bluuebunny/crossref_metadata_2025 huggingface dataset:
In-line three-dimensional holography of nanocrystalline objects at atomic resolution
Authors: Chen F.-R. , Van Dyck D. , Kisielowski C.
Published: February 2016

Resolution and sensitivity of the latest generation aberration-corrected transmission electron microscopes allow the vast majority of single atoms to be imaged with sub-Ångstrom resolution and their locations determined in an image plane with a precision that exceeds the 1.9-pm wavelength of 300 kV electrons. Such unprecedented performance allows expansion of electron microscopic investigations with atomic resolution into the third dimension. Here we report a general tomographic method to recover the three-dimensional shape of a crystalline particle from high-resolution images of a single projection without the need for sample rotation. The method is compatible with low dose rate electron microscopy, which improves on signal quality, while minimizing electron beam-induced structure modifications even for small particles or surfaces. We apply it to germanium, gold and magnesium oxide particles, and achieve a depth resolution of 1–2 Å, which is smaller than inter-atomic distances.
Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis
Authors: Gomez-Ospina Natalia , Potter Carol J. , Xiao Rui , Manickam Kandamurugu , Kim Mi-Sun , Kim Kang Ho , Shneider Benjamin L. , Picarsic Jennifer L. , Jacobson Theodora A. , Zhang Jing , He Weimin , Liu Pengfei , Knisely A. S. , Finegold Milton J. , Muzny Donna M. , Boerwinkle Eric , Lupski James R. , Plon Sharon E. , Gibbs Richard A. , Eng Christine M. , Yang Yaping , Washington Gabriel C. , Porteus Matthew H. , Berquist William E. , Kambham Neeraja , Singh Ravinder J. , Xia Fan , Enns Gregory M. , Moore David D.
Published: February 2016

Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection.
Myosin light-chain phosphatase regulates basal actomyosin oscillations during morphogenesis
Authors: Valencia-Expósito Andrea , Grosheva Inna , Míguez David G. , González-Reyes Acaimo , Martín-Bermudo María D.
Published: February 2016

Contractile actomyosin networks generate forces that drive tissue morphogenesis. Actomyosin contractility is controlled primarily by reversible phosphorylation of the myosin-II regulatory light chain through the action of myosin kinases and phosphatases. While the role of myosin light-chain kinase in regulating contractility during morphogenesis has been largely characterized, there is surprisingly little information on myosin light-chain phosphatase (MLCP) function in this context. Here, we use live imaging of Drosophila follicle cells combined with mathematical modelling to demonstrate that the MLCP subunit flapwing (flw) is a key regulator of basal myosin oscillations and cell contractions underlying egg chamber elongation. Flw expression decreases specifically on the basal side of follicle cells at the onset of contraction and flw controls the initiation and periodicity of basal actomyosin oscillations. Contrary to previous reports, basal F-actin pulsates similarly to myosin. Finally, we propose a quantitative model in which periodic basal actomyosin oscillations arise in a cell-autonomous fashion from intrinsic properties of motor assemblies.
Voltage collapse in complex power grids
Authors: Simpson-Porco John W. , Dörfler Florian , Bullo Francesco
Published: February 2016

A large-scale power grid’s ability to transfer energy from producers to consumers is constrained by both the network structure and the nonlinear physics of power flow. Violations of these constraints have been observed to result in voltage collapse blackouts, where nodal voltages slowly decline before precipitously falling. However, methods to test for voltage collapse are dominantly simulation-based, offering little theoretical insight into how grid structure influences stability margins. For a simplified power flow model, here we derive a closed-form condition under which a power network is safe from voltage collapse. The condition combines the complex structure of the network with the reactive power demands of loads to produce a node-by-node measure of grid stress, a prediction of the largest nodal voltage deviation, and an estimate of the distance to collapse. We extensively test our predictions on large-scale systems, highlighting how our condition can be leveraged to increase grid stability margins.
Correction: Corrigendum: Loess Plateau storage of Northeastern Tibetan Plateau-derived Yellow River sediment
Authors: Nie Junsheng , Stevens Thomas , Rittner Martin , Stockli Daniel , Garzanti Eduardo , Limonta Mara , Bird Anna , Andò Sergio , Vermeesch Pieter , Saylor Joel , Lu Huayu , Breecker Daniel , Hu Xiaofei , Liu Shanpin , Resentini Alberto , Vezzoli Giovanni , Peng Wenbin , Carter Andrew , Ji Shunchuan , Pan Baotian
Published: February 2016

Nature Communications 6: Article number: 8511 (2015); Published: 9 October 2015; Updated: 18 February 2016. The original version of this Article contained errors in the Supplementary Information files: Zircon U-Pb age results for sample 23, shown in Supplementary Fig. 3, are incorrect, and missing from Supplementary Data 1, while several identification labels relating to Yellow River Lanzhou terraces samples are missing from Supplementary Data 2.
Deficits in cholinergic neurotransmission and their clinical correlates in Parkinson’s disease
Authors: Perez-Lloret Santiago , Barrantes Francisco J
Published: February 2016

In view of its ability to explain the most frequent motor symptoms of Parkinson’s Disease (PD), degeneration of dopaminergic neurons has been considered one of the disease’s main pathophysiological features. Several studies have shown that neurodegeneration also affects noradrenergic, serotoninergic, cholinergic and other monoaminergic neuronal populations. In this work, the characteristics of cholinergic deficits in PD and their clinical correlates are reviewed. Important neurophysiological processes at the root of several motor and cognitive functions remit to cholinergic neurotransmission at the synaptic, pathway, and circuital levels. The bulk of evidence highlights the link between cholinergic alterations and PD motor symptoms, gait dysfunction, levodopa-induced dyskinesias, cognitive deterioration, psychosis, sleep abnormalities, autonomic dysfunction, and altered olfactory function. The pathophysiology of these symptoms is related to alteration of the cholinergic tone in the striatum and/or to degeneration of cholinergic nuclei, most importantly the nucleus basalis magnocellularis and the pedunculopontine nucleus. Several results suggest the clinical usefulness of antimuscarinic drugs for treating PD motor symptoms and of inhibitors of the enzyme acetylcholinesterase for the treatment of dementia. Data also suggest that these inhibitors and pedunculopontine nucleus deep-brain stimulation might also be effective in preventing falls. Finally, several drugs acting on nicotinic receptors have proved efficacious for treating levodopa-induced dyskinesias and cognitive impairment and as neuroprotective agents in PD animal models. Results in human patients are still lacking.
A Modular Assembly Platform for Rapid Generation of DNA Constructs
Authors: Akama-Garren Elliot H. , Joshi Nikhil S. , Tammela Tuomas , Chang Gregory P. , Wagner Bethany L. , Lee Da-Yae , Rideout III William M. , Papagiannakopoulos Thales , Xue Wen , Jacks Tyler
Published: February 2016

Traditional cloning methods have limitations on the number of DNA fragments that can be simultaneously manipulated, which dramatically slows the pace of molecular assembly. Here we describe GMAP, a Gibson assembly-based modular assembly platform consisting of a collection of promoters and genes, which allows for one-step production of DNA constructs. GMAP facilitates rapid assembly of expression and viral constructs using modular genetic components, as well as increasingly complicated genetic tools using contextually relevant genomic elements. Our data demonstrate the applicability of GMAP toward the validation of synthetic promoters, identification of potent RNAi constructs, establishment of inducible lentiviral systems, tumor initiation in genetically engineered mouse models and gene-targeting for the generation of knock-in mice. GMAP represents a recombinant DNA technology designed for widespread circulation and easy adaptation for other uses, such as synthetic biology, genetic screens and CRISPR-Cas9.
Dysfunction of Wntless triggers the retrograde Golgi-to-ER transport of Wingless and induces ER stress
Authors: Zhang Peng , Zhou Lujun , Pei Chunli , Lin Xinhua , Yuan Zengqiang
Published: February 2016

Secreted Wnts play diverse roles in a non-cell-autonomous fashion. However, the cell-autonomous effect of unsecreted Wnts remains unknown. Endoplasmic reticulum (ER) stress is observed in specialized secretory cells and participates in pathophysiological processes. The correlation between Wnt secretion and ER stress remains poorly understood. Here, we demonstrated that Drosophila miR-307a initiates ER stress specifically in wingless (wg)-expressing cells through targeting wntless (wls/evi). This phenotype could be mimicked by retromer loss-of-function or porcupine (porc) depletion and rescued by wg knockdown, arguing that unsecreted Wg triggers ER stress. Consistently, we found that disrupting the secretion of human Wnt5a also induced ER stress in mammalian cells. Furthermore, we showed that a C-terminal KKVY-motif of Wg is required for its retrograde Golgi-to-ER transport, thus inducing ER stress. Next, we investigated if COPI, the regulator of retrograde transport, is responsible for unsecreted Wg to induce ER stress. To our surprise, we found that COPI acts as a novel regulator of Wg secretion. Taken together, this study reveals a previously unknown Golgi-to-ER retrograde route of Wg and elucidates a correlation between Wnt secretion and ER stress during development.
An approach to quantifying 3D responses of cells to extreme strain
Authors: Li Yuhui , Huang Guoyou , Li Moxiao , Wang Lin , Elson Elliot L. , Jian Lu Tian , Genin Guy M. , Xu Feng
Published: February 2016

The tissues of hollow organs can routinely stretch up to 2.5 times their length. Although significant pathology can arise if relatively large stretches are sustained, the responses of cells are not known at these levels of sustained strain. A key challenge is presenting cells with a realistic and well-defined three-dimensional (3D) culture environment that can sustain such strains. Here, we describe an in vitro system called microscale, magnetically-actuated synthetic tissues (micro-MASTs) to quantify these responses for cells within a 3D hydrogel matrix. Cellular strain-threshold and saturation behaviors were observed in hydrogel matrix, including strain-dependent proliferation, spreading, polarization and differentiation and matrix adhesion retained at strains sufficient for apoptosis. More broadly, the system shows promise for defining and controlling the effects of mechanical environment upon a broad range of cells.
How does curcumin work with poor bioavailability? Clues from experimental and theoretical studies
Authors: Shen Liang , Liu Cui-Cui , An Chun-Yan , Ji Hong-Fang
Published: February 2016

