bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of electric field on the band structure of graphene/boron nitride and boron nitride/boron nitride bilayers
Authors: Balu Radhakrishnan , Zhong Xiaoliang , Pandey Ravindra , Karna Shashi P.
Published: January 2012

Effect of electric field on the band structures of graphene/boron nitride (BN) and BN/BN bilayers is investigated within the framework of density functional theory. The calculated bandgap of the graphene/BN bilayer increases, although by small amount, with applied electric field. In the case of BN/BN bilayer, the bandgap decreases with the applied field in agreement with earlier studies. The modulation of bandgap in graphene/BN bilayers is dominated by the features of graphene and appears to be related to the modification in molecular orbitals as revealed by the calculated projected density of states.
Optical modeling and experimental verification of light induced phenomena in In-Ga-Zn-O thin film transistors with varying gate insulator thickness
Authors: Chung Yoon Jang , Kim Jeong Hwan , Kim Un Ki , Rha Sang Ho , Hwang Eric , Hwang Cheol Seong
Published: January 2012

A simple optical model based on the transfer matrix method was used to simulate photon absorption in oxide semiconductor systems with varying insulator thickness in the thin film transistor (TFT) structure. For comparison with actual experimental results, hole current was measured in transparent metal/semiconductor/insulator/metal capacitor stacks under light illumination, and the threshold voltage shift under negative bias illumination stress conditions was also measured in the TFT structure. In each structure, experimental data showed variance as the insulator thickness changed, and these results agreed well with the simulations. The results showed that light interference in multi-layered devices has a crucial influence on the reliability of them under illumination and that they should be considered when designing systems that work under these conditions. The accuracy of the simulations suggests they can be implemented to minimize instability issues in oxide TFTs for display.
Coherences of accelerated detectors and the local character of the Unruh effect
Authors: Anastopoulos Charis , Savvidou Ntina
Published: January 2012

We study the locality of the acceleration temperature in the Unruh effect. To this end, we develop a new formalism for the modeling of macroscopic irreversible detectors. In particular, the formalism allows for the derivation of the higher-order coherence functions, analogous to the ones employed in quantum optics, that encode temporal fluctuations and correlations in particle detection. We derive a causal and approximately local-in-time expression for an Unruh-DeWitt detector moving in a general path in Minkowski spacetime. Moreover, we derive the second-order coherence function for uniformly accelerated Unruh-DeWitt detectors. We find that the fluctuations in detection time for a single Unruh-DeWitt detector are thermal. However, the correlations in detection time between two Unruh-DeWitt detectors with the same acceleration but separated by a finite distance are not thermal. This result suggests that the Unruh effect is fundamentally local, in the sense that the notion of acceleration temperature applies only to the properties of local field observables.
Effect of Ta content on the phase transition and piezoelectric properties of lead-free (K0.48Na0.48Li0.04)(Nb0.995-xMn0.005Tax)O3 thin film
Authors: Won Ahn Chang , Jin Seog Hae , Ullah Aman , Young Lee Sun , Won Kim Jin , Su Kim Sang , Park Moonkyu , No Kwangsoo , Won Kim Ill
Published: January 2012

Lead-free (K0.48Na0.48Li0.04)(Nb0.995−xMn0.005Tax)O3 (abbreviated KNL-NMT-x, x = 0 ∼ 0.20) thin films were prepared using a chemical solution deposition method, and the effects of Ta content on the structural, dielectric, ferroelectric, and piezoelectric properties were investigated. X ray diffraction results indicate that the phase structure of KNL-NMT-x films undergoes a transition from orthorhombic to pseudocubic phase with increasing Ta content. The substitution of Ta5+ for the Nb5+ site in the KNL-NMT-x films produced to the relaxor-like ferroelectric with a diffuse phase transition. The KNL-NMT-0.10 thin film at the orthorhombic-pseudocubic phase boundary showed optimum dielectric and piezoelectric properties; dielectric constant ɛr = 2650, Curie temperature Tc = 323 °C, remnant polarization Pr = 16.1 μC/cm2, coercive field Ec = 22.2 kV/cm, and effective piezoelectric coefficient d33,f = 61 pm/V.
Contribution of organic arsenic species to total arsenic measurements using ferrihydrite-backed diffusive gradients in thin films (DGT)
Authors: Österlund Heléne , Faarinen Mikko , Ingri Johan , Baxter Douglas C.
Published: January 2012

Environmental contextBoth the mobility and toxicity of arsenic in natural waters are related to the aqueous species distribution. Passive sampling using ferrihydrite-backed diffusive gradients in thin films (DGT) devices has in previous studies been characterised to measure labile inorganic arsenic, and the possible contribution of organic species has been disregarded. This study shows that the two most prevalent organic arsenic species might be included in DGT measurements, which should be taken into consideration when evaluating DGT data in future studies.
AbstractIn previous publications discussing arsenic determination using ferrihydrite-backed diffusive gradients in thin films (DGT) devices, organic arsenic forms have been disregarded, even though it is known that the two most prevalent in natural waters, dimethylarsinate (DMA) and monomethylarsonate (MMA), may adsorb to ferrihydrite and thereby be included in the measurement. In this work the accumulation of DMA and MMA, as well as inorganic arsenite and arsenate, to ferrihydrite-backed DGT devices was investigated. It could be demonstrated that MMA, and under acidic conditions also DMA, adsorbed to the binding layer and might therefore contribute to the total mass of measured arsenic. Diffusion coefficients were measured for all four species to enable quantification of DGT-labile concentrations of organic and inorganic arsenic. Elution of the analytes from the ferrihydrite binding layer was performed using 1 mL of 1 M NaOH to facilitate arsenic speciation analysis using chromatographic separation. Average recovery rates were between 87 and 108 %. This study shows that the contribution of DMA and MMA to the total accumulated mass must be taken into consideration when evaluating DGT data in future studies.
A new method for determination of potassium in soils using diffusive gradients in thin films (DGT)
Authors: Tandy Susan , Mundus Simon , Zhang Hao , Lombi Enzo , Frydenvang Jens , Holm Peter E. , Husted Søren
Published: January 2012

Environmental contextPotassium is an essential plant nutrient and farmers need to be able to predict how much soil K is plant available in order to optimise fertiliser applications and crop production. Traditional methods such as chemical extraction are generally poor predictors. A DGT based methodology that could enhance the assessment of plant available K is developed, which will assist plant growers to determine the correct fertiliser application, thereby avoiding crop deficiencies and limiting the misuse of K as a precious natural resource.
AbstractPotassium is an essential plant nutrient often limiting plant productivity. Ammonium acetate extraction is often used to predict the potassium status of soils. However, correlation between extracted K and plant uptake is often poor, especially over a range of different soil textures. Diffusive gradients in thin films (DGT), which determines the diffusive supply of elements, has been shown to accurately measure plant available elements in several cases. Up until now, however, the DGT devices available have not been suitable for measuring K. We set out to develop a DGT device suitable for the measurement of K in soil and test its ability to predict plant available K. The DGT device contained a binding layer based on Amberlite IRP-69 cation exchange resin. It proved suitable for the measurement of K under conditions similar to those usually found in soil if a 2-h deployment time was used and the labile K concentration was limited to 400 µM. Prediction of plant K concentrations with DGT were similar to those with ammonium acetate extractions over a range of typical agricultural soils with sandy and sandy loam textures. The results indicate that this new type of DGT has the potential to improve the accuracy of predictions of the K status of soils, although more tests using a wider range of plant species and soils are necessary.
Src tyrosine kinase phosphorylation of nuclear receptor HNF4α correlates with isoform-specific loss of HNF4α in human colon cancer
Authors: Chellappa Karthikeyani , Jankova Lucy , Schnabl Jake M. , Pan Songqin , Brelivet Yann , Fung Caroline L-S. , Chan Charles , Dent Owen F. , Clarke Stephen J. , Robertson Graham R. , Sladek Frances M.
Published: January 2012

Src tyrosine kinase has long been implicated in colon cancer but much remains to be learned about its substrates. The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) has just recently been implicated in colon cancer but its role is poorly defined. Here we show that c-Src phosphorylates human HNF4α on three tyrosines in an interdependent and isoform-specific fashion. The initial phosphorylation site is a Tyr residue (Y14) present in the N-terminal A/B domain of P1- but not P2-driven HNF4α. Phospho-Y14 interacts with the Src SH2 domain, leading to the phosphorylation of two additional tyrosines in the ligand binding domain (LBD) in P1-HNF4α. Phosphomimetic mutants in the LBD decrease P1-HNF4α protein stability, nuclear localization and transactivation function. Immunohistochemical analysis of approximately 450 human colon cancer specimens (Stage III) reveals that P1-HNF4α is either lost or localized in the cytoplasm in approximately 80% of tumors, and that staining for active Src correlates with those events in a subset of samples. Finally, three SNPs in the human HNF4α protein, two of which are in the HNF4α F domain that interacts with the Src SH3 domain, increase phosphorylation by Src and decrease HNF4α protein stability and function, suggesting that individuals with those variants may be more susceptible to Src-mediated effects. This newly identified interaction between Src kinase and HNF4α has important implications for colon and other cancers.
foraging
alters resilience/vulnerability to sleep disruption and starvation in
Drosophila
Authors: Donlea Jeffrey , Leahy Averi , Thimgan Matthew S. , Suzuki Yasuko , Hughson Bryon N. , Sokolowski Marla B. , Shaw Paul J.
Published: January 2012

Recent human studies suggest that genetic polymorphisms allow an individual to maintain optimal cognitive functioning during sleep deprivation. If such polymorphisms were not associated with additional costs, selective pressures would allow these alleles to spread through the population such that an evolutionary alternative to sleep would emerge. To determine whether there are indeed costs associated with resiliency to sleep loss, we challenged natural allelic variants of the
foraging
gene (
for
) with either sleep deprivation or starvation. Flies with high levels of Protein Kinase G (PKG) (

for
R

) do not display deficits in short-term memory following 12 h of sleep deprivation. However, short-term memory is significantly disrupted when

for
R

flies are starved overnight. In contrast, flies with low levels of PKG (

for
s

,

for
s2

) show substantial deficits in short-term memory following sleep deprivation but retain their ability to learn after 12 h of starvation. We found that

for
R

phenotypes could be largely recapitulated in

for
s

flies by selectively increasing the level of PKG in the α/β lobes of the mushroom bodies, a structure known to regulate both sleep and memory. Together, these data indicate that whereas the expression of
for
may appear to provide resilience in one environmental context, it may confer an unexpected vulnerability in other situations. Understanding how these tradeoffs confer resilience or vulnerability to specific environmental challenges may provide additional clues as to why an evolutionary alternative to sleep has not emerged.
Optimizing ring assembly reveals the strength of weak interactions
Authors: Deeds Eric J. , Bachman John A. , Fontana Walter
Published: January 2012

Most cellular processes rely on large multiprotein complexes that must assemble into a well-defined quaternary structure in order to function. A number of prominent examples, including the 20S core particle of the proteasome and the AAA+ family of ATPases, contain ring-like structures. Developing an understanding of the complex assembly pathways employed by ring-like structures requires a characterization of the problems these pathways have had to overcome as they evolved. In this work, we use computational models to uncover one such problem: a deadlocked plateau in the assembly dynamics. When the molecular interactions between subunits are too strong, this plateau leads to significant delays in assembly and a reduction in steady-state yield. Conversely, if the interactions are too weak, assembly delays are caused by the instability of crucial intermediates. Intermediate affinities thus maximize the efficiency of assembly for homomeric ring-like structures. In the case of heteromeric rings, we find that rings including at least one weak interaction can assemble efficiently and robustly. Estimation of affinities from solved structures of ring-like complexes indicates that heteromeric rings tend to contain a weak interaction, confirming our prediction. In addition to providing an evolutionary rationale for structural features of rings, our work forms the basis for understanding the complex assembly pathways of stacked rings like the proteasome and suggests principles that would aid in the design of synthetic ring-like structures that self-assemble efficiently.
Near-infrared fluorescent sensor for in vivo copper imaging in a murine Wilson disease model
Authors: Hirayama Tasuku , Van de Bittner Genevieve C. , Gray Lawrence W. , Lutsenko Svetlana , Chang Christopher J.
Published: January 2012

Copper is an essential metal nutrient that is tightly regulated in the body because loss of its homeostasis is connected to severe diseases such as Menkes and Wilson diseases, Alzheimer’s disease, prion disorders, and amyotrophic lateral sclerosis. The complex relationships between copper status and various stages of health and disease remain challenging to elucidate, in part due to a lack of methods for monitoring dynamic changes in copper pools in whole living organisms. Here we present the synthesis, spectroscopy, and in vivo imaging applications of Coppersensor 790, a first-generation fluorescent sensor for visualizing labile copper pools in living animals. Coppersensor 790 combines a near-infrared emitting cyanine dye with a sulfur-rich receptor to provide a selective and sensitive turn-on response to copper. This probe is capable of monitoring fluctuations in exchangeable copper stores in living cells and mice under basal conditions, as well as in situations of copper overload or deficiency. Moreover, we demonstrate the utility of this unique chemical tool to detect aberrant increases in labile copper levels in a murine model of Wilson disease, a genetic disorder that is characterized by accumulation of excess copper. The ability to monitor real-time copper fluxes in living animals offers potentially rich opportunities to examine copper physiology in health and disease.
Actin filament curvature biases branching direction
Authors: Risca Viviana I. , Wang Evan B. , Chaudhuri Ovijit , Chia Jia Jun , Geissler Phillip L. , Fletcher Daniel A.
Published: January 2012

Mechanical cues affect many important biological processes in metazoan cells, such as migration, proliferation, and differentiation. Such cues are thought to be detected by specialized mechanosensing molecules linked to the cytoskeleton, an intracellular network of protein filaments that provide mechanical rigidity to the cell and drive cellular shape change. The most abundant such filament, actin, forms branched networks nucleated by the actin-related protein (Arp) 2/3 complex that support or induce membrane protrusions and display adaptive behavior in response to compressive forces. Here we show that filamentous actin serves in a mechanosensitive capacity itself, by biasing the location of actin branch nucleation in response to filament bending. Using an in vitro assay to measure branching from curved sections of immobilized actin filaments, we observed preferential branch formation by the Arp2/3 complex on the convex face of the curved filament. To explain this behavior, we propose a fluctuation gating model in which filament binding or branch nucleation by Arp2/3 occur only when a sufficiently large, transient, local curvature fluctuation causes a favorable conformational change in the filament, and we show with Monte Carlo simulations that this model can quantitatively account for our experimental data. We also show how the branching bias can reinforce actin networks in response to compressive forces. These results demonstrate how filament curvature can alter the interaction of cytoskeletal filaments with regulatory proteins, suggesting that direct mechanotransduction by actin may serve as a general mechanism for organizing the cytoskeleton in response to force.
Continuous and discontinuous quantum phase transitions in a model two-dimensional magnet
Authors: Haravifard S. , Banerjee A. , Lang J. C. , Srajer G. , Silevitch D. M. , Gaulin B. D. , Dabkowska H. A. , Rosenbaum T. F.
Published: January 2012

