bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectroscopic study of gold nanoparticle formation through high intensity laser irradiation of solution
Authors: Nakamura Takahiro , Herbani Yuliati , Ursescu Daniel , Banici Romeo , Dabu Razvan Victor , Sato Shunichi
Published: August 2013

A spectroscopic study of the gold nanoparticle (NP) formation by high-intensity femtosecond laser irradiation of a gold ion solution was reported. The effect of varying energy density of the laser on the formation of gold NPs was also investigated. The surface plasmon resonance (SPR) peak of the gold nanocolloid in real-time UV-visible absorption spectra during laser irradiation showed a distinctive progress; the SPR absorption peak intensity increased after a certain irradiation time, reached a maximum and then gradually decreased. During this absorption variation, at the same time, the peak wavelength changed from 530 to 507 nm. According to an empirical equation derived from a large volume of experimental data, the estimated mean size of the gold NPs varied from 43.4 to 3.2 nm during the laser irradiation. The mean size of gold NPs formed at specific irradiation times by transmission electron microscopy showed the similar trend as that obtained in the spectroscopic analysis. From these observations, the formation mechanism of gold NPs during laser irradiation was considered to have two steps. The first is a reduction of gold ions by reactive species produced through a non-linear reaction during high intensity laser irradiation of the solution; the second is the laser fragmentation of produced gold particles into smaller pieces. The gold nanocolloid produced after the fragmentation by excess irradiation showed high stability for at least a week without the addition of any dispersant because of the negative charge on the surface of the nanoparticles probably due to the surface oxidation of gold nanoparticles. A higher laser intensity resulted in a higher efficiency of gold NPs fabrication, which was attributed to a larger effective volume of the reaction.
Compact and broadband directional coupling and demultiplexing in dielectric-loaded surface plasmon polariton waveguides based on the multimode interference effect
Authors: Zhu Zhihong , Garcia-Ortiz Cesar E. , Han Zhanghua , Radko Ilya P. , Bozhevolnyi Sergey I.
Published: August 2013

We theoretically, numerically, and experimentally demonstrate that a directional coupling function can be realized with a wide bandwidth (greater than 200 nm) in dielectric-loaded surface plasmon polariton waveguides based on the multimode interference effect. The functional size of the structures is in the range of several micrometers, which is much shorter than traditional directional couplers consisting of two parallel dielectric or plasmonic metallic waveguides. In addition, 1 × 2 beam splitting and demultiplexing function was realized. Such devices with wide bandwidth and small size indicate potential applications in high density lab-on-chip photonic integration and circuits.
Fluidic patch antenna based on liquid metal alloy/single-wall carbon-nanotubes operating at the S-band frequency
Authors: Aïssa B. , Nedil M. , Habib M. A. , Haddad E. , Jamroz W. , Therriault D. , Coulibaly Y. , Rosei F.
Published: August 2013

This letter describes the fabrication and characterization of a fluidic patch antenna operating at the S-band frequency (4 GHz). The antenna prototype is composed of a nanocomposite material made by a liquid metal alloy (eutectic gallium indium) blended with single-wall carbon-nanotube (SWNTs). The nanocomposite is then enclosed in a polymeric substrate by employing the UV-assisted direct-writing technology. The fluidic antennas specimens feature excellent performances, in perfect agreement with simulations, showing an increase in the electrical conductivity and reflection coefficient with respect to the SWNTs concentration. The effect of the SWNTs on the long-term stability of antenna's mechanical properties is also demonstrated.
Tunable out-of-plane slow light in resonance induced transparent grating waveguide structures
Authors: Chen Yongyao , Zhang Zhijian , Yu Miao
Published: August 2013

We investigate the unexplored physics of slow light effect in resonance induced transparent grating waveguide structures. We show that with a simple three-layer thin-film structure, a narrow transparent window can be obtained, enabling substantially slow down the speed of out-of-plane propagation of light. Further, we numerically demonstrate an active slow light device that potentially achieves high-speed control of slow light at the optical communication band. This work paves a way for the design of functional devices, such as slow-light chips, switches, and modulators functioning in optical and infrared regimes.
Ultra-compliant liquid metal electrodes with in-plane self-healing capability for dielectric elastomer actuators
Authors: Liu Yang , Gao Meng , Mei Shengfu , Han Yanting , Liu Jing
Published: August 2013

The method of directly printing liquid metal films as highly conductive and super compliant electrodes for dielectric elastomer actuator (DEA) was proposed and experimentally demonstrated with working mechanisms interpreted. Such soft electrodes enable DE film to approach its maximum strain and stress at relatively low voltages. Further, its unique capability of achieving two-dimensional in-plane self-healing by merely actuating the DEA was disclosed, which would allow actuators more tolerant to fault and resilient to abusive environments. This high performance actuator has important value in a wide spectrum of situations ranging from artificial muscle, flexible electronics to smart clothing etc.
Frequency response of atmospheric pressure gas breakdown in micro/nanogaps
Authors: Semnani Abbas , Venkattraman Ayyaswamy , Alexeenko Alina A. , Peroulis Dimitrios
Published: August 2013

In this paper, we study gas breakdown in micro/nanogaps at atmospheric pressure from low RF to high millimeter band. For gaps larger than about 10 μm, the breakdown voltage agrees with macroscale vacuum experiments, exhibiting a sharp decrease at a critical frequency, due to transition between the boundary- and diffusion-controlled regimes, and a gradual increase at very high frequencies as a result of inefficient energy transfer by field. For sub-micron gaps, a much lower breakdown is obtained almost independent of frequency because of the dominance of field emission.
The resistive switching in TiO2 films studied by conductive atomic force microscopy and Kelvin probe force microscopy
Authors: Du Yuanmin , Kumar Amit , Pan Hui , Zeng Kaiyang , Wang Shijie , Yang Ping , Wee Andrew Thye Shen
Published: August 2013

The resistive switching characteristics of TiO2 thin films were investigated using conductive atomic force microscopy (CAFM) and Kelvin probe force microscopy (KPFM). The as-prepared TiO2 thin films were modulated into higher and lower resistance states by applying a local electric field. We showed that the resistive switching results from charge injection and release assisted by electro-migration of oxygen ions. An integrated model combined with filamentary and interfacial effects was utilized to elucidate the experimentally observed phenomenon.
Bifurcation, mode coupling and noise in a nonlinear multimode superconducting microwave resonator
Authors: Tancredi G. , Ithier G. , Meeson P. J.
Published: August 2013

The addition of nonlinearity to an harmonic resonator provides a route to complex dynamical behaviour of resonant modes, including coupling between them. We present a superconducting device that makes use of the nonlinearity of Josephson junctions to introduce a controlled, tunable, nonlinear inductance to a thin film coplanar waveguide resonator. Considering the device as a potential quantum optical component in the microwave regime, we create a sensitive bifurcation amplifier and then demonstrate spectroscopy of other resonant modes via the intermode coupling. We find that the sensitivity of the device approaches within a factor two quantitative agreement with a quantum model by Dykman but is limited by a noise that has its source(s) on-chip.
Simulation of the enhanced infrared photoresponse of type-II GaSb/GaAs quantum ring solar cells
Authors: Wagener M. C. , Carrington P. J. , Botha J. R. , Krier A.
Published: August 2013

The extended photo-response of solar cells containing ten periods of GaSb/GaAs quantum rings imbedded in the p-i-n junction has been described using a single-band representation of the type-II quantum ring structure. By fitting the experimental data, the authors were able to deduce that the quantum rings are well represented by a Gaussian height distribution and a large valence band discontinuity. The simulated band of states is shown to be well matched to the photoluminescence analysis of the structure, with the inhomogeneous size distribution resulting in a band of hole states roughly 390 meV above the valence band.
Synthesis of Novel Biaryl Derivatives of Sesamol (5-Benzodioxolol) and Evaluation of their Antioxidant Activity Against DPPH Radical
Authors: Rodríguez Sergio A. , Nazareno Mónica A. , Baumgartner María T.
Published: August 2013

A simple and direct arylation of sesamol with aryl halides by a photoinduced reaction is reported. Five 6-arylsesamol derivatives were synthesized in order to evaluate possible changes in their antioxidant properties as a function of the C6 aryl substituent nature. Extension of the procedure to the reaction with o-dihalobenzenes leads to the synthesis of ring-closure products bearing a tetracyclic aromatic condensed ring system, although in lower overall yields (~45 %). The antioxidant activity of the synthetic derivatives towards 1,1-diphenyl-2-picrylhydrazyl radical was determined taking sesamol as the reference compound. In addition, the relationship between the antiradical activities of these molecules against this radical and the bond dissociation energies of their phenolic O–H group was calculated using computational chemistry methods.
Unusual Potassium-η2-Aromatic Interactions in the Crystal Structure of the Diphenylarsenide Transfer Reagent, KAsPh2·2(1,4-Dioxane)
Authors: Adams Michael C. , Koutsantonis George A. , Skelton Brian W. , White Allan H.
Published: August 2013

In attempting the metallation of 1,2-bis(diphenylarsino)ethane, the title compound KAsPh2·2(1,4-dioxane) was obtained and characterised with a single crystal X-ray structure determination. Like the sodium counterpart, which is a monosolvate, NaAsPh2·1,4-dioxane, the complex may be considered as a two-dimensional polymer, the potassium atoms being linked by bridging 1,4-dioxane units, the oxygen atoms of which form a quasi-square planar array about the potassium atom (K–O 2.676–2.839(3) Å). Unlike the sodium complex, in which arsenide bridging is an intrinsic motif in the construction of the polymer, the K⋯As distance here is long (3.4662(10) Å), with the anion being terminal/monodentate, and counterposed in what may be considered a quasi-octahedral coordination sphere, by a trans-approach to two atoms of a neighbouring aromatic ring (K⋯C(ar) 3.361, 3.416(4) Å), extending the polymer in the third dimension.
‘This is a forever project’: supporting lifestyle changes in a regional Queensland community-based cardiac rehabilitation program
Authors: Madsen Wendy
Published: August 2013

Cardiac rehabilitation programs throughout the world have struggled for several years to attract more participants and facilitate behaviour changes in these clients. Over the past few years, there has been an increased level of attention in the role that self-efficacy and social support may play in this respect. The main aim of this study was to explore self-efficacy and social support within a regional, community-based cardiac rehabilitation program that does not adhere to traditional cardiac rehabilitation structures. Twelve participants were interviewed and two major themes emerged from the thematic analysis of the interview transcripts: making personal lifestyle changes; and supportive environment for lifestyle changes. Although this study is exploratory in nature, it has highlighted the significance of social support from within a program as opposed to participants’ friends and family, the subject of most social-support research. It also contributes to the challenges others are starting to make regarding the limited timeframes associated with traditional cardiac rehabilitation programs, suggesting more time may be needed to build firmer psychosocial foundations for behaviour change after cardiac events.
Walking patterns in pregnancy
Authors: Doran Frances M. , Buckley Nellie A.
Published: August 2013

