Mechanisms of developmental neurite pruning.
Schuldiner, Oren; Yaron, Avraham
2015-01-01
The precise wiring of the nervous system is a combined outcome of progressive and regressive events during development. Axon guidance and synapse formation intertwined with cell death and neurite pruning sculpt the mature circuitry. It is now well recognized that pruning of dendrites and axons as means to refine neuronal networks, is a wide spread phenomena required for the normal development of vertebrate and invertebrate nervous systems. Here we will review the arising principles of cellular and molecular mechanisms of neurite pruning. We will discuss these principles in light of studies in multiple neuronal systems, and speculate on potential explanations for the emergence of neurite pruning as a mechanism to sculpt the nervous system.
Mechanisms of developmental neurite pruning
Schuldiner, Oren; Yaron, Avraham
2016-01-01
The precise wiring of the nervous system is a combined outcome of progressive and regressive events during development. Axon guidance and synapse formation intertwined with cell death and neurite pruning sculpt the mature circuitry. It is now well recognized that pruning of dendrites and axons as means to refine neuronal networks, is a wide spread phenomena required for the normal development of vertebrate and invertebrate nervous systems. Here we will review the arising principles of cellular and molecular mechanisms of neurite pruning. We will discuss these principles in light of studies in multiple neuronal systems, and speculate on potential explanations for the emergence of neurite pruning as a mechanism to sculpt the nervous system. PMID:25213356
Tessier, Charles R.; Broadie, Kendal
2014-01-01
Summary Fragile X Syndrome (FraX) is a broad-spectrum neurological disorder with symptoms ranging from hyperexcitability to mental retardation and autism. Loss of the fragile X mental retardation 1 (fmr1) gene product, the mRNA-binding translational regulator FMRP, causes structural over-elaboration of dendritic and axonal processes as well as functional alterations in synaptic plasticity at maturity. It is unclear, however, whether FraX is primarily a disease of development, a disease of plasticity or both; a distinction vital for engineering intervention strategies. To address this critical issue, we have used the Drosophila FraX model to investigate the developmental roles of Drosophila FMRP (dFMRP). dFMRP expression and regulation of chickadee/profilin coincides with a transient window of late brain development. During this time, dFMRP is positively regulated by sensory input activity, and required to limit axon growth and for efficient activity-dependent pruning of axon branches in the Mushroom Body learning/memory center. These results demonstrate that dFMRP has a primary role in activity-dependent neural circuit refinement in late brain development. PMID:18321984
Borgen, Melissa; Rowland, Kimberly; Boerner, Jana; Lloyd, Brandon; Khan, Aruna; Murphey, Rodney
2017-03-01
The ubiquitin ligase Highwire has a conserved role in synapse formation. Here, we show that Highwire coordinates several facets of central synapse formation in the Drosophila melanogaster giant fiber system, including axon termination, axon pruning, and synaptic function. Despite the similarities to the fly neuromuscular junction, the role of Highwire and the underlying signaling pathways are distinct in the fly's giant fiber system. During development, branching of the giant fiber presynaptic terminal occurs and, normally, the transient branches are pruned away. However, in highwire mutants these ectopic branches persist, indicating that Highwire promotes axon pruning. highwire mutants also exhibit defects in synaptic function. Highwire promotes axon pruning and synaptic function cell-autonomously by attenuating a mitogen-activated protein kinase pathway including Wallenda, c-Jun N-terminal kinase/Basket, and the transcription factor Jun. We also show a novel role for Highwire in non-cell autonomous promotion of synaptic function from the midline glia. Highwire also regulates axon termination in the giant fibers, as highwire mutant axons exhibit severe overgrowth beyond the pruning defect. This excessive axon growth is increased by manipulating Fos expression in the cells surrounding the giant fiber terminal, suggesting that Fos regulates a trans -synaptic signal that promotes giant fiber axon growth. Copyright © 2017 by the Genetics Society of America.
Death Receptor 6 Promotes Wallerian Degeneration in Peripheral Axons.
Gamage, Kanchana K; Cheng, Irene; Park, Rachel E; Karim, Mardeen S; Edamura, Kazusa; Hughes, Christopher; Spano, Anthony J; Erisir, Alev; Deppmann, Christopher D
2017-03-20
Axon degeneration during development is required to sculpt a functional nervous system and is also a hallmark of pathological insult, such as injury [1, 2]. Despite similar morphological characteristics, very little overlap in molecular mechanisms has been reported between pathological and developmental degeneration [3-5]. In the peripheral nervous system (PNS), developmental axon pruning relies on receptor-mediated extrinsic degeneration mechanisms to determine which axons are maintained or degenerated [5-7]. Receptors have not been implicated in Wallerian axon degeneration; instead, axon autonomous, intrinsic mechanisms are thought to be the primary driver for this type of axon disintegration [8-10]. Here we survey the role of neuronally expressed, paralogous tumor necrosis factor receptor super family (TNFRSF) members in Wallerian degeneration. We find that an orphan receptor, death receptor 6 (DR6), is required to drive axon degeneration after axotomy in sympathetic and sensory neurons cultured in microfluidic devices. We sought to validate these in vitro findings in vivo using a transected sciatic nerve model. Consistent with the in vitro findings, DR6 -/- animals displayed preserved axons up to 4 weeks after injury. In contrast to phenotypes observed in Wld s and Sarm1 -/- mice, preserved axons in DR6 -/- animals display profound myelin remodeling. This indicates that deterioration of axons and myelin after axotomy are mechanistically distinct processes. Finally, we find that JNK signaling after injury requires DR6, suggesting a link between this novel extrinsic pathway and the axon autonomous, intrinsic pathways that have become established for Wallerian degeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.
Wong, Jack Jing Lin; Wang, Cheng; Zhang, Heng; Kirilly, Daniel; Wu, Chunlai; Liou, Yih-Cherng; Wang, Hongyan; Yu, Fengwei
2013-01-01
Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroom body γ neurons specifically eliminate their axon branches within dorsal and medial lobes. However, it is unknown which E3 ligase directs these two modes of pruning. Here, we identified a conserved SCF E3 ubiquitin ligase that plays a critical role in pruning of both ddaC dendrites and mushroom body γ axons. The SCF E3 ligase consists of four core components Cullin1/Roc1a/SkpA/Slimb and promotes ddaC dendrite pruning downstream of EcR-B1 and Sox14, but independently of Mical. Moreover, we demonstrate that the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway. We show that the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination. Activation of the InR/PI3K/TOR pathway is sufficient to inhibit ddaC dendrite pruning. Thus, our findings provide a novel link between the E3 ligase and the InR/PI3K/TOR pathway during dendrite pruning. PMID:24068890
The Indispensable Roles of Microglia and Astrocytes during Brain Development
Reemst, Kitty; Noctor, Stephen C.; Lucassen, Paul J.; Hol, Elly M.
2016-01-01
Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same developmental processes such as neuro-/gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis and synaptic pruning. Due to their important instructive roles in these processes, dysfunction of microglia or astrocytes during brain development could contribute to neurodevelopmental disorders and potentially even late-onset neuropathology. A better understanding of the origin, differentiation process and developmental functions of microglia and astrocytes will help to fully appreciate their role both in the developing as well as in the adult brain, in health and disease. PMID:27877121
Jeon, Tina; Mishra, Virendra; Ouyang, Minhui; Chen, Min; Huang, Hao
2015-01-01
Cortical thickness (CT) changes during normal brain development is associated with complicated cellular and molecular processes including synaptic pruning and apoptosis. In parallel, the microstructural enhancement of developmental white matter (WM) axons with their neuronal bodies in the cerebral cortex has been widely reported with measurements of metrics derived from diffusion tensor imaging (DTI), especially fractional anisotropy (FA). We hypothesized that the changes of CT and microstructural enhancement of corresponding axons are highly interacted during development. DTI and T1-weighted images of 50 healthy children and adolescents between the ages of 7 and 25 years were acquired. With the parcellated cortical gyri transformed from T1-weighted images to DTI space as the tractography seeds, probabilistic tracking was performed to delineate the WM fibers traced from specific parcellated cortical regions. CT was measured at certain cortical regions and FA was measured from the WM fibers traced from same cortical regions. The CT of all frontal cortical gyri, including Brodmann areas 4, 6, 8, 9, 10, 11, 44, 45, 46, and 47, decreased significantly and heterogeneously; concurrently, significant, and heterogeneous increases of FA of WM traced from corresponding regions were found. We further revealed significant correlation between the slopes of the CT decrease and the slopes of corresponding WM FA increase in all frontal cortical gyri, suggesting coherent cortical pruning and corresponding WM microstructural enhancement. Such correlation was not found in cortical regions other than frontal cortex. The molecular and cellular mechanisms of these synchronous changes may be associated with overlapping signaling pathways of axonal guidance, synaptic pruning, neuronal apoptosis, and more prevalent interstitial neurons in the prefrontal cortex. Revealing the coherence of cortical and WM structural changes during development may open a new window for understanding the underlying mechanisms of developing brain circuits and structural abnormality associated with mental disorders. PMID:26696839
Zhang, Heng; Wang, Yan; Wong, Jack Jing Lin; Lim, Kah-Leong; Liou, Yih-Cherng; Wang, Hongyan; Yu, Fengwei
2014-08-25
Pruning of unnecessary axons and/or dendrites is crucial for maturation of the nervous system. However, little is known about cell adhesion molecules (CAMs) that control neuronal pruning. In Drosophila, dendritic arborization neurons, ddaCs, selectively prune their larval dendrites. Here, we report that Rab5/ESCRT-mediated endocytic pathways are critical for dendrite pruning. Loss of Rab5 or ESCRT function leads to robust accumulation of the L1-type CAM Neuroglian (Nrg) on enlarged endosomes in ddaC neurons. Nrg is localized on endosomes in wild-type ddaC neurons and downregulated prior to dendrite pruning. Overexpression of Nrg alone is sufficient to inhibit dendrite pruning, whereas removal of Nrg causes precocious dendrite pruning. Epistasis experiments indicate that Rab5 and ESCRT restrain the inhibitory role of Nrg during dendrite pruning. Thus, this study demonstrates the cell-surface molecule that controls dendrite pruning and defines an important mechanism whereby sensory neurons, via endolysosomal pathway, downregulate the cell-surface molecule to trigger dendrite pruning. Copyright © 2014 Elsevier Inc. All rights reserved.
Wu, Xiaoyun; Fu, Yu; Knott, Graham; Lu, Jiangteng; Di Cristo, Graziella
2012-01-01
Accumulating evidence indicates that GABA acts beyond inhibitory synaptic transmission and regulates the development of inhibitory synapses in the vertebrate brain, but the underlying cellular mechanism is not well understood. We have combined live imaging of cortical GABAergic axons across time scales from minutes to days with single-cell genetic manipulation of GABA release to examine its role in distinct steps of inhibitory synapse formation in the mouse neocortex. We have shown previously, by genetic knockdown of GABA synthesis in developing interneurons, that GABA signaling promotes the maturation of inhibitory synapses and axons. Here we found that a complete blockade of GABA release in basket interneurons resulted in an opposite effect, a cell-autonomous increase in axon and bouton density with apparently normal synapse structures. These results not only demonstrate that GABA is unnecessary for synapse formation per se but also uncover a novel facet of GABA in regulating synapse elimination and axon pruning. Live imaging revealed that developing GABAergic axons form a large number of transient boutons, but only a subset was stabilized. Release blockade led to significantly increased bouton stability and filopodia density, increased axon branch extension, and decreased branch retraction. Our results suggest that a major component of GABA function in synapse development is transmission-mediated elimination of subsets of nascent contacts. Therefore, GABA may regulate activity-dependent inhibitory synapse formation by coordinately eliminating certain nascent contacts while promoting the maturation of other nascent synapses. PMID:22219294
NASA Astrophysics Data System (ADS)
Ouyang, Minhui; Jeon, Tina; Mishra, Virendra; Du, Haixiao; Wang, Yu; Peng, Yun; Huang, Hao
2016-03-01
From early childhood to adulthood, synaptogenesis and synaptic pruning continuously reshape the structural architecture and neural connection in developmental human brains. Disturbance of the precisely balanced strengthening of certain axons and pruning of others may cause mental disorders such as autism and schizophrenia. To characterize this balance, we proposed a novel measurement based on cortical parcellation and diffusion MRI (dMRI) tractography, a cortical connectivity maturation index (CCMI). To evaluate the spatiotemporal sensitivity of CCMI as a potential biomarker, dMRI and T1 weighted datasets of 21 healthy subjects 2-25 years were acquired. Brain cortex was parcellated into 68 gyral labels using T1 weighted images, then transformed into dMRI space to serve as the seed region of interest for dMRI-based tractography. Cortico-cortical association fibers initiated from each gyrus were categorized into long- and short-range ones, based on the other end of fiber terminating in non-adjacent or adjacent gyri of the seed gyrus, respectively. The regional CCMI was defined as the ratio between number of short-range association tracts and that of all association tracts traced from one of 68 parcellated gyri. The developmental trajectory of the whole brain CCMI follows a quadratic model with initial decreases from 2 to 16 years followed by later increases after 16 years. Regional CCMI is heterogeneous among different cortical gyri with CCMI dropping to the lowest value earlier in primary somatosensory cortex and visual cortex while later in the prefrontal cortex. The proposed CCMI may serve as sensitive biomarker for brain development under normal or pathological conditions.
Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits.
Tang, Guomei; Gudsnuk, Kathryn; Kuo, Sheng-Han; Cotrina, Marisa L; Rosoklija, Gorazd; Sosunov, Alexander; Sonders, Mark S; Kanter, Ellen; Castagna, Candace; Yamamoto, Ai; Yue, Zhenyu; Arancio, Ottavio; Peterson, Bradley S; Champagne, Frances; Dwork, Andrew J; Goldman, James; Sulzer, David
2014-09-03
Developmental alterations of excitatory synapses are implicated in autism spectrum disorders (ASDs). Here, we report increased dendritic spine density with reduced developmental spine pruning in layer V pyramidal neurons in postmortem ASD temporal lobe. These spine deficits correlate with hyperactivated mTOR and impaired autophagy. In Tsc2 ± ASD mice where mTOR is constitutively overactive, we observed postnatal spine pruning defects, blockade of autophagy, and ASD-like social behaviors. The mTOR inhibitor rapamycin corrected ASD-like behaviors and spine pruning defects in Tsc2 ± mice, but not in Atg7(CKO) neuronal autophagy-deficient mice or Tsc2 ± :Atg7(CKO) double mutants. Neuronal autophagy furthermore enabled spine elimination with no effects on spine formation. Our findings suggest that mTOR-regulated autophagy is required for developmental spine pruning, and activation of neuronal autophagy corrects synaptic pathology and social behavior deficits in ASD models with hyperactivated mTOR. Copyright © 2014 Elsevier Inc. All rights reserved.
Metabolic reprogramming during neuronal differentiation.
Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G
2016-09-01
Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.
Metabolic reprogramming during neuronal differentiation
Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G
2016-01-01
Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate–glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K–Akt–mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation. PMID:27058317
Alterations in a Unique Class of Cortical Chandelier Cell Axon Cartridges in Schizophrenia.
Rocco, Brad R; DeDionisio, Adam M; Lewis, David A; Fish, Kenneth N
2017-07-01
The axons of chandelier cells (ChCs) target the axon initial segment of pyramidal neurons, forming an array of boutons termed a cartridge. In schizophrenia, the density of cartridges detectable by gamma-aminobutyric acid (GABA) membrane transporter 1 immunoreactivity is lower, whereas the density of axon initial segments detectable by immunoreactivity for the α2 subunit of the GABA A receptor is higher in layers 2/superficial 3 of the prefrontal cortex. These findings were interpreted as compensatory responses to lower GABA levels in ChCs. However, we recently found that in schizophrenia, ChC cartridge boutons contain normal levels of the 67 kDa isoform of glutamic acid decarboxylase (GAD67) protein, the enzyme responsible for GABA synthesis in these boutons. To understand these findings we quantified the densities of ChC cartridges immunoreactive for vesicular GABA transporter (vGAT+), which is present in all cartridge boutons, and the subset of cartridges that contain calbindin (CB+). Prefrontal cortex tissue sections from 20 matched pairs of schizophrenia and unaffected comparison subjects were immunolabeled for vGAT, GAD67, and CB. The mean density of vGAT+/CB+ cartridges was 2.7-fold higher, exclusively in layer 2 of schizophrenia subjects, whereas the density of vGAT+/CB- cartridges did not differ between subject groups. Neither vGAT, CB, or GAD67 protein levels per ChC bouton nor the number of boutons per cartridge differed between subject groups. Our findings of a greater density of CB+ ChC cartridges in prefrontal cortex layer 2 from schizophrenia subjects suggests that the normal developmental pruning of these cartridges is blunted in the illness. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Wang, Yan; Zhang, Heng; Shi, Meng; Liou, Yih-Cherng; Lu, Lei; Yu, Fengwei
2017-05-15
Pruning, whereby neurons eliminate their excess neurites, is central for the maturation of the nervous system. In Drosophila , sensory neurons, ddaCs, selectively prune their larval dendrites without affecting their axons during metamorphosis. However, it is unknown whether the secretory pathway plays a role in dendrite pruning. Here, we show that the small GTPase Arf1, an important regulator of the secretory pathway, is specifically required for dendrite pruning of ddaC/D/E sensory neurons but dispensable for apoptosis of ddaF neurons. Analyses of the GTP- and GDP-locked forms of Arf1 indicate that the cycling of Arf1 between GDP-bound and GTP-bound forms is essential for dendrite pruning. We further identified Sec71 as a guanine nucleotide exchange factor for Arf1 that preferentially interacts with its GDP-bound form. Like Arf1, Sec71 is also important for dendrite pruning, but not for apoptosis, of sensory neurons. Arf1 and Sec71 are interdependent for their localizations on Golgi. Finally, we show that the Sec71/Arf1-mediated trafficking process is a prerequisite for Rab5-dependent endocytosis to facilitate endocytosis and degradation of the cell-adhesion molecule Neuroglian (Nrg). © 2017. Published by The Company of Biologists Ltd.
Wang, Qiwei; Wang, Yan; Yu, Fengwei
2018-05-16
Pruning that selectively removes unnecessary neurites without causing neuronal death is essential for sculpting the mature nervous system during development. In Drosophila , ddaC sensory neurons specifically prune their larval dendrites with intact axons during metamorphosis. However, it remains unknown about an important role of ER-to-Golgi transport in dendrite pruning. Here, in a clonal screen we identified Yif1, an uncharacterized Drosophila homologue of Yif1p that is known as a regulator of ER-to-Golgi transport in yeast. We show that Yif1 is required for dendrite pruning of ddaC neurons but not for apoptosis of ddaF neurons. We further identified the Yif1-binding partner Yip1 which is also crucial for dendrite pruning. Yif1 forms a protein complex with Yip1 in S2 cells and ddaC neurons. Yip1 and Yif1 colocalize on ER/Golgi and are required for the integrity of Golgi apparatus and outposts. Moreover, we show that two GTPases Rab1 and Sar1, known to regulate ER-to-Golgi transport, are essential for dendrite pruning of ddaC neurons. Finally, our data reveal that ER-to-Golgi transport promotes endocytosis and downregulation of cell adhesion molecule Neuroglian and thereby dendrite pruning. © 2018. Published by The Company of Biologists Ltd.
Spinal motor neuron involvement in a patient with homozygous PRUNE mutation.
Iacomino, Michele; Fiorillo, Chiara; Torella, Annalaura; Severino, Mariasavina; Broda, Paolo; Romano, Catia; Falsaperla, Raffaele; Pozzolini, Giulia; Minetti, Carlo; Striano, Pasquale; Nigro, Vincenzo; Zara, Federico
2018-05-01
In the last few years, whole exome sequencing (WES) allowed the identification of PRUNE mutations in patients featuring a complex neurological phenotype characterized by severe neurodevelopmental delay, microcephaly, epilepsy, optic atrophy, and brain or cerebellar atrophy. We describe an additional patient with homozygous PRUNE mutation who presented with spinal muscular atrophy phenotype, in addition to the already known brain developmental disorder. This novel feature expands the clinical consequences of PRUNE mutations and allow to converge PRUNE syndrome with previous descriptions of neurodevelopmental/neurodegenerative disorders linked to altered microtubule dynamics. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Decreasing-Rate Pruning Optimizes the Construction of Efficient and Robust Distributed Networks.
Navlakha, Saket; Barth, Alison L; Bar-Joseph, Ziv
2015-07-01
Robust, efficient, and low-cost networks are advantageous in both biological and engineered systems. During neural network development in the brain, synapses are massively over-produced and then pruned-back over time. This strategy is not commonly used when designing engineered networks, since adding connections that will soon be removed is considered wasteful. Here, we show that for large distributed routing networks, network function is markedly enhanced by hyper-connectivity followed by aggressive pruning and that the global rate of pruning, a developmental parameter not previously studied by experimentalists, plays a critical role in optimizing network structure. We first used high-throughput image analysis techniques to quantify the rate of pruning in the mammalian neocortex across a broad developmental time window and found that the rate is decreasing over time. Based on these results, we analyzed a model of computational routing networks and show using both theoretical analysis and simulations that decreasing rates lead to more robust and efficient networks compared to other rates. We also present an application of this strategy to improve the distributed design of airline networks. Thus, inspiration from neural network formation suggests effective ways to design distributed networks across several domains.
Decreasing-Rate Pruning Optimizes the Construction of Efficient and Robust Distributed Networks
Navlakha, Saket; Barth, Alison L.; Bar-Joseph, Ziv
2015-01-01
Robust, efficient, and low-cost networks are advantageous in both biological and engineered systems. During neural network development in the brain, synapses are massively over-produced and then pruned-back over time. This strategy is not commonly used when designing engineered networks, since adding connections that will soon be removed is considered wasteful. Here, we show that for large distributed routing networks, network function is markedly enhanced by hyper-connectivity followed by aggressive pruning and that the global rate of pruning, a developmental parameter not previously studied by experimentalists, plays a critical role in optimizing network structure. We first used high-throughput image analysis techniques to quantify the rate of pruning in the mammalian neocortex across a broad developmental time window and found that the rate is decreasing over time. Based on these results, we analyzed a model of computational routing networks and show using both theoretical analysis and simulations that decreasing rates lead to more robust and efficient networks compared to other rates. We also present an application of this strategy to improve the distributed design of airline networks. Thus, inspiration from neural network formation suggests effective ways to design distributed networks across several domains. PMID:26217933
Romi, Erez; Gokhman, Irena; Wong, Eitan; Antonovsky, Niv; Ludwig, Andreas; Sagi, Irit; Saftig, Paul; Tessier-Lavigne, Marc; Yaron, Avraham
2014-06-05
During embryonic development, axons can gain and lose sensitivity to guidance cues, and this flexibility is essential for the correct wiring of the nervous system. Yet, the underlying molecular mechanisms are largely unknown. Here we show that receptor cleavage by ADAM (A Disintegrin And Metalloprotease) metalloproteases promotes murine sensory axons loss of responsiveness to the chemorepellant Sema3A. Genetic ablation of ADAM10 and ADAM17 disrupts the developmental downregulation of Neuropilin-1 (Nrp1), the receptor for Sema3A, in sensory axons. Moreover, this is correlated with gain of repulsive response to Sema3A. Overexpression of Nrp1 in neurons reverses axonal desensitization to Sema3A, but this is hampered in a mutant Nrp1 with high susceptibility to cleavage. Lastly, we detect guidance errors of proprioceptive axons in ADAM knockouts that are consistent with enhanced response to Sema3A. Our results provide the first evidence for involvement of ADAMs in regulating developmental switch in responsiveness to axonal guidance cues.
Exclusion of Integrins from CNS Axons Is Regulated by Arf6 Activation and the AIS
Franssen, Elske H. P.; Zhao, Rong-Rong; Koseki, Hiroaki; Kanamarlapudi, Venkateswarlu; Hoogenraad, Casper C.
2015-01-01
Integrins are adhesion and survival molecules involved in axon growth during CNS development, as well as axon regeneration after injury in the peripheral nervous system (PNS). Adult CNS axons do not regenerate after injury, partly due to a low intrinsic growth capacity. We have previously studied the role of integrins in axon growth in PNS axons; in the present study, we investigate whether integrin mechanisms involved in PNS regeneration may be altered or lacking from mature CNS axons by studying maturing CNS neurons in vitro. In rat cortical neurons, we find that integrins are present in axons during initial growth but later become restricted to the somato-dendritic domain. We investigated how this occurs and whether it can be altered to enhance axonal growth potential. We find a developmental change in integrin trafficking; transport becomes predominantly retrograde throughout axons, but not dendrites, as neurons mature. The directionality of transport is controlled through the activation state of ARF6, with developmental upregulation of the ARF6 GEF ARNO enhancing retrograde transport. Lowering ARF6 activity in mature neurons restores anterograde integrin flow, allows transport into axons, and increases axon growth. In addition, we found that the axon initial segment is partly responsible for exclusion of integrins and removal of this structure allows integrins into axons. Changing posttranslational modifications of tubulin with taxol also allows integrins into the proximal axon. The experiments suggest that the developmental loss of regenerative ability in CNS axons is due to exclusion of growth-related molecules due to changes in trafficking. PMID:26019348
Zollo, Massimo; Ahmed, Mustafa; Ferrucci, Veronica; Salpietro, Vincenzo; Asadzadeh, Fatemeh; Carotenuto, Marianeve; Maroofian, Reza; Al-Amri, Ahmed; Singh, Royana; Scognamiglio, Iolanda; Mojarrad, Majid; Musella, Luca; Duilio, Angela; Di Somma, Angela; Karaca, Ender; Rajab, Anna; Al-Khayat, Aisha; Mohan Mohapatra, Tribhuvan; Eslahi, Atieh; Ashrafzadeh, Farah; Rawlins, Lettie E; Prasad, Rajniti; Gupta, Rashmi; Kumari, Preeti; Srivastava, Mona; Cozzolino, Flora; Kumar Rai, Sunil; Monti, Maria; Harlalka, Gaurav V; Simpson, Michael A; Rich, Philip; Al-Salmi, Fatema; Patton, Michael A; Chioza, Barry A; Efthymiou, Stephanie; Granata, Francesca; Di Rosa, Gabriella; Wiethoff, Sarah; Borgione, Eugenia; Scuderi, Carmela; Mankad, Kshitij; Hanna, Michael G; Pucci, Piero; Houlden, Henry; Lupski, James R; Crosby, Andrew H; Baple, Emma L
2017-04-01
PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.
Regulation of branching dynamics by axon-intrinsic asymmetries in Tyrosine Kinase Receptor signaling
Zschätzsch, Marlen; Oliva, Carlos; Langen, Marion; De Geest, Natalie; Özel, Mehmet Neset; Williamson, W Ryan; Lemon, William C; Soldano, Alessia; Munck, Sebastian; Hiesinger, P Robin; Sanchez-Soriano, Natalia; Hassan, Bassem A
2014-01-01
Axonal branching allows a neuron to connect to several targets, increasing neuronal circuit complexity. While axonal branching is well described, the mechanisms that control it remain largely unknown. We find that in the Drosophila CNS branches develop through a process of excessive growth followed by pruning. In vivo high-resolution live imaging of developing brains as well as loss and gain of function experiments show that activation of Epidermal Growth Factor Receptor (EGFR) is necessary for branch dynamics and the final branching pattern. Live imaging also reveals that intrinsic asymmetry in EGFR localization regulates the balance between dynamic and static filopodia. Elimination of signaling asymmetry by either loss or gain of EGFR function results in reduced dynamics leading to excessive branch formation. In summary, we propose that the dynamic process of axon branch development is mediated by differential local distribution of signaling receptors. DOI: http://dx.doi.org/10.7554/eLife.01699.001 PMID:24755286
Chlorpyrifos-Oxon Disrupts Zebrafish Axonal Growth and Motor Behavior
Yang, Dongren; Lauridsen, Holly; Buels, Kalmia; Chi, Lai-Har; La Du, Jane; Bruun, Donald A.; Olson, James R.; Tanguay, Robert L.; Lein, Pamela J.
2011-01-01
Axonal morphology is a critical determinant of neuronal connectivity, and perturbation of the rate or extent of axonal growth during development has been linked to neurobehavioral deficits in animal models and humans. We previously demonstrated that the organophosphorus pesticide (OP) chlorpyrifos (CPF) inhibits axonal growth in cultured neurons. In this study, we used a zebrafish model to determine whether CPF, its oxon metabolite (CPFO), or the excreted metabolite trichloro-2-pyridinol (TCPy) alter spatiotemporal patterns of axonal growth in vivo. Static waterborne exposure to CPFO, but not CPF or TCPy, at concentrations ≥ 0.03μM from 24- to 72-h post fertilization significantly inhibited acetylcholinesterase, and high-performance liquid chromatography detected significantly more TCPy in zebrafish exposed to 0.1μM CPFO versus 1.0μM CPF. These data suggest that zebrafish lack the metabolic enzymes to activate CPF during these early developmental stages. Consistent with this, CPFO, but not CPF, significantly inhibited axonal growth of sensory neurons, primary motoneurons, and secondary motoneurons at concentrations ≥ 0.1μM. Secondary motoneurons were the most sensitive to axonal growth inhibition by CPFO, which was observed at concentrations that did not cause mortality, gross developmental defects, or aberrant somatic muscle differentiation. CPFO effects on axonal growth correlated with adverse effects on touch-induced swimming behavior, suggesting the functional relevance of these structural changes. These data suggest that altered patterns of neuronal connectivity contribute to the developmental neurotoxicity of CPF and demonstrate the relevance of zebrafish as a model for studying OP developmental neurotoxicity. PMID:21346248
Kridsada, Kim; Niu, Jingwen; Haldipur, Parthiv; Wang, Zhiping; Ding, Long; Li, Jian J; Lindgren, Anne G; Herrera, Eloisa; Thomas, Gareth M; Chizhikov, Victor V; Millen, Kathleen J; Luo, Wenqin
2018-06-05
Spinal cord longitudinal axons comprise some of the longest axons in our body. However, mechanisms that drive this extra long-distance axonal growth are largely unclear. We found that ascending axons of rapidly adapting (RA) mechanoreceptors closely abut a previously undescribed population of roof plate-derived radial glial-like cells (RGLCs) in the spinal cord dorsal column, which form a network of processes enriched with growth-promoting factors. In dreher mutant mice that lack RGLCs, the lengths of ascending RA mechanoreceptor axon branches are specifically reduced, whereas their descending and collateral branches, and other dorsal column and sensory pathways, are largely unaffected. Because the number and intrinsic growth ability of RA mechanoreceptors are normal in dreher mice, our data suggest that RGLCs provide critical non-cell autonomous growth support for the ascending axons of RA mechanoreceptors. Together, our work identifies a developmental mechanism specifically required for long-range spinal cord longitudinal axons. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Kondo, Yohei; Yada, Yuichiro; Haga, Tatsuya; Takayama, Yuzo; Isomura, Takuya; Jimbo, Yasuhiko; Fukayama, Osamu; Hoshino, Takayuki; Mabuchi, Kunihiko
2017-04-29
Synapse elimination and neurite pruning are essential processes for the formation of neuronal circuits. These regressive events depend on neural activity and occur in the early postnatal days known as the critical period, but what makes this temporal specificity is not well understood. One possibility is that the neural activities during the developmentally regulated shift of action of GABA inhibitory transmission lead to the critical period. Moreover, it has been reported that the shifting action of the inhibitory transmission on immature neurons overlaps with synapse elimination and neurite pruning and that increased inhibitory transmission by drug treatment could induce temporal shift of the critical period. However, the relationship among these phenomena remains unclear because it is difficult to experimentally show how the developmental shift of inhibitory transmission influences neural activities and whether the activities promote synapse elimination and neurite pruning. In this study, we modeled synapse elimination in neuronal circuits using the modified Izhikevich's model with functional shifting of GABAergic transmission. The simulation results show that synaptic pruning within a specified period like the critical period is spontaneously generated as a function of the developmentally shifting inhibitory transmission and that the specific firing rate and increasing synchronization of neural circuits are seen at the initial stage of the critical period. This temporal relationship was experimentally supported by an in vitro primary culture of rat cortical neurons in a microchannel on a multi-electrode array (MEA). The firing rate decreased remarkably between the 18-25 days in vitro (DIV), and following these changes in the firing rate, the neurite density was slightly reduced. Our simulation and experimental results suggest that decreasing neural activity due to developing inhibitory synaptic transmission could induce synapse elimination and neurite pruning at particular time such as the critical period. Additionally, these findings indicate that we can estimate the maturity level of inhibitory transmission and the critical period by measuring the firing rate and the degree of synchronization in engineered neural networks. Copyright © 2017 Elsevier Inc. All rights reserved.
The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans
Chisholm, Andrew D.; Hutter, Harald; Jin, Yishi; Wadsworth, William G.
2016-01-01
The correct wiring of neuronal circuits depends on outgrowth and guidance of neuronal processes during development. In the past two decades, great progress has been made in understanding the molecular basis of axon outgrowth and guidance. Genetic analysis in Caenorhabditis elegans has played a key role in elucidating conserved pathways regulating axon guidance, including Netrin signaling, the slit Slit/Robo pathway, Wnt signaling, and others. Axon guidance factors were first identified by screens for mutations affecting animal behavior, and by direct visual screens for axon guidance defects. Genetic analysis of these pathways has revealed the complex and combinatorial nature of guidance cues, and has delineated how cues guide growth cones via receptor activity and cytoskeletal rearrangement. Several axon guidance pathways also affect directed migrations of non-neuronal cells in C. elegans, with implications for normal and pathological cell migrations in situations such as tumor metastasis. The small number of neurons and highly stereotyped axonal architecture of the C. elegans nervous system allow analysis of axon guidance at the level of single identified axons, and permit in vivo tests of prevailing models of axon guidance. C. elegans axons also have a robust capacity to undergo regenerative regrowth after precise laser injury (axotomy). Although such axon regrowth shares some similarities with developmental axon outgrowth, screens for regrowth mutants have revealed regeneration-specific pathways and factors that were not identified in developmental screens. Several areas remain poorly understood, including how major axon tracts are formed in the embryo, and the function of axon regeneration in the natural environment. PMID:28114100
Sidlauskaite, Eva; Gibson, Jack W; Megson, Ian L; Whitfield, Philip D; Tovmasyan, Artak; Batinic-Haberle, Ines; Murphy, Michael P; Moult, Peter R; Cobley, James N
2018-06-01
Developmental synapse pruning refines burgeoning connectomes. The basic mechanisms of mitochondrial reactive oxygen species (ROS) production suggest they select inactive synapses for pruning: whether they do so is unknown. To begin to unravel whether mitochondrial ROS regulate pruning, we made the local consequences of neuromuscular junction (NMJ) pruning detectable as motor deficits by using disparate exogenous and endogenous models to induce synaptic inactivity en masse in developing Xenopus laevis tadpoles. We resolved whether: (1) synaptic inactivity increases mitochondrial ROS; and (2) chemically heterogeneous antioxidants rescue synaptic inactivity induced motor deficits. Regardless of whether it was achieved with muscle (α-bungarotoxin), nerve (α-latrotoxin) targeted neurotoxins or an endogenous pruning cue (SPARC), synaptic inactivity increased mitochondrial ROS in vivo. The manganese porphyrins MnTE-2-PyP 5+ and/or MnTnBuOE-2-PyP 5+ blocked mitochondrial ROS to significantly reduce neurotoxin and endogenous pruning cue induced motor deficits. Selectively inducing mitochondrial ROS-using mitochondria-targeted Paraquat (MitoPQ)-recapitulated synaptic inactivity induced motor deficits; which were significantly reduced by blocking mitochondrial ROS with MnTnBuOE-2-PyP 5+ . We unveil mitochondrial ROS as synaptic activity sentinels that regulate the phenotypical consequences of forced synaptic inactivity at the NMJ. Our novel results are relevant to pruning because synaptic inactivity is one of its defining features. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Visual Map Development: Bidirectional Signaling, Bifunctional Guidance Molecules, and Competition
Feldheim, David A.; O’Leary, Dennis D. M.
2010-01-01
Topographic maps are a two-dimensional representation of one neural structure within another and serve as the main strategy to organize sensory information. The retina’s projection via axons of retinal ganglion cells to midbrain visual centers, the optic tectum/superior colliculus, is the leading model to elucidate mechanisms of topographic map formation. Each axis of the retina is mapped independently using different mechanisms and sets of axon guidance molecules expressed in gradients to achieve the goal of representing a point in the retina onto a point within the target. An axon’s termination along the temporal-nasal mapping axis is determined by opposing gradients of EphAs and ephrin-As that act through their forward and reverse signaling, respectively, within the projecting axons, each of which inhibits interstitial branching, cooperating with a branch-promoting activity, to generate topographic specific branching along the shaft of the parent axons that overshoot their correct termination zone along the anterior-posterior axis of the target. The dorsal-ventral termination position is then determined using a gradient of ephrin-B that can act as a repellent or attractant depending on the ephrin-B concentration relative to EphB levels on the interstitial branches to guide them along the medial-lateral axis of the target to their correct termination zone, where they arborize. In both cases, axon-axon competition results in axon mapping based on relative rather than absolute levels of repellent or attractant activity. The map is subsequently refined through large-scale pruning driven in large part by patterned retinal activity. PMID:20880989
Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.
2015-01-01
Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMN). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30µM). Previous work showed that the paralytic mutant zebrafish known as sofa potato, exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. PMID:25668718
Alan, Jamie K; Struckhoff, Eric C; Lundquist, Erik A
2013-01-01
Rho GTPases are key regulators of cellular protrusion and are involved in many developmental events including axon guidance during nervous system development. Rho GTPase pathways display functional redundancy in developmental events, including axon guidance. Therefore, their roles can often be masked when using simple loss-of-function genetic approaches. As a complement to loss-of-function genetics, we constructed a constitutively activated CDC-42(G12V) expressed in C. elegans neurons. CDC-42(G12V) drove the formation of ectopic lamellipodial and filopodial protrusions in the PDE neurons, which resembled protrusions normally found on migrating growth cones of axons. We then used a candidate gene approach to identify molecules that mediate CDC-42(G12V)-induced ectopic protrusions by determining if loss of function of the genes could suppress CDC-42(G12V). Using this approach, we identified 3 cytoskeletal pathways previously implicated in axon guidance, the Arp2/3 complex, UNC-115/abLIM, and UNC-43/Ena. We also identified the Nck-interacting kinase MIG-15/NIK and p21-activated kinases (PAKs), also implicated in axon guidance. Finally, PI3K signaling was required, specifically the Rictor/mTORC2 branch but not the mTORC1 branch that has been implicated in other aspects of PI3K signaling including stress and aging. Our results indicate that multiple pathways can mediate CDC-42-induced neuronal protrusions that might be relevant to growth cone protrusions during axon pathfinding. Each of these pathways involves Rac GTPases, which might serve to integrate the pathways and coordinate the multiple CDC-42 pathways. These pathways might be relevant to developmental events such as axon pathfinding as well as disease states such as metastatic melanoma.
Alan, Jamie K; Struckhoff, Eric C; Lundquist, Erik A
2013-01-01
Rho GTPases are key regulators of cellular protrusion and are involved in many developmental events including axon guidance during nervous system development. Rho GTPase pathways display functional redundancy in developmental events, including axon guidance. Therefore, their roles can often be masked when using simple loss-of-function genetic approaches. As a complement to loss-of-function genetics, we constructed a constitutively activated CDC-42(G12V) expressed in C. elegans neurons. CDC-42(G12V) drove the formation of ectopic lamellipodial and filopodial protrusions in the PDE neurons, which resembled protrusions normally found on migrating growth cones of axons. We then used a candidate gene approach to identify molecules that mediate CDC-42(G12V)-induced ectopic protrusions by determining if loss of function of the genes could suppress CDC-42(G12V). Using this approach, we identified 3 cytoskeletal pathways previously implicated in axon guidance, the Arp2/3 complex, UNC-115/abLIM, and UNC-43/Ena. We also identified the Nck-interacting kinase MIG-15/NIK and p21-activated kinases (PAKs), also implicated in axon guidance. Finally, PI3K signaling was required, specifically the Rictor/mTORC2 branch but not the mTORC1 branch that has been implicated in other aspects of PI3K signaling including stress and aging. Our results indicate that multiple pathways can mediate CDC-42-induced neuronal protrusions that might be relevant to growth cone protrusions during axon pathfinding. Each of these pathways involves Rac GTPases, which might serve to integrate the pathways and coordinate the multiple CDC-42 pathways. These pathways might be relevant to developmental events such as axon pathfinding as well as disease states such as metastatic melanoma. PMID:24149939
Factoring neurotrophins into a neurite-based pathophysiological model of schizophrenia.
Bellon, Alfredo; Krebs, Marie-Odile; Jay, Thérèse M
2011-06-01
Neurotrophins are growth factors that, through variations in concentration and changes in receptor expression, regulate the formation of axons and dendrites during development and throughout adult life. Here we review these growth factors, particularly in the context of schizophrenia, a psychiatric disorder characterized by neurodevelopmental abnormalities. We first discuss emerging information derived from physiologically relevant organotypic cultures and in vivo studies regarding the effects of neurotrophins on the neuronal structure including pruning and GABAergic neurons. We then review postmortem studies of neurotrophin levels and their receptors in brains of individuals with schizophrenia, and compare them with what is known about neurotrophin effects on neuronal structure. This comparison indicates that only some neuropathological defects encountered in patients with schizophrenia can be explained by the single action of neurotrophins on dendrites and axons. However, we propose that a number of inconsistent findings and apparently unrelated results in the schizophrenia field can be reconciled if neurons are considered structurally plastic cells capable of extending and retracting dendrites and axons throughout life. Copyright © 2011 Elsevier Ltd. All rights reserved.
Linking Essential Tremor to the Cerebellum: Neuropathological Evidence.
Louis, Elan D
2016-06-01
A fundamental question about essential tremor (ET) is whether its associated pathological changes and disease mechanisms are linkable to a specific brain region. To that end, recent tissue-based studies have made significant strides in elucidating changes in the ET brain. Emerging from these studies is increasing neuropathological evidence linking ET to the cerebellum. These studies have systematically identified a broad range of structural, degenerative changes in the ET cerebellum, spanning across all Purkinje cell compartments. These include the dendritic compartment (where there is an increase in number of Purkinje cell dendritic swellings, a pruning of the dendritic arbor, and a reduction in spine density), the cell body (where, aside from reductions in Purkinje cell linear density in some studies, there is an increase in the number of heterotopic Purkinje cell soma), and the axonal compartment (where a plethora of changes in axonal morphology have been observed, including an increase in the number of thickened axonal profiles, torpedoes, axonal recurrent collaterals, axonal branching, and terminal axonal sprouting). Additional changes, possibly due to secondary remodeling, have been observed in neighboring neuronal populations. These include a hypertrophy of basket cell axonal processes and changes in the distribution of climbing fiber-Purkinje cell synapses. These changes all distinguish ET from normal control brains. Initial studies further indicate that the profile (i.e., constellation) of these changes may separate ET from other diseases of the cerebellum, thereby serving as a disease signature. With the discovery of these changes, a new model of ET has arisen, which posits that it may be a neurodegenerative disorder centered in the cerebellar cortex. These newly emerging neuropathological studies pave the way for anatomically focused, hypothesis-driven, molecular mechanistic studies of disease pathogenesis.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.
Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at differentmore » developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner. • The nicotine-induced secondary motoneuron axonal pathfinding errors can occur independent of any muscle fiber alterations. • Nicotine exposure primarily affects dorsal projecting secondary motoneurons axons. • Nicotine-induced primary motoneuron axon pathfinding errors can influence secondary motoneuron axon morphology.« less
Loverde, Joseph R.; Pfister, Bryan J.
2015-01-01
Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18% applied over 5 min. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25% strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury. PMID:26379492
Can injured adult CNS axons regenerate by recapitulating development?
Hilton, Brett J; Bradke, Frank
2017-10-01
In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial function/axonal transport and the efficacy of synaptic transmission. In turn, these intracellular processes are linked to extracellular differences between the developing and adult CNS. During development, the extracellular environment directs axon growth and circuit formation. In adulthood, by contrast, extracellular factors, such as myelin and the extracellular matrix, restrict axon growth. Here, we discuss whether the reactivation of developmental processes can elicit axon regeneration in the injured CNS. © 2017. Published by The Company of Biologists Ltd.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Kai; Olsen, Olav; Tzvetkova-Robev, Dorothea
The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6 ectodomain in complex with the E2 domain of APP and show that it supports a model for APP-induced dimerization and activation of cell surface DR6.
Xu, Kai; Olsen, Olav; Tzvetkova-Robev, Dorothea; ...
2015-04-02
The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6 ectodomain in complex with the E2 domain of APP and show that it supports a model for APP-induced dimerization and activation of cell surface DR6.
Cell intrinsic control of axon regeneration
Mar, Fernando M; Bonni, Azad; Sousa, Mónica M
2014-01-01
Although neurons execute a cell intrinsic program of axonal growth during development, following the establishment of connections, the developmental growth capacity declines. Besides environmental challenges, this switch largely accounts for the failure of adult central nervous system (CNS) axons to regenerate. Here, we discuss the cell intrinsic control of axon regeneration, including not only the regulation of transcriptional and epigenetic mechanisms, but also the modulation of local protein translation, retrograde and anterograde axonal transport, and microtubule dynamics. We further explore the causes underlying the failure of CNS neurons to mount a vigorous regenerative response, and the paradigms demonstrating the activation of cell intrinsic axon growth programs. Finally, we present potential mechanisms to support axon regeneration, as these may represent future therapeutic approaches to promote recovery following CNS injury and disease. PMID:24531721
Netrins and UNC5 receptors in angiogenesis.
Freitas, Catarina; Larrivée, Bruno; Eichmann, Anne
2008-01-01
Both neuronal and vascular development require guidance to establish a precise branching pattern of these systems in the vertebrate body. Several molecules implicated in axon navigation have also been shown to regulate vessel sprouting. Among these guidance cues, Netrins constitute a family of diffusible molecules with a bifuncional role in axon pathfinding. Recent findings implicate Netrins in other developmental processes, including vascular development. We here review recent studies and discuss the possible dual function of Netrins and its receptors during branching of blood vessels in developmental and pathological angiogenesis.
Kaplan, Andrew; Bueno, Mardja; Hua, Luyang; Fournier, Alyson E
2018-01-01
The failure of damaged axons to regrow underlies disability in central nervous system injury and disease. Therapies that stimulate axon repair will be critical to restore function. Extensive axon regeneration can be induced by manipulation of oncogenes and tumor suppressors; however, it has been difficult to translate this into functional recovery in models of spinal cord injury. The current challenge is to maximize the functional integration of regenerating axons to recover motor and sensory behaviors. Insights into axonal growth and wiring during nervous system development are helping guide new approaches to boost regeneration and functional connectivity after injury in the mature nervous system. Here we discuss our current understanding of axonal behavior after injury and prospects for the development of drugs to optimize axon regeneration and functional recovery after CNS injury. Developmental Dynamics 247:18-23, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Oren-Suissa, Meital; Gattegno, Tamar; Kravtsov, Veronika; Podbilewicz, Benjamin
2017-01-01
Injury triggers regeneration of axons and dendrites. Research has identified factors required for axonal regeneration outside the CNS, but little is known about regeneration triggered by dendrotomy. Here, we study neuronal plasticity triggered by dendrotomy and determine the fate of complex PVD arbors following laser surgery of dendrites. We find that severed primary dendrites grow toward each other and reconnect via branch fusion. Simultaneously, terminal branches lose self-avoidance and grow toward each other, meeting and fusing at the tips via an AFF-1-mediated process. Ectopic branch growth is identified as a step in the regeneration process required for bypassing the lesion site. Failure of reconnection to the severed dendrites results in degeneration of the distal end of the neuron. We discover pruning of excess branches via EFF-1 that acts to recover the original wild-type arborization pattern in a late stage of the process. In contrast, AFF-1 activity during dendritic auto-fusion is derived from the lateral seam cells and not autonomously from the PVD neuron. We propose a model in which AFF-1-vesicles derived from the epidermal seam cells fuse neuronal dendrites. Thus, EFF-1 and AFF-1 fusion proteins emerge as new players in neuronal arborization and maintenance of arbor connectivity following injury in Caenorhabditis elegans. Our results demonstrate that there is a genetically determined multi-step pathway to repair broken dendrites in which EFF-1 and AFF-1 act on different steps of the pathway. EFF-1 is essential for dendritic pruning after injury and extrinsic AFF-1 mediates dendrite fusion to bypass injuries. PMID:28283540
Developmental time windows for axon growth influence neuronal network topology.
Lim, Sol; Kaiser, Marcus
2015-04-01
Early brain connectivity development consists of multiple stages: birth of neurons, their migration and the subsequent growth of axons and dendrites. Each stage occurs within a certain period of time depending on types of neurons and cortical layers. Forming synapses between neurons either by growing axons starting at similar times for all neurons (much-overlapped time windows) or at different time points (less-overlapped) may affect the topological and spatial properties of neuronal networks. Here, we explore the extreme cases of axon formation during early development, either starting at the same time for all neurons (parallel, i.e., maximally overlapped time windows) or occurring for each neuron separately one neuron after another (serial, i.e., no overlaps in time windows). For both cases, the number of potential and established synapses remained comparable. Topological and spatial properties, however, differed: Neurons that started axon growth early on in serial growth achieved higher out-degrees, higher local efficiency and longer axon lengths while neurons demonstrated more homogeneous connectivity patterns for parallel growth. Second, connection probability decreased more rapidly with distance between neurons for parallel growth than for serial growth. Third, bidirectional connections were more numerous for parallel growth. Finally, we tested our predictions with C. elegans data. Together, this indicates that time windows for axon growth influence the topological and spatial properties of neuronal networks opening up the possibility to a posteriori estimate developmental mechanisms based on network properties of a developed network.
Pruning or tuning? Maturational profiles of face specialization during typical development.
Zhu, Xun; Bhatt, Ramesh S; Joseph, Jane E
2016-06-01
Face processing undergoes significant developmental change with age. Two kinds of developmental changes in face specialization were examined in this study: specialized maturation, or the continued tuning of a region to faces but little change in the tuning to other categories; and competitive interactions, or the continued tuning to faces accompanied by decreased tuning to nonfaces (i.e., pruning). Using fMRI, in regions where adults showed a face preference, a face- and object-specialization index were computed for younger children (5-8 years), older children (9-12 years) and adults (18-45 years). The specialization index was scaled to each subject's maximum activation magnitude in each region to control for overall age differences in the activation level. Although no regions showed significant face specialization in the younger age group, regions strongly associated with social cognition (e.g., right posterior superior temporal sulcus, right inferior orbital cortex) showed specialized maturation, in which tuning to faces increased with age but there was no pruning of nonface responses. Conversely, regions that are associated with more basic perceptual processing or motor mirroring (right middle temporal cortex, right inferior occipital cortex, right inferior frontal opercular cortex) showed competitive interactions in which tuning to faces was accompanied by pruning of object responses with age. The overall findings suggest that cortical maturation for face processing is regional-specific and involves both increased tuning to faces and diminished response to nonfaces. Regions that show competitive interactions likely support a more generalized function that is co-opted for face processing with development, whereas regions that show specialized maturation increase their tuning to faces, potentially in an activity-dependent, experience-driven manner.
Allodi, S; Reese, B E; Cavalcante, L A
1990-01-01
The spectra of fiber sizes at different depths of the optic tract of the opossum Didelphis marsupialis were examined by electron microscopy in order to test for correlations between the eventual location of axons and relevant developmental events. Frequency histograms showed 1) a predominant representation of medium-sized axons and the virtual exclusion of coarse fibers from the deepest portion of that pathway, and 2) a progressive increase in the proportion of thin axons from deep to superficial sites of the tract. These findings are discussed in terms of the view of the optic tract as a chronological map of axon arrival.
Cell-Autonomous Regulation of Dendritic Spine Density by PirB.
Vidal, George S; Djurisic, Maja; Brown, Kiana; Sapp, Richard W; Shatz, Carla J
2016-01-01
Synapse density on cortical pyramidal neurons is modulated by experience. This process is highest during developmental critical periods, when mechanisms of synaptic plasticity are fully engaged. In mouse visual cortex, the critical period for ocular dominance (OD) plasticity coincides with the developmental pruning of synapses. At this time, mice lacking paired Ig-like receptor B (PirB) have excess numbers of dendritic spines on L5 neurons; these spines persist and are thought to underlie the juvenile-like OD plasticity observed in adulthood. Here we examine whether PirB is required specifically in excitatory neurons to exert its effect on dendritic spine and synapse density during the critical period. In mice with a conditional allele of PirB (PirB fl/fl ), PirB was deleted only from L2/3 cortical pyramidal neurons in vivo by timed in utero electroporation of Cre recombinase. Sparse mosaic expression of Cre produced neurons lacking PirB in a sea of wild-type neurons and glia. These neurons had significantly elevated dendritic spine density, as well as increased frequency of miniature EPSCs, suggesting that they receive a greater number of synaptic inputs relative to Cre - neighbors. The effect of cell-specific PirB deletion on dendritic spine density was not accompanied by changes in dendritic branching complexity or axonal bouton density. Together, results imply a neuron-specific, cell-autonomous action of PirB on synaptic density in L2/3 pyramidal cells of visual cortex. Moreover, they are consistent with the idea that PirB functions normally to corepress spine density and synaptic plasticity, thereby maintaining headroom for cells to encode ongoing experience-dependent structural change throughout life.
The Evolution and Development of Neural Superposition
Agi, Egemen; Langen, Marion; Altschuler, Steven J.; Wu, Lani F.; Zimmermann, Timo
2014-01-01
Visual systems have a rich history as model systems for the discovery and understanding of basic principles underlying neuronal connectivity. The compound eyes of insects consist of up to thousands of small unit eyes that are connected by photoreceptor axons to set up a visual map in the brain. The photoreceptor axon terminals thereby represent neighboring points seen in the environment in neighboring synaptic units in the brain. Neural superposition is a special case of such a wiring principle, where photoreceptors from different unit eyes that receive the same input converge upon the same synaptic units in the brain. This wiring principle is remarkable, because each photoreceptor in a single unit eye receives different input and each individual axon, among thousands others in the brain, must be sorted together with those few axons that have the same input. Key aspects of neural superposition have been described as early as 1907. Since then neuroscientists, evolutionary and developmental biologists have been fascinated by how such a complicated wiring principle could evolve, how it is genetically encoded, and how it is developmentally realized. In this review article, we will discuss current ideas about the evolutionary origin and developmental program of neural superposition. Our goal is to identify in what way the special case of neural superposition can help us answer more general questions about the evolution and development of genetically “hard-wired” synaptic connectivity in the brain. PMID:24912630
The evolution and development of neural superposition.
Agi, Egemen; Langen, Marion; Altschuler, Steven J; Wu, Lani F; Zimmermann, Timo; Hiesinger, Peter Robin
2014-01-01
Visual systems have a rich history as model systems for the discovery and understanding of basic principles underlying neuronal connectivity. The compound eyes of insects consist of up to thousands of small unit eyes that are connected by photoreceptor axons to set up a visual map in the brain. The photoreceptor axon terminals thereby represent neighboring points seen in the environment in neighboring synaptic units in the brain. Neural superposition is a special case of such a wiring principle, where photoreceptors from different unit eyes that receive the same input converge upon the same synaptic units in the brain. This wiring principle is remarkable, because each photoreceptor in a single unit eye receives different input and each individual axon, among thousands others in the brain, must be sorted together with those few axons that have the same input. Key aspects of neural superposition have been described as early as 1907. Since then neuroscientists, evolutionary and developmental biologists have been fascinated by how such a complicated wiring principle could evolve, how it is genetically encoded, and how it is developmentally realized. In this review article, we will discuss current ideas about the evolutionary origin and developmental program of neural superposition. Our goal is to identify in what way the special case of neural superposition can help us answer more general questions about the evolution and development of genetically "hard-wired" synaptic connectivity in the brain.
Gates, Michael A; Kannan, Ramakrishnan; Giniger, Edward
2011-11-30
The phylogenetically conserved transcription factor Lola is essential for many aspects of axon growth and guidance, synapse formation and neural circuit development in Drosophila. To date it has been difficult, however, to obtain an overall view of Lola functions and mechanisms. We use expression microarrays to identify the lola-dependent transcriptome in the Drosophila embryo. We find that lola regulates the expression of a large selection of genes that are known to affect each of several lola-dependent developmental processes. Among other loci, we find lola to be a negative regulator of spire, an actin nucleation factor that has been studied for its essential role in oogenesis. We show that spire is expressed in the nervous system and is required for a known lola-dependent axon guidance decision, growth of ISNb motor axons. We further show that reducing spire gene dosage suppresses this aspect of the lola phenotype, verifying that derepression of spire is an important contributor to the axon stalling phenotype of embryonic motor axons in lola mutants. These data shed new light on the molecular mechanisms of many lola-dependent processes, and also identify several developmental processes not previously linked to lola that are apt to be regulated by this transcription factor. These data further demonstrate that excessive expression of the actin nucleation factor Spire is as deleterious for axon growth in vivo as is the loss of Spire, thus highlighting the need for a balance in the elementary steps of actin dynamics to achieve effective neuronal morphogenesis.
Oren-Suissa, Meital; Gattegno, Tamar; Kravtsov, Veronika; Podbilewicz, Benjamin
2017-05-01
Injury triggers regeneration of axons and dendrites. Research has identified factors required for axonal regeneration outside the CNS, but little is known about regeneration triggered by dendrotomy. Here, we study neuronal plasticity triggered by dendrotomy and determine the fate of complex PVD arbors following laser surgery of dendrites. We find that severed primary dendrites grow toward each other and reconnect via branch fusion. Simultaneously, terminal branches lose self-avoidance and grow toward each other, meeting and fusing at the tips via an AFF-1-mediated process. Ectopic branch growth is identified as a step in the regeneration process required for bypassing the lesion site. Failure of reconnection to the severed dendrites results in degeneration of the distal end of the neuron. We discover pruning of excess branches via EFF-1 that acts to recover the original wild-type arborization pattern in a late stage of the process. In contrast, AFF-1 activity during dendritic auto-fusion is derived from the lateral seam cells and not autonomously from the PVD neuron. We propose a model in which AFF-1-vesicles derived from the epidermal seam cells fuse neuronal dendrites. Thus, EFF-1 and AFF-1 fusion proteins emerge as new players in neuronal arborization and maintenance of arbor connectivity following injury in Caenorhabditis elegans Our results demonstrate that there is a genetically determined multi-step pathway to repair broken dendrites in which EFF-1 and AFF-1 act on different steps of the pathway. EFF-1 is essential for dendritic pruning after injury and extrinsic AFF-1 mediates dendrite fusion to bypass injuries. Copyright © 2017 by the Genetics Society of America.
Onishi, Keisuke
2017-01-01
Commissural axons switch on responsiveness to Wnt attraction during midline crossing and turn anteriorly only after exiting the floor plate. We report here that Sonic Hedgehog (Shh)-Smoothened signaling downregulates Shisa2, which inhibits the glycosylation and cell surface presentation of Frizzled3 in rodent commissural axon growth cones. Constitutive Shisa2 expression causes randomized turning of post-crossing commissural axons along the anterior–posterior (A–P) axis. Loss of Shisa2 led to precocious anterior turning of commissural axons before or during midline crossing. Post-crossing commissural axon turning is completely randomized along the A–P axis when Wntless, which is essential for Wnt secretion, is conditionally knocked out in the floor plate. This regulatory link between Shh and planar cell polarity (PCP) signaling may also occur in other developmental processes. PMID:28885142
Netrin-4 regulates thalamocortical axon branching in an activity-dependent fashion.
Hayano, Yasufumi; Sasaki, Kensuke; Ohmura, Nami; Takemoto, Makoto; Maeda, Yurie; Yamashita, Toshihide; Hata, Yoshio; Kitada, Kazuhiro; Yamamoto, Nobuhiko
2014-10-21
Axon branching is remodeled by sensory-evoked and spontaneous neuronal activity. However, the underlying molecular mechanism is largely unknown. Here, we demonstrate that the netrin family member netrin-4 (NTN4) contributes to activity-dependent thalamocortical (TC) axon branching. In the postnatal developmental stages of rodents, ntn4 expression was abundant in and around the TC recipient layers of sensory cortices. Neuronal activity dramatically altered the ntn4 expression level in the cortex in vitro and in vivo. TC axon branching was promoted by exogenous NTN4 and suppressed by depletion of the endogenous protein. Moreover, unc-5 homolog B (Unc5B), which strongly bound to NTN4, was expressed in the sensory thalamus, and knockdown of Unc5B in thalamic cells markedly reduced TC axon branching. These results suggest that NTN4 acts as a positive regulator for TC axon branching through activity-dependent expression.
The over-pruning hypothesis of autism.
Thomas, Michael S C; Davis, Rachael; Karmiloff-Smith, Annette; Knowland, Victoria C P; Charman, Tony
2016-03-01
This article outlines the over-pruning hypothesis of autism. The hypothesis originates in a neurocomputational model of the regressive sub-type (Thomas, Knowland & Karmiloff-Smith, 2011a, 2011b). Here we develop a more general version of the over-pruning hypothesis to address heterogeneity in the timing of manifestation of ASD, including new computer simulations which reconcile the different observed developmental trajectories (early onset, late onset, regression) via a single underlying atypical mechanism; and which show how unaffected siblings of individuals with ASD may differ from controls either by inheriting a milder version of the pathological mechanism or by co-inheriting the risk factors without the pathological mechanism. The proposed atypical mechanism involves overly aggressive synaptic pruning in infancy and early childhood, an exaggeration of a normal phase of brain development. We show how the hypothesis generates novel predictions that differ from existing theories of ASD including that (1) the first few months of development in ASD will be indistinguishable from typical, and (2) the earliest atypicalities in ASD will be sensory and motor rather than social. Both predictions gain cautious support from emerging longitudinal studies of infants at-risk of ASD. We review evidence consistent with the over-pruning hypothesis, its relation to other current theories (including C. Frith's under-pruning proposal; C. Frith, 2003, 2004), as well as inconsistent data and current limitations. The hypothesis situates causal accounts of ASD within a framework of protective and risk factors (Newschaffer et al., 2012); clarifies different versions of the broader autism phenotype (i.e. the implication of observed similarities between individuals with autism and their family members); and integrates data from multiple disciplines, including behavioural studies, neuroscience studies, genetics, and intervention studies. © 2015 John Wiley & Sons Ltd.
2011-01-01
Background The phylogenetically conserved transcription factor Lola is essential for many aspects of axon growth and guidance, synapse formation and neural circuit development in Drosophila. To date it has been difficult, however, to obtain an overall view of Lola functions and mechanisms. Results We use expression microarrays to identify the lola-dependent transcriptome in the Drosophila embryo. We find that lola regulates the expression of a large selection of genes that are known to affect each of several lola-dependent developmental processes. Among other loci, we find lola to be a negative regulator of spire, an actin nucleation factor that has been studied for its essential role in oogenesis. We show that spire is expressed in the nervous system and is required for a known lola-dependent axon guidance decision, growth of ISNb motor axons. We further show that reducing spire gene dosage suppresses this aspect of the lola phenotype, verifying that derepression of spire is an important contributor to the axon stalling phenotype of embryonic motor axons in lola mutants. Conclusions These data shed new light on the molecular mechanisms of many lola-dependent processes, and also identify several developmental processes not previously linked to lola that are apt to be regulated by this transcription factor. These data further demonstrate that excessive expression of the actin nucleation factor Spire is as deleterious for axon growth in vivo as is the loss of Spire, thus highlighting the need for a balance in the elementary steps of actin dynamics to achieve effective neuronal morphogenesis. PMID:22129300
Maor-Nof, Maya; Romi, Erez; Sar Shalom, Hadas; Ulisse, Valeria; Raanan, Calanit; Nof, Aviv; Leshkowitz, Dena; Lang, Roland; Yaron, Avraham
2016-12-07
Developmental neuronal cell death and axonal elimination are controlled by transcriptional programs, of which their nature and the function of their components remain elusive. Here, we identified the dual specificity phosphatase Dusp16 as part of trophic deprivation-induced transcriptome in sensory neurons. Ablation of Dusp16 enhanced axonal degeneration in response to trophic withdrawal, suggesting that it has a protective function. Moreover, axonal skin innervation was severely reduced while neuronal elimination was increased in the Dusp16 knockout. Mechanistically, Dusp16 negatively regulates the transcription factor p53 and antagonizes the expression of the pro-degenerative factor, Puma (p53 upregulated modulator of apoptosis). Co-ablation of Puma with Dusp16 protected axons from rapid degeneration and specifically reversed axonal innervation loss early in development with no effect on neuronal deficits. Overall, these results reveal that physiological axonal elimination is regulated by a transcriptional program that integrates regressive and progressive elements and identify Dusp16 as a new axonal preserving factor. Copyright © 2016 Elsevier Inc. All rights reserved.
Huria, Tahani; Beeraka, Narasimha Murthy; Al-Ghamdi, Badrah; Fern, Robert
2015-01-01
Ischemic-type injury to developing white matter is associated with the significant clinical condition cerebral palsy and with the cognitive deficits associated with premature birth. Premyelinated axons are the major cellular component of fetal white matter and loss of axon function underlies the disability, but the cellular mechanisms producing ischemic injury to premyelinated axons have not previously been described. Injury was found to require longer periods of modelled ischemia than at latter developmental points. Ischemia produced initial hyperexcitability in axons followed by loss of function after Na+ and Ca2+ influx. N-methyl-D-aspartate- (NMDA) type glutamate receptor (GluR) agonists potentiated axon injury while antagonists were protective. The NMDA GluR obligatory Nr1 subunit colocalized with markers of small premyelinated axons and expression was found at focal regions of axon injury. Ischemic injury of glial cells present in early developing white matter was NMDA GluR independent. Axons in human postconception week 18 to 23 white matter had a uniform prediameter expansion phenotype and postembedded immuno-gold labelling showed Nr1 subunit expression on the membrane of these axons, demonstrating a shared key neuropathologic feature with the rodent model. Premyelinated central axons therefore express high levels of functional NMDA GluRs that confer sensitivity to ischemic injury. PMID:25515212
Shaping dendritic spines in autism spectrum disorder: mTORC1-dependent macroautophagy.
Bowling, Heather; Klann, Eric
2014-09-03
In this issue of Neuron, Tang et al. (2014) explore the relationship between developmental dendritic pruning, elevated mTORC1 signaling, macroautophagy, and autism spectrum disorder. The study provides valuable new insight into mTORC1-dependent cellular dysfunction and neurodevelopmental disorders. Copyright © 2014 Elsevier Inc. All rights reserved.
In search of intelligence: evolving a developmental neuron capable of learning
NASA Astrophysics Data System (ADS)
Khan, Gul Muhammad; Miller, Julian Francis
2014-10-01
A neuro-inspired multi-chromosomal genotype for a single developmental neuron capable of learning and developing memory is proposed. This genotype is evolved so that the phenotype which changes and develops during an agent's lifetime (while problem-solving) gives the agent the capacity for learning by experience. Seven important processes of signal processing and neural structure development are identified from biology and encoded using Cartesian Genetic Programming. These chromosomes represent the electrical and developmental aspects of dendrites, axonal branches, synapses and the neuron soma. The neural morphology that occurs by running these chromosomes is highly dynamic. The dendritic/axonal branches and synaptic connections form and change in response to situations encountered in the learning task. The approach has been evaluated in the context of maze-solving and the board game of checkers (draughts) demonstrating interesting learning capabilities. The motivation underlying this research is to, ab initio, evolve genotypes that build phenotypes with an ability to learn.
Optimization of interneuron function by direct coupling of cell migration and axonal targeting.
Lim, Lynette; Pakan, Janelle M P; Selten, Martijn M; Marques-Smith, André; Llorca, Alfredo; Bae, Sung Eun; Rochefort, Nathalie L; Marín, Oscar
2018-06-18
Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb-a gene that is preferentially expressed by these cells-cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex.
dMyc is required in retinal progenitors to prevent JNK-mediated retinal glial activation
Correia, Andreia; Santos, Marília A.; Relvas, João B.; Pereira, Paulo S.
2017-01-01
In the nervous system, glial cells provide crucial insulation and trophic support to neurons and are important for neuronal survival. In reaction to a wide variety of insults, glial cells respond with changes in cell morphology and metabolism to allow repair. Additionally, these cells can acquire migratory and proliferative potential. In particular, after axonal damage or pruning the clearance of axonal debris by glial cells is key for a healthy nervous system. Thus, bidirectional neuron-glial interactions are crucial in development, but little is known about the cellular sensors and signalling pathways involved. In here, we show that decreased cellular fitness in retinal progenitors caused by reduced Drosophila Myc expression triggers non cell-autonomous activation of retinal glia proliferation and overmigration. Glia migration occurs beyond its normal limit near the boundary between differentiated photoreceptors and precursor cells, extending into the progenitor domain. This overmigration is stimulated by JNK activation (and the function of its target Mmp1), while proliferative responses are mediated by Dpp/TGF-β signalling activation. PMID:28267791
Dock and Pak regulate olfactory axon pathfinding in Drosophila.
Ang, Lay-Hong; Kim, Jenny; Stepensky, Vitaly; Hing, Huey
2003-04-01
The convergence of olfactory axons expressing particular odorant receptor (Or) genes on spatially invariant glomeruli in the brain is one of the most dramatic examples of precise axon targeting in developmental neurobiology. The cellular and molecular mechanisms by which olfactory axons pathfind to their targets are poorly understood. We report here that the SH2/SH3 adapter Dock and the serine/threonine kinase Pak are necessary for the precise guidance of olfactory axons. Using antibody localization, mosaic analyses and cell-type specific rescue, we observed that Dock and Pak are expressed in olfactory axons and function autonomously in olfactory neurons to regulate the precise wiring of the olfactory map. Detailed analyses of the mutant phenotypes in whole mutants and in small multicellular clones indicate that Dock and Pak do not control olfactory neuron (ON) differentiation, but specifically regulate multiple aspects of axon trajectories to guide them to their cognate glomeruli. Structure/function studies show that Dock and Pak form a signaling pathway that mediates the response of olfactory axons to guidance cues in the developing antennal lobe (AL). Our findings therefore identify a central signaling module that is used by ONs to project to their cognate glomeruli.
Partial Agenesis and Hypoplasia of the Corpus Callosum in Idiopathic Autism
Wegiel, Jarek; Flory, Michael; Kaczmarski, Wojciech; Brown, W. Ted; Chadman, Kathryn; Wisniewski, Thomas; Nowicki, Krzysztof; Kuchna, Izabela; Ma, Shuang Yong; Wegiel, Jerzy
2017-01-01
Abstract To test the hypothesis that developmental anomalies of the corpus callosum (CC), contribute to the pathogenesis of autism, we characterized the type, topography, and severity of CC pathology corresponding to reduced CC areas that are detected by magnetic resonance imaging in the brains of 11 individuals with autism and 11 controls. In the brains of 3 autistic subjects, partial CC agenesis resulted in complete or partial lack of interhemispheric axonal connections in CC segments III–V. In these cases, a combination of focal agenesis and uniform axonal deficit caused reduction of CC areas by 37%, of axon numbers by 62%, and of the numerical density of axons by 39%. In the CC of 8 autistic subjects without agenesis, there was an 18% deficit of the midsagittal CC area, 48.4% deficit of axon numbers, and 37% reduction of the numerical density of axons. The significantly thinner CC, reduced CC area, and uniform axonal deficit in all autistic subjects were classified as CC hypoplasia. Thus, the byproduct of partial CC agenesis and hypoplasia is reduction of axonal connections between cortical areas known to be involved in behavioral alterations observed in people with autism. PMID:28395085
Yoo, Soonmoon; Kim, Hak Hee; Kim, Paul; Donnelly, Christopher J.; Kalinski, Ashley L.; Vuppalanchi, Deepika; Park, Michael; Lee, Seung Joon; Merianda, Tanuja T.; Perrone-Bizzozero, Nora I.; Twiss, Jeffery L.
2013-01-01
Localized translation of axonal mRNAs contributes to developmental and regenerative axon growth. Although untranslated regions (UTRs) of many different axonal mRNAs appear to drive their localization, there has been no consensus RNA structure responsible for this localization. We recently showed that limited expression of ZBP1 protein restricts axonal localization of both β-actin and GAP-43 mRNAs. β-actin 3′UTR has a defined element for interaction with ZBP1, but GAP-43 mRNA shows no homology to this RNA sequence. Here, we show that an AU-rich element (ARE) in GAP-43’s 3′UTR is necessary and sufficient for its axonal localization. Axonal GAP-43 mRNA levels increase after in vivo injury, and GAP-43 mRNA shows an increased half-life in regenerating axons. GAP-43 mRNA interacts with both HuD and ZBP1, and HuD and ZBP1 coimmunoprecipitate in an RNA-dependent fashion. Reporter mRNA with the GAP-43 ARE competes with endogenous β-actin mRNA for axonal localization and decreases axon length and branching similar to the β-actin 3′UTR competing with endogenous GAP-43 mRNA. Conversely, overexpressing GAP-43 coding sequence with it’s 3′UTR ARE increases axonal elongation and this effect is lost when just the ARE is deleted from GAP-43’s 3′UTR. PMID:23586486
Zhang, Xiaona; Xu, Lei; Tian, Hua; Wang, Cuicui; Wang, Wei; Ru, Shaoguo
2017-09-01
Netrins, chemotropic guidance cues, can guide the extension of serotonergic axons by binding to netrin receptors during neural development. However, little is known about whether disruption of netrin signaling is involved in the mechanisms by which organophosphorus pesticides affect serotonergic nervous system (SNS) development. In this study, we evaluated the effects of the pesticide monocrotophos (MCP) on the expression patterns of HpNetrin and its receptor neogenin as well as on the intracellular calcium ion (Ca 2+ ) levels in Hemicentrotus pulcherrimus (sea urchin) by exposing fertilized embryos to 0, 0.01, 0.10, and 1.00mg/L MCP. The results showed that MCP disrupted HpNetrin and neogenin expression at different developmental stages in H. pulcherrimus and that Ca 2+ appeared to be involved in the MCP-induced developmental neurotoxicity. Specifically, the lower concentrations of MCP elevated HpNetrin and neogenin transcription, resulting in higher intracellular Ca 2+ levels during the early developmental stages in the sea urchin; this may affect netrin-directed cell migration/axon extension and subsequently disrupt serotonergic axon branching and synapse formation. In contrast, 1.00mg/L MCP exhibited an inhibitory effect on HpNetrin and neogenin transcription. This finding implies that the regulatory roles of these factors may be diminished during early development, thereby causing developmental defects in the sea urchin. Collectively, our results provide a basis for exploring the involvement of netrin and neogenin in the organophosphate-induced disruption of the SNS during development. Copyright © 2017 Elsevier B.V. All rights reserved.
Song, Yuanquan; Ori-McKenney, Kassandra M.; Zheng, Yi; Han, Chun; Jan, Lily Yeh; Jan, Yuh Nung
2012-01-01
Both cell-intrinsic and extrinsic pathways govern axon regeneration, but only a limited number of factors have been identified and it is not clear to what extent axon regeneration is evolutionarily conserved. Whether dendrites also regenerate is unknown. Here we report that, like the axons of mammalian sensory neurons, the axons of certain Drosophila dendritic arborization (da) neurons are capable of substantial regeneration in the periphery but not in the CNS, and activating the Akt pathway enhances axon regeneration in the CNS. Moreover, those da neurons capable of axon regeneration also display dendrite regeneration, which is cell type-specific, developmentally regulated, and associated with microtubule polarity reversal. Dendrite regeneration is restrained via inhibition of the Akt pathway in da neurons by the epithelial cell-derived microRNA bantam but is facilitated by cell-autonomous activation of the Akt pathway. Our study begins to reveal mechanisms for dendrite regeneration, which depends on both extrinsic and intrinsic factors, including the PTEN–Akt pathway that is also important for axon regeneration. We thus established an important new model system—the fly da neuron regeneration model that resembles the mammalian injury model—with which to study and gain novel insights into the regeneration machinery. PMID:22759636
Molecular mechanisms of optic axon guidance
NASA Astrophysics Data System (ADS)
Inatani, Masaru
2005-12-01
Axon guidance is one of the critical processes during vertebrate central nervous system (CNS) development. The optic nerve, which contains the axons of retinal ganglion cells, has been used as a powerful model to elucidate some of the mechanisms underlying axon guidance because it is easily manipulated experimentally, and its function is well understood. Recent molecular biology studies have revealed that numerous guidance molecules control the development of the visual pathway. This review introduces the molecular mechanisms involved in each critical step during optic axon guidance. Axonal projections to the optic disc are thought to depend on adhesion molecules and inhibitory extracellular matrices such as chondroitin sulfate. The formation of the head of the optic nerve and the optic chiasm require ligand-receptor interactions between netrin-1 and the deleted in colorectal cancer receptor, and Slit proteins and Robo receptors, respectively. The gradient distributions of ephrin ligands and Eph receptors are essential for correct ipsilateral projections at the optic chiasm and the topographic mapping of axons in the superior colliculus/optic tectum. The precise gradient is regulated by transcription factors determining the retinal dorso-ventral and nasal-temporal polarities. Moreover, the axon guidance activities by Slit and semaphorin 5A require the existence of heparan sulfate, which binds to numerous guidance molecules. Recent discoveries about the molecular mechanisms underlying optic nerve guidance will facilitate progress in CNS developmental biology and axon-regeneration therapy.
Moya, K L; Confaloni, A M; Allinquant, B
1994-11-01
We have shown previously that the amyloid precursor protein (APP) is synthesized in retinal ganglion cells and is rapidly transported down the axons, and that different molecular weight forms of the precursor have different developmental time courses. Some APP isoforms contain a Kunitz protease inhibitor (KPI) domain, and APP that lacks the KPI domain is considered the predominant isoform in neurons. We now show that, among the various rapidly transported APPs, a 140-kDa isoform contains the KPI domain. This APP isoform is highly expressed in rapidly growing retinal axons, and it is also prominent in adult axon endings. This 140-kDa KPI-containing APP is highly sulfated compared with other axonally transported isoforms. These results show that APP with the KPI domain is a prominent isoform synthesized in neurons in vivo, and they suggest that the regulation of protease activity may be an important factor during the establishment of neuronal connections.
Tom, Veronica J.; Sandrow-Feinberg, Harra R.; Miller, Kassi; Domitrovich, Cheryl; Bouyer, Julien; Zhukareva, Victoria; Klaw, Michelle C.; Lemay, Michel A.; Houlé, John D.
2016-01-01
Although axons lose some of their intrinsic capacity for growth after their developmental period, some axons retain the potential for regrowth after injury. When provided with a growth-promoting substrate such as a peripheral nerve graft (PNG), severed axons regenerate into and through the graft; however, they stop when they reach the glial scar at the distal graft-host interface that is rich with inhibitory chondroitin sulfate proteoglycans. We previously showed that treatment of a spinal cord injury site with chondroitinase (ChABC) allows axons within the graft to traverse the scar and reinnervate spinal cord, where they form functional synapses. While this improvement in outgrowth was significant, it still represented only a small percentage (<20%) of axons compared to the total number of axons that regenerated into the PNG. Here we tested whether providing exogenous brain-derived neurotrophic factor (BDNF) via lentivirus in tissue distal to the PNG would augment regeneration beyond a ChABC-treated glial interface. We found that ChABC treatment alone promoted axonal regeneration but combining ChABC with BDNF-lentivirus did not increase the number of axons that regenerated back into spinal cord. Combining BDNF with ChABC did increase the number of spinal cord neurons that were trans-synaptically activated during electrical stimulation of the graft, as indicated by c-Fos expression, suggesting that BDNF overexpression improved the functional significance of axons that did reinnervate distal spinal cord tissue. PMID:23022460
Henson, Maile A.; Tucker, Charles J.; Zhao, Meilan; Dudek, Serena M.
2016-01-01
Activity-dependent pruning of synaptic contacts plays a critical role in shaping neuronal circuitry in response to the environment during postnatal brain development. Although there is compelling evidence that shrinkage of dendritic spines coincides with synaptic long-term depression (LTD), and that LTD is accompanied by synapse loss, whether NMDA receptor (NMDAR)-dependent LTD is a required step in the progression toward synapse pruning is still unknown. Using repeated applications of NMDA to induce LTD in dissociated rat neuronal cultures, we found that synapse density, as measured by colocalization of fluorescent markers for pre- and postsynaptic structures, was decreased irrespective of the presynaptic marker used, post-treatment recovery time, and the dendritic location of synapses. Consistent with previous studies, we found that synapse loss could occur without apparent net spine loss or cell death. Furthermore, synapse loss was unlikely to require direct contact with microglia, as the number of these cells was minimal in our culture preparations. Supporting a model by which NMDAR-LTD is required for synapse loss, the effect of NMDA on fluorescence colocalization was prevented by phosphatase and caspase inhibitors. In addition, gene transcription and protein translation also appeared to be required for loss of putative synapses. These data support the idea that NMDAR-dependent LTD is a required step in synapse pruning and contribute to our understanding of the basic mechanisms of this developmental process. PMID:27794462
Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment
Tapia, Mónica; Dominguez, Ana; Zhang, Wei; del Puerto, Ana; Ciorraga, María; Benitez, María José; Guaza, Carmen; Garrido, Juan José
2017-01-01
Neuronal polarization underlies the ability of neurons to integrate and transmit information. This process begins early in development with axon outgrowth, followed by dendritic growth and subsequent maturation. In between these two steps, the axon initial segment (AIS), a subcellular domain crucial for generating action potentials (APs) and maintaining the morphological and functional polarization, starts to develop. However, the cellular/molecular mechanisms and receptors involved in AIS initial development and maturation are mostly unknown. In this study, we have focused on the role of the type-1 cannabinoid receptor (CB1R), a highly abundant G-protein coupled receptor (GPCR) in the nervous system largely involved in different phases of neuronal development and differentiation. Although CB1R activity modulation has been related to changes in axons or dendrites, its possible role as a modulator of AIS development has not been yet explored. Here we analyzed the potential role of CB1R on neuronal morphology and AIS development using pharmacological and RNA interference approaches in cultured hippocampal neurons. CB1R inhibition, at a very early developmental stage, has no effect on axonal growth, yet CB1R activation can promote it. By contrast, subsequent dendritic growth is impaired by CB1R inhibition, which also reduces ankyrinG density at the AIS. Moreover, our data show a significant correlation between early dendritic growth and ankyrinG density. However, CB1R inhibition in later developmental stages after dendrites are formed only reduces ankyrinG accumulation at the AIS. In conclusion, our data suggest that neuronal CB1R basal activity plays a role in initial development of dendrites and indirectly in AIS proteins accumulation. Based on the lack of CB1R expression at the AIS, we hypothesize that CB1R mediated modulation of dendritic arbor size during early development indirectly determines the accumulation of ankyrinG and AIS development. Further studies will be necessary to determine which CB1R-dependent mechanisms can coordinate these two domains, and what may be the impact of these early developmental changes once neurons mature and are embedded in a functional brain network. PMID:28179879
Efficient self-organizing multilayer neural network for nonlinear system modeling.
Han, Hong-Gui; Wang, Li-Dan; Qiao, Jun-Fei
2013-07-01
It has been shown extensively that the dynamic behaviors of a neural system are strongly influenced by the network architecture and learning process. To establish an artificial neural network (ANN) with self-organizing architecture and suitable learning algorithm for nonlinear system modeling, an automatic axon-neural network (AANN) is investigated in the following respects. First, the network architecture is constructed automatically to change both the number of hidden neurons and topologies of the neural network during the training process. The approach introduced in adaptive connecting-and-pruning algorithm (ACP) is a type of mixed mode operation, which is equivalent to pruning or adding the connecting of the neurons, as well as inserting some required neurons directly. Secondly, the weights are adjusted, using a feedforward computation (FC) to obtain the information for the gradient during learning computation. Unlike most of the previous studies, AANN is able to self-organize the architecture and weights, and to improve the network performances. Also, the proposed AANN has been tested on a number of benchmark problems, ranging from nonlinear function approximating to nonlinear systems modeling. The experimental results show that AANN can have better performances than that of some existing neural networks. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.
Control of neuronal polarity and plasticity--a renaissance for microtubules?
Hoogenraad, Casper C; Bradke, Frank
2009-12-01
Microtubules have been regarded as essential structures for stable neuronal morphology but new studies are highlighting their role in dynamic neuronal processes. Recent work demonstrates that the microtubule cytoskeleton has an active role during different phases of neuronal polarization - microtubules and their stability determine axon formation, they maintain the identity of axons and they regulate the dynamics of dendritic spines, the major sites of excitatory synaptic input. Although microtubules fulfill distinct cellular functions at different developmental stages, the underlying molecular mechanisms are remarkably similar. Reccurring themes are that microtubules direct specific membrane traffic and affect actin dynamics to locally organize axon growth and spine dynamics. We review the novel role of microtubules during neuronal development and discuss models for microtubule-dependent signaling in neuronal plasticity.
Sánchez-Ponce, Diana; DeFelipe, Javier; Garrido, Juan José; Muñoz, Alberto
2012-01-01
Axonal outgrowth and the formation of the axon initial segment (AIS) are early events in the acquisition of neuronal polarity. The AIS is characterized by a high concentration of voltage-dependent sodium and potassium channels. However, the specific ion channel subunits present and their precise localization in this axonal subdomain vary both during development and among the types of neurons, probably determining their firing characteristics in response to stimulation. Here, we characterize the developmental expression of different subfamilies of voltage-gated potassium channels in the AISs of cultured mouse hippocampal neurons, including subunits Kv1.2, Kv2.2 and Kv7.2. In contrast to the early appearance of voltage-gated sodium channels and the Kv7.2 subunit at the AIS, Kv1.2 and Kv2.2 subunits were tethered at the AIS only after 10 days in vitro. Interestingly, we observed different patterns of Kv1.2 and Kv2.2 subunit expression, with each confined to distinct neuronal populations. The accumulation of Kv1.2 and Kv2.2 subunits at the AIS was dependent on ankyrin G tethering, it was not affected by disruption of the actin cytoskeleton and it was resistant to detergent extraction, as described previously for other AIS proteins. This distribution of potassium channels in the AIS further emphasizes the heterogeneity of this structure in different neuronal populations, as proposed previously, and suggests corresponding differences in action potential regulation. PMID:23119056
Forbes, Lindsey H.
2018-01-01
The extracellular environment of the central nervous system (CNS) becomes highly structured and organized as the nervous system matures. The extracellular space of the CNS along with its subdomains plays a crucial role in the function and stability of the CNS. In this review, we have focused on two components of the neuronal extracellular environment, which are important in regulating CNS plasticity including the extracellular matrix (ECM) and myelin. The ECM consists of chondroitin sulfate proteoglycans (CSPGs) and tenascins, which are organized into unique structures called perineuronal nets (PNNs). PNNs associate with the neuronal cell body and proximal dendrites of predominantly parvalbumin-positive interneurons, forming a robust lattice-like structure. These developmentally regulated structures are maintained in the adult CNS and enhance synaptic stability. After injury, however, CSPGs and tenascins contribute to the structure of the inhibitory glial scar, which actively prevents axonal regeneration. Myelin sheaths and mature adult oligodendrocytes, despite their important role in signal conduction in mature CNS axons, contribute to the inhibitory environment existing after injury. As such, unlike the peripheral nervous system, the CNS is unable to revert to a “developmental state” to aid neuronal repair. Modulation of these external factors, however, has been shown to promote growth, regeneration, and functional plasticity after injury. This review will highlight some of the factors that contribute to or prevent plasticity, sprouting, and axonal regeneration after spinal cord injury. PMID:29849554
Modeling Early Cortical Serotonergic Deficits in Autism
Boylan, Carolyn B.; Blue, Mary E.; Hohmann, Christine F.
2007-01-01
Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro- and macroscopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas. PMID:17034875
Modeling early cortical serotonergic deficits in autism.
Boylan, Carolyn B; Blue, Mary E; Hohmann, Christine F
2007-01-10
Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro- and macro-scopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas.
Naftelberg, Shiran; Abramovitch, Ziv; Gluska, Shani; Yannai, Sivan; Joshi, Yuvraj; Donyo, Maya; Ben-Yaakov, Keren; Gradus, Tal; Zonszain, Jonathan; Farhy, Chen; Ashery-Padan, Ruth
2016-01-01
Familial Dysautonomia (FD) is a neurodegenerative disease in which aberrant tissue-specific splicing of IKBKAP exon 20 leads to reduction of IKAP protein levels in neuronal tissues. Here we generated a conditional knockout (CKO) mouse in which exon 20 of IKBKAP is deleted in the nervous system. The CKO FD mice exhibit developmental delays, sensory abnormalities, and less organized dorsal root ganglia (DRGs) with attenuated axons compared to wild-type mice. Furthermore, the CKO FD DRGs show elevated HDAC6 levels, reduced acetylated α-tubulin, unstable microtubules, and impairment of axonal retrograde transport of nerve growth factor (NGF). These abnormalities in DRG properties underlie neuronal degeneration and FD symptoms. Phosphatidylserine treatment decreased HDAC6 levels and thus increased acetylation of α-tubulin. Further PS treatment resulted in recovery of axonal outgrowth and enhanced retrograde axonal transport by decreasing histone deacetylase 6 (HDAC6) levels and thus increasing acetylation of α-tubulin levels. Thus, we have identified the molecular pathway that leads to neurodegeneration in FD and have demonstrated that phosphatidylserine treatment has the potential to slow progression of neurodegeneration. PMID:27997532
Naftelberg, Shiran; Abramovitch, Ziv; Gluska, Shani; Yannai, Sivan; Joshi, Yuvraj; Donyo, Maya; Ben-Yaakov, Keren; Gradus, Tal; Zonszain, Jonathan; Farhy, Chen; Ashery-Padan, Ruth; Perlson, Eran; Ast, Gil
2016-12-01
Familial Dysautonomia (FD) is a neurodegenerative disease in which aberrant tissue-specific splicing of IKBKAP exon 20 leads to reduction of IKAP protein levels in neuronal tissues. Here we generated a conditional knockout (CKO) mouse in which exon 20 of IKBKAP is deleted in the nervous system. The CKO FD mice exhibit developmental delays, sensory abnormalities, and less organized dorsal root ganglia (DRGs) with attenuated axons compared to wild-type mice. Furthermore, the CKO FD DRGs show elevated HDAC6 levels, reduced acetylated α-tubulin, unstable microtubules, and impairment of axonal retrograde transport of nerve growth factor (NGF). These abnormalities in DRG properties underlie neuronal degeneration and FD symptoms. Phosphatidylserine treatment decreased HDAC6 levels and thus increased acetylation of α-tubulin. Further PS treatment resulted in recovery of axonal outgrowth and enhanced retrograde axonal transport by decreasing histone deacetylase 6 (HDAC6) levels and thus increasing acetylation of α-tubulin levels. Thus, we have identified the molecular pathway that leads to neurodegeneration in FD and have demonstrated that phosphatidylserine treatment has the potential to slow progression of neurodegeneration.
Yoo, Soonmoon; Kim, Hak H; Kim, Paul; Donnelly, Christopher J; Kalinski, Ashley L; Vuppalanchi, Deepika; Park, Michael; Lee, Seung J; Merianda, Tanuja T; Perrone-Bizzozero, Nora I; Twiss, Jeffery L
2013-09-01
Localized translation of axonal mRNAs contributes to developmental and regenerative axon growth. Although untranslated regions (UTRs) of many different axonal mRNAs appear to drive their localization, there has been no consensus RNA structure responsible for this localization. We recently showed that limited expression of ZBP1 protein restricts axonal localization of both β-actin and GAP-43 mRNAs. β-actin 3'UTR has a defined element for interaction with ZBP1, but GAP-43 mRNA shows no homology to this RNA sequence. Here, we show that an AU-rich regulatory element (ARE) in GAP-43's 3'UTR is necessary and sufficient for its axonal localization. Axonal GAP-43 mRNA levels increase after in vivo injury, and GAP-43 mRNA shows an increased half-life in regenerating axons. GAP-43 mRNA interacts with both HuD and ZBP1, and HuD and ZBP1 co-immunoprecipitate in an RNA-dependent fashion. Reporter mRNA with the GAP-43 ARE competes with endogenous β-actin mRNA for axonal localization and decreases axon length and branching similar to the β-actin 3'UTR competing with endogenous GAP-43 mRNA. Conversely, over-expressing GAP-43 coding sequence with its 3'UTR ARE increases axonal elongation and this effect is lost when just the ARE is deleted from GAP-43's 3'UTR. We have recently found that over-expression of GAP-43 using an axonally targeted construct with the 3'UTRs of GAP-43 promoted elongating growth of axons, while restricting the mRNA to the cell body with the 3'UTR of γ-actin had minimal effect on axon length. In this study, we show that the ARE in GAP-43's 3'UTR is responsible for localization of GAP-43 mRNA into axons and is sufficient for GAP-43 protein's role in elongating axonal growth. © 2013 International Society for Neurochemistry.
Modeling Development in Retinal Afferents: Retinotopy, Segregation, and EphrinA/EphA Mutants
Godfrey, Keith B.; Swindale, Nicholas V.
2014-01-01
During neural development, neurons extend axons to target areas of the brain. Through processes of growth, branching and retraction these axons establish stereotypic patterns of connectivity. In the visual system, these patterns include retinotopic organization and the segregation of individual axons onto different subsets of target neurons based on the eye of origin (ocular dominance) or receptive field type (ON or OFF). Characteristic disruptions to these patterns occur when neural activity or guidance molecule expression is perturbed. In this paper we present a model that explains how these developmental patterns might emerge as a result of the coordinated growth and retraction of individual axons and synapses responding to position-specific markers, trophic factors and spontaneous neural activity. This model derives from one presented earlier (Godfrey et al., 2009) but which is here extended to account for a wider range of phenomena than previously described. These include ocular dominance and ON-OFF segregation and the results of altered ephrinA and EphA guidance molecule expression. The model takes into account molecular guidance factors, realistic patterns of spontaneous retinal wave activity, trophic molecules, homeostatic mechanisms, axon branching and retraction rules and intra-axonal signaling mechanisms that contribute to the survival of nearby synapses on an axon. We show that, collectively, these mechanisms can account for a wider range of phenomena than previous models of retino-tectal development. PMID:25122119
Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria A; Cilleros, Victor; Tomàs, Josep
2017-01-01
The development of the nervous system involves the overproduction of synapses but connectivity is refined by Hebbian activity-dependent axonal competition. The newborn skeletal muscle fibers are polyinnervated but, at the end of the competition process, some days later, become innervated by a single axon. We used quantitative confocal imaging of the autofluorescent axons from transgenic B6.Cg-Tg (Thy1-YFP)16 Jrs/J mice to investigate the possible cooperation of the muscarinic autoreceptors (mAChR, M 1 -, M 2 - and M 4 -subtypes) and the tyrosine kinase B (TrkB) receptor in the control of axonal elimination after the mice Levator auris longus (LAL) muscle had been exposed to several selective antagonist of the corresponding receptor pathways in vivo . Our previous results show that M 1 , M 2 and TrkB signaling individually increase axonal loss rate around P9. Here we show that although the M 1 and TrkB receptors cooperate and add their respective individual effects to increase axonal elimination rate even more, the effect of the M 2 receptor is largely independent of both M 1 and TrkB receptors. Thus both, cooperative and non-cooperative signaling mechanisms contribute to developmental synapse elimination.
Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria A.; Cilleros, Victor; Tomàs, Josep
2017-01-01
The development of the nervous system involves the overproduction of synapses but connectivity is refined by Hebbian activity-dependent axonal competition. The newborn skeletal muscle fibers are polyinnervated but, at the end of the competition process, some days later, become innervated by a single axon. We used quantitative confocal imaging of the autofluorescent axons from transgenic B6.Cg-Tg (Thy1-YFP)16 Jrs/J mice to investigate the possible cooperation of the muscarinic autoreceptors (mAChR, M1-, M2- and M4-subtypes) and the tyrosine kinase B (TrkB) receptor in the control of axonal elimination after the mice Levator auris longus (LAL) muscle had been exposed to several selective antagonist of the corresponding receptor pathways in vivo. Our previous results show that M1, M2 and TrkB signaling individually increase axonal loss rate around P9. Here we show that although the M1 and TrkB receptors cooperate and add their respective individual effects to increase axonal elimination rate even more, the effect of the M2 receptor is largely independent of both M1 and TrkB receptors. Thus both, cooperative and non-cooperative signaling mechanisms contribute to developmental synapse elimination. PMID:28228723
Neuroma prevention by end-to-side neurorraphy: an experimental study in rats.
Aszmann, Oskar C; Korak, Klaus J; Rab, Matthias; Grünbeck, Matthias; Lassmann, Hans; Frey, Manfred
2003-11-01
The successful treatment of painful neuromas remains a difficult goal to attain. In this report we explore the feasibility of neuroma prevention by insertion of the proximal end of a nerve through an end-to-side neurorraphy into an adjacent mixed nerve to provide a pathway and target for axons deprived of their end organ. Experiments were performed on a total of twenty 250-g Sprague-Dawley rats. Two groups of 10 animals were prepared. Group A served as an anatomic control. In group B the right saphenous nerve was transected and implanted end-to-side through an epineurial window into the tibial nerve distal to the trifurcation of the sciatic nerve. After 12 weeks the corresponding sensory neurons were identified by retrograde labeling techniques and histomorphometric analysis of the proximal and distal tibial nerve segments, and regular histology of the end-to-side site were performed. The results of the retrograde labeling of the corresponding sensory neuron pool of the saphenus nerve showed extensive labelling of the L1 to L3 spinal ganglions after intracutaneous tracer application of the planta pedis. The morphology of the end-to-side coaptation site and histomorphologic analysis prove that sensory neurons penetrate the perineurial sheath and axons regenerate along the tibial Schwann cell tubes toward their targets. Axons of a severed peripheral nerve that are provided with a pathway and target through an end-to-side coaptation will either be pruned or establish some type of end-organ contact so that a neuroma can be prevented. Whether these axons will lead to disturbing sensations such as paresthesia or dysesthesia in the newly found environment or remain silent codwellers, this experiment cannot answer. Long-term results of future clinical work will have to decide whether the prevention of the neuroma through end-to-side coaptation will be an appropriate therapy for this difficult problem.
Jin, YiShi
2015-11-01
Since Caenorhabditis elegans was chosen as a model organism by Sydney Brenner in 1960's, genetic studies in this organism have been instrumental in discovering the function of genes and in deciphering molecular signaling network. The small size of the organism and the simple nervous system enable the complete reconstruction of the first connectome. The stereotypic developmental program and the anatomical reproducibility of synaptic connections provide a blueprint to dissect the mechanisms underlying synapse formation. Recent technological innovation using laser surgery of single axons and in vivo imaging has also made C. elegans a new model for axon regeneration. Importantly, genes regulating synaptogenesis and axon regeneration are highly conserved in function across animal phyla. This mini-review will summarize the main approaches and the key findings in understanding the mechanisms underlying the development and maintenance of the nervous system. The impact of such findings underscores the awesome power of C. elegans genetics.
NASA Astrophysics Data System (ADS)
Johnson, Christopher M.
Neurofilaments are the intermediate filaments of neurons and are the most abundant structure of the neuronal cytoskeleton. Once synthesized within the cell body they are then transported throughout the axon along microtubule tracks, driven by the molecular motors kinesin and dynein. This movement is characterized by long pauses with no movement interrupted by infrequent bouts of rapid movement, resulting in an aggregate dense cytoskeletal structure, which serves to regulate an axon's shape and size. Curiously, the modulated kinetics of these polymers produces a very regular, yet non-uniform, morphology in myelinated axons which are composed of discretely spaced myelin-ensheathed segments that are separated by short constricted regions called "nodes of Ranvier". This unique design optimizes the conduction velocity of myelinated axons at minimal fiber size. Hence, neurofilaments regulate the axon caliber to optimize neuron function. The goal of this dissertation is to investigate the motile mechanism of neurofilament transport as well as the resulting electrophysiological effects that follow. We start by examining highly time-resolved kymograph images generated from recorded neurofilament movement via epifluorescence microscopy. Using kymograph analysis, edge detection algorithms, and pixel smoothing tactics, neurofilament trajectories are extracted and used to obtain statistical distributions for the characteristics of how these filaments move within cells. The results suggest that the observed intermittent and bidirectional motions of these filaments might be explained by a model in which dynein and kinesin motors attach to a single neurofilament cargo and interact through mechanical forces only (i.e. a "tug-of-war" model). We test this hypothesis by developing two discrete-state stochastic models for the kinetic cycles of kinesin and dynein, which are then incorporated into a separate stochastic model that represents the posed tug-of-war scenario. We then systematically vary the number of motors in the model and attempt to identify those combinations of motors that show an agreement with the motility characteristic found from the above mentioned kymographs. By pruning the modeled data in accordance with the experimental results, our model can render an estimate of how many motors are attached to the cargo during transport. The model predicts that, on average, the total number of active motors on each neurofilament is relatively small and relatively independent of polymer length, which suggests that the motors may not be distributed uniformly along the filaments. Finally, we develop a model to explore the physiological function of axon morphology sculpted by neurofilament kinetics. Specifically, nodal constrictions are generated by slowing of neurofilaments in the internodal domain (Monsma et al., 2014), but the physiological function of these constrictions is unknown. To address this, we develop a computational model to investigate the effect of nodal constrictions on the axonal conduction velocity. For a fixed number of ion channels, we find that there is an optimal extent of nodal constriction which minimizes the internodal axon caliber that is required to achieve a given target conduction velocity, and we show that this is sensitive to the precise geometry of the axon and myelin sheath in the flanking paranodal regions. Thus axonal constrictions appear to be a biological adaptation that serves to minimize axonal volume, thereby maximizing the spatial and metabolic efficiency of these processes.
Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó, Anna; Cilleros, Víctor
2017-01-01
During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ) are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR), adenosine autoreceptors (AR) and trophic factor receptors (TFR, for neurotrophins and trophic cytokines) during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.
Zhu, Qiang; Tan, Zhou; Zhao, Shufang; Huang, Hao; Zhao, Xiaofeng; Hu, Xuemei; Zhang, Yiping; Shields, Christopher B; Uetani, Noriko; Qiu, Mengsheng
2015-01-01
Receptor protein tyrosine phosphatases (RPTPs) are extensively expressed in the central nervous system (CNS), and have distinct spatial and temporal patterns in different cell types during development. Previous studies have demonstrated possible roles for RPTPs in axon outgrowth, guidance, and synaptogenesis. In the present study, our results revealed that protein tyrosine phosphatase, receptor type D (PTPRD) was initially expressed in mature neurons in embryonic CNS, and later in oligodendroglial cells at postnatal stages when oligodendrocyte undergo active axonal myelination process. In PTPRD mutants, oligodendrocyte differentiation was normal and a transient myelination delay occurred at early postnatal stages, indicating the contribution of PTPRD to the initiation of axonal myelination. Our results also showed that the remyelination process was not affected in the absence of PTPRD function after a cuprizone-induced demyelination in adult animals. PMID:26341907
Broggini, Thomas; Schnell, Lisa; Ghoochani, Ali; Mateos, José María; Buchfelder, Michael; Wiendieck, Kurt; Schäfer, Michael K.; Eyupoglu, Ilker Y.; Savaskan, Nicolai E.
2016-01-01
The Plasticity Related Gene family covers five, brain-specific, transmembrane proteins (PRG1-5, also termed LPPR1-5) that operate in neuronal plasticity during development, aging and brain trauma. Here we investigated the role of the PRG family on axonal and filopodia outgrowth. Comparative analysis revealed the strongest outgrowth induced by PRG3 (LPPR1). During development, PRG3 is ubiquitously located at the tip of neuronal processes and at the plasma membrane and declines with age. In utero electroporation of PRG3 induced dendritic protrusions and accelerated spine formations in cortical pyramidal neurons. The neurite growth promoting activity of PRG3 requires RasGRF1 (RasGEF1/Cdc25) mediated downstream signaling. Moreover, in axon collapse assays, PRG3-induced neurites resisted growth inhibitors such as myelin, Nogo-A (Reticulon/RTN-4), thrombin and LPA and impeded the RhoA-Rock-PIP5K induced neurite repulsion. Transgenic adult mice with constitutive PRG3 expression displayed strong axonal sprouting distal to a spinal cord lesion. Moreover, fostered PRG3 expression promoted complex motor-behavioral recovery compared to wild type controls as revealed in the Schnell swim test (SST). Thus, PRG3 emerges as a developmental RasGRF1-dependent conductor of filopodia formation and axonal growth enhancer. PRG3-induced neurites resist brain injury-associated outgrowth inhibitors and contribute to functional recovery after spinal cord lesions. Here, we provide evidence that PRG3 operates as an essential neuronal growth promoter in the nervous system. Maintaining PRG3 expression in aging brain may turn back the developmental clock for neuronal regeneration and plasticity. PMID:27744421
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang Dongren; Howard, Angela; Bruun, Donald
2008-04-01
A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrationsmore » that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE{sup -/-}) versus wild type (AChE{sup +/+}) mice indicated that while these OPs inhibited axonal growth in AChE{sup +/+} DRG neurons, they had no effect on axonal growth in AChE{sup -/-} DRG neurons. However, transfection of AChE{sup -/-} DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs.« less
Semaphorin 3A is a retrograde cell death signal in developing sympathetic neurons
Wehner, Amanda B.; Abdesselem, Houari; Dickendesher, Travis L.; Imai, Fumiyasu; Yoshida, Yutaka; Giger, Roman J.; Pierchala, Brian A.
2016-01-01
ABSTRACT During development of the peripheral nervous system, excess neurons are generated, most of which will be lost by programmed cell death due to a limited supply of neurotrophic factors from their targets. Other environmental factors, such as ‘competition factors' produced by neurons themselves, and axon guidance molecules have also been implicated in developmental cell death. Semaphorin 3A (Sema3A), in addition to its function as a chemorepulsive guidance cue, can also induce death of sensory neurons in vitro. The extent to which Sema3A regulates developmental cell death in vivo, however, is debated. We show that in compartmentalized cultures of rat sympathetic neurons, a Sema3A-initiated apoptosis signal is retrogradely transported from axon terminals to cell bodies to induce cell death. Sema3A-mediated apoptosis utilizes the extrinsic pathway and requires both neuropilin 1 and plexin A3. Sema3A is not retrogradely transported in older, survival factor-independent sympathetic neurons, and is much less effective at inducing apoptosis in these neurons. Importantly, deletion of either neuropilin 1 or plexin A3 significantly reduces developmental cell death in the superior cervical ganglia. Taken together, a Sema3A-initiated apoptotic signaling complex regulates the apoptosis of sympathetic neurons during the period of naturally occurring cell death. PMID:27143756
7 CFR 993.150 - Disposition of prunes by handlers.
Code of Federal Regulations, 2014 CFR
2014-01-01
...) Tolerances for non-French prunes. Any lot of standard prunes or standard processed prunes containing more than 2 percent by weight of non-French prunes shall be disposed of only in prune product outlets as prescribed in § 993.50(c) unless the non-French prunes therein have an average count of 40 or less per pound...
Li, Li; Fothergill, Thomas; Hutchins, B Ian; Dent, Erik W; Kali, Katherine
2014-01-01
Wnt5a guides cortical axons in vivo by repulsion and in vitro evokes cortical axon outgrowth and repulsion by calcium signaling pathways. Here we examined the role of microtubule (MT) reorganization and dynamics in mediating effects of Wnt5a. Inhibiting MT dynamics with nocodazole and taxol abolished Wnt5a evoked axon outgrowth and repulsion of cultured hamster cortical neurons. EGFP-EB3 labeled dynamic MTs visualized in live cell imaging revealed that growth cone MTs align with the nascent axon. Wnt5a increased axon outgrowth by reorganization of dynamic MTs from a splayed to a bundled array oriented in the direction of axon extension, and Wnt5a gradients induced asymmetric redistribution of dynamic MTs toward the far side of the growth cone. Wnt5a gradients also evoked calcium transients that were highest on the far side of the growth cone. Calcium signaling and the reorganization of dynamic MTs could be linked by tau, a MT associated protein that stabilizes MTs. Tau is phosphorylated at the Ser 262 MT binding site by CaMKII, and is required for Wnt5a induced axon outgrowth and repulsive turning. Phosphorylation of tau at Ser262 is known to detach tau from MTs to increase their dynamics. Using transfection with tau constructs mutated at Ser262, we found that this site is required for the growth and guidance effects of Wnt5a by mediating reorganization of dynamic MTs in cortical growth cones. Moreover, CaMKII inhibition also prevents MT reorganization required for Wnt5a induced axon outgrowth, thus linking Wnt/calcium signaling to tau mediated MT reorganization during growth cone behaviors. © 2013 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc.Develop Neurobiol 74: 797–817, 2014 PMID:23818454
Wang, Yan; Morkin, Melina I.; Fernandez, Stephanie G.; Mlacker, Gregory M.; Shechter, Jesse M.; Liu, Xiongfei; Patel, Karan H.; Lapins, Allison; Yang, Steven; Dombrowski, Susan M.
2014-01-01
The failure of the CNS neurons to regenerate axons after injury or stroke is a major clinical problem. Transcriptional regulators like Set-β are well positioned to regulate intrinsic axon regeneration capacity, which declines developmentally in maturing CNS neurons. Set-β also functions at cellular membranes and its subcellular localization is disrupted in Alzheimer's disease, but many of its biological mechanisms have not been explored in neurons. We found that Set-β was upregulated postnatally in CNS neurons, and was primarily localized to the nucleus but was also detected in the cytoplasm and adjacent to the plasma membrane. Remarkably, nuclear Set-β suppressed, whereas Set-β localized to cytoplasmic membranes promoted neurite growth in rodent retinal ganglion cells and hippocampal neurons. Mimicking serine 9 phosphorylation, as found in Alzheimer's disease brains, delayed nuclear import and furthermore blocked the ability of nuclear Set-β to suppress neurite growth. We also present data on gene regulation and protein binding partner recruitment by Set-β in primary neurons, raising the hypothesis that nuclear Set-β may preferentially regulate gene expression whereas Set-β at cytoplasmic membranes may regulate unique cofactors, including PP2A, which we show also regulates axon growth in vitro. Finally, increasing recruitment of Set-β to cellular membranes promoted adult rat optic nerve axon regeneration after injury in vivo. Thus, Set-β differentially regulates axon growth and regeneration depending on subcellular localization and phosphorylation. PMID:24849368
Action potentials reliably invade axonal arbors of rat neocortical neurons
Cox, Charles L.; Denk, Winfried; Tank, David W.; Svoboda, Karel
2000-01-01
Neocortical pyramidal neurons have extensive axonal arborizations that make thousands of synapses. Action potentials can invade these arbors and cause calcium influx that is required for neurotransmitter release and excitation of postsynaptic targets. Thus, the regulation of action potential invasion in axonal branches might shape the spread of excitation in cortical neural networks. To measure the reliability and extent of action potential invasion into axonal arbors, we have used two-photon excitation laser scanning microscopy to directly image action-potential-mediated calcium influx in single varicosities of layer 2/3 pyramidal neurons in acute brain slices. Our data show that single action potentials or bursts of action potentials reliably invade axonal arbors over a range of developmental ages (postnatal 10–24 days) and temperatures (24°C-30°C). Hyperpolarizing current steps preceding action potential initiation, protocols that had previously been observed to produce failures of action potential propagation in cultured preparations, were ineffective in modulating the spread of action potentials in acute slices. Our data show that action potentials reliably invade the axonal arbors of neocortical pyramidal neurons. Failures in synaptic transmission must therefore originate downstream of action potential invasion. We also explored the function of modulators that inhibit presynaptic calcium influx. Consistent with previous studies, we find that adenosine reduces action-potential-mediated calcium influx in presynaptic terminals. This reduction was observed in all terminals tested, suggesting that some modulatory systems are expressed homogeneously in most terminals of the same neuron. PMID:10931955
KCC3 axonopathy: neuropathological features in the central and peripheral nervous system.
Auer, Roland N; Laganière, Janet L; Robitaille, Yves O; Richardson, John; Dion, Patrick A; Rouleau, Guy A; Shekarabi, Masoud
2016-09-01
Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC) is an autosomal recessive disease of the central and peripheral nervous system that presents as early-onset polyneuropathy. Patients are hypotonic and areflexic from birth, with abnormal facial features and atrophic muscles. Progressive peripheral neuropathy eventually confines them to a wheelchair in the second decade of life, and death occurs by the fourth decade. We here define the neuropathologic features of the disease in autopsy tissues from eight cases. Both developmental and neurodegenerative features were found. Hypoplasia or absence of the major telencephalic commissures and a hypoplasia of corticospinal tracts to half the normal size, were the major neurodevelopmental defects we observed. Despite being a neurodegenerative disease, preservation of brain weight and a conspicuous absence of neuronal or glial cell death were signal features of this disease. Small tumor-like overgrowths of axons, termed axonomas, were found in the central and peripheral nervous system, indicating attempted axonal regeneration. We conclude that the neurodegenerative deficits in HMSN/ACC are primarily caused by an axonopathy superimposed upon abnormal development, affecting peripheral but also central nervous system axons, all ultimately because of a genetic defect in the axonal cotransporter KCC3.
Oliva, Carlos; Sierralta, Jimena
2010-08-15
The molecules and networks involved in the process of acquisition and maintenance of the form of a mature neuron are not completely known. Using a misexpression screen we identified the gene hindsight as a gene involved in the process of acquisition of the neuronal morphogenesis in the Drosophila adult nervous system. hindsight encodes a transcription factor known for its role in early developmental processes such as embryonic germ band retraction and dorsal closure, as well as in the establishment of cell morphology, planar cell polarity, and epithelial integrity during retinal development. We describe here a novel function for HNT by showing that both loss and gain of function of HNT affects the pathfinding of the photoreceptors axons. By manipulating the timing and level of HNT expression, together with the number of cells manipulated we show here that the function of HNT in axonal guidance is independent of the HNT functions previously reported in retinal cells. Based on genetic interaction experiments we show that part of HNT function in axonal development is exerted through the regulation of genes involved in the dynamics of the actin cytoskeleton. Copyright 2010 Elsevier Inc. All rights reserved.
Statistical physics approach to quantifying differences in myelinated nerve fibers
Comin, César H.; Santos, João R.; Corradini, Dario; Morrison, Will; Curme, Chester; Rosene, Douglas L.; Gabrielli, Andrea; da F. Costa, Luciano; Stanley, H. Eugene
2014-01-01
We present a new method to quantify differences in myelinated nerve fibers. These differences range from morphologic characteristics of individual fibers to differences in macroscopic properties of collections of fibers. Our method uses statistical physics tools to improve on traditional measures, such as fiber size and packing density. As a case study, we analyze cross–sectional electron micrographs from the fornix of young and old rhesus monkeys using a semi-automatic detection algorithm to identify and characterize myelinated axons. We then apply a feature selection approach to identify the features that best distinguish between the young and old age groups, achieving a maximum accuracy of 94% when assigning samples to their age groups. This analysis shows that the best discrimination is obtained using the combination of two features: the fraction of occupied axon area and the effective local density. The latter is a modified calculation of axon density, which reflects how closely axons are packed. Our feature analysis approach can be applied to characterize differences that result from biological processes such as aging, damage from trauma or disease or developmental differences, as well as differences between anatomical regions such as the fornix and the cingulum bundle or corpus callosum. PMID:24676146
Statistical physics approach to quantifying differences in myelinated nerve fibers
NASA Astrophysics Data System (ADS)
Comin, César H.; Santos, João R.; Corradini, Dario; Morrison, Will; Curme, Chester; Rosene, Douglas L.; Gabrielli, Andrea; da F. Costa, Luciano; Stanley, H. Eugene
2014-03-01
We present a new method to quantify differences in myelinated nerve fibers. These differences range from morphologic characteristics of individual fibers to differences in macroscopic properties of collections of fibers. Our method uses statistical physics tools to improve on traditional measures, such as fiber size and packing density. As a case study, we analyze cross-sectional electron micrographs from the fornix of young and old rhesus monkeys using a semi-automatic detection algorithm to identify and characterize myelinated axons. We then apply a feature selection approach to identify the features that best distinguish between the young and old age groups, achieving a maximum accuracy of 94% when assigning samples to their age groups. This analysis shows that the best discrimination is obtained using the combination of two features: the fraction of occupied axon area and the effective local density. The latter is a modified calculation of axon density, which reflects how closely axons are packed. Our feature analysis approach can be applied to characterize differences that result from biological processes such as aging, damage from trauma or disease or developmental differences, as well as differences between anatomical regions such as the fornix and the cingulum bundle or corpus callosum.
Street tree pruning and removal needs
David J. Nowak
1990-01-01
Street tree pruning and removal needs were examined for 11 species from inventory data collected in 11 cities in the North Central and Northeastern United States. The needs ranged from predominantly no pruning and routine pruning of small trees to safety pruning and removal of large trees. Species were ranked in terms of overall pruning and removal urgency, with London...
7 CFR 993.109 - Modified definition of non-French prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Modified definition of non-French prunes. 993.109... definition of non-French prunes. The definition of non-French prunes set forth in § 993.6 is modified to read as follows: Non-French Prunes means prunes commonly known as Imperial, Sugar, Robe de Sargent, Burton...
Synapsins Are Downstream Players of the BDNF-Mediated Axonal Growth.
Marte, Antonella; Messa, Mirko; Benfenati, Fabio; Onofri, Franco
2017-01-01
Synapsins (Syns) are synaptic vesicle-associated phosphoproteins involved in neuronal development and neurotransmitter release. While Syns are implicated in the regulation of brain-derived neurotrophic factor (BDNF)-induced neurotransmitter release, their role in the BDNF developmental effects has not been fully elucidated. By using primary cortical neurons from Syn I knockout (KO) and Syn I/II/III KO mice, we studied the effects of BDNF and nerve growth factor (NGF) on axonal growth. While NGF had similar effects in all genotypes, BDNF induced significant differences in Syn KO axonal outgrowth compared to wild type (WT), an effect that was rescued by the re-expression of Syn I. Moreover, the significant increase of axonal branching induced by BDNF in WT neurons was not detectable in Syn KO neurons. The expression analysis of BDNF receptors in Syn KO neurons revealed a significant decrease of the full length TrkB receptor and an increase in the levels of the truncated TrkB.t1 isoform and p75 NTR associated with a marked reduction of the BDNF-induced MAPK/Erk activation. By using the Trk inhibitor K252a, we demonstrated that these differences in BDNF effects were dependent on a TrkB/p75 NTR imbalance. The data indicate that Syn I plays a pivotal role in the BDNF signal transduction during axonal growth.
Palevitch, Ori; Abraham, Eytan; Borodovsky, Natalya; Levkowitz, Gil; Zohar, Yonathan; Gothilf, Yoav
2009-01-01
The initiation of puberty and the functioning of the reproductive system depend on proper development of the hypophysiotropic gonadotropin-releasing hormone (GnRH) system. One critical step in this process is the embryonic migration of GnRH neurons from the olfactory area to the hypothalamus. Using a transgenic zebrafish model, Tg(gnrh3:EGFP), in which GnRH3 neurons and axons are fluorescently labeled, we investigated whether zebrafish NELF is essential for the development of GnRH3 neurons. The zebrafish nelf cDNA was cloned and characterized. During embryonic development, nelf is expressed in GnRH3 neurons and in target sites of GnRH3 projections and perikarya, before the initiation of their migration. Nelf knockdown resulted in a disruption of the GnRH3 system which included absence or misguiding of GnRH3 axonal outgrowth and incorrect or arrested migration of GnRH3 perikarya. These results suggest that Nelf is an important factor in the developmental migration and projection of GnRH3 neurons in zebrafish. Copyright (c) 2008 Wiley-Liss, Inc.
Time and distance to clear wood in pruned red alder saplings.
Dean S. DeBell; Constance A. Harrington; Barbara L. Gartner; Ryan. Singleton
2006-01-01
Pruning trials in young alder stands were sampled to evaluate response to pruning. Effects of pruning (1) live branches on different dates, and (2) dead branches with or without damaging the branch collar were assessed on trees pruned in 3- and 6-year-old plantations, respectively. Six years after pruning, stem sections were collected and dissected in the longitudinal-...
Shakir, M. Afaq; Gill, Jason S.; Lundquist, Erik A.
2006-01-01
Many genes that affect axon pathfinding and cell migration have been identified. Mechanisms by which these genes and the molecules they encode interact with one another in pathways and networks to control developmental events are unclear. Rac GTPases, the cytoskeletal signaling molecule Enabled, and NIK kinase have all been implicated in regulating axon pathfinding and cell migration. Here we present evidence that, in Caenorhabditis elegans, three Rac GTPases, CED-10, RAC-2, and MIG-2, define three redundant pathways that each control axon pathfinding, and that the NIK kinase MIG-15 acts in each Rac pathway. Furthermore, we show that the Enabled molecule UNC-34 defines a fourth partially redundant pathway that acts in parallel to Rac/MIG-15 signaling in axon pathfinding. Enabled and the three Racs also act redundantly to mediate AQR and PQR neuronal cell migration. The Racs and UNC-34 Ena might all control the formation of actin-based protrusive structures (lamellipodia and filopodia) that mediate growth cone outgrowth and cell migration. MIG-15 does not act with the three Racs in execution of cell migration. Rather, MIG-15 affects direction of PQR neuronal migration, similar to UNC-40 and DPY-19, which control initial Q cell polarity, and Wnt signaling, which acts later to control Q cell-directed migration. MIG-2 Rac, which acts with CED-10 Rac, RAC-2 Rac, and UNC-34 Ena in axon pathfinding and cell migration, also acts with MIG-15 in PQR directional migration. PMID:16204220
Pruning artificial neural networks using neural complexity measures.
Jorgensen, Thomas D; Haynes, Barry P; Norlund, Charlotte C F
2008-10-01
This paper describes a new method for pruning artificial neural networks, using a measure of the neural complexity of the neural network. This measure is used to determine the connections that should be pruned. The measure computes the information-theoretic complexity of a neural network, which is similar to, yet different from previous research on pruning. The method proposed here shows how overly large and complex networks can be reduced in size, whilst retaining learnt behaviour and fitness. The technique proposed here helps to discover a network topology that matches the complexity of the problem it is meant to solve. This novel pruning technique is tested in a robot control domain, simulating a racecar. It is shown, that the proposed pruning method is a significant improvement over the most commonly used pruning method Magnitude Based Pruning. Furthermore, some of the pruned networks prove to be faster learners than the benchmark network that they originate from. This means that this pruning method can also help to unleash hidden potential in a network, because the learning time decreases substantially for a pruned a network, due to the reduction of dimensionality of the network.
Effects of pruning height on the diameter growth of yellow birch
Dale S. Solomon; Barton M. Blum
1977-01-01
The diameter growth rate of pruned trees increased the second year after pruning, whereas the diameter growth of unpruned trees was not as fast during the second year. Diameter growth rate was positively correlated with the height to which all branches were pruned. After the pruning shock of the first year, trees pruned to 50 percent of their height showed the greatest...
Schwieterman, Alicia A.; Steves, Alyse N.; Yee, Vivian; Donelson, Cory J.; Bentley, Melissa R.; Santorella, Elise M.; Mehlenbacher, Taylor V.; Pital, Aaron; Howard, Austin M.; Wilson, Melissa R.; Ereddia, Danielle E.; Effrein, Kelsie S.; McMurry, Jonathan L.; Ackley, Brian D.; Chisholm, Andrew D.; Hudson, Martin L.
2016-01-01
The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for the Caenorhabditis elegans ephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in a C. elegans model of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body-wall muscle and in parallel with HS modification genes and HSPG core proteins. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system. PMID:26645816
Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others.
Norsworthy, Michael W; Bei, Fengfeng; Kawaguchi, Riki; Wang, Qing; Tran, Nicholas M; Li, Yi; Brommer, Benedikt; Zhang, Yiming; Wang, Chen; Sanes, Joshua R; Coppola, Giovanni; He, Zhigang
2017-06-21
At least 30 types of retinal ganglion cells (RGCs) send distinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Here we tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regeneration of other types. From a screen of transcription factors, we identified Sox11 as one that could induce substantial axon regeneration. Transcriptome profiling indicated that Sox11 activates genes involved in cytoskeletal remodeling and axon growth. Remarkably, α-RGCs, which preferentially regenerate following treatments such as Pten deletion, were killed by Sox11 overexpression. Thus, Sox11 promotes regeneration of non-α-RGCs, which are refractory to Pten deletion-induced regeneration. We conclude that Sox11 can reprogram adult RGCs to a growth-competent state, suggesting that different growth-promoting interventions promote regeneration in distinct neuronal types. Copyright © 2017 Elsevier Inc. All rights reserved.
A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.
Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J
2012-02-23
The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. Copyright © 2012 Elsevier Inc. All rights reserved.
A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation
Choe, Youngshik; Siegenthaler, Julie A.; Pleasure, Samuel J.
2012-01-01
Summary The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. Using mice with either meningeal overgrowth or selective loss of meninges, we’ve identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonizes the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. PMID:22365545
7 CFR 993.50 - Outgoing regulation.
Code of Federal Regulations, 2013 CFR
2013-01-01
... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... any lot of French prunes for human consumption as prunes, or any lot of mixed dried fruit containing French prunes for human consumption as mixed dried fruit, unless the average count of French prunes...
7 CFR 993.50 - Outgoing regulation.
Code of Federal Regulations, 2011 CFR
2011-01-01
... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... any lot of French prunes for human consumption as prunes, or any lot of mixed dried fruit containing French prunes for human consumption as mixed dried fruit, unless the average count of French prunes...
7 CFR 993.50 - Outgoing regulation.
Code of Federal Regulations, 2012 CFR
2012-01-01
... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... any lot of French prunes for human consumption as prunes, or any lot of mixed dried fruit containing French prunes for human consumption as mixed dried fruit, unless the average count of French prunes...
7 CFR 993.50 - Outgoing regulation.
Code of Federal Regulations, 2014 CFR
2014-01-01
... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... any lot of French prunes for human consumption as prunes, or any lot of mixed dried fruit containing French prunes for human consumption as mixed dried fruit, unless the average count of French prunes...
Early pruning affects 15-year growth of cottonwood planted at 40- by 40-foot spacing
James S. Meadows; Roger M. Krinard
2013-01-01
We compared the growth of eastern cottonwood (Populus deltoides Bartr. ex Marsh.) trees planted at 40- by 40-foot spacing and subjected to four pruning treatments from the 2nd through the 8th year of growth. Treatments were (1) no pruning, (2) prune to one-third of total height annually, (3) prune to one-half of total height annually, and (4) prune...
Code of Federal Regulations, 2010 CFR
2010-01-01
... means “Application for Prune Tree Removal Program.” (d) Committee means the Prune Marketing Committee... of prune-plum trees after approval of applications by the Committee through June 30, 2002. (f... prune/plums that are dehydrated into dried plums for market. (g) Removal means that the prune-plum trees...
7 CFR 993.6 - Non-French prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Non-French prunes. 993.6 Section 993.6 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Order Regulating Handling Definitions § 993.6 Non-French prunes. Non-French prunes means prunes commonly...
7 CFR 993.6 - Non-French prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Non-French prunes. 993.6 Section 993.6 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Order Regulating Handling Definitions § 993.6 Non-French prunes. Non-French prunes means prunes commonly...
Jiménez-Brenes, F M; López-Granados, F; de Castro, A I; Torres-Sánchez, J; Serrano, N; Peña, J M
2017-01-01
Tree pruning is a costly practice with important implications for crop harvest and nutrition, pest and disease control, soil protection and irrigation strategies. Investigations on tree pruning usually involve tedious on-ground measurements of the primary tree crown dimensions, which also might generate inconsistent results due to the irregular geometry of the trees. As an alternative to intensive field-work, this study shows a innovative procedure based on combining unmanned aerial vehicle (UAV) technology and advanced object-based image analysis (OBIA) methodology for multi-temporal three-dimensional (3D) monitoring of hundreds of olive trees that were pruned with three different strategies (traditional, adapted and mechanical pruning). The UAV images were collected before pruning, after pruning and a year after pruning, and the impacts of each pruning treatment on the projected canopy area, tree height and crown volume of every tree were quantified and analyzed over time. The full procedure described here automatically identified every olive tree on the orchard and computed their primary 3D dimensions on the three study dates with high accuracy in the most cases. Adapted pruning was generally the most aggressive treatment in terms of the area and volume (the trees decreased by 38.95 and 42.05% on average, respectively), followed by trees under traditional pruning (33.02 and 35.72% on average, respectively). Regarding the tree heights, mechanical pruning produced a greater decrease (12.15%), and these values were minimal for the other two treatments. The tree growth over one year was affected by the pruning severity and by the type of pruning treatment, i.e., the adapted-pruning trees experienced higher growth than the trees from the other two treatments when pruning intensity was low (<10%), similar to the traditionally pruned trees at moderate intensity (10-30%), and lower than the other trees when the pruning intensity was higher than 30% of the crown volume. Combining UAV-based images and an OBIA procedure allowed measuring tree dimensions and quantifying the impacts of three different pruning treatments on hundreds of trees with minimal field work. Tree foliage losses and annual canopy growth showed different trends as affected by the type and severity of the pruning treatments. Additionally, this technology offers valuable geo-spatial information for designing site-specific crop management strategies in the context of precision agriculture, with the consequent economic and environmental benefits.
Maffei, Helen M; Filip, Gregory M; Gruelke, Nancy E; Oblinger, Brent W; Margolis, Ellis; Chadwick, Kristen L
2016-01-01
Mid- to very large-sized Douglas-fir (Pseudotsuga menzieseii var. menziesii) that were lightly- to moderately-infected by dwarf mistletoe (Arceuthobium douglasii) were analyzed over a 14-year period to evaluate whether mechanical pruning could eradicate mistletoe (or at least delay the onset of severe infection) without significantly affecting tree vitality and by inference, longevity. Immediate and longterm pruning effects on mistletoe infection severity were assessed by comparing pruned trees (n = 173) to unpruned trees (n = 55) with respect to: (1) percentage of trees with no visible infections 14 years post-pruning, (2) Broom Volume Rating (BVR), and (3) rate of BVR increase 14 years postpruning. Vitality/longevity (compared with unpruned trees) was assessed using six indicators: (1) tree survival, (2) the development of severe infections, (3) the development of dead tops, (4) tree-ring width indices, (5) Normalized Difference Vegetation Index (NDVI) from high-resolution multi-spectral imagery, and (6) live-crown ratio (LCR) and increment. Twenty-four percent of the pruned trees remained free of mistletoe 14 years post-pruning. Pruning is most likely to successfully eradicate mistletoe in lightly infected trees (BVR 1 or 2) without infected neighbors. Pruning significantly decreased mean BVR in the pruned versus the unpruned trees. However, the subsequent average rate of intensification (1.3–1.5 BVR per decade) was not affected, implying that a single pruning provides ~14 years respite in the progression of infection levels. Post-pruning infection intensification was slower on dominant and co-dominants than on intermediate or suppressed trees. The success of mistletoe eradication via pruning and need for follow-up pruning should be evaluated no sooner than 14 years after pruning to allow for the development of detectable brooms. Based on six indicators, foliage from witches brooms contribute little to long-term tree vitality since removal appears to have little effect on resources available for tree growth and maintenance. In the severely pruned trees, tree-ring width was reduced for several years post-pruning, but then compensated with larger ring width in later years. Both NDVI and LCR increment were significantly higher for the pruned trees than the control trees, while the development of severe infections and/or dead tops was significantly (5X and 3X) higher for the controls. If possible, multiple indicators of tree vitality should be evaluated. Pruning can be worthwhile even if all the mistletoe is not removed, because mistletoe intensification is delayed. The impact of removing the brooms seems to be minimal, and post-pruning crowns had greater NDVI values.
N.A. Bolon; R.D. Fight; J.M. Cahill
1992-01-01
The PP PRUNE program allows users to conduct a financial analysis of pruning ponderosa pine (Pinus ponderosa Dougl. ex Laws.). The increase in product value and rate of return from pruning the butt 16.5-foot log can be estimated. Lumber recovery information is based on actual mill experience with pruned and unpruned logs. Users supply lumber prices...
ERMs colocalize transiently with L1 during neocortical axon outgrowth.
Mintz, C David; Dickson, Tracey C; Gripp, Mark L; Salton, Stephen R J; Benson, Deanna L
2003-09-29
L1 is a member of the Ig superfamily of cell adhesion molecules (CAMs) that functions in many aspects of neuronal development including axonal outgrowth and neuronal migration. These functions require coordination between L1 and the actin cytoskeleton. Because CAMs and the cytoskeleton do not bind directly, membrane-cytoskeletal linkers (MCLs) such as ankyrin are thought to be crucial to their interactions, but data from a knockout mouse suggest that ankyrin is not necessary for the earliest events attributed to L1 function. Recent findings in hippocampal cell culture show that members of the ERM family of proteins (ezrin, radixin, and moesin) can also serve as MCLs between L1 and actin in neurons. Here, we demonstrate that ERM proteins are expressed in extending neuronal processes in the intermediate zone of the developing cortex, a region that is densely packed with migrating neurons and growing axons. ERMs and L1 are codistributed extensively over a transient time course that coincides with rapid axon growth and cortical expansion. This codistribution is strong at embryonic day 17 and 19 but diminishes by postnatal day 0, at which time ankyrin-L1 codistribution increases dramatically. These findings suggest that in the developing neocortex, ERMs are the predominant MCL for L1 during migration and axon extension, neither of which requires ankyrin function. Furthermore, these data suggest that there is a developmentally regulated switch in MCL function in the developing brain. Copyright 2003 Wiley-Liss, Inc.
Transcallosal Projections Require Glycoprotein M6-Dependent Neurite Growth and Guidance.
Mita, Sakura; de Monasterio-Schrader, Patricia; Fünfschilling, Ursula; Kawasaki, Takahiko; Mizuno, Hidenobu; Iwasato, Takuji; Nave, Klaus-Armin; Werner, Hauke B; Hirata, Tatsumi
2015-11-01
The function of mature neurons critically relies on the developmental outgrowth and projection of their cellular processes. It has long been postulated that the neuronal glycoproteins M6a and M6b are involved in axon growth because these four-transmembrane domain-proteins of the proteolipid protein family are highly enriched on growth cones, but in vivo evidence has been lacking. Here, we report that the function of M6 proteins is required for normal axonal extension and guidance in vivo. In mice lacking both M6a and M6b, a severe hypoplasia of axon tracts was manifested. Most strikingly, the corpus callosum was reduced in thickness despite normal densities of cortical projection neurons. In single neuron tracing, many axons appeared shorter and disorganized in the double-mutant cortex, and some of them were even misdirected laterally toward the subcortex. Probst bundles were not observed. Upon culturing, double-mutant cortical and cerebellar neurons displayed impaired neurite outgrowth, indicating a cell-intrinsic function of M6 proteins. A rescue experiment showed that the intracellular loop of M6a is essential for the support of neurite extension. We propose that M6 proteins are required for proper extension and guidance of callosal axons that follow one of the most complex trajectories in the mammalian nervous system. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Butz, Markus; van Ooyen, Arjen
2013-01-01
Lasting alterations in sensory input trigger massive structural and functional adaptations in cortical networks. The principles governing these experience-dependent changes are, however, poorly understood. Here, we examine whether a simple rule based on the neurons' need for homeostasis in electrical activity may serve as driving force for cortical reorganization. According to this rule, a neuron creates new spines and boutons when its level of electrical activity is below a homeostatic set-point and decreases the number of spines and boutons when its activity exceeds this set-point. In addition, neurons need a minimum level of activity to form spines and boutons. Spine and bouton formation depends solely on the neuron's own activity level, and synapses are formed by merging spines and boutons independently of activity. Using a novel computational model, we show that this simple growth rule produces neuron and network changes as observed in the visual cortex after focal retinal lesions. In the model, as in the cortex, the turnover of dendritic spines was increased strongest in the center of the lesion projection zone, while axonal boutons displayed a marked overshoot followed by pruning. Moreover, the decrease in external input was compensated for by the formation of new horizontal connections, which caused a retinotopic remapping. Homeostatic regulation may provide a unifying framework for understanding cortical reorganization, including network repair in degenerative diseases or following focal stroke. PMID:24130472
Knott, Thomas K; Madany, Pasil A; Faden, Ashley A; Xu, Mei; Strotmann, Jörg; Henion, Timothy R; Schwarting, Gerald A
2012-07-04
The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a small number of targets in the olfactory bulb such that each glomerulus is made up of axon terminals expressing just one odorant receptor. It is thought that this precision in axon targeting is required to maintain highly refined odor discrimination. We previously showed that β3GnT2(-/-) mice have severe developmental and axon guidance defects. The phenotype of these mice is similar to adenylyl cyclase 3 (AC3) knockout mice largely due to the significant down-regulation of AC3 activity in β3GnT2(-/-) neurons. Microarray analysis reveals that nearly one quarter of all odorant receptor genes are down regulated in β3GnT2(-/-) mice compared to controls. Analysis of OR expression by quantitative PCR and in situ hybridization demonstrates that the number of neurons expressing some odorant receptors, such as mOR256-17, is increased by nearly 60% whereas for others such as mOR28 the number of neurons is decreased by more than 75% in β3GnT2(-/-) olfactory epithelia. Analysis of axon trajectories confirms that many axons track to inappropriate targets in β3GnT2(-/-) mice, and some glomeruli are populated by axons expressing more than one odorant receptor. Results show that mutant mice perform nearly as well as control mice in an odor discrimination task. In addition, in situ hybridization studies indicate that the expression of several activity dependent genes is unaffected in β3GnT2(-/-) olfactory neurons. Results presented here show that many odorant receptors are under-expressed in β3GnT2(-/-) mice and further demonstrate that additional axon subsets grow into inappropriate targets or minimally innervate glomeruli in the olfactory bulb. Odor evoked gene expression is unchanged and β3GnT2(-/-) mice exhibit a relatively small deficit in their ability to discriminate divergent odors. Results suggest that despite the fact that β3GnT2(-/-) mice have decreased AC3 activity, decreased expression of many ORs, and display many axon growth and guidance errors, odor-evoked activity in cilia of mutant olfactory neurons remains largely intact.
Financial analysis of pruning coast Douglas-fir.
Roger D. Fight; James M. Cahlll; Thomas D. Fahey; Thomas A. Snellgrove
1987-01-01
Pruning of coast Douglas-fir was evaluated; recent product recovery information for pruned and unpruned logs for both sawn and peeled products was used. Dimensions of pruned and unpruned trees were simulated with the Douglas-fir stand simulator (DFSIM). Results are presented for a range of sites, ages at time of pruning, ages at time of harvest, product prices, and...
Better marking means cheaper pruning.
Kenneth R. Eversole
1953-01-01
Careful selection of trees to be pruned can make the difference between profit and loss on the pruning investment, especially in stands where no thinning is contemplated. Expert marking is required to make sure that the pruned trees will grow rapidly. The most important variable influencing the cost of clear wood produced by pruning is growth rate. For example, at 3...
7 CFR 993.409 - Undersized prune regulation for the 2002-03 crop year.
Code of Federal Regulations, 2014 CFR
2014-01-01
...) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Undersized Prune Regulation § 993.409 Undersized prune...
Kolk, Sharon M.; Gunput, Rou-Afza F.; Tran, Tracy S.; van den Heuvel, Dianne M. A.; Prasad, Asheeta A.; Hellemons, Anita J. C. G. M.; Adolfs, Youri; Ginty, David D.; Kolodkin, Alex L.; Burbach, J. Peter H.; Smidt, Marten P.; Pasterkamp, R. Jeroen
2010-01-01
Dopaminergic neurons in the mesodiencephalon (mdDA neurons) make precise synaptic connections with targets in the forebrain via the mesostriatal, mesolimbic, and mesoprefrontal pathways. Because of the functional importance of these remarkably complex ascending axon pathways and their implication in human disease, the mechanisms underlying the development of these connections are of considerable interest. Despite extensive in vitro studies, the molecular determinants that ensure the perfect formation of these pathways in vivo remain mostly unknown. Here, we determine the embryonic origin and ontogeny of the mouse mesoprefrontal pathway and use these data to reveal an unexpected requirement for semaphorin 3F (Sema3F) and its receptor neuropilin-2 (Npn-2) during mdDA pathway development using tissue culture approaches and analysis of sema3F−/−, npn-2−/−, and npn-2−/−;TH-Cre mice. We show that Sema3F is a bifunctional guidance cue for mdDA axons, some of which have the remarkable ability to regulate their responsiveness to Sema3F as they develop. During early developmental stages, Sema3F chemorepulsion controls previously uncharacterized aspects of mdDA pathway development through both Npn-2-dependent (axon fasciculation and channeling) and Npn-2-independent (rostral growth) mechanisms. Later on, chemoattraction mediated by Sema3F and Npn-2 is required to orient mdDA axon projections in the cortical plate of the medial prefrontal cortex. This latter finding demonstrates that regulation of axon orientation in the target field occurs by chemoattractive mechanisms, and this is likely to also apply to other neural systems. In all, this study provides a framework for additional dissection of the molecular basis of mdDA pathway development and disease. PMID:19812329
Formation of acrylamide at temperatures lower than 100°C: the case of prunes and a model study
Becalski, A.; Brady, B.; Feng, S.; Gauthier, B.R.; Zhao, T.
2011-01-01
Acrylamide concentrations in prune products – baby strained prunes (range = 75–265 μg kg−−1), baby apple/prune juice (33–61 μg kg−−1), prune juice (186–916 μg kg−−1) and prunes (58–332 μg kg−−1) – on the Canadian market were determined. The formation of acrylamide in a simulated plum juice was also investigated under ‘drying conditions’ in an open vessel at temperatures <100°C for 24 h and under ‘wet conditions’ in a closed vessel at a temperature of 120°C for 1 h. Acrylamide was produced in a simulated plum juice under ‘drying conditions’ in amounts comparable with those found in prunes and prune juices. Acrylamide was not produced in simulated plum juice under ‘wet conditions’ in a closed vessel at temperature of 120°C for 1 h, but under the same condition an authentic prune juice doubled its acrylamide concentration. Formation of acrylamide in prune products was attributed to the presence of asparagine and sugars in the starting materials. PMID:21623495
Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven
2015-08-05
Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal action potentials to synaptic terminals. GABA transmission was not disrupted. The disruption did not involve detectable morphological changes to axons of glutamate neurons. Our work identifies a developmental role for astrocytes in the temporal precision of excitatory signals. Copyright © 2015 the authors 0270-6474/15/3511105-13$15.00/0.
Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C.
2015-01-01
Neuron–astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (−astrocyte) within the same culture dish. −Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. SIGNIFICANCE STATEMENT Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal action potentials to synaptic terminals. GABA transmission was not disrupted. The disruption did not involve detectable morphological changes to axons of glutamate neurons. Our work identifies a developmental role for astrocytes in the temporal precision of excitatory signals. PMID:26245971
Ten Years' Growth of Pruned and Unpruned Cottonwood Planted at 40- by 40-Foot Spacing
Roger M. Krinard
1985-01-01
Diameters at age 10 of cottonwood (Populus deltoides Bartr. ex Marsh.) select clone Stoneville 66 planted at 40- by 40-foot spacing varied from 13.4 to 16.4 inches depending on height of pruning. Pruning treatments, applied from the 2nd through 8th years, were (1) unpruned, (2) pruned to a third of height yearly, (3) pruned to half of height yearly...
7 CFR 993.8 - Natural condition prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Natural condition prunes. 993.8 Section 993.8 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... CALIFORNIA Order Regulating Handling Definitions § 993.8 Natural condition prunes. Natural condition prunes...
7 CFR 993.8 - Natural condition prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Natural condition prunes. 993.8 Section 993.8 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... CALIFORNIA Order Regulating Handling Definitions § 993.8 Natural condition prunes. Natural condition prunes...
Bhogal, Balpreet; Plaza-Jennings, Amara
2016-01-01
Dendritic arbor morphology is a key determinant of neuronal function. Once established, dendrite branching patterns must be maintained as the animal develops to ensure receptive field coverage. The translational repressors Nanos (Nos) and Pumilio (Pum) are required to maintain dendrite growth and branching of Drosophila larval class IV dendritic arborization (da) neurons, but their specific regulatory role remains unknown. We show that Nos-Pum-mediated repression of the pro-apoptotic gene head involution defective (hid) is required to maintain a balance of dendritic growth and retraction in class IV da neurons and that upregulation of hid results in decreased branching because of an increase in caspase activity. The temporal requirement for nos correlates with an ecdysone-triggered switch in sensitivity to apoptotic stimuli that occurs during the mid-L3 transition. We find that hid is required during pupariation for caspase-dependent pruning of class IV da neurons and that Nos and Pum delay pruning. Together, these results suggest that Nos and Pum provide a crucial neuroprotective regulatory layer to ensure that neurons behave appropriately in response to developmental cues. PMID:27256879
Bhogal, Balpreet; Plaza-Jennings, Amara; Gavis, Elizabeth R
2016-06-15
Dendritic arbor morphology is a key determinant of neuronal function. Once established, dendrite branching patterns must be maintained as the animal develops to ensure receptive field coverage. The translational repressors Nanos (Nos) and Pumilio (Pum) are required to maintain dendrite growth and branching of Drosophila larval class IV dendritic arborization (da) neurons, but their specific regulatory role remains unknown. We show that Nos-Pum-mediated repression of the pro-apoptotic gene head involution defective (hid) is required to maintain a balance of dendritic growth and retraction in class IV da neurons and that upregulation of hid results in decreased branching because of an increase in caspase activity. The temporal requirement for nos correlates with an ecdysone-triggered switch in sensitivity to apoptotic stimuli that occurs during the mid-L3 transition. We find that hid is required during pupariation for caspase-dependent pruning of class IV da neurons and that Nos and Pum delay pruning. Together, these results suggest that Nos and Pum provide a crucial neuroprotective regulatory layer to ensure that neurons behave appropriately in response to developmental cues. © 2016. Published by The Company of Biologists Ltd.
7 CFR 993.149 - Receiving of prunes by handlers.
Code of Federal Regulations, 2010 CFR
2010-01-01
... SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED... certifies that the dehydration process of the prunes being certified resulted in prunes eligible to be... conditioning by further drying or dehydration: Provided, That such prunes shall be identified and kept separate...
CDKL5 and Shootin1 Interact and Concur in Regulating Neuronal Polarization.
Nawaz, Mohammad Sarfaraz; Giarda, Elisa; Bedogni, Francesco; La Montanara, Paolo; Ricciardi, Sara; Ciceri, Dalila; Alberio, Tiziana; Landsberger, Nicoletta; Rusconi, Laura; Kilstrup-Nielsen, Charlotte
2016-01-01
In the last years, the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with epileptic encephalopathies characterized by the early onset of intractable epilepsy, severe developmental delay, autistic features, and often the development of Rett syndrome-like features. Still, the role of CDKL5 in neuronal functions is not fully understood. By way of a yeast two hybrid screening we identified the interaction of CDKL5 with shootin1, a brain specific protein acting as a determinant of axon formation during neuronal polarization. We found evidence that CDKL5 is involved, at least in part, in regulating neuronal polarization through its interaction with shootin1. Indeed, the two proteins interact in vivo and both are localized in the distal tip of outgrowing axons. By using primary hippocampal neurons as model system we find that adequate CDKL5 levels are required for axon specification. In fact, a significant number of neurons overexpressing CDKL5 is characterized by supernumerary axons, while the silencing of CDKL5 disrupts neuronal polarization. Interestingly, shootin1 phosphorylation is reduced in neurons silenced for CDKL5 suggesting that the kinase affects, directly or indirectly, the post-translational modification of shootin1. Finally, we find that the capacity of CDKL5 to generate surplus axons is attenuated in neurons with reduced shootin1 levels, in agreement with the notion that two proteins act in a common pathway. Altogether, these results point to a role of CDKL5 in the early steps of neuronal differentiation that can be explained, at least in part, by its association with shootin1.
CDKL5 and Shootin1 Interact and Concur in Regulating Neuronal Polarization
Nawaz, Mohammad Sarfaraz; Giarda, Elisa; Bedogni, Francesco; La Montanara, Paolo; Ricciardi, Sara; Ciceri, Dalila; Alberio, Tiziana; Landsberger, Nicoletta; Rusconi, Laura; Kilstrup-Nielsen, Charlotte
2016-01-01
In the last years, the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with epileptic encephalopathies characterized by the early onset of intractable epilepsy, severe developmental delay, autistic features, and often the development of Rett syndrome-like features. Still, the role of CDKL5 in neuronal functions is not fully understood. By way of a yeast two hybrid screening we identified the interaction of CDKL5 with shootin1, a brain specific protein acting as a determinant of axon formation during neuronal polarization. We found evidence that CDKL5 is involved, at least in part, in regulating neuronal polarization through its interaction with shootin1. Indeed, the two proteins interact in vivo and both are localized in the distal tip of outgrowing axons. By using primary hippocampal neurons as model system we find that adequate CDKL5 levels are required for axon specification. In fact, a significant number of neurons overexpressing CDKL5 is characterized by supernumerary axons, while the silencing of CDKL5 disrupts neuronal polarization. Interestingly, shootin1 phosphorylation is reduced in neurons silenced for CDKL5 suggesting that the kinase affects, directly or indirectly, the post-translational modification of shootin1. Finally, we find that the capacity of CDKL5 to generate surplus axons is attenuated in neurons with reduced shootin1 levels, in agreement with the notion that two proteins act in a common pathway. Altogether, these results point to a role of CDKL5 in the early steps of neuronal differentiation that can be explained, at least in part, by its association with shootin1. PMID:26849555
Veneer grade yield from pruned Douglas-fir.
Edward J. II Dimock; Henry H. Haskell
1962-01-01
This paper reports actual veneer yields obtained from 10 trees pruned at age 38 and harvested 20 years later. Information of this kind is needed to help determine if and when to prune and ultimately will be essential to a thorough economic analysis of expected returns from pruning.
7 CFR 993.22 - Consumer package.
Code of Federal Regulations, 2014 CFR
2014-01-01
... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... container holding less than 10 pounds of prunes and other dried fruit if more than 60 percent of the net weight of mixed dried fruit in the lot consists of standard processed prunes or standard prunes. ...
7 CFR 993.22 - Consumer package.
Code of Federal Regulations, 2012 CFR
2012-01-01
... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... container holding less than 10 pounds of prunes and other dried fruit if more than 60 percent of the net weight of mixed dried fruit in the lot consists of standard processed prunes or standard prunes. ...
7 CFR 993.22 - Consumer package.
Code of Federal Regulations, 2013 CFR
2013-01-01
... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... container holding less than 10 pounds of prunes and other dried fruit if more than 60 percent of the net weight of mixed dried fruit in the lot consists of standard processed prunes or standard prunes. ...
Code of Federal Regulations, 2011 CFR
2011-01-01
... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Order Regulating Handling Definitions § 993.5 Prunes. Prunes means and includes all sun-dried or artificially...) plums which have not been dried or dehydrated to a point where they are capable of being stored prior to...
Code of Federal Regulations, 2012 CFR
2012-01-01
... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Order Regulating Handling Definitions § 993.5 Prunes. Prunes means and includes all sun-dried or artificially...) plums which have not been dried or dehydrated to a point where they are capable of being stored prior to...
Code of Federal Regulations, 2014 CFR
2014-01-01
... ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Order Regulating Handling Definitions § 993.5 Prunes. Prunes means and includes all sun-dried or artificially...) plums which have not been dried or dehydrated to a point where they are capable of being stored prior to...
Code of Federal Regulations, 2013 CFR
2013-01-01
... ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Order Regulating Handling Definitions § 993.5 Prunes. Prunes means and includes all sun-dried or artificially...) plums which have not been dried or dehydrated to a point where they are capable of being stored prior to...
Preventing Trunk Diseases in the Vineyard: Choosing the Best Practices
USDA-ARS?s Scientific Manuscript database
Over years of research on control of grapevine trunk diseases, field trials identified cultural and chemical practices that prevent and limit infections of pruning wounds by the spores. These practices include delayed pruning, double pruning, and applications of pruning-wound protectants (e.g., thio...
Jing, Da-Wei; Liu, Fang-Chun; Wang, Ming-You; Ma, Hai-Lin; Du, Zhen-Yu; Ma, Bing-Yao; Dong, Yu-Feng
2017-01-01
This study aimed to determine the effects of root pruning on the physicochemical characteristics and microbial activities of poplar rhizosphere soil. The root systems of 5-year-old poplar (Populus×euramericana cv. 'Neva') trees were manually pruned at 6, 8, or 10 times diameter at breast height (DBH) from the trunk (severe, moderate, and light, respectively) along both inter-row sides. Moderate root pruning significantly increased the concentrations of amino acids, organic acids, and total sugars in the root exudates and decreased the pH of rhizosphere soil. This treatment also increased the contents of available nitrogen, phosphorus, potassium, and total organic carbon as well as high-, medium-, and low-activity organic carbon in rhizosphere soil. Moreover, moderate pruning increased the contents of microbial biomass carbon and nitrogen, and enhanced basal respiration, in addition to decreasing the metabolic quotients in rhizosphere soil by 8.9%, 5.0%, and 11.4% compared with control, light, and severe root pruning treatments, respectively. Moderate pruning increased the growth rates of DBH, tree height, and volume to the highest levels. Furthermore, these indices were not significantly different between the light root pruning and control groups, but varied significantly between severe and moderate root-pruning treatments. Thus, root pruning, depending on the distance from the trunk, significantly influences the physicochemical properties and microbial activities in poplar rhizosphere soil.
Jing, Da-Wei; Liu, Fang-Chun; Wang, Ming-You; Ma, Hai-Lin; Du, Zhen-Yu; Ma, Bing-Yao; Dong, Yu-Feng
2017-01-01
This study aimed to determine the effects of root pruning on the physicochemical characteristics and microbial activities of poplar rhizosphere soil. The root systems of 5-year-old poplar (Populus×euramericana cv. ‘Neva’) trees were manually pruned at 6, 8, or 10 times diameter at breast height (DBH) from the trunk (severe, moderate, and light, respectively) along both inter-row sides. Moderate root pruning significantly increased the concentrations of amino acids, organic acids, and total sugars in the root exudates and decreased the pH of rhizosphere soil. This treatment also increased the contents of available nitrogen, phosphorus, potassium, and total organic carbon as well as high-, medium-, and low-activity organic carbon in rhizosphere soil. Moreover, moderate pruning increased the contents of microbial biomass carbon and nitrogen, and enhanced basal respiration, in addition to decreasing the metabolic quotients in rhizosphere soil by 8.9%, 5.0%, and 11.4% compared with control, light, and severe root pruning treatments, respectively. Moderate pruning increased the growth rates of DBH, tree height, and volume to the highest levels. Furthermore, these indices were not significantly different between the light root pruning and control groups, but varied significantly between severe and moderate root-pruning treatments. Thus, root pruning, depending on the distance from the trunk, significantly influences the physicochemical properties and microbial activities in poplar rhizosphere soil. PMID:29117215
Growth of white pine and red spruce trees after pruning
Grant Davis
1958-01-01
Are pines the only coniferous trees suitable for pruning in the Northeast, or is it feasible to prune red spruce as well? Although red spruce is an important lumber species in the spruce-fir region, it is seldom pruned because of its relatively slow rate of growth.
7 CFR 993.149 - Receiving of prunes by handlers.
Code of Federal Regulations, 2011 CFR
2011-01-01
... certifies that the dehydration process of the prunes being certified resulted in prunes eligible to be... conditioning by further drying or dehydration: Provided, That such prunes shall be identified and kept separate... with such drying or dehydration, notify an inspector of the inspection service of his election, and the...
7 CFR 993.149 - Receiving of prunes by handlers.
Code of Federal Regulations, 2012 CFR
2012-01-01
... certifies that the dehydration process of the prunes being certified resulted in prunes eligible to be... conditioning by further drying or dehydration: Provided, That such prunes shall be identified and kept separate... with such drying or dehydration, notify an inspector of the inspection service of his election, and the...
7 CFR 993.149 - Receiving of prunes by handlers.
Code of Federal Regulations, 2013 CFR
2013-01-01
... certifies that the dehydration process of the prunes being certified resulted in prunes eligible to be... conditioning by further drying or dehydration: Provided, That such prunes shall be identified and kept separate... with such drying or dehydration, notify an inspector of the inspection service of his election, and the...
7 CFR 993.149 - Receiving of prunes by handlers.
Code of Federal Regulations, 2014 CFR
2014-01-01
... certifies that the dehydration process of the prunes being certified resulted in prunes eligible to be... conditioning by further drying or dehydration: Provided, That such prunes shall be identified and kept separate... with such drying or dehydration, notify an inspector of the inspection service of his election, and the...
Grapevine pruning systems and cultivars influence the diversity of wood-colonizing fungi
USDA-ARS?s Scientific Manuscript database
Grapevines host diverse fungal species, including pruning-wound pathogens and wood decomposers, with detrimental effects on crop productivity. This study aims at comparing the effects of two pruning systems, minimal (min-) or spur-pruning, on the sanitary status of vine trunks and the diversity of w...
Peter Bedker; Joseph O' Brien; Manfred Mielke
2012-01-01
The objective of pruning is to produce strong, healthy, attractive plants. By understanding how, when and why to prune, and by following a few simple principles, this objective can be achievedHow to Prune Trees (Revised 2012) Agency Publisher: Agriculture Dept., Forest Service, Northeastern Area State and Price forestry USA List Price:$4.00 Sale...
Grower perceptions of preventative practices for management of trunk diseases of grape
USDA-ARS?s Scientific Manuscript database
Trials on prevention of trunk diseases (e.g., Eutypa dieback) show that three practices [delayed pruning, double pruning, pruning-wound protectants] prevent pruning-wound infections by 25-100%. Nonetheless, they are often not adopted until disease incidence is >20% in mature vineyards. There are no ...
USDA-ARS?s Scientific Manuscript database
Experimental trials on prevention of trunk diseases Botryosphaeria dieback, Esca, and Eutypa dieback have shown that delayed pruning, double pruning, and applications of the pruning-wound protectant thiophanate-methyl (Topsin) can reduce pruning-wound infections by 25-75%. Despite this biological e...
Siu, Caitlin R; Balsor, Justin L; Jones, David G; Murphy, Kathryn M
2015-01-01
Traditionally, myelin is viewed as insulation around axons, however, more recent studies have shown it also plays an important role in plasticity, axonal metabolism, and neuroimmune signaling. Myelin is a complex multi-protein structure composed of hundreds of proteins, with Myelin Basic Protein (MBP) being the most studied. MBP has two families: Classic-MBP that is necessary for activity driven compaction of myelin around axons, and Golli-MBP that is found in neurons, oligodendrocytes, and T-cells. Furthermore, Golli-MBP has been called a "molecular link" between the nervous and immune systems. In visual cortex specifically, myelin proteins interact with immune processes to affect experience-dependent plasticity. We studied myelin in human visual cortex using Western blotting to quantify Classic- and Golli-MBP expression in post-mortem tissue samples ranging in age from 20 days to 80 years. We found that Classic- and Golli-MBP have different patterns of change across the lifespan. Classic-MBP gradually increases to 42 years and then declines into aging. Golli-MBP has early developmental changes that are coincident with milestones in visual system sensitive period, and gradually increases into aging. There are three stages in the balance between Classic- and Golli-MBP expression, with Golli-MBP dominating early, then shifting to Classic-MBP, and back to Golli-MBP in aging. Also Golli-MBP has a wave of high inter-individual variability during childhood. These results about cortical MBP expression are timely because they compliment recent advances in MRI techniques that produce high resolution maps of cortical myelin in normal and diseased brain. In addition, the unique pattern of Golli-MBP expression across the lifespan suggests that it supports high levels of neuroimmune interaction in cortical development and in aging.
Suh, Yeunsu; Davis, Michael E.; Lee, Kichoon
2013-01-01
Understanding the tissue-specific pattern of gene expression is critical in elucidating the molecular mechanisms of tissue development, gene function, and transcriptional regulations of biological processes. Although tissue-specific gene expression information is available in several databases, follow-up strategies to integrate and use these data are limited. The objective of the current study was to identify and evaluate novel tissue-specific genes in human and mouse tissues by performing comparative microarray database analysis and semi-quantitative PCR analysis. We developed a powerful approach to predict tissue-specific genes by analyzing existing microarray data from the NCBI′s Gene Expression Omnibus (GEO) public repository. We investigated and confirmed tissue-specific gene expression in the human and mouse kidney, liver, lung, heart, muscle, and adipose tissue. Applying our novel comparative microarray approach, we confirmed 10 kidney, 11 liver, 11 lung, 11 heart, 8 muscle, and 8 adipose specific genes. The accuracy of this approach was further verified by employing semi-quantitative PCR reaction and by searching for gene function information in existing publications. Three novel tissue-specific genes were discovered by this approach including AMDHD1 (amidohydrolase domain containing 1) in the liver, PRUNE2 (prune homolog 2) in the heart, and ACVR1C (activin A receptor, type IC) in adipose tissue. We further confirmed the tissue-specific expression of these 3 novel genes by real-time PCR. Among them, ACVR1C is adipose tissue-specific and adipocyte-specific in adipose tissue, and can be used as an adipocyte developmental marker. From GEO profiles, we predicted the processes in which AMDHD1 and PRUNE2 may participate. Our approach provides a novel way to identify new sets of tissue-specific genes and to predict functions in which they may be involved. PMID:23741331
2012-01-01
Background The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a small number of targets in the olfactory bulb such that each glomerulus is made up of axon terminals expressing just one odorant receptor. It is thought that this precision in axon targeting is required to maintain highly refined odor discrimination. We previously showed that β3GnT2−/− mice have severe developmental and axon guidance defects. The phenotype of these mice is similar to adenylyl cyclase 3 (AC3) knockout mice largely due to the significant down-regulation of AC3 activity in β3GnT2−/− neurons. Results Microarray analysis reveals that nearly one quarter of all odorant receptor genes are down regulated in β3GnT2−/− mice compared to controls. Analysis of OR expression by quantitative PCR and in situ hybridization demonstrates that the number of neurons expressing some odorant receptors, such as mOR256-17, is increased by nearly 60% whereas for others such as mOR28 the number of neurons is decreased by more than 75% in β3GnT2−/− olfactory epithelia. Analysis of axon trajectories confirms that many axons track to inappropriate targets in β3GnT2−/− mice, and some glomeruli are populated by axons expressing more than one odorant receptor. Results show that mutant mice perform nearly as well as control mice in an odor discrimination task. In addition, in situ hybridization studies indicate that the expression of several activity dependent genes is unaffected in β3GnT2−/− olfactory neurons. Conclusions Results presented here show that many odorant receptors are under-expressed in β3GnT2−/− mice and further demonstrate that additional axon subsets grow into inappropriate targets or minimally innervate glomeruli in the olfactory bulb. Odor evoked gene expression is unchanged and β3GnT2−/− mice exhibit a relatively small deficit in their ability to discriminate divergent odors. Results suggest that despite the fact that β3GnT2−/− mice have decreased AC3 activity, decreased expression of many ORs, and display many axon growth and guidance errors, odor-evoked activity in cilia of mutant olfactory neurons remains largely intact. PMID:22559903
Tanaka, Akemi J.; Cho, Megan T.; Willaert, Rebecca; Retterer, Kyle; Zarate, Yuri A.; Bosanko, Katie; Stefans, Vikki; Oishi, Kimihiko; Williamson, Amy; Wilson, Golder N.; Basinger, Alice; Barbaro-Dieber, Tina; Ortega, Lucia; Sorrentino, Susanna; Gabriel, Melissa K.; Anderson, Ilse J.; Sacoto, Maria J. Guillen; Schnur, Rhonda E.; Chung, Wendy K.
2017-01-01
Using whole-exome sequencing, we identified seven unrelated individuals with global developmental delay, hypotonia, dysmorphic facial features, and an increased frequency of short stature, ataxia, and autism with de novo heterozygous frameshift, nonsense, splice, and missense variants in the Early B-cell Transcription Factor Family Member 3 (EBF3) gene. EBF3 is a member of the collier/olfactory-1/early B-cell factor (COE) family of proteins, which are required for central nervous system (CNS) development. COE proteins are highly evolutionarily conserved and regulate neuronal specification, migration, axon guidance, and dendritogenesis during development and are essential for maintaining neuronal identity in adult neurons. Haploinsufficiency of EBF3 may affect brain development and function, resulting in developmental delay, intellectual disability, and behavioral differences observed in individuals with a deleterious variant in EBF3. PMID:29162653
Tomàs, Josep M; Garcia, Neus; Lanuza, Maria A; Nadal, Laura; Tomàs, Marta; Hurtado, Erica; Simó, Anna; Cilleros, Víctor
2017-01-01
Synapses that are overproduced during histogenesis in the nervous system are eventually lost and connectivity is refined. Membrane receptor signaling leads to activity-dependent mutual influence and competition between axons directly or with the involvement of the postsynaptic cell and the associated glial cell/s. Presynaptic muscarinic acetylcholine (ACh) receptors (subtypes mAChR; M 1 , M 2 and M 4 ), adenosine receptors (AR; A 1 and A 2A ) and the tropomyosin-related kinase B receptor (TrkB), among others, all cooperate in synapse elimination. Between these receptors there are several synergistic, antagonic and modulatory relations that clearly affect synapse elimination. Metabotropic receptors converge in a limited repertoire of intracellular effector kinases, particularly serine protein kinases A and C (PKA and PKC), to phosphorylate protein targets and bring about structural and functional changes leading to axon loss. In most cells A 1 , M 1 and TrkB operate mainly by stimulating PKC whereas A 2A , M 2 and M 4 inhibit PKA. We hypothesize that a membrane receptor-induced shifting in the protein kinases A and C activity (inhibition of PKA and/or stimulation of PKC) in some nerve endings may play an important role in promoting developmental synapse elimination at the neuromuscular junction (NMJ). This hypothesis is supported by: (i) the tonic effect (shown by using selective inhibitors) of several membrane receptors that accelerates axon loss between postnatal days P5-P9; (ii) the synergistic, antagonic and modulatory effects (shown by paired inhibition) of the receptors on axonal loss; (iii) the fact that the coupling of these receptors activates/inhibits the intracellular serine kinases; and (iv) the increase of the PKA activity, the reduction of the PKC activity or, in most cases, both situations simultaneously that presumably occurs in all the situations of singly and paired inhibition of the mAChR, AR and TrkB receptors. The use of transgenic animals and various combinations of selective and specific PKA and PKC inhibitors could help to elucidate the role of these kinases in synapse maturation.
21 CFR 145.190 - Canned prunes.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Canned prunes. 145.190 Section 145.190 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...) Ingredients. Canned prunes is the food prepared from dried prunes, which may be packed as a solid pack or in...
21 CFR 145.190 - Canned prunes.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Canned prunes. 145.190 Section 145.190 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...) Ingredients. Canned prunes is the food prepared from dried prunes, which may be packed as a solid pack or in...
21 CFR 145.190 - Canned prunes.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Canned prunes. 145.190 Section 145.190 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...) Ingredients. Canned prunes is the food prepared from dried prunes, which may be packed as a solid pack or in...
Pruning open-grown black cherry
T. J. Grisez
1967-01-01
Black cherry trees that had large crown ratios and were 4 to 6 inches d. b. h. were pruned to various heights. Epicormic sprouting was severe and diameter growth at breast height was reduced on trees pruned to 75 percent of their height. Most trees pruned to 50 percent show little or no adverse effect after 3 years.
21 CFR 146.187 - Canned prune juice.
Code of Federal Regulations, 2010 CFR
2010-04-01
... Beverages § 146.187 Canned prune juice. (a) Canned prune juice is the food prepared from a water extract of... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Canned prune juice. 146.187 Section 146.187 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR...
7 CFR 993.159 - Payments for services performed with respect to reserve tonnage prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... (natural condition rate) for necessary services rendered by the handler in connection with such prunes so... year when the Committee recommends a reserve pool (except the Committee may extend this date by not... tonnage prunes. The Committee will compute the average industry cost for holding reserve pool prunes by...
7 CFR 993.159 - Payments for services performed with respect to reserve tonnage prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... (natural condition rate) for necessary services rendered by the handler in connection with such prunes so... year when the Committee recommends a reserve pool (except the Committee may extend this date by not... tonnage prunes. The Committee will compute the average industry cost for holding reserve pool prunes by...
Coast redwood responses to pruning
Kevin L. O' Hara
2012-01-01
A large-scale pruning study was established in the winter of 1999 to 2000 at seven different sites on Green Diamond Resource Company forestlands in Humboldt County. The objective of this study was to determine the effects of pruning on increment, epicormic sprouting, stem taper, heartwood formation, and bear damage on these young trees. Pruning treatments varied...
Process and formulation effects on solar thermal drum dried prune pomace
USDA-ARS?s Scientific Manuscript database
The processing of dried plums into prune juice and concentrate yields prune pomace as a coproduct; the pomace could potentially be utilized as a food ingredient but requires stabilization for long-term storage. Drum drying is one method that could be used to dry and stabilize prune pomace, and a dru...
Growth and Branching of Young Cottonwoods After Pruning
Roger M. Krinard
1976-01-01
Although spring and summer pruning to various heights reduced diameter growth for the treatment year, diameter increment of most pruned trees did not differ significantly from that of controls 2 years after treatment. Total diameter growth during the test period was significantly less for pruned trees than for controls. Epicormic branching increased with spring...
7 CFR 993.501 - Consumer package of prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Consumer package of prunes. 993.501 Section 993.501... CALIFORNIA Pack Specification as to Size Definitions § 993.501 Consumer package of prunes. Consumer package of prunes means consumer package as defined in § 993.22. Effective Date Note: At 70 FR 30613, May 27...
Zhang, Jin-Zhi; Zhao, Kun; Ai, Xiao-Yan; Hu, Chun-Gen
2014-10-13
Citrus shoot tips abscise at an anatomically distinct abscission zone (AZ) that separates the top part of the shoots into basal and apical portions (citrus self-pruning). Cell separation occurs only at the AZ, which suggests its cells have distinctive molecular regulation. Although several studies have looked into the morphological aspects of self-pruning process, the underlying molecular mechanisms remain unknown. In this study, the hallmarks of programmed cell death (PCD) were identified by TUNEL experiments, transmission electron microscopy (TEM) and histochemical staining for reactive oxygen species (ROS) during self-pruning of the spring shoots in sweet orange. Our results indicated that PCD occurred systematically and progressively and may play an important role in the control of self-pruning of citrus. Microarray analysis was used to examine transcriptome changes at three stages of self-pruning, and 1,378 differentially expressed genes were identified. Some genes were related to PCD, while others were associated with cell wall biosynthesis or metabolism. These results strongly suggest that abscission layers activate both catabolic and anabolic wall modification pathways during the self-pruning process. In addition, a strong correlation was observed between self-pruning and the expression of hormone-related genes. Self-pruning plays an important role in citrus floral bud initiation. Therefore, several key flowering homologs of Arabidopsis and tomato shoot apical meristem (SAM) activity genes were investigated in sweet orange by real-time PCR and in situ hybridization, and the results indicated that these genes were preferentially expressed in SAM as well as axillary meristem. Based on these findings, a model for sweet orange spring shoot self-pruning is proposed, which will enable us to better understand the mechanism of self-pruning and abscission.
Simple modification of Oja rule limits L1-norm of weight vector and leads to sparse connectivity.
Aparin, Vladimir
2012-03-01
This letter describes a simple modification of the Oja learning rule, which asymptotically constrains the L1-norm of an input weight vector instead of the L2-norm as in the original rule. This constraining is local as opposed to commonly used instant normalizations, which require the knowledge of all input weights of a neuron to update each one of them individually. The proposed rule converges to a weight vector that is sparser (has more zero weights) than the vector learned by the original Oja rule with or without the zero bound, which could explain the developmental synaptic pruning.
5,7-Dihydroxitryptamine toxicity to serotonergic neurons in serum free raphe cultures.
Capela, João Paulo; Lautenschlager, Marion; Dirnagl, Ulrich; Bastos, Maria Lourdes; Carvalho, Félix; Meisel, Andreas
2008-07-07
5,7-Dihydroxytryptamine (5,7-DHT), is an experimentally widely used selective serotonergic neurotoxin, though the mechanisms of toxicity remain to be fully elucidated. In the present study, we evaluated 5,7-dihydroxitryptamine (5,7-DHT) induced serotonergic neurotoxicity in foetal raphe serum free cultures from the rat. For this purpose, a model of foetal raphe serum free neuronal cultures from the rat was established, containing about 16% serotonergic neurons and studied up to 3 months. Two weeks old raphe cultures were exposed to the serotonergic neurotoxin 5,7-DHT (concentration range 10-100 microM) for 72 h, after which the medium was replaced and neurotoxicity was evaluated by immunocitochemistry 1 week later. Lactate dehydrogenase release into the medium, 72 h after exposure to 5,7-DHT, showed a concentration-dependent neurotoxicity. To access morphologically the serotonergic toxicity tryptophan hydroxylase (TPH) was used as a specific marker of these neurons. Immunocitochemistry using TPH antisera showed a concentration-dependent serotonergic neurotoxicity induced by 5,7-DHT. Serotonergic neurons showed the typical pattern of "pruning" accompanied by axon terminals and dendrites loss, which were either partial or total. The axotomy induced by the neurotoxin was morphologically characteristic of retrograde axonal degeneration. Fluoxetine (0.1 microM) pre-treatment reduced 5,7-DHT-induced serotonergic neurotoxicity. These results indicate that the mechanism by which 5,7-DHT-induces serotonergic neurotoxicity is, at least partially, dependent on the toxin uptake by the serotonin transporter. Finally, we have established a robust model of primary raphe neuronal culture to evaluate serotonergic neurons development and the mechanisms of toxicity involving this neuronal population.
Teriakidis, Adrianna; Willshaw, David J; Ribchester, Richard R
2012-10-01
During development, neurons form supernumerary synapses, most of which are selectively pruned leading to stereotyped patterns of innervation. During the development of skeletal muscle innervation, or its regeneration after nerve injury, each muscle fiber is transiently innervated by multiple motor axon branches but eventually by a single branch. The selective elimination of all but one branch is the result of competition between the converging arbors. It is thought that motor neurons initially innervate muscle fibers randomly, but that axon branches from the same neuron (sibling branches) do not converge to innervate the same muscle fiber. However, random innervation would result in many neonatal endplates that are co-innervated by sibling branches. To investigate whether this occurs we examined neonatal levator auris longus (LAL) and 4th deep lumbrical (4DL) muscles, as well as adult reinnervated deep lumbrical muscles (1-4) in transgenic mice expressing yellow fluorescent protein (YFP) as a reporter. We provide direct evidence of convergence of sibling neurites within single fluorescent motor units, both during development and during regeneration after nerve crush. The incidence of sibling neurite convergence was 40% lower in regeneration and at least 75% lower during development than expected by chance. Therefore, there must be a mechanism that decreases the probability of its occurrence. As sibling neurite convergence is not seen in normal adults, or at later timepoints in regeneration, synapse elimination must also remove convergent synaptic inputs derived from the same motor neuron. Mechanistic theories of synaptic competition should now accommodate this form of isoaxonal plasticity. Copyright © 2012 Wiley Periodicals, Inc.
C. B. Briscoe; R. W. Nobles
1966-01-01
Teak plantations, 8 to 10 years old, were pruned to improve log quality. Of the pruned trees at the ends of rows and adjacent to road clearings, 40 percent produced adventitious branches; 28 percent of trees within the stand branched; only 6 percent of trees inside the stand but without immediate n eighbors re-branched. Trees pruned in August branched less than those...
Pruning and occurrence of heart rot in young Douglas-fir.
Thomas W. Childs; Ernest Wright
1956-01-01
Heart rot is sometimes common in pole-size Douglas-firs that had been heavily live-pruned for trail clearance when they were long-crowned saplings, This observation suggested that benefits from pruning for quality increment might be reduced appreciably by heart rot infections occurring through pruning wounds. The study described in this paper was therefore undertaken...
Financial analysis of pruning ponderosa pine.
Roger D. Fight; Natalie A. Bolon; James M. Cahill
1992-01-01
A recent lumber recovery study of pruned and unpruned ponderosa pine (Pinus ponderosa Dougl. ex Laws.) was used to project the financial return from pruning ponderosa pine in the Medford District of the Bureau of Land Management and in the Ochoco and Deschutes National Forests. The cost of pruning at which the investment would yield an expected 4-...
USDA-ARS?s Scientific Manuscript database
Most Korean vineyards employed spur-pruning type modified-T trellis system. This produce system is suitable to spur-pruning type cultivars. But most European table grape is not adaptable to this produce system because their fruitfulness is sufficient to cane-pruning type system. Total 20 of fruit ch...
Li, Ying; van den Pol, Anthony N
2009-12-02
In contrast to the local axons of GABA neurons of the cortex and hippocampus, lateral hypothalamic neurons containing melanin concentrating hormone (MCH) and GABA send long axons throughout the brain and play key roles in energy homeostasis and mental status. In adults, MCH neurons maintain a hyperpolarized membrane potential and most of the synaptic input is inhibitory. In contrast, we found that developing MCH neurons received substantially more excitatory synaptic input. Based on gramicidin-perforated patch recordings in hypothalamic slices from MCH-green fluorescent protein transgenic mice, we found that GABA was the primary excitatory synaptic transmitter in embryonic and neonatal ages up to postnatal day 10. Surprisingly, glutamate assumed only a minor excitatory role, if any. GABA plays a complex role in developing MCH neurons, with its actions conditionally dependent on a number of factors. GABA depolarization could lead to an increase in spikes either independently or in summation with other depolarizing stimuli, or alternately, depending on the relative timing of other depolarizing events, could lead to shunting inhibition. The developmental shift from depolarizing to hyperpolarizing occurred later in the dendrites than in the cell body. Early GABA depolarization was based on a Cl(-)-dependent inward current. An interesting secondary depolarization in mature neurons that followed an initial hyperpolarization was based on a bicarbonate mechanism. Thus during the early developmental period when food consumption is high, MCH neurons are more depolarized than in the adult, and an increased level of excitatory synaptic input to these orexigenic cells is mediated by GABA.
Li, Ying; van den Pol, Anthony N.
2010-01-01
In contrast to the local axons of GABA neurons of the cortex and hippocampus, lateral hypothalamic neurons containing melanin concentrating hormone (MCH) and GABA send long axons throughout the brain and play key roles in energy homeostasis and mental status. In adults, MCH neurons maintain a hyperpolarized membrane potential and most of the synaptic input is inhibitory. In contrast, we found that developing MCH neurons received substantially more excitatory synaptic input. Based on gramicidicin-perforated patch recordings in hypothalamic slices from MCH-GFP transgenic mice, we found that GABA was the primary excitatory synaptic transmitter in embryonic and neonatal ages up to postnatal day 10. Surprisingly, glutamate assumed only a minor excitatory role, if any. GABA plays a complex role in developing MCH neurons, with its actions conditionally dependent on a number of factors. GABA depolarization could lead to an increase in spikes either independently or in summation with other depolarizing stimuli, or alternately, depending on the relative timing of other depolarizing events, could lead to shunting inhibition. The developmental shift from depolarizing to hyperpolarizing occurred later in the dendrites than in the cell body. Early GABA depolarization was based on a Cl− dependent inward current. An interesting secondary depolarization in mature neurons that followed an initial hyperpolarization was based on a bicarbonate mechanism. Thus during the early developmental period when food consumption is high, MCH neurons are more depolarized than in the adult, and an increased level of excitatory synaptic input to these orexigenic cells is mediated by GABA. PMID:19955372
Blüml, Stefan; Wisnowski, Jessica L.; Nelson, Marvin D.; Paquette, Lisa; Gilles, Floyd H.; Kinney, Hannah C.; Panigrahy, Ashok
2013-01-01
Between birth and late adolescence, the human brain undergoes exponential maturational changes. Using in vivo magnetic resonance spectroscopy, we determined the developmental profile for 6 metabolites in 5 distinct brain regions based on spectra from 309 children from 0 to 18 years of age. The concentrations of N-acetyl-aspartate (an indicator for adult-type neurons and axons), creatine (energy metabolite), and glutamate (excitatory neurotransmitter) increased rapidly between birth and 3 months, a period of rapid axonal growth and synapse formation. Myo-inositol, implicated in cell signaling and a precursor of membrane phospholipid, as well as an osmolyte and astrocyte marker, declined rapidly during this period. Choline, a membrane metabolite and indicator for de novo myelin and cell membrane synthesis, peaked from birth until approximately 3 months, and then declined gradually, reaching a plateau at early childhood. Similarly, taurine, involved in neuronal excitability, synaptic potentiation, and osmoregulation, was high until approximately 3 months and thereafter declined. These data indicate that the first 3 months of postnatal life are a critical period of rapid metabolic changes in the development of the human brain. This study of the developmental profiles of the major brain metabolites provides essential baseline information for future analyses of the pediatric health and disease. PMID:22952278
Cadmium affects muscle type development and axon growth in zebrafish embryonic somitogenesis.
Hen Chow, Elly Suk; Cheng, Shuk Han
2003-05-01
We have previously reported that exposure to cadmium during zebrafish embryonic development caused morphological malformations of organs and ectopic expression of genes involved in regulating developmental process. One of the most common developmental defects observed was altered axial curvature resulting from defects in the myotomes of the somites. In this study, we investigated the mechanisms of cadmium-induced toxicity in zebrafish somitogenesis. We showed that the critical period of exposure was the gastrulation period, which actually preceded the formation of the first morphologically distinct somites. The somites thus formed lost the typical chevron V-shape and are packed disorderly. The myogenic lineage commitment of the axial mesodermal cells was not affected, as the myogenic regulatory transcription factors were expressed normally. There were, however, losses of fast and slow muscle fibers in the myotomes. The innervation of the muscle blocks by spinal motoneurons is an important process of the somitogenesis. Both primary and secondary motoneurons appear to form normally while the axon growth is affected in cadmium-treated embryos. The notochord, which is essential in the patterning of the somites and the central nervous system, showed abnormal morphological features and failed to extend to the tail region. Taken together, it appears that cadmium exposure led to abnormal somite patterning of the muscle fibers and defects in axonogenesis.
Control of Spine Maturation and Pruning through ProBDNF Synthesized and Released in Dendrites
Orefice, Lauren L.; Shih, Chien-Cheng; Xu, Haifei; Waterhouse, Emily G.; Xu, Baoji
2015-01-01
Excess synapses formed during early postnatal development are pruned over an extended period, while the remaining synapses mature. Synapse pruning is critical for activity-dependent refinement of neuronal connections and its dysregulation has been found in neurodevelopmental disorders such as autism spectrum disorders; however, the mechanism underlying synapse pruning remains largely unknown. As dendritic spines are the postsynaptic sites for the vast majority of excitatory synapses, spine maturation and pruning are indicators for maturation and elimination of these synapses. Our previous studies have found that dendritically localized mRNA for brain-derived neurotrophic factor (BDNF) regulates spine maturation and pruning. Here we investigated the mechanism by which dendritic Bdnf mRNA, but not somatically restricted Bdnf mRNA, promotes spine maturation and pruning. We found that neuronal activity stimulates both translation of dendritic Bdnf mRNA and secretion of its translation product mainly as proBDNF. The secreted proBDNF promotes spine maturation and pruning, and its effect on spine pruning is in part mediated by the p75NTR receptor via RhoA activation. Furthermore, some proBDNF is extracellularly converted to mature BDNF and then promotes maturation of stimulated spines by activating Rac1 through the TrkB receptor. In contrast, translation of somatic Bdnf mRNA and the release of its translation product mainly as mature BDNF are independent of action potentials. These results not only reveal a biochemical pathway regulating synapse pruning, but also suggest that BDNF synthesized in the soma and dendrites is released through distinct secretory pathways. PMID:26705735
Stanislawski, L.V.
2009-01-01
The United States Geological Survey has been researching generalization approaches to enable multiple-scale display and delivery of geographic data. This paper presents automated methods to prune network and polygon features of the United States high-resolution National Hydrography Dataset (NHD) to lower resolutions. Feature-pruning rules, data enrichment, and partitioning are derived from knowledge of surface water, the NHD model, and associated feature specification standards. Relative prominence of network features is estimated from upstream drainage area (UDA). Network and polygon features are pruned by UDA and NHD reach code to achieve a drainage density appropriate for any less detailed map scale. Data partitioning maintains local drainage density variations that characterize the terrain. For demonstration, a 48 subbasin area of 1:24 000-scale NHD was pruned to 1:100 000-scale (100 K) and compared to a benchmark, the 100 K NHD. The coefficient of line correspondence (CLC) is used to evaluate how well pruned network features match the benchmark network. CLC values of 0.82 and 0.77 result from pruning with and without partitioning, respectively. The number of polygons that remain after pruning is about seven times that of the benchmark, but the area covered by the polygons that remain after pruning is only about 10% greater than the area covered by benchmark polygons. ?? 2009.
... treat or help prevent urinary tract infections. Support Groups The following resources can provide more information on prune belly syndrome: Prune Belly Syndrome Network -- www.prunebelly.org National Organization for Rare Disorders -- ...
Ten-year observations on pruned ponderosa and jeffrey pine
Donald T. Gordon
1959-01-01
In 1956 Hallinl reported some observed effects of pruning ponderosa and Jeffrey pine based on the response after 5 years. This report is an extension of those observations, after a 10-year reexamination of the experiment. Hallin suggested that half the live crown, or six-tenths of total height of the tree could be pruned without adverse effects on growth. Pruning out...
Synapto-protective drugs evaluation in reconstructed neuronal network.
Deleglise, Bérangère; Lassus, Benjamin; Soubeyre, Vaneyssa; Alleaume-Butaux, Aurélie; Hjorth, Johannes J; Vignes, Maéva; Schneider, Benoit; Brugg, Bernard; Viovy, Jean-Louis; Peyrin, Jean-Michel
2013-01-01
Chronic neurodegenerative syndromes such as Alzheimer's and Parkinson's diseases, or acute syndromes such as ischemic stroke or traumatic brain injuries are characterized by early synaptic collapse which precedes axonal and neuronal cell body degeneration and promotes early cognitive impairment in patients. Until now, neuroprotective strategies have failed to impede the progression of neurodegenerative syndromes. Drugs preventing the loss of cell body do not prevent the cognitive decline, probably because they lack synapto-protective effects. The absence of physiologically realistic neuronal network models which can be easily handled has hindered the development of synapto-protective drugs suitable for therapies. Here we describe a new microfluidic platform which makes it possible to study the consequences of axonal trauma of reconstructed oriented mouse neuronal networks. Each neuronal population and sub-compartment can be chemically addressed individually. The somatic, mid axon, presynaptic and postsynaptic effects of local pathological stresses or putative protective molecules can thus be evaluated with the help of this versatile "brain on chip" platform. We show that presynaptic loss is the earliest event observed following axotomy of cortical fibers, before any sign of axonal fragmentation or post-synaptic spine alteration. This platform can be used to screen and evaluate the synapto-protective potential of several drugs. For instance, NAD⁺ and the Rho-kinase inhibitor Y27632 can efficiently prevent synaptic disconnection, whereas the broad-spectrum caspase inhibitor zVAD-fmk and the stilbenoid resveratrol do not prevent presynaptic degeneration. Hence, this platform is a promising tool for fundamental research in the field of developmental and neurodegenerative neurosciences, and also offers the opportunity to set up pharmacological screening of axon-protective and synapto-protective drugs.
Nakamura, Kouichi; Hioki, Hiroyuki; Fujiyama, Fumino; Kaneko, Takeshi
2005-11-21
Vesicular glutamate transporter 1 (VGluT1) and VGluT2 accumulate neurotransmitter glutamate into synaptic vesicles at presynaptic terminals, and their antibodies are thus considered to be a good marker for glutamatergic axon terminals. In the present study, we investigated the postnatal development and maturation of glutamatergic neuronal systems by single- and double-immunolabelings for VGluT1 and VGluT2 in mouse forebrain including the telencephalon and diencephalon. VGluT2 immunoreactivity was widely distributed in the forebrain, particularly in the diencephalon, from postnatal day 0 (P0) to adulthood, suggesting relatively early maturation of VGluT2-loaded glutamatergic axons. In contrast, VGluT1 immunoreactivity was intense only in the limbic regions at P0, and drastically increased in the other telencephalic and diencephalic regions during three postnatal weeks. Interestingly, VGluT1 immunoreactivity was frequently colocalized with VGluT2 immunoreactivity at single axon terminal-like profiles in layer IV of the primary somatosensory area from P5 to P10 and in the ventral posteromedial thalamic nucleus from P0 to P14. This was in sharp contrast to the finding that almost no colocalization was found in glomeruli of the olfactory bulb, patchy regions of the caudate-putamen, and the ventral posterolateral thalamic nucleus, where moderate to intense immunoreactivities for VGluT1 and VGluT2 were intermingled with each other in neuropil during postnatal development. The present results indicate that VGluT2-loaded glutamatergic axons maturate earlier than VGluT1-laden axons in the mouse telencephalic and diencephalic regions, and suggest that VGluT1 plays a transient developmental role in some glutamatergic systems that mainly use VGluT2 in the adulthood. (c) 2005 Wiley-Liss, Inc.
Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria Angel; Cilleros, Victor; Tomàs, Josep Maria
2016-01-01
The development of the nervous system involves the initial overproduction of synapses, which promotes connectivity. Hebbian competition between axons with different activities leads to the loss of roughly half of the overproduced elements and this refines connectivity. We used quantitative immunohistochemistry to investigate, in the postnatal day 7 (P7) to P9 neuromuscular junctions, the involvement of muscarinic receptors (muscarinic acetylcholine autoreceptors and the M1, M2, and M4 subtypes) and adenosine receptors (A1 and A2A subtypes) in the control of axonal elimination after the mouse levator auris longus muscle had been exposed to selective antagonists in vivo. In a previous study we analyzed the role of each of the individual receptors. Here we investigate the additive or occlusive effects of their inhibitors and thus the existence of synergistic activity between the receptors. The main results show that the A2A, M1, M4, and A1 receptors (in this order of ability) delayed axonal elimination at P7. M4 produces some occlusion of the M1 pathway and some addition to the A1 pathway, which suggests that they cooperate. M2 receptors may modulate (by allowing a permissive action) the other receptors, mainly M4 and A1. The continued action of these receptors (now including M2 but not M4) finally promotes axonal loss at P9. All 4 receptors (M2, M1, A1, and A2A, in this order of ability) are necessary. The M4 receptor (which in itself does not affect axon loss) seems to modulate the other receptors. We found a synergistic action between the M1, A1, and A2A receptors, which show an additive effect, whereas the potent M2 effect is largely independent of the other receptors (though can be modulated by M4). At P9, there is a full mutual dependence between the A1 and A2A receptors in regulating axon loss. In summary, postnatal axonal elimination is a regulated multireceptor mechanism that involves the cooperation of several muscarinic and adenosine receptor subtypes. © 2017 S. Karger AG, Basel.
Five Years' Growth of Pruned and Unpruned Cottonwood Planted at 40- by 40-Foot Spacing
Roger M. Krinard
1979-01-01
Four pruning treatments have been applied for 5 years on cottonwood (Populus deltoides Bartr.) select clone Stoneville 66, planted at 40- by 40-ft spacing. As pruning severity increased, average diameter and maximum crown width decreased. Diameters ranged from 9.2 inches for trees pruned half of height yearly to 11.4 inches for unpruned trees; crown widths ranged from...
Black Walnut on Kansas Strip Mine Spoils: Some Observations 25 Years after Pruning
Alex L. Shigo; Nelson F. Rogers; E. Allen, Jr. McGinnes; David T. Funk
1978-01-01
Dissections of 14 slow-growing black walnut trees on a strip-mine site revealed that bands of discolored heartwood were associated with pruned and nonpruned branch stubs. Ring shakes were associated with a few pruned and nonpruned stubs, especially with groups of stubs at the same position on the stem. The advantage of early pruning was that even the defects that...
Profits from pruning ponderosa pine in relation to pruning diameter
Grant. Davis
1958-01-01
Pruning to obtain clear wood on the lower portion of forest trees has been practiced on a limited scale for many years. It became an important operation in the management of national forests after the enactment of the Knutson-Vandenberg Act in 1930. This act provided a means for retaining a portion of timber-sale receipts to finance pruning and other stand improvement...
Xu, Gang; Takahashi, Emi; Folkerth, Rebecca D.; Haynes, Robin L.; Volpe, Joseph J.; Grant, P. Ellen; Kinney, Hannah C.
2014-01-01
High angular resolution diffusion imaging (HARDI) demonstrates transient radial coherence of telencephalic white matter in the human fetus. Our objective was to define the neuroanatomic basis of this radial coherence through correlative HARDI- and postmortem tissue analyses. Applying immunomarkers to radial glial fibers (RGFs), axons, and blood vessels in 18 cases (19 gestational weeks to 3 postnatal years), we compared their developmental profiles to HARDI tractography in brains of comparable ages (n = 11). At midgestation, radial coherence corresponded with the presence of RGFs. At 30–31 weeks, the transition from HARDI-defined radial coherence to corticocortical coherence began simultaneously with the transformation of RGFs to astrocytes. By term, both radial coherence and RGFs had disappeared. White matter axons were radial, tangential, and oblique over the second half of gestation, whereas penetrating blood vessels were consistently radial. Thus, radial coherence in the fetal white matter likely reflects a composite of RGFs, penetrating blood vessels, and radial axons of which its transient expression most closely matches that of RGFs. This study provides baseline information for interpreting radial coherence in tractography studies of the preterm brain in the assessment of the encephalopathy of prematurity. PMID:23131806
Murray, Robin M; Bhavsar, Vishal; Tripoli, Giada; Howes, Oliver
2017-10-21
At its re-birth 30 years ago, the neurodevelopment hypothesis of schizophrenia focussed on aberrant genes and early neural hazards, but then it grew to include ideas concerning aberrant synaptic pruning in adolescence. The hypothesis had its own stormy development and it endured some difficult teenage years when a resurgence of interest in neurodegeneration threatened its survival. In early adult life, it over-reached itself with some reductionists claiming that schizophrenia was simply a neurodevelopmental disease. However, by age 30, the hypothesis has matured sufficiently to incorporated childhood and adult adversity, urban living and migration, as well as heavy cannabis use, as important risk factors. Thus, it morphed into the developmental risk factor model of psychosis and integrated new evidence concerning dysregulated striatal dopamine as the final step on the pathway linking risk factors to psychotic symptoms. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Yuan, Zhongyue; Li, Ying; Hu, Yulan; You, Jian; Higashisaka, Kazuma; Nagano, Kazuya; Tsutsumi, Yasuo; Gao, Jianqing
2016-12-30
Chitosan nanoparticles (CS-NPs) and their Tween 80 modified counterparts (TmCS-NPs) are among the most commonly used brain-targeted vehicles. However, their potential developmental toxicity is poorly understood. In this study, zebrafish embryos are introduced as an in vivo platform. Both NPs showed a dose-dependent increase in developmental toxicity (decreased hatching rate, increased mortality and incidences of malformation). Neurobehavioral changes included decreased spontaneous movement in TmCS-NP treated embryos and hyperactive effect in CS-NP treated larvae. Both NPs remarkably inhibited axonal development of primary and secondary motor neurons, and affected the muscle structure. Overall, this study demonstrated that CS-NPs and TmCS-NPs could affect embryonic development, disrupt neurobehavior of zebrafish larvae and affect muscle and neuron development, suggesting more attention on biodegradable chitosan nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.
Tanaka, Akemi J; Cho, Megan T; Willaert, Rebecca; Retterer, Kyle; Zarate, Yuri A; Bosanko, Katie; Stefans, Vikki; Oishi, Kimihiko; Williamson, Amy; Wilson, Golder N; Basinger, Alice; Barbaro-Dieber, Tina; Ortega, Lucia; Sorrentino, Susanna; Gabriel, Melissa K; Anderson, Ilse J; Sacoto, Maria J Guillen; Schnur, Rhonda E; Chung, Wendy K
2017-11-01
Using whole-exome sequencing, we identified seven unrelated individuals with global developmental delay, hypotonia, dysmorphic facial features, and an increased frequency of short stature, ataxia, and autism with de novo heterozygous frameshift, nonsense, splice, and missense variants in the Early B-cell Transcription Factor Family Member 3 ( EBF3 ) gene. EBF3 is a member of the collier/olfactory-1/early B-cell factor (COE) family of proteins, which are required for central nervous system (CNS) development. COE proteins are highly evolutionarily conserved and regulate neuronal specification, migration, axon guidance, and dendritogenesis during development and are essential for maintaining neuronal identity in adult neurons. Haploinsufficiency of EBF3 may affect brain development and function, resulting in developmental delay, intellectual disability, and behavioral differences observed in individuals with a deleterious variant in EBF3 . © 2017 Tanaka et al.; Published by Cold Spring Harbor Laboratory Press.
Patel, Ankur B.; Loerwald, Kristofer W.; Huber, Kimberly M.
2014-01-01
Pruning of structural synapses occurs with development and learning. A deficit in pruning of cortical excitatory synapses and the resulting hyperconnectivity is hypothesized to underlie the etiology of fragile X syndrome (FXS) and related autistic disorders. However, clear evidence for pruning in neocortex and its impairment in FXS remains elusive. Using simultaneous recordings of pyramidal neurons in the layer 5A neocortical network of the wild-type (WT) mouse to observe cell-to-cell connections in isolation, we demonstrate here a specific form of “connection pruning.” Connection frequency among pyramidal neurons decreases between the third and fifth postnatal weeks, indicating a period of connection pruning. Over the same interval in the FXS model mouse, the Fmr1 knock-out (KO), connection frequency does not decrease. Therefore, connection frequency in the fifth week is higher in the Fmr1 KO compared with WT, indicating a state of hyperconnectivity. These alterations are due to postsynaptic deletion of Fmr1. At early ages (2 weeks), postsynaptic Fmr1 promoted the maturation of cell-to-cell connections, but not their number. These findings indicate that impaired connection pruning at later ages, and not an excess of connection formation, underlies the hyperconnectivity in the Fmr1 KO mouse. FMRP did not appear to regulate synapses individually, but instead regulated cell-to-cell connectivity in which groups of synapses mediating a single cell-to-cell connection are uniformly removed, retained, and matured. Although we do not link connection pruning directly to the pruning of structurally defined synapses, this study nevertheless provides an important model system for studying altered pruning in FXS. PMID:24573297
Patel, Ankur B; Loerwald, Kristofer W; Huber, Kimberly M; Gibson, Jay R
2014-02-26
Pruning of structural synapses occurs with development and learning. A deficit in pruning of cortical excitatory synapses and the resulting hyperconnectivity is hypothesized to underlie the etiology of fragile X syndrome (FXS) and related autistic disorders. However, clear evidence for pruning in neocortex and its impairment in FXS remains elusive. Using simultaneous recordings of pyramidal neurons in the layer 5A neocortical network of the wild-type (WT) mouse to observe cell-to-cell connections in isolation, we demonstrate here a specific form of "connection pruning." Connection frequency among pyramidal neurons decreases between the third and fifth postnatal weeks, indicating a period of connection pruning. Over the same interval in the FXS model mouse, the Fmr1 knock-out (KO), connection frequency does not decrease. Therefore, connection frequency in the fifth week is higher in the Fmr1 KO compared with WT, indicating a state of hyperconnectivity. These alterations are due to postsynaptic deletion of Fmr1. At early ages (2 weeks), postsynaptic Fmr1 promoted the maturation of cell-to-cell connections, but not their number. These findings indicate that impaired connection pruning at later ages, and not an excess of connection formation, underlies the hyperconnectivity in the Fmr1 KO mouse. FMRP did not appear to regulate synapses individually, but instead regulated cell-to-cell connectivity in which groups of synapses mediating a single cell-to-cell connection are uniformly removed, retained, and matured. Although we do not link connection pruning directly to the pruning of structurally defined synapses, this study nevertheless provides an important model system for studying altered pruning in FXS.
Pruning of the Pulmonary Vasculature in Asthma: The SARP Cohort.
Ash, Samuel Y; Rahaghi, Farbod N; Come, Carolyn E; Ross, James C; Colon, Alysha G; Cardet-Guisasola, Juan Carlos; Dunican, Eleanor M; Bleecker, Eugene R; Castro, Mario; Fahy, John V; Fain, Sean B; Gaston, Benjamin M; Hoffman, Eric A; Jarjour, Nizar N; Mauger, David T; Wenzel, Sally E; Levy, Bruce D; San Jose Estepar, Raul; Israel, Elliot; Washko, George R
2018-04-19
Loss of the peripheral pulmonary vasculature, termed vascular pruning, is associated with disease severity in patients with chronic obstructive pulmonary disease. To determine if pulmonary vascular pruning is associated with asthma severity and exacerbations. We measured the total pulmonary blood vessel volume (TBV) and the blood vessel volume of vessels less than 5mm2 in cross sectional area (BV5) and of vessels less than 10mm2 (BV10) in cross sectional area on non-contrast computed tomographic scans of participants from the Severe Asthma Research Program. Lower values of the BV5 to TBV ratio (BV5/TBV) and the BV10 to TBV ratio (BV10/TBV) represented vascular pruning (loss of the peripheral pulmonary vasculature). Compared to healthy controls, severe asthmatics had more pulmonary vascular pruning. Among asthmatics, those with poor asthma control had more pruning than those well-controlled disease. Pruning of the pulmonary vasculature was also associated with lower percent predicted forced expiratory volume in one second and forced vital capacity, greater peripheral and sputum eosinophilia and higher bronchoalveolar lavage SAA/LXA4, but not with low attenuation area or with sputum neutrophilia. Compared with individuals with less pruning, individuals with the most vascular pruning had a 150% greater odds of reporting an asthma exacerbation (OR 2.50; CI: 1.05, 5.98; p=0.039 for BV10/TBV), and reported 45% more asthma exacerbations during follow-up (IRR 1.45; CI: 1.02, 2.06; p=0.036 for BV10/TBV). Pruning of the peripheral pulmonary vasculature is associated with asthma severity, control and exacerbations, as well as with lung function and eosinophilia.
Xu, Dongyang; Miao, Jiahang; Yumoto, Emi; Yokota, Takao; Asahina, Masashi; Watahiki, Masaaki
2017-01-01
Abstract Recovery of the root system following physical damage is an essential issue for plant survival. An injured root system is able to regenerate by increases in lateral root (LR) number and acceleration of root growth. The horticultural technique of root pruning (root cutting) is an application of this response and is a common garden technique for controlling plant growth. Although root pruning is widely used, the molecular mechanisms underlying the subsequent changes in the root system are poorly understood. In this study, root pruning was employed as a model system to study the molecular mechanisms of root system regeneration. Notably, LR defects in wild-type plants treated with inhibitors of polar auxin transport (PAT) or in the auxin signaling mutant auxin/indole-3-acetic acid19/massugu2 were recovered by root pruning. Induction of IAA19 following root pruning indicates an enhancement of auxin signaling by root pruning. Endogenous levels of IAA increased after root pruning, and YUCCA9 was identified as the primary gene responsible. PAT-related genes were induced after root pruning, and the YUCCA inhibitor yucasin suppressed root regeneration in PAT-related mutants. Therefore, we demonstrate the crucial role of YUCCA9, along with other redundant YUCCA family genes, in the enhancement of auxin biosynthesis following root pruning. This further enhances auxin transport and activates downstream auxin signaling genes, and thus increases LR number. PMID:29016906
Scholz, Beate; Korn, Claudia; Wojtarowicz, Jessica; Mogler, Carolin; Augustin, Iris; Boutros, Michael; Niehrs, Christof; Augustin, Hellmut G
2016-01-11
The WNT signaling enhancer R-spondin3 (RSPO3) is prominently expressed in the vasculature. Correspondingly, embryonic lethality of Rspo3-deficient mice is caused by vessel remodeling defects. Yet the mechanisms underlying vascular RSPO3 function remain elusive. Inducible endothelial Rspo3 deletion (Rspo3-iECKO) resulted in perturbed developmental and tumor vascular remodeling. Endothelial cell apoptosis and vascular pruning led to reduced microvessel density in Rspo3-iECKO mice. Rspo3-iECKO mice strikingly phenocopied the non-canonical WNT signaling-induced vascular defects of mice deleted for the WNT secretion factor Evi/Wls. An endothelial screen for RSPO3 and EVI/WLS co-regulated genes identified Rnf213, Usp18, and Trim30α. RNF213 targets filamin A and NFAT1 for proteasomal degradation attenuating non-canonical WNT/Ca(2+) signaling. Likewise, USP18 and TRIM5α inhibited NFAT1 activation. Consequently, NFAT protein levels were decreased in endothelial cells of Rspo3-iECKO mice and pharmacological NFAT inhibition phenocopied Rspo3-iECKO mice. The data identify endothelial RSPO3-driven non-canonical WNT/Ca(2+)/NFAT signaling as a critical maintenance pathway of the remodeling vasculature. Copyright © 2016 Elsevier Inc. All rights reserved.
Pruning Black Cherry in Understocked Stands
Ted J. Grisez
1978-01-01
Black cherry trees 4 to 6 inches in diameter at breast height (dbh) with live crown ratios ranging from 73 to 92 percent were pruned to 25, 50, or 75 percent of tree height or were left unpruned. Most trees can be pruned to 50 percent of tree height in one operation. Trees that have large crowns and that are frilly exposed on the southwest side should be pruned less...
Ikinci, Ali
2014-01-01
Winter and summer pruning are widely applied processes in all fruit trees, including in peach orchard management. This study was conducted to determine the effects of summer prunings (SP), as compared to winter pruning (WP), on shoot length, shoot diameter, trunk cross sectional area (TCSA) increment, fruit yield, fruit quality, and carbohydrate content of two early ripening peach cultivars (“Early Red” and “Maycrest”) of six years of age, grown in semiarid climate conditions, in 2008 to 2010. The trees were grafted on GF 677 rootstocks, trained with a central leader system, and spaced 5 × 5 m apart. The SP carried out after harvesting in July and August decreased the shoot length significantly; however, it increased its diameter. Compared to 2009, this effect was more marked in year 2010. In general, control and winter pruned trees of both cultivars had the highest TCSA increment and yield efficiency. The SP increased the average fruit weight and soluble solids contents (SSC) more than both control and WP. The titratable acidity showed no consistent response to pruning time. The carbohydrate accumulation in shoot was higher in WP and in control than in SP trees. SP significantly affected carbohydrate accumulation; postharvest pruning showed higher carbohydrate content than preharvest pruning. PMID:24737954
Siembab, Valerie C.; Gomez-Perez, Laura; Rotterman, Travis M.; Shneider, Neil A.; Alvarez, Francisco J.
2015-01-01
Motor function in mammalian species depends on the maturation of spinal circuits formed by a large variety of interneurons that regulate motoneuron firing and motor output. Interneuron activity is in turn modulated by the organization of their synaptic inputs, but the principles governing the development of specific synaptic architectures unique to each premotor interneuron are unknown. For example, Renshaw cells receive, at least in the neonate, convergent inputs from sensory afferents (likely Ia) and motor axons raising the question of whether they interact during Renshaw cell development. In other well-studied neurons, like Purkinje cells, heterosynaptic competition between inputs from different sources shapes synaptic organization. To examine the possibility that sensory afferents modulate synaptic maturation on developing Renshaw cells, we used three animal models in which afferent inputs in the ventral horn are dramatically reduced (Er81(−/−) knockout), weakened (Egr3(−/−) knockout) or strengthened (mlcNT3(+/−) transgenic). We demonstrate that increasing the strength of sensory inputs on Renshaw cells prevents their de-selection and reduces motor axon synaptic density and, in contrast, absent or diminished sensory afferent inputs correlate with increased densities of motor axons synapses. No effects were observed on other glutamatergic inputs. We conclude that the early strength of Ia synapses influences their maintenance or weakening during later development and that heterosynaptic influences from sensory synapses during early development regulates the density and organization of motor inputs on mature Renshaw cells. PMID:26660356
Sepp, Katharine J; Auld, Vanessa J
2003-09-10
A major developmental role of peripheral glia is to mediate sensory axon guidance; however, it is not known whether sensory neurons influence peripheral glial development. To determine whether glia and neurons reciprocally interact during embryonic development, we ablated each cell type by overexpressing the apoptosis gene, grim, and observed the effects on peripheral nervous system (PNS) development. When neurons are ablated, glial defects occur as a secondary effect, and vice versa. Therefore glia and neurons are codependent during embryogenesis. To further explore glial-neuronal interactions, we genetically disrupted glial migration or differentiation and observed the secondary effects on sensory neuron development. Glial migration and ensheathment of PNS axons was blocked by overexpression of activated Rho GTPase, a regulator of actin dynamics. Here, sensory axons extended to the CNS without exhibiting gross pathfinding errors. In contrast, disrupting differentiation by expression of dominant-negative Ras GTPase in glia resulted in major sensory axon pathfinding errors, similar to those seen in glial ablations. Glial overexpression of transgenic components of the epidermal growth factor receptor (EGFR) signaling pathway yielded similar sensory neuron defects and also downregulated the expression of the glial marker Neuroglian. Mutant analysis also suggested that the EGFR ligands Spitz and Vein play roles in peripheral glial development. The observations support a model in which glia express genes necessary for sensory neuron development, and these genes are potentially under the control of the EGFR/Ras signaling pathway.
NASA Astrophysics Data System (ADS)
Márquez San Emeterio, Layla; Martín Reyes, Marino Pedro; Ortiz Bernad, Irene; Fernández Ondoño, Emilia; Sierra Aragón, Manuel
2017-04-01
The amount of carbon that can be stored in a soil depends on many factors, such as the type of soil, the chemical composition of plant rests and the climate, and is also highly affected by land use and soil management. Agricultural ecosystems are proved to absorb a large amount of CO2 from the atmosphere through several sustainable management practices. In addition, organic materials such as leaves, grass, prunings, etc., comprise a significant type of agricultural practices as a result of waste recycling. The aim of this research was to evaluate the effects of the addition of different organic prunings on the potential for carbon sequestration in agricultural soils placed in terraces. Three subtropical orchards were sampled in Almuñécar (Granada, S Spain): mango (Mangifera indica L.), avocado (Persea americana Mill.) and cherimoya (Annonacherimola Mill.). The predominant climate is Subtropical Mediterranean and the soil is an Eutric Anthrosol. The experimental design consisted in the application of prunings from avocado, cherimoya and mango trees, placed on the surface soil underneath their correspondent trees, as well as garden prunings from the green areas surrounding the town center on the surface soils under the three orchard trees. Control experiences without the addition of prunings were also evaluated. These experiences were followed for three years. Soil samples were taken at4 cm depth. They were dried for 3-4 days and then sieved (<2 mm).Total soil organic C, water-soluble soil organic C, mineral-associated organic C and non-oxidable C were analyzed and expressed as carbon pools (Mg C ha-1for total soil organic C, or Kg C ha-1for the others). The results showed an increase of all organic carbon pools in all pruning treatments compared to the control experiences. Differences in total organic carbon pool were statistically significant between soils under avocado prunings and their control soil, and between soils under garden prunings with cherimoya and their control soil. Regarding the water-soluble soil organic carbon, low differences were shown. Differences in mineral-associated and non-oxidable organic carbon fractions were also statistically significant between soils under avocado prunings and their control soil, and between soils under garden prunings with cherimoya and their control soil. No significant differences in any organic carbon pool were founded for the soils under mango. The climate in this area enhances mineralization processes of organic matter. Thus, both in mango soils under mango and garden prunings the organic carbon does not significantly increase compared to the control soil. In avocado soils under avocado prunings humification of organic matter predominates, probably due to differences in the biochemical structure of the prunings. Finally, organic carbon contents in soils under garden prunings compared to their respective control soils only increase in cherimoya orchard. Our findings suggest that the addition of prunings and other organic debris may be a very useful practice for increasing the content of organic matter within the surface soil layer. Acknowledgements Authors thank the financial support of this work to the Spanish Ministry of Economy and Competitiveness (Project CGL-2013-46665-R) and the European Regional Development Fund (ERDF).
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false French prunes. 993.7 Section 993.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... characteristics similar to those of the prunes named in this section. ...
Stem cell autotomy and niche interaction in different systems
Dorn, David C; Dorn, August
2015-01-01
The best known cases of cell autotomy are the formation of erythrocytes and thrombocytes (platelets) from progenitor cells that reside in special niches. Recently, autotomy of stem cells and its enigmatic interaction with the niche has been reported from male germline stem cells (GSCs) in several insect species. First described in lepidopterans, the silkmoth, followed by the gipsy moth and consecutively in hemipterans, foremost the milkweed bug. In both, moths and the milkweed bug, GSCs form finger-like projections toward the niche, the apical cells (homologs of the hub cells in Drosophila). Whereas in the milkweed bug the projection terminals remain at the surface of the niche cells, in the gipsy moth they protrude deeply into the singular niche cell. In both cases, the projections undergo serial retrograde fragmentation with progressing signs of autophagy. In the gipsy moth, the autotomized vesicles are phagocytized and digested by the niche cell. In the milkweed bug the autotomized vesicles accumulate at the niche surface and disintegrate. Autotomy and sprouting of new projections appears to occur continuously. The significance of the GSC-niche interactions, however, remains enigmatic. Our concept on the signaling relationship between stem cell-niche in general and GSC and niche (hub cells and cyst stem cells) in particular has been greatly shaped by Drosophila melanogaster. In comparing the interactions of GSCs with their niche in Drosophila with those in species exhibiting GSC autotomy it is obvious that additional or alternative modes of stem cell-niche communication exist. Thus, essential signaling pathways, including niche-stem cell adhesion (E-cadherin) and the direction of asymmetrical GSC division - as they were found in Drosophila - can hardly be translated into the systems where GSC autotomy was reported. It is shown here that the serial autotomy of GSC projections shows remarkable similarities with Wallerian axonal destruction, developmental axon pruning and dying-back degeneration in neurodegenerative diseases. Especially the hypothesis of an existing evolutionary conserved “autodestruction program” in axons that might also be active in GSC projections appears attractive. Investigations on the underlying signaling pathways have to be carried out. There are two other well known cases of programmed cell autotomy: the enucleation of erythroblasts in the process of erythrocyte maturation and the segregation of thousands of thrombocytes (platelets) from one megakaryocyte. Both progenitor cell types - erythroblasts and megakaryocytes - are associated with a niche in the bone marrow, erythroblasts with a macrophage, which they surround, and the megakaryocytes with the endothelial cells of sinusoids and their extracellular matrix. Although the regulatory mechanisms may be specific in each case, there is one aspect that connects all described processes of programmed cell autotomy and neuronal autodestruction: apoptotic pathways play always a prominent role. Studies on the role of male GSC autotomy in stem cell-niche interaction have just started but are expected to reveal hitherto unknown ways of signal exchange. Spermatogenesis in mammals advance our understanding of insect spermatogenesis. Mammal and insect spermatogenesis share some broad principles, but a comparison of the signaling pathways is difficult. We have intimate knowledge from Drosophila, but of almost no other insect, and we have only limited knowledge from mammals. The discovery of stem cell autotomy as part of the interaction with the niche promises new general insights into the complicated stem cell-niche interdependence. PMID:26240680
Microglia in CNS development: Shaping the brain for the future.
Mosser, Coralie-Anne; Baptista, Sofia; Arnoux, Isabelle; Audinat, Etienne
Microglial cells are the resident macrophages of the central nervous system (CNS) and are mainly known for their roles in neuropathologies. However, major recent developments have revealed that these immune cells actively interact with neurons in physiological conditions and can modulate the fate and functions of synapses. Originating from myeloid precursors born in the yolk sac, microglial cells invade the CNS during early embryonic development. As a consequence they can potentially influence neuronal proliferation, migration and differentiation as well as the formation and maturation of neuronal networks, thereby contributing to the entire shaping of the CNS. We review here recent evidence indicating that microglial cells are indeed involved in crucial steps of the CNS development, including neuronal survival and apoptosis, axonal growth, migration of neurons, pruning of supernumerary synapses and functional maturation of developing synapses. We also discuss current hypotheses proposing that diverting microglial cells of their physiological functions, by promoting the expression of an immune phenotype during development, may be central to neurodevelopmental disorders such as autism, schizophrenia and epilepsy. Copyright © 2017 Elsevier Ltd. All rights reserved.
Christine Todoroki; Eini Lowell
2006-01-01
The silvicultural practice of pruning juvenile stems is a value-adding operation due to the formation of knot-free wood after the pruned branch stubs have healed. However it is not until after the log has been processed that the added value is realized. The motivation for this paper stems from wanting to extract as much of that added value as possible while minimizing...
Time pruning to avoid disease - black walnuts
Jerry. Van Sambeek
2017-01-01
The prime season to prune black walnut trees may be winding down with the unseasonably warm temperatures. Routinely pruning during the dormant season in Missouri can extend well into March and possibly longer. This dormant period may not be routine this year.
7 CFR 993.12 - Substandard prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Substandard prunes. 993.12 Section 993.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.9 - Processed prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Processed prunes. 993.9 Section 993.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false French prunes. 993.7 Section 993.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.12 - Substandard prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Substandard prunes. 993.12 Section 993.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.9 - Processed prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Processed prunes. 993.9 Section 993.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.10 - Standard prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Standard prunes. 993.10 Section 993.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.9 - Processed prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Processed prunes. 993.9 Section 993.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.12 - Substandard prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Substandard prunes. 993.12 Section 993.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.12 - Substandard prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Substandard prunes. 993.12 Section 993.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.12 - Substandard prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Substandard prunes. 993.12 Section 993.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.9 - Processed prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Processed prunes. 993.9 Section 993.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.10 - Standard prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Standard prunes. 993.10 Section 993.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.10 - Standard prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Standard prunes. 993.10 Section 993.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.10 - Standard prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Standard prunes. 993.10 Section 993.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false French prunes. 993.7 Section 993.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.10 - Standard prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Standard prunes. 993.10 Section 993.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false French prunes. 993.7 Section 993.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.9 - Processed prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Processed prunes. 993.9 Section 993.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false French prunes. 993.7 Section 993.7 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
Billeh, Yazan N.; Bernard, Amy; de Vivo, Luisa; Honjoh, Sakiko; Mihalas, Stefan; Ng, Lydia; Koch, Christof
2016-01-01
Abstract Cortical circuits mature in stages, from early synaptogenesis and synaptic pruning to late synaptic refinement, resulting in the adult anatomical connection matrix. Because the mature matrix is largely fixed, genetic or environmental factors interfering with its establishment can have irreversible effects. Sleep disruption is rarely considered among those factors, and previous studies have focused on very young animals and the acute effects of sleep deprivation on neuronal morphology and cortical plasticity. Adolescence is a sensitive time for brain remodeling, yet whether chronic sleep restriction (CSR) during adolescence has long-term effects on brain connectivity remains unclear. We used viral-mediated axonal labeling and serial two-photon tomography to measure brain-wide projections from secondary motor cortex (MOs), a high-order area with diffuse projections. For each MOs target, we calculated the projection fraction, a combined measure of passing fibers and axonal terminals normalized for the size of each target. We found no homogeneous differences in MOs projection fraction between mice subjected to 5 days of CSR during early adolescence (P25–P30, ≥50% decrease in daily sleep, n=14) and siblings that slept undisturbed (n=14). Machine learning algorithms, however, classified animals at significantly above chance levels, indicating that differences between the two groups exist, but are subtle and heterogeneous. Thus, sleep disruption in early adolescence may affect adult brain connectivity. However, because our method relies on a global measure of projection density and was not previously used to measure connectivity changes due to behavioral manipulations, definitive conclusions on the long-term structural effects of early CSR require additional experiments. PMID:27351022
7 CFR 993.23 - Part and subpart.
Code of Federal Regulations, 2013 CFR
2013-01-01
... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... handling of dried prunes produced in California, and all rules, regulations, and supplementary orders issued thereunder. This order regulating the handling of dried prunes produced in California shall be a...
7 CFR 993.23 - Part and subpart.
Code of Federal Regulations, 2011 CFR
2011-01-01
... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... handling of dried prunes produced in California, and all rules, regulations, and supplementary orders issued thereunder. This order regulating the handling of dried prunes produced in California shall be a...
7 CFR 993.6 - Non-French prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Non-French prunes. 993.6 Section 993.6 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.8 - Natural condition prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Natural condition prunes. 993.8 Section 993.8 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.11 - Standard processed prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Standard processed prunes. 993.11 Section 993.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.11 - Standard processed prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Standard processed prunes. 993.11 Section 993.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.6 - Non-French prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Non-French prunes. 993.6 Section 993.6 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.11 - Standard processed prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Standard processed prunes. 993.11 Section 993.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.8 - Natural condition prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Natural condition prunes. 993.8 Section 993.8 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.8 - Natural condition prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Natural condition prunes. 993.8 Section 993.8 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.23 - Part and subpart.
Code of Federal Regulations, 2010 CFR
2010-01-01
... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... handling of dried prunes produced in California, and all rules, regulations, and supplementary orders issued thereunder. This order regulating the handling of dried prunes produced in California shall be a...
7 CFR 993.23 - Part and subpart.
Code of Federal Regulations, 2012 CFR
2012-01-01
... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... handling of dried prunes produced in California, and all rules, regulations, and supplementary orders issued thereunder. This order regulating the handling of dried prunes produced in California shall be a...
7 CFR 993.11 - Standard processed prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Standard processed prunes. 993.11 Section 993.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.11 - Standard processed prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Standard processed prunes. 993.11 Section 993.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.6 - Non-French prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Non-French prunes. 993.6 Section 993.6 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.23 - Part and subpart.
Code of Federal Regulations, 2014 CFR
2014-01-01
... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... handling of dried prunes produced in California, and all rules, regulations, and supplementary orders issued thereunder. This order regulating the handling of dried prunes produced in California shall be a...
Cabrera, Rosina; López-Peña, Damian; Asaff, Ali; Esqueda, Martín; Valenzuela-Soto, Elisa M
2018-01-01
Grapes are widely produced in northwestern Mexico, generating many wood trimmings (vineyard prunings) that have no further local use. This makes vineyard prunings a very attractive alternative for the cultivation of white-rot medicinal mushrooms such as Lentinus edodes. This type of wood can also offer a model for the evaluation of oxidative enzyme production during the fermentation process. We tested the effect of wood from vineyard prunings on the vegetative growth of and production of ligninolytic enzymes in L. edodes in solid-state fermentation and with wheat straw as the control substrate. The specific growth rate of the fungus was 2-fold higher on vineyard pruning culture (μM = 0.95 day-1) than on wheat straw culture (μM = 0.47 day-1). Laccase-specific production was 4 times higher in the vineyard prunings culture than on wheat straw (0.34 and 0.08 mU · mg protein-1 · ppm CO2-1, respectively), and manganese peroxidase production was 3.7 times higher on wheat straw culture than on vineyard prunings (2.21 and 0.60 mU · mg protein-1 · ppm CO2-1, respectively). To explain accurately these differences in growth and ligninolytic enzyme activity, methanol extracts were obtained from each substrate and characterized. Resveratrol and catechins were the main compounds identified in vineyard prunings, whereas epigallocatechin was the only one detected in wheat straw. Compounds susceptible to enzymatic oxidation are more bioavailable in vineyard prunings than in wheat straw, and thus the highest L. edodes growth rate is associated with the presence of these compounds.
Prolonged myelination in human neocortical evolution.
Miller, Daniel J; Duka, Tetyana; Stimpson, Cheryl D; Schapiro, Steven J; Baze, Wallace B; McArthur, Mark J; Fobbs, Archibald J; Sousa, André M M; Sestan, Nenad; Wildman, Derek E; Lipovich, Leonard; Kuzawa, Christopher W; Hof, Patrick R; Sherwood, Chet C
2012-10-09
Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.
7 CFR 457.133 - Prune crop insurance provisions.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 6 2010-01-01 2010-01-01 false Prune crop insurance provisions. 457.133 Section 457.133 Agriculture Regulations of the Department of Agriculture (Continued) FEDERAL CROP INSURANCE CORPORATION, DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.133 Prune crop insurance...
R.D. Fight; J.M. Cahill; T.A. Snellgrove; T.D. Fahey
1987-01-01
PRUNE-SIM is a spreadsheet template (program) that allows users to simulate a financial analysis of pruning coast Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. menziesii). The program estimates the increase in product value resulting from pruning the butt 17-foot log. Product recovery information is based on actual...
7 CFR 993.19b - Undersized prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Undersized prunes. 993.19b Section 993.19b Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.19b - Undersized prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Undersized prunes. 993.19b Section 993.19b Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.65 - Disposition of reserve prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Disposition of reserve prunes. 993.65 Section 993.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.165 - Disposition of reserve prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Disposition of reserve prunes. 993.165 Section 993.165 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.165 - Disposition of reserve prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Disposition of reserve prunes. 993.165 Section 993.165 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.65 - Disposition of reserve prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Disposition of reserve prunes. 993.65 Section 993.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.65 - Disposition of reserve prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Disposition of reserve prunes. 993.65 Section 993.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.21d - Reserve prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Reserve prunes. 993.21d Section 993.21d Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.19b - Undersized prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Undersized prunes. 993.19b Section 993.19b Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.21c - Salable prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Salable prunes. 993.21c Section 993.21c Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.501 - Consumer package of prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Consumer package of prunes. 993.501 Section 993.501 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.21c - Salable prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Salable prunes. 993.21c Section 993.21c Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.21d - Reserve prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Reserve prunes. 993.21d Section 993.21d Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.21d - Reserve prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Reserve prunes. 993.21d Section 993.21d Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.165 - Disposition of reserve prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Disposition of reserve prunes. 993.165 Section 993.165 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.65 - Disposition of reserve prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Disposition of reserve prunes. 993.65 Section 993.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.19b - Undersized prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Undersized prunes. 993.19b Section 993.19b Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.65 - Disposition of reserve prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Disposition of reserve prunes. 993.65 Section 993.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN...
7 CFR 993.21d - Reserve prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Reserve prunes. 993.21d Section 993.21d Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.21c - Salable prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Salable prunes. 993.21c Section 993.21c Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.19b - Undersized prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Undersized prunes. 993.19b Section 993.19b Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
7 CFR 993.21c - Salable prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Salable prunes. 993.21c Section 993.21c Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA...
Code of Federal Regulations, 2011 CFR
2011-01-01
.../DRIED PLUM DIVERSION PROGRAM § 81.3 Definitions. (a) Administrator means the Administrator of AMS. (b... means “Application for Prune Tree Removal Program.” (d) Committee means the Prune Marketing Committee... of prune-plum trees after approval of applications by the Committee through June 30, 2002. (f...
Code of Federal Regulations, 2014 CFR
2014-01-01
.../DRIED PLUM DIVERSION PROGRAM § 81.3 Definitions. (a) Administrator means the Administrator of AMS. (b... means “Application for Prune Tree Removal Program.” (d) Committee means the Prune Marketing Committee... of prune-plum trees after approval of applications by the Committee through June 30, 2002. (f...
Code of Federal Regulations, 2012 CFR
2012-01-01
.../DRIED PLUM DIVERSION PROGRAM § 81.3 Definitions. (a) Administrator means the Administrator of AMS. (b... means “Application for Prune Tree Removal Program.” (d) Committee means the Prune Marketing Committee... of prune-plum trees after approval of applications by the Committee through June 30, 2002. (f...
Code of Federal Regulations, 2013 CFR
2013-01-01
.../DRIED PLUM DIVERSION PROGRAM § 81.3 Definitions. (a) Administrator means the Administrator of AMS. (b... means “Application for Prune Tree Removal Program.” (d) Committee means the Prune Marketing Committee... of prune-plum trees after approval of applications by the Committee through June 30, 2002. (f...
Pruning Neural Networks with Distribution Estimation Algorithms
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cantu-Paz, E
2003-01-15
This paper describes the application of four evolutionary algorithms to the pruning of neural networks used in classification problems. Besides of a simple genetic algorithm (GA), the paper considers three distribution estimation algorithms (DEAs): a compact GA, an extended compact GA, and the Bayesian Optimization Algorithm. The objective is to determine if the DEAs present advantages over the simple GA in terms of accuracy or speed in this problem. The experiments used a feed forward neural network trained with standard back propagation and public-domain and artificial data sets. The pruned networks seemed to have better or equal accuracy than themore » original fully-connected networks. Only in a few cases, pruning resulted in less accurate networks. We found few differences in the accuracy of the networks pruned by the four EAs, but found important differences in the execution time. The results suggest that a simple GA with a small population might be the best algorithm for pruning networks on the data sets we tested.« less
Fumey, Damien; Lauri, Pierre-Éric; Guédon, Yann; Godin, Christophe; Costes, Evelyne
2011-11-01
Manipulation of tree architecture by pruning provides an experimental context to analyze architectural plasticity resulting from competition between developing organs. The objective of this study was to quantify the effects of the removal of all or part of shoots through pruning on the redistribution of growth and flowering at spatial and temporal levels. Two types of pruning cuts were applied: (1) heading cuts of either the main stem or laterals and (2) thinning cuts (i.e., complete removal) of laterals. These two types of cuts were applied in summer and winter on 1-yr-old cultivars of Fuji and Braeburn apple trees. Tree topology and geometry were described over 3 years, and responses were analyzed for both local and distant scales. Heading cuts induced quasi-deterministic local responses on pruned axes, whereas responses to thinning cuts were more variable. For the main stem and laterals, responses over greater spatial and temporal scales were highlighted with (1) stronger growth the year after summer pruning and (2) modification of branching and flowering along the unpruned parts after winter pruning. Pruning typically induced growth redistribution toward traumatic reiterations and enhanced growth of the remaining unpruned axes with a concomitant decrease of flowering and cambial growth. Although results could be interpreted in relation to the root-shoot balance, tree responses appeared highly cultivar-specific.
7 CFR 993.50 - Outgoing regulation.
Code of Federal Regulations, 2010 CFR
2010-01-01
... marketing of prunes as will be in the public interest, whether prices are above or below parity, no handler... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... any lot of French prunes for human consumption as prunes, or any lot of mixed dried fruit containing...
R.D. Fight; J.M. Cahill; T.D. Fahey
1992-01-01
The DFPRUNE spreadsheet program is designed to estimate the expected financial return from pruning coast Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. menziesii. It is a significant revision of the PRUNE-SIM program. The PRUNE-SIM program was based on the average product recovery for unpruned logs from a single stand...
USDA-ARS?s Scientific Manuscript database
Trunk diseases poses a serious threat to winegrape growers. Despite high prevalence and substantial consequences, growers routinely wait to adopt field-tested, preventative practices (delayed pruning, double pruning, or application of pruning wound protectant) until symptomatic vines appear (~10 yea...
Bridging the gaps between scientific literature and grower perceptions of trunk disease management
USDA-ARS?s Scientific Manuscript database
Trunk diseases significantly limit the productivity of California vineyards. Field trials have shown three practices to minimize infection of pruning wounds: delayed pruning, double pruning, and the fungicide thiophanate-methyl (Topsin M). For optimal efficacy, such preventative practices must be a...
Mapping an index of the myelin g-ratio in infants using magnetic resonance imaging
Dean, Douglas C.; O'Muircheartaigh, Jonathan; Dirks, Holly; Travers, Brittany G.; Adluru, Nagesh; Alexander, Andrew L.; Deoni, Sean C.L.
2016-01-01
Optimal myelination of neuronal axons is essential for effective brain and cognitive function. The ratio of the axon diameter to the outer fiber diameter, known as the g-ratio, is a reliable measure to assess axonal myelination and is an important index reflecting the efficiency and maximal conduction velocity of white matter pathways. Although advanced neuroimaging techniques including multicomponent relaxometry (MCR) and diffusion tensor imaging afford insight into the microstructural characteristics of brain tissue, by themselves they do not allow direct analysis of the myelin g-ratio. Here, we show that by combining myelin content information (obtained with mcDESPOT MCR) with neurite density information (obtained through NODDI diffusion imaging) an index of the myelin g-ratio may be estimated. Using this framework, we present the first quantitative study of myelin g-ratio index changes across childhood, examining 18 typically developing children 3 months to 7.5 years of age. We report a spatio-temporal pattern of maturation that is consistent with histological and developmental MRI studies, as well as theoretical studies of the myelin g-ratio. This work represents the first ever in vivo visualization of the evolution of white matter g-ratio indices throughout early childhood. PMID:26908314
Wang, Quanxin; Tanigawa, Hisashi; Fujita, Ichiro
2017-04-01
Two distinct areas along the ventral visual stream of monkeys, the primary visual (V1) and inferior temporal (TE) cortices, exhibit different projection patterns of intrinsic horizontal axons with patchy terminal fields in adult animals. The differences between the patches in these 2 areas may reflect differences in cortical representation and processing of visual information. We studied the postnatal development of patches by injecting an anterograde tracer into TE and V1 in monkeys of various ages. At 1 week of age, labeled patches with distribution patterns reminiscent of those in adults were already present in both areas. The labeling intensity of patches decayed exponentially with projection distance in monkeys of all ages in both areas, but this trend was far less evident in TE. The number and extent of patches gradually decreased with age in V1, but not in TE. In V1, axonal and bouton densities increased postnatally only in patches with short projection distances, whereas in TE this density change occurred in patches with various projection distances. Thus, patches with area-specific distribution patterns are formed early in life, and area-specific postnatal developmental processes shape the connectivity of patches into adulthood. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Martella, Andrea; Sepe, Rosa M; Silvestri, Cristoforo; Zang, Jingjing; Fasano, Giulia; Carnevali, Oliana; De Girolamo, Paolo; Neuhauss, Stephan C F; Sordino, Paolo; Di Marzo, Vincenzo
2016-12-01
The developmental role of the endocannabinoid system still remains to be fully understood. Here, we report the presence of a complete endocannabinoid system during zebrafish development and show that the genes that code for enzymes that catalyze the anabolism and catabolism (mgll and dagla) of the endocannabinoid, 2-AG (2-arachidonoylglycerol), as well as 2-AG main receptor in the brain, cannabinoid receptor type 1, are coexpressed in defined regions of axonal growth. By using morpholino-induced transient knockdown of the zebrafish Daglα homolog and its pharmacologic rescue, we suggest that synthesis of 2-AG is implicated in the control of axon formation in the midbrain-hindbrain region and that animals that lack Daglα display abnormal physiological behaviors in tests that measure stereotyped movement and motion perception. Our results suggest that the well-established role for 2-AG in axonal outgrowth has implications for the control of vision and movement in zebrafish and, thus, is likely common to all vertebrates.-Martella, A., Sepe, R. M., Silvestri, C., Zang, J., Fasano, G., Carnevali, O., De Girolamo, P., Neuhauss, S. C. F., Sordino, P., Di Marzo, V. Important role of endocannabinoid signaling in the development of functional vision and locomotion in zebrafish. © FASEB.
W. D. Zeedyk; A. F. Hough
1958-01-01
The continuing heavy demand for high-quality Allegheny hardwoods, particularly black cherry and sugar maple, impresses on us the need for more information responses of hardwoods to pruning. Pruning may have beneficial effects: it may increase quality without sacrificing growth. Or it may have detrimental effects: it may cause dieback of cambium, decay, staining and...