The Shasty–Sutherland model, which consists of a set of spin 1/2 dimers on a 2D square lattice, is simple and soluble but captures a central theme of condensed matter physics by sitting precariously on the quantum edge between isolated, gapped excitations and collective, ordered ground states. We compress the model Shastry–Sutherland material, SrCu
2
(BO
3
)
2
, in a diamond anvil cell at cryogenic temperatures to continuously tune the coupling energies and induce changes in state. High-resolution X-ray measurements exploit what emerges as a remarkably strong spin-lattice coupling to both monitor the magnetic behavior and the absence or presence of structural discontinuities. In the low-pressure spin-singlet regime, the onset of magnetism results in an expansion of the lattice with decreasing temperature, which permits a determination of the pressure-dependent energy gap and the almost isotropic spin-lattice coupling energies. The singlet-triplet gap energy is suppressed continuously with increasing pressure, vanishing completely by 2 GPa. This continuous quantum phase transition is followed by a structural distortion at higher pressure.
Light-driven oxygen production from superoxide by Mn-binding bacterial reaction centers
Authors: Allen James P. , Olson Tien L. , Oyala Paul , Lee Wei-Jen , Tufts Aaron A. , Williams JoAnn C.
Published: January 2012

One of the outstanding questions concerning the early Earth is how ancient phototrophs made the evolutionary transition from anoxygenic to oxygenic photosynthesis, which resulted in a substantial increase in the amount of oxygen in the atmosphere. We have previously demonstrated that reaction centers from anoxygenic photosynthetic bacteria can be modified to bind a redox-active Mn cofactor, thus gaining a key functional feature of photosystem II, which contains the site for water oxidation in cyanobacteria, algae, and plants [Thielges M, et al. (2005)Biochemistry44:7389–7394]. In this paper, the Mn-binding reaction centers are shown to have a light-driven enzymatic function; namely, the ability to convert superoxide into molecular oxygen. This activity has a relatively high efficiency with akcatof approximately 1 s-1that is significantly larger than typically observed for designed enzymes, and aKmof 35–40 μM that is comparable to the value of 50 μM for Mn-superoxide dismutase, which catalyzes a similar reaction. Unlike wild-type reaction centers, the highly oxidizing reaction centers are not stable in the light unless they have a bound Mn. The stability and enzymatic ability of this type of Mn-binding reaction centers would have provided primitive phototrophs with an environmental advantage before the evolution of organisms with a more complex Mn4Ca cluster needed to perform the multielectron reactions required to oxidize water.
Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection
Authors: Onodera Taishi , Takahashi Yoshimasa , Yokoi Yusuke , Ato Manabu , Kodama Yuichi , Hachimura Satoshi , Kurosaki Tomohiro , Kobayashi Kazuo
Published: January 2012

After pulmonary virus infection, virus-binding B cells ectopically accumulate in the lung. However, their contribution to protective immunity against reinfecting viruses remains unknown. Here, we show the phenotypes and protective functions of virus-binding memory B cells that persist in the lung following pulmonary infection with influenza virus. A fraction of virus-binding B-cell population in the lung expressed surface markers for splenic mature memory B cells (CD73, CD80, and CD273) along with CD69 and CXCR3 that are up-regulated on lung effector/memory T cells. The lung B-cell population with memory phenotype persisted for more than 5 mo after infection, and on reinfection promptly differentiated into plasma cells that produced virus-neutralizing antibodies locally. This production of local IgG and IgA neutralizing antibody was correlated with reduced virus spread in adapted hosts. Our data demonstrates that infected lungs harbor a memory B-cell subset with distinctive phenotype and ability to provide protection against pulmonary virus reinfection.
Leghemoglobin green derivatives with nitrated hemes evidence production of highly reactive nitrogen species during aging of legume nodules
Authors: Navascués Joaquín , Pérez-Rontomé Carmen , Gay Marina , Marcos Manuel , Yang Fei , Walker F. Ann , Desbois Alain , Abián Joaquín , Becana Manuel
Published: January 2012

Globins constitute a superfamily of proteins widespread in all kingdoms of life, where they fulfill multiple functions, such as efficient O
2
transport and modulation of nitric oxide bioactivity. In plants, the most abundant Hbs are the symbiotic leghemoglobins (Lbs) that scavenge O
2
and facilitate its diffusion to the N
2
-fixing bacteroids in nodules. The biosynthesis of Lbs during nodule formation has been studied in detail, whereas little is known about the green derivatives of Lbs generated during nodule senescence. Here we characterize modified forms of Lbs, termed Lb

a
m

, Lb

c
m

, and Lb

d
m

, of soybean nodules. These green Lbs have identical globins to the parent red Lbs but their hemes are nitrated. By combining UV-visible, MS, NMR, and resonance Raman spectroscopies with reconstitution experiments of the apoprotein with protoheme or mesoheme, we show that the nitro group is on the 4-vinyl. In vitro nitration of Lb
a
with excess nitrite produced several isomers of nitrated heme, one of which is identical to those found in vivo. The use of antioxidants, metal chelators, and heme ligands reveals that nitration is contingent upon the binding of nitrite to heme Fe, and that the reactive nitrogen species involved derives from nitrous acid and is most probably the nitronium cation. The identification of these green Lbs provides conclusive evidence that highly oxidizing and nitrating species are produced in nodules leading to nitrosative stress. These findings are consistent with a previous report showing that the modified Lbs are more abundant in senescing nodules and have aberrant O
2
binding.
Differential modulation of the default mode network via serotonin-1A receptors
Authors: Hahn Andreas , Wadsak Wolfgang , Windischberger Christian , Baldinger Pia , Höflich Anna S. , Losak Jan , Nics Lukas , Philippe Cécile , Kranz Georg S. , Kraus Christoph , Mitterhauser Markus , Karanikas Georgios , Kasper Siegfried , Lanzenberger Rupert
Published: January 2012

Reflecting one's mental self is a fundamental process for evaluating the personal relevance of life events and for moral decision making and future envisioning. Although the corresponding network has been receiving growing attention, the driving neurochemical mechanisms of the default mode network (DMN) remain unknown. Here we combined positron emission tomography and functional magnetic resonance imaging to investigate modulations of the DMN via serotonin-1A receptors (5-HT1A), separated for 5-HT autoinhibition (dorsal raphe nucleus) and local inhibition (heteroreceptors in projection areas). Using two independent approaches, regional 5-HT1Abinding consistently predicted DMN activity in the retrosplenial cortex for resting-state functional magnetic resonance imaging and the Tower of London task. On the other hand, both local and autoinhibitory 5-HT1Abinding inversely modulated the posterior cingulate cortex, the strongest hub in the resting human brain. In the frontal part of the DMN, a negative association was found between the dorsal medial prefrontal cortex and local 5-HT1Ainhibition. Our results indicate a modulation of key areas involved in self-referential processing by serotonergic neurotransmission, whereas variations in 5-HT1Abinding explained a considerable amount of the individual variability in the DMN. Moreover, the brain regions associated with distinct introspective functions seem to be specifically regulated by the different 5-HT1Abinding sites. Together with previously reported modulations of dopamine and GABA, this regional specialization suggests complex interactions of several neurotransmitters driving the default mode network.
Auditory circuit in the
Drosophila
brain
Authors: Lai Jason Sih-Yu , Lo Shih-Jie , Dickson Barry J. , Chiang Ann-Shyn
Published: January 2012

Most animals exhibit innate auditory behaviors driven by genetically hardwired neural circuits. In
Drosophila
, acoustic information is relayed by Johnston organ neurons from the antenna to the antennal mechanosensory and motor center (AMMC) in the brain. Here, by using structural connectivity analysis, we identified five distinct types of auditory projection neurons (PNs) interconnecting the AMMC, inferior ventrolateral protocerebrum (IVLP), and ventrolateral protocerebrum (VLP) regions of the central brain. These auditory PNs are also functionally distinct; AMMC-B1a, AMMC-B1b, and AMMC-A2 neurons differ in their responses to sound (i.e., they are narrowly tuned or broadly tuned); one type of audioresponsive IVLP commissural PN connecting the two hemispheres is GABAergic; and one type of IVLP-VLP PN acts as a generalist responding to all tested audio frequencies. Our findings delineate an auditory processing pathway involving AMMC→IVLP→VLP in the
Drosophila
brain.
Maternal support in early childhood predicts larger hippocampal volumes at school age
Authors: Luby Joan L. , Barch Deanna M. , Belden Andy , Gaffrey Michael S. , Tillman Rebecca , Babb Casey , Nishino Tomoyuki , Suzuki Hideo , Botteron Kelly N.
Published: January 2012

Early maternal support has been shown to promote specific gene expression, neurogenesis, adaptive stress responses, and larger hippocampal volumes in developing animals. In humans, a relationship between psychosocial factors in early childhood and later amygdala volumes based on prospective data has been demonstrated, providing a key link between early experience and brain development. Although much retrospective data suggests a link between early psychosocial factors and hippocampal volumes in humans, to date there has been no prospective data to inform this potentially important public health issue. In a longitudinal study of depressed and healthy preschool children who underwent neuroimaging at school age, we investigated whether early maternal support predicted later hippocampal volumes. Maternal support observed in early childhood was strongly predictive of hippocampal volume measured at school age. The positive effect of maternal support on hippocampal volumes was greater in nondepressed children. These findings provide prospective evidence in humans of the positive effect of early supportive parenting on healthy hippocampal development, a brain region key to memory and stress modulation.
Defects in purine nucleotide metabolism lead to substantial incorporation of xanthine and hypoxanthine into DNA and RNA
Authors: Pang Bo , McFaline Jose L. , Burgis Nicholas E. , Dong Min , Taghizadeh Koli , Sullivan Matthew R. , Elmquist C. Eric , Cunningham Richard P. , Dedon Peter C.
Published: January 2012

Deamination of nucleobases in DNA and RNA results in the formation of xanthine (X), hypoxanthine (I), oxanine, and uracil, all of which are miscoding and mutagenic in DNA and can interfere with RNA editing and function. Among many forms of nucleic acid damage, deamination arises from several unrelated mechanisms, including hydrolysis, nitrosative chemistry, and deaminase enzymes. Here we present a fourth mechanism contributing to the burden of nucleobase deamination: incorporation of hypoxanthine and xanthine into DNA and RNA caused by defects in purine nucleotide metabolism. Using
Escherichia coli
and
Saccharomyces cerevisiae
with defined mutations in purine metabolism in conjunction with analytical methods for quantifying deaminated nucleobases in DNA and RNA, we observed large increases (up to 600-fold) in hypoxanthine in both DNA and RNA in cells unable to convert IMP to XMP or AMP (IMP dehydrogenase,
guaB
; adenylosuccinate synthetase,
purA
, and
ADE12
), and unable to remove dITP/ITP and dXTP/XTP from the nucleotide pool (dITP/XTP pyrophosphohydrolase,
rdgB
and
HAM1
). Conversely, modest changes in xanthine levels were observed in RNA (but not DNA) from
E. coli
lacking
purA
and
rdgB
and the enzyme converting XMP to GMP (GMP synthetase,
guaA
). These observations suggest that disturbances in purine metabolism caused by known genetic polymorphisms could increase the burden of mutagenic deaminated nucleobases in DNA and interfere with gene expression and RNA function, a situation possibly exacerbated by the nitrosative stress of concurrent inflammation. The results also suggest a mechanistic basis for the pathophysiology of human inborn errors of purine nucleotide metabolism.
Cofilin under control of β-arrestin-2 in NMDA-dependent dendritic spine plasticity, long-term depression (LTD), and learning
Authors: Pontrello Crystal G. , Sun Min-Yu , Lin Alice , Fiacco Todd A. , DeFea Kathryn A. , Ethell Iryna M.
Published: January 2012

Dendritic spines are dynamic, actin-rich structures that form the postsynaptic sites of most excitatory synapses in the brain. The F-actin severing protein cofilin has been implicated in the remodeling of dendritic spines and synapses under normal and pathological conditions, by yet unknown mechanisms. Here we report that β-arrestin-2 plays an important role in NMDA-induced remodeling of dendritic spines and synapses via translocation of active cofilin to dendritic spines. NMDAR activation triggers cofilin activation through calcineurin and phosphatidylinositol 3-kinase (PI3K)-mediated dephosphorylation and promotes cofilin translocation to dendritic spines that is mediated by β-arrestin-2. Hippocampal neurons lacking β-arrestin-2 develop mature spines that fail to remodel in response to NMDA. β-Arrestin-2–deficient mice exhibit normal hippocampal long-term potentiation, but significantly impaired NMDA-dependent long-term depression and spatial learning deficits. Moreover, β-arrestin-2–deficient hippocampal neurons are resistant to Aβ-induced dendritic spine loss. Our studies demonstrate unique functions of β-arrestin-2 in NMDAR-mediated dendritic spine and synapse plasticity through spatial control over cofilin activation.
Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells
Authors: Lujan Ernesto , Chanda Soham , Ahlenius Henrik , Südhof Thomas C. , Wernig Marius
Published: January 2012

We recently showed that defined sets of transcription factors are sufficient to convert mouse and human fibroblasts directly into cells resembling functional neurons, referred to as “induced neuronal” (iN) cells. For some applications however, it would be desirable to convert fibroblasts into proliferative neural precursor cells (NPCs) instead of neurons. We hypothesized that NPC-like cells may be induced using the same principal approach used for generating iN cells. Toward this goal, we infected mouse embryonic fibroblasts derived from
Sox2
-EGFP mice with a set of 11 transcription factors highly expressed in NPCs. Twenty-four days after transgene induction,
Sox2
-EGFP
+
colonies emerged that expressed NPC-specific genes and differentiated into neuronal and astrocytic cells. Using stepwise elimination, we found that
Sox2
and
FoxG1
are capable of generating clonal self-renewing, bipotent induced NPCs that gave rise to astrocytes and functional neurons. When we added the Pou and Homeobox domain-containing transcription factor
Brn2
to
Sox2
and
FoxG1
, we were able to induce tripotent NPCs that could be differentiated not only into neurons and astrocytes but also into oligodendrocytes. The transcription factors
FoxG1
and
Brn2
alone also were capable of inducing NPC-like cells; however, these cells generated less mature neurons, although they did produce astrocytes and even oligodendrocytes capable of integration into dysmyelinated
Shiverer
brain. Our data demonstrate that direct lineage reprogramming using target cell-type–specific transcription factors can be used to induce NPC-like cells that potentially could be used for autologous cell transplantation-based therapies in the brain or spinal cord.
Functional redundancy between repair factor XLF and damage response mediator 53BP1 in V(D)J recombination and DNA repair
Authors: Oksenych Valentyn , Alt Frederick W. , Kumar Vipul , Schwer Bjoern , Wesemann Duane R. , Hansen Erica , Patel Harin , Su Arthur , Guo Chunguang
Published: January 2012

The classical nonhomologous DNA end-joining (C-NHEJ) double-strand break (DSB) repair pathway in mammalian cells maintains genome stability and is required for V(D)J recombination and lymphocyte development. Mutations in the XLF C-NHEJ factor or ataxia telangiectasia-mutated (ATM) DSB response protein cause radiosensitivity and immunodeficiency in humans. Although potential roles for XLF in C-NHEJ are unknown, ATM activates a general DSB response by phosphorylating substrates, including histone H2AX and 53BP1, which are assembled into chromatin complexes around DSBs. In mice, C-NHEJ, V(D)J recombination, and lymphocyte development are, at most, modestly impaired in the absence of XLF or ATM, but are severely impaired in the absence of both. Redundant functions of XLF and ATM depend on ATM kinase activity; correspondingly, combined XLF and H2AX deficiency severely impairs V(D)J recombination, even though H2AX deficiency alone has little impact on this process. These and other findings suggest that XLF may provide functions that overlap more broadly with assembled DSB response factors on chromatin. As one test of this notion, we generated mice and cells with a combined deficiency for XLF and 53BP1. In this context, 53BP1 deficiency, although leading to genome instability, has only modest effects on V(D)J recombination or lymphocyte development. Strikingly, we find that combined XLF/53BP1 deficiency in mice severely impairs C-NHEJ, V(D)J recombination, and lymphocyte development while also leading to general genomic instability and growth defects. We conclude that XLF is functionally redundant with multiple members of the ATM-dependent DNA damage response in facilitating C-NHEJ and discuss implications of our findings for potential functions of these factors.
Spatial navigation impairment is proportional to right hippocampal volume
Authors: Nedelska Zuzana , Andel Ross , Laczó Jan , Vlcek Kamil , Horinek Daniel , Lisy Jiri , Sheardova Katerina , Bureš Jan , Hort Jakub
Published: January 2012

Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (
n
= 23) or mild and moderate AD (
n
= 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real-space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (β = −0.62,
P
< 0.001) and virtual (β = −0.43,
P
= 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (
P
≤ 0.05) but not in cognitively healthy (
P
> 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present.
G
o
2 G protein mediates galanin inhibitory effects on insulin release from pancreatic β cells
Authors: Tang Guanghua , Wang Ying , Park Sangeun , Bajpayee Neil S. , Vi Diana , Nagaoka Yoshiko , Birnbaumer Lutz , Jiang Meisheng
Published: January 2012

The neuropeptide galanin regulates numerous physiological activities in the body, including feeding and metabolism, learning and memory, nociception and spinal reflexes, and anxiety and related behaviors. Modulation of blood glucose levels by suppressing insulin release was the first reported activity for galanin. This inhibition was mediated by one or more pertussis toxin-sensitive G proteins of the G
i/o
subfamily. However, the molecular identities of the specific G protein(s) and intracellular effectors have not been fully revealed. Recently, we demonstrated that mice lacking G
o
2, but not other members of the G
i/o
protein family, secrete more insulin than controls upon glucose challenge, indicating that G
o
2 is a major transducer for the inhibitory regulation of insulin secretion. In this study, we investigated galanin signaling mechanisms in β cells using cell biological and electrophysiological approaches. We found that islets lacking G
o
2, but not other G
i/o
proteins, lose the inhibitory effect of galanin on insulin release. Potentiation of ATP-sensitive potassium (K
ATP
) and inhibition of calcium currents by galanin were disrupted by anti-G
o
2α antibodies. Galanin actions on K
ATP
and calcium currents were completely lost in G
o
2
−/−
β cells. Furthermore, the hyperglycemic effect of galanin is also blunted in G
o
2
−/−
mice. Our results demonstrate that G
o
2 mediates the inhibition of insulin release by galanin by regulating both K
ATP
and Ca
2+
channels in mice. Our findings provide insight into galanin's action in glucose homeostasis. The results may also be relevant to the understanding of galanin signaling in other biological systems, especially the central nervous system.
Modes of pointing to existing spaces and the use of frames of reference
Authors: Le Guen Olivier
Published: January 2012

This paper aims at providing a systematic framework for investigating differences in how people point to existing spaces. Pointing is considered according to two conditions: (1) A non-transposed condition where the body of the speaker always constitutes the origo and where the various types of pointing are differentiated by the status of the target and (2) a transposed condition where both the distant figure and the distant ground are identified and their relation specified according to two frames of reference (FoRs): the egocentric FoR (where spatial relationships are coded with respect to the speaker’s point of view) and the geocentric FoR (where spatial relationships are coded in relation to external cues in the environment). The preference for one or the other frame of reference not only has consequences for pointing to real spaces but has some resonance in other domains, constraining the production of gesture in these related domains.
‘It's not supposed to be this way’: Psychological aspects of a premature menopause
Authors: Singer Dani
Published: January 2012

Background: Premature menopause (menopause diagnosed at 40 years or under) is a challenging condition with no prevention or cure. Causes can be the result of surgical intervention or spontaneous and largely unknown. It affects 1–6% of women aged 14–40. Aim: This study investigated women's experience of diagnosis, perception of cause, treatment received, main concerns, perceived long‐term consequences and impact on psychological wellbeing. Method: A cross‐sectional single group design questionnaire study that included both quantitative and qualitative measures was used. It was distributed to women on the database of two specialist London clinics and an internet‐based patient support group. A thematic analysis was undertaken. Findings: The response rate was 62%. Women's experiences varied but showed common themes regardless of timing of diagnosis and services accessed. Improved understanding by health professionals could help this group accept and adjust to the condition more effectively as could psychological support. Fertility was a primary concern regardless of parity and there were several secondary impacts both physiological and psychological. Discussion: A clear need for the offer of emotional support was indicated for all, but particularly for teenage girls and single women who tended not to access support from their own social network. Conclusion: Young women with this diagnosis could benefit from the offer of counselling, though uptake may be influenced by individual factors and vary according to age and circumstances. A good understanding of the physical aspects of this condition is important in the counselling of this group.
On the role of the upper part of words in lexical access: Evidence with masked priming
Authors: Perea Manuel , Comesaña Montserrat , Soares Ana P. , Moret-Tatay Carmen
Published: January 2012

More than 100 years ago, Huey (1908/1968) indicated that the upper part of words was more relevant for perception than the lower part. Here we examined whether mutilated words, in their upper/lower portions (e.g., [Formula: see text]), can automatically access their word units in the mental lexicon. To that end, we conducted four masked repetition priming experiments with the lexical decision task. Results showed that mutilated primes produced a sizeable masked repetition priming effect. Furthermore, the magnitude of the masked repetition priming effect was greater when the upper part of the primes was preserved than when the lower portion was preserved—this was the case not only when the mutilated words were presented in lower case but also when the mutilated words were presented in upper case. Taken together, these findings suggest that the front-end of computational models of visual-word recognition should be modified to provide a more realistic account at the level of letter features.
Invasive matrix degradation at focal adhesions occurs via protease recruitment by a FAK–p130Cas complex
Authors: Wang Yu , McNiven Mark A.
Published: January 2012

Tumor cell migration and the concomitant degradation of extracellular matrix (ECM) are two essential steps in the metastatic process. It is well established that focal adhesions (FAs) play an important role in regulating migration; however, whether these structures contribute to matrix degradation is not clear. In this study, we report that multiple cancer cell lines display degradation of ECM at FA sites that requires the targeted action of MT1-MMP. Importantly, we have found that this MT1-MMP targeting is dependent on an association with a FAK–p130Cas complex situated at FAs and is regulated by Src-mediated phosphorylation of Tyr 573 at the cytoplasmic tail of MT1. Disrupting the FAK–p130Cas–MT1 complex significantly impairs FA-mediated degradation and tumor cell invasion yet does not appear to affect invadopodia formation or function. These findings demonstrate a novel function for FAs and also provide molecular insights into MT1-MMP targeting and function.
Synthesis and in vitro evaluation of hydroxyapatite with controlled morphology
Authors: Kamitakahara M , Saito T , Ioku K
Published: January 2012

Hydroxyapatite (HA) ceramics have been used as bone-repairing materials. Particles in HA ceramics show different properties depending on their compositions and morphologies. It is expected that the control of the composition and morphology contributes to improvement of biological properties of HA ceramics. In order to reveal the effect of the composition and morphology, the HA ceramics composed of rod-shaped or plate-shaped particles with calcium-deficient composition were prepared by the hydrothermal process. Thein vitroevaluation, simulated body fluid (SBF) soaking test, was then conducted for these samples. The calcium-deficient HA ceramics composed of rod-shaped or plate-shaped particles were reacted with SBF and incorporated calcium and phosphate ions from SBF. This implies that these HA ceramics show high affinity to bone in the body.
Preparation of α-Fe2O3particles with controlled shape and size via a facile hydrothermal route
Authors: Dong Q , Yin S , Guo C S , Li H H , Kumada N , Takei T , Yonesaki Y , Kinomura N , Sato T
Published: January 2012

α-Fe2O3particles with controlled shape and size have been prepared by a facile hydrothermal reaction between ferric chloride hexahydrate (FeCl3·6H2O) and sodium hydroxide (NaOH) at 160°C. X-ray powder diffraction pattern indicates that the product is single-phase of α-Fe2O3.The morphology of α-Fe2O3particles changed as homogenous sphere, top-shape and cube, depending on solution pH. Meanwhile, monodispersed cube particles ofα-Fe2O3are also prepared under the same conditions using surfactant of hexadecyl trimethyl ammonium bromide (CTAB). The experimental results suggest that particle size can be controlled by adjusting the solution pH and amount of CTAB.