bluuebunny/crossref_metadata_2025 huggingface dataset:
HCF-1 self-association via an interdigitated Fn3 structure facilitates transcriptional regulatory complex formation
Authors: Park Jihye , Lammers Fabienne , Herr Winship , Song Ji-Joon
Published: October 2012

Host-cell factor 1 (HCF-1) is an unusual transcriptional regulator that undergoes a process of proteolytic maturation to generate N- (HCF-1
N
) and C- (HCF-1
C
) terminal subunits noncovalently associated via self-association sequence elements. Here, we present the crystal structure of the self-association sequence 1 (SAS1) including the adjacent C-terminal HCF-1 nuclear localization signal (NLS). SAS1 elements from each of the HCF-1
N
and HCF-1
C
subunits form an interdigitated fibronectin type 3 (Fn3) tandem repeat structure. We show that the C-terminal NLS recruited by the interdigitated SAS1 structure is required for effective formation of a transcriptional regulatory complex: the herpes simplex virus VP16-induced complex. Thus, HCF-1
N
–HCF-1
C
association via an integrated Fn3 structure permits an NLS to facilitate formation of a transcriptional regulatory complex.
Natriuretic peptides block synaptic transmission by activating phosphodiesterase 2A and reducing presynaptic PKA activity
Authors: Hu Fei , Ren Jing , Zhang Ju-en , Zhong Weixin , Luo Minmin
Published: October 2012

The heart peptide hormone atrial natriuretic peptide (ANP) regulates blood pressure by stimulating guanylyl cyclase-A to produce cyclic guanosine monophosphate (cGMP). ANP and guanylyl cyclase-A are also expressed in many brain areas, but their physiological functions and downstream signaling pathways remain enigmatic. Here we investigated the physiological functions of ANP signaling in the neural pathway from the medial habenula (MHb) to the interpeduncular nucleus (IPN). Biochemical assays indicate that ANP increases cGMP accumulation in the IPN of mouse brain slices. Using optogenetic stimulation and electrophysiological recordings, we show that both ANP and brain natriuretic peptide profoundly block glutamate release from MHb neurons. Pharmacological applications reveal that this blockade is mediated by phosphodiesterase 2A (PDE2A) but not by cGMP-stimulated protein kinase-G or cGMP-sensitive cyclic nucleotide-gated channels. In addition, focal infusion of ANP into the IPN enhances stress-induced analgesia, and the enhancement is prevented by PDE2A inhibitors. PDE2A is richly expressed in the axonal terminals of MHb neurons, and its activation by cGMP depletes cyclic adenosine monophosphates. The inhibitory effect of ANP on glutamate release is reversed by selectively activating protein kinase A. These results demonstrate strong presynaptic inhibition by natriuretic peptides in the brain and suggest important physiological and behavioral roles of PDE2A in modulating neurotransmitter release by negative crosstalk between cGMP-signaling and cyclic adenosine monophosphate-signaling pathways.
Differential expression of SUMO-specific protease 7 variants regulates epithelial–mesenchymal transition
Authors: Bawa-Khalfe Tasneem , Lu Long-Sheng , Zuo Yong , Huang Chao , Dere Ruhee , Lin Feng-Ming , Yeh Edward T. H.
Published: October 2012

Two Sentrin/small ubiquitin-like modifier (SUMO)-specific protease 7 (SENP7) variants are naturally expressed in breast epithelia. Breast cancer (BCa) onset down-regulates the short SENP7 splice variant (SENP7S) and enhances the long transcript (SENP7L). Here, we show that SENP7L induction promotes gene expression profiles that favor aberrant proliferation and initiate epithelial–mesenchymal transition (EMT). SENP7L exhibits an interaction domain for the epigenetic remodeler heterochromatin protein 1 α (HP1α) and isopeptidase activity against SUMO-modified HP1α. Loss of this interaction domain, as observed with SENP7S, favors HP1α SUMOylation. SUMOylated HP1α is enriched at E2F-responsive and mesenchymal gene promoters, silences transcription of these genes, and promotes cellular senescence. Elevated SENP7L renders HP1α hypo-SUMOylated, which relieves transcriptional repression of the same genes and concurrently decreases transcription of epithelial-promoting genes via an HP1α-independent mechanism. Consequently, SENP7L levels correlate with EMT, motility, and invasiveness of BCa cells. Stable knockdown of elevated SENP7L levels lessens the dissemination of highly metastatic BCa cells to the lungs from primary implantation sites in in vivo studies. Thus, differential splicing of the
SENP7
regulates either tumor suppression or progression.
Flexible graphene-based lithium ion batteries with ultrafast charge and discharge rates
Authors: Li Na , Chen Zongping , Ren Wencai , Li Feng , Cheng Hui-Ming
Published: October 2012

There is growing interest in thin, lightweight, and flexible energy storage devices to meet the special needs for next-generation, high-performance, flexible electronics. Here we report a thin, lightweight, and flexible lithium ion battery made from graphene foam, a three-dimensional, flexible, and conductive interconnected network, as a current collector, loaded with Li
4
Ti
5
O
12
and LiFePO
4
, for use as anode and cathode, respectively. No metal current collectors, conducting additives, or binders are used. The excellent electrical conductivity and pore structure of the hybrid electrodes enable rapid electron and ion transport. For example, the Li
4
Ti
5
O
12
/graphene foam electrode shows a high rate up to 200 C, equivalent to a full discharge in 18 s. Using them, we demonstrate a thin, lightweight, and flexible full lithium ion battery with a high-rate performance and energy density that can be repeatedly bent to a radius of 5 mm without structural failure and performance loss.
Prolonged nerve blockade delays the onset of neuropathic pain
Authors: Shankarappa Sahadev A. , Tsui Jonathan H. , Kim Kristine N. , Reznor Gally , Dohlman Jenny C. , Langer Robert , Kohane Daniel S.
Published: October 2012

Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain. Pharmacological blockade of that activity has been shown to mitigate the onset of associated molecular events in the nervous system. However, results in preventing onset of pain behaviors by providing prolonged nerve blockade have been mixed. Furthermore, the experimental techniques used to date to provide that blockade were limited in clinical potential in that they would require surgical implantation. To address these issues, we have used liposomes (SDLs) containing saxitoxin (STX), a site 1 sodium channel blocker, and the glucocorticoid agonist dexamethasone to provide nerve blocks lasting ∼1 wk from a single injection. This formulation is easily injected percutaneously. Animals undergoing spared nerve injury (SNI) developed mechanical allodynia in 1 wk; nerve blockade with a single dose of SDLs (duration of block 6.9 ± 1.2 d) delayed the onset of allodynia by 2 d. Treatment with three sequential SDL injections resulting in a nerve block duration of 18.1 ± 3.4 d delayed the onset of allodynia by 1 mo. This very prolonged blockade decreased activation of astrocytes in the lumbar dorsal horn of the spinal cord due to SNI. Changes in expression of injury-related genes due to SNI in the dorsal root ganglia were not affected by SDLs. These findings suggest that formulations of this kind, which could be easy to apply clinically, can mitigate the development of neuropathic pain.
Slime mold uses an externalized spatial “memory” to navigate in complex environments
Authors: Reid Chris R. , Latty Tanya , Dussutour Audrey , Beekman Madeleine
Published: October 2012

Spatial memory enhances an organism’s navigational ability. Memory typically resides within the brain, but what if an organism has no brain? We show that the brainless slime mold
Physarum polycephalum
constructs a form of spatial memory by avoiding areas it has previously explored. This mechanism allows the slime mold to solve the U-shaped trap problem—a classic test of autonomous navigational ability commonly used in robotics—requiring the slime mold to reach a chemoattractive goal behind a U-shaped barrier. Drawn into the trap, the organism must rely on other methods than gradient-following to escape and reach the goal. Our data show that spatial memory enhances the organism’s ability to navigate in complex environments. We provide a unique demonstration of a spatial memory system in a nonneuronal organism, supporting the theory that an externalized spatial memory may be the functional precursor to the internal memory of higher organisms.
Counting single photoactivatable fluorescent molecules by photoactivated localization microscopy (PALM)
Authors: Lee Sang-Hyuk , Shin Jae Yen , Lee Antony , Bustamante Carlos
Published: October 2012

We present a single molecule method for counting proteins within a diffraction-limited area when using photoactivated localization microscopy. The intrinsic blinking of photoactivatable fluorescent proteins mEos2 and Dendra2 leads to an overcounting error, which constitutes a major obstacle for their use as molecular counting tags. Here, we introduce a kinetic model to describe blinking and show that Dendra2 photobleaches three times faster and blinks seven times less than mEos2, making Dendra2 a better photoactivated localization microscopy tag than mEos2 for molecular counting. The simultaneous activation of multiple molecules is another source of error, but it leads to molecular undercounting instead. We propose a photoactivation scheme that maximally separates the activation of different molecules, thus helping to overcome undercounting. We also present a method that quantifies the total counting error and minimizes it by balancing over- and undercounting. This unique method establishes that Dendra2 is better for counting purposes than mEos2, allowing us to count in vitro up to 200 molecules in a diffraction-limited spot with a bias smaller than 2% and an uncertainty less than 6% within 10 min. Finally, we demonstrate that this counting method can be applied to protein quantification in vivo by counting the bacterial flagellar motor protein FliM fused to Dendra2.
Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation
Authors: Martyn Amanda C. , De Jaeger Xavier , Magalhães Ana C. , Kesarwani Rohit , Gonçalves Daniela F. , Raulic Sanda , Guzman Monica S. , Jackson Michael F. , Izquierdo Ivan , MacDonald John F. , Prado Marco A. M. , Prado Vania F.
Published: October 2012

Basal forebrain cholinergic neurons, which innervate the hippocampus and cortex, have been implicated in many forms of cognitive function. Immunolesion-based methods in animal models have been widely used to study the role of acetylcholine (ACh) neurotransmission in these processes, with variable results. Cholinergic neurons have been shown to release both glutamate and ACh, making it difficult to deduce the specific contribution of each neurotransmitter on cognition when neurons are eliminated. Understanding the precise roles of ACh in learning and memory is critical because drugs that preserve ACh are used as treatment for cognitive deficits. It is therefore important to define which cholinergic-dependent behaviors could be improved pharmacologically. Here we investigate the contributions of forebrain ACh on hippocampal synaptic plasticity and cognitive behavior by selective elimination of the vesicular ACh transporter, which interferes with synaptic storage and release of ACh. We show that elimination of vesicular ACh transporter in the hippocampus results in deficits in long-term potentiation and causes selective deficits in spatial memory. Moreover, decreased cholinergic tone in the forebrain is linked to hyperactivity, without changes in anxiety or depression-related behavior. These data uncover the specific contribution of forebrain cholinergic tone for synaptic plasticity and behavior. Moreover, these experiments define specific cognitive functions that could be targeted by cholinergic replacement therapy.
Efficient targeted gene disruption in
Xenopus
embryos using engineered transcription activator-like effector nucleases (TALENs)
Authors: Lei Yong , Guo Xiaogang , Liu Yun , Cao Yang , Deng Yi , Chen Xiongfeng , Cheng Christopher H. K. , Dawid Igor B. , Chen Yonglong , Zhao Hui
Published: October 2012

Transcription activator-like effector nucleases (TALENs) are an approach for directed gene disruption and have been proved to be effective in various animal models. Here, we report that TALENs can induce somatic mutations in
Xenopus
embryos with reliably high efficiency and that such mutations are heritable through germ-line transmission. We modified the Golden Gate method for TALEN assembly to make the product suitable for RNA transcription and microinjection into
Xenopus
embryos. Eight pairs of TALENs were constructed to target eight
Xenopu
s genes, and all resulted in indel mutations with high efficiencies of up to 95.7% at the targeted loci. Furthermore, mutations induced by TALENs were highly efficiently passed through the germ line to F
1
frogs. Together with simple and reliable PCR-based approaches for detecting TALEN-induced mutations, our results indicate that TALENs are an effective tool for targeted gene editing/knockout in
Xenopus
.
Altered hematopoiesis in trisomy 21 as revealed through in vitro differentiation of isogenic human pluripotent cells
Authors: MacLean Glenn A. , Menne Tobias F. , Guo Guoji , Sanchez Danielle J. , Park In-Hyun , Daley George Q. , Orkin Stuart H.
Published: October 2012

Trisomy 21 is associated with hematopoietic abnormalities in the fetal liver, a preleukemic condition termed transient myeloproliferative disorder, and increased incidence of acute megakaryoblastic leukemia. Human trisomy 21 pluripotent cells of various origins, human embryionic stem (hES), and induced pluripotent stem (iPS) cells, were differentiated in vitro as a model to recapitulate the effects of trisomy on hematopoiesis. To mitigate clonal variation, we isolated disomic and trisomic subclones from the same parental iPS line, thereby generating subclones isogenic except for chromosome 21. Under differentiation conditions favoring development of fetal liver-like, γ-globin expressing, definitive hematopoiesis, we found that trisomic cells of hES, iPS, or isogenic origins exhibited a two- to fivefold increase in a population of CD43
+
(Leukosialin)/CD235
+
(Glycophorin A) hematopoietic cells, accompanied by increased multilineage colony-forming potential in colony-forming assays. These findings establish an intrinsic disturbance of multilineage myeloid hematopoiesis in trisomy 21 at the fetal liver stage.
Direction-selective retinal ganglion cells arise from molecularly specified multipotential progenitors
Authors: De la Huerta Irina , Kim In-Jung , Voinescu P. Emanuela , Sanes Joshua R.
Published: October 2012

Single progenitors can give rise to any and all of the main retinal cell types: photoreceptors, interneurons (horizontal, bipolar, and amacrine cells), retinal ganglion cells (RGCs), and glia. Many of these types are divisible into multiple functionally, structurally, and molecularly distinct subtypes (e.g., ∼25 for RGCs). It remains unknown when and how progenitors become committed to generate such subtypes. Here, we determine the origin of RGCs that respond selectively to vertical motion and express cadherin 6 (
cdh6
). Using Cre recombinase-based lineage tracing, we show that these RGCs arise from progenitors that themselves express cdh6. These progenitors are capable of generating all major retinal cell types, but the RGCs they generate are predominantly of the single direction-selective subtype. In contrast,
cdh6
-positive progenitors retain the ability to generate multiple subtypes of amacrine and bipolar cells. Our results demonstrate that type and subtype specification are regulated in different ways and suggest that multipotential but fate-restricted progenitors contribute to subtype specification in retina.
Transposon mutagenesis identifies genes that transform neural stem cells into glioma-initiating cells
Authors: Koso Hideto , Takeda Haruna , Yew Christopher Chin Kuan , Ward Jerrold M. , Nariai Naoki , Ueno Kazuko , Nagasaki Masao , Watanabe Sumiko , Rust Alistair G. , Adams David J. , Copeland Neal G. , Jenkins Nancy A.
Published: October 2012

Neural stem cells (NSCs) are considered to be the cell of origin of glioblastoma multiforme (GBM). However, the genetic alterations that transform NSCs into glioma-initiating cells remain elusive. Using a unique transposon mutagenesis strategy that mutagenizes NSCs in culture, followed by additional rounds of mutagenesis to generate tumors in vivo, we have identified genes and signaling pathways that can transform NSCs into glioma-initiating cells. Mobilization of
Sleeping Beauty
transposons in NSCs induced the immortalization of astroglial-like cells, which were then able to generate tumors with characteristics of the mesenchymal subtype of GBM on transplantation, consistent with a potential astroglial origin for mesenchymal GBM. Sequence analysis of transposon insertion sites from tumors and immortalized cells identified more than 200 frequently mutated genes, including human GBM-associated genes, such as
Met
and
Nf1
, and made it possible to discriminate between genes that function during astroglial immortalization vs. later stages of tumor development. We also functionally validated five GBM candidate genes using a previously undescribed high-throughput method. Finally, we show that even clonally related tumors derived from the same immortalized line have acquired distinct combinations of genetic alterations during tumor development, suggesting that tumor formation in this model system involves competition among genetically variant cells, which is similar to the Darwinian evolutionary processes now thought to generate many human cancers. This mutagenesis strategy is faster and simpler than conventional transposon screens and can potentially be applied to any tissue stem/progenitor cells that can be grown and differentiated in vitro.
Effect of Feeding–Fasting Cycles on Oxygen Consumption and Bioenergetics of Female Yellow Perch
Authors: Schaeffer Travis W. , Spengler Daniel E. , Schoenebeck Casey W. , Brown Michael L. , Chipps Steven R.
Published: October 2012

We measured growth and oxygen consumption of age‐1 yellow perch Perca flavescens subjected to ad libitum (control) or variable feeding cycles of 2 (i.e., 2 d of feed, 2 d of deprivation), 6, or 12 d for a 72‐d period. Individual, female yellow perch (initial weight = 51.9 ± 0.9 g [mean ± SE]) were stocked in 110‐L aquaria to provide six replicates per treatment and fed measured rations of live fathead minnow Pimephales promelas. Consumption, absolute growth rate, growth efficiency, and oxygen consumption were similar among feeding regimens. However, growth trajectories for fish on the 2‐d cycle were significantly lower than other feed–fast cycles. Hyperphagia occurred in all treatments. Bioenergetics model simulations indicated that consumption was significantly underestimated (t = 5.4, df = 4, P = 0.006), while growth was overestimated (t = −5.5, df = 4, P = 0.005) for fish on the 12‐d cycle. However, model errors detected between observed and predicted values were low, ranging from −10.1% to +7.8%. We found that juvenile yellow perch exhibited compensatory growth (CG), but none of the feed–fast treatments resulted in growth overcompensation. Likewise, we found no evidence that respiration rates varied with CG, implying that yellow perch bioenergetics models could be used to predict the effects of feeding history and CG response on food consumption and fish growth.
The submitochondrial distribution of ubiquinone affects respiration in long-lived Mclk1+/− mice
Authors: Lapointe Jérôme , Wang Ying , Bigras Eve , Hekimi Siegfried
Published: October 2012

Mclk1 (also known as Coq7) and Coq3 code for mitochondrial enzymes implicated in the biosynthetic pathway of ubiquinone (coenzyme Q or UQ). Mclk1+/− mice are long-lived but have dysfunctional mitochondria. This phenotype remains unexplained, as no changes in UQ content were observed in these mutants. By producing highly purified submitochondrial fractions, we report here that Mclk1+/− mice present a unique mitochondrial UQ profile that was characterized by decreased UQ levels in the inner membrane coupled with increased UQ in the outer membrane. Dietary-supplemented UQ10 was actively incorporated in both mitochondrial membranes, and this was sufficient to reverse mutant mitochondrial phenotypes. Further, although homozygous Coq3 mutants die as embryos like Mclk1 homozygous null mice, Coq3+/− mice had a normal lifespan and were free of detectable defects in mitochondrial function or ubiquinone distribution. These findings indicate that MCLK1 regulates both UQ synthesis and distribution within mitochondrial membranes.
TLR4 activation of TRPC6-dependent calcium signaling mediates endotoxin-induced lung vascular permeability and inflammation
Authors: Tauseef Mohammad , Knezevic Nebojsa , Chava Koteswara R. , Smith Monica , Sukriti Sukriti , Gianaris Nicholas , Obukhov Alexander G. , Vogel Stephen M. , Schraufnagel Dean E. , Dietrich Alexander , Birnbaumer Lutz , Malik Asrar B. , Mehta Dolly
Published: October 2012

Lung vascular endothelial barrier disruption and the accompanying inflammation are primary pathogenic features of acute lung injury (ALI); however, the basis for the development of both remains unclear. Studies have shown that activation of transient receptor potential canonical (TRPC) channels induces Ca2+ entry, which is essential for increased endothelial permeability. Here, we addressed the role of Toll-like receptor 4 (TLR4) intersection with TRPC6-dependent Ca2+ signaling in endothelial cells (ECs) in mediating lung vascular leakage and inflammation. We find that the endotoxin (lipopolysaccharide; LPS) induces Ca2+ entry in ECs in a TLR4-dependent manner. Moreover, deletion of TRPC6 renders mice resistant to endotoxin-induced barrier dysfunction and inflammation, and protects against sepsis-induced lethality. TRPC6 induces Ca2+ entry in ECs, which is secondary to the generation of diacylglycerol (DAG) induced by LPS. Ca2+ entry mediated by TRPC6, in turn, activates the nonmuscle myosin light chain kinase (MYLK), which not only increases lung vascular permeability but also serves as a scaffold to promote the interaction of myeloid differentiation factor 88 and IL-1R–associated kinase 4, which are required for NF-κB activation and lung inflammation. Our findings suggest that TRPC6-dependent Ca2+ entry into ECs, secondary to TLR4-induced DAG generation, participates in mediating both lung vascular barrier disruption and inflammation induced by endotoxin.
B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1
Authors: Karnowski Alex , Chevrier Stephane , Belz Gabrielle T. , Mount Adele , Emslie Dianne , D’Costa Kathy , Tarlinton David M. , Kallies Axel , Corcoran Lynn M.
Published: October 2012

A strong humoral response to infection requires the collaboration of several hematopoietic cell types that communicate via antigen presentation, surface coreceptors and their ligands, and secreted factors. The proinflammatory cytokine IL-6 has been shown to promote the differentiation of activated CD4+ T cells into T follicular helper cells (TFH cells) during an immune response. TFH cells collaborate with B cells in the formation of germinal centers (GCs) during T cell–dependent antibody responses, in part through secretion of critical cytokines such as IL-21. In this study, we demonstrate that loss of either IL-6 or IL-21 has marginal effects on the generation of TFH cells and on the formation of GCs during the response to acute viral infection. However, mice lacking both IL-6 and IL-21 were unable to generate a robust TFH cell–dependent immune response. We found that IL-6 production in follicular B cells in the draining lymph node was an important early event during the antiviral response and that B cell–derived IL-6 was necessary and sufficient to induce IL-21 from CD4+ T cells in vitro and to support TFH cell development in vivo. Finally, the transcriptional activator Oct2 and its cofactor OBF-1 were identified as regulators of Il6 expression in B cells.
Extensive evolutionary and functional diversity among mammalian AIM2-like receptors
Authors: Brunette Rebecca L. , Young Janet M. , Whitley Deborah G. , Brodsky Igor E. , Malik Harmit S. , Stetson Daniel B.
Published: October 2012

Innate immune detection of nucleic acids is important for initiation of antiviral responses. Detection of intracellular DNA activates STING-dependent type I interferons (IFNs) and the ASC-dependent inflammasome. Certain members of the AIM2-like receptor (ALR) gene family contribute to each of these pathways, but most ALRs remain uncharacterized. Here, we identify five novel murine ALRs and perform a phylogenetic analysis of mammalian ALRs, revealing a remarkable diversification of these receptors among mammals. We characterize the expression, localization, and functions of the murine and human ALRs and identify novel activators of STING-dependent IFNs and the ASC-dependent inflammasome. These findings validate ALRs as key activators of the antiviral response and provide an evolutionary and functional framework for understanding their roles in innate immunity.
Enhanced capacitance ratio and low minimum capacitance of varactor devices based on depletion-mode Ga-doped ZnO TFTs with a drain-offset structure
Authors: Remashan K , Choi Y S , Park S J , Jang J H
Published: October 2012

Depletion-mode Ga-doped ZnO thin-film transistors (TFTs) with a drain-offset configuration were fabricated employing a plasma-enhanced chemical vapour deposited Si3N4 gate insulator and a metal organic chemical vapour deposition grown Ga-doped ZnO channel layer. For comparison, conventional TFTs with drain-to-gate overlap were also fabricated. Capacitance–voltage characteristics of gate-to-drain capacitors and current–voltage characteristics of TFTs were measured. Although drain-offset TFTs exhibit poor device characteristics compared with conventional TFTs, these TFTs show better C
max/C
min ratio and C
min values. The C
max/C
min ratio is as large as 71.83 and C
min is as small as 0.3 fF µm−1 normalized for channel width, demonstrating the potential of these devices as varactors for circuit applications. Their better varactor performance is ascribed to the presence of a very small capacitance in the drain-offset region. The effect of drain-offset length variation on TFT and gate-to-drain capacitor performance is also reported.
Study of ultrasound-assisted radio-frequency plasma discharges in n-dodecane
Authors: Camerotto Elisabeth , Schepper Peter De , Nikiforov Anton Y , Brems Steven , Shamiryan Denis , Boullart Werner , Leys Christophe , Gendt Stefan De
Published: October 2012

This paper investigates the generation of a stable plasma phase in a liquid hydrocarbon (n-dodecane) by means of ultrasound (US) and radio-frequency (RF) or electromagnetic radiation. It is demonstrated for the first time that ultrasonic aided RF plasma discharges can be generated in a liquid. Plasma discharges are obtained for different gas mixtures at a pressure of 12 kPa and at low ignition powers (100 W for RF and 2.4 W cm−2 for US). Direct carbon deposition from the liquid precursor on Cu, Ni, SiO2 and Si substrates has been obtained and no apparent compositional or structural difference among the substrate materials was observed. Characterization of the deposited solid phase revealed an amorphous structure. In addition, structural changes in the liquid precursor after plasma treatment have been analysed. Optical emission spectroscopy (OES) allowed the estimation of several plasma characteristic temperatures. The plasma excitation temperature was estimated to be about 2.3–2.4 eV. The rotational and vibrational temperatures of the discharge in n-dodecane with Ar as a feed gas were 1400 K and 6500 K, respectively. In Ar/O2 plasma, an increased rotational (1630 K) and vibrational temperature (7200 K) were obtained.
Shack–Hartmann type laser wavefront sensor for measuring two-dimensional electron density distribution over extinguishing arc discharge
Authors: Inada Yuki , Matsuoka Shigeyasu , Kumada Akiko , Ikeda Hisatoshi , Hidaka Kunihiko
Published: October 2012

Shack–Hartmann type laser wavefront sensors were developed for measuring a two-dimensional electron density distribution over an arc channel in an extinguishing phase by only a single measurement with high temporal and spatial resolutions. The sensors were applied to pulsed arcs in a 3 mm air gap between rod-to-rod tungsten electrodes with a diameter of 1mm. Electron densities in the arc discharges with currents of several tens of amperes were 2 × 1023 m−3 around the gap centre, which were more than twice lower than those near the anode and cathode.
Characterization of nucleation and growth kinetics of the formation of water-soluble CdSe quantum dots by their optical properties
Authors: Mi Wen , Tian Jintao , Jia Jinqian , Tian Weiguo , Dai Jinhui , Wang Xin
Published: October 2012

