bluuebunny/crossref_metadata_2025 huggingface dataset:
Multibeam Microstrip Patch Antennas Excited by Parallel‐Plate Beam‐Forming Network With Shaped Reflecting Boundary and Optimized Slot Feeding Transition Structures
Authors: Chou Hsi‐Tseng , Chang Chia‐Hung , Chen Ying‐Shan
Published: October 2018

This paper presents the design of a multibeam phased array of microstrip patch antennas at 38 GHz with a parallel‐plate beam‐forming network (BFN). This antenna set, including the antenna elements and BFN, is equivalently triple‐folded into two stacked printed circuit board substrates for a compact design of nearly 60% size reduction in comparison to conventional implementation on a single planar dielectric substrate. In particular, the BFN employs a shaped metal reflecting boundary in the bottom substrate to transform the cylindrical waves of feed excitations into planar ones for a relatively linear phase variation to feed the column subarrays on the top substrate. A slot feeding transition structure is designed to couple the energy from the BFN to feed the microstrip patch antenna ports. These two mechanisms are then used to compensate the phase distortions due to BFN cavity disturbance and mutual coupling from subarrays of antennas at millimeter wave frequencies. Numerical techniques to optimize both the metal reflecting boundary and slot feeding transition structure are introduced to minimize phase distortions. Numerical and experimental results are presented to demonstrate the radiation characteristics of the integrated antenna set.
Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death
Authors: Syc-Mazurek Stephanie B. , Rausch Rebecca L. , Fernandes Kimberly A. , Wilson Michael P. , Libby Richard T.
Published: October 2018

The mitogen-activated protein kinase (MAPK) pathway has been shown to be involved in both neurodevelopment and neurodegeneration. c-Jun N-terminal kinase (JNK), a MAPK important in retinal development and after optic nerve crush injury, is regulated by two upstream kinases: MKK4 and MKK7. The specific requirements of MKK4 and MKK7 in retinal development and retinal ganglion cell (RGC) death after axonal injury, however, are currently undefined. Optic nerve injury is an important insult in many neurologic conditions including traumatic, ischemic, inflammatory, and glaucomatous optic neuropathies. Mice deficient in Mkk4, Mkk7, and both Mkk4 and Mkk7 were generated. Immunohistochemistry was used to study the distribution and structure of retinal cell types and to assess RGC survival after optic nerve injury (mechanical controlled optic nerve crush (CONC)). Adult Mkk4- and Mkk7-deficient retinas had all retinal cell types, and with the exception of small areas of disrupted photoreceptor lamination in Mkk4-deficient mice, the retinas of both mutants were grossly normal. Deficiency of Mkk4 or Mkk7 reduced JNK signaling in RGCs after axonal injury and resulted in a significantly greater percentage of surviving RGCs 35 days after CONC as compared to wild-type controls (Mkk4: 51.5%, Mkk7: 29.1%, WT: 15.2%; p < 0.001). Combined deficiency of Mkk4 and Mkk7 caused failure of optic nerve formation, irregular retinal axonal trajectories, disruption of retinal lamination, clumping of RGC bodies, and dendritic fasciculation of dopaminergic amacrine cells. These results suggest that MKK4 and MKK7 may serve redundant and unique roles in molecular signaling important for retinal development and injury response following axonal insult.
Leptin in depression: a potential therapeutic target
Authors: Ge Tongtong , Fan Jie , Yang Wei , Cui Ranji , Li Bingjin
Published: October 2018

Leptin, produced and secreted by white adipose tissue, plays a critical role in regulating body weight, food intake, and energy metabolism. Recently, several studies have identified an underlying role for leptin in regulation of mood and cognition via regulation of synaptic changes in the brain that have been associated with antidepressant-like actions. Brain neural plasticity occurs in response to a range of intrinsic and extrinsic stimuli, including those that may mediate the effects of antidepressants. Neural plasticity theories of depression are thought to explain multiple aspects of depression and the effects of antidepressants. It is also well documented that leptin has effects on neural plasticity. This review summarizes the recent literature on the role of leptin in neural plasticity in order to elaborate the possible mechanism of leptin’s antidepressant-like effects. Recent findings provide new insights into the underlying mechanisms of neural plasticity in depression. Leptin may influence these mechanisms and consequently constitute a possible target for novel therapeutic approaches to the treatment of depression.
Distinct functional elements for outer-surface anti-interference and inner-wall ion gating of nanochannels
Authors: Gao Pengcheng , Ma Qun , Ding Defang , Wang Dagui , Lou Xiaoding , Zhai Tianyou , Xia Fan
Published: October 2018

Over the decades, widespread advances have been achieved on nanochannels, including nanochannel-based DNA sequencing, single-molecule detection, smart sensors, and energy transfer and storage. However, most interest has been focused on the contribution from the functional elements (FEs) at the inner wall (IW) of nanochannels, whereas little attention has been paid to the contribution from the FEs at the nanochannels’ outer surface (OS). Herein, we achieve explicit partition of FEOS and FEIW based on accurate regional-modification of OS and IW. The FEIW are served for ionic gating, and the chosen FEOS (hydrophobic or charged) are served for blocking interference molecules into the nanochannels, decreasing the false signals for the ionic gating in complex environments. Furthermore, we define a composite factor, areas of a radar map, to evaluate the FEOS performance for blocking interference molecules.
Non-resonant light scattering in dispersions of 2D nanosheets
Authors: Harvey Andrew , Backes Claudia , Boland John B. , He Xiaoyun , Griffin Aideen , Szydlowska Beata , Gabbett Cian , Donegan John F. , Coleman Jonathan N.
Published: October 2018

Extinction spectra of nanomaterial suspensions can be dominated by light scattering, hampering quantitative spectral analysis. No simple models exist for the wavelength-dependence of the scattering coefficients in suspensions of arbitrary-sized, high-aspect-ratio nanoparticles. Here, suspensions of BN, talc, GaS, Ni(OH)2, Mg(OH)2 and Cu(OH)2 nanosheets are used to explore non-resonant scattering in wide-bandgap 2D nanomaterials. Using an integrating sphere, scattering coefficient (σ) spectra were measured for a number of size-selected fractions for each nanosheet type. Generally, σ scales as a power-law with wavelength in the non-resonant regime: σ(λ)∝[λ/〈L〉]−m, where 〈L〉 is the mean nanosheet length. For all materials, the scattering exponent, m, forms a master-curve, transitioning from m = 4 to m = 2, as the characteristic nanosheet area increases, indicating a transition from Rayleigh to van der Hulst scattering. In addition, once material density and refractive index are factored out, the proportionality constant relating σ to [λ/〈L〉]−m, also forms a master-curve when plotted versus 〈L〉.
Transcriptional read-through of the long non-coding RNA SVALKA governs plant cold acclimation
Authors: Kindgren Peter , Ard Ryan , Ivanov Maxim , Marquardt Sebastian
Published: October 2018

Most DNA in the genomes of higher organisms does not encode proteins, yet much is transcribed by RNA polymerase II (RNAPII) into long non-coding RNAs (lncRNAs). The biological significance of most lncRNAs is largely unclear. Here, we identify a lncRNA (SVALKA) in a cold-sensitive region of the Arabidopsis genome. Mutations in SVALKA affect CBF1 expression and freezing tolerance. RNAPII read-through transcription of SVALKA results in a cryptic lncRNA overlapping CBF1 on the antisense strand, termed asCBF1. Our molecular dissection reveals that CBF1 is suppressed by RNAPII collision stemming from the SVALKA-asCBF1 lncRNA cascade. The SVALKA-asCBF1 cascade provides a mechanism to tightly control CBF1 expression and timing that could be exploited to maximize freezing tolerance with mitigated fitness costs. Our results provide a compelling example of local gene regulation by lncRNA transcription having a profound impact on the ability of plants to appropriately acclimate to challenging environmental conditions.
Metasurface eyepiece for augmented reality
Authors: Lee Gun-Yeal , Hong Jong-Young , Hwang SoonHyoung , Moon Seokil , Kang Hyeokjung , Jeon Sohee , Kim Hwi , Jeong Jun-Ho , Lee Byoungho
Published: October 2018

Recently, metasurfaces composed of artificially fabricated subwavelength structures have shown remarkable potential for the manipulation of light with unprecedented functionality. Here, we first demonstrate a metasurface application to realize a compact near-eye display system for augmented reality with a wide field of view. A key component is a see-through metalens with an anisotropic response, a high numerical aperture with a large aperture, and broadband characteristics. By virtue of these high-performance features, the metalens can overcome the existing bottleneck imposed by the narrow field of view and bulkiness of current systems, which hinders their usability and further development. Experimental demonstrations with a nanoimprinted large-area see-through metalens are reported, showing full-color imaging with a wide field of view and feasibility of mass production. This work on novel metasurface applications shows great potential for the development of optical display systems for future consumer electronics and computer vision applications.
Short-chain ketone production by engineered polyketide synthases in Streptomyces albus
Authors: Yuzawa Satoshi , Mirsiaghi Mona , Jocic Renee , Fujii Tatsuya , Masson Fabrice , Benites Veronica T. , Baidoo Edward E. K. , Sundstrom Eric , Tanjore Deepti , Pray Todd R. , George Anthe , Davis Ryan W. , Gladden John M. , Simmons Blake A. , Katz Leonard , Keasling Jay D.
Published: October 2018

Microbial production of fuels and commodity chemicals has been performed primarily using natural or slightly modified enzymes, which inherently limits the types of molecules that can be produced. Type I modular polyketide synthases (PKSs) are multi-domain enzymes that can produce unique and diverse molecular structures by combining particular types of catalytic domains in a specific order. This catalytic mechanism offers a wealth of engineering opportunities. Here we report engineered microbes that produce various short-chain (C5–C7) ketones using hybrid PKSs. Introduction of the genes into the chromosome of Streptomyces albus enables it to produce >1 g · l−1 of C6 and C7 ethyl ketones and several hundred mg · l−1 of C5 and C6 methyl ketones from plant biomass hydrolysates. Engine tests indicate these short-chain ketones can be added to gasoline as oxygenates to increase the octane of gasoline. Together, it demonstrates the efficient and renewable microbial production of biogasolines by hybrid enzymes.
The impact of Arctic sea ice loss on mid-Holocene climate
Authors: Park Hyo-Seok , Kim Seong-Joong , Seo Kyong-Hwan , Stewart Andrew L. , Kim Seo-Yeon , Son Seok-Woo
Published: October 2018

Mid-Holocene climate was characterized by strong summer solar heating that decreased Arctic sea ice cover. Motivated by recent studies identifying Arctic sea ice loss as a key driver of future climate change, we separate the influences of Arctic sea ice loss on mid-Holocene climate. By performing idealized climate model perturbation experiments, we show that Arctic sea ice loss causes zonally asymmetric surface temperature responses especially in winter: sea ice loss warms North America and the North Pacific, which would otherwise be much colder due to weaker winter insolation. In contrast, over East Asia, sea ice loss slightly decreases the temperature in early winter. These temperature responses are associated with the weakening of mid-high latitude westerlies and polar stratospheric warming. Sea ice loss also weakens the Atlantic meridional overturning circulation, although this weakening signal diminishes after 150–200 years of model integration. These results suggest that mid-Holocene climate changes should be interpreted in terms of both Arctic sea ice cover and insolation forcing.
Structural insights into the π-π-π stacking mechanism and DNA-binding activity of the YEATS domain
Authors: Klein Brianna J. , Vann Kendra R. , Andrews Forest H. , Wang Wesley W. , Zhang Jibo , Zhang Yi , Beloglazkina Anastasia A. , Mi Wenyi , Li Yuanyuan , Li Haitao , Shi Xiaobing , Kutateladze Andrei G. , Strahl Brian D. , Liu Wenshe R. , Kutateladze Tatiana G.
Published: October 2018

The YEATS domain has been identified as a reader of histone acylation and more recently emerged as a promising anti-cancer therapeutic target. Here, we detail the structural mechanisms for π-π-π stacking involving the YEATS domains of yeast Taf14 and human AF9 and acylated histone H3 peptides and explore DNA-binding activities of these domains. Taf14-YEATS selects for crotonyllysine, forming π stacking with both the crotonyl amide and the alkene moiety, whereas AF9-YEATS exhibits comparable affinities to saturated and unsaturated acyllysines, engaging them through π stacking with the acyl amide. Importantly, AF9-YEATS is capable of binding to DNA, whereas Taf14-YEATS is not. Using a structure-guided approach, we engineered a mutant of Taf14-YEATS that engages crotonyllysine through the aromatic-aliphatic-aromatic π stacking and shows high selectivity for the crotonyl H3K9 modification. Our findings shed light on the molecular principles underlying recognition of acyllysine marks and reveal a previously unidentified DNA-binding activity of AF9-YEATS.
Plasmonic Pt nanoparticles—TiO2 hierarchical nano-architecture as a visible light photocatalyst for water splitting
Authors: Qin Lipei , Wang Guojing , Tan Yiwei
Published: October 2018

Visible light-driven water splitting (VLWS) into hydrogen and oxygen is attractive and depends on efficient photocatalysts. Herein, we demonstrate the first exploration of the capability to control the morphology of nanostructured TiO2 in conjunction with the choice of a suitable plasmonic metal (PM) to fabricate novel photocatalysts that are capable of harvesting visible light for more efficient VL-fuel conversion. This methodology affords us to successful access to the novel plasmonic Pt/TiO2-HA (large Pt nanoparticles (NPs) supported on TiO2 hierarchical nano-architecture (TiO2-HA)) photocatalysts that exhibit plasmon absorption in the visible range and consequent outstanding activity and durability for VLWS. Particularly, the Pt/TiO2-HA shows an excellent photocatalytic activity for overall water splitting rather than only for hydrogen evolution (HE), which is superior to those of the conventional plasmonic Au/TiO2 photocatalysts. The synergistic effects of the high Schottky barrier at the Pt–TiO2-HA interface, which induces the stronger reduction ability of hot electrons, and intrinsic Pt catalytic activity are responsible for the exceptional photocatalytic performance of Pt/TiO2-HA and simplify the composition of plasmonic photocatalysts.
Copper Redox Cycling Inhibits Aβ Fibre Formation and Promotes Fibre Fragmentation, while Generating a Dityrosine Aβ Dimer
Authors: Gu Miao , Bode David C. , Viles John H.
Published: October 2018

Oxidative stress and the formation of plaques which contain amyloid-β (Aβ) peptides are two key hallmarks of Alzheimer’s disease (AD). Dityrosine is found in the plaques of AD patients and Aβ dimers have been linked to neurotoxicity. Here we investigate the formation of Aβ dityrosine dimers promoted by Cu2+/+ Fenton reactions. Using fluorescence measurements and UV absorbance, we show that dityrosine can be formed aerobically when Aβ is incubated with Cu2+ and hydrogen-peroxide, or in a Cu2+ and ascorbate redox mixture. The dityrosine cross-linking can occur for both monomeric and fibrillar forms of Aβ. We show that oxidative modification of Aβ impedes the ability for Aβ monomer to form fibres, as indicated by the amyloid specific dye Thioflavin T (ThT). Transmission electron microscopy (TEM) indicates the limited amyloid assemblies that form have a marked reduction in fibre length for Aβ(1–40). Importantly, the addition of Cu2+ and a reductant to preformed Aβ(1–40) fibers causes their widespread fragmentation, reducing median fibre lengths from 800 nm to 150 nm upon oxidation. The processes of covalent cross-linking of Aβ fibres, dimer formation, and fibre fragmentation within plaques are likely to have a significant impact on Aβ clearance and neurotoxicity.
Modelling of Cellular Survival Following Radiation-Induced DNA Double-Strand Breaks
Authors: Wang Wenjing , Li Chunyan , Qiu Rui , Chen Yizheng , Wu Zhen , Zhang Hui , Li Junli
Published: October 2018

A mechanistic model of cellular survival following radiation-induced DNA double-strand breaks (DSBs) was proposed in this study. DSBs were assumed as the initial lesions in the DNA of the cell nucleus induced by ionizing radiation. The non-homologous end-joining (NHEJ) pathway was considered as the domain pathway of DSB repair in mammalian cells. The model was proposed to predict the relationship between radiation-induced DSBs in nucleus and probability of cell survival, which was quantitatively described by two input parameters and six fitting parameters. One input parameter was the average number of primary particles which caused DSB, the other input parameter was the average number of DSBs yielded by each primary particle that caused DSB. The fitting parameters were used to describe the biological characteristics of the irradiated cells. By determining the fitting parameters of the model with experimental data, the model is able to estimate surviving fractions for the same type of cells exposed to particles with different physical parameters. The model further revealed the mechanism of cell death induced by the DSB effect. Relative biological effectiveness (RBE) of charged particles at different survival could be calculated with the model, which would provide reference for clinical treatment.
Direct visualization of DNA baton pass between replication factors bound to PCNA
Authors: Mayanagi Kouta , Ishino Sonoko , Shirai Tsuyoshi , Oyama Takuji , Kiyonari Shinichi , Kohda Daisuke , Morikawa Kosuke , Ishino Yoshizumi
Published: October 2018

In Eukarya and Archaea, the lagging strand synthesis is accomplished mainly by three key factors, DNA polymerase (Pol), flap endonuclease (FEN), and DNA ligase (Lig), in the DNA replication process. These three factors form important complexes with proliferating cell nuclear antigen (PCNA), thereby constructing a platform that enable each protein factor to act successively and smoothly on DNA. The structures of the Pol-PCNA-DNA and Lig-PCNA-DNA complexes alone have been visualized by single particle analysis. However, the FEN-PCNA-DNA complex structure remains unknown. In this report, we for the first time present this tertiary structure determined by single particle analysis. We also successfully visualized the structure of the FEN-Lig-PCNA-DNA complex, corresponding to a putative intermediate state between the removal of the DNA flap by FEN and the sealing of the nicked DNA by Lig. This structural study presents the direct visualization of the handing-over action, which proceeds between different replication factors on a single PCNA clamp bound to DNA. We detected a drastic conversion of the DNA from a bent form to a straight form, in addition to the dynamic motions of replication factors in the switching process.
Pannexin 1 regulates adipose stromal cell differentiation and fat accumulation
Authors: Lee Vanessa R. , Barr Kevin J. , Kelly John J. , Johnston Danielle , Brown Cody F. C. , Robb Kevin P. , Sayedyahossein Samar , Huang Kenneth , Gros Robert , Flynn Lauren E. , Penuela Silvia
Published: October 2018

Pannexin 1 (Panx1) is a channel-forming glycoprotein important in paracrine signaling and cellular development. In this study, we discovered that mice globally lacking Panx1 (KO) have significantly greater total fat mass and reduced lean mass compared to wild type (WT) mice under a normal diet. Despite having higher fat content, Panx1 KO mice on a high fat diet exhibited no differences in weight gain and blood markers of obesity as compared to WT controls, except for an increase in glucose and insulin levels. However, metabolic cage data revealed that these Panx1 KO mice display significantly increased activity levels, higher ambulatory activity, and reduced sleep duration relative to their WT littermates on a high-fat diet. To uncover the cellular mechanism responsible for the increased fat content in the KO, we isolated primary cultures of adipose-derived stromal cells (ASCs) from WT and KO fat pads. In WT ASCs we observed that Panx1 protein levels increase upon induction into an adipogenic lineage. ASCs isolated from Panx1 KO mice proliferate less but demonstrate enhanced adipogenic differentiation with increased intracellular lipid accumulation, glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity, and adipokine secretion, as compared to WT ASCs. This was consistent with the increased adipocyte size and decreased adipocyte numbers observed in subcutaneous fat of the Panx1 KO mice compared to WT. We concluded that Panx1 plays a key role in adipose stromal cells during the early stages of adipogenic proliferation and differentiation, regulating fat accumulation in vivo.
The effect of anxiety on emotional recognition: evidence from an ERP study
Authors: Yu Qianqian , Zhuang Qian , Wang Bo , Liu Xingze , Zhao Guang , Zhang Meng
Published: October 2018

Anxiety-related bias in the recognition memory based on trait anxiety has induced some studies. Their results, however, were conflicting. In fact, anxious differences not only differed from personality traits but also from different anxiety mood levels. We explored the emotional memory bias in both trait and state anxiety individuals, the high trait and high state anxiety group, the high trait and low state anxiety group, the low trait and high state anxiety group, and the low trait and low state anxiety group, on classic recognition paradigm using event-related potentials (ERPs). The behavioral results showed high state anxiety levels increased the d’ of negative words, regardless of the trait anxiety of participant is high or low, and a lower d’ of recognition memory for negative words than for neutral and positive words in all participants. Moreover, Electrophysiological results supported the findings of behavior, showing an earlier N400 (250–500 ms) latency elicited for new-negative words in high state level than in low state levels in right parietal region. These results suggested that the memory bias to negative events resides in state anxiety, but not in trait anxiety.
The Roles of Climate Change and Climate Variability in the 2017 Atlantic Hurricane Season
Authors: Lim Young-Kwon , Schubert Siegfried D. , Kovach Robin , Molod Andrea M. , Pawson Steven
Published: October 2018

The 2017 Atlantic hurricane season was extremely active with six major hurricanes, the third most on record. The sea-surface temperatures (SSTs) over the eastern Main Development Region (EMDR), where many tropical cyclones (TCs) developed during active months of August/September, were ~0.96 °C above the 1901–2017 average (warmest on record): about ~0.42 °C from a long-term upward trend and the rest (~80%) attributed to the Atlantic Meridional Mode (AMM). The contribution to the SST from the North Atlantic Oscillation (NAO) over the EMDR was a weak warming, while that from El Niño–Southern Oscillation (ENSO) was negligible. Nevertheless, ENSO, the NAO, and the AMM all contributed to favorable wind shear conditions, while the AMM also produced enhanced atmospheric instability. Compared with the strong hurricane years of 2005/2010, the ocean heat content (OHC) during 2017 was larger across the tropics, with higher SST anomalies over the EMDR and Caribbean Sea. On the other hand, the dynamical/thermodynamical atmospheric conditions, while favorable for enhanced TC activity, were less prominent than in 2005/2010 across the tropics. The results suggest that unusually warm SST in the EMDR together with the long fetch of the resulting storms in the presence of record-breaking OHC may be key factors in driving the strong TC activity in 2017.
Progressive impairment of directional and spatially precise trajectories by TgF344-Alzheimer’s disease rats in the Morris Water Task
Authors: Berkowitz Laura E. , Harvey Ryan E. , Drake Emma , Thompson Shannon M. , Clark Benjamin J.
Published: October 2018

Spatial navigation is impaired in early stages of Alzheimer’s disease, and may be a defining behavioral marker of preclinical AD. A new rat model (TgF344-AD) of AD overcomes many limitations of other rodent models, though spatial navigation has not been comprehensively assessed. Using the hidden and cued platform variants of the Morris water task, a longitudinal assessment of spatial navigation was conducted on TgF344-AD (n = 16) and Fischer 344 (n = 12) male and female rats at three age ranges: 4 to 5 months, 7 to 8, and 10 to 11 months of age. TgF344-AD rats exhibited largely intact navigation at 4–5 months, with deficits in the hidden platform task emerging at 7–8 months and becoming significantly pronounced at 10–11 months of age. In general, TgF344-AD rats displayed less accurate swim trajectories to the platform and searched a wider area around the platform region compared to wildtype rats. Impaired navigation occurred in the absence of deficits in acquiring the procedural task demands or navigation to the cued platform location. Together, the results indicate that TgF344-AD rats exhibit comparable navigational deficits to those found in individuals with preclinical-AD.
Eliminating deformation incompatibility in composites by gradient nanolayer architectures
Authors: Li Jianjun , Lu Wenjun , Gibson James , Zhang Siyuan , Chen Tianyu , Korte-Kerzel Sandra , Raabe Dierk
Published: October 2018

Composite materials usually possess a severe deformation incompatibility between the soft and hard phases. Here, we show how this incompatibility problem is overcome by a novel composite design. A gradient nanolayer-structured Cu-Zr material has been synthesized by magnetron sputtering and tested by micropillar compression. The interface spacing between the alternating Cu and Zr nanolayers increases gradually by one order of magnitude from 10 nm at the surface to 100 nm in the centre. The interface spacing gradient creates a mechanical gradient in the depth direction, which generates a deformation gradient during loading that accumulates a substantial amount of geometrically necessary dislocations. These dislocations render the component layers of originally high mechanical contrast compatible. As a result, we revealed a synergetic mechanical response in the material, which is characterized by fully compatible deformation between the constituent Cu and Zr nanolayers with different thicknesses, resulting in a maximum uniform layer strain of up to 60% in the composite. The deformed pillars have a smooth surface, validating the absence of deformation incompatibility between the layers. The joint deformation response is discussed in terms of a micromechanical finite element simulation.
Surgical and Functional Outcome after Endoprosthetic Reconstruction in Patients with Osteosarcoma of the Humerus
Authors: Böhler Christoph , Brönimann Stephan , Kaider Alexandra , Puchner Stephan E. , Sigmund Irene K. , Windhager Reinhard , Funovics Philipp T.
Published: October 2018

Endoprosthetic reconstruction (EPR) is the most widely used reconstruction technique after humeral osteosarcoma (OSA). Complications are common and function is often compromised due to the premise of wide resection. In the current study we evaluated (1) the risk of complications after resection and EPR; (2) the functional outcome and how it is influenced by the preservation/resection of deltoid muscle (DM), rotator cuff (RC), axillary nerve or the type of resection (intra-/extraarticular) and (3) if the preservation/resection of DM, RC, axillary nerve or the type of resection has a negative influence on the oncological outcome. We retrospectively evaluated data of 49 patients with humeral OSA. All patients underwent resection and EPR. Complication-free survival according to the ISOLS classification was estimated by a competing risk model. Functional outcome was evaluated by range of motion (ROM) in abduction and the MSTS score. Eleven patients (22%) had at least one complication. The estimated cumulative incidence for the first complication was 18% at one year, 23% at five years, and 28% at ten years, respectively. Soft tissue failure was the most common complication. ROM and MSTS scores were significantly higher in patients where DM and RC (p = 0.043/p = 0.046) and axillary nerve (p = 0.014/p = 0.021) could be preserved. Preservation of these structures had no negative influence on the surgical margins. In conclusion, EPR is a good treatment method with an acceptable complication rate. Preservation of the abductor mechanism, when possible in the setting of obtaining negative margins, provides superior functional outcome.
Species generalization and differences in Hedgehog pathway regulation of fungiform and circumvallate papilla taste function and somatosensation demonstrated with sonidegib
Authors: Kumari A. , Yokota Y. , Li L. , Bradley R. M. , Mistretta C. M.
Published: October 2018

Species generalization in the profound, modality-specific effects of Hedgehog pathway inhibition (HPI) in taste organ homeostasis and sensation is shown. With the HPI, cancer drug sonidegib, we demonstrate that the rat taste system, in addition to mouse, is regulated by Hedgehog signaling. After sonidegib treatment for 16–36 days in rat, there is loss of taste buds (TB) in soft palate, in fungiform (FP) and circumvallate papillae (CV), and elimination of taste responses from chorda tympani and glossopharyngeal nerves. The retained innervation in FP and CV during HPI cannot sustain TB. Responses to tactile stimuli are not altered, and temperature responses are reduced only after 28 days treatment, demonstrating modality-specific effects. Rat FP and neural effects are similar to those in mouse whereas TB and neural response effects from the rat CV are much more severe. When recovery is introduced in mouse after prolonged, 48 days HPI, the TB in CV are restored whereas those in FP are not. Overall, Hedgehog signaling regulation is shown to generalize to the rat taste system, and the modality-specific controls in taste organ sensation are affirmed. The reported, debilitating taste disturbances in patients who use HPI drugs can be better understood based on these data.
A rapid quality control test to foster the development of genetic control in mosquitoes
Authors: Culbert Nicole J. , Balestrino Fabrizio , Dor Ariane , Herranz Gustavo S. , Yamada Hanano , Wallner Thomas , Bouyer Jérémy
Published: October 2018

Vector-borne diseases are responsible for more than one million deaths per year. Alternative methods of mosquito control to insecticides such as genetic control techniques are thus urgently needed. In genetic techniques involving the release of sterile insects, it is critical to release insects of high quality. Sterile males must be able to disperse, survive and compete with wild males in order to inseminate wild females. There is currently no standardized, fast-processing method to assess mosquito male quality. Since male competitiveness is linked to their ability to fly, we developed a flight test device that aimed to measure the quality of sterile male mosquitoes via their capacity to escape a series of flight tubes within two hours and compared it to two other reference methods (survival rate and mating propensity). This comparison was achieved in three different stress treatment settings usually encountered when applying the sterile insect technique, i.e. irradiation, chilling and compaction. In all treatments, survival and insemination rates could be predicted by the results of a flight test, with over 80% of the inertia predicted. This novel tool could become a standardised quality control method to evaluate cumulative stress throughout the processes related to genetic control of mosquitoes.
Endogenous Chemiluminescence from Germinating Arabidopsis Thaliana Seeds
Authors: Saeidfirozeh Homa , Shafiekhani Azizollah , Cifra Michal , Masoudi Amir Ali
Published: October 2018

It is well known that all biological systems which undergo oxidative metabolism or oxidative stress generate a small amount of light. Since the origin of excited states producing this light is generally accepted to come from chemical reactions, the term endogenous biological chemiluminescence is appropriate. Apart from biomedicine, this phenomenon has potential applications also in plant biology and agriculture like monitoring the germination rate of seeds. While chemiluminescence capability to monitor germination has been measured on multiple agriculturally relevant plants, the standard model plant Arabidopsis thaliana has not been analyzed for this process so far. To fill in this gap, we demonstrate here on A. thaliana that the intensity of endogenous chemiluminescence increases during the germination stage. We showed that the chemiluminescence intensity increases since the second day of germination, but reaches a plateau on the third day, in contrast to other plants germinating from larger seeds studied so far. We also showed that intensity increases after topical application of hydrogen peroxide in a dose-dependent manner. Further, we demonstrated that the entropy of the chemiluminescence time series is similar to random Poisson signals. Our results support a notion that metabolism and oxidative reactions are underlying processes which generate endogenous biological chemiluminescence. Our findings contribute to novel methods for non-invasive and label-free sensing of oxidative processes in plant biology and agriculture.
The small molecule alpha-synuclein misfolding inhibitor, NPT200-11, produces multiple benefits in an animal model of Parkinson’s disease
Authors: Price Diana L. , Koike Maya A. , Khan Asma , Wrasidlo Wolfgang , Rockenstein Edward , Masliah Eliezer , Bonhaus Douglas
Published: October 2018

Accumulation of alpha-synuclein (ASYN) in neurons and other CNS cell types may contribute to the underlying pathology of synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and Multiple Systems Atrophy (MSA). In support of this hypothesis for PD, ASYN immunopositive aggregates are a prominent pathological feature of PD, and mutations and gene multiplications of human wild type (WT) ASYN cause rare familial autosomal-dominant forms of PD. Targeted therapeutics that reduce the accumulation of ASYN could prevent or slow the neurodegenerative processes in PD and other synucleinopathies. NPT200-11 is a novel small molecule inhibitor of ASYN misfolding and aggregation. The effects of NPT200-11 on ASYN neuropathology were evaluated in animal models over expressing human alpha synuclein. Longitudinal studies using retinal imaging in mice expressing a hASYN::GFP fusion protein revealed that 2 months of once daily administration of NPT200-11 (5 mg/kg IP) resulted in a time-dependent and progressive reduction in retinal ASYN pathology. The effects of NPT200-11 on ASYN pathology in cerebral cortex and on other disease-relevant endpoints was evaluated in the Line 61 transgenic mouse model overexpressing human wild type ASYN. Results from these studies demonstrated that NPT200-11 reduced alpha-synuclein pathology in cortex, reduced associated neuroinflammation (astrogliosis), normalized striatal levels of the dopamine transporter (DAT) and improved motor function. To gain insight into the relationship between dose, exposure, and therapeutic benefit pharmacokinetic studies were also conducted in mice. These studies demonstrated that NPT200-11 is orally bioavailable and brain penetrating and established target plasma and brain exposures for future studies of potential therapeutic benefit.
Genome-Scale Analysis of Perturbations in Translation Elongation Based on a Computational Model
Authors: Levin Doron , Tuller Tamir
Published: October 2018

Perturbations play an important role both in engineered systems and cellular processes. Thus, understanding their effect on protein synthesis should contribute to all biomedical disciplines. Here we describe the first genome-scale analysis of perturbations in translation-related factors in S. cerevisiae. To this end, we used simulations based on a computational model that takes into consideration the fundamental stochastic and bio-physical nature of translation. We found that the initiation rate has a key role in determining the sensitivity to perturbations. For low initiation rates, the first codons of the coding region dominate the sensitivity, which is highly correlated with the ratio between initiation rate and mean elongation rate (r = −0.95), with the open reading frame (ORF) length (r = 0.6) and with protein abundance (r = 0.45). For high initiation rates (that may rise, for example, due to cellular growth), the sensitivity of a gene is dominated by all internal codons and is correlated with the decoding rate. We found that various central intracellular functions are associated with the sensitivity: for example, both genes that are sensitive and genes that are robust to perturbations are over-represented in the group of genes related to translation regulation; this may suggest that robustness to perturbations is a trait that undergoes evolutionary selection in relation to the function of the encoded protein. We believe that the reported results, due to their quantitative value and genome-wide perspective, should contribute to disciplines such as synthetic biology, functional genomics, comparative genomics and molecular evolution.
Protective effect of pre- and post-vitamin C treatments on UVB-irradiation-induced skin damage
Authors: Kawashima Saki , Funakoshi Tomoko , Sato Yasunori , Saito Norikatsu , Ohsawa Hajime , Kurita Katsumi , Nagata Kisaburo , Yoshida Masayuki , Ishigami Akihito
Published: October 2018

Several studies have reported the effects of vitamin C (L-ascorbic acid, AA) on ultraviolet B (UVB)-induced cell damage using cultured keratinocytes. However, the epidermis consists of multiple cell layers, and the effect of AA on UVB-induced damage to the human epidermis remains unclear. Therefore, we investigated the effect of AA on UVB-induced skin damage using reconstituted human epidermis. The reconstituted human epidermal surface was treated with 100 and 500 mM AA and cultured for 3 h before (pre-AA treatment) or after (post-AA treatment) 120 mJ/cm2 UVB irradiation. Pre- and post-AA treatments of the epidermal surface suppressed UVB-induced cell death, apoptosis, DNA damage, reactive oxygen species (ROS) production, and the inflammatory response by downregulating tumour necrosis factor-α (TNF-α) expression and release. Moreover, the pre-AA treatment was more effective at preventing UVB-induced skin damage than the post-AA treatment. In summary, pre- and post-AA treatments of the epidermis prevent UVB-induced damage.
Intermediate-temperature electrolysis of energy grass Miscanthus sinensis for sustainable hydrogen production
Authors: Ito Masaya , Hori Tetsuya , Teranishi Shinya , Nagao Masahiro , Hibino Takashi
Published: October 2018

Biohydrogen produced from the electrolysis of biomass is promising because the onset voltages are less than 1.0 V and comparable to those of water and alcohol-water electrolysis. The present study focuses on Miscanthus sinensis as a model grass because of its abundance and ease of cultivation in Japan. The electrochemical performance and hydrogen formation properties of electrolysis cells using grass as a biohydrogen source were evaluated at intermediate temperature to achieve electrolysis. The components, such as holocellulose, cellulose, lignin, and extractives, were separated from Miscanthus sinensis to understand the reactions of Miscanthus sinensis in the electrolysis cell. The relatively high resistivity and low current-voltage performance of an electrolysis cell using lignin were responsible for degradation of the electrolysis properties compared to those with pure cellulose or holocellulose as biohydrogen resources. Biohydrogen was formed according to Faraday’s law and evolved continuously at 0.1 A cm−2 for 3,000 seconds.
MMP-1 overexpression selectively alters inhibition in D1 spiny projection neurons in the mouse nucleus accumbens core
Authors: Al-muhtasib Nour , Forcelli Patrick A. , Conant Katherine E. , Vicini Stefano
Published: October 2018

Protease activated receptor-1 (PAR-1) and its ligand, matrix metalloproteinase-1 (MMP-1), are altered in several neurodegenerative diseases. PAR-1/MMP-1 signaling impacts neuronal activity in various brain regions, but their role in regulating synaptic physiology in the ventral striatum, which is implicated in motor function, is unknown. The ventral striatum contains two populations of GABAergic spiny projection neurons, D1 and D2 SPNs, which differ with respect to both synaptic inputs and projection targets. To evaluate the role of MMP-1/PAR-1 signaling in the regulation of ventral striatal synaptic function, we performed whole-cell recordings (WCR) from D1 and D2 SPNs in control mice, mice that overexpress MMP-1 (MMP-1OE), and MMP-1OE mice lacking PAR-1 (MMP-1OE/PAR-1KO). WCRs from MMP1-OE mice revealed an increase in spontaneous inhibitory post-synaptic current (sIPSC), miniature IPSC, and miniature excitatory PSC frequency in D1 SPNs but not D2 SPNs. This alteration may be partially PAR-1 dependent, as it was not present in MMP-1OE/PAR-1KO mice. Morphological reconstruction of D1 SPNs revealed increased dendritic complexity in the MMP-1OE, but not MMP-1OE/PAR-1KO mice. Moreover, MMP-1OE mice exhibited blunted locomotor responses to amphetamine, a phenotype also observed in MMP-1OE/PAR-1KO mice. Our data suggest PAR-1 dependent and independent MMP-1 signaling may lead to alterations in striatal neuronal function.
Target site specificity and in vivo complexity of the mammalian arginylome
Authors: Wang Junling , Pejaver Vikas Rao , Dann Geoffrey P. , Wolf Max Y. , Kellis Manolis , Huang Yun , Garcia Benjamin A. , Radivojac Predrag , Kashina Anna
Published: October 2018

Protein arginylation mediated by arginyltransferase ATE1 is a key regulatory process essential for mammalian embryogenesis, cell migration, and protein regulation. Despite decades of studies, very little is known about the specificity of ATE1-mediated target site recognition. Here, we used in vitro assays and computational analysis to dissect target site specificity of mouse arginyltransferases and gain insights into the complexity of the mammalian arginylome. We found that the four ATE1 isoforms have different, only partially overlapping target site specificