bluuebunny/crossref_metadata_2025 huggingface dataset:
Facioscapulohumeral muscular dystrophy region gene-1 (FRG-1) is an actin-bundling protein associated with muscle-attachment sites
Authors: Liu Qian , Jones Takako Iida , Tang Vivian W. , Brieher William M. , Jones Peter L.
Published: March 2010

In vertebrates, overexpression of facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) recapitulates the pathophysiology exhibited by FSHD patients, although the role of FRG1 in FSHD remains controversial and no precise function for FRG1 has been described in any organism. To gain insight into the function and potential role of FRG1 in FSHD, we analyzed the highly conserved Caenorhabditis elegans ortholog, frg-1. C. elegans body-wall muscles contain two distinct subcellular pools of FRG-1: nuclear FRG-1, concentrated in the nucleoli; and cytoplasmic FRG-1, associated with the Z-disk and costamere-like structures known as dense bodies. Functionally, we demonstrate that FRG-1 is an F-actin-bundling protein, consistent with its localization to dense bodies; this activity is conserved in human FRG1. This is particularly intriguing because it places FRG-1 along side the list of dense-body components whose vertebrate orthologs are involved in the myriad myopathies associated with disrupted costameres and Z-disks. Interestingly, overexpressed FRG-1 preferentially accumulates in the nucleus and, when overexpressed specifically from the frg-1 promoter, disrupts the adult ventral muscle structure and organization. Together, these data further support a role for FRG1 overexpression in FSHD pathophysiology and reveal the previously unsuspected direct involvement of FRG-1 in muscle structure and integrity.
HGF-induced invasion by prostate tumor cells requires anterograde lysosome trafficking and activity of Na+-H+ exchangers
Authors: Steffan Joshua J. , Williams Brittany C. , Welbourne Tomas , Cardelli James A.
Published: March 2010

Hepatocyte growth factor (HGF) is found in tumor microenvironments, and interaction with its tyrosine kinase receptor Met triggers cell invasion and metastasis. It was previously shown that acidic extracellular pH stimulated peripheral lysosome trafficking, resulting in increased cathepsin B secretion and tumor cell invasion, which was dependent upon sodium-proton exchanger (NHE) activity. We now demonstrate that HGF induced the trafficking of lysosomes to the cell periphery, independent of HGF-induced epithelial-mesenchymal transition. HGF-induced anterograde lysosome trafficking depended upon the PI3K pathway, microtubules and RhoA, resulting in increased cathepsin B secretion and invasion by the cells. HGF-induced NHE activity via increased net acid production, and inhibition of NHE activity with 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), or a combination of the NHE1-specific drug cariporide and the NHE3-specific drug s3226 prevented HGF-induced anterograde trafficking and induced retrograde trafficking in HGF-overexpressing cells. EIPA treatment reduced cathepsin B secretion and HGF-induced invasion by the tumor cells. Lysosomes were located more peripherally in Rab7-shRNA-expressing cells and these cells were more invasive than control cells. Overexpression of the Rab7 effector protein, RILP, resulted in a juxtanuclear location of lysosomes and reduced HGF-induced invasion. Together, these results suggest that the location of lysosomes is an inherently important aspect of invasion by tumor cells.
Psychometric properties of a brief inventory for the screening of personality disorders: The SCATI
Authors: Coolidge Frederick L. , Segal Daniel L. , Cahill Brian S. , Simenson Jeremy T.
Published: March 2010

The purpose of the present study was to report on the psychometric properties of a revised version of a brief inventory designed to screen and assess personality disorders. The short form of the Coolidge Axis II Inventory (SCATI) is a 70‐item, self‐report, form of the 250‐item Coolidge Axis II Inventory (CATI). On a community sample of 588 adults (range=16–88 years), the median internal scale reliability for the 14 personality disorder scales was .66, and the median test–retest reliability (1 week) was .83. Principal components analysis (PCA) revealed a four‐component structure, essentially similar to previous PCA studies of the SCATI and CATI. Good convergent validity was obtained between a five‐factor model of psychopathology and the 14 SCATI personality disorder scales. Gender differences were obtained on some scales, although the effect sizes were generally small. These preliminary psychometric properties establish that the SCATI has sufficient reliability and validity to warrant further research, particularly in clinical samples.
Tetradehydrodinaphtho[10]annulene and its transformation into zethrene: A hitherto unknown dehydroannulene and a forgotten aromatic hydrocarbon
Authors: Umeda Rui , Hibi Daijiro , Miki Koji , Tobe Yoshito
Published: March 2010

The synthesis and structural characterization of a hitherto unknown tetradehydro-dinaphtho[10]annulene, which had eluded isolation since attempts initiated during the late 1960s, was achieved. Moreover, the dehydroannulene was transformed into stable derivatives of zethrene, which was first reported in 1955, but forgotten for a long time. These molecules are substituted at the 7,14-positions and open the door to the zethrene family for potential application as optoelectronic materials.
Geometric conditions on three-dimensional CR submanifolds in S
6
Authors: Djorić Mirjana , Vrancken Luc
Published: March 2010

A six-dimensional unit sphere has an almost complex structure J defined by the vector cross product on the space of purely imaginary Cayley numbers, which makes S
6 a nearly Kähler manifold. In this paper, we study 3-dimensional CR submanifolds of S
6(1), investigating certain geometric conditions. We show that if such a submanifold attains equality in Chen's inequality, it is always minimal. We recall that a classification of minimal 3-dimensional submanifolds was obtained in [Djorić, Vrancken, J. Geom. Phys. 56: 2279–2288, 2006].