Women are encouraged to be active before, during and after pregnancy. However, most pregnant women do not engage in sufficient levels of physical activity. For women who experience gestational diabetes mellitus (GDM), physical activity recommendations are part of the standard management. Walking is the most common activity undertaken by women across the lifespan and often recommended by health professionals. Little research specifically exploring the patterns of walking before, during and after pregnancy has been undertaken. This study investigated patterns of walking undertaken by pregnant women, including those who experienced GDM. A sample of convenience was used to recruit pregnant or postpartum women in regional New South Wales, Australia. Women completed a self-report physical activity survey. The survey also included demographic questions, GDM diagnosis and physical activity advice received from health professionals. The respondents were divided into two groups; those with GDM (GDM) and those without GDM (NoGDM). In both groups, walking declined during pregnancy and returned to prepregnancy levels in the postpartum. This decline was similar to the decline observed in leisure-time physical activity. The GDM group walked more than the NoGDM group and a higher percentage of GDM reported being advised to engage in physical activity by health professionals. Even though walking is the most common activity undertaken for women across the lifespan, prepregnancy walking levels do not necessarily continue during pregnancy. Advice from health professionals may assist in maintaining walking levels during pregnancy. Encouraging pregnant women to continue their prepregnancy walking level may be a relatively simple strategy to increase participation in physical activity.
Interferon regulatory factor 3 controls interleukin-17 expression in CD8 T lymphocytes
Authors: Ysebrant de Lendonck Laure , Tonon Sandrine , Nguyen Muriel , Vandevenne Patricia , Welsby Iain , Martinet Valerie , Molle Céline , Charbonnier Louis-Marie , Leo Oberdan , Goriely Stanislas
Published: August 2013

Significance

Interferon regulatory factor (IRF) 3 is one of the key transcription factors implicated in innate antiviral responses. In recent years its role in shaping adaptive immune responses through activation of a specific transcriptional program in antigen-presenting cells has been appreciated. In this work we show that within CD8 T cells, IRF3 interacts with the transcriptional network that controls their polarization, thereby limiting the capacity of these cells to produce IL-17. These findings shed light on the functions of IRF3 in adaptive immune responses.
Generation of hair cells in neonatal mice by β-catenin overexpression in Lgr5-positive cochlear progenitors
Authors: Shi Fuxin , Hu Lingxiang , Edge Albert S. B.
Published: August 2013

Mammalian hair cells do not regenerate, and their loss is a major cause of deafness. We recently identified leucine-rich repeat containing, G-protein-coupled receptor 5 (Lgr5)-expressing cochlear supporting cells with the capacity for self-renewal and hair cell differentiation in vitro. We found that these cells, a subset of cochlear supporting cells, were responsive to Wnt signaling. Here we asked whether these Lgr5-positive cells, despite their lack of contribution to hair cell replacement after degenerative loss, could be driven by forced expression of β-catenin to act as hair cell progenitors in vivo. We showed that forced stabilization of β-catenin in supporting cells in neonatal animals resulted in proliferation of supporting cells and generation of hair cells. Although β-catenin expression was increased by genetic means in all supporting cells, entry to the cell cycle and differentiation to hair cells of the normally postmitotic cells was restricted to the Lgr5-positive population. Our finding suggests that Wnt/β-catenin can drive Lgr5-positive cells to act as hair cell progenitors, even after their exit from the cell cycle and apparent establishment of cell fate.
Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis
Authors: Awojoodu Anthony O. , Ogle Molly E. , Sefcik Lauren S. , Bowers Daniel T. , Martin Kyle , Brayman Kenneth L. , Lynch Kevin R. , Peirce-Cottler Shayn M. , Botchwey Edward
Published: August 2013

Endothelial cells play significant roles in conditioning tissues after injury by the production and secretion of angiocrine factors. At least two distinct subsets of monocytes, CD45
+
CD11b
+
Gr1
+
Ly6C
+
inflammatory and CD45
+
CD11b
+
Gr1
−
Ly6C
−
anti-inflammatory monocytes, respond differentially to these angiocrine factors and promote pathogen/debris clearance and arteriogenesis/tissue regeneration, respectively. We demonstrate here that local sphingosine 1-phosphate receptor 3 (S1P
3
) agonism recruits anti-inflammatory monocytes to remodeling vessels. Poly(lactic-co-glycolic acid) thin films were used to deliver FTY720, an S1P
1/3
agonist, to inflamed and ischemic tissues, which resulted in a reduction in proinflammatory cytokine secretion and an increase in regenerative cytokine secretion. The altered balance of cytokine secretion results in preferential recruitment of anti-inflammatory monocytes from circulation. The chemotaxis of these cells, which express more S1P
3
than inflammatory monocytes, toward SDF-1α was also enhanced with FTY720 treatment, but not in S1P
3
knockout cells. FTY720 delivery enhanced arteriolar diameter expansion and increased length density of the local vasculature. This work establishes a role for S1P receptor signaling in the local conditioning of tissues by angiocrine factors that preferentially recruit regenerative monocytes that can enhance healing outcomes, tissue regeneration, and biomaterial implant functionality.
Release of arsenic to deep groundwater in the Mekong Delta, Vietnam, linked to pumping-induced land subsidence
Authors: Erban Laura E. , Gorelick Steven M. , Zebker Howard A. , Fendorf Scott
Published: August 2013

Deep aquifers in South and Southeast Asia are increasingly exploited as presumed sources of pathogen- and arsenic-free water, although little is known of the processes that may compromise their long-term viability. We analyze a large area (>1,000 km
2
) of the Mekong Delta, Vietnam, in which arsenic is found pervasively in deep, Pliocene–Miocene-age aquifers, where nearly 900 wells at depths of 200–500 m are contaminated. There, intensive groundwater extraction is causing land subsidence of up to 3 cm/y as measured using satellite-based radar images from 2007 to 2010 and consistent with transient 3D aquifer simulations showing similar subsidence rates and total subsidence of up to 27 cm since 1988. We propose a previously unrecognized mechanism in which deep groundwater extraction is causing interbedded clays to compact and expel water containing dissolved arsenic or arsenic-mobilizing solutes (e.g., dissolved organic carbon and competing ions) to deep aquifers over decades. The implication for the broader Mekong Delta region, and potentially others like it across Asia, is that deep, untreated groundwater will not necessarily remain a safe source of drinking water.
On-chip phenotypic analysis of inflammatory monocytes in atherogenesis and myocardial infarction
Authors: Foster Greg A. , Gower R. Michael , Stanhope Kimber L. , Havel Peter J. , Simon Scott I. , Armstrong Ehrin J.
Published: August 2013

Monocyte recruitment to inflamed arterial endothelium initiates plaque formation and drives progression of atherosclerosis. Three distinct monocyte subsets are detected in circulation (CD14
++
CD16
−
, CD14
++
CD16
+
, and CD14
+
CD16
++
), and each may play distinct roles during atherogenesis and myocardial infarction. We studied a range of subjects that included otherwise healthy patients with elevated serum triglyceride levels to patients presenting with acute myocardial infarction. Our objective was to correlate an individual’s risk with the activation state of each monocyte subset as a function of changes in adhesion receptor expression using flow cytometric quantitation of integrins and
l
-selectin membrane expression. A microfluidic-based laboratory-on-a-chip was developed to quantify the adhesion efficiency of monocytes sheared in whole blood on vascular cell adhesion molecule-1, while characterizing adhesion receptor expression and topography on captured monocytes. CD14
++
CD16
+
monocytes adhered with sevenfold higher efficiency than other subsets, and in patients with myocardial infarction the capture efficiency of this subset was double that for healthy subjects. In patients with hypertriglyceridemia, this increase in monocyte adhesion was attributable to CD14
++
CD16
+
uptake of triglyceride-rich lipoproteins and subsequent signaling via a Phospholipase C–dependent mechanism to increase CD11c expression, very late antigen–4 function, and integrin coclustering within focal adhesive sites on vascular cell adhesion molecule-1. In summary, we introduce a unique laboratory-on-a-chip method for quantifying the activation state of monocyte subsets. These experiments reveal that CD11c/CD18 is an inducible integrin whose expression correlates with a monocyte inflammatory state in subjects at risk for atherogenesis and in patients with myocardial infarction.
Inhibitory role of the transcription repressor Gfi1 in the generation of thymus-derived regulatory T cells
Authors: Shi Lewis Zhichang , Kalupahana Nishan S. , Turnis Meghan E. , Neale Geoffrey , Hock Hanno , Vignali Dario A. A. , Chi Hongbo
Published: August 2013

Significance

Thymic development of regulatory T cells (Treg) is a crucial event for immune homeostasis. Despite extensive descriptions of molecular pathways functioning within Tregcells, little is known how Tregdevelopment is shaped by the control of extrinsic factors. Here, we show that the transcription factor growth factor independent 1 (Gfi1) restrains thymic generation of Tregcells. Loss of Gfi1 led to aberrant production of the cytokine IL-2. Elevated IL-2 then drove the expansion of Tregcells. Accordingly, deficiency of Gfi1 dampened antitumor immunity. Our results establish that Gfi1 actively controls thymocyte IL-2 production, thereby shaping thymic generation of Tregcells.
Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I
Authors: Pang Iris K. , Pillai Padmini S. , Iwasaki Akiko
Published: August 2013

Induction of a proinflammatory response is the hallmark of host innate defense against invading pathogens. Host recognition of influenza A virus (IAV) infection relies on pattern-recognition receptors, including Toll-like receptor 7 (TLR7) and retinoic acid inducible gene-1 (RIG-I) for the activation of innate-immune responses. Here, we show that following a physiological low dose of IAV infection, viral sensing by either TLR7 or RIG-I induces a proinflammatory program that promotes viral replication. Transfer of bronchoalveolar lavage from infected wild-type mice into the airway of mice deficient in TLR7 and RIG-I pathways was sufficient to restore viral replication efficiency. Comparison of IAV-infected cells revealed that inflammatory mediators elicited by TLR7 and RIG-I signaling recruit viral target cells to the airway, thereby enhancing viral load within the respiratory tract. Our data suggest that IAV uses physiological levels of inflammatory responses for its replicative advantage and highlight the complex interplay between viruses and the host innate-immune responses.
Odor representations in the olfactory bulb evolve after the first breath and persist as an odor afterimage
Authors: Patterson Michael Andrew , Lagier Samuel , Carleton Alan
Published: August 2013