The Over-Pruning Hypothesis of Autism
ERIC Educational Resources Information Center
Thomas, Michael S. C.; Davis, Rachael; Karmiloff-Smith, Annette; Knowland, Victoria C. P.; Charman, Tony
2016-01-01
This article outlines the "over-pruning hypothesis" of autism. The hypothesis originates in a neurocomputational model of the regressive sub-type (Thomas, Knowland & Karmiloff-Smith, 2011a, 2011b). Here we develop a more general version of the over-pruning hypothesis to address heterogeneity in the timing of manifestation of ASD,…
Effect of pruning on growth of western white pine
Austin E. Helmers
1946-01-01
Pruning for production of clear lumber is being recognized more and more as a desirable silvicultural measure. The author's study on western white pine confirms earlier findings on other species that not more than one-third of the line crown should be removed in any pruning operation.
7 CFR 993.21c - Salable prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Salable prunes. 993.21c Section 993.21c Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... § 993.54, or, if no reserve percentage is in effect for a crop year, all prunes, excluding the quantity...
Effect of pruning on growth of ponderosa pine.
Edwin L. Mowat
1947-01-01
A study of the influence of pruning various proportions of the crowns of young ponderosa pine trees upon growth, vigor, and mortality was started on the Pringle Falls Experimental Forest in 1941. After 5 years of tree growth, the study throws some light on how severely young pines should be pruned.
7 CFR 993.162 - Voluntary prune plum diversion.
Code of Federal Regulations, 2014 CFR
2014-01-01
... SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED... dried weight equivalent of prune plums so diverted on a dryaway basis as follows: (1) For prune plums of..., which would not, under normal producer practices, be dried and delivered to a handler. On or before July...
7 CFR 993.162 - Voluntary prune plum diversion.
Code of Federal Regulations, 2013 CFR
2013-01-01
... SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED... dried weight equivalent of prune plums so diverted on a dryaway basis as follows: (1) For prune plums of..., which would not, under normal producer practices, be dried and delivered to a handler. On or before July...
7 CFR 993.162 - Voluntary prune plum diversion.
Code of Federal Regulations, 2011 CFR
2011-01-01
... SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED... dried weight equivalent of prune plums so diverted on a dryaway basis as follows: (1) For prune plums of..., which would not, under normal producer practices, be dried and delivered to a handler. On or before July...
7 CFR 993.162 - Voluntary prune plum diversion.
Code of Federal Regulations, 2012 CFR
2012-01-01
... SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED... dried weight equivalent of prune plums so diverted on a dryaway basis as follows: (1) For prune plums of..., which would not, under normal producer practices, be dried and delivered to a handler. On or before July...
7 CFR 993.501 - Consumer package of prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Consumer package of prunes. 993.501 Section 993.501 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... of prunes means consumer package as defined in § 993.22. Effective Date Note: At 70 FR 30613, May 27...
A review of pruning fruit trees
NASA Astrophysics Data System (ADS)
Zhang, L.; Koc, A. B.; Wang, X. N.; Jiang, Y. X.
2018-05-01
The focus of this review is to present the results of studies and articles about ways to prune fruit trees. Pruning should be done in late winter or early spring so that the infection risk can be significantly decreased. This review will also offer an overview of methods to prevent infections and speed up recovery on the trees. The following is an interpretation of why high-power ultrasonic assisted pruning in the fruits trees is needed and will elaborate on the efficiency, labor costs, and safety, as well as space, location, and some environmental issues.
2011-01-01
Background The tomato (Solanum lycopersicum L.) plant is both an economically important food crop and an ideal dicot model to investigate various physiological phenomena not possible in Arabidopsis thaliana. Due to the great diversity of tomato cultivars used by the research community, it is often difficult to reliably compare phenotypes. The lack of tomato developmental mutants in a single genetic background prevents the stacking of mutations to facilitate analysis of double and multiple mutants, often required for elucidating developmental pathways. Results We took advantage of the small size and rapid life cycle of the tomato cultivar Micro-Tom (MT) to create near-isogenic lines (NILs) by introgressing a suite of hormonal and photomorphogenetic mutations (altered sensitivity or endogenous levels of auxin, ethylene, abscisic acid, gibberellin, brassinosteroid, and light response) into this genetic background. To demonstrate the usefulness of this collection, we compared developmental traits between the produced NILs. All expected mutant phenotypes were expressed in the NILs. We also created NILs harboring the wild type alleles for dwarf, self-pruning and uniform fruit, which are mutations characteristic of MT. This amplified both the applications of the mutant collection presented here and of MT as a genetic model system. Conclusions The community resource presented here is a useful toolkit for plant research, particularly for future studies in plant development, which will require the simultaneous observation of the effect of various hormones, signaling pathways and crosstalk. PMID:21714900
Spatial distribution of block falls using volumetric GIS-decision-tree models
NASA Astrophysics Data System (ADS)
Abdallah, C.
2010-10-01
Block falls are considered a significant aspect of surficial instability contributing to losses in land and socio-economic aspects through their damaging effects to natural and human environments. This paper predicts and maps the geographic distribution and volumes of block falls in central Lebanon using remote sensing, geographic information systems (GIS) and decision-tree modeling (un-pruned and pruned trees). Eleven terrain parameters (lithology, proximity to fault line, karst type, soil type, distance to drainage line, elevation, slope gradient, slope aspect, slope curvature, land cover/use, and proximity to roads) were generated to statistically explain the occurrence of block falls. The latter were discriminated using SPOT4 satellite imageries, and their dimensions were determined during field surveys. The un-pruned tree model based on all considered parameters explained 86% of the variability in field block fall measurements. Once pruned, it classifies 50% in block falls' volumes by selecting just four parameters (lithology, slope gradient, soil type, and land cover/use). Both tree models (un-pruned and pruned) were converted to quantitative 1:50,000 block falls' maps with different classes; starting from Nil (no block falls) to more than 4000 m 3. These maps are fairly matching with coincidence value equal to 45%; however, both can be used to prioritize the choice of specific zones for further measurement and modeling, as well as for land-use management. The proposed tree models are relatively simple, and may also be applied to other areas (i.e. the choice of un-pruned or pruned model is related to the availability of terrain parameters in a given area).
Bahrami, R Nikkhah; Khodadadi, M; Pirivatlo, S Piry; Hassanpanah, D
2009-03-15
This experiment carried out to evaluate the effects of planting methods (seed sowing and transplanting) and head pruning (no pruning, pruning after 12th node and pruning after 16th node) on yield and yield components such as number of branches (sub-branches) per plant, fruits per plant, growth, fruit size, weight of fresh fruit, weight of seeds per fruit, number of seeds per fruit and seed yield of medicinal pumpkin. The experiment was carried out based of factorial experiment with Randomized Completely Blocks Design (RCBD) by three replications in Ardabil Agricultural and Natural Resources Researches Station at 2007. Seedlings were grown in heated greenhouse. When the climatic condition became suitable and seedlings were at the four leaves stage, both seeds and seedlings were planted at the same time in the farm. Maintenance operations were done during the growth season. Head pruning treatments were done the forecast time. The results showed that the planting methods had significant effect on the number of ripen fruits per plant, fruits diameter, weight of seeds per fruit, weight of 1000 seeds and seed yield and had no significant effect on the other traits. Also the results indicated that head pruning treatments had significant effects on the number of branches per plant, growth and seed yield and no significant on the other traits. In this experiment the most seed yield (997.8 kg ha(-1)) obtained from transplanting method with head pruning after 12th node and the least seed yield obtained from control.
Wheaton, Benjamin J.; Noor, Natassya M.; Whish, Sophie C.; Truettner, Jessie S.; Dietrich, W. Dalton; Zhang, Moses; Crack, Peter J.; Dziegielewska, Katarzyna M.; Saunders, Norman R.
2013-01-01
Complete spinal transection in the mature nervous system is typically followed by minimal axonal repair, extensive motor paralysis and loss of sensory functions caudal to the injury. In contrast, the immature nervous system has greater capacity for repair, a phenomenon sometimes called the infant lesion effect. This study investigates spinal injuries early in development using the marsupial opossum Monodelphis domestica whose young are born very immature, allowing access to developmental stages only accessible in utero in eutherian mammals. Spinal cords of Monodelphis pups were completely transected in the lower thoracic region, T10, on postnatal-day (P)7 or P28 and the animals grew to adulthood. In P7-injured animals regrown supraspinal and propriospinal axons through the injury site were demonstrated using retrograde axonal labelling. These animals recovered near-normal coordinated overground locomotion, but with altered gait characteristics including foot placement phase lags. In P28-injured animals no axonal regrowth through the injury site could be demonstrated yet they were able to perform weight-supporting hindlimb stepping overground and on the treadmill. When placed in an environment of reduced sensory feedback (swimming) P7-injured animals swam using their hindlimbs, suggesting that the axons that grew across the lesion made functional connections; P28-injured animals swam using their forelimbs only, suggesting that their overground hindlimb movements were reflex-dependent and thus likely to be generated locally in the lumbar spinal cord. Modifications to propriospinal circuitry in P7- and P28-injured opossums were demonstrated by changes in the number of fluorescently labelled neurons detected in the lumbar cord following tracer studies and changes in the balance of excitatory, inhibitory and neuromodulatory neurotransmitter receptors’ gene expression shown by qRT-PCR. These results are discussed in the context of studies indicating that although following injury the isolated segment of the spinal cord retains some capability of rhythmic movement the mechanisms involved in weight-bearing locomotion are distinct. PMID:23951105
Wheaton, Benjamin J; Noor, Natassya M; Whish, Sophie C; Truettner, Jessie S; Dietrich, W Dalton; Zhang, Moses; Crack, Peter J; Dziegielewska, Katarzyna M; Saunders, Norman R
2013-01-01
Complete spinal transection in the mature nervous system is typically followed by minimal axonal repair, extensive motor paralysis and loss of sensory functions caudal to the injury. In contrast, the immature nervous system has greater capacity for repair, a phenomenon sometimes called the infant lesion effect. This study investigates spinal injuries early in development using the marsupial opossum Monodelphis domestica whose young are born very immature, allowing access to developmental stages only accessible in utero in eutherian mammals. Spinal cords of Monodelphis pups were completely transected in the lower thoracic region, T10, on postnatal-day (P)7 or P28 and the animals grew to adulthood. In P7-injured animals regrown supraspinal and propriospinal axons through the injury site were demonstrated using retrograde axonal labelling. These animals recovered near-normal coordinated overground locomotion, but with altered gait characteristics including foot placement phase lags. In P28-injured animals no axonal regrowth through the injury site could be demonstrated yet they were able to perform weight-supporting hindlimb stepping overground and on the treadmill. When placed in an environment of reduced sensory feedback (swimming) P7-injured animals swam using their hindlimbs, suggesting that the axons that grew across the lesion made functional connections; P28-injured animals swam using their forelimbs only, suggesting that their overground hindlimb movements were reflex-dependent and thus likely to be generated locally in the lumbar spinal cord. Modifications to propriospinal circuitry in P7- and P28-injured opossums were demonstrated by changes in the number of fluorescently labelled neurons detected in the lumbar cord following tracer studies and changes in the balance of excitatory, inhibitory and neuromodulatory neurotransmitter receptors' gene expression shown by qRT-PCR. These results are discussed in the context of studies indicating that although following injury the isolated segment of the spinal cord retains some capability of rhythmic movement the mechanisms involved in weight-bearing locomotion are distinct.
Factors that regulate embryonic gustatory development
Krimm, Robin F
2007-01-01
Numerous molecular factors orchestrate the development of the peripheral taste system. The unique anatomy/function of the taste system makes this system ideal for understanding the mechanisms by which these factors function; yet the taste system is underutilized for this role. This review focuses on some of the many factors that are known to regulate gustatory development, and discusses a few topics where more work is needed. Some attention is given to factors that regulate epibranchial placode formation, since gustatory neurons are thought to be primarily derived from this region. Epibranchial placodes appear to arise from a pan-placodal region and a number of regulatory factors control the differentiation of individual placodes. Gustatory neuron differentiation is regulated by a series of transcription factors and perhaps bone morphongenic proteins (BMP). As neurons differentiate, they also proliferate such that their numbers exceed those in the adult, and this is followed by developmental death. Some of these cell-cycling events are regulated by neurotrophins. After gustatory neurons become post-mitotic, axon outgrowth occurs. Axons are guided by multiple chemoattractive and chemorepulsive factors, including semaphorins, to the tongue epithelium. Brain derived neurotrophic factor (BDNF), functions as a targeting factor in the final stages of axon guidance and is required for gustatory axons to find and innervate taste epithelium. Numerous factors are involved in the development of gustatory papillae including Sox-2, Sonic hedge hog and Wnt-β-catenin signaling. It is likely that just as many factors regulate taste bud differentiation; however, these factors have not yet been identified. Studies examining the molecular factors that regulate terminal field formation in the nucleus of the solitary tract are also lacking. However, it is possible that some of the factors that regulate geniculate ganglion development, outgrowth, guidance and targeting of peripheral axons may have the same functions in the gustatory CNS. PMID:17903280
Code of Federal Regulations, 2012 CFR
2012-01-01
... plums (fresh prunes), and table grapes regulated under section 8e of the Agricultural Marketing..., oranges, prune variety plums (fresh prunes), and table grapes regulated under section 8e of the...), and table grapes that are imported into the United States. Agriculture and Agri-Food Canada is also...
Code of Federal Regulations, 2013 CFR
2013-01-01
... plums (fresh prunes), and table grapes regulated under section 8e of the Agricultural Marketing..., oranges, prune variety plums (fresh prunes), and table grapes regulated under section 8e of the...), and table grapes that are imported into the United States. Agriculture and Agri-Food Canada is also...
7 CFR 52.3182 - Varietal types of dried prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Dried Prunes Product Description, Varietal Types, Sizes, Grades § 52.3182 Varietal types of dried prunes. (a) Type I. French; or Robe; or a mixture of French and Robe. (b) Type II. Italian. (c) Type III. Imperial; or Sugar; or a mixture of Imperial...
Response of smaller European elm bark beetles to pruning wounds on American elm
Jack H. Barger; William N. Cannon
1987-01-01
From 1982 to 1984, inflight smaller European elm bark beetles, Scolytus multistriatus, were captured on American elms, Ulmus americana, that were therapeutically pruned for Dutch elm disease control. Pruning wounds were treated with wound dressing or left untreated to determine effects of the treatments on beetle attraction....
R. L. Johnson
1959-01-01
Planting cottonwood trees can be a profitable investment, but to get the most for their money land-owners should consider the possibilities of pruning. At present, there are wide differentials in the stumpage value of cottonwood stands, primarily because of variation in log quality. By restricting knots to the inner core, artificial pruning of small open-grown trees...
7 CFR 993.159 - Payments for services performed with respect to reserve tonnage prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... overhead costs, which include those for supervision, indirect labor, fuel, power and water, taxes and... tonnage prunes. The Committee will compute the average industry cost for holding reserve pool prunes by... choose to exclude the high and low data in computing an industry average. The industry average costs may...
7 CFR 993.159 - Payments for services performed with respect to reserve tonnage prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... overhead costs, which include those for supervision, indirect labor, fuel, power and water, taxes and... tonnage prunes. The Committee will compute the average industry cost for holding reserve pool prunes by... choose to exclude the high and low data in computing an industry average. The industry average costs may...
7 CFR 993.159 - Payments for services performed with respect to reserve tonnage prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... overhead costs, which include those for supervision, indirect labor, fuel, power and water, taxes and... tonnage prunes. The Committee will compute the average industry cost for holding reserve pool prunes by... choose to exclude the high and low data in computing an industry average. The industry average costs may...
Minimal Pruning and Reduced Plant Protection Promote Predatory Mites in Grapevine
Pennington, Theresa; Kraus, Christian; Alakina, Ekatarina; Entling, Martin H.; Hoffmann, Christoph
2017-01-01
Improving natural pest control by promoting high densities of predatory mites (Acari: Phytoseiidae) is an effective way to prevent damage by pest mites (e.g., Eriophyidae, Tetranychidae) and other arthropod taxa that can cause serious damage to vineyards. Here, we investigate the influence of innovative management on predatory mite densities. We compare (i) full versus reduced fungicide applications and (ii) minimal pruning versus a traditional trellis pruning system in four fungus-resistant grapevine varieties. As predatory mites also feed on fungus mycelium, we assessed fungal infection of grapevine leaves in the experimental vineyard. Predatory mites were significantly more abundant in both minimal pruning and under reduced plant protection. Increases in predatory mites appeared to be independent of fungal infection, suggesting mostly direct effects of reduced fungicides and minimal pruning. In contrast to predatory mites, pest mites did not increase under innovative management. Thus, conditions for natural pest control are improved in fungus-resistant grapevines and under minimal pruning, which adds to other advantages such as environmental safety and reduced production cost. PMID:28820436
Wajja-Musukwe, Tellie-Nelson; Wilson, Julia; Sprent, Janet I; Ong, Chin K; Deans, J Douglas; Okorio, John
2008-02-01
Tree root pruning is a potential tool for managing belowground competition when trees and crops are grown together in agroforestry systems. We investigated the effects of tree root pruning on shoot growth and root distribution of Alnus acuminata (H.B. & K.), Casuarina equisetifolia L., Grevillea robusta A. Cunn. ex R. Br., Maesopsis eminii Engl. and Markhamia lutea (Benth.) K. Schum. and on yield of adjacent crops in sub-humid Uganda. The trees were 3 years old at the commencement of the study, and most species were competing strongly with crops. Tree roots were pruned 41 months after planting by cutting and back-filling a trench to a depth of 0.3 m, at a distance of 0.3 m from the trees, on one side of the tree row. The trench was reopened and roots recut at 50 and 62 months after planting. We assessed the effects on tree growth and root distribution over a 3 year period, and crop yield after the third root pruning at 62 months. Overall, root pruning had only a slight effect on aboveground tree growth: height growth was unaffected and diameter growth was reduced by only 4%. A substantial amount of root regrowth was observed by 11 months after pruning. Tree species varied in the number and distribution of roots, and C. equisetifolia and M. lutea had considerably more roots per unit of trunk volume than the other species, especially in the surface soil layers. Casuarina equisetifolia and M. eminii were the tree species most competitive with crops and G. robusta and M. lutea the least competitive. Crop yield data provided strong evidence of the redistribution of root activity following root pruning, with competition increasing on the unpruned side of tree rows. Thus, one-sided root pruning will be useful in only a few circumstances.
Unified commutation-pruning technique for efficient computation of composite DFTs
NASA Astrophysics Data System (ADS)
Castro-Palazuelos, David E.; Medina-Melendrez, Modesto Gpe.; Torres-Roman, Deni L.; Shkvarko, Yuriy V.
2015-12-01
An efficient computation of a composite length discrete Fourier transform (DFT), as well as a fast Fourier transform (FFT) of both time and space data sequences in uncertain (non-sparse or sparse) computational scenarios, requires specific processing algorithms. Traditional algorithms typically employ some pruning methods without any commutations, which prevents them from attaining the potential computational efficiency. In this paper, we propose an alternative unified approach with automatic commutations between three computational modalities aimed at efficient computations of the pruned DFTs adapted for variable composite lengths of the non-sparse input-output data. The first modality is an implementation of the direct computation of a composite length DFT, the second one employs the second-order recursive filtering method, and the third one performs the new pruned decomposed transform. The pruned decomposed transform algorithm performs the decimation in time or space (DIT) data acquisition domain and, then, decimation in frequency (DIF). The unified combination of these three algorithms is addressed as the DFTCOMM technique. Based on the treatment of the combinational-type hypotheses testing optimization problem of preferable allocations between all feasible commuting-pruning modalities, we have found the global optimal solution to the pruning problem that always requires a fewer or, at most, the same number of arithmetic operations than other feasible modalities. The DFTCOMM method outperforms the existing competing pruning techniques in the sense of attainable savings in the number of required arithmetic operations. It requires fewer or at most the same number of arithmetic operations for its execution than any other of the competing pruning methods reported in the literature. Finally, we provide the comparison of the DFTCOMM with the recently developed sparse fast Fourier transform (SFFT) algorithmic family. We feature that, in the sensing scenarios with sparse/non-sparse data Fourier spectrum, the DFTCOMM technique manifests robustness against such model uncertainties in the sense of insensitivity for sparsity/non-sparsity restrictions and the variability of the operating parameters.
Jensen, Sarah K G; Pangelinan, Melissa; Björnholm, Lassi; Klasnja, Anja; Leemans, Alexander; Drakesmith, Mark; Evans, C J; Barker, Edward D; Paus, Tomáš
2017-10-21
Previous studies have shown that both pre- and post-natal adversities, the latter including exposures to stress during childhood and adolescence, explain variation in structural properties of white matter (WM) in the brain. While previous studies have examined effects of independent stress exposures within one developmental period, such as childhood, we examine effects of stress across development using data from a prospective longitudinal study. More specifically, we ask how stressful events during prenatal development, childhood, and adolescence relate to variation in WM properties in early adulthood in young men recruited from a birth cohort. Using data from 393 mother-son pairs from a community-based birth cohort from England (Avon Longitudinal Study of Parents and Children), we examined how stressful life events relate to variation in different structural properties of WM in the corpus callosum and across the whole brain in early adulthood in men aged 18-21 years. We distinguish between stress occurring during three developmental periods: a) prenatal maternal stress, b) postnatal stress within the first four years of life, c) stress during adolescence (age 12-16 years). To obtain a comprehensive quantification of variation in WM, we assess structural properties of WM using four different measures, namely fractional anisotropy (FA), mean diffusivity (MD), magnetization transfer ratio (MTR) and myelin water fraction (MWF). The developmental model shows that prenatal stress is associated with lower MTR and MWF in the genu and/or splenium of the corpus callosum, and with lower MTR in global (lobar) WM. Stress during early childhood is associated with higher MTR in the splenium, and stress during adolescence is associated with higher MTR in the genu and lower MD in the splenium. We see no associations between postnatal stress and variation in global (lobar) WM. The current study found evidence for independent effects of stress on WM properties during distinct neurodevelopmental periods. We speculate that these independent effects are due to differences in the developmental processes unfolding at different developmental time points. We suggest that associations between prenatal stress and WM properties may relate to abnormalities in neurogenesis, affecting the number and density of axons, while postnatal stress may interfere with processes related to myelination or radial growth of axons. Potential consequences of prenatal glucocorticoid exposure should be considered in obstetric care. Copyright © 2017 Elsevier Inc. All rights reserved.
A developmental and genetic classification for midbrain-hindbrain malformations
Millen, Kathleen J.; Dobyns, William B.
2009-01-01
Advances in neuroimaging, developmental biology and molecular genetics have increased the understanding of developmental disorders affecting the midbrain and hindbrain, both as isolated anomalies and as part of larger malformation syndromes. However, the understanding of these malformations and their relationships with other malformations, within the central nervous system and in the rest of the body, remains limited. A new classification system is proposed, based wherever possible, upon embryology and genetics. Proposed categories include: (i) malformations secondary to early anteroposterior and dorsoventral patterning defects, or to misspecification of mid-hindbrain germinal zones; (ii) malformations associated with later generalized developmental disorders that significantly affect the brainstem and cerebellum (and have a pathogenesis that is at least partly understood); (iii) localized brain malformations that significantly affect the brain stem and cerebellum (pathogenesis partly or largely understood, includes local proliferation, cell specification, migration and axonal guidance); and (iv) combined hypoplasia and atrophy of putative prenatal onset degenerative disorders. Pertinent embryology is discussed and the classification is justified. This classification will prove useful for both physicians who diagnose and treat patients with these disorders and for clinical scientists who wish to understand better the perturbations of developmental processes that produce them. Importantly, both the classification and its framework remain flexible enough to be easily modified when new embryologic processes are described or new malformations discovered. PMID:19933510
75 FR 51956 - Dried Prunes Produced in California; Increased Assessment Rate
Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-24
... Service 7 CFR Part 993 [Doc. No. AMS-FV-10-0057; FV10-993-1 PR] Dried Prunes Produced in California... amended (7 CFR part 993), regulating the handling of dried prunes grown in California, hereinafter... the 165,488 tons produced last year. At the proposed assessment rate the assessment income for the...
Richard C. Schlesinger; Alex L. Shigo
1989-01-01
Pruning, properly done, is one of the best ways to assure high quality wood. Although the overall volume of hardwood has been increasing during the last several years, the volume of high quality hardwood continues to be in short supply. So high quality logs will continue to be worth more at market time. Potentially, pruning can be an important silvicultural treatment...
Code of Federal Regulations, 2013 CFR
2013-01-01
... the producing area or at port of loading for ship stores or overseas shipment, or, in the case of... defects of plums or prunes other than Italian type prunes en route or at destination. 12 percent for fruit... Italian type prunes en route or at destination. Not more than a total of 18 percent of the fruit in any...
Code of Federal Regulations, 2014 CFR
2014-01-01
... the producing area or at port of loading for ship stores or overseas shipment, or, in the case of... defects of plums or prunes other than Italian type prunes en route or at destination. 12 percent for fruit... Italian type prunes en route or at destination. Not more than a total of 18 percent of the fruit in any...
Pruning to manage white pine blister rust in the southern Rocky Mountains
Amanda Crump; William R. Jacobi; Kelly S. Burns; Brian E. Howell
2011-01-01
White pine blister rust is an exotic, invasive disease that severely damages and kills white pines in the southern Rocky Mountains. We evaluated the efficacy of preventive pruning (removing lower branches) and/or sanitation pruning (removing cankered branches) to reduce disease impacts in limber (Pinus flexilis James) and Rocky Mountain bristlecone (P. aristata Englm...
Gholipouri, Abdolghayoum; Nazarnejad, H
2007-10-15
To investigate the effects of stem pruning (No heading, head pruning of stem after formation of 10 and 14 nodes) and nitrogen levels (0, 50, 100 and 200 kg ha(-1)) on physical and chemical characteristic of pumpkin seed a Factorial experiment based on randomized complete block design with three replication was carried out in Gorgan at 2003 and repeated in 2004 years. Results showed that the stem pruning has significant effect on traits such as seed oil, linoleic acid and oleic acid content. Nitrogen levels also have significant effect on seed dimension, seed oil, linoleic acid and oleic acid content. The largest amount of oil and linoleic acid content was obtained by stem pruning after forming 14 node and 100 kg ha(-1) nitrogen in separately, but the interaction of treatments were not significant difference for all of traits.
Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas
2016-03-17
The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila.
Dellinger, R.D.
1997-12-09
The present invention is an automated pruning apparatus that requires little or no follow-up hand pruning and requires no sensors to avoid supportive trunks or posts. The present invention uses at least one pair of flat, close angled toothed, counter rotating blades. Woody branches are directed to the counter rotating blades first with a lifting arm and secondly by a quilled drum. 16 figs.
J.W." Jerry" Van Sambeek; Larry D. Godsey; William D. Walter; Harold E. Garrett; John P. Dwyer
2016-01-01
Benefits of repeated air-root-pruning of seedlings when stepping up to progressively larger containers include excellent lateral root distribution immediately below the root collar and an exceptionally fibrous root ball. To evaluate long-term field performance of repeatedly air-root-pruned container stock, three plantings of swamp white oak (Quercus bicolor...
Olive Crown Porosity Measurement Based on Radiation Transmittance: An Assessment of Pruning Effect.
Castillo-Ruiz, Francisco J; Castro-Garcia, Sergio; Blanco-Roldan, Gregorio L; Sola-Guirado, Rafael R; Gil-Ribes, Jesus A
2016-05-19
Crown porosity influences radiation interception, air movement through the fruit orchard, spray penetration, and harvesting operation in fruit crops. The aim of the present study was to develop an accurate and reliable methodology based on transmitted radiation measurements to assess the porosity of traditional olive trees under different pruning treatments. Transmitted radiation was employed as an indirect method to measure crown porosity in two olive orchards of the Picual and Hojiblanca cultivars. Additionally, three different pruning treatments were considered to determine if the pruning system influences crown porosity. This study evaluated the accuracy and repeatability of four algorithms in measuring crown porosity under different solar zenith angles. From a 14° to 30° solar zenith angle, the selected algorithm produced an absolute error of less than 5% and a repeatability higher than 0.9. The described method and selected algorithm proved satisfactory in field results, making it possible to measure crown porosity at different solar zenith angles. However, pruning fresh weight did not show any relationship with crown porosity due to the great differences between removed branches. A robust and accurate algorithm was selected for crown porosity measurements in traditional olive trees, making it possible to discern between different pruning treatments.
Ruthazer, Edward S; Bachleda, Amelia R; Olavarria, Jaime F
2010-12-15
We combined fixed-tissue and time-lapse analyses to investigate the axonal branching phenomena underlying the development of topographically organized ipsilateral projections from area 17 to area 18a in the rat. These complementary approaches allowed us to relate static, large-scale information provided by traditional fixed-tissue analysis to highly dynamic, local, small-scale branching phenomena observed with two-photon time-lapse microscopy in acute slices of visual cortex. Our fixed-tissue data revealed that labeled area 17 fibers invaded area 18a gray matter at topographically restricted sites, reaching superficial layers in significant numbers by postnatal day 6 (P6). Moreover, most parental axons gave rise to only one or occasionally a small number of closely spaced interstitial branches beneath 18a. Our time-lapse data showed that many filopodium-like branches emerged along parental axons in white matter or deep layers in area 18a. Most of these filopodial branches were transient, often disappearing after several minutes to hours of exploratory extension and retraction. These dynamic behaviors decreased significantly from P4, when the projection is first forming, through the second postnatal week, suggesting that the expression of, or sensitivity to, cortical cues promoting new branch addition in the white matter is developmentally down-regulated coincident with gray matter innervation. Together, these data demonstrate that the development of topographically organized corticocortical projections in rats involves extensive exploratory branching along parental axons and invasion of cortex by only a small number of interstitial branches, rather than the widespread innervation of superficial cortical layers by an initially exuberant population of branches. © 2010 Wiley-Liss, Inc.
2014-01-01
Background Localization of mRNAs encoding cytoskeletal or signaling proteins to neuronal processes is known to contribute to axon growth, synaptic differentiation and plasticity. In addition, a still increasing spectrum of mRNAs has been demonstrated to be localized under different conditions and developing stages thus reflecting a highly regulated mechanism and a role of mRNA localization in a broad range of cellular processes. Results Applying fluorescence in-situ-hybridization with specific riboprobes on cultured neurons and nervous tissue sections, we investigated whether the mRNAs for two metabolic enzymes, namely glycogen synthase (GS) and glycogen phosphorylase (GP), the key enzymes of glycogen metabolism, may also be targeted to neuronal processes. If it were so, this might contribute to clarify the so far enigmatic role of neuronal glycogen. We found that the mRNAs for both enzymes are localized to axonal and dendritic processes in cultured lumbar spinal motoneurons, but not in cultured trigeminal neurons. In cultured cortical neurons which do not store glycogen but nevertheless express glycogen synthase, the GS mRNA is also subject to axonal and dendritic localization. In spinal motoneurons and trigeminal neurons in situ, however, the mRNAs could only be demonstrated in the neuronal somata but not in the nerves. Conclusions We could demonstrate that the mRNAs for major enzymes of neural energy metabolism can be localized to neuronal processes. The heterogeneous pattern of mRNA localization in different culture types and developmental stages stresses that mRNA localization is a versatile mechanism for the fine-tuning of cellular events. Our findings suggest that mRNA localization for enzymes of glycogen metabolism could allow adaptation to spatial and temporal energy demands in neuronal events like growth, repair and synaptic transmission. PMID:24898526
Pfeiffer-Guglielmi, Brigitte; Dombert, Benjamin; Jablonka, Sibylle; Hausherr, Vanessa; van Thriel, Christoph; Schöbel, Nicole; Jansen, Ralf-Peter
2014-06-04
Localization of mRNAs encoding cytoskeletal or signaling proteins to neuronal processes is known to contribute to axon growth, synaptic differentiation and plasticity. In addition, a still increasing spectrum of mRNAs has been demonstrated to be localized under different conditions and developing stages thus reflecting a highly regulated mechanism and a role of mRNA localization in a broad range of cellular processes. Applying fluorescence in-situ-hybridization with specific riboprobes on cultured neurons and nervous tissue sections, we investigated whether the mRNAs for two metabolic enzymes, namely glycogen synthase (GS) and glycogen phosphorylase (GP), the key enzymes of glycogen metabolism, may also be targeted to neuronal processes. If it were so, this might contribute to clarify the so far enigmatic role of neuronal glycogen. We found that the mRNAs for both enzymes are localized to axonal and dendritic processes in cultured lumbar spinal motoneurons, but not in cultured trigeminal neurons. In cultured cortical neurons which do not store glycogen but nevertheless express glycogen synthase, the GS mRNA is also subject to axonal and dendritic localization. In spinal motoneurons and trigeminal neurons in situ, however, the mRNAs could only be demonstrated in the neuronal somata but not in the nerves. We could demonstrate that the mRNAs for major enzymes of neural energy metabolism can be localized to neuronal processes. The heterogeneous pattern of mRNA localization in different culture types and developmental stages stresses that mRNA localization is a versatile mechanism for the fine-tuning of cellular events. Our findings suggest that mRNA localization for enzymes of glycogen metabolism could allow adaptation to spatial and temporal energy demands in neuronal events like growth, repair and synaptic transmission.
POSTNATAL PHENOTYPE AND LOCALIZATION OF SPINAL CORD V1 DERIVED INTERNEURONS
Alvarez, Francisco J.; Jonas, Philip C.; Sapir, Tamar; Hartley, Robert; Berrocal, Maria C.; Geiman, Eric J.; Todd, Andrew J.; Goulding, Martyn
2010-01-01
Developmental studies identified four classes (V0, V1, V2, V3) of embryonic interneurons in the ventral spinal cord. Very little however is known about their adult phenotypes. In order to further characterize interneuron cell types in the adult, the location, neurotransmitter phenotype, calcium-buffering protein expression and axon distributions of V1-derived neurons in the mouse spinal cord was determined. In the mature (P20 and older) spinal cord, most V1-derived neurons are located in lateral LVII and in LIX, few in medial LVII and none in LVIII. Approximately 40% express calbindin and/or parvalbumin, while few express calretinin. Of seven groups of ventral interneurons identified according to calcium-buffering protein expression, two groups (1 and 4) correspond with V1-derived neurons. Group 1 are Renshaw cells and intensely express calbindin and coexpress parvalbumin and calretinin. They represent 9% of the V1 population. Group 4 express only parvalbumin and represent 27% of V1-derived neurons. V1-derived group 4 neurons receive contacts from primary sensory afferents and are therefore proprioceptive interneurons and the most ventral neurons in this group receive convergent calbindin-IR Renshaw cell inputs. This subgroup resembles Ia inhibitory interneurons (IaINs) and represents 13% of V1-derived neurons. Adult V1-interneuron axons target LIX and LVII and some enter the deep dorsal horn. V1-axons do not cross the midline. V1 derived axonal varicosities were mostly (>80%) glycinergic and a third were GABAergic. None were glutamatergic or cholinergic. In summary, V1 interneurons develop into ipsilaterally projecting, inhibitory interneurons that include Renshaw cells, Ia inhibitory interneurons and other unidentified proprioceptive interneurons. PMID:16255029
An Essential Postdevelopmental Role for Lis1 in Mice
Hines, Timothy J.; Gao, Xu; Sahu, Subhshri; Lange, Meghann M.; Turner, Jill R.
2018-01-01
LIS1 mutations cause lissencephaly (LIS), a severe developmental brain malformation. Much less is known about its role in the mature nervous system. LIS1 regulates the microtubule motor cytoplasmic dynein 1 (dynein), and as LIS1 and dynein are both expressed in the adult nervous system, Lis1 could potentially regulate dynein-dependent processes such as axonal transport. We therefore knocked out Lis1 in adult mice using tamoxifen-induced, Cre-ER-mediated recombination. When an actin promoter was used to drive Cre-ER expression (Act-Cre-ER), heterozygous Lis1 knockout (KO) caused no obvious change in viability or behavior, despite evidence of widespread recombination by a Cre reporter three weeks after tamoxifen exposure. In contrast, homozygous Lis1 KO caused the rapid onset of neurological symptoms in both male and female mice. One tamoxifen-dosing regimen caused prominent recombination in the midbrain/hindbrain, PNS, and cardiac/skeletal muscle within a week; these mice developed severe symptoms in that time frame and were killed. A different tamoxifen regimen resulted in delayed recombination in midbrain/hindbrain, but not in other tissues, and also delayed the onset of symptoms. This indicates that Lis1 loss in the midbrain/hindbrain causes the severe phenotype. In support of this, brainstem regions known to house cardiorespiratory centers showed signs of axonal dysfunction in KO animals. Transport defects, neurofilament (NF) alterations, and varicosities were observed in axons in cultured DRG neurons from KO animals. Because no symptoms were observed when a cardiac specific Cre-ER promoter was used, we propose a vital role for Lis1 in autonomic neurons and implicate defective axonal transport in the KO phenotype. PMID:29404402
Short- and long-term effects of LRRK2 on axon and dendrite growth.
Sepulveda, Bryan; Mesias, Roxana; Li, Xianting; Yue, Zhenyu; Benson, Deanna L
2013-01-01
Mutations in leucine-rich repeat kinase 2 (LRRK2) underlie an autosomal-dominant form of Parkinson's disease (PD) that is clinically indistinguishable from idiopathic PD. The function of LRRK2 is not well understood, but it has become widely accepted that LRRK2 levels or its kinase activity, which is increased by the most commonly observed mutation (G2019S), regulate neurite growth. However, growth has not been measured; it is not known whether mean differences in length correspond to altered rates of growth or retraction, whether axons or dendrites are impacted differentially or whether effects observed are transient or sustained. To address these questions, we compared several developmental milestones in neurons cultured from mice expressing bacterial artificial chromosome transgenes encoding mouse wildtype-LRRK2 or mutant LRRK2-G2019S, Lrrk2 knockout mice and non-transgenic mice. Over the course of three weeks of development on laminin, the data show a sustained, negative effect of LRRK2-G2019S on dendritic growth and arborization, but counter to expectation, dendrites from Lrrk2 knockout mice do not elaborate more rapidly. In contrast, young neurons cultured on a slower growth substrate, poly-L-lysine, show significantly reduced axonal and dendritic motility in Lrrk2 transgenic neurons and significantly increased motility in Lrrk2 knockout neurons with no significant changes in length. Our findings support that LRRK2 can regulate patterns of axonal and dendritic growth, but they also show that effects vary depending on growth substrate and stage of development. Such predictable changes in motility can be exploited in LRRK2 bioassays and guide exploration of LRRK2 function in vivo.
Ruthazer, Edward S.; Bachleda, Amelia R.; Olavarria, Jaime F.
2013-01-01
We combined fixed-tissue and time-lapse analyses to investigate the axonal branching phenomena underlying the development of topographically organized ipsilateral projections from area 17 to area 18a in the rat. These complementary approaches allowed us to relate static, large-scale information provided by traditional fixed-tissue analysis to highly dynamic, local, small-scale branching phenomena observed with two-photon time-lapse microscopy in acute slices of visual cortex. Our fixed-tissue data revealed that labeled area 17 fibers invaded area 18a gray matter at topographically restricted sites, reaching superficial layers in significant numbers by postnatal day 6 (P6). Moreover, most parental axons gave rise to only one or occasionally a small number of closely spaced interstitial branches beneath 18a. Our time-lapse data showed that many filopodium-like branches emerged along parental axons in white matter or deep layers in area 18a. Most of these filopo-dial branches were transient, often disappearing after several minutes to hours of exploratory extension and retraction. These dynamic behaviors decreased significantly from P4, when the projection is first forming, through the second postnatal week, suggesting that the expression of, or sensitivity to, cortical cues promoting new branch addition in the white matter is developmentally down-regulated coincident with gray matter innervation. Together, these data demonstrate that the development of topographically organized corticocortical projections in rats involves extensive exploratory branching along parental axons and invasion of cortex by only a small number of interstitial branches, rather than the widespread innervation of superficial cortical layers by an initially exuberant population of branches. PMID:21031561
Synaptic inhibition and γ-aminobutyric acid in the mammalian central nervous system
OBATA, Kunihiko
2013-01-01
Signal transmission through synapses connecting two neurons is mediated by release of neurotransmitter from the presynaptic axon terminals and activation of its receptor at the postsynaptic neurons. γ-Aminobutyric acid (GABA), non-protein amino acid formed by decarboxylation of glutamic acid, is a principal neurotransmitter at inhibitory synapses of vertebrate and invertebrate nervous system. On one hand glutamic acid serves as a principal excitatory neurotransmitter. This article reviews GABA researches on; (1) synaptic inhibition by membrane hyperpolarization, (2) exclusive localization in inhibitory neurons, (3) release from inhibitory neurons, (4) excitatory action at developmental stage, (5) phenotype of GABA-deficient mouse produced by gene-targeting, (6) developmental adjustment of neural network and (7) neurological/psychiatric disorder. In the end, GABA functions in simple nervous system and plants, and non-amino acid neurotransmitters were supplemented. PMID:23574805
Sethi, Sunjay; Keil, Kimberly P.
2017-01-01
PCB 11 is an emerging global pollutant that we recently showed promotes axonal and dendritic growth in primary rat neuronal cell cultures. Here, we address the influence of sex and species on neuronal responses to PCB 11. Neuronal morphology was quantified in sex-specific primary hippocampal and cortical neuron-glia co-cultures derived from neonatal C57BL/6J mice and Sprague Dawley rats exposed for 48 h to vehicle (0.1% DMSO) or PCB 11 at concentrations ranging from 1 fM to 1 nM. Total axonal length was quantified in tau-1 immunoreactive neurons at day in vitro (DIV) 2; dendritic arborization was assessed by Sholl analysis at DIV 9 in neurons transfected with MAP2B-FusRed. In mouse cultures, PCB 11 enhanced dendritic arborization in female, but not male, hippocampal neurons and male, but not female, cortical neurons. In rat cultures, PCB 11 promoted dendritic arborization in male and female hippocampal and cortical neurons. PCB 11 also increased axonal growth in mouse and rat neurons of both sexes and neuronal cell types. These data demonstrate that PCB 11 exerts sex-specific effects on neuronal morphogenesis that vary depending on species, neurite type, and neuronal cell type. These findings have significant implications for risk assessment of this emerging developmental neurotoxicant. PMID:29295518
Sethi, Sunjay; Keil, Kimberly P; Lein, Pamela J
2017-12-23
PCB 11 is an emerging global pollutant that we recently showed promotes axonal and dendritic growth in primary rat neuronal cell cultures. Here, we address the influence of sex and species on neuronal responses to PCB 11. Neuronal morphology was quantified in sex-specific primary hippocampal and cortical neuron-glia co-cultures derived from neonatal C57BL/6J mice and Sprague Dawley rats exposed for 48 h to vehicle (0.1% DMSO) or PCB 11 at concentrations ranging from 1 fM to 1 nM. Total axonal length was quantified in tau-1 immunoreactive neurons at day in vitro (DIV) 2; dendritic arborization was assessed by Sholl analysis at DIV 9 in neurons transfected with MAP2B-FusRed. In mouse cultures, PCB 11 enhanced dendritic arborization in female, but not male, hippocampal neurons and male, but not female, cortical neurons. In rat cultures, PCB 11 promoted dendritic arborization in male and female hippocampal and cortical neurons. PCB 11 also increased axonal growth in mouse and rat neurons of both sexes and neuronal cell types. These data demonstrate that PCB 11 exerts sex-specific effects on neuronal morphogenesis that vary depending on species, neurite type, and neuronal cell type. These findings have significant implications for risk assessment of this emerging developmental neurotoxicant.
Donald J. Kaczmarek; Phillip E. Pope
1993-01-01
Northern red oak (Quercus rubra L.) seedlings exhibit relatively high survival rates following planting, but their growth rates are often slow and extensive stem dieback can occur. This study was designed to investigate the growth responses of northern red oak seedlings planted with or without root-pruning or shoot-pruning. One-year-old (1-0) northern red oak nursery...
Qingjiang Hou; James Brandle; Kenneth Hubbard; Michele Schoeneberger; Carlos Nieto; Charles Francis
2003-01-01
Root-pruning is generally recommended as an appropriate treatment to reduce competition for soil water and/or nutrients and suppression of crop yield in areas adjacent to windbreaks. Several recent studies suggest, however, that factors other than soil water might be causing yield reduction at the interface. For two consecutive years, we evaluated root-pruning effects...
Weevil - red rot associations in eastern white pine
Myron D. Ostrander; Clifford H. Foster
1957-01-01
The presence of red rot (Fomes pini) in pruned white pine stands has often been attributed to the act of pruning. This assumption may well be true for heavily stocked stands where thinning has been neglected and pruning scars are slow to heal. The question then arises: How do we account for the red rot often found in vigorous unpruned white pine stands? Evidence...
An Extension of CART's Pruning Algorithm. Program Statistics Research Technical Report No. 91-11.
ERIC Educational Resources Information Center
Kim, Sung-Ho
Among the computer-based methods used for the construction of trees such as AID, THAID, CART, and FACT, the only one that uses an algorithm that first grows a tree and then prunes the tree is CART. The pruning component of CART is analogous in spirit to the backward elimination approach in regression analysis. This idea provides a tool in…
Greene, C; Wilson, A; Shapira, E
1985-01-01
One of twins was born with prune belly syndrome and congenital heart defect following exposure to Bendectin and Tigan. Red cell antigens and HLA typing were compatible with monozygosity. The possible associations of the prune belly syndrome to monozygotic twinning or to teratogenic agents is considered in light of this patient and review of the literature.
D.L. Copes
1985-01-01
In 1983, a study was conducted to evaluate the effects of leader topping and branch pruning on the efficiency to tree shaking to remove Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) cones. Removal efficiency for three topping and pruning treatments averaged 69 percent, whereas for the uncut control treatment it was 62 percent. The treatment...
Mary Anne Sword Sayer; Shi-Jean Susana Sung; James D. Haywood
2011-01-01
Cultural practices that modify root system structure in the plug of container-grown seedlings have the potential to improve root system function after planting. Our objective was to assess how copper root pruning affects the quality and root system development of longleaf pine seedlings grown in three cavity sizes in a greenhouse. Copper root pruning increased seedling...
Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria A; Santafé, Manel; Tomàs, Josep
2016-06-23
The development of the nervous system involves an initially exuberant production of neurons that make an excessive number of synaptic contacts. The initial overproduction of synapses promotes connectivity. Hebbian competition between axons with different activities (the least active are punished) leads to the loss of roughly half of the overproduced elements and this refines connectivity and increases specificity. The neuromuscular junction is innervated by a single axon at the end of the synapse elimination process and, because of its relative simplicity, has long been used as a model for studying the general principles of synapse development. The involvement of the presynaptic muscarinic ACh autoreceptors may allow for the direct competitive interaction between nerve endings through differential activity-dependent acetylcholine release in the synaptic cleft. Then, the most active ending may directly punish the less active ones. Our previous results indicate the existence in the weakest axons on the polyinnervated neonatal NMJ of an ACh release inhibition mechanism based on mAChR coupled to protein kinase C and voltage-dependent calcium channels. We suggest that this mechanism plays a role in the elimination of redundant neonatal synapses. Here we used confocal microscopy and quantitative morphological analysis to count the number of brightly fluorescent axons per endplate in P7, P9 and P15 transgenic B6.Cg-Tg (Thy1-YFP)16 Jrs/J mice. We investigate the involvement of individual mAChR M1-, M2- and M4-subtypes in the control of axonal elimination after the Levator auris longus muscle had been exposed to agonist and antagonist in vivo. We also analysed the role of adenosine receptor subtypes (A1 and A2A) and the tropomyosin-related kinase B receptor. The data show that postnatal axonal elimination is a regulated multireceptor mechanism that guaranteed the monoinnervation of the neuromuscular synapses. The three receptor sets considered (mAChR, AR and TrkB receptors) intervene in modulating the conditions of the competition between nerve endings, possibly helping to determine the winner or the lossers but, thereafter, the final elimination would occur with some autonomy and independently of postsynaptic maturation.
Growth of a pole-size ponderosa on cutover land in relation to selection of trees for pruning.
Lloyd G. Gillmore; Forrest W. Jones
1954-01-01
The expected growth of pole-size ponderosa pine on cutover land should be considered in selecting those trees which will grow fast enough in the future to warrant investment in pruning. This consideration is especially important because most pruning work is done within 2 or 3 years after cutting and before the release effect of cutting is evident on reserved trees....
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wodraszka, Robert, E-mail: Robert.Wodraszka@chem.queensu.ca; Carrington, Tucker, E-mail: Tucker.Carrington@queensu.ca
In this paper, we propose a pruned, nondirect product multi-configuration time dependent Hartree (MCTDH) method for solving the Schrödinger equation. MCTDH uses optimized 1D basis functions, called single particle functions, but the size of the standard direct product MCTDH basis scales exponentially with D, the number of coordinates. We compare the pruned approach to standard MCTDH calculations for basis sizes small enough that the latter are possible and demonstrate that pruning the basis reduces the CPU cost of computing vibrational energy levels of acetonitrile (D = 12) by more than two orders of magnitude. Using the pruned method, it ismore » possible to do calculations with larger bases, for which the cost of standard MCTDH calculations is prohibitive. Pruning the basis complicates the evaluation of matrix-vector products. In this paper, they are done term by term for a sum-of-products Hamiltonian. When no attempt is made to exploit the fact that matrices representing some of the factors of a term are identity matrices, one needs only to carefully constrain indices. In this paper, we develop new ideas that make it possible to further reduce the CPU time by exploiting identity matrices.« less
Morton, Russell A; Yanagawa, Yuchio; Valenzuela, C Fernando
2015-01-01
Alterations in the development of the serotonin system can have prolonged effects, including depression and anxiety disorders later in life. Serotonin axonal projections from the dorsal raphe undergo extensive refinement during the first 2 weeks of postnatal life in rodents (equivalent to the third trimester of human pregnancy). However, little is known about the functional properties of serotonin and GABA neurons in the dorsal raphe during this critical developmental period. We assessed the functional properties and synaptic connectivity of putative serotoninergic neurons and GABAergic neurons in the dorsal raphe during early [postnatal day (P) P5-P7] and late (P15-P17) stages of the third trimester equivalent period using electrophysiology. Our studies demonstrate that GABAergic neurons are hyperexcitable at P5-P7 relative to P15-P17. Furthermore, putative serotonin neurons exhibit an increase in both excitatory and GABAA receptor-mediated spontaneous postsynaptic currents during this developmental period. Our data suggest that GABAergic neurons and putative serotonin neurons undergo significant electrophysiological changes during neonatal development.
7 CFR 993.56 - Reserve obligation.
Code of Federal Regulations, 2010 CFR
2010-01-01
... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... dehydrators plus that diverted tonnage (dried weight natural condition prune basis) on diversion certificates...
7 CFR 993.56 - Reserve obligation.
Code of Federal Regulations, 2012 CFR
2012-01-01
... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... dehydrators plus that diverted tonnage (dried weight natural condition prune basis) on diversion certificates...
7 CFR 993.56 - Reserve obligation.
Code of Federal Regulations, 2011 CFR
2011-01-01
... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... dehydrators plus that diverted tonnage (dried weight natural condition prune basis) on diversion certificates...
7 CFR 993.56 - Reserve obligation.
Code of Federal Regulations, 2014 CFR
2014-01-01
... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... dehydrators plus that diverted tonnage (dried weight natural condition prune basis) on diversion certificates...
7 CFR 993.56 - Reserve obligation.
Code of Federal Regulations, 2013 CFR
2013-01-01
... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... dehydrators plus that diverted tonnage (dried weight natural condition prune basis) on diversion certificates...
Developmental Self-Construction and -Configuration of Functional Neocortical Neuronal Networks
Bauer, Roman; Zubler, Frédéric; Pfister, Sabina; Hauri, Andreas; Pfeiffer, Michael; Muir, Dylan R.; Douglas, Rodney J.
2014-01-01
The prenatal development of neural circuits must provide sufficient configuration to support at least a set of core postnatal behaviors. Although knowledge of various genetic and cellular aspects of development is accumulating rapidly, there is less systematic understanding of how these various processes play together in order to construct such functional networks. Here we make some steps toward such understanding by demonstrating through detailed simulations how a competitive co-operative (‘winner-take-all’, WTA) network architecture can arise by development from a single precursor cell. This precursor is granted a simplified gene regulatory network that directs cell mitosis, differentiation, migration, neurite outgrowth and synaptogenesis. Once initial axonal connection patterns are established, their synaptic weights undergo homeostatic unsupervised learning that is shaped by wave-like input patterns. We demonstrate how this autonomous genetically directed developmental sequence can give rise to self-calibrated WTA networks, and compare our simulation results with biological data. PMID:25474693
The flowering hormone florigen functions as a general systemic regulator of growth and termination
Shalit, Akiva; Rozman, Alexander; Goldshmidt, Alexander; Alvarez, John P.; Bowman, John L.; Eshed, Yuval; Lifschitz, Eliezer
2009-01-01
The florigen paradigm implies a universal flowering-inducing hormone that is common to all flowering plants. Recent work identified FT orthologues as originators of florigen and their polypeptides as the likely systemic agent. However, the developmental processes targeted by florigen remained unknown. Here we identify local balances between SINGLE FLOWER TRUSS (SFT), the tomato precursor of florigen, and SELF-PRUNING (SP), a potent SFT-dependent SFT inhibitor as prime targets of mobile florigen. The graft-transmissible impacts of florigen on organ-specific traits in perennial tomato show that in addition to import by shoot apical meristems, florigen is imported by organs in which SFT is already expressed. By modulating local SFT/SP balances, florigen confers differential flowering responses of primary and secondary apical meristems, regulates the reiterative growth and termination cycles typical of perennial plants, accelerates leaf maturation, and influences the complexity of compound leaves, the growth of stems and the formation of abscission zones. Florigen is thus established as a plant protein functioning as a general growth hormone. Developmental interactions and a phylogenetic analysis suggest that the SFT/SP regulatory hierarchy is a recent evolutionary innovation unique to flowering plants. PMID:19416824
D.L. Copes
1992-01-01
The rooting percentages of 14 Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) clones were examined annually from 1974 to 1988. The trees were 10 and 13 years old in 1974 and were pruned to 2.0 m in 1978 and 1979 and then recut annually to 0.5, 1.0, or 1.5 m, starting in 1983. The pruned trees showed no evidence of decreased rooting percentage...
Ferrucci, Veronica; de Antonellis, Pasqualino; Pennino, Francesco Paolo; Asadzadeh, Fatemeh; Virgilio, Antonella; Montanaro, Donatella; Galeone, Aldo; Boffa, Iolanda; Pisano, Ida; Scognamiglio, Iolanda; Navas, Luigi; Diana, Donatella; Pedone, Emilia; Gargiulo, Sara; Gramanzini, Matteo; Brunetti, Arturo; Danielson, Laura; Carotenuto, Marianeve; Liguori, Lucia; Verrico, Antonio; Quaglietta, Lucia; Errico, Maria Elena; Del Monaco, Valentina; D'Argenio, Valeria; Tirone, Felice; Mastronuzzi, Angela; Donofrio, Vittoria; Giangaspero, Felice; Picard, Daniel; Remke, Marc; Garzia, Livia; Daniels, Craig; Delattre, Olivier; Swartling, Fredrik J; Weiss, William A; Salvatore, Francesco; Fattorusso, Roberto; Chesler, Louis; Taylor, Michael D; Cinalli, Giuseppe; Zollo, Massimo
2018-05-01
Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common 'non-synonymous homozygous' deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-β/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3.10.1093/brain/awy039_video1awy039media15742053534001.
Effect of edge pruning on structural controllability and observability of complex networks
Mengiste, Simachew Abebe; Aertsen, Ad; Kumar, Arvind
2015-01-01
Controllability and observability of complex systems are vital concepts in many fields of science. The network structure of the system plays a crucial role in determining its controllability and observability. Because most naturally occurring complex systems show dynamic changes in their network connectivity, it is important to understand how perturbations in the connectivity affect the controllability of the system. To this end, we studied the control structure of different types of artificial, social and biological neuronal networks (BNN) as their connections were progressively pruned using four different pruning strategies. We show that the BNNs are more similar to scale-free networks than to small-world networks, when comparing the robustness of their control structure to structural perturbations. We introduce a new graph descriptor, ‘the cardinality curve’, to quantify the robustness of the control structure of a network to progressive edge pruning. Knowing the susceptibility of control structures to different pruning methods could help design strategies to destroy the control structures of dangerous networks such as epidemic networks. On the other hand, it could help make useful networks more resistant to edge attacks. PMID:26674854
[Treatment of painful neuromas via end-to-side neurorraphy].
Aszmann, O C; Moser, V; Frey, M
2010-08-01
Management of the painful neuroma has been subject to controversy since the earliest descriptions of this disabling problem. Today, treatment is limited to resection of the neuroma and implantation of the nerve in a muscle at a location where it is safe from irritation and trauma. This however is not attainable in many cases and it is our clinical experience, that nerves without a target remain a source of constant discomfort and pain. Recently we reported of the feasibility of neuroma prevention through end-to-side neurorraphy into adjacent sensory and/or motor nerves to provide a target for axons deprived of their endorgan. Here we report of our first clinical experience with this method in sixteen patients with longstanding upper and lower extremity neuromas. 16 patients were included in this study. All had neuromas of different sensory nerves of both the upper and lower extremity. 11 were of iatrogenic origin, 5 were caused by different traumas. 8 had previous attempts to surgically treat the neuroma. Finally, all were treated by end-to-side neurorraphy into adjacent nerves. Postoperatively quantitative sensorymotor testing was performed to evaluate possible changes of nerve function of the recipient nerves. Pain was evaluated by visual analogue score and changes in pain medication. In no patient a sensory or motor deficit or painful sensations were induced in the target area of the recipient nerve. Some had dysaesthesias for about 6 months, which finally subsided. All but 1 patient improved in their symptoms at a follow-up of more than 2 years. Previous experimental work and present clinical results suggest that axons of a severed peripheral nerve that are provided with a pathway and target through an end-to-side coaptation will either be pruned or establish some type of end-organ contact so that a neuroma can be prevented without inducing sensory or motor dysfunctions in the recipient nerve. Georg Thieme Verlag KG Stuttgart New York.
7 CFR 993.109 - Modified definition of non-French prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Administrative Rules and Regulations Definitions § 993.109 Modified...
7 CFR 993.109 - Modified definition of non-French prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Administrative Rules and Regulations Definitions § 993.109 Modified...
7 CFR 993.157 - Holding and delivery of reserve prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Administrative Rules and Regulations Reserve Control § 993.157...
7 CFR 993.109 - Modified definition of non-French prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Administrative Rules and Regulations Definitions § 993.109 Modified...
7 CFR 993.109 - Modified definition of non-French prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Administrative Rules and Regulations Definitions § 993.109 Modified...
7 CFR 993.157 - Holding and delivery of reserve prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Administrative Rules and Regulations Reserve Control § 993.157...
7 CFR 993.157 - Holding and delivery of reserve prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Administrative Rules and Regulations Reserve Control § 993.157...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-10-27
...The Department of Agriculture (USDA) is adopting, as a final rule, without change, an interim rule that suspended the reporting and assessment requirements prescribed under the Washington-Oregon fresh prune marketing order. The marketing order regulates the handling of fresh prunes grown in designated counties in Washington and in Umatilla County, Oregon, and is administered locally by the Washington-Oregon Fresh Prune Marketing Committee (Committee). On June 1, 2010, the Committee unanimously voted to terminate Marketing Order No. 924. Since the only regulatory actions then in effect were the reporting and assessment requirements, the Committee included a recommendation to immediately suspend those activities while USDA processes the termination request. The reporting and assessment requirements will remain suspended until reinstated or permanently terminated.
Composability-Centered Convolutional Neural Network Pruning
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shen, Xipeng; Guan, Hui; Lim, Seung-Hwan
This work studies the composability of the building blocks ofstructural CNN models (e.g., GoogleLeNet and Residual Networks) in thecontext of network pruning. We empirically validate that a networkcomposed of pre-trained building blocks (e.g. residual blocks andInception modules) not only gives a better initial setting fortraining, but also allows the training process to converge at asignificantly higher accuracy in much less time. Based on thatinsight, we propose a {\\em composability-centered} design for CNNnetwork pruning. Experiments show that this new scheme shortens theconfiguration process in CNN network pruning by up to 186.8X forResNet-50 and up to 30.2X for Inception-V3, and meanwhile, themore » modelsit finds that meet the accuracy requirement are significantly morecompact than those found by default schemes.« less
Code of Federal Regulations, 2010 CFR
2010-01-01
... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... amended, and Order No. 993, as amended (§§ 993.1 through 993.97), regulating the handling of dried prunes...
Code of Federal Regulations, 2012 CFR
2012-01-01
... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... amended, and Order No. 993, as amended (§§ 993.1 through 993.97), regulating the handling of dried prunes...
Code of Federal Regulations, 2013 CFR
2013-01-01
... ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... amended, and Order No. 993, as amended (§§ 993.1 through 993.97), regulating the handling of dried prunes...
Code of Federal Regulations, 2011 CFR
2011-01-01
... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA... amended, and Order No. 993, as amended (§§ 993.1 through 993.97), regulating the handling of dried prunes...
Kayano, Shin-ichi; Kikuzaki, Hiroe; Ikami, Takao; Suzuki, Tomoo; Mitani, Takahiko; Nakatani, Nobuji
2004-04-01
Isolation and structural elucidation of prune constituents were performed and total 10 compounds were determined by NMR and MS analyses. A novel compound was identified to be 2-(5-hydroxymethyl-2',5'-dioxo-2',3',4',5'-tetrahydro-1'H-1,3'-bipyrrole)carbaldehyde, and 7 phenolic compounds were isolated from prunes for the first time. In addition, antioxidant activity of them was evaluated on the basis of the oxygen radical absorbance capacity (ORAC).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Perrot, F.
The low background gamma spectroscopy has been applied to try to sign the geographical origin of the French atlantic marine salts and of the prunes from Agen. Most of the activity measurements have been done using low background Ge spectrometers located in Bordeaux. Results have shown that a clear signature exists in the case of the French atlantic salts using the 40K, 137Cs and 226Ra isotopes but not in the case of the prunes.
Parekh, Ruchi; Armañanzas, Rubén; Ascoli, Giorgio A
2015-04-01
Digital reconstructions of axonal and dendritic arbors provide a powerful representation of neuronal morphology in formats amenable to quantitative analysis, computational modeling, and data mining. Reconstructed files, however, require adequate metadata to identify the appropriate animal species, developmental stage, brain region, and neuron type. Moreover, experimental details about tissue processing, neurite visualization and microscopic imaging are essential to assess the information content of digital morphologies. Typical morphological reconstructions only partially capture the underlying biological reality. Tracings are often limited to certain domains (e.g., dendrites and not axons), may be incomplete due to tissue sectioning, imperfect staining, and limited imaging resolution, or can disregard aspects irrelevant to their specific scientific focus (such as branch thickness or depth). Gauging these factors is critical in subsequent data reuse and comparison. NeuroMorpho.Org is a central repository of reconstructions from many laboratories and experimental conditions. Here, we introduce substantial additions to the existing metadata annotation aimed to describe the completeness of the reconstructed neurons in NeuroMorpho.Org. These expanded metadata form a suitable basis for effective description of neuromorphological data.
Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas
2016-01-01
The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila. DOI: http://dx.doi.org/10.7554/eLife.13715.001 PMID:26987017
Gatti, Matteo; Pirez, Facundo J.; Chiari, Giorgio; Tombesi, Sergio; Palliotti, Alberto; Merli, Maria C.; Poni, Stefano
2016-01-01
Manipulating or shifting annual grapevine growing cycle to offset limitations imposed by global warming is a must today, and delayed winter pruning is a tool to achieve it. However, no information is available about its physiological background, especially in relation to modifications in canopy phenology, demography and seasonal carbon budget. Mechanistic hypothesis underlying this work was that very late winter pruning (LWP) can achieve significant postponement of phenological stages so that ripening might occur in a cooler period and, concurrently, ripening potential can be improved due to higher efficiency and prolonged longevity of the canopy. Variability in the dynamics of the annual cycle was created in mature potted cv. Sangiovese grapevines subjected to either standard winter pruning (SWP) or late and very late winter pruning (LWP, VLWP) performed when apical shoots on the unpruned canes were at the stage of 2 and 7 unfolded leaves. Vegetative growth, phenology and canopy net CO2 exchange (NCER) were followed throughout the season. Despite LWP and VLWP induced a bud-burst delay of 17 and 31 days vs. SWP, the delay was fully offset at harvest for LWP and was reduced to 6 days in VLWP. LWP showed notably higher canopy efficiency as shorter time needed to reach maximum NCER/leaf area (22 days vs. 34 in SWP), highest maximum NCER/leaf area (+37% as compared to SWP) and higher NCER/leaf area rates from veraison to end of season. As a result, seasonal cumulated carbon in LWP was 17% higher than SWP. A negative functional relationship was also established between amount of leaf area removed at winter pruning and yield per vine and berry number per cluster. Although retarded winter pruning was not able to postpone late-season phenological stages under the warm conditions of this study, it showed a remarkable potential to limit yield while improving grape quality, thereby fostering the hypothesis that it could be used to replace time-consuming and costly cluster thinning. This preliminary study indicates that proper winter pruning date should be timed so as not to exceed the stage of two unfolded leaves. PMID:27242860
Nikodemova, Maria; Kimyon, Rebecca S; De, Ishani; Small, Alissa L; Collier, Lara S; Watters, Jyoti J
2015-01-15
During postnatal development, microglia, CNS resident innate immune cells, are essential for synaptic pruning, neuronal apoptosis and remodeling. During this period microglia undergo morphological and phenotypic transformations; however, little is known about how microglial number and density is regulated during postnatal CNS development. We found that after an initial increase during the first 14 postnatal days, microglial numbers in mouse brain began declining in the third postnatal week and were reduced by 50% by 6weeks of age; these "adult" levels were maintained until at least 9months of age. Microglial CD11b levels increased, whereas CD45 and ER-MP58 declined between P10 and adulthood, consistent with a maturing microglial phenotype. Our data indicate that both increased microglial apoptosis and a decreased proliferative capacity contribute to the developmental reduction in microglial numbers. We found no correlation between developmental reductions in microglial numbers and brain mRNA levels of Cd200, Cx3Cl1, M-Csf or Il-34. We tested the ability of M-Csf-overexpression, a key growth factor promoting microglial proliferation and survival, to prevent microglial loss in the third postnatal week. Mice overexpressing M-Csf in astrocytes had higher numbers of microglia at all ages tested. However, the developmental decline in microglial numbers still occurred, suggesting that chronically elevated M-CSF is unable to overcome the developmental decrease in microglial numbers. Whereas the identity of the factor(s) regulating microglial number and density during development remains to be determined, it is likely that microglia respond to a "maturation" signal since the reduction in microglial numbers coincides with CNS maturation. Copyright © 2014 Elsevier B.V. All rights reserved.
7 CFR 52.3187 - Definitions and explanations of defects.
Code of Federal Regulations, 2010 CFR
2010-01-01
... prune. (e) Fermentation. “Fermentation” means that the prune is fermented as evidenced by a distinct sour taste or odor or by darkening in color characteristic of fermentation or souring. (f) Scars...
7 CFR 993.400 - Modifications.
Code of Federal Regulations, 2012 CFR
2012-01-01
... larger size openings. For French prunes, any undersized regulation may prescribe an opening of 23/32 of an inch or 24/32 of an inch; for non-French prunes, any undersized regulation may prescribe an...
7 CFR 993.400 - Modifications.
Code of Federal Regulations, 2011 CFR
2011-01-01
... larger size openings. For French prunes, any undersized regulation may prescribe an opening of 23/32 of an inch or 24/32 of an inch; for non-French prunes, any undersized regulation may prescribe an...
7 CFR 993.400 - Modifications.
Code of Federal Regulations, 2013 CFR
2013-01-01
... larger size openings. For French prunes, any undersized regulation may prescribe an opening of 23/32 of an inch or 24/32 of an inch; for non-French prunes, any undersized regulation may prescribe an...
7 CFR 993.400 - Modifications.
Code of Federal Regulations, 2010 CFR
2010-01-01
... larger size openings. For French prunes, any undersized regulation may prescribe an opening of 23/32 of an inch or 24/32 of an inch; for non-French prunes, any undersized regulation may prescribe an...
Recombination algorithms and jet substructure: Pruning as a tool for heavy particle searches
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ellis, Stephen D.; Vermilion, Christopher K.; Walsh, Jonathan R.
2010-05-01
We discuss jet substructure in recombination algorithms for QCD jets and single jets from heavy particle decays. We demonstrate that the jet algorithm can introduce significant systematic effects into the substructure. By characterizing these systematic effects and the substructure from QCD, splash-in, and heavy particle decays, we identify a technique, pruning, to better identify heavy particle decays into single jets and distinguish them from QCD jets. Pruning removes protojets typical of soft, wide-angle radiation, improves the mass resolution of jets reconstructing heavy particle decays, and decreases the QCD background to these decays. We show that pruning provides significant improvements overmore » unpruned jets in identifying top quarks and W bosons and separating them from a QCD background, and may be useful in a search for heavy particles.« less
O'Reilly, Kally C.; Kao, Hsin-Yi; Lee, Heekyung; Fenton, André A.
2014-01-01
Despite substantial effort and immense need, the treatment options for major neuropsychiatric illnesses like schizophrenia are limited and largely ineffective at improving the most debilitating cognitive symptoms that are central to mental illness. These symptoms include cognitive control deficits, the inability to selectively use information that is currently relevant and ignore what is currently irrelevant. Contemporary attempts to accelerate progress are in part founded on an effort to reconceptualize neuropsychiatric illness as a disorder of neural development. This neuro-developmental framework emphasizes abnormal neural circuits on the one hand, and on the other, it suggests there are therapeutic opportunities to exploit the developmental processes of excitatory neuron pruning, inhibitory neuron proliferation, elaboration of myelination, and other circuit refinements that extend through adolescence and into early adulthood. We have crafted a preclinical research program aimed at cognition failures that may be relevant to mental illness. By working with a variety of neurodevelopmental rodent models, we strive to identify a common pathophysiology that underlies cognitive control failure as well as a common strategy for improving cognition in the face of neural circuit abnormalities. Here we review our work to characterize cognitive control deficits in rats with a neonatal ventral hippocampus lesion and rats that were exposed to Methylazoxymethanol acetate (MAM) in utero. We review our findings as they pertain to early developmental processes, including neurogenesis, as well as the power of cognitive experience to refine neural circuit function within the mature and maturing brain's cognitive circuitry. PMID:24966811
Sensitivity of directed networks to the addition and pruning of edges and vertices
NASA Astrophysics Data System (ADS)
Goltsev, A. V.; Timár, G.; Mendes, J. F. F.
2017-08-01
Directed networks have various topologically different extensive components, in contrast to a single giant component in undirected networks. We study the sensitivity (response) of the sizes of these extensive components in directed complex networks to the addition and pruning of edges and vertices. We introduce the susceptibility, which quantifies this sensitivity. We show that topologically different parts of a directed network have different sensitivity to the addition and pruning of edges and vertices and, therefore, they are characterized by different susceptibilities. These susceptibilities diverge at the critical point of the directed percolation transition, signaling the appearance (or disappearance) of the giant strongly connected component in the infinite size limit. We demonstrate this behavior in randomly damaged real and synthetic directed complex networks, such as the World Wide Web, Twitter, the Caenorhabditis elegans neural network, directed Erdős-Rényi graphs, and others. We reveal a nonmonotonic dependence of the sensitivity to random pruning of edges or vertices in the case of C. elegans and Twitter that manifests specific structural peculiarities of these networks. We propose the measurements of the susceptibilities during the addition or pruning of edges and vertices as a new method for studying structural peculiarities of directed networks.
Afroz, Sonia; Parato, Julie; Shen, Hui; Smith, Sheryl Sue
2016-01-01
Adolescent synaptic pruning is thought to enable optimal cognition because it is disrupted in certain neuropathologies, yet the initiator of this process is unknown. One factor not yet considered is the α4βδ GABAA receptor (GABAR), an extrasynaptic inhibitory receptor which first emerges on dendritic spines at puberty in female mice. Here we show that α4βδ GABARs trigger adolescent pruning. Spine density of CA1 hippocampal pyramidal cells decreased by half post-pubertally in female wild-type but not α4 KO mice. This effect was associated with decreased expression of kalirin-7 (Kal7), a spine protein which controls actin cytoskeleton remodeling. Kal7 decreased at puberty as a result of reduced NMDAR activation due to α4βδ-mediated inhibition. In the absence of this inhibition, Kal7 expression was unchanged at puberty. In the unpruned condition, spatial re-learning was impaired. These data suggest that pubertal pruning requires α4βδ GABARs. In their absence, pruning is prevented and cognition is not optimal. DOI: http://dx.doi.org/10.7554/eLife.15106.001 PMID:27136678
The association between prune belly syndrome and dental anomalies: a case report.
Basso, Maria Daniela; Favretto, Carla Oliveira; Cunha, Robson Frederico
2012-12-18
Prune belly syndrome is a rare condition produced by an early mesodermal defect that causes abdominal abnormalities. However, the literature indicates that disturbances related to ectodermal development may also be present. This is the first case report in the literature to suggest that dental abnormalities are part of the broad spectrum of clinical features of prune belly syndrome. Because the syndrome causes many serious medical problems, early diagnosis of abnormalities involving the primary and permanent dentitions are encouraged. The authors report the clinical case of a 4-year-old Caucasian boy with prune belly syndrome. In addition to the triad of abdominal muscle deficiency, abnormalities of the gastrointestinal and urinary tracts, and cryptorchidism, a geminated mandibular right central incisor, agenesis of a mandibular permanent left incisor, and congenitally missing primary teeth (namely, the mandibular right and left lateral incisors) were noted. This original case report about prune belly syndrome highlights the possibility that dental abnormalities are a part of the broad spectrum of clinical features of the syndrome. Therefore, an accurate intra-oral clinical examination and radiographic evaluation are required for patients with this syndrome in order to provide an early diagnosis of abnormalities involving the primary and permanent dentitions.
7 CFR 999.200 - Regulation governing the importation of prunes.
Code of Federal Regulations, 2013 CFR
2013-01-01
... preservation; and (iii) brine dried prunes that have been impregnated with brine or salt during the dehydration... means injury by sunburn or excessive heat in dehydration to the extent that the characteristic...
7 CFR 999.200 - Regulation governing the importation of prunes.
Code of Federal Regulations, 2014 CFR
2014-01-01
... preservation; and (iii) brine dried prunes that have been impregnated with brine or salt during the dehydration... means injury by sunburn or excessive heat in dehydration to the extent that the characteristic...
7 CFR 999.200 - Regulation governing the importation of prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... preservation; and (iii) brine dried prunes that have been impregnated with brine or salt during the dehydration... means injury by sunburn or excessive heat in dehydration to the extent that the characteristic...
7 CFR 999.200 - Regulation governing the importation of prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... preservation; and (iii) brine dried prunes that have been impregnated with brine or salt during the dehydration... means injury by sunburn or excessive heat in dehydration to the extent that the characteristic...
Ensemble Pruning for Glaucoma Detection in an Unbalanced Data Set.
Adler, Werner; Gefeller, Olaf; Gul, Asma; Horn, Folkert K; Khan, Zardad; Lausen, Berthold
2016-12-07
Random forests are successful classifier ensemble methods consisting of typically 100 to 1000 classification trees. Ensemble pruning techniques reduce the computational cost, especially the memory demand, of random forests by reducing the number of trees without relevant loss of performance or even with increased performance of the sub-ensemble. The application to the problem of an early detection of glaucoma, a severe eye disease with low prevalence, based on topographical measurements of the eye background faces specific challenges. We examine the performance of ensemble pruning strategies for glaucoma detection in an unbalanced data situation. The data set consists of 102 topographical features of the eye background of 254 healthy controls and 55 glaucoma patients. We compare the area under the receiver operating characteristic curve (AUC), and the Brier score on the total data set, in the majority class, and in the minority class of pruned random forest ensembles obtained with strategies based on the prediction accuracy of greedily grown sub-ensembles, the uncertainty weighted accuracy, and the similarity between single trees. To validate the findings and to examine the influence of the prevalence of glaucoma in the data set, we additionally perform a simulation study with lower prevalences of glaucoma. In glaucoma classification all three pruning strategies lead to improved AUC and smaller Brier scores on the total data set with sub-ensembles as small as 30 to 80 trees compared to the classification results obtained with the full ensemble consisting of 1000 trees. In the simulation study, we were able to show that the prevalence of glaucoma is a critical factor and lower prevalence decreases the performance of our pruning strategies. The memory demand for glaucoma classification in an unbalanced data situation based on random forests could effectively be reduced by the application of pruning strategies without loss of performance in a population with increased risk of glaucoma.
Pittman, Andrew J.; Law, Mei-Yee; Chien, Chi-Bin
2008-01-01
Summary Navigating axons respond to environmental guidance signals, but can also follow axons that have gone before—pioneer axons. Pioneers have been studied extensively in simple systems, but the role of axon-axon interactions remains largely unexplored in large vertebrate axon tracts, where cohorts of identical axons could potentially use isotypic interactions to guide each other through multiple choice points. Furthermore, the relative importance of axon-axon interactions compared to axon-autonomous receptor function has not been assessed. Here we test the role of axon-axon interactions in retinotectal development, by devising a technique to selectively remove or replace early-born retinal ganglion cells (RGCs). We find that early RGCs are both necessary and sufficient for later axons to exit the eye. Furthermore, introducing misrouted axons by transplantation reveals that guidance from eye to tectum relies heavily on interactions between axons, including both pioneer-follower and community effects. We conclude that axon-axon interactions and ligand-receptor signaling have coequal roles, cooperating to ensure the fidelity of axon guidance in developing vertebrate tracts. PMID:18653554
Group Cohesiveness, Deviation, Stress, and Conformity
1993-08-11
Cola number of cups, __ Chocolate, cocoa, wine, beer/alcohol, decaffeinated coffee. Breads containing raisins, prunes, orange peel , banana , or...pudding, mince pie. Banana , avocado, pineapple, canned figs, raisins, plums and prunes. Oranges, orange juice, fru~ cocktail with pineapple. Tomato
REM sleep selectively prunes and maintains new synapses in development and learning.
Li, Wei; Ma, Lei; Yang, Guang; Gan, Wen-Biao
2017-03-01
The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation during development and when a new motor task is learned, indicating a role for REM sleep in pruning to balance the number of new spines formed over time. Moreover, REM sleep also strengthens and maintains newly formed spines, which are critical for neuronal circuit development and behavioral improvement after learning. We further show that dendritic calcium spikes arising during REM sleep are important for pruning and strengthening new spines. Together, these findings indicate that REM sleep has multifaceted functions in brain development, learning and memory consolidation by selectively eliminating and maintaining newly formed synapses via dendritic calcium spike-dependent mechanisms.
Lusch, Bethany; Weholt, Jake; Maia, Pedro D; Kutz, J Nathan
2018-06-01
The accurate diagnosis and assessment of neurodegenerative disease and traumatic brain injuries (TBI) remain open challenges. Both cause cognitive and functional deficits due to focal axonal swellings (FAS), but it is difficult to deliver a prognosis due to our limited ability to assess damaged neurons at a cellular level in vivo. We simulate the effects of neurodegenerative disease and TBI using convolutional neural networks (CNNs) as our model of cognition. We utilize biophysically relevant statistical data on FAS to damage the connections in CNNs in a functionally relevant way. We incorporate energy constraints on the brain by pruning the CNNs to be less over-engineered. Qualitatively, we demonstrate that damage leads to human-like mistakes. Our experiments also provide quantitative assessments of how accuracy is affected by various types and levels of damage. The deficit resulting from a fixed amount of damage greatly depends on which connections are randomly injured, providing intuition for why it is difficult to predict impairments. There is a large degree of subjectivity when it comes to interpreting cognitive deficits from complex systems such as the human brain. However, we provide important insight and a quantitative framework for disorders in which FAS are implicated. Copyright © 2018 Elsevier Inc. All rights reserved.
Synaptic Spinules in the Olfactory Circuit of Drosophila melanogaster
Gruber, Lydia; Rybak, Jürgen; Hansson, Bill S.; Cantera, Rafael
2018-01-01
Here we report on ultrastructural features of brain synapses in the fly Drosophila melanogaster and outline a perspective for the study of their functional significance. Images taken with the aid of focused ion beam-scanning electron microscopy (EM) at 20 nm intervals across olfactory glomerulus DA2 revealed that some synaptic boutons are penetrated by protrusions emanating from other neurons. Similar structures in the brain of mammals are known as synaptic spinules. A survey with transmission EM (TEM) disclosed that these structures are frequent throughout the antennal lobe. Detailed neuronal tracings revealed that spinules are formed by all three major types of neurons innervating glomerulus DA2 but the olfactory sensory neurons (OSNs) receive significantly more spinules than other olfactory neurons. Double-membrane vesicles (DMVs) that appear to represent material that has pinched-off from spinules are also most abundant in presynaptic boutons of OSNs. Inside the host neuron, a close association was observed between spinules, the endoplasmic reticulum (ER) and mitochondria. We propose that by releasing material into the host neuron, through a process triggered by synaptic activity and analogous to axonal pruning, synaptic spinules could function as a mechanism for synapse tagging, synaptic remodeling and neural plasticity. Future directions of experimental work to investigate this theory are proposed. PMID:29636666
DeepNeuron: an open deep learning toolbox for neuron tracing.
Zhou, Zhi; Kuo, Hsien-Chi; Peng, Hanchuan; Long, Fuhui
2018-06-06
Reconstructing three-dimensional (3D) morphology of neurons is essential for understanding brain structures and functions. Over the past decades, a number of neuron tracing tools including manual, semiautomatic, and fully automatic approaches have been developed to extract and analyze 3D neuronal structures. Nevertheless, most of them were developed based on coding certain rules to extract and connect structural components of a neuron, showing limited performance on complicated neuron morphology. Recently, deep learning outperforms many other machine learning methods in a wide range of image analysis and computer vision tasks. Here we developed a new Open Source toolbox, DeepNeuron, which uses deep learning networks to learn features and rules from data and trace neuron morphology in light microscopy images. DeepNeuron provides a family of modules to solve basic yet challenging problems in neuron tracing. These problems include but not limited to: (1) detecting neuron signal under different image conditions, (2) connecting neuronal signals into tree(s), (3) pruning and refining tree morphology, (4) quantifying the quality of morphology, and (5) classifying dendrites and axons in real time. We have tested DeepNeuron using light microscopy images including bright-field and confocal images of human and mouse brain, on which DeepNeuron demonstrates robustness and accuracy in neuron tracing.
Development of Human Brain Structural Networks Through Infancy and Childhood
Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J.; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong
2015-01-01
During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. PMID:24335033
Synaptic Spinules in the Olfactory Circuit of Drosophila melanogaster.
Gruber, Lydia; Rybak, Jürgen; Hansson, Bill S; Cantera, Rafael
2018-01-01
Here we report on ultrastructural features of brain synapses in the fly Drosophila melanogaster and outline a perspective for the study of their functional significance. Images taken with the aid of focused ion beam-scanning electron microscopy (EM) at 20 nm intervals across olfactory glomerulus DA2 revealed that some synaptic boutons are penetrated by protrusions emanating from other neurons. Similar structures in the brain of mammals are known as synaptic spinules. A survey with transmission EM (TEM) disclosed that these structures are frequent throughout the antennal lobe. Detailed neuronal tracings revealed that spinules are formed by all three major types of neurons innervating glomerulus DA2 but the olfactory sensory neurons (OSNs) receive significantly more spinules than other olfactory neurons. Double-membrane vesicles (DMVs) that appear to represent material that has pinched-off from spinules are also most abundant in presynaptic boutons of OSNs. Inside the host neuron, a close association was observed between spinules, the endoplasmic reticulum (ER) and mitochondria. We propose that by releasing material into the host neuron, through a process triggered by synaptic activity and analogous to axonal pruning, synaptic spinules could function as a mechanism for synapse tagging, synaptic remodeling and neural plasticity. Future directions of experimental work to investigate this theory are proposed.
Developmental distribution of CaM kinase II in the antennal lobe of the sphinx moth Manduca sexta.
Lohr, Christian; Bergstein, Sandra; Hirnet, Daniela
2007-01-01
The antennal lobe (primary olfactory center of insects) is completely reorganized during metamorphosis. This reorganization is accompanied by changing patterns of calcium signaling in neurons and glial cells. In the present study, we investigated the developmental distribution of a major calcium-dependent protein, viz., calcium/calmodulin-dependent protein kinase II (CaM kinase II), in the antennal lobe of the sphinx moth Manduca sexta by using a monoclonal antibody. During synaptogenesis (developmental stages 6-10), we found a redistribution of CaM kinase II immunoreactivity, from a homogeneous distribution in the immature neuropil to an accumulation in the neuropil of the glomeruli. CaM kinase II immunoreactivity was less intense in olfactory receptor axons of the antennal nerve and antennal lobe glial cells. Western blot analysis revealed a growing content of CaM kinase II in antennal lobe tissue throughout metamorphosis. Injection of the CaM kinase inhibitor KN-93 into pupae resulted in a reduced number of antennal lobe glial cells migrating into the neuropil to form borders around glomeruli. The results suggest that CaM kinase II is involved in glial cell migration.
Tashiro, Yasura; Oyabu, Akiko; Imura, Yoshio; Uchida, Atsuko; Narita, Naoko; Narita, Masaaki
2011-06-01
Autism is often associated with multiple developmental anomalies including asymmetric facial palsy. In order to establish the etiology of autism with facial palsy, research into developmental abnormalities of the peripheral facial nerves is necessary. In the present study, to investigate the development of peripheral cranial nerves for use in an animal model of autism, rat embryos were treated with valproic acid (VPA) in utero and their cranial nerves were visualized by immunostaining. Treatment with VPA after embryonic day 9 had a significant effect on the peripheral fibers of several cranial nerves. Following VPA treatment, immunoreactivity within the trigeminal, facial, glossopharyngeal and vagus nerves was significantly reduced. Additionally, abnormal axonal pathways were observed in the peripheral facial nerves. Thus, the morphology of several cranial nerves, including the facial nerve, can be affected by prenatal VPA exposure as early as E13. Our findings indicate that disruption of early facial nerve development is involved in the etiology of asymmetric facial palsy, and may suggest a link to the etiology of autism. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.
Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants
Ten, Vadim S.
2017-01-01
At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units—alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise. PMID:27901512
Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants.
Ten, Vadim S
2017-02-01
At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units-alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise.
NASA Astrophysics Data System (ADS)
Tommy, Lukas; Hardjianto, Mardi; Agani, Nazori
2017-04-01
Connect Four is a two-player game which the players take turns dropping discs into a grid to connect 4 of one’s own discs next to each other vertically, horizontally, or diagonally. At Connect Four, Computer requires artificial intelligence (AI) in order to play properly like human. There are many AI algorithms that can be implemented to Connect Four, but the suitable algorithms are unknown. The suitable algorithm means optimal in choosing move and its execution time is not slow at search depth which is deep enough. In this research, analysis and comparison between standard alpha beta (AB) Pruning and MTD(f) will be carried out at the prototype of Connect Four in terms of optimality (win percentage) and speed (execution time and the number of leaf nodes). Experiments are carried out by running computer versus computer mode with 12 different conditions, i.e. varied search depth (5 through 10) and who moves first. The percentage achieved by MTD(f) based on experiments is win 45,83%, lose 37,5% and draw 16,67%. In the experiments with search depth 8, MTD(f) execution time is 35, 19% faster and evaluate 56,27% fewer leaf nodes than AB Pruning. The results of this research are MTD(f) is as optimal as AB Pruning at Connect Four prototype, but MTD(f) on average is faster and evaluates fewer leaf nodes than AB Pruning. The execution time of MTD(f) is not slow and much faster than AB Pruning at search depth which is deep enough.
7 CFR 993.150 - Disposition of prunes by handlers.
Code of Federal Regulations, 2010 CFR
2010-01-01
....150 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED... handler, and any other place where he handles prunes. (b) Outgoing inspection. Except as otherwise...
40 CFR 180.553 - Fenhexamid; tolerances for residues.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 10 Pepper, nonbell 0.02 Pistachio 0.02 Plum, prune, dried 2.5 Plum, prune, fresh 1.5 Pomegranate 2.0 Salal 5.0 Strawberry 3.0 Vegetable, fruiting, group 8, except nonbell pepper 2.0 (b) Section 18...
Parent, Maxime; Li, Ying; Santhakumar, Vijayalakshmi; Hyder, Fahmeed; Sanganahalli, Basavaraju G; Kannurpatti, Sridhar
2018-06-01
TBI is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence. 1 Based on the non-localized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity and neurovascular function are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2-months after injury, using functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). fMRI based resting state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus and thalamus accompanied by decrease in the spatial extent of their corresponding RSFC networks and inter-hemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus and motor cortex. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), reporting on axonal and microstructural integrity of the brain, indicated similar inter-hemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in inter-hemispheric structural connectivity. Hippocampus, thalamus and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance and parenchymal microstructure in the adolescent brain, indicating the highly diffuse and persistent nature of the lateral fluid percussion TBI early in development.
The Neural Basis of Aversive Pavlovian Guidance during Planning
Faulkner, Paul
2017-01-01
Important real-world decisions are often arduous as they frequently involve sequences of choices, with initial selections affecting future options. Evaluating every possible combination of choices is computationally intractable, particularly for longer multistep decisions. Therefore, humans frequently use heuristics to reduce the complexity of decisions. We recently used a goal-directed planning task to demonstrate the profound behavioral influence and ubiquity of one such shortcut, namely aversive pruning, a reflexive Pavlovian process that involves neglecting parts of the decision space residing beyond salient negative outcomes. However, how the brain implements this important decision heuristic and what underlies individual differences have hitherto remained unanswered. Therefore, we administered an adapted version of the same planning task to healthy male and female volunteers undergoing functional magnetic resonance imaging (fMRI) to determine the neural basis of aversive pruning. Through both computational and standard categorical fMRI analyses, we show that when planning was influenced by aversive pruning, the subgenual cingulate cortex was robustly recruited. This neural signature was distinct from those associated with general planning and valuation, two fundamental cognitive components elicited by our task but which are complementary to aversive pruning. Furthermore, we found that individual variation in levels of aversive pruning was associated with the responses of insula and dorsolateral prefrontal cortices to the receipt of large monetary losses, and also with subclinical levels of anxiety. In summary, our data reveal the neural signatures of an important reflexive Pavlovian process that shapes goal-directed evaluations and thereby determines the outcome of high-level sequential cognitive processes. SIGNIFICANCE STATEMENT Multistep decisions are complex because initial choices constrain future options. Evaluating every path for long decision sequences is often impractical; thus, cognitive shortcuts are often essential. One pervasive and powerful heuristic is aversive pruning, in which potential decision-making avenues are curtailed at immediate negative outcomes. We used neuroimaging to examine how humans implement such pruning. We found it to be associated with activity in the subgenual cingulate cortex, with neural signatures that were distinguishable from those covarying with planning and valuation. Individual variations in aversive pruning levels related to subclinical anxiety levels and insular cortex activation. These findings reveal the neural mechanisms by which basic negative Pavlovian influences guide decision-making during planning, with implications for disrupted decision-making in psychiatric disorders. PMID:28924006
The Neural Basis of Aversive Pavlovian Guidance during Planning.
Lally, Níall; Huys, Quentin J M; Eshel, Neir; Faulkner, Paul; Dayan, Peter; Roiser, Jonathan P
2017-10-18
Important real-world decisions are often arduous as they frequently involve sequences of choices, with initial selections affecting future options. Evaluating every possible combination of choices is computationally intractable, particularly for longer multistep decisions. Therefore, humans frequently use heuristics to reduce the complexity of decisions. We recently used a goal-directed planning task to demonstrate the profound behavioral influence and ubiquity of one such shortcut, namely aversive pruning, a reflexive Pavlovian process that involves neglecting parts of the decision space residing beyond salient negative outcomes. However, how the brain implements this important decision heuristic and what underlies individual differences have hitherto remained unanswered. Therefore, we administered an adapted version of the same planning task to healthy male and female volunteers undergoing functional magnetic resonance imaging (fMRI) to determine the neural basis of aversive pruning. Through both computational and standard categorical fMRI analyses, we show that when planning was influenced by aversive pruning, the subgenual cingulate cortex was robustly recruited. This neural signature was distinct from those associated with general planning and valuation, two fundamental cognitive components elicited by our task but which are complementary to aversive pruning. Furthermore, we found that individual variation in levels of aversive pruning was associated with the responses of insula and dorsolateral prefrontal cortices to the receipt of large monetary losses, and also with subclinical levels of anxiety. In summary, our data reveal the neural signatures of an important reflexive Pavlovian process that shapes goal-directed evaluations and thereby determines the outcome of high-level sequential cognitive processes. SIGNIFICANCE STATEMENT Multistep decisions are complex because initial choices constrain future options. Evaluating every path for long decision sequences is often impractical; thus, cognitive shortcuts are often essential. One pervasive and powerful heuristic is aversive pruning, in which potential decision-making avenues are curtailed at immediate negative outcomes. We used neuroimaging to examine how humans implement such pruning. We found it to be associated with activity in the subgenual cingulate cortex, with neural signatures that were distinguishable from those covarying with planning and valuation. Individual variations in aversive pruning levels related to subclinical anxiety levels and insular cortex activation. These findings reveal the neural mechanisms by which basic negative Pavlovian influences guide decision-making during planning, with implications for disrupted decision-making in psychiatric disorders. Copyright © 2017 the authors 0270-6474/17/3710216-15$15.00/0.
Code of Federal Regulations, 2013 CFR
2013-01-01
... plums (fresh prunes), and table grapes for processing; (3) Olives for processing into oil; (4) Grapefruit for animal feed; or (5) Avocados for seed shall obtain an “Importer's Exempt Commodity Form” (FV-6...