For 3-dimensional CR submanifolds, the restriction of the almost complex structure J to the tangent space automatically induces an almost contact structure on the submanifold. We prove that this structure is not Sasakian with respect to the induced metric. We also give an example from [Hashimoto, Mashimo, J. Math. 28: 579–591, 2005], see also [Ejiri, Trans. Amer. Math. Soc. 297: 105–124, 1986], of a tube around a superminimal almost complex curve in S
6(1) for which this almost contact structure is Sasakian with respect to a constant scalar multiple of the induced metric.
On line arrangements with applications to 3-nets
Authors: Urzúa Giancarlo
Published: March 2010

We show a one-to-one correspondence between arrangements of d lines in ℙ2, and lines in ℙ
d–2. We apply this correspondence to classify (3, q)-nets over ℂ for all q ≤ 6. When q = 6, we have twelve possible combinatorial cases, but we prove that only nine of them are realizable over ℂ. This new case shows several new properties for 3-nets: different dimensions for moduli, strict realization over certain fields, etc. We also construct a three-dimensional family of (3, 8)-nets corresponding to the quaternion group.
The DNA Inequality in non-convex regions
Authors: Larson Eric
Published: March 2010

A simple plane closed curve Γ satisfies the DNA Inequality if the average curvature of any closed curve contained inside Γ exceeds the average curvature of Γ. In 1997 Lagarias and Richardson proved that all convex curves satisfy the DNA Inequality and asked whether this is true for some non-convex curve. They conjectured that the DNA Inequality holds for certain L-shaped curves. In this paper, we disprove this conjecture for all L-shapes and construct a large class of non-convex curves for which the DNA Inequality holds. We also give a polynomial-time procedure for determining whether any specific curve in a much larger class satisfies the DNA Inequality.
On characterizing the long-root geometries
Authors: Shult Ernest
Published: March 2010

The long-root geometries of symplectic rank at least three are the polar Grassmannians of lines, the metasymplectic spaces, and three Lie incidence geometries of exceptional Lie type. These geometries were characterized as a class of parapolar spaces of symplectic rank at least three satisfying four axioms (see Theorem 1 below). In this note, it is shown that one can dispense with two of the axioms, if one adds to the set of conclusion geometries all strong parapolar spaces of point-diameter 2 for which x
⊥ ∩ S is never a point for any point-symplecton pair (x, S). Connections with root filtration spaces are discussed.
Existence of spin structures on flat four-manifolds
Authors: Putrycz Bartosz , Szczepański Andrzej
Published: March 2010

We prove that all but 3 of the 27 closed, orientable, flat, four-dimensional manifolds have a spin structure.
Die Internationalität nationaler Literaturen: Das anglo-amerikanische Beispiel im 19. Jahrhundert
Authors: Frank Armin Paul
Published: March 2010

Both inter-literary and translational transfer contributed to the making of a distinctive English-language literature in British America and the early United States. Writers residing in America either kept the Britain-based Atlantic reading culture homogeneous by catering to the British reading tastes of many immigrants or, by means of “deviating responses” to eminent British works, helped to bring about an “Americanizing” dissociation. – We need a conceptual frame of reference for this kind of historical study. Americans who studied at German universities, German immigrants, and American literati working from their own country gave nineteenth-century American literary culture a recognizably German dimension.
Transfer and Integration of Latin and Vernacular Drama in the Early Modern Period. The case of Everyman, Elckerlijc, Homulus and Hecastus
Authors: Bloemendal Jan
Published: March 2010

The Dutch morality play Elckerlijc, written at the end of the fifteenth century, and its translations and adaptations into English and Latin, may add some new insight into the role of systems and polysystems in the early modern period. It also modifies the concept of foreign literature, since Latin and vernacular literatures written within one country influenced each other intricately. Thus, the international Latin Republic of Letters was foreign in its use of another language, but it was common in the use of the same subjects, motifs and structures.
Foreign Literatures in National Media. Comparing the International Focus of Literary Coverage in Europe and the United States, 1955 – 2005
Authors: Janssen Susanne
Published: March 2010

This article examines key developments and cross-national variations in the coverage of foreign literatures in U.S., Dutch, French, and German elite newspapers between 1955 and 2005. Such coverage is indicative of the interest in foreign literatures among literary mediators and readers and the degree and direction of “globalization from within.” Using content analysis, the degree, direction, and diversity of the international orientation of literary journalism are charted for each country. The results indicate that the degree of international orientation is inversely related to the centrality of a country's literary production. Results show a clear internationalization of literary coverage in the French newspapers, which coincides with the declining dominance of French literature in the late twentieth century literary world-system. German and Dutch papers' literary coverage already showed a high level of internationalization in 1955 and remained fairly constant, with foreign literature taking up around half of the total coverage devoted to literature. The NY Times, by contrast, devoted roughly one quarter of its coverage to foreign literature throughout the research period. Although the global diversity of coverage in all four countries has increased, international coverage is largely confined to a select group of “core” countries and to countries belonging to the same language area or region, and domestic literature remains important.
Exile and Assimilation. Some Notes on Vladimir Nabokov's Journey through Space and Time
Authors: Levie Sophie
Published: March 2010

Vladimir Nabokov once inimitably reflected on a consequence of exile: “I don't seem to belong to any clear-cut continent. I'm the shuttle-cock above the Atlantic, and how bright and blue it is there, in my private sky, far from the pigeon-holes and the clay pigeons.”