The nucleation and growth kinetics of the formation of water-soluble CdSe quantum dots (QDs) was characterized by measurements of their optical properties of ultraviolet–visible and fluorescence spectra. The QDs were synthesized using thioglycolic acid as a capping agent. Two kinetic parameters, reaction temperature and time, were varied over wide ranges 20–90 °C and 0–12 h, respectively. Our results showed that a low reaction temperature was preferable for the nucleation process, resulting in relatively small particles and a narrow size distribution. The subsequent grain growth was mainly achieved within 1 h. The reaction temperature virtually affected the kinetic features of the QDs. The fluorescence measurements revealed largest variations of the fluorescence features for the 70 °C samples. From a viewpoint of controls of fluorescence colour and intensity over a wide range, a reaction temperature of 70 °C was appropriate for the CdSe QD synthesis.
An investigation of the growth of bismuth whiskers and nanowires during physical vapour deposition
Authors: Stanley S A , Stuttle C , Caruana A J , Cropper M D , Walton A S O
Published: October 2012

Bismuth thin films of thickness in the region of 500 nm have been prepared by planar magnetron sputtering onto glass, silicon and GaAs substrates. Electron microscopy of these films reveals that bismuth whiskers grow spontaneously when the substrate is heated to temperatures between 110 and 140 °C during deposition and the optimum temperature for such growth is largely independent of substrate. Depositing films under similar conditions using thermal evaporation does not, however, produce the whisker growth. X-ray diffraction has been employed to investigate film texture with temperature and it has been shown that the film crystallites are predominantly [1 1 0] and [1 1 1] oriented. The [1 1 0] orientation of the crystallites dominates at deposition temperatures above 110 °C for sputter deposition and the [1 1 1] at lower temperatures. The optimum temperature for whisker growth coincides with the temperature for the change between predominant orientations. While sputter deposition appears to favour films with crystallite orientation of [1 1 0], thermal evaporation favours [1 1 1] and has a higher change-over temperature. The whiskers that grow from the film emerge at off-normal angles between 43.3° and 69.2° with a mean of 54 ± 3°. The projected length of whiskers on a 500 nm film on a GaAs substrate shows a wide distribution to a maximum of more than 100 µm. The mean projected length for this sample was 16 ± 1 µm and the diameter is around 0.5 µm. Measurements of the electrical properties of the whiskers at room temperature reveals ohmic behaviour with an estimated resistivity of 2.2 ± 0.2 µΩ m. Detailed examination of scanning electron micrographs, eliminates all growth mechanisms except tip growth by a non-catalysed vapour–solid/vapour–liquid–solid method. By depositing thinner films it is shown that this spontaneous growth of whiskers offers a route to fabricate high quality bismuth nanowires of lengths exceeding 10 µm.
Interfacial and electrical properties of HfO2 gate dielectrics grown on GaAs by atomic layer deposition using different oxidants
Authors: Byun Young-Chul , Mahata Chandreswar , An Chee-Hong , Oh Jungwoo , Choi Rino , Kim Hyoungsub
Published: October 2012

In this paper, we examined the effects of two different oxidants (H2O and O3) used during the atomic layer deposition (ALD) of HfO2 films on GaAs, particularly focusing on its interfacial and electrical properties. In comparison with the H2O-based ALD process, the O3-based process produced a large amount of elemental As and Ga–O related bonds near the HfO2/GaAs interface due to its stronger oxidizing power. High interface state and border trap densities of the O3-based sample degraded the low-field electrical stability, which was confirmed by the capacitance and leakage current measurements under various voltage-stressing conditions. However, in terms of high-field stability, the O3-based sample showed a much stronger resistance to stress-induced trap generation than the H2O-based sample.
MGAviewer: a desktop visualization tool for analysis of metagenomics alignment data
Authors: Zhu Zhengwei , Niu Beifang , Chen Jing , Wu Sitao , Sun Shulei , Li Weizhong
Published: October 2012

Summary: Numerous metagenomics projects have produced tremendous amounts of sequencing data. Aligning these sequences to reference genomes is an essential analysis in metagenomics studies. Large-scale alignment data call for intuitive and efficient visualization tool. However, current tools such as various genome browsers are highly specialized to handle intraspecies mapping results. They are not suitable for alignment data in metagenomics, which are often interspecies alignments. We have developed a web browser-based desktop application for interactively visualizing alignment data of metagenomic sequences. This viewer is easy to use on all computer systems with modern web browsers and requires no software installation.

Availability:  http://weizhongli-lab.org/mgaviewer

Contact:  liwz@sdsc.edu
‘Location, Location, Location’: a spatial approach for rare variant analysis and an application to a study on non-syndromic cleft lip with or without cleft palate
Authors: Fier Heide , Won Sungho , Prokopenko Dmitry , AlChawa Taofik , Ludwig Kerstin U. , Fimmers Rolf , Silverman Edwin K. , Pagano Marcello , Mangold Elisabeth , Lange Christoph
Published: October 2012

Motivation: For the analysis of rare variants in sequence data, numerous approaches have been suggested. Fixed and flexible threshold approaches collapse the rare variant information of a genomic region into a test statistic with reduced dimensionality. Alternatively, the rare variant information can be combined in statistical frameworks that are based on suitable regression models, machine learning, etc. Although the existing approaches provide powerful tests that can incorporate information on allele frequencies and prior biological knowledge, differences in the spatial clustering of rare variants between cases and controls cannot be incorporated. Based on the assumption that deleterious variants and protective variants cluster or occur in different parts of the genomic region of interest, we propose a testing strategy for rare variants that builds on spatial cluster methodology and that guides the identification of the biological relevant segments of the region. Our approach does not require any assumption about the directions of the genetic effects.

Results: In simulation studies, we assess the power of the clustering approach and compare it with existing methodology. Our simulation results suggest that the clustering approach for rare variants is well powered, even in situations that are ideal for standard methods. The efficiency of our spatial clustering approach is not affected by the presence of rare variants that have opposite effect size directions. An application to a sequencing study for non-syndromic cleft lip with or without cleft palate (NSCL/P) demonstrates its practical relevance. The proposed testing strategy is applied to a genomic region on chromosome 15q13.3 that was implicated in NSCL/P etiology in a previous genome-wide association study, and its results are compared with standard approaches.

Availability: Source code and documentation for the implementation in R will be provided online. Currently, the R-implementation only supports genotype data. We currently are working on an extension for VCF files.

Contact:  heide.fier@googlemail.com
Pinstripe: a suite of programs for integrating transcriptomic and proteomic datasets identifies novel proteins and improves differentiation of protein-coding and non-coding genes
Authors: Gascoigne Dennis K. , Cheetham Seth W. , Cattenoz Pierre B. , Clark Michael B. , Amaral Paulo P. , Taft Ryan J. , Wilhelm Dagmar , Dinger Marcel E. , Mattick John S.
Published: October 2012

Motivation: Comparing transcriptomic data with proteomic data to identify protein-coding sequences is a long-standing challenge in molecular biology, one that is exacerbated by the increasing size of high-throughput datasets. To address this challenge, and thereby to improve the quality of genome annotation and understanding of genome biology, we have developed an integrated suite of programs, called Pinstripe. We demonstrate its application, utility and discovery power using transcriptomic and proteomic data from publicly available datasets.

Results: To demonstrate the efficacy of Pinstripe for large-scale analysis, we applied Pinstripe’s reverse peptide mapping pipeline to a transcript library including de novo assembled transcriptomes from the human Illumina Body Atlas (IBA2) and GENCODE v10 gene annotations, and the EBI Proteomics Identifications Database (PRIDE) peptide database. This analysis identified 736 canonical open reading frames (ORFs) supported by three or more PRIDE peptide fragments that are positioned outside any known coding DNA sequence (CDS). Because of the unfiltered nature of the PRIDE database and high probability of false discovery, we further refined this list using independent evidence for translation, including the presence of a Kozak sequence or functional domains, synonymous/non-synonymous substitution ratios and ORF length. Using this integrative approach, we observed evidence of translation from a previously unknown let7e primary transcript, the archetypical lncRNA H19, and a homolog of RD3. Reciprocally, by exclusion of transcripts with mapped peptides or significant ORFs (>80 codon), we identify 32 187 loci with RNAs longer than 2000 nt that are unlikely to encode proteins.

Availability and implementation: Pinstripe (pinstripe.matticklab.com) is freely available as source code or a Mono binary. Pinstripe is written in C# and runs under the Mono framework on Linux or Mac OS X, and both under Mono and .Net under Windows.

Contact:  m.dinger@garvan.org.au or j.mattick@garvan.org.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
fRMA ST: frozen robust multiarray analysis for Affymetrix Exon and Gene ST arrays
Authors: McCall Matthew N. , Jaffee Harris A. , Irizarry Rafael A.
Published: October 2012

Summary: Frozen robust multiarray analysis (fRMA) is a single-array preprocessing algorithm that retains the advantages of multiarray algorithms and removes certain batch effects by downweighting probes that have high between-batch residual variance. Here, we extend the fRMA algorithm to two new microarray platforms—Affymetrix Human Exon and Gene 1.0 ST—by modifying the fRMA probe-level model and extending the frma package to work with oligo ExonFeatureSet and GeneFeatureSet objects.

Availability and implementation: All packages are implemented in R. Source code and binaries are freely available through the Bioconductor project. Convenient links to all software and data packages can be found at http://mnmccall.com/software

Contact:  mccallm@gmail.com
miR-EdiTar: a database of predicted A-to-I edited miRNA target sites
Authors: Laganà Alessandro , Paone Alessio , Veneziano Dario , Cascione Luciano , Gasparini Pierluigi , Carasi Stefania , Russo Francesco , Nigita Giovanni , Macca Valentina , Giugno Rosalba , Pulvirenti Alfredo , Shasha Dennis , Ferro Alfredo , Croce Carlo M.
Published: October 2012

Motivation: A-to-I RNA editing is an important mechanism that consists of the conversion of specific adenosines into inosines in RNA molecules. Its dysregulation has been associated to several human diseases including cancer. Recent work has demonstrated a role for A-to-I editing in microRNA (miRNA)-mediated gene expression regulation. In fact, edited forms of mature miRNAs can target sets of genes that differ from the targets of their unedited forms. The specific deamination of mRNAs can generate novel binding sites in addition to potentially altering existing ones.

Results: This work presents miR-EdiTar, a database of predicted A-to-I edited miRNA binding sites. The database contains predicted miRNA binding sites that could be affected by A-to-I editing and sites that could become miRNA binding sites as a result of A-to-I editing.

Availability: miR-EdiTar is freely available online at http://microrna.osumc.edu/mireditar.

Contact:  alessandro.lagana@osumc.edu or carlo.croce@osumc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Multivariate Mixed Linear Model Analysis of Longitudinal Data: An Information-Rich Statistical Technique for Analyzing Plant Disease Resistance
Authors: Veturi Yogasudha , Kump Kristen , Walsh Ellie , Ott Oliver , Poland Jesse , Kolkman Judith M. , Balint-Kurti Peter J. , Holland James B. , Wisser Randall J.
Published: October 2012

The mixed linear model (MLM) is an advanced statistical technique applicable to many fields of science. The multivariate MLM can be used to model longitudinal data, such as repeated ratings of disease resistance taken across time. In this study, using an example data set from a multi-environment trial of northern leaf blight disease on 290 maize lines with diverse levels of resistance, multivariate MLM analysis was performed and its utility was examined. In the population and environments tested, genotypic effects were highly correlated across disease ratings and followed an autoregressive pattern of correlation decay. Because longitudinal data are often converted to the univariate measure of area under the disease progress curve (AUDPC), comparisons between univariate MLM analysis of AUDPC and multivariate MLM analysis of longitudinal data were made. Univariate analysis had the advantage of simplicity and reduced computational demand, whereas multivariate analysis enabled a comprehensive perspective on disease development, providing the opportunity for unique insights into disease resistance. To aid in the application of multivariate MLM analysis of longitudinal data on disease resistance, annotated program syntax for model fitting is provided for the software ASReml.
EXTENSIVE CHOROIDAL INFILTRATES IN CHOROIDAL BIOPSY PROVEN OCULAR SARCOIDOSIS
Authors: Chen Ling , Xu Gezhi
Published: October 2012

Purpose:

To report a rare manifestation of ocular sarcoidosis.

Methods:

Case report.

Results:

A 50-year-old man was misdiagnosed and treated as acute retinal necrosis and was referred to our clinic. Fundus examination revealed bilateral, extensive, confluent, subretinal yellowish white infiltrates throughout the fundus. Choroidal biopsy was performed and revealed noncaseating granuloma.

Conclusion:

This case presents a rare manifestation of ocular sarcoidosis as extensive confluent choroidal infiltrates throughout the fundus. The lack of the evidence for systemic sarcoidosis and unusual ocular presentation necessitate choroidal biopsy to confirm the diagnosis.
MACULAR HOLE OVERLYING PIGMENT EPITHELIAL DETACHMENT AFTER INTRAVITREAL INJECTION WITH RANIBIZUMAB
Authors: Raiji Veena R. , Eliott Dean , Sadda Srinivas R.
Published: October 2012

Purpose:

To describe a previously unrecognized complication of intravitreal injection in a patient with exudative macular degeneration and vitreomacular adhesion.

Methods:

Case report of a 69-year-old woman.

Results:

One month after intravitreal injection with ranibizumab for exudative macular degeneration, our patient developed a full-thickness macular hole with visual acuity of 20/100. After pars plana vitrectomy with membrane peeling and fluid-gas exchange, the macular hole was closed and the visual acuity improved to 20/60.

Conclusions:

Macular hole formation after intravitreal injection with ranibizumab is a potential complication that should be considered before treatment, especially in those patients with large subfoveal pigment epithelial detachments and vitreomacular adhesion. Although successful closure may be attained after pars plana vitrectomy, this potential morbidity should be considered when treating these patients. In addition to the already well-described tractional forces of the vitreous overlying the fovea, and the potential contractile nature of a choroidal neovascular complex in response to ranibizumab, a posterior pushing or stretching mechanism of a large pigment epithelial detachment may also contribute to macular hole formation.
A new method of calculating interplanar spacing: the position-factor method
Authors: Fan Quncheng
Published: October 2012

When the formulae for calculating the interplanar spacingd′hklfor the seven primary lattices among the 14 Bravais lattices are used for crystal structures containing an additional atom,d′hklmust be corrected by multiplying by a correction coefficient. Based on a simple principle of analytical geometry, a new position-factor method has been developed to calculate these correction coefficients. The position factorP[whereP=hx+ky+lz=s+m/q, the scalar product of the position (x, y, z) of an additional atom in a unit cell and any plane (hkl) passing through the additional atom] indicates the following characteristics of the (hkl) plane: whether there is an additional plane (m≠ 0) or not (m= 0), what the correction coefficient (m/q) is for the interplanar spacing ifm≠ 0, and what the distance [(s+m/q)d′hkl] is from the plane to the origin. In order to provide two examples of calculations usingP, six possible interplanar spacings were obtained for a hexagonal close-packed crystal, and four possible interplanar spacings and the structure factor were obtained for a diamond crystal. In addition, the 12 undetermined plane indices in X-ray diffraction card 1-1249 (PDF-2, ICDD, Newtown Square, PA, USA) for diamond were determined using the new calculation.
A fast, simple and robust protocol for growing crystals in the lipidic cubic phase
Authors: Aherne Margaret , Lyons Joseph A. , Caffrey Martin
Published: October 2012

A simple and inexpensive protocol for producing crystals in the sticky and viscous mesophase used for membrane protein crystallization by thein mesomethod is described. It provides crystals that appear within 15–30 min of setup at 293 K. The protocol gives the experimenter a convenient way of gaining familiarity and a level of comfort with the lipidic cubic mesophase, which can be daunting as a material when first encountered. Having used the protocol to produce crystals of the test protein, lysozyme, the experimenter can proceed with confidence to apply the method to more valuable membrane (and soluble) protein targets. The glass sandwich plates prepared using this robust protocol can further be used to practice harvesting and snap-cooling ofin meso-grown crystals, to explore diffraction data collection with mesophase-embedded crystals, and for an assortment of quality control and calibration applications when used in combination with a crystallization robot.