Code of Federal Regulations, 2012 CFR
2012-01-01
... plums (fresh prunes), and table grapes for processing; (3) Olives for processing into oil; (4) Grapefruit for animal feed; or (5) Avocados for seed shall obtain an “Importer's Exempt Commodity Form” (FV-6...
Code of Federal Regulations, 2014 CFR
2014-01-01
... plums (fresh prunes), and table grapes for processing; (3) Olives for processing into oil; (4) Grapefruit for animal feed; or (5) Avocados for seed shall obtain an “Importer's Exempt Commodity Form” (FV-6...
Code of Federal Regulations, 2011 CFR
2011-01-01
... plums (fresh prunes), and table grapes for processing; (3) Olives for processing into oil; (4) Grapefruit for animal feed; or (5) Avocados for seed shall obtain an “Importer's Exempt Commodity Form” (FV-6...
Code of Federal Regulations, 2010 CFR
2010-01-01
... plums (fresh prunes), and table grapes for processing; (3) Olives for processing into oil; (4) Grapefruit for animal feed; or (5) Avocados for seed shall obtain an “Importer's Exempt Commodity Form” (FV-6...
21 CFR 150.110 - Fruit butter.
Code of Federal Regulations, 2011 CFR
2011-04-01
..., canned, and/or dried (evaporated) mature fruits, with or without added water, and screening out skins... Apricot 7.0 Grape 7.0 Peach 8.5 Pear 6.5 Plum (other than prune) 7.0 Prune 7.0 Quince 7.5 (2) The...
21 CFR 150.110 - Fruit butter.
Code of Federal Regulations, 2014 CFR
2014-04-01
..., canned, and/or dried (evaporated) mature fruits, with or without added water, and screening out skins... Apricot 7.0 Grape 7.0 Peach 8.5 Pear 6.5 Plum (other than prune) 7.0 Prune 7.0 Quince 7.5 (2) The...
21 CFR 150.110 - Fruit butter.
Code of Federal Regulations, 2013 CFR
2013-04-01
..., canned, and/or dried (evaporated) mature fruits, with or without added water, and screening out skins... Apricot 7.0 Grape 7.0 Peach 8.5 Pear 6.5 Plum (other than prune) 7.0 Prune 7.0 Quince 7.5 (2) The...
Code of Federal Regulations, 2010 CFR
2010-01-01
... the Food Technology Division, College of Agriculture, University of California, for the specialty pack... 7 Agriculture 8 2010-01-01 2010-01-01 false Prunes. 993.5 Section 993.5 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and...
Galati, Vincenzo; Beeson, James H; Confer, Stephen D; Frimberger, Dominic; Campbell, Jeffrey B; Ramji, Faridali G; Kropp, Bradley P
2008-04-01
Patients with severe prune belly syndrome rarely survive beyond the first days of life. We present a case of prune belly syndrome that initially presented with severe oligohydramnios, megacystis and associated poor urine biochemistries. Due to an anteriorly located placenta the patient was referred to three major centers, but was turned down because of the unfavorable prognostic findings. Therefore, fetal intervention was performed with 32 vesicocentesis and amnioinfusion procedures. Despite the unfavorable prenatal findings, and having undergone numerous fetal interventions, the birth resulted in a viable infant.
The association between prune belly syndrome and dental anomalies: a case report
2012-01-01
Background Prune belly syndrome is a rare condition produced by an early mesodermal defect that causes abdominal abnormalities. However, the literature indicates that disturbances related to ectodermal development may also be present. This is the first case report in the literature to suggest that dental abnormalities are part of the broad spectrum of clinical features of prune belly syndrome. Because the syndrome causes many serious medical problems, early diagnosis of abnormalities involving the primary and permanent dentitions are encouraged. Case presentation The authors report the clinical case of a 4-year-old Caucasian boy with prune belly syndrome. In addition to the triad of abdominal muscle deficiency, abnormalities of the gastrointestinal and urinary tracts, and cryptorchidism, a geminated mandibular right central incisor, agenesis of a mandibular permanent left incisor, and congenitally missing primary teeth (namely, the mandibular right and left lateral incisors) were noted. Conclusion This original case report about prune belly syndrome highlights the possibility that dental abnormalities are a part of the broad spectrum of clinical features of the syndrome. Therefore, an accurate intra-oral clinical examination and radiographic evaluation are required for patients with this syndrome in order to provide an early diagnosis of abnormalities involving the primary and permanent dentitions. PMID:23249412
Vecino, X; Devesa-Rey, R; Moldes, A B; Cruz, J M
2014-09-01
The cellulosic fraction of vineyard pruning waste (free of hemicellulosic sugars) was entrapped in calcium alginate beads and evaluated as an eco-friendly adsorbent for the removal of different nutrients and micronutrients (Mg, P, Zn, K, N-NH4, SO4, TN, TC and PO4) from an agroindustrial effluent (winery wastewater). Batch adsorption studies were performed by varying the amounts of cellulosic adsorbent (0.5-2%), sodium alginate (1-5%) and calcium chloride (0.05-0.9M) included in the biocomposite. The optimal formulation of the adsorbent composite varied depending on the target contaminant. Thus, for the adsorption of cationic contaminants (Mg, Zn, K, N-NH4 and TN), the best mixture comprised 5% sodium alginate, 0.05M calcium chloride and 0.5% cellulosic vineyard pruning waste, whereas for removal of anionic compounds (P, SO4 and PO4), the optimal mixture comprised 1% sodium alginate, 0.9M calcium chloride and 0.5% cellulosic vineyard pruning waste. To remove TC from the winery wastewater, the optimal mixture comprised 3% of sodium alginate, 0.475M calcium chloride and 0.5% cellulosic vineyard pruning waste. Copyright © 2014 Elsevier Ltd. All rights reserved.
Holland, Linda Z
2005-07-15
In chordates, the ectoderm is divided into the neuroectoderm and the so-called non-neural ectoderm. In spite of its name, however, the non-neural ectoderm contains numerous sensory cells. Therefore, the term "non-neural" ectoderm should be replaced by "general ectoderm." At least in amphioxus and tunicates and possibly in vertebrates as well, both the neuroectoderm and the general ectoderm are patterned anterior/posteriorly by mechanisms involving retinoic acid and Hox genes. In amphioxus and tunicates the ectodermal sensory cells, which have a wide range of ciliary and microvillar configurations, are mostly primary neurons sending axons to the CNS, although a minority lack axons. In contrast, vertebrate mechanosensory cells, called hair cells, are all secondary neurons that lack axons and have a characteristic eccentric cilium adjacent to a group of microvilli of graded lengths. It has been highly controversial whether the ectodermal sensory cells in the oral siphons of adult tunicates are homologous to vertebrate hair cells. In some species of tunicates, these cells appear to be secondary neurons, and microvillar and ciliary configurations of some of these cells approach those of vertebrate hair cells. However, none of the tunicate cells has all the characteristics of a hair cell, and there is a high degree of variation among ectodermal sensory cells within and between different species. Thus, similarities between the ectodermal sensory cells of any one species of tunicate and craniate hair cells may well represent convergent evolution rather than homology. Copyright 2005 Wiley-Liss, Inc.
Manuel, Martine; Pratt, Thomas; Liu, Min; Jeffery, Glen; Price, David J
2008-01-01
Background The transcription factor Pax6 is expressed by many cell types in the developing eye. Eyes do not form in homozygous loss-of-function mouse mutants (Pax6Sey/Sey) and are abnormally small in Pax6Sey/+ mutants. Eyes are also abnormally small in PAX77 mice expressing multiple copies of human PAX6 in addition to endogenous Pax6; protein sequences are identical in the two species. The developmental events that lead to microphthalmia in PAX77 mice are not well-characterised, so it is not clear whether over- and under-expression of Pax6/PAX6 cause microphthalmia through similar mechanisms. Here, we examined the consequences of over-expression for the eye and its axonal connections. Results Eyes form in PAX77+/+ embryos but subsequently degenerate. At E12.5, we found no abnormalities in ocular morphology, retinal cell cycle parameters and the incidence of retinal cell death. From E14.5 on, we observed malformations of the optic disc. From E16.5 into postnatal life there is progressively more severe retinal dysplasia and microphthalmia. Analyses of patterns of gene expression indicated that PAX77+/+ retinae produce a normal range of cell types, including retinal ganglion cells (RGCs). At E14.5 and E16.5, quantitative RT-PCR with probes for a range of molecules associated with retinal development showed only one significant change: a slight reduction in levels of mRNA encoding the secreted morphogen Shh at E16.5. At E16.5, tract-tracing with carbocyanine dyes in PAX77+/+ embryos revealed errors in intraretinal navigation by RGC axons, a decrease in the number of RGC axons reaching the thalamus and an increase in the proportion of ipsilateral projections among those RGC axons that do reach the thalamus. A survey of embryos with different Pax6/PAX6 gene dosage (Pax6Sey/+, Pax6+/+, PAX77+ and PAX77+/+) showed that (1) the total number of RGC axons projected by the retina and (2) the proportions that are sorted into the ipsilateral and contralateral optic tracts at the optic chiasm vary differently with gene dosage. Increasing dosage increases the proportion projecting ipsilaterally regardless of the size of the total projection. Conclusion Pax6 overexpression does not obviously impair the initial formation of the eye and its major cell-types but prevents normal development of the retina from about E14.5, leading eventually to severe retinal degeneration in postnatal life. This sequence is different to that underlying microphthalmia in Pax6+/- heterozygotes, which is due primarily to defects in the initial stages of lens formation. Before the onset of severe retinal dysplasia, Pax6 overexpression causes defects of retinal axons, preventing their normal growth and navigation through the optic chiasm. PMID:18507827
Lower urinary tract development and disease
Rasouly, Hila Milo; Lu, Weining
2013-01-01
Congenital Anomalies of the Lower Urinary Tract (CALUT) are a family of birth defects of the ureter, the bladder and the urethra. CALUT includes ureteral anomalies such as congenital abnormalities of the ureteropelvic junction (UPJ) and ureterovesical junction (UVJ), and birth defects of the bladder and the urethra such as bladder-exstrophy-epispadias complex (BEEC), prune belly syndrome (PBS), and posterior urethral valves (PUV). CALUT is one of the most common birth defects and is often associated with antenatal hydronephrosis, vesicoureteral reflux (VUR), urinary tract obstruction, urinary tract infections (UTI), chronic kidney disease and renal failure in children. Here, we discuss the current genetic and molecular knowledge about lower urinary tract development and genetic basis of CALUT in both human and mouse models. We provide an overview of the developmental processes leading to the formation of the ureter, bladder, and urethra, and different genes and signaling pathways controlling these developmental processes. Human genetic disorders that affect the ureter, bladder and urethra and associated gene mutations are also presented. As we are entering the post-genomic era of personalized medicine, information in this article may provide useful interpretation for the genetic and genomic test results collected from patients with lower urinary tract birth defects. With evidence-based interpretations, clinicians may provide more effective personalized therapies to patients and genetic counseling for their families. PMID:23408557
7 CFR 993.24 - Establishment and membership.
Code of Federal Regulations, 2010 CFR
2010-01-01
... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... CALIFORNIA Order Regulating Handling Prune Marketing Committee § 993.24 Establishment and membership. A Prune Marketing Committee (herein referred to as the “Committee”), consisting of 22 members with an alternate...
40 CFR 180.578 - Acetamiprid; tolerances for residues.
Code of Federal Regulations, 2010 CFR
2010-07-01
... shelled, subgroup 6B 0.40 Pistachio 0.10 Plum, prune, dried 0.40 Plum, prune, fresh 0.20 Tea, dried1 50.0... 10, 2010, for the use of acetamiprid on dried tea. (2) Tolerances are established for residues of the...
40 CFR 180.578 - Acetamiprid; tolerances for residues.
Code of Federal Regulations, 2011 CFR
2011-07-01
... shelled, subgroup 6B 0.40 Pistachio 0.10 Plum, prune, dried 0.40 Plum, prune, fresh 0.20 Tea, dried1 50.0... 10, 2010, for the use of acetamiprid on dried tea. (2) Tolerances are established for residues of the...
7 CFR 993.54 - Establishment of salable and reserve percentages.
Code of Federal Regulations, 2012 CFR
2012-01-01
... MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Order Regulating Handling Reserve Control § 993.54 Establishment of... that diverted tonnage (dried weight natural condition prune basis) on diversion certificates issued...
7 CFR 993.54 - Establishment of salable and reserve percentages.
Code of Federal Regulations, 2014 CFR
2014-01-01
... MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Order Regulating Handling Reserve Control § 993.54 Establishment of... that diverted tonnage (dried weight natural condition prune basis) on diversion certificates issued...
7 CFR 993.150 - Disposition of prunes by handlers.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Disposition of prunes by handlers. 993.150 Section 993.150 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED...
7 CFR 993.54 - Establishment of salable and reserve percentages.
Code of Federal Regulations, 2013 CFR
2013-01-01
... MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Order Regulating Handling Reserve Control § 993.54 Establishment of... that diverted tonnage (dried weight natural condition prune basis) on diversion certificates issued...
7 CFR 993.150 - Disposition of prunes by handlers.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Disposition of prunes by handlers. 993.150 Section 993.150 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED...
7 CFR 993.54 - Establishment of salable and reserve percentages.
Code of Federal Regulations, 2011 CFR
2011-01-01
... MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Order Regulating Handling Reserve Control § 993.54 Establishment of... that diverted tonnage (dried weight natural condition prune basis) on diversion certificates issued...
7 CFR 993.54 - Establishment of salable and reserve percentages.
Code of Federal Regulations, 2010 CFR
2010-01-01
... MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Order Regulating Handling Reserve Control § 993.54 Establishment of... that diverted tonnage (dried weight natural condition prune basis) on diversion certificates issued...
7 CFR 993.150 - Disposition of prunes by handlers.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Disposition of prunes by handlers. 993.150 Section 993.150 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED...
7 CFR 944.700 - Fresh prune import regulation.
Code of Federal Regulations, 2010 CFR
2010-01-01
... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing....700 Fresh prune import regulation. (a) Pursuant to section 8e of the Agricultural Marketing Agreement... means release from custody of the United States Customs Service. (g) Inspection and certification...
Gutterman, Yitzchak; Chauser-Volfson, Elena
2008-10-01
Aloe arborescens plants, originating from the deserts of South Africa, are grown in the Introduction Garden at Sede Boker in the Negev Desert of Israel. In previous studies, we developed agro-technical methods to raise the content of secondary phenol metabolites (SPhMs) in the Aloe leaves. Plants that are subjected to repeated leaf pruning respond by increasing the content of their SPhMs. The SPhMs found in Aloe arborescens include barbaloin, aloenin and derivatives of aloeresin. Such compounds are used for many purposes, including human skin protection from sun and fire burns and high radiation, as products of the pharmaceutics and cosmetics industries, and as food supplements for treating stomach ulcers and diabetes. In the current study, the SPhMs were separated from pruned leaves of the same A. arborescens plants at the same time by two methods: (1) exudation by squeezing the tissues of the leaves, (2) immersion of the leaves' pruned cut bottom in water and collection of the extract. The exudates and extract were frozen, freeze-dried to a powder and the SPhMs were then separated by chromatography. The yield of powder from water extraction from pruned leaves was much lower than the yield from the exudates. However, higher percentages of the powder from the water extraction contained SPhMs (between 80 and 92.7%). The content of powder in leaf exudates from pruned leaves was much higher because the SPhMs were squeezed out from the cells and tissues. However, the percentages of SPhMs in this powder were much lower (between 39 and 62%).
Whole-plant adjustments in coconut (Cocos nucifera) in response to sink-source imbalance.
Mialet-Serra, I; Clement-Vidal, A; Roupsard, O; Jourdan, C; Dingkuhn, M
2008-08-01
Coconut (Cocos nucifera L.) is a perennial tropical monocotyledon that produces fruit continuously. The physiological function of the large amounts of sucrose stored in coconut stems is unknown. To test the hypothesis that reserve storage and mobilization enable the crop to adjust to variable sink-source relationships at the scale of the whole plant, we investigated the dynamics of dry matter production, yield and yield components, and concentrations of nonstructural carbohydrate reserves in a coconut plantation on Vanuatu Island in the South Pacific. Two treatments were implemented continuously over 29 months (April 2002 to August 2004): 50% leaf pruning (to reduce the source) and 100% fruit and inflorescence pruning (to reduce the sink). The pruning treatments had little effect on carbohydrate reserves because they affected only petioles, not the main reserve pool in the stem. Both pruning treatments greatly reduced dry matter production of the reproductive compartment, but vegetative growth and development were negligibly affected by treatment and season. Leaf pruning increased radiation-use efficiency (RUE) initially, and fruit pruning greatly reduced RUE throughout the experiment. Changes in RUE were negatively correlated with leaflet soluble sugar concentration, indicating feedback inhibition of photosynthesis. We conclude that vegetative development and growth of coconut show little phenotypic plasticity, assimilate demand for growth being largely independent of a fluctuating assimilate supply. The resulting sink-source imbalances were partly compensated for by transitory reserves and, more importantly, by variable RUE in the short term, and by adjustment of fruit load in the long term. Possible physiological mechanisms are discussed, as well as modeling concepts that may be applied to coconut and similar tree crops.
Teotia, Pooja; Chopra, Divyan A; Dravid, Shashank Manohar; Van Hook, Matthew J; Qiu, Fang; Morrison, John; Rizzino, Angie; Ahmad, Iqbal
2017-03-01
Glaucoma is a complex group of diseases wherein a selective degeneration of retinal ganglion cells (RGCs) lead to irreversible loss of vision. A comprehensive approach to glaucomatous RGC degeneration may include stem cells to functionally replace dead neurons through transplantation and understand RGCs vulnerability using a disease in a dish stem cell model. Both approaches require the directed generation of stable, functional, and target-specific RGCs from renewable sources of cells, that is, the embryonic stem cells and induced pluripotent stem cells. Here, we demonstrate a rapid and safe, stage-specific, chemically defined protocol that selectively generates RGCs across species, including human, by recapitulating the developmental mechanism. The de novo generated RGCs from pluripotent cells are similar to native RGCs at the molecular, biochemical, functional levels. They also express axon guidance molecules, and discriminate between specific and nonspecific targets, and are nontumorigenic. Stem Cells 2017;35:572-585. © 2016 AlphaMed Press.
Pivetta, Chiara; Esposito, Maria Soledad; Sigrist, Markus; Arber, Silvia
2014-01-30
Accurate motor-task execution relies on continuous comparison of planned and performed actions. Motor-output pathways establish internal circuit collaterals for this purpose. Here we focus on motor collateral organization between spinal cord and upstream neurons in the brainstem. We used a newly developed mouse genetic tool intersectionally with viruses to uncover the connectivity rules of these ascending pathways by capturing the transient expression of neuronal subpopulation determinants. We reveal a widespread and diverse network of spinal dual-axon neurons, with coincident input to forelimb motor neurons and the lateral reticular nucleus (LRN) in the brainstem. Spinal information to the LRN is not segregated by motor pool or neurotransmitter identity. Instead, it is organized according to the developmental domain origin of the progenitor cells. Thus, excerpts of most spinal information destined for action are relayed to supraspinal centers through exquisitely organized ascending connectivity modules, enabling precise communication between command and execution centers of movement. Copyright © 2014 Elsevier Inc. All rights reserved.
Effects of nitric oxide on neuromuscular properties of developing zebrafish embryos.
Jay, Michael; Bradley, Sophie; McDearmid, Jonathan Robert
2014-01-01
Nitric oxide is a bioactive signalling molecule that is known to affect a wide range of neurodevelopmental processes. However, its functional relevance to neuromuscular development is not fully understood. Here we have examined developmental roles of nitric oxide during formation and maturation of neuromuscular contacts in zebrafish. Using histochemical approaches we show that elevating nitric oxide levels reduces the number of neuromuscular synapses within the axial swimming muscles whilst inhibition of nitric oxide biosynthesis has the opposite effect. We further show that nitric oxide signalling does not change synapse density, suggesting that the observed effects are a consequence of previously reported changes in motor axon branch formation. Moreover, we have used in vivo patch clamp electrophysiology to examine the effects of nitric oxide on physiological maturation of zebrafish neuromuscular junctions. We show that developmental exposure to nitric oxide affects the kinetics of spontaneous miniature end plate currents and impacts the neuromuscular drive for locomotion. Taken together, our findings implicate nitrergic signalling in the regulation of zebrafish neuromuscular development and locomotor maturation.
Developmental expression of VGF mRNA in the prenatal and postnatal rat.
Snyder, S E; Pintar, J E; Salton, S R
1998-04-27
VGF is a developmentally regulated, secretory peptide precursor that is expressed by neurons and neuroendocrine cells and that has its transcription and secretion induced rapidly by neurotrophins and by depolarization. To gain insight into the possible functions and regulation of VGF in vivo, we have characterized the distribution of VGF mRNA in the developing rat nervous system. VGF expression was first detectable at embryonic day 11.5 in the primordia of cranial, sympathetic, and dorsal root ganglia, and its distribution expanded throughout development to include significant expression throughout the brain, spinal cord, and retina of the adult rat. The earliest expression of VGF, therefore, appeared in the peripheral nervous system as developing neurons settled in their designated ganglia. In many regions of the brain, VGF mRNA levels were found to be highest during periods when axonal outgrowth and synaptogenesis predominate. Areas of the central nervous system that contain predominantly dividing cells never displayed any VGF mRNA expression, nor did the vast majority of nonneural tissues.
The mouse F3/contactin glycoprotein
Bizzoca, Antonella; Corsi, Patrizia
2009-01-01
F3/Contactin is an immunoglobulin superfamily component expressed in the nervous tissue of several species. Here we focus on the structural and functional properties of its mouse relative, on the mechanisms driving its regulated expression and on its developmental role. F3/Contactin is differentially expressed in distinct populations of central and peripheral neurons and in some non-neuronal cells. Accordingly, the regulatory region of the underlying gene includes promoter elements undergoing differential activation, associated with an intricate splicing profile, indicating that transcriptional and posttranscriptional mechanisms contribute to its expression. Transgenic models allowed to follow F3/Contactin promoter activation in vivo and to modify F3/Contactin gene expression under a heterologous promoter, which resulted in morphological and functional phenotypes. Besides axonal growth and pathfinding, these concerned earlier events, including precursor proliferation and commitment. This wide role in neural ontogenesis is consistent with the recognized interaction of F3/Contactin with developmental control genes belonging to the Notch pathway. PMID:19372728
Ozernov-Palchik, Ola; Gaab, Nadine
2016-01-01
Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5–17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in prereading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure. PMID:26836227
7 CFR 993.22 - Consumer package.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Consumer package. 993.22 Section 993.22 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... weight of mixed dried fruit in the lot consists of standard processed prunes or standard prunes. ...
7 CFR 993.22 - Consumer package.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Consumer package. 993.22 Section 993.22 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... weight of mixed dried fruit in the lot consists of standard processed prunes or standard prunes. ...
7 CFR 944.700 - Fresh prune import regulation.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 8 2011-01-01 2011-01-01 false Fresh prune import regulation. 944.700 Section 944.700 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE FRUITS; IMPORT REGULATIONS § 944...
7 CFR 944.700 - Fresh prune import regulation.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 8 2012-01-01 2012-01-01 false Fresh prune import regulation. 944.700 Section 944.700 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE FRUITS; IMPORT REGULATIONS § 944...
7 CFR 944.700 - Fresh prune import regulation.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 8 2014-01-01 2014-01-01 false Fresh prune import regulation. 944.700 Section 944.700 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE FRUITS; IMPORT REGULATIONS § 944...
7 CFR 944.700 - Fresh prune import regulation.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 8 2013-01-01 2013-01-01 false Fresh prune import regulation. 944.700 Section 944.700 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE FRUITS; IMPORT REGULATIONS § 944...
The Effects of Predictability on Stress and Immune Function
1993-06-24
number of cups ______________ _ Chocolate, cocoa, wine, beer/alcohol, decaffeinated coffee. Breads containing raisins, prunes, orange peel , banana or...pudding,. mince pie ••••• ) Banana , avocado, pineapple, canned figs, raisins, plums and prune •• Orange., orange juice, fruit cocktail with pineapple
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Reports. 924.60 Section 924.60 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... carrier transporting such prunes; and (4) the destination of each shipment of such prunes. (b) All such...
Epicormic branching on pruned white fir
Richard D. Cosens
1952-01-01
Epicormic branches have developed on white fir (Abies concolor) one to two years after part of the live limbs were removed in a pruning experiment. The appearance of an average of six epicormic sprouts per tree raises some doubt as to the desirability of planting this species.
REM sleep selectively prunes and maintains new synapses in development and learning
Li, Wei; Ma, Lei; Yang, Guang; Gan, Wenbiao
2017-01-01
The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly-formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation in development and when a new motor task is learned, indicating a role of REM sleep in pruning to balance the number of new spines formed over time. In addition, REM sleep also strengthens and maintains some newly-formed spines that are critical for neuronal circuit development and behavioral improvement after learning. We further show that dendritic calcium spikes arising during REM sleep are important for pruning and strengthening of new spines. Together, these findings indicate that REM sleep has multifaceted functions in brain development, learning, and memory consolidation by selectively eliminating and maintaining newly-formed synapses via dendritic calcium spike-dependent mechanisms. PMID:28092659
Partial polygon pruning of hydrographic features in automated generalization
Stum, Alexander K.; Buttenfield, Barbara P.; Stanislawski, Larry V.
2017-01-01
This paper demonstrates a working method to automatically detect and prune portions of waterbody polygons to support creation of a multi-scale hydrographic database. Water features are known to be sensitive to scale change; and thus multiple representations are required to maintain visual and geographic logic at smaller scales. Partial pruning of polygonal features—such as long and sinuous reservoir arms, stream channels that are too narrow at the target scale, and islands that begin to coalesce—entails concurrent management of the length and width of polygonal features as well as integrating pruned polygons with other generalized point and linear hydrographic features to maintain stream network connectivity. The implementation follows data representation standards developed by the U.S. Geological Survey (USGS) for the National Hydrography Dataset (NHD). Portions of polygonal rivers, streams, and canals are automatically characterized for width, length, and connectivity. This paper describes an algorithm for automatic detection and subsequent processing, and shows results for a sample of NHD subbasins in different landscape conditions in the United States.
NASA Astrophysics Data System (ADS)
Muslim, M. A.; Herowati, A. J.; Sugiharti, E.; Prasetiyo, B.
2018-03-01
A technique to dig valuable information buried or hidden in data collection which is so big to be found an interesting patterns that was previously unknown is called data mining. Data mining has been applied in the healthcare industry. One technique used data mining is classification. The decision tree included in the classification of data mining and algorithm developed by decision tree is C4.5 algorithm. A classifier is designed using applying pessimistic pruning in C4.5 algorithm in diagnosing chronic kidney disease. Pessimistic pruning use to identify and remove branches that are not needed, this is done to avoid overfitting the decision tree generated by the C4.5 algorithm. In this paper, the result obtained using these classifiers are presented and discussed. Using pessimistic pruning shows increase accuracy of C4.5 algorithm of 1.5% from 95% to 96.5% in diagnosing of chronic kidney disease.
Fusaoka, Eri; Inoue, Takeshi; Mineta, Katsuhiko; Agata, Kiyokazu; Takeuchi, Kosei
2006-05-01
Precise wiring and proper remodeling of the neural network are essential for its normal function. The freshwater planarian is an attractive animal in which to study the formation and maintenance of the neural network due to its high regenerative capability and developmental plasticity. Although a recent study revealed that homologs of netrin and its receptors are required for regeneration and maintenance of the planarian central nervous system (CNS), the roles of cell adhesion in the formation and maintenance of the planarian neural network remain poorly understood. In the present study, we found primitive immunoglobulin superfamily cell adhesion molecules (IgCAMs) in a planarian that are homologous to vertebrate neural IgCAMs. We identified planarian orthologs of NCAM, L1CAM, contactin and DSCAM, and designated them DjCAM, DjLCAM, DjCTCAM and DjDSCAM, respectively. We further confirmed that they function as cell adhesion molecules using cell aggregation assays. DjCAM and DjDSCAM were found to be differentially expressed in the CNS. Functional analyses using RNA interference revealed that DjCAM is partly involved in axon formation, and that DjDSCAM plays crucial roles in neuronal cell migration, axon outgrowth, fasciculation and projection.
Schratt, Gerhard M; Nigh, Elizabeth A; Chen, Wen G; Hu, Linda; Greenberg, Michael E
2004-08-18
Local regulation of mRNA translation plays an important role in axon guidance, synaptic development, and neuronal plasticity. Little is known, however, regarding the mechanisms that control translation in neurons, and only a few mRNAs have been identified that are locally translated within axon and dendrites. Using Affymetrix gene arrays to identify mRNAs that are newly associated with polysomes after exposure to BDNF, we identified subsets of mRNAs for which translation is enhanced in neurons at different developmental stages. In mature neurons, many of these mRNAs encode proteins that are known to function at synapses, including CamKIIalpha, NMDA receptor subunits, and the postsynaptic density (PSD) scaffolding protein Homer2. BDNF regulates the translation of Homer2 locally in the synaptodendritic compartment by activating translational initiation via a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway. These findings suggest that BDNF likely regulates synaptic function by inducing the local synthesis of numerous synaptic proteins. The local translation of the cytoskeleton-associated protein Homer2 in particular might have important implications for growth cone dynamics and dendritic spine development.
The retina as a window to the brain-from eye research to CNS disorders.
London, Anat; Benhar, Inbal; Schwartz, Michal
2013-01-01
Philosophers defined the eye as a window to the soul long before scientists addressed this cliché to determine its scientific basis and clinical relevance. Anatomically and developmentally, the retina is known as an extension of the CNS; it consists of retinal ganglion cells, the axons of which form the optic nerve, whose fibres are, in effect, CNS axons. The eye has unique physical structures and a local array of surface molecules and cytokines, and is host to specialized immune responses similar to those in the brain and spinal cord. Several well-defined neurodegenerative conditions that affect the brain and spinal cord have manifestations in the eye, and ocular symptoms often precede conventional diagnosis of such CNS disorders. Furthermore, various eye-specific pathologies share characteristics of other CNS pathologies. In this Review, we summarize data that support examination of the eye as a noninvasive approach to the diagnosis of select CNS diseases, and the use of the eye as a valuable model to study the CNS. Translation of eye research to CNS disease, and deciphering the role of immune cells in these two systems, could improve our understanding and, potentially, the treatment of neurodegenerative disorders.
Kerlin, Aaron M; Lindsley, Tara A
2008-08-15
Time-lapse imaging of living neurons both in vivo and in vitro has revealed that the growth of axons and dendrites is highly dynamic and characterized by alternating periods of extension and retraction. These growth dynamics are associated with important features of neuronal development and are differentially affected by experimental treatments, but the underlying cellular mechanisms are poorly understood. NeuroRhythmics was developed to semi-automate specific quantitative tasks involved in analysis of two-dimensional time-series images of processes that exhibit saltatory elongation. This software provides detailed information on periods of growth and nongrowth that it identifies by transitions in elongation (i.e. initiation time, average rate, duration) and information regarding the overall pattern of saltatory growth (i.e. time of pattern onset, frequency of transitions, relative time spent in a state of growth vs. nongrowth). Plots and numeric output are readily imported into other applications. The user has the option to specify criteria for identifying transitions in growth behavior, which extends the potential application of the software to neurons of different types or developmental stage and to other time-series phenomena that exhibit saltatory dynamics. NeuroRhythmics will facilitate mechanistic studies of periodic axonal and dendritic growth in neurons.
Zielinski, B.S.; Fredricks, Keith; McDonald, R.; Zaidi, A.U.
2005-01-01
This study examined olfactory sensory neuron morphology and physiological responsiveness in newly hatched sea lamprey, Petromyzon marinus L. These prolarvae hatch shortly after neural tube formation, and stay within nests for approximately 18 days, before moving downstream to silty areas where they burrow, feed and pass to the larval stage. To explore the possibility that the olfactory system is functioning during this prolarval stage, morphological and physiological development of olfactory sensory neurons was examined. The nasal cavity contained an olfactory epithelium with ciliated olfactory sensory neurons. Axons formed aggregates in the basal portion of the olfactory epithelium and spanned the narrow distance between the olfactory epithelium and the brain. The presence of asymmetric synapses with agranular vesicles within fibers in the brain, adjacent to the olfactory epithelium suggests that there was synaptic connectivity between olfactory sensory axons and the brain. Neural recordings from the surface of the olfactory epithelium showed responses following the application of L-arginine, taurocholic acid, petromyzonol sulfate (a lamprey migratory pheromone), and water conditioned by conspecifics. These results suggest that lampreys may respond to olfactory sensory input during the prolarval stage. ?? 2006 Springer Science + Business Media, LLC.
N-CADHERIN PRODOMAIN CLEAVAGE REGULATES SYNAPSE FORMATION IN VIVO
Latefi, Nazlie S.; Pedraza, Liliana; Schohl, Anne; Li, Ziwei; Ruthazer, Edward S.
2009-01-01
Cadherins are initially synthesized bearing a prodomain that is thought to limit adhesion during early stages of biosynthesis. Functional cadherins lack this prodomain, raising the intriguing possibility that cells may utilize prodomain cleavage as a means to temporally or spatially regulate adhesion after delivery of cadherin to the cell surface. In support of this idea, immunostaining for the prodomain of zebrafish N-cadherin revealed enriched labeling at neuronal surfaces at the soma and along axonal processes. To determine whether post-translational cleavage of the prodomain affects synapse formation, we imaged Rohon-Beard cells in zebrafish embryos expressing GFP-tagged wild-type N-cadherin (NCAD-GFP) or a GFP-tagged N-cadherin mutant expressing an uncleavable prodomain (PRON-GFP) rendering it non-adhesive. NCAD-GFP accumulated at synaptic microdomains in a developmentally regulated manner, and its overexpression transiently accelerated synapse formation. PRON-GFP was much more diffusely distributed along the axon and its overexpression delayed synapse formation. Our results support the notion that N-cadherin serves to stabilize pre- to postsynaptic contacts early in synapse development and suggests that regulated cleavage of the N-cadherin prodomain may be a mechanism by which the kinetics of synaptogenesis are regulated. PMID:19365814
Activation of EGF receptor kinase by L1-mediated homophilic cell interactions.
Islam, Rafique; Kristiansen, Lars V; Romani, Susana; Garcia-Alonso, Luis; Hortsch, Michael
2004-04-01
Neural cell adhesion molecules (CAMs) are important players during neurogenesis and neurite outgrowth as well as axonal fasciculation and pathfinding. Some of these developmental processes entail the activation of cellular signaling cascades. Pharmacological and genetic evidence indicates that the neurite outgrowth-promoting activity of L1-type CAMs is at least in part mediated by the stimulation of neuronal receptor tyrosine kinases (RTKs), especially FGF and EGF receptors. It has long been suspected that neural CAMs might physically interact with RTKs, but their activation by specific cell adhesion events has not been directly demonstrated. Here we report that gain-of-function conditions of the Drosophila L1-type CAM Neuroglian result in profound sensory axon pathfinding defects in the developing Drosophila wing. This phenotype can be suppressed by decreasing the normal gene dosage of the Drosophila EGF receptor gene. Furthermore, in Drosophila S2 cells, cell adhesion mediated by human L1-CAM results in the specific activation of human EGF tyrosine kinase at cell contact sites and EGF receptors engage in a physical interaction with L1-CAM molecules. Thus L1-type CAMs are able to promote the adhesion-dependent activation of EGF receptor signaling in vitro and in vivo.
Grammatical complexity for two-dimensional maps
NASA Astrophysics Data System (ADS)
Hagiwara, Ryouichi; Shudo, Akira
2004-11-01
We calculate the grammatical complexity of the symbol sequences generated from the Hénon map and the Lozi map using the recently developed methods to construct the pruning front. When the map is hyperbolic, the language of symbol sequences is regular in the sense of the Chomsky hierarchy and the corresponding grammatical complexity takes finite values. It is found that the complexity exhibits a self-similar structure as a function of the system parameter, and the similarity of the pruning fronts is discussed as an origin of such self-similarity. For non-hyperbolic cases, it is observed that the complexity monotonically increases as we increase the resolution of the pruning front.
Differential effects of myostatin deficiency on motor and sensory axons.
Jones, Maria R; Villalón, Eric; Northcutt, Adam J; Calcutt, Nigel A; Garcia, Michael L
2017-12-01
Deletion of myostatin in mice (MSTN -/- ) alters structural properties of peripheral axons. However, properties like axon diameter and myelin thickness were analyzed in mixed nerves, so it is unclear whether loss of myostatin affects motor, sensory, or both types of axons. Using the MSTN -/- mouse model, we analyzed the effects of increasing the number of muscle fibers on axon diameter, myelin thickness, and internode length in motor and sensory axons. Axon diameter and myelin thickness were increased in motor axons of MSTN -/- mice without affecting internode length or axon number. The number of sensory axons was increased without affecting their structural properties. These results suggest that motor and sensory axons establish structural properties by independent mechanisms. Moreover, in motor axons, instructive cues from the neuromuscular junction may play a role in co-regulating axon diameter and myelin thickness, whereas internode length is established independently. Muscle Nerve 56: E100-E107, 2017. © 2017 Wiley Periodicals, Inc.
Root Pruning of Mahogany Nursery Stock
R. W. Nobles; C. B. Briscoe
1966-01-01
Root pruning had no effect on growth or survival of either young or held-over mahogany nursery stock. Potted mahogany seedlings may be held in the nursery an extra year or more without reducing-either growth or survival following outplanting. Growth may be slightly better for the older stock.
7 CFR 81.17 - Death, incompetency, or disappearance.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 3 2010-01-01 2010-01-01 false Death, incompetency, or disappearance. 81.17 Section... DOMESTIC CONSUMPTION PROGRAMS PRUNE/DRIED PLUM DIVERSION PROGRAM § 81.17 Death, incompetency, or disappearance. In the case of death, incompetency, disappearance, or dissolution of a prune/plum producer that...
Tagore, Koyye Ravindranath; Ramineni, Asok Kumar S.; Vijaya Lakshmi, A. R.; N., Bhavani
2011-01-01
Prune belly syndrome is a rare congenital disorder of the urinary system, characterized by a triad of abnormalities. The aetiology is not known. Many infants are either stillborn or die within the first few weeks of life from severe lung or kidney problems, or a combination of congenital anomalies. PMID:22606508
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Handle. 993.13 Section 993.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and..., or ship (except as a carrier of prunes owned by another person), or in any other way to place prunes...
7 CFR 993.106 - In-line inspection.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false In-line inspection. 993.106 Section 993.106 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... means inspection of prunes where samples are drawn from a flow of prunes prior to packaging. Effective...
7 CFR 993.504 - In-line inspection.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false In-line inspection. 993.504 Section 993.504 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... inspection of prunes where samples are drawn from a flow of prunes prior to packaging. Effective Date Note...
78 FR 63128 - Dried Prunes Produced in California; Increased Assessment Rate
Federal Register 2010, 2011, 2012, 2013, 2014
2013-10-23
...; Increased Assessment Rate AGENCY: Agricultural Marketing Service, USDA. ACTION: Proposed rule. SUMMARY: This... the Regulatory Flexibility Act (RFA) (5 U.S.C. 601-612), the Agricultural Marketing Service (AMS) has... prunes. Dated: October 17, 2013. Rex A. Barnes, Associate Administrator, Agricultural Marketing Service...
7 CFR 81.17 - Death, incompetency, or disappearance.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 3 2013-01-01 2013-01-01 false Death, incompetency, or disappearance. 81.17 Section... DOMESTIC CONSUMPTION PROGRAMS PRUNE/DRIED PLUM DIVERSION PROGRAM § 81.17 Death, incompetency, or disappearance. In the case of death, incompetency, disappearance, or dissolution of a prune/plum producer that...
7 CFR 81.17 - Death, incompetency, or disappearance.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 3 2014-01-01 2014-01-01 false Death, incompetency, or disappearance. 81.17 Section... DOMESTIC CONSUMPTION PROGRAMS PRUNE/DRIED PLUM DIVERSION PROGRAM § 81.17 Death, incompetency, or disappearance. In the case of death, incompetency, disappearance, or dissolution of a prune/plum producer that...
7 CFR 81.17 - Death, incompetency, or disappearance.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 3 2012-01-01 2012-01-01 false Death, incompetency, or disappearance. 81.17 Section... DOMESTIC CONSUMPTION PROGRAMS PRUNE/DRIED PLUM DIVERSION PROGRAM § 81.17 Death, incompetency, or disappearance. In the case of death, incompetency, disappearance, or dissolution of a prune/plum producer that...
7 CFR 81.17 - Death, incompetency, or disappearance.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 3 2011-01-01 2011-01-01 false Death, incompetency, or disappearance. 81.17 Section... DOMESTIC CONSUMPTION PROGRAMS PRUNE/DRIED PLUM DIVERSION PROGRAM § 81.17 Death, incompetency, or disappearance. In the case of death, incompetency, disappearance, or dissolution of a prune/plum producer that...
Sundaresan, Srividya; Kong, Jee-Hyun; Fang, Qing; Salles, Felipe T.; Wangsawihardja, Felix; Ricci, Anthony J.; Mustapha, Mirna
2016-01-01
Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell dwarf mouse (Pit1dw) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1dw mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1dw IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1dw IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1dw IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses. PMID:26386265
7 CFR 52.3182 - Varietal types of dried prunes.
Code of Federal Regulations, 2011 CFR
2011-01-01
... MARKETING ACT OF 1946 PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Dried Prunes Product Description, Varietal... of French and Robe. (b) Type II. Italian. (c) Type III. Imperial; or Sugar; or a mixture of Imperial...
7 CFR 52.3182 - Varietal types of dried prunes.
Code of Federal Regulations, 2012 CFR
2012-01-01
... MARKETING ACT OF 1946 PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Dried Prunes Product Description, Varietal... of French and Robe. (b) Type II. Italian. (c) Type III. Imperial; or Sugar; or a mixture of Imperial...
Criteria for Pruning Academic Programs: Actual vs. Ideal. ASHE 1988 Annual Meeting Paper.
ERIC Educational Resources Information Center
Ross, Cynthia S.; Gardiner, John J.
Two decades following the publication of David G. Brown's "Criteria for Pruning Programs," (which recognized that traditional financial support to higher education was decreasing and proposed 10 guidelines for evaluating existing programs) a study was developed to determine what criteria are actually being used by comprehensive…
Chemical root pruning of conifer seedlings in Mexico
Arnulfo Aldrete; John G. Mexal
2002-01-01
Many countries grow seedlings for reforestation in polybags where root spiraling and root egression can decrease seedling survival and growth following outplanting. The overall objectives of this study were to investigate the effect of chemical root pruning on root spiraling, root egression, and nursery performance of Pinus pseudostrobus, P...
76 FR 53813 - Dried Prunes Produced in California; Decreased Assessment Rate
Federal Register 2010, 2011, 2012, 2013, 2014
2011-08-30
... DEPARTMENT OF AGRICULTURE Agricultural Marketing Service 7 CFR Part 993 [Doc. No. AMS-FV-11-0068... Marketing Service, USDA. ACTION: Interim rule with request for comments. SUMMARY: This rule decreases the assessment rate established for the Prune Marketing Committee (Committee) for the 2011-12 and subsequent crop...
75 FR 67607 - Dried Prunes Produced in California; Increased Assessment Rate
Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-03
... Order 12988, Civil Justice Reform. Under the marketing order now in effect, California dried prune... DEPARTMENT OF AGRICULTURE Agricultural Marketing Service 7 CFR Part 993 [Doc. No. AMS-FV-10-0057... Marketing Service, USDA. ACTION: Final rule. SUMMARY: This rule increases the assessment rate established...
Code of Federal Regulations, 2011 CFR
2011-01-01
..., quality, and maturity of avocados, grapefruit, nectarines, oranges, prune variety plums (fresh prunes... designated as a governmental inspection service for the purpose of certifying grade, size, quality and... New Mexico, Officer In Charge, New Mexico Market and Development Branch, New Mexico Department of...
7 CFR 52.3185 - Moisture limits.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 2 2012-01-01 2012-01-01 false Moisture limits. 52.3185 Section 52.3185 Agriculture... United States Standards for Grades of Dried Prunes Moisture, Uniformity of Size, Defects § 52.3185 Moisture limits. Dried prunes shall not exceed the moisture limits for the applicable grades and kind and...
7 CFR 52.3185 - Moisture limits.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 2 2013-01-01 2013-01-01 false Moisture limits. 52.3185 Section 52.3185 Agriculture... CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Dried Prunes Moisture, Uniformity of Size, Defects § 52.3185 Moisture limits. Dried prunes shall not exceed the moisture limits for...
7 CFR 52.3185 - Moisture limits.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 2 2014-01-01 2014-01-01 false Moisture limits. 52.3185 Section 52.3185 Agriculture... CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Dried Prunes Moisture, Uniformity of Size, Defects § 52.3185 Moisture limits. Dried prunes shall not exceed the moisture limits for...
7 CFR 993.21d - Reserve prunes.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 8 2010-01-01 2010-01-01 false Reserve prunes. 993.21d Section 993.21d Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... percentage established by the Secretary pursuant to § 993.54. [30 FR 9798, Aug. 6, 1965] Effective Date Note...
7 CFR 52.3187 - Definitions and explanations of defects.
Code of Federal Regulations, 2011 CFR
2011-01-01
... flesh, or both, of the prune. (h) Insect injury. “Insect injury” means healed or unhealed surface..., edibility, or keeping quality of the prune but which do not possess evidence of insect infestation. (i..., twigs, pieces of wood, and similar extraneous materials which are objectionable. (m) Insect infestation...
Three-dimensional reconstruction of fruit trees by a shape from silhouette method
USDA-ARS?s Scientific Manuscript database
In order to robotically prune a dormant fruit tree, the branches must be identified in a three-dimensional space. Furthermore, the branches need to be measured in order to determine which branches should be pruned. Both the identification and measurement of branches can be accomplished by generati...
Heinrich, J E; Nordeen, K W; Nordeen, E J
2005-03-01
Several instances of early learning coincide with significant rearrangements of neural connections in regions contributing to these behaviors. In fact developmentally restricted learning may be constrained temporally by the opportunity for experience to selectively maintain appropriate synapses amidst the elimination of exuberant connections. Consistent with this notion, during the normal sensitive period for vocal learning in zebra finches (Taenopygia guttata), there is a decline in the density of dendritic spines within a region essential for song development, the lateral magnocellular nucleus of the anterior nidopallium (lMAN). Moreover, in birds isolated from conspecific song shortly after hatching, both the closure of the sensitive period for vocal learning and the pruning of spines from lMAN neurons is delayed. Here, we employed a more subtle form of deprivation to delay the close of the sensitive period for song learning, and found that late song learning occurred without obvious alterations in the pruning of dendritic spines on lMAN neurons. At posthatch day (PHD) 65 (beyond the end of the normal sensitive period for song memorization in zebra finches), birds isolated from song beginning on PHD30 did not differ from normally reared birds in measures of dendritic spine density on Golgi-Cox stained lMAN neurons. Moreover, tutor exposure from PHD65 to 90 did not increase spine elimination in these isolates (who memorized new song material) relative to controls (who did not). Thus, we conclude that the extent of normally occurring lMAN spine loss is not sufficient to account for the timing of the sensitive period for zebra finch song learning.