Looking into aspects of Nabokov's work related to exile and assimilation, I suggest that Nabokov's cosmopolitanism is mirrored in the current international reception of his work. The article makes use of Kwame Anthony Appiah's notion of “cosmopolitan contamination” and that of John Burt Foster Jr.'s “cultural multiplicity.”
A Proposal to Include Book History in Translation Studies. Illustrated with German Translations of Scott and Flaubert
Authors: Bachleitner Norbert
Published: March 2010

The systems approach of book history should be applied to the study of translations, because it sheds light on the agents who influence their genesis and distribution – such as mediators, translators, publishers, censors and readers. In the 1820s, which saw a significant increase in book production and translation, the translation of Walter Scott's works was mainly carried out as ‘hackwork’ by ‘speculative’ publishers unhindered by international copyright protection. In Austria, translations of his work were censored in order to conform to religious and political standards. Despite such interventions, Scott quickly became a favourite of the German reading public, as reflected in unprecedented print runs. Flaubert shared a similar fate: integrated into a popular novel series, the first German translation of Madame Bovary abounds with traces of the translator's self-censorship.
On the Change of Word Stress in the History of German
Authors: Speyer Augustin
Published: March 2010

Word stress in German is usually thought of as following the Germanic stress pattern (main stress on first stem syllable); quasi-monomorphemic words like Forélle or Holúnder suggest, however, that Modern German follows a Latinate stress pattern (last syllable extrametrical; stress on the penultima or the antepenultima, depending on weight of the second-to-last syllable). The change in stress pattern occurred in the 16th and 17th century, judging from evidence of metrical texts, due to a heavy influx of Latin and Romance loan words in this period, which followed the Latinate stress pattern and were taken as sample for the stressing of monomorphemic words longer than two syllables.
Unversöhnte Motivierungen. Der Schatz als Hindernis kohärenten Erzählens im ›Beowulf‹
Authors: Sahm Heike
Published: March 2010

The story of the hoard in ›Beowulf‹ is not consistent. Different answers are given concerning its origin and its function. This essay is trying to make sense of the contradictory specifications by reading the text structurally: In the context of the first story about the treasure, Beowulf is right to fight the dragon in order to defend his people and gain the treasure for them. After his death, a second story is told revealing the underlying rule that a buried hoard must not be plundered. From then on, Beowulf is seen ambivalent for not observing this rule he had not known before. From this point of view, not only the dragon, but also the treasure is Beowulf's opponent.
Nicht mit rechten Dingen, nicht mit dem rechten Ding, nicht am rechten Ort. Zur tarnkappe und zum hort im Nibelungenlied
Authors: Mühlherr Anna
Published: March 2010

Literary criticism regards such objects as the magical concealing cloak (tarnkappe) and the Nibelungen hoard as poorly integrated into the ›Nibelungenlied‹. It is generally accepted that these so-called fairy tale motifs in the first part of the narrative should not be taken too seriously. By way of contrast this article argues for the significance of these objects. It suggests establishing objects (»things«) as a historically reflected basic category of text analysis, a category which at present is underestimated or even ignored in narratological theories. Thus a new way of reading the ›Nibelungenlied‹ is presented: The magical cloak and the treasure should never have been separated and taken away from the ›Nibelungenland‹. Breaking this rule inevitably leads to disastrous results for human action.
Metaphor and metonymy: Making their connections more slippery
Authors: Barnden John A.
Published: March 2010

This paper continues the debate about how to distinguish metaphor from metonymy, and whether this can be done. It examines some of the differences that have been alleged to exist, and augments the already existing doubt about them. The main differences addressed are the similarity/contiguity distinction and the issue of whether source-target links are part of the message in metonymy or metaphor. In particular, the paper argues that metaphorical links can always be used metonymically and regarded as contiguities, and conversely that two particular, central types of metonymic contiguity essentially involve similarity. The paper also touches briefly on how metaphor and metonymy interact with domains, frames, etc. and on the role of imaginary identification/categorization of target as/under source items. With the possible exception of this last issue, the paper suggests that no combination of the alleged differences addressed can serve cleanly to categorize source/target associations into metaphorical ones and metonymic ones. It also suggests that it can be more profitable to analyse utterances at the level of the dimensions involved in the differences than at the higher level of metaphor and metonymy as such.
Age-Dependent Maintenance of Motor Controland Corticostriatal Innervation by Death Receptor 3
Authors: Twohig Jason Peter , Roberts Malcolm I. , Gavalda Nuria , Rees-Taylor Emma L. , Giralt Albert , Adams Debbie , Brooks Simon P. , Bull Melanie J. , Calder Claudia J. , Cuff Simone , Yong Audrey A. , Alberch Jordi , Davies Alun , Dunnett Stephen B. , Tolkovsky Aviva M. , Wang Eddie C. Y.
Published: March 2010