Significance

Even when presented with steady stimuli, sensory systems respond dynamically, including adaptation or responses after the stimuli are gone (afterimages). To measure these dynamics in smell, we recorded electrical signals from the mouse brain. We found that the neuronal representation of odors changes between breaths, and not by simple adaptation, showing that the olfactory system also undergoes these dynamics. After the end of the odor, the brain continued responding, showing that there are olfactory afterimages. Finally, we tried to isolate where afterimages are generated and found that, while the nose has some contribution, afterimages are mainly maintained in the brain.
Target specificity among canonical nuclear poly(A) polymerases in plants modulates organ growth and pathogen response
Authors: Vi Son Lang , Trost Gerda , Lange Peggy , Czesnick Hjördis , Rao Nishta , Lieber Diana , Laux Thomas , Gray William M. , Manley James L. , Groth Detlef , Kappel Christian , Lenhard Michael
Published: August 2013

Polyadenylation of pre-mRNAs is critical for efficient nuclear export, stability, and translation of the mature mRNAs, and thus for gene expression. The bulk of pre-mRNAs are processed by canonical nuclear poly(A) polymerase (PAPS). Both vertebrate and higher-plant genomes encode more than one isoform of this enzyme, and these are coexpressed in different tissues. However, in neither case is it known whether the isoforms fulfill different functions or polyadenylate distinct subsets of pre-mRNAs. Here we show that the three canonical nuclear PAPS isoforms in
Arabidopsis
are functionally specialized owing to their evolutionarily divergent C-terminal domains. A strong loss-of-function mutation in
PAPS1
causes a male gametophytic defect, whereas a weak allele leads to reduced leaf growth that results in part from a constitutive pathogen response. By contrast, plants lacking both
PAPS2
and
PAPS4
function are viable with wild-type leaf growth. Polyadenylation of
SMALL AUXIN UP RNA
(
SAUR
) mRNAs depends specifically on
PAPS1
function. The resulting reduction in
SAUR
activity in
paps1
mutants contributes to their reduced leaf growth, providing a causal link between polyadenylation of specific pre-mRNAs by a particular PAPS isoform and plant growth. This suggests the existence of an additional layer of regulation in plant and possibly vertebrate gene expression, whereby the relative activities of canonical nuclear PAPS isoforms control de novo synthesized poly(A) tail length and hence expression of specific subsets of mRNAs.
Presenilins regulate calcium homeostasis and presynaptic function via ryanodine receptors in hippocampal neurons
Authors: Wu Bei , Yamaguchi Hiroo , Lai F. Anthony , Shen Jie
Published: August 2013

Presenilin (PS) plays a central role in the pathogenesis of Alzheimer’s disease, and loss of PS causes progressive memory impairment and age-related neurodegeneration in the mouse cerebral cortex. In hippocampal neurons, PS is essential for neurotransmitter release, NMDA receptor-mediated responses, and long-term potentiation. PS is also involved in the regulation of calcium homeostasis, although the precise site of its action is less clear. Here we investigate the mechanism by which PS regulates synaptic function and calcium homeostasis using acute hippocampal slices from
PS
conditional knockout mice and primary cultured postnatal hippocampal neurons, in which PS is inducibly inactivated. Using two different calcium probes, Fura-2 and Mag–Fura-2, we found that inactivation of PS in primary hippocampal neurons does not affect calcium concentration in the endoplasmic reticulum. Rather, in the absence of PS, levels of ryanodine receptor (RyR) are reduced in the hippocampus, measured by Western analysis and radioligand binding assay, although the mRNA expression is unaffected. RyR-mediated function is also impaired, as indicated by reduced RyR agonist-induced calcium release from the ER and RyR-mediated synaptic responses in the absence of PS. Furthermore, knockdown of RyR expression in wild-type hippocampal neurons by two independent shRNAs to levels comparable with the RyR protein reduction in
PS-
deficient hippocampal neurons mimics the defects exhibited in calcium homeostasis and presynaptic function. Collectively, our findings show that PS regulates calcium homeostasis and synaptic function via RyR and suggest that disruption of intracellular calcium homeostasis may be an early pathogenic event leading to presynaptic dysfunction in Alzheimer’s disease.
TNFSF15 inhibits vasculogenesis by regulating relative levels of membrane-bound and soluble isoforms of VEGF receptor 1
Authors: Qi Jian-Wei , Qin Ting-Ting , Xu Li-Xia , Zhang Kun , Yang Gui-Li , Li Jie , Xiao Huai-Yuan , Zhang Zhi-Song , Li Lu-Yuan
Published: August 2013

Mouse bone marrow-derived Lin
−
-Sca-1
+
endothelial progenitor cell (EPC) has pluripotent abilities such as supporting neovascularization. Vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) (Flt1) recognizes various VEGF isoforms and is critically implicated in a wide range of physiological and pathological settings, including vasculogenesis. Mouse EPC expresses two isoforms of VEGFR1: mFlt1, which transmits ligand-induced signals; and sFlt1, which acts as a negative regulator by sequestering ligands of VEGF receptors. How the relative levels of mFlt1 and sFlt1 are regulated is not yet clear. We report here that tumor necrosis factor superfamily 15 (TNFSF15) (also known as VEGI or TL1A), an endothelial cell-secreted cytokine, simultaneously promotes mFlt1 degradation and up-regulates sFlt1 expression in EPC, giving rise to disruption of VEGF- or PlGF-induced activation of eNOS and MAPK p38 and effective inhibition of VEGF-driven, EPC-supported vasculogenesis in a murine Matrigel implant model. TNFSF15 treatment of EPC cultures facilitates Akt deactivation-dependent, ubiquitin-assisted degradation of mFlt1 and stimulates sFlt1 expression by activating the PKC, Src, and Erk1/2 signaling pathway. Additionally, TNFSF15 promotes alternative splicing of the Flt1 gene in favor of sFlt1 production by down-regulating nuclear protein Jumonji domain-containing protein 6 (Jmjd6), thus alleviating Jmjd6-inhibited sFlt1 expression. These findings indicate that TNFSF15 is a key component of a molecular mechanism that negatively modulates EPC-supported vasculogenesis through regulation of the relative levels of mFlt1 and sFlt1 in EPC.
R-loop formation at
Snord116
mediates topotecan inhibition of
Ube3a-antisense
and allele-specific chromatin decondensation
Authors: Powell Weston T. , Coulson Rochelle L. , Gonzales Michael L. , Crary Florence K. , Wong Spencer S. , Adams Sarrita , Ach Robert A. , Tsang Peter , Yamada Nazumi Alice , Yasui Dag H. , Chédin Frédéric , LaSalle Janine M.
Published: August 2013

Prader–Willi syndrome (PWS) and Angelman syndrome (AS) are oppositely imprinted autism-spectrum disorders with known genetic bases, but complex epigenetic mechanisms underlie their pathogenesis. The PWS/AS locus on 15q11–q13 is regulated by an imprinting control region that is maternally methylated and silenced. The PWS imprinting control region is the promoter for a one megabase paternal transcript encoding the ubiquitous protein-coding
Snrpn
gene and multiple neuron-specific noncoding RNAs, including the PWS-related
Snord116
repetitive locus of small nucleolar RNAs and host genes, and the antisense transcript to AS-causing ubiquitin ligase encoding
Ube3a
(
Ube3a-ATS
). Neuron-specific transcriptional progression through
Ube3a-ATS
correlates with paternal
Ube3a
silencing and chromatin decondensation. Interestingly, topoisomerase inhibitors, including topotecan, were recently identified in an unbiased drug screen for compounds that could reverse the silent paternal allele of
Ube3a
in neurons, but the mechanism of topotecan action on the PWS/AS locus is unknown. Here, we demonstrate that topotecan treatment stabilizes the formation of RNA:DNA hybrids (R loops) at G-skewed repeat elements within paternal
Snord116,
corresponding to increased chromatin decondensation and inhibition of
Ube3a-ATS
expression. Neural precursor cells from paternal
Snord116
deletion mice exhibit increased
Ube3a-ATS
levels in differentiated neurons and show a reduced effect of topotecan compared with wild-type neurons. These results demonstrate that the AS candidate drug topotecan acts predominantly through stabilizing R loops and chromatin decondensation at the paternally expressed PWS
Snord116
locus. Our study holds promise for targeted therapies to the
Snord116
locus for both AS and PWS.
Search strategy has influenced the discovery rate of human viruses
Authors: Rosenberg Ronald , Johansson Michael A. , Powers Ann M. , Miller Barry R.
Published: August 2013

A widely held concern is that the pace of infectious disease emergence has been increasing. We have analyzed the rate of discovery of pathogenic viruses, the preeminent source of newly discovered causes of human disease, from 1897 through 2010. The rate was highest during 1950–1969, after which it moderated. This general picture masks two distinct trends: for arthropod-borne viruses, which comprised 39% of pathogenic viruses, the discovery rate peaked at three per year during 1960–1969, but subsequently fell nearly to zero by 1980; however, the rate of discovery of nonarboviruses remained stable at about two per year from 1950 through 2010. The period of highest arbovirus discovery coincided with a comprehensive program supported by The Rockefeller Foundation of isolating viruses from humans, animals, and arthropod vectors at field stations in Latin America, Africa, and India. The productivity of this strategy illustrates the importance of location, approach, long-term commitment, and sponsorship in the discovery of emerging pathogens.
Optical imaging of the chorioretinal vasculature in the living human eye
Authors: Kim Dae Yu , Fingler Jeff , Zawadzki Robert J. , Park Susanna S. , Morse Lawrence S. , Schwartz Daniel M. , Fraser Scott E. , Werner John S.
Published: August 2013

Detailed visualization of microvascular changes in the human retina is clinically limited by the capabilities of angiography imaging, a 2D fundus photograph that requires an intravenous injection of fluorescent dye. Whereas current angiography methods enable visualization of some retinal capillary detail, they do not adequately reveal the choriocapillaris or other microvascular features beneath the retina. We have developed a noninvasive microvascular imaging technique called phase-variance optical coherence tomography (pvOCT), which identifies vasculature three dimensionally through analysis of data acquired with OCT systems. The pvOCT imaging method is not only capable of generating capillary perfusion maps for the retina, but it can also use the 3D capabilities to segment the data in depth to isolate vasculature in different layers of the retina and choroid. This paper demonstrates some of the capabilities of pvOCT imaging of the anterior layers of choroidal vasculature of a healthy normal eye as well as of eyes with geographic atrophy (GA) secondary to age-related macular degeneration. The pvOCT data presented permit digital segmentation to produce 2D depth-resolved images of the retinal vasculature, the choriocapillaris, and the vessels in Sattler’s and Haller’s layers. Comparisons are presented between
en face
projections of pvOCT data within the superficial choroid and clinical angiography images for regions of GA. Abnormalities and vascular dropout observed within the choriocapillaris for pvOCT are compared with regional GA progression. The capability of pvOCT imaging of the microvasculature of the choriocapillaris and the anterior choroidal vasculature has the potential to become a unique tool to evaluate therapies and understand the underlying mechanisms of age-related macular degeneration progression.
Subset of heat-shock transcription factors required for the early response of
Arabidopsis
to excess light
Authors: Jung Hou-Sung , Crisp Peter A. , Estavillo Gonzalo M. , Cole Benjamin , Hong Fangxin , Mockler Todd C. , Pogson Barry J. , Chory Joanne
Published: August 2013

Sunlight provides energy for photosynthesis and is essential for nearly all life on earth. However, too much or too little light or rapidly fluctuating light conditions cause stress to plants. Rapid changes in the amount of light are perceived as a change in the reduced/oxidized (redox) state of photosynthetic electron transport components in chloroplasts. However, how this generates a signal that is relayed to changes in nuclear gene expression is not well understood. We modified redox state in the reference plant,
Arabidopsis thaliana
, using either excess light or low light plus the herbicide DBMIB (2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone), a well-known inhibitor of photosynthetic electron transport. Modification of redox state caused a change in expression of a common set of about 750 genes, many of which are known stress-responsive genes. Among the most highly enriched promoter elements in the induced gene set were heat-shock elements (HSEs), known motifs that change gene expression in response to high temperature in many systems. We show that HSEs from the promoter of the
ASCORBATE PEROXIDASE 2
(
APX2
) gene were necessary and sufficient for
APX2
expression in conditions of excess light, or under low light plus the herbicide. We tested
APX2
expression phenotypes in overexpression and loss-of-function mutants of 15
Arabidopsis
A-type heat-shock transcription factors (HSFs), and identified HSFA1D, HSFA2, and HSFA3 as key factors regulating
APX2
expression in diverse stress conditions. Excess light regulates both the subcellular location of HSFA1D and its biochemical properties, making it a key early component of the excess light stress network of plants.
Polo kinase Cdc5 is a central regulator of meiosis I
Authors: Attner Michelle A. , Miller Matthew P. , Ee Ly-sha , Elkin Sheryl K. , Amon Angelika
Published: August 2013

During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that
CDC5
-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome segregation.
CDC5
also establishes conditions for centromeric cohesin removal during meiosis II by promoting the degradation of Spo13, a protein that protects centromeric cohesin during meiosis I. Despite
CDC5
’s central role in meiosis I, the protein kinase is dispensable during meiosis II and does not even phosphorylate its meiosis I targets during the second meiotic division. We conclude that Cdc5 has evolved into a master regulator of the unique meiosis I chromosome segregation pattern.
The Great Recession, genetic sensitivity, and maternal harsh parenting
Authors: Lee Dohoon , Brooks-Gunn Jeanne , McLanahan Sara S. , Notterman Daniel , Garfinkel Irwin
Published: August 2013

Using data from the Fragile Families and Child Wellbeing Study, this study examined the effects of the Great Recession on maternal harsh parenting. We found that changes in macroeconomic conditions, rather than current conditions, affected harsh parenting, that declines in macroeconomic conditions had a stronger impact on harsh parenting than improvements in conditions, and that mothers’ responses to adverse economic conditions were moderated by the
DRD2 Taq1A
genotype. We found no evidence of a moderating effect for two other, less well-studied SNPs from the
DRD4
and
DAT1
genes.
PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression
Authors: Anggono Victor , Koç-Schmitz Yeliz , Widagdo Jocelyn , Kormann Jan , Quan Annie , Chen Chih-Ming , Robinson Phillip J. , Choi Se-Young , Linden David J. , Plomann Markus , Huganir Richard L.
Published: August 2013

The dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses is crucial for synaptic transmission, plasticity, learning, and memory. The protein interacting with C-kinase 1 (PICK1) directly interacts with GluA2/3 subunits of the AMPARs. Although the role of PICK1 in regulating AMPAR trafficking and multiple forms of synaptic plasticity is known, the exact molecular mechanisms underlying this process remain unclear. Here, we report a unique interaction between PICK1 and all three members of the protein kinase C and casein kinase II substrate in neurons (PACSIN) family and show that they form a complex with AMPARs. Our results reveal that knockdown of the neuronal-specific protein, PACSIN1, leads to a significant reduction in AMPAR internalization following the activation of NMDA receptors in hippocampal neurons. The interaction between PICK1 and PACSIN1 is regulated by PACSIN1 phosphorylation within the variable region and is required for AMPAR endocytosis. Similarly, the binding of PICK1 to the ubiquitously expressed PACSIN2 is also regulated by the homologous phosphorylation sites within the PACSIN2-variable region. Genetic deletion of PACSIN2, which is highly expressed in Purkinje cells, eliminates cerebellar long-term depression. This deficit can be fully rescued by overexpressing wild-type PACSIN2, but not by a PACSIN2 phosphomimetic mutant, which does not bind PICK1 efficiently. Taken together, our data demonstrate that the interaction of PICK1 and PACSIN is required for the activity-dependent internalization of AMPARs and for the expression of long-term depression in the cerebellum.
Arf guanine nucleotide-exchange factors BIG1 and BIG2 regulate nonmuscle myosin IIA activity by anchoring myosin phosphatase complex
Authors: Le Kang , Li Chun-Chun , Ye Guan , Moss Joel , Vaughan Martha
Published: August 2013

Significance

Phosphorylation of myosin regulatory light chain (RLC) alters actomyosin contractility and cell mobility. Finding that myosin IIA interacted directly with brefeldin A-inhibited guanine nucleotide-exchange factors (BIG)1 and BIG2, best known as activators of ADP ribosylation factor (Arf) GTPases for intracellular vesicular trafficking, we showed that BIG1 or -2 depletion increased RLC phosphorylation, which interfered with cell mobility independent of Arf activation. By acting noncatalytically as scaffolds for the assembly and operation of multimolecular phosphatase complexes that included phosphatase 1δ and myosin phosphatase-targeting subunit 1, BIG1 and BIG2 contribute to regulation of F-actin formation and cytoskeleton dynamics required for cell polarization and directed migration.
Minimum of the order parameter fluctuations of seismicity before major earthquakes in Japan
Authors: Sarlis Nicholas V. , Skordas Efthimios S. , Varotsos Panayiotis A. , Nagao Toshiyasu , Kamogawa Masashi , Tanaka Haruo , Uyeda Seiya
Published: August 2013

It has been shown that some dynamic features hidden in the time series of complex systems can be uncovered if we analyze them in a time domain called natural time
χ
. The order parameter of seismicity introduced in this time domain is the variance of
χ
weighted for normalized energy of each earthquake. Here, we analyze the Japan seismic catalog in natural time from January 1, 1984 to March 11, 2011, the day of the M9 Tohoku earthquake, by considering a sliding natural time window of fixed length comprised of the number of events that would occur in a few months. We find that the fluctuations of the order parameter of seismicity exhibit distinct minima a few months before all of the shallow earthquakes of magnitude 7.6 or larger that occurred during this 27-y period in the Japanese area. Among the minima, the minimum before the M9 Tohoku earthquake was the deepest. It appears that there are two kinds of minima, namely precursory and nonprecursory, to large earthquakes.
Hippo pathway effector Yap promotes cardiac regeneration
Authors: Xin Mei , Kim Yuri , Sutherland Lillian B. , Murakami Masao , Qi Xiaoxia , McAnally John , Porrello Enzo R. , Mahmoud Ahmed I. , Tan Wei , Shelton John M. , Richardson James A. , Sadek Hesham A. , Bassel-Duby Rhonda , Olson Eric N.
Published: August 2013

The adult mammalian heart has limited potential for regeneration. Thus, after injury, cardiomyocytes are permanently lost, and contractility is diminished. In contrast, the neonatal heart can regenerate owing to sustained cardiomyocyte proliferation. Identification of critical regulators of cardiomyocyte proliferation and quiescence represents an important step toward potential regenerative therapies. Yes-associated protein (Yap), a transcriptional cofactor in the Hippo signaling pathway, promotes proliferation of embryonic cardiomyocytes by activating the insulin-like growth factor and Wnt signaling pathways. Here we report that mice bearing mutant alleles of
Yap
and its paralog WW domain containing transcription regulator 1 (
Taz
) exhibit gene dosage-dependent cardiac phenotypes, suggesting redundant roles of these Hippo pathway effectors in establishing proper myocyte number and maintaining cardiac function. Cardiac-specific deletion of
Yap
impedes neonatal heart regeneration, resulting in a default fibrotic response. Conversely, forced expression of a constitutively active form of Yap in the adult heart stimulates cardiac regeneration and improves contractility after myocardial infarction. The regenerative activity of Yap is correlated with its activation of embryonic and proliferative gene programs in cardiomyocytes. These findings identify Yap as an important regulator of cardiac regeneration and provide an experimental entry point to enhance this process.
Experiments on the role of deleterious mutations as stepping stones in adaptive evolution
Authors: Covert Arthur W. , Lenski Richard E. , Wilke Claus O. , Ofria Charles
Published: August 2013

Significance

It might seem obvious that deleterious mutations must impede evolution. However, a later mutation may interact with a deleterious predecessor, facilitating otherwise inaccessible adaptations. Although such interactions have been reported before, it is unclear whether they are rare and inconsequential or, alternatively, are important for sustaining adaptation. We studied digital organisms—computer programs that replicate and evolve—to compare adaptation in populations where deleterious mutations were disallowed with unrestricted controls. Control populations achieved higher fitness values because some deleterious mutations acted as stepping stones across otherwise impassable fitness valleys. Deleterious mutations can thus sometimes play a constructive role in adaptive evolution.
Frame-semantic issues in building a bilingual lexicographic resource
Authors: Dalpanagioti Thomai
Published: August 2013

This paper discusses the issues that emerged from applying frame semantics to the development of a small-scale bilingual database for Greek and English motion verbs. Proposing an alternative to current lexicography in Greece, the database exploits available corpora and query systems, and carries out a (manual) frame-semantic analysis of the extracted data. The most important theoretical implication of the database is that by combining frame semantics with conceptual metaphor theory and corpus-based information on usage patterns, we can make precise (monolingual) descriptions and effective (cross-linguistic) comparisons. From a practical perspective, the database complements existing English FrameNet and contributes to the creation of a new resource, i.e. a FrameNet for Greek.