the structure that provides the necessary circuitry for the sensory system to extract temporal information and for the motor system to learn to produce a precisely timed response.

Sensory-motor networks involved in speech production and motor control: an fMRI study.

PubMed

Behroozmand, Roozbeh; Shebek, Rachel; Hansen, Daniel R; Oya, Hiroyuki; Robin, Donald A; Howard, Matthew A; Greenlee, Jeremy D W

2015-04-01

Speaking is one of the most complex motor behaviors developed to facilitate human communication. The underlying neural mechanisms of speech involve sensory-motor interactions that incorporate feedback information for online monitoring and control of produced speech sounds. In the present study, we adopted an auditory feedback pitch perturbation paradigm and combined it with functional magnetic resonance imaging (fMRI) recordings in order to identify brain areas involved in speech production and motor control. Subjects underwent fMRI scanning while they produced a steady vowel sound /a/ (speaking) or listened to the playback of their own vowel production (playback). During each condition, the auditory feedback from vowel production was either normal (no perturbation) or perturbed by an upward (+600 cents) pitch-shift stimulus randomly. Analysis of BOLD responses during speaking (with and without shift) vs. rest revealed activation of a complex network including bilateral superior temporal gyrus (STG), Heschl's gyrus, precentral gyrus, supplementary motor area (SMA), Rolandic operculum, postcentral gyrus and right inferior frontal gyrus (IFG). Performance correlation analysis showed that the subjects produced compensatory vocal responses that significantly correlated with BOLD response increases in bilateral STG and left precentral gyrus. However, during playback, the activation network was limited to cortical auditory areas including bilateral STG and Heschl's gyrus. Moreover, the contrast between speaking vs. playback highlighted a distinct functional network that included bilateral precentral gyrus, SMA, IFG, postcentral gyrus and insula. These findings suggest that speech motor control involves feedback error detection in sensory (e.g. auditory) cortices that subsequently activate motor-related areas for the adjustment of speech parameters during speaking. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhanced Seismic Imaging of Turbidite Deposits in Chicontepec Basin, Mexico

NASA Astrophysics Data System (ADS)

Chavez-Perez, S.; Vargas-Meleza, L.

2007-05-01

We test, as postprocessing tools, a combination of migration deconvolution and geometric attributes to attack the complex problems of reflector resolution and detection in migrated seismic volumes. Migration deconvolution has been empirically shown to be an effective approach for enhancing the illumination of migrated images, which are blurred versions of the subsurface reflectivity distribution, by decreasing imaging artifacts, improving spatial resolution, and alleviating acquisition footprint problems. We utilize migration deconvolution as a means to improve the quality and resolution of 3D prestack time migrated results from Chicontepec basin, Mexico, a very relevant portion of the producing onshore sector of Pemex, the Mexican petroleum company. Seismic data covers the Agua Fria, Coapechaca, and Tajin fields. It exhibits acquisition footprint problems, migration artifacts and a severe lack of resolution in the target area, where turbidite deposits need to be characterized between major erosional surfaces. Vertical resolution is about 35 m and the main hydrocarbon plays are turbidite beds no more than 60 m thick. We also employ geometric attributes (e.g., coherent energy and curvature), computed after migration deconvolution, to detect and map out depositional features, and help design development wells in the area. Results of this workflow show imaging enhancement and allow us to identify meandering channels and individual sand bodies, previously undistinguishable in the original seismic migrated images.

Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kioka, Noriyuki, E-mail: nkioka@kais.kyoto-u.ac.jp; Ito, Takuya; Yamashita, Hiroshi

2010-06-10

In the process of tissue injury and repair, epithelial cells rapidly migrate and form epithelial sheets. Vinexin is a cytoplasmic molecule of the integrin-containing cell adhesion complex localized at focal contacts in vitro. Here, we investigated the roles of vinexin in keratinocyte migration in vitro and wound healing in vivo. Vinexin knockdown using siRNA delayed migration of both HaCaT human keratinocytes and A431 epidermoid carcinoma cells in scratch assay but did not affect cell proliferation. Induction of cell migration by scratching the confluent monolayer culture of these cells activated both EGFR and ERK, and their inhibitors AG1478 and U0126 substantiallymore » suppressed scratch-induced keratinocyte migration. Vinexin knockdown in these cells inhibited the scratch-induced activation of EGFR, but not that of ERK, suggesting that vinexin promotes cell migration via activation of EGFR. We further generated vinexin (-/-) mice and isolated their keratinocytes. They similarly showed slow migration in scratch assay. Furthermore, vinexin (-/-) mice exhibited a delay in cutaneous wound healing in both the back skin and tail without affecting the proliferation of keratinocytes. Together, these results strongly suggest a crucial role of vinexin in keratinocyte migration in vitro and cutaneous wound healing in vivo.« less

WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration.