Death receptor 3 is a proinflammatory member of the immunomodulatory tumor necrosis factor receptor superfamily, which has been implicated in several inflammatory diseases such as arthritis and inflammatory bowel disease. Intriguingly however, constitutive DR3 expression has been detected in the brains of mice, rats, and humans, although its neurological function remains unknown. By mapping the normal brain expression pattern of DR3, we found that DR3 is expressed specifically by cells of the neuron lineage in a developmentally regulated and region-specific pattern. Behavioral studies on DR3-deficient (DR3ko) mice showed that constitutive neuronal DR3 expression was required for stable motor control function in the aging adult. DR3komice progressively developed behavioral defects characterized by altered gait, dyskinesia, and hyperactivity, which were associated with elevated dopamine and lower serotonin levels in the striatum. Importantly, retrograde tracing showed that absence of DR3 expression led to the loss of corticostriatal innervation without significant neuronal loss in aged DR3komice. These studies indicate that DR3 plays a key nonredundant role in the retention of normal motor control function during aging in mice and implicate DR3 in progressive neurological disease.
Novel and Direct Access to the Human Locomotor Spinal Circuitry
Authors: Gerasimenko Yury , Gorodnichev Ruslan , Machueva Ekaterina , Pivovarova Elena , Semyenov Denis , Savochin Alexandr , Roy Roland R. , Edgerton V. Reggie
Published: March 2010

The degree of automaticity of locomotion in primates compared with other mammals remains unclear. Here, we examine the possibility for activation of the spinal locomotor circuitry in noninjured humans by spinal electromagnetic stimulation (SEMS). SEMS (3 Hz and 1.3–1.82 tesla) at the T11-T12 vertebrae induced involuntary bilateral locomotor-like movements in the legs of individuals placed in a gravity-neutral position. The formation of locomotor-like activity during SEMS started with a latency of 0.68 ± 0.1 s after delivering the first stimulus, unlike continuous vibration of muscles, which requires several seconds. The first EMG burst in response to SEMS was observed most often in a proximal flexor muscle. We speculate that SEMS directly activates the circuitry intrinsic to the spinal cord, as suggested by the immediate response and the electrophysiological observations demonstrating an absence of strictly time-linked responses within the EMG burst associated with individual stimuli during SEMS. SEMS in the presence of vibration of the leg muscles was more effective in facilitating locomotor-like activity than SEMS alone. The present results suggest that SEMS could be an effective noninvasive clinical tool to determine the potential of an individual to recover locomotion after a spinal cord injury, as well as being an effective rehabilitation tool itself.
Functional Dissociation of the Frontoinsular and Anterior Cingulate Cortices in Empathy for Pain
Authors: Gu Xiaosi , Liu Xun , Guise Kevin G. , Naidich Thomas P. , Hof Patrick R. , Fan Jin
Published: March 2010

The frontoinsular cortex (FI) and the anterior cingulate cortex (ACC) are thought to be involved in empathy for others' pain. However, the functional roles of FI and ACC in empathetic responses have not yet been clearly dissociated in previous studies. In this study, participants viewed color photographs depicting human body parts in painful or nonpainful situations and performed either pain judgment (painful/nonpainful) or laterality judgment (left/right) of the body parts. We found that activation of FI, rather than ACC, showed significant increase for painful compared with nonpainful images, regardless of the task requirement. Our data suggest a clear functional dissociation between FI and ACC in which FI is more domain-specific than ACC when processing empathy for pain.
Hedgehog Signaling Governs the Development of Otic Sensory Epithelium and Its Associated Innervation in Zebrafish
Authors: Sapède Dora , Pujades Cristina
Published: March 2010

The inner ear is responsible for the perception of motion and sound in vertebrates. Its functional unit, the sensory patch, contains mechanosensory hair cells innervated by sensory neurons from the statoacoustic ganglion (SAG) that project to the corresponding nuclei in the brainstem. How hair cells develop at specific positions, and how otic neurons are sorted to specifically innervate each endorgan and to convey the extracted information to the hindbrain is not completely understood. In this work, we study the generation of macular sensory patches and investigate the role of Hedgehog (Hh) signaling in the production of their neurosensory elements. Using zebrafish transgenic lines to visualize the dynamics of hair cell and neuron production, we show that the development of the anterior and posterior maculae is asynchronic, suggesting they are independently regulated. Tracing experiments demonstrate the SAG is topologically organized in two different neuronal subpopulations, which are spatially segregated and innervate specifically each macula. Functional experiments identify the Hh pathway as crucial in coordinating the production of hair cells in the posterior macula, and the formation of its specific innervation. Finally, gene expression analyses suggest that Hh influences the balance between different SAG neuronal subpopulations. These results lead to a model in which Hh orients functionally the development of inner ear towards an auditory fate in all vertebrate species.
Protein Phosphatase 2A Facilitates Axonogenesis by Dephosphorylating CRMP2
Authors: Zhu Ling-Qiang , Zheng Hong-Yun , Peng Cai-Xia , Liu Dan , Li Hong-Lian , Wang Qun , Wang Jian-Zhi
Published: March 2010