Curcumin is a natural product with multiple biological activities and numerous potential therapeutic applications. However, its poor systemic bioavailability fails to explain the potent pharmacological effects and hinders its clinical application. Using experimental and theoretical approaches, we compared curcumin and its degradation products for its biological activities against Alzheimer’s disease (AD), including the superoxide anion radical (O2.–)-scavenging activity, Aβ fibrils (fAβ) formation-inhibiting activity, and enzymatic inhibition activity. We showed that compared to the parent compound curcumin, the degradation products mixture possessed higher O2.–-scavenging activity and stronger inhibition against fAβ formation. The docking simulations revealed that the bioactive degradation products should make important contribution to the experimentally observed enzymatic inhibition activities of curcumin. Given that curcumin is readily degraded under physiological condition, our findings strongly suggested that the degradation products should make important contribution to the diverse biological activities of curcumin. Our novel findings not only provide novel insights into the complex pharmacology of curcumin due to its poor bioavailability, but also open new avenues for developing therapeutic applications of this natural product.
Continuous-wave phase-matched molecular optical modulator
Authors: Zaitsu Shin-ichi , Izaki Hirotomo , Tsuchiya Takao , Imasaka Totaro
Published: February 2016

In optical modulation, the highest available modulation rate is basically limited to the GHz frequency range at best. This is because optical modulation is often performed using electro-optic or acousto-optic effects that require application of an external signal to solid-state nonlinear optical materials. Here we describe optical modulation of continuous-wave radiation at frequencies exceeding 10 THz based on ultrafast variation of molecule polarizability arising from coherent molecular motion. The optical modulation efficiency is extensively enhanced by fulfilling phase-matching conditions with the help of dispersion control of the optical cavity, generating sidebands with a highest ratio of 7.3 × 10−3. These results will pave the way for development of versatile optical modulation-based techniques in a wide range of research fields in optical sciences, such as mode-locked lasers operating in the THz range.
Laser induced mortality of Anopheles stephensi mosquitoes
Authors: Keller Matthew D. , Leahy David J. , Norton Bryan J. , Johanson ric , Mullen Emma R. , Marvit Maclen , Makagon Arty
Published: February 2016

Small, flying insects continue to pose great risks to both human health and agricultural production throughout the world, so there remains a compelling need to develop new vector and pest control approaches. Here, we examined the use of short (<25 ms) laser pulses to kill or disable anesthetized femaleAnopheles stephensimosquitoes, which were chosen as a representative species. The mortality of mosquitoes exposed to laser pulses of various wavelength, power, pulse duration, and spot size combinations was assessed 24 hours after exposure. For otherwise comparable conditions, green and far-infrared wavelengths were found to be more effective than near- and mid-infrared wavelengths. Pulses with larger laser spot sizes required lower lethal energy densities, or fluence, but more pulse energy than for smaller spot sizes with greater fluence. Pulse duration had to be reduced by several orders of magnitude to significantly lower the lethal pulse energy or fluence required. These results identified the most promising candidates for the lethal laser component in a system being designed to identify, track, and shoot down flying insects in the wild.
Sulphur Kβ emission spectra reveal protonation states of aqueous sulfuric acid
Authors: Niskanen Johannes , Sahle Christoph J. , Ruotsalainen Kari O. , Müller Harald , Kavčič Matjaž , Žitnik Matjaž , Bučar Klemen , Petric Marko , Hakala Mikko , Huotari Simo
Published: February 2016

In this paper we report an X-ray emission study of bulk aqueous sulfuric acid. Throughout the range of molarities from 1 M to 18 M the sulfur Kβ emission spectra from H2SO4 (aq) depend on the molar fractions and related deprotonation of H2SO4. We compare the experimental results with results from emission spectrum calculations based on atomic structures of single molecules and structures from ab initio molecular dynamics simulations. We show that the S Kβ emission spectrum is a sensitive probe of the protonation state of the acid molecules. Using non-negative matrix factorization we are able to extract the fractions of different protonation states in the spectra and the results are in good agreement with the simulation for the higher part of the concentration range.
Comparative genomics of mitochondria in chlorarachniophyte algae: endosymbiotic gene transfer and organellar genome dynamics
Authors: Tanifuji Goro , Archibald John M. , Hashimoto Tetsuo
Published: February 2016

Chlorarachniophyte algae possess four DNA-containing compartments per cell, the nucleus, mitochondrion, plastid and nucleomorph, the latter being a relic nucleus derived from a secondary endosymbiont. While the evolutionary dynamics of plastid and nucleomorph genomes have been investigated, a comparative investigation of mitochondrial genomes (mtDNAs) has not been carried out. We have sequenced the complete mtDNA of Lotharella oceanica and compared it to that of another chlorarachniophyte, Bigelowiella natans. The linear mtDNA of L. oceanica is 36.7 kbp in size and contains 35 protein genes, three rRNAs and 24 tRNAs. The codons GUG and UUG appear to be capable of acting as initiation codons in the chlorarachniophyte mtDNAs, in addition to AUG. Rpl16, rps4 and atp8 genes are missing in L.oceanica mtDNA, despite being present in B. natans mtDNA. We searched for and found, mitochondrial rpl16 and rps4 genes with spliceosomal introns in the L. oceanica nuclear genome, indicating that mitochondrion-to-host-nucleus gene transfer occurred after the divergence of these two genera. Despite being of similar size and coding capacity, the level of synteny between L. oceanica and B. natans mtDNA is low, suggesting frequent rearrangements. Overall, our results suggest that chlorarachniophyte mtDNAs are more evolutionarily dynamic than their plastid counterparts.
Acute knockdown of the insulin receptor or its substrates Irs1 and 2 in 3T3-L1 adipocytes suppresses adiponectin production
Authors: Groeneveld Matthijs P. , Brierley Gemma V. , Rocha Nuno M. , Siddle Kenneth , Semple Robert K.
Published: February 2016