PubMed

Xie, Min-Jue; Yagi, Hideshi; Kuroda, Kazuki; Wang, Chen-Chi; Komada, Munekazu; Zhao, Hong; Sakakibara, Akira; Miyata, Takaki; Nagata, Koh-Ichi; Oka, Yuichiro; Iguchi, Tokuichi; Sato, Makoto

2013-06-01

Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially.

Motor speech skills in children with Down syndrome: A descriptive study.

PubMed

Rupela, Vani; Velleman, Shelley L; Andrianopoulos, Mary V

2016-10-01

Motor speech characteristics of children with Down syndrome (DS) have historically been viewed as either Childhood Dysarthria (CD) or, more infrequently, as Childhood Apraxia of Speech (CAS). The objective of this study was to investigate motor speech deficits in a systematic manner, considering characteristics from both CAS and CD. Motor speech assessments were carried out on seven 3;4-8;11-year old children with DS in comparison with younger, typically-developing children using a Language-Neutral Assessment of Motor Speech for young children (LAMS). Additionally, the motor speech and non-speech oral motor skills of all participants were analysed qualitatively using an investigator checklist of characteristics of CAS, CD and Motor Speech Disorder-Not Otherwise Specified (MSD-NOS). Results indicated that the children with DS exhibited symptoms of CAS, CD and MSD-NOS, with variability within the group and overlapping symptoms of the disorder types. This finding is different from previous assumptions that children with DS have either CD or CAS. The motor speech disorder accompanying DS is complex. The data provide some preliminary descriptions of motor speech disorders in this population and some tools that clinicians would find useful when assessing motor speech skills of young children with DS.

Coupling MAST-1D, a sediment routing model for channel-floodplain complexes, with channel migration relationships to predict reach-averaged river morphodynamics. Preliminary results

NASA Astrophysics Data System (ADS)

Viparelli, E.; Eke, E. C.; Lauer, J. W.

2017-12-01

Sediment exchange between the channel and floodplain can occur via meander migration, overbank deposition or erosion, and changes in channel geometry. Depending on channel and floodplain history, floodplains can act either as sources or sinks of bed material and/or wash load. Here we present preliminary modeling results that explicitly account for the feedbacks between the changes in floodplain geometry and sediment size distribution and the changes in channel geometry and migration. These results are obtained by coupling the Morphodynamics And Sediment Tracers in 1D (MAST-1D) program with the results of meander migration studies linking the bankfull flow depth and mean velocity to channel migration, sinuosity and channel geometry. MAST-1D is a numerical model built to describe grain size specific transport of sediment and tracers and the long-term - i.e. decadal and longer - evolution of channel floodplain complexes. MAST-1D differs from other 1D numerical models because it allows for 1) uneven exchange of sediment and tracers between the river channel and the floodplain, 2) temporal changes in channel geometry, bed elevation and floodplain thickness, which result in changes in the channel hydraulic capacity, and 3) temporal changes of size distribution and tracer content in the floodplain, in the load and in the underlying substrate. Under conditions of constant base level, water and sediment supply, the system evolves toward a steady state wherein the amount of sediment deposited through point bar deposition and overbank sedimentation is balanced by the erosion of sediment from the floodplain through lateral migration. The current formulation couples MAST-1D with empirical channel migration relationships that link bankfull flow depth and mean velocity to channel migration, sinuosity and channel geometry. Future development of this preliminary work will involve a fully coupled MAST-1D model with a standard meander migration model that will allow for the building of floodplain stratigraphy and tracking of the position of the meandering channel in space and time.

The transport of Staufen2-containing ribonucleoprotein complexes involves kinesin motor protein and is modulated by mitogen-activated protein kinase pathway.

PubMed

Jeong, Ji-Hye; Nam, Yeon-Ju; Kim, Seok-Yong; Kim, Eung-Gook; Jeong, Jooyoung; Kim, Hyong Kyu

2007-09-01

There is increasing evidence showing that mRNA is transported to the neuronal dendrites in ribonucleoprotein (RNP) complexes or RNA granules, which are aggregates of mRNA, rRNA, ribosomal proteins, and RNA-binding proteins. In these RNP complexes, Staufen, a double-stranded RNA-binding protein, is believed to be a core component that plays a key role in the dendritic mRNA transport. This study investigated the molecular mechanisms of the dendritic mRNA transport using green fluorescent protein-tagged Staufen2 produced employing a Sindbis viral expression system. The kinesin heavy chain was found to be associated with Staufen2. The inhibition of kinesin resulted in a significant decrease in the level of dendritic transport of the Staufen2-containing RNP complexes in neurons under non-stimulating or stimulating conditions. This suggests that the dendritic transport of the Staufen2-containing RNP complexes use kinesin as a motor protein. A mitogen-activated protein kinase inhibitor, PD98059, inhibited the activity-induced increase in the amount of both the Staufen2-containing RNP complexes and Ca(2+)/calmodulin-dependent protein kinase II alpha-subunit mRNA in the distal dendrites of cultured hippocampal neurons. Overall, these results suggest that dendritic mRNA transport is mediated via the Staufen2 and kinesin motor proteins and might be modulated by the neuronal activity and mitogen-activated protein kinase pathway.

Ancient X chromosomes reveal contrasting sex bias in Neolithic and Bronze Age Eurasian migrations.

PubMed

Goldberg, Amy; Günther, Torsten; Rosenberg, Noah A; Jakobsson, Mattias

2017-03-07

Dramatic events in human prehistory, such as the spread of agriculture to Europe from Anatolia and the late Neolithic/Bronze Age migration from the Pontic-Caspian Steppe, can be investigated using patterns of genetic variation among the people who lived in those times. In particular, studies of differing female and male demographic histories on the basis of ancient genomes can provide information about complexities of social structures and cultural interactions in prehistoric populations. We use a mechanistic admixture model to compare the sex-specifically-inherited X chromosome with the autosomes in 20 early Neolithic and 16 late Neolithic/Bronze Age human remains. Contrary to previous hypotheses suggested by the patrilocality of many agricultural populations, we find no evidence of sex-biased admixture during the migration that spread farming across Europe during the early Neolithic. For later migrations from the Pontic Steppe during the late Neolithic/Bronze Age, however, we estimate a dramatic male bias, with approximately five to 14 migrating males for every migrating female. We find evidence of ongoing, primarily male, migration from the steppe to central Europe over a period of multiple generations, with a level of sex bias that excludes a pulse migration during a single generation. The contrasting patterns of sex-specific migration during these two migrations suggest a view of differing cultural histories in which the Neolithic transition was driven by mass migration of both males and females in roughly equal numbers, perhaps whole families, whereas the later Bronze Age migration and cultural shift were instead driven by male migration, potentially connected to new technology and conquest.

Periodic direct current does not promote wound closure in an in vitro dynamic model of cell migration.

PubMed

Godbout, Charles; Frenette, Jérôme

2006-01-01

A prevailing paradigm is that electrical fields can promote cell migration and tissue healing. To further validate this paradigm, we tested the hypothesis that periodic direct current (DC) can enhance wound closure using an in vitro dynamic model of cell migration. Layers of primary fibroblasts were wounded and treated with DC under various voltages. Repair area, cell velocity, and directionality as well as lamellipodium area were evaluated at different times. Direct current had no beneficial effect on cell migration. Moreover, prolonged stimulation under the highest voltage led to significant reduction in wound closure and cell velocity. The reduction of membrane protusions in stimulated cells may be associated with the deleterious effect of DC. Contrary to the authors' expectations, they found that periodic DC did not promote wound closure, a finding that emphasizes the need to clarify the complex effects of electrical fields on migrating cells.

Working in the global world: looking for more modern workplace overseas

NASA Astrophysics Data System (ADS)

Joko Pitoyo, Agus

2018-04-01

International labor migration overseas is very complex and involves multiple dimensional issues, ranging from economic to social, political, and cultural issues. A very long history migration has affect the live of households which has been dependent very much on it, not only in economic terms but also in broader aspects.This research aim is to understand the history and process of international labor migration from the District of Ponorogo. The research was done using mixed method design, combining quantitative and qualitative approaches. Firstly, a survey was done by involving about a thousand households and followed with qualitative method applying in-depth interviews and FGDs to sub-samples households and some key informants. The results have shown that intergenerational migration has established in Ponogoro. There has been an expansion of destination countries with the establishment of many international migration routes. Migrant workers from Ponorogo have traveled to very distant continents and to more modern countries.