Protein phosphatase 2A (PP2A) is indispensable in development, and deficits of PP2A and deterioration of neuronal axons have been observed in several neurodegenerative disorders, but the direct link between PP2A and the neuronal axon development is still missing. Here, we show that PP2A is essential for axon development in transfected rat brain and the dissociated hippocampal neurons. Upregulation of PP2A catalytic subunit (PP2Ac) not only promotes formation and elongation of the functional axons but also rescues axon retardation induced by PP2A inhibition. PP2A can dephosphorylate collapsin response mediator protein-2 (CRMP2) that implements the axon polarization, whereas constitutive expression of phosphomimic-CRMP2 abrogates the effect of PP2A upregulation. We also demonstrate that PP2Ac is enriched in the distal axon of the hippocampal neurons. Our results reveal a mechanistic link between PP2A and axonogenesis/axonopathy, suggesting that upregulation of PP2A may be a promising therapeutic for some neurodegenerative disorders.
Cellular Mechanisms of Temporal Sensitivity in Visual Cortex Neurons
Authors: Cardin Jessica A. , Kumbhani Romesh D. , Contreras Diego , Palmer Larry A.
Published: March 2010

The ability of cortical neurons to accurately encode the temporal pattern of their inputs has important consequences for cortical function and perceptual acuity. Here we identify cellular mechanisms underlying the sensitivity of cortical neurons to the timing of sensory-evoked synaptic inputs. We find that temporally coincident inputs to layer 4 neurons in primary visual cortex evoke an increase in spike precision and supralinear spike summation. Underlying this nonlinear summation are changes in the evoked excitatory conductance and the associated membrane potential response, and a lengthening of the window between excitation and inhibition. Furthermore, fast-spiking inhibitory interneurons in layer 4 exhibit a shorter window of temporal sensitivity compared with excitatory neurons. In contrast to the enhanced response to synchronous inputs by layer 4 neurons, sensory input integration in downstream cortical layers is more linear and less sensitive to timing. Neurons in the input layer of cortex are thus uniquely optimized to detect and encode synchronous sensory-evoked inputs.
Subliminally Presented and Stored Objects Capture Spatial Attention
Authors: Astle Duncan E. , Nobre Anna C. , Scerif Gaia
Published: March 2010

When objects disappear from view, we can still bring them to mind, at least for brief periods of time, because we can represent those objects in visual short-term memory (VSTM) (Sperling, 1960; Cowan, 2001). A defining characteristic of this representation is that it is topographic, that is, it preserves a spatial organization based on the original visual percept (Vogel and Machizawa, 2004; Astle et al., 2009; Kuo et al., 2009). Recent research has also shown that features or locations of visual items that match those being maintained in conscious VSTM automatically capture our attention (Awh and Jonides, 2001; Olivers et al., 2006; Soto et al., 2008). But do objects leave some trace that can guide spatial attention, even without participants intentionally remembering them? Furthermore, could subliminally presented objects leave a topographically arranged representation that can capture attention? We presented objects either supraliminally or subliminally and then 1 s later re-presented one of those objects in a new location, as a “probe” shape. As participants made an arbitrary perceptual judgment on the probe shape, their covert spatial attention was drawn to the original location of that shape, regardless of whether its initial presentation had been supraliminal or subliminal. We demonstrate this with neural and behavioral measures of memory-driven attentional capture. These findings reveal the existence of a topographically arranged store of “visual” objects, the content of which is beyond our explicit awareness but which nonetheless guides spatial attention.
Necdin Promotes Tangential Migration of Neocortical Interneurons from Basal Forebrain
Authors: Kuwajima Takaaki , Hasegawa Koichi , Yoshikawa Kazuaki
Published: March 2010

Necdin is a pleiotropic protein that promotes neuronal differentiation and survival. In mammals, the necdin gene on the maternal chromosome is silenced by genomic imprinting, and only the paternal necdin gene is expressed in virtually all postmitotic neurons. Necdin forms a complex with the homeodomain protein Dlx2 to enhance its transcriptional activity. Dlx2 plays a major role in controlling tangential migration of GABAergic interneurons from the basal forebrain to the neocortex. Here, we examined whether Dlx2-expressing interneurons migrate properlyin vivoin mutant mice lacking the paternal necdin gene. In necdin-deficient mice at birth, the population of Dlx2-expressing cells significantly decreased in the neocortex but increased in the preoptic area. DiI-labeled cell migration assay using organotypic forebrain slice cultures revealed that the number of cells migrating from the medial ganglionic eminence into the neocortex was significantly reduced in necdin-deficient embryos. Furthermore, necdin-deficient mice had a decreased population of neocortical GABA-containing neurons and were highly susceptible to pentylenetetrazole-induced seizures. These results suggest that necdin promotes tangential migration of neocortical GABAergic interneurons during mammalian forebrain development.
Excitability and Synaptic Communication within the Oligodendrocyte Lineage
Authors: De Biase Lindsay M. , Nishiyama Akiko , Bergles Dwight E.
Published: March 2010