Loss of function of the insulin receptor (INSR) in humans produces severe insulin resistance. Unlike “common” insulin resistance, this is associated with elevated plasma levels of the insulin-sensitising, adipose-derived protein adiponectin. The underlying mechanism for this paradox is unclear and it is at odds with the acute stimulation of adiponectin secretion reported on insulin treatment of cultured adipocytes. Given recent evidence for ligand-independent actions of the INSR, we used a lentiviral system to knock down Insr or its substrates Irs1 and Irs2 conditionally in 3T3-L1 murine preadipocytes/adipocytes to assess whether acute loss of their expression has different consequences to withdrawal of insulin. Efficient knockdown of either Insr or Irs1/2 was achieved by conditional shRNA expression, severely attenuating insulin-stimulated AKT phosphorylation and glucose uptake. Dual knockdown of Irs1 and Irs2 but not Insr in preadipocytes impaired differentiation to adipocytes. Acute knockdown of Insr or both Irs1 and Irs2 in adipocytes increased Adipoq mRNA expression but reduced adiponectin secretion, assessed by immunoassay. Knockdown sustained for 14 days also reduced immunoassay-detected adiponectin secretion and moreover induced delipidation of the cells. These findings argue against a distinct effect of Insr deficiency to promote adiponectin secretion as the explanation for paradoxical insulin receptoropathy-related hyperadiponectinaemia.
Thermodynamics and efficiency of an autonomous on-chip Maxwell’s demon
Authors: Kutvonen Aki , Koski Jonne , Ala-Nissila Tapio
Published: February 2016

In his famous letter in 1870, Maxwell describes how Joule’s law can be violated “only by the intelligent action of a mere guiding agent”, later coined as Maxwell’s demon by Lord Kelvin. In this letter we study thermodynamics of information using an experimentally feasible Maxwell’s demon setup based a single electron transistor capacitively coupled to a single electron box, where both the system and the Demon can be clearly identified. Such an engineered on-chip Demon measures and performes feedback on the system, which can be observed as cooling whose efficiency can be adjusted. We present a detailed analysis of the system and the Demon, including the second law of thermodynamics for bare and coarse grained entropy production and the flow of information as well as efficiency of information production and utilization. Our results demonstrate how information thermodynamics can be used to improve functionality of modern nanoscale devices.
Photoluminescence and photocatalytic properties of rhombohedral CuGaO2 nanoplates
Authors: Shi Linlin , Wang Fei , Wang Yunpeng , Wang Dengkui , Zhao Bin , Zhang Ligong , Zhao Dongxu , Shen Dezhen
Published: February 2016

Rhombohedral phase CuGaO2 nanoplates with a diameter of about 10 μm were synthesized via low temperature hydrothermal method. Room temperature and low temperature photoluminescence of the obtained CuGaO2 nanoplates were characterized. CuGaO2 nanoplates exhibited blue emission at room temperature and free exciton emission were appeared at low temperature. The blue emission is originated from defects such as Cu vacancies, which is the possible origin of p-type conductivity. The appearance of free exciton emission can demonstrate the direct bandgap transition behavior of CuGaO2 nanoplates. The as-prepared p-type CuGaO2 nanoplates were further decorated by n-type ZnO nanoparticles via calcination method to fabricate p-n junction nanocomposites. The nanocomposites exhibited enhanced photocatalytic activity which can be ascribed to the effective separation of photogenerated carriers by the internal electrostatic field in the p-n junction region and the enhanced light absorption properties resulted from sub-bandgap absorption effect of p-n junction. This work has offered a new insight into the design of p-n junction devices using p-type CuGaO2 nanoplates.
Recurrent Spiking Networks Solve Planning Tasks
Authors: Rueckert Elmar , Kappel David , Tanneberg Daniel , Pecevski Dejan , Peters Jan
Published: February 2016

A recurrent spiking neural network is proposed that implements planning as probabilistic inference for finite and infinite horizon tasks. The architecture splits this problem into two parts: The stochastic transient firing of the network embodies the dynamics of the planning task. With appropriate injected input this dynamics is shaped to generate high-reward state trajectories. A general class of reward-modulated plasticity rules for these afferent synapses is presented. The updates optimize the likelihood of getting a reward through a variant of an Expectation Maximization algorithm and learning is guaranteed to convergence to a local maximum. We find that the network dynamics are qualitatively similar to transient firing patterns during planning and foraging in the hippocampus of awake behaving rats. The model extends classical attractor models and provides a testable prediction on identifying modulating contextual information. In a real robot arm reaching and obstacle avoidance task the ability to represent multiple task solutions is investigated. The neural planning method with its local update rules provides the basis for future neuromorphic hardware implementations with promising potentials like large data processing abilities and early initiation of strategies to avoid dangerous situations in robot co-worker scenarios.
Rhus coriaria suppresses angiogenesis, metastasis and tumor growth of breast cancer through inhibition of STAT3, NFκB and nitric oxide pathways
Authors: El Hasasna Hussain , Saleh Alaaeldin , Samri Halima Al , Athamneh Khawlah , Attoub Samir , Arafat Kholoud , Benhalilou Nehla , Alyan Sofyan , Viallet Jean , Dhaheri Yusra Al , Eid Ali , Iratni Rabah
Published: February 2016

Recently, we reported that Rhus coriaria exhibits anticancer activities by promoting cell cycle arrest and autophagic cell death of the metastatic triple negative MDA-MB-231 breast cancer cells. Here, we investigated the effect of Rhus coriaria on the migration, invasion, metastasis and tumor growth of TNBC cells. Our current study revealed that non-cytotoxic concentrations of Rhus coriaria significantly inhibited migration and invasion, blocked adhesion to fibronectin and downregulated MMP-9 and prostaglandin E2 (PgE2). Not only did Rhus coriaria decrease their adhesion to HUVECs and to lung microvascular endothelial (HMVEC-L) cells, but it also inhibited the transendothelial migration of MDA-MB-231 cells through TNF-α-activated HUVECs. Furthermore, we found that Rhus coriaria inhibited angiogenesis, reduced VEGF production in both MDA-MB-231 and HUVECs and downregulated the inflammatory cytokines TNF-α, IL-6 and IL-8. The underlying mechanism for Rhus coriaria effects appears to be through inhibiting NFκB, STAT3 and nitric oxide (NO) pathways. Most importantly, by using chick embryo tumor growth assay, we showed that Rhus coriaria suppressed tumor growth and metastasis in vivo. The results described in the present study identify Rhus coriaria as a promising chemopreventive and therapeutic candidate that modulate triple negative breast cancer growth and metastasis.
Effects of memory on the shapes of simple outbreak trees
Authors: Plazzotta Giacomo , Kwan Christopher , Boyd Michael , Colijn Caroline
Published: February 2016

Genomic tools, including phylogenetic trees derived from sequence data, are increasingly used to understand outbreaks of infectious diseases. One challenge is to link phylogenetic trees to patterns of transmission. Particularly in bacteria that cause chronic infections, this inference is affected by variable infectious periods and infectivity over time. It is known that non-exponential infectious periods can have substantial effects on pathogens’ transmission dynamics. Here we ask how this non-Markovian nature of an outbreak process affects the branching trees describing that process, with particular focus on tree shapes. We simulate Crump-Mode-Jagers branching processes and compare different patterns of infectivity over time. We find that memory (non-Markovian-ness) in the process can have a pronounced effect on the shapes of the outbreak’s branching pattern. However, memory also has a pronounced effect on the sizes of the trees, even when the duration of the simulation is fixed. When the sizes of the trees are constrained to a constant value, memory in our processes has little direct effect on tree shapes, but can bias inference of the birth rate from trees. We compare simulated branching trees to phylogenetic trees from an outbreak of tuberculosis in Canada, and discuss the relevance of memory to this dataset.
Neuroimaging evidence of deficient axon myelination in Wolfram syndrome
Authors: Lugar Heather M. , Koller Jonathan M. , Rutlin Jerrel , Marshall Bess A. , Kanekura Kohsuke , Urano Fumihiko , Bischoff Allison N. , Shimony Joshua S. , Hershey Tamara ,   the Washington University Wolfram Syndrome Research Study Group, Austin P. , Beato B. , Bihun E. , Doty T. , Earhart G. , Eisenstein S. , Hoekel J. , Karzon R. , Licis A. , Manwaring L. , Paciorkowski A. R. , Pepino de Gruev Y. , Permutt A. , Pickett K. , Ranck S. , Reiersen A. , Tychsen L. , Viehoever A. , Wasson J. , White N. H.
Published: February 2016

Wolfram syndrome is a rare autosomal recessive genetic disease characterized by insulin dependent diabetes and vision, hearing and brain abnormalities which generally emerge in childhood. Mutations in the WFS1 gene predispose cells to endoplasmic reticulum stress-mediated apoptosis and may induce myelin degradation in neuronal cell models. However, in vivo evidence of this phenomenon in humans is lacking. White matter microstructure and regional volumes were measured using magnetic resonance imaging in children and young adults with Wolfram syndrome (n = 21) and healthy and diabetic controls (n = 50). Wolfram patients had lower fractional anisotropy and higher radial diffusivity in major white matter tracts and lower volume in the basilar (ventral) pons, cerebellar white matter and visual cortex. Correlations were found between key brain findings and overall neurological symptoms. This pattern of findings suggests that reduction in myelin is a primary neuropathological feature of Wolfram syndrome. Endoplasmic reticulum stress-related dysfunction in Wolfram syndrome may interact with the development of myelin or promote degeneration of myelin during the progression of the disease. These measures may provide objective indices of Wolfram syndrome pathophysiology that will be useful in unraveling the underlying mechanisms and in testing the impact of treatments on the brain.
Synthesis and characterization of vertically standing MoS2 nanosheets
Authors: Li Han , Wu Huaqiang , Yuan Shuoguo , Qian He
Published: February 2016

Molybdenum disulfide (MoS2) has been attracting much attentions due to its excellent electrical and optical properties. We report here the synthesis of large-scale and uniform MoS2 nanosheets with vertically standing morphology using chemical vapor deposition method. TEM observations clearly reveal the growth mechanism of these vertical structures. It is suggested that the vertical structures are caused by the compression and extrusion between MoS2 islands. More importantly, the vertical morphology of two dimensional (2D) materials hold many promising potential applications. We demonstrate here the as-synthesized vertically standing MoS2 nanosheets could be used for hydrogen evolution reaction, where the exchange current density is about 70 times of bulk MoS2. The field emission performance of vertically standing MoS2 were also improved due to the abundantly exposed edges.
Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II
Authors: Mulholland Sam , Turpin Eleanor R. , Bonev Boyan B. , Hirst Jonathan D.
Published: February 2016

Lanthionine antibiotics are an important class of naturally-occurring antimicrobial peptides. The best-known, nisin, is a commercial food preservative. However, structural and mechanistic details on nisin-lipid II membrane complexes are currently lacking. Recently, we have developed empirical force-field parameters to model lantibiotics. Docking and molecular dynamics (MD) simulations have been used to study the nisin2:lipid II complex in bacterial membranes, which has been put forward as the building block of nisin/lipid II binary membrane pores. An Ile1Trp mutation of the N-terminus of nisin has been modelled and docked onto lipid II models; the computed binding affinity increased compared to wild-type. Wild-type nisin was also docked onto three different lipid II structures and a stable 2:1 nisin:lipid II complex formed. This complex was inserted into a membrane. Six independent MD simulations revealed key interactions in the complex, specifically the N-terminal engagement of nisin with lipid II at the pyrophosphate and C-terminus of the pentapeptide chain. Nisin2inserts into the membrane and we propose this as the first step in pore formation, mediated by the nisin N-terminus–lipid II pentapeptide hydrogen bond. The lipid II undecaprenyl chain adopted different conformations in the presence of nisin, which may also have implications for pore formation.
Large pinning forces and matching effects in YBa2Cu3O7-δ thin films with Ba2Y(Nb/Ta)O6 nano-precipitates
Authors: Opherden Lars , Sieger Max , Pahlke Patrick , Hühne Ruben , Schultz Ludwig , Meledin Alexander , Van Tendeloo Gustaaf , Nast Rainer , Holzapfel Bernhard , Bianchetti Marco , MacManus-Driscoll Judith L. , Hänisch Jens
Published: February 2016

The addition of mixed double perovskite Ba2Y(Nb/Ta)O6(BYNTO) to YBa2Cu3O7−δ(YBCO) thin films leads to a large improvement of the in-field current carrying capability. For low deposition rates, BYNTO grows as well-oriented, densely distributed nanocolumns. We achieved a pinning force density of 25 GN/m3at 77 K at a matching field of 2.3 T, which is among the highest values reported for YBCO. The anisotropy of the critical current density shows a complex behavior whereby additional maxima are developed at field dependent angles. This is caused by a matching effect of the magnetic fieldsc-axis component. The exponentNof the current-voltage characteristics (inversely proportional to the creep rateS) allows the depinning mechanism to be determined. It changes from a double-kink excitation below the matching field to pinning-potential-determined creep above it.
Conserved miR-26b enhances ovarian granulosa cell apoptosis through HAS2-HA-CD44-Caspase-3 pathway by targeting HAS2
Authors: Liu Jiying , Tu Fei , Yao Wang , Li Xinyu , Xie Zhuang , Liu Honglin , Li Qifa , Pan Zengxiang
Published: February 2016

The hyaluronan synthase 2 (HAS2)-hyaluronic acid (HA)-CD44-Caspase-3 pathway is involved in ovarian granulosa cell (GC) functions in mammals. HAS2 is a key enzyme required for HA synthesis and is the key factor in this pathway. However, the regulation of HAS2 and the HAS2-mediated pathway by microRNAs in GCs is poorly understood. Here, we report that miR-26b regulates porcine GC (pGC) apoptosis through the HAS2-HA-CD44-Caspase-3 pathway by binding directly to the 3′- untranslated region of HAS2 mRNA. Knockdown of miR-26b reduced pGC apoptosis. Luciferase reporter assays demonstrated that HAS2 is a direct target of miR-26b in pGCs. Knockdown and overexpression of miR-26b increased and decreased, respectively, HA content and HAS2 and CD44 expression in pGCs. At the same time, inhibition and overexpression of miR-26b decreased and increased the expression of Caspase-3, a downstream factor in the HAS2-HA-CD44 pathway. Moreover, knockdown of HAS2 enhanced pGC apoptosis, reduced the inhibitory effects of a miR-26b inhibitor on pGC apoptosis, repressed HA content and CD44 expression and promoted Caspase-3 expression. In addition, overexpression of HAS2 has a opposite effect. Collectively, miR-26b positively regulates pGC apoptosis via a novel HAS2-HA-CD44-Caspase-3 pathway by targeting the HAS2 gene.
Giant absorption of light by molecular vibrations on a chip
Authors: Karabchevsky A. , Kavokin A. V.
Published: February 2016

Vibrational overtone spectroscopy of molecules is a powerful tool for drawing information on molecular structure and dynamics. It relies on absorption of near infrared radiation (NIR) by molecular vibrations. Here we show the experimental evidence of giant enhancement of the absorption of light in solutions of organic molecules due to the switch from ballistic to diffusive propagation of light through a channel silicate glass waveguide. We also experimentally address a dynamics of absorption as a function of time of adsorption of the organic molecules on a waveguide. The observed enhancement in diffusion regime is by a factor of 300 in N-Methylaniline and by factor of 80 in Aniline compared to the expected values in the case of ballistic propagation of light in a waveguide. Our results underscore the importance of a guide surface modification and the disordered molecular nano-layer in enhancement of absorption by amines on engineered integrated system.
BDNF-induced LTP is associated with rapid Arc/Arg3.1-dependent enhancement in adult hippocampal neurogenesis
Authors: Kuipers Sjoukje D. , Trentani Andrea , Tiron Adrian , Mao Xiaosong , Kuhl Dietmar , Bramham Clive R.
Published: February 2016

Adult neurogenesis in the hippocampus is a remarkable phenomenon involved in various aspects of learning and memory as well as disease pathophysiology. Brain-derived neurotrophic factor (BDNF) represents a major player in the regulation of this unique form of neuroplasticity, yet the mechanisms underlying its pro-neurogenic actions remain unclear. Here, we examined the effects associated with brief (25 min), unilateral infusion of BDNF in the rat dentate gyrus. Acute BDNF infusion induced long-term potentiation (LTP) of medial perforant path-evoked synaptic transmission and, concomitantly, enhanced hippocampal neurogenesis bilaterally, reflected by increased dentate gyrus BrdU + cell numbers. Importantly, inhibition of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) translation through local, unilateral infusion of anti-sense oligodeoxynucleotides (ArcAS) prior to BDNF infusion blocked both BDNF-LTP induction and the associated pro-neurogenic effects. Notably, basal rates of proliferation and newborn cell survival were unaltered in homozygous Arc/Arg3.1 knockout mice. Taken together these findings link the pro-neurogenic effects of acute BDNF infusion to induction of Arc/Arg3.1-dependent LTP in the adult rodent dentate gyrus.
Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals
Authors: Sankhyan Anurag , Sharma Chandresh , Dutta Durgashree , Sharma Tarang , Chosdol Kunzang , Wakita Takaji , Watashi Koichi , Awasthi Amit , Acharya Subrat K. , Khanna Navin , Tiwari Ashutosh , Sinha Subrata
Published: February 2016

Neutralizing monoclonal antibodies are being found to be increasingly useful in viral infections. In hepatitis B infection, antibodies are proven to be useful for passive prophylaxis. The preS1 region (21–47a.a.) of HBV contains the viral hepatocyte-binding domain crucial for its attachment and infection of hepatocytes. Antibodies against this region are neutralizing and are best suited for immune-based neutralization of HBV, especially in view of their not recognizing decoy particles. Anti-preS1 (21–47a.a.) antibodies are present in serum of spontaneously recovered individuals. We generated a phage-displayed scFv library using circulating lymphocytes from these individuals and selected four preS1-peptide specific scFvs with markedly distinct sequences from this library. All the antibodies recognized the blood-derived and recombinant preS1 containing antigens. Each scFv showed a discrete binding signature, interacting with different amino acids within the preS1-peptide region. Ability to prevent binding of the preS1 protein (N-terminus 60a.a.) to HepG2 cells stably expressing hNTCP (HepG2-hNTCP-C4 cells), the HBV receptor on human hepatocytes was taken as a surrogate marker for neutralizing capacity. These antibodies inhibited preS1-hepatocyte interaction individually and even better in combination. Such a combination of potentially neutralizing recombinant antibodies with defined specificities could be used for preventing/managing HBV infections, including those by possible escape mutants.
G6PDH activity highlights the operation of the cyclic electron flow around PSI in Physcomitrella patens during salt stress
Authors: Gao Shan , Zheng Zhenbing , Huan Li , Wang Guangce
Published: February 2016

Photosynthetic performances and glucose-6-phosphate dehydrogenase (G6PDH) activity inPhyscomitrella patenschanged greatly during salt stress and recovery. InP. patens, the cyclic electron flow around photosystem (PS) I was much more tolerant to high salt stress than PSII. After high salt stress, the PSII activity recovered much more slowly than that of PSI, which was rapidly restored to pretreatment levels even as PSII was almost inactivate. This result suggested that after salt stress the recovery of the cyclic electron flow around PSI was independent of PSII activity. In addition, G6PDH activity and NADPH content increased under high salt stress. When G6PDH activity was inhibited by glucosamine (Glucm, a G6PDH inhibitor), the cyclic electron flow around PSI and the NADPH content decreased significantly. Additionally, after recovery in liquid medium containing Glucm, the PSI activity was much lower than in liquid medium without Glucm. These results suggested the PSI activity was affected significantly by G6PDH activity and the NADPH content. Based on the above results, we propose that G6PDH inP. patenshas a close relationship with the photosynthetic process, possibly providing NADPH for the operation of the cyclic electron flow around PSI during salt stress and promoting the restoration of PSI.
Enrichment of G2/M cell cycle phase in human pluripotent stem cells enhances HDR-mediated gene repair with customizable endonucleases
Authors: Yang Diane , Scavuzzo Marissa A , Chmielowiec Jolanta , Sharp Robert , Bajic Aleksandar , Borowiak Malgorzata
Published: February 2016

Efficient gene editing is essential to fully utilize human pluripotent stem cells (hPSCs) in regenerative medicine. Custom endonuclease-based gene targeting involves two mechanisms of DNA repair: homology directed repair (HDR) and non-homologous end joining (NHEJ). HDR is the preferred mechanism for common applications such knock-in, knock-out or precise mutagenesis, but remains inefficient in hPSCs. Here, we demonstrate that synchronizing synchronizing hPSCs in G2/M with ABT phase increases on-target gene editing, defined as correct targeting cassette integration, 3 to 6 fold. We observed improved efficiency using ZFNs, TALENs, two CRISPR/Cas9, and CRISPR/Cas9 nickase to target five genes in three hPSC lines: three human embryonic stem cell lines, neural progenitors and diabetic iPSCs. neural progenitors and diabetic iPSCs. Reversible synchronization has no effect on pluripotency or differentiation. The increase in on-target gene editing is locus-independent and specific to the cell cycle phase as G2/M phase enriched cells show a 6-fold increase in targeting efficiency compared to cells in G1 phase. Concurrently inhibiting NHEJ with SCR7 does not increase HDR or improve gene targeting efficiency further, indicating that HR is the major DNA repair mechanism after G2/M phase arrest. The approach outlined here makes gene editing in hPSCs a more viable tool for disease modeling, regenerative medicine and cell-based therapies.
Collective chemotaxis and segregation of active bacterial colonies
Authors: Amar M. Ben
Published: February 2016

Still recently, bacterial fluid suspensions have motivated a lot of works, both experimental and theoretical, with the objective to understand their collective dynamics from universal and simple rules. Since some species are active, most of these works concern the strong interactions that these bacteria exert on a forced flow leading to instabilities, chaos and turbulence. Here, we investigate the self-organization of expanding bacterial colonies under chemotaxis, proliferation and eventually active-reaction. We propose a simple model to understand and quantify the physical properties of these living organisms which either give cohesion or on the contrary dispersion to the colony. Taking into account the diffusion and capture of morphogens complicates the model since it induces a bacterial density gradient coupled to bacterial density fluctuations and dynamics. Nevertheless under some specific conditions, it is possible to investigate the pattern formation as a usual viscous fingering instability. This explains the similarity and differences of patterns according to the physical bacterial suspension properties and explain the factors which favor compactness or branching.
Semimetallization of dielectrics in strong optical fields
Authors: Kwon Ojoon , Paasch-Colberg Tim , Apalkov Vadym , Kim Bum-Kyu , Kim Ju-Jin , Stockman Mark I. , Kim D.
Published: February 2016

At the heart of ever growing demands for faster signal processing is ultrafast charge transport and control by electromagnetic fields in semiconductors. Intense optical fields have opened fascinating avenues for new phenomena and applications in solids. Because the period of optical fields is on the order of a femtosecond, the current switching and its control by an optical field may pave a way to petahertz optoelectronic devices. Lately, a reversible semimetallization in fused silica on a femtosecond time scale by using a few-cycle strong field (~1 V/Å) is manifested. The strong Wannier-Stark localization and Zener-type tunneling were expected to drive this ultrafast semimetallization. Wider spread of this technology demands better understanding of whether the strong field behavior is universally similar for different dielectrics. Here we employ a carrier-envelope-phase stabilized, few-cycle strong optical field to drive the semimetallization in sapphire, calcium fluoride and quartz and to compare this phenomenon and show its remarkable similarity between them. The similarity in response of these materials, despite the distinguishable differences in their physical properties, suggests the universality of the physical picture explained by the localization of Wannier-Stark states. Our results may blaze a trail to PHz-rate optoelectronics.
Interfacial Atomic Structure of Twisted Few-Layer Graphene
Authors: Ishikawa Ryo , Lugg Nathan R. , Inoue Kazutoshi , Sawada Hidetaka , Taniguchi Takashi , Shibata Naoya , Ikuhara Yuichi
Published: February 2016

A twist in bi- or few-layer graphene breaks the local symmetry, introducing a number of intriguing physical properties such as opening new bandgaps. Therefore, determining the twisted atomic structure is critical to understanding and controlling the functional properties of graphene. Combining low-angle annular dark-field electron microscopy with image simulations, we directly determine the atomic structure of twisted few-layer graphene in terms of a moiré superstructure which is parameterized by a single twist angle and lattice constant. This method is shown to be a powerful tool for accurately determining the atomic structure of two-dimensional materials such as graphene, even in the presence of experimental errors. Using coincidence-site-lattice and displacement-shift-complete theories, we show that the in-plane translation state between layers is not a significant structure parameter, explaining why the present method is adequate not only for bilayer graphene but also a few-layered twisted graphene.
Organic heterojunctions: Contact-induced molecular reorientation, interface states and charge re-distribution
Authors: Opitz Andreas , Wilke Andreas , Amsalem Patrick , Oehzelt Martin , Blum Ralf-Peter , Rabe Jürgen P. , Mizokuro Toshiko , Hörmann Ulrich , Hansson Rickard , Moons Ellen , Koch Norbert
Published: February 2016

We reveal the rather complex interplay of contact-induced re-orientation and interfacial electronic structure – in the presence of Fermi-level pinning – at prototypical molecular heterojunctions comprising copper phthalocyanine (H16CuPc) and its perfluorinated analogue (F16CuPc), by employing ultraviolet photoelectron and X-ray absorption spectroscopy. For both layer sequences, we find that Fermi-level (EF) pinning of the first layer on the conductive polymer substrate modifies the work function encountered by the second layer such that it also becomes EF-pinned, however, at the interface towards the first molecular layer. This results in a charge transfer accompanied by a sheet charge density at the organic/organic interface. While molecules in the bulk of the films exhibit upright orientation, contact formation at the heterojunction results in an interfacial bilayer with lying and co-facial orientation. This interfacial layer is not EF-pinned, but provides for an additional density of states at the interface that is not present in the bulk. With reliable knowledge of the organic heterojunction’s electronic structure we can explain the poor performance of these in photovoltaic cells as well as their valuable function as charge generation layer in electronic devices.