The mammalian CNS contains an abundant, widely distributed population of glial cells that serve as oligodendrocyte progenitors. It has been reported that these NG2-immunoreactive cells (NG2+cells) form synapses and generate action potentials, suggesting that neural-evoked excitation of these progenitors may regulate oligodendrogenesis. However, recent studies also suggest that NG2+cells are comprised of functionally distinct groups that differ in their ability to respond to neuronal activity, undergo differentiation, and experience injury following ischemia. To better define the physiological properties of NG2+cells, we used transgenic mice that allowed an unbiased sampling of this population and unambiguous identification of cells in discrete states of differentiation. Using acute brain slices prepared from developing and mature mice, we found that NG2+cells in diverse brain regions share a core set of physiological properties, including expression of voltage-gated Na+(NaV) channels and ionotropic glutamate receptors, and formation of synapses with glutamatergic neurons. Although small amplitude Na+spikes could be elicited in some NG2+cells during the first postnatal week, they were not capable of generating action potentials. Transition of these progenitors to the premyelinating stage was accompanied by the rapid removal of synaptic input, as well as downregulation of AMPA and NMDA receptors and NaV channels. Thus, prior reports of physiological heterogeneity among NG2+cells may reflect analysis of cells in later stages of maturation. These results suggest that NG2+cells are uniquely positioned within the oligodendrocyte lineage to monitor the firing patterns of surrounding neurons.
Synaptic Localization and Function of Sidekick Recognition Molecules Require MAGI Scaffolding Proteins
Authors: Yamagata Masahito , Sanes Joshua R.
Published: March 2010

Four transmembrane adhesion molecules—Sidekick-1, Sidekick-2, Down's syndrome cell adhesion molecule (Dscam), and Dscam-like—are determinants of lamina-specific synapse formation in the vertebrate retina. Their C termini are predicted to bind postsynaptic density (PSD)-95/Discs Large/ZO-1 (PDZ) domains, which are present in many synaptic scaffolding proteins. We identify members of the membrane-associated guanylate kinase with inverted orientation (MAGI) and PSD-95 subfamilies of multi-PDZ domain proteins as binding partners for Sidekicks and Dscams. Specific MAGI and PSD-95 family members are present in distinct subsets of retinal synapses, as are Sidekicks and Dscams. Using Sidekick-2 as an exemplar, we show that its PDZ-binding C terminus is required for both its synaptic localization in photoreceptors and its ability to promote lamina-specific arborization of presynaptic and postsynaptic processes in the inner plexiform layer. In photoreceptor synapses that contain both MAGI-1 and PSD-95, Sidekick-2 preferentially associates with MAGI-1. Depletion of MAGI-1 from photoreceptors by RNA interference blocks synaptic localization of Sidekick-2 in photoreceptors without affecting localization of PSD-95. Likewise, depletion of MAGI-2 from retinal ganglion cells and interneurons interferes with Sidekick-2-dependent laminar targeting of processes. These results demonstrate that localization and function of Sidekick-2 require its incorporation into a MAGI-containing synaptic scaffold.
Impact of linoleic acid on bovine oocyte maturation and embryo development
Authors: Marei Waleed F , Wathes D Claire , Fouladi-Nashta Ali A
Published: March 2010

Linoleic acid (LA; 18:2n-6) is the most abundant fatty acid in bovine follicular fluid, and it was previously reported that LA concentration significantly decreases when follicle size increases. This suggests that LA may have a role in the regulation of oocyte maturation. The present study investigated the effect of LA supplementation on bovine oocyte maturation and early embryo developmentin vitro. Treatment of cumulus–oocyte complexes (COCs) with LA significantly inhibited cumulus cell expansion and retarded development of the oocytes to the metaphase II (MII) stage in a dose-dependent manner. This effect was reversible, and the oocytes developed to the MII stage after extended culture in the absence of LA. Treatment of COCs with LA also resulted in a significantly lower percentage of cleaved embryos and blastocyst yield. Furthermore, COCs treated with LA had significant effects compared with controls in i) increasing prostaglandin E2concentration in the medium, ii) decreasing intracellular cAMP at 6 and 24 h of maturation and iii) decreasing phosphorylation of the MAPK1 and 3 at 24 h, and AKT at 6 h of maturation. In conclusion, LA supplementation to bovine oocytes during maturation altered the molecular mechanisms regulating oocyte maturation and resulted in decreased percentage of oocytes at MII stage and inhibition of the subsequent early embryo development. These data provide evidence for adverse effects of LA on oocyte development, which can be associated with dietary increased level of LA in the follicular fluid and the decline in fertility in farm animals and human.
Hearing in Drosophila Requires TilB, a Conserved Protein Associated With Ciliary Motility
Authors: Kavlie Ryan G , Kernan Maurice J , Eberl Daniel F
Published: March 2010

Cilia were present in the earliest eukaryotic ancestor and underlie many biological processes ranging from cell motility and propulsion of extracellular fluids to sensory physiology. We investigated the contribution of the touch  insensitive larva B (tilB) gene to cilia function in Drosophila melanogaster. Mutants of tilB exhibit dysfunction in sperm flagella and ciliated dendrites of chordotonal organs that mediate hearing and larval touch sensitivity. Mutant sperm axonemes as well as sensory neuron dendrites of Johnston's organ, the fly's auditory organ, lack dynein arms. Through deficiency mapping and sequencing candidate genes, we identified tilB mutations in the annotated gene CG14620. A genomic CG14620 transgene rescued deafness and male sterility of tilB mutants. TilB is a 395-amino-acid protein with a conserved N-terminal leucine-rich repeat region at residues 16–164 and a coiled-coil domain at residues 171–191. A tilB-Gal4 transgene driving fluorescently tagged TilB proteins elicits cytoplasmic expression in embryonic chordotonal organs, in Johnston's organ, and in sperm flagella. TilB does not appear to affect tubulin polyglutamylation or polyglycylation. The phenotypes and expression of tilB indicate function in cilia construction or maintenance, but not in intraflagellar transport. This is also consistent with phylogenetic association of tilB homologs with presence of genes encoding axonemal dynein arm components. Further elucidation of tilB functional mechanisms will provide greater understanding of cilia function and will facilitate understanding ciliary diseases.
The Tandem Inversion Duplication inSalmonella enterica: Selection Drives Unstable Precursors to Final Mutation Types
Authors: Kugelberg Elisabeth , Kofoid Eric , Andersson Dan I , Lu Yong , Mellor Joseph , Roth Frederick P , Roth John R
Published: March 2010

During growth under selection, mutant types appear that are rare in unselected populations. Stress-induced mechanisms may cause these structures or selection may favor a series of standard events that modify common preexisting structures. One such mutation is the short junction (SJ) duplication with long repeats separated by short sequence elements: AB*(CD)*(CD)*E (* = a few bases). Another mutation type, described here, is the tandem inversion duplication (TID), where two copies of a parent sequence flank an inverse-order segment: AB(CD)(E′D′C′B′)(CD)E. Both duplication types can amplify by unequal exchanges between direct repeats (CD), and both are rare in unselected cultures but common after prolonged selection for amplification. The observed TID junctions are asymmetric (aTIDs) and may arise from a symmetrical precursor (sTID)—ABCDE(E′D′C′B′A′)ABCDE—when sequential deletions remove each palindromic junction. Alternatively, one deletion can remove both sTID junctions to generate an SJ duplication. It is proposed that sTID structures form frequently under all growth conditions, but are usually lost due to their instability and fitness cost. Selection for increased copy number helps retain the sTID and favors deletions that remodel junctions, improve fitness, and allow higher amplification. Growth improves with each step in formation of an SJ or aTID amplification, allowing selection to favor completion of the mutation process.
The Steroid Molting Hormone Ecdysone Regulates Sleep in Adult Drosophila melanogaster
Authors: Ishimoto Hiroshi , Kitamoto Toshihiro
Published: March 2010

Ecdysone is the major steroid hormone in insects and plays essential roles in coordinating developmental transitions such as larval molting and metamorphosis through its active metabolite 20-hydroxyecdysone (20E). Although ecdysone is present throughout life in both males and females, its functions in adult physiology remain largely unknown. In this study we demonstrate that ecdysone-mediated signaling in the adult is intimately involved in transitions between the physiological states of sleep and wakefulness. First, administering 20E to adult Drosophila melanogaster promoted sleep in a dose-dependent manner, and it did so primarily by altering the length of sleep and wake bouts without affecting waking activity. Second, mutants for ecdysone synthesis displayed the “short-sleep phenotype,” and this was alleviated by administering 20E at the adult stage. Third, mutants for nuclear ecdysone receptors showed reduced sleep, and conditional overexpression of wild-type ecdysone receptors in the adult mushroom bodies resulted in an isoform-specific increase in sleep. Finally, endogenous ecdysone levels increased after sleep deprivation, and mutants defective for ecdysone signaling displayed little sleep rebound, suggesting that ecdysone is involved in homeostatic sleep regulation. In light of the recent finding that lethargus—a period at larval-stage transitions in the nematode worm Caenorhabditis elegans—is a sleep-like state, our results suggest that sleep is functionally and mechanistically linked to a genetically programmed, quiescent behavioral state during development.
Mutations in Caenorhabditis elegans eIF2β Permit Translation Initiation From Non-AUG Start Codons
Authors: Zhang Yinhua , Maduzia Lisa L
Published: March 2010

Recognition of the AUG start codon on mRNAs during translation initiation in eukaryotes occurs in a preinitiation complex that includes small ribosomal subunits and multiple translation initiation factors. The complexity of this process and the lack of appropriate tools have prevented its genetic study in multicellular organisms. Here we describe a genetic system in the nematode Caenorhabditis elegans to study how the AUG start codon is selected. We have generated a sensitive reporter assay that allows for the isolation of mutants with reduced fidelity to recognize the AUG start codon. Two mutants were identified to have dominant missense mutations in iftb-1, which encodes the β-subunit of eIF2 (eIF2β). Both mutations occur in a conserved region located outside of the C2–C2 zinc finger domain where yeast SUI3 mutations are localized in Saccharomyces cerevisiae eIF2β. C. elegans iftb-1, as well as mutant eIF2βs carrying the equivalent SUI3 mutations, are able to initiate translation at non-AUG codons that retain two potential base-pairing interactions with the anticodon of the initiator methionyl tRNA. These analyses further support the critical role of eIF2β in start codon selection, and two functional domains within eIF2β are likely involved, one defined by our C. elegans mutants and the other by the yeast SUI3 mutants.
Dominant Mutations in the Late 40S Biogenesis Factor Ltv1 Affect Cytoplasmic Maturation of the Small Ribosomal Subunit in Saccharomyces cerevisiae
Authors: Fassio Claire A , Schofield Brett J , Seiser Robert M , Johnson Arlen W , Lycan Deborah E
Published: March 2010

In eukaryotes, 40S and 60S ribosomal subunits are assembled in the nucleus from rRNAs and ribosomal proteins, exported as premature complexes, and processed in final maturation steps in the cytoplasm. Ltv1 is a conserved 40S ribosome biogenesis factor that interacts with pre-40S complexes in vivo and is proposed to function in yeast in nuclear export. Cells lacking LTV1 grow slowly and are significantly impaired in mature 40S subunit production. Here we show that mutation or deletion of a putative nuclear export sequence in LTV1 is strongly dominant negative, but the protein does not accumulate in the nucleus, as expected for a mutation affecting export. In fact, most of the mutant protein is cytoplasmic and associated with pre-40S subunits. Cells expressing mutant Ltv1 have a 40S biogenesis defect, accumulate 20S rRNA in the cytoplasm as detected by FISH, and retain the late-acting biogenesis factor Tsr1 in the cytoplasm. Finally, overexpression of mutant Ltv1 is associated with nuclear retention of 40S subunit marker proteins, RpS2–GFP and RpS3–GFP. We suggest that the proximal consequence of these LTV1 mutations is inhibition of the cytoplasmic maturation of 40S subunits and that nuclear retention of pre-40S subunits is a downstream consequence of the failure to release and recycle critical factors back to the nucleus.
Developmental Timing of DNA Elimination Following Allopolyploidization in Wheat
Authors: Khasdan Vadim , Yaakov Beery , Kraitshtein Zina , Kashkush Khalil
Published: March 2010

The elimination of DNA sequences following allopolyploidization is a well-known phenomenon. Yet, nothing is known about the biological significance, the mechanism, or the precise developmental timing of this event. In this study, we have observed reproducible elimination of an Aegilops tauschii allele in the genome of the second generation (S2) of a newly synthesized allohexaploid derived from a cross between Triticum turgidum and Ae. tauschii. We show that elimination of the Ae. tauschii allele did not occur in germ cells but instead occurred during S2 embryo development. This work shows that deletion of DNA sequences following allopolyploidization might occur also in a tissue-specific manner.
Towards Heterogeneous Biodegradable Nanorods for Controlled Drug Delivery
Authors: Dougherty Shelley , Liang Jianyu
Published: March 2010

Heterogeneous, one-dimensional (1D) nanomaterials, such as nanorods and nanowires, have been utilized for a variety of different biomedical applications because they offer a unique combination of properties and provide a material platform for integrating multiple functions. In this paper, we propose a template-assisted wetting approach to fabricate segmented polymer nanorods using biodegradable polymers for controlled drug delivery. Our previous work with polystyrene (PS) and poly(methyl methacrylate) (PMMA) heterogeneous, segmented nanorods is described briefly to introduce our current preliminary work with the fabrication of homogeneous biodegradable nanorods and drug release from polymer thin films. Since the template-assisted fabrication approach provides us unprecedented control over the size, spacing, and length of the heterogeneous polymer nanorods, this technique will provide for the opportunity to evaluate drug release kinetics as a function of the segment spacing, size of the nanorods, and aspect ratio in the future.
Nano-scale Debye Capacitive Sensors for Highly Sensitive, Label-free, Nucleic Acid Analysis
Authors: Sebastian Mannoor Manu , James Teena , Ivanov Dentcho V. , Braunlin Bill , Beadling Les
Published: March 2010

An electrochemical capacitive sensor with electrode separation in the order of the Electrical Double Layer width (Debye length) of the analyte solution is presented for extremely sensitive and label-free analysis of Nucleic Acids. As the Electrical Double Layers (EDL) from both the capacitive electrodes interact and overlap each other in the reduced space confinement, the contribution from the electrode polarization effects and noises due to bulk sample resistance are found to be minimized. The dielectric property changes during hybridization reaction were measured using 10-mer nucleotide sequences. A 30-45% change in relative permittivity (capacitance) was observed due to DNA hybridization at 10Hz.
A Study to Estimate the Number of Active Particles in CMP
Authors: Mpagazehe Jeremiah , Thukalil Geo , Higgs C. Fred
Published: March 2010

To improve yield rates during integrated circuit fabrication a better understanding of the material removal process during CMP is sought. Many material removal models have been generated to predict the material removal rate (MRR) during CMP. The majority of such models estimate that the MRR is equal to the material removed by a single particle multiplied by the total number of particles contributing to the wear process. Particles contributing to the wear process are known as ‘active particles’. Several authors have proposed analytical models to estimate this quantity. This work introduces a new method for estimating the number of active particles in CMP by deducing it from the polish results of a multi-physics CMP model. By employing the particle-augmented mixed lubrication model (PAML) developed by Terrell and Higgs (2008), it is possible to determine the number of active particles in CMP. The predictions of PAML are compared with two popular analytical approaches which have been commonly used to predict the number of active particles during CMP.
Opportunities and Challenges to Sustainable Manufacturing and CMP
Authors: Dornfeld David
Published: March 2010

Today the requirements for reducing the impact of our manufacturing activities are increasing as the world awakes to and addresses the environmental impacts of our society. Energy consumption, greenhouse gas emissions, materials availability and use, environmental impact levels, etc. are all topics of interest. Semiconductor manufacturing in general and process steps such as CMP are not exempt from this and, in many cases, the industry has led the efforts in reducing impacts. This paper will first review some of the drivers for sustainable manufacturing, then define some of the terms that will be useful for determining the engineering aspects of sustainability and sustainable manufacturing, as well as metrics for assessing the impact of manufacturing in general and CMP in particular. An assessments of CMP will be given to illustrate the potential for “design for the environment” in CMP and related processes. Consideration will be given to research opportunities, including process modeling, that this focus provides to CMP researchers, consumable suppliers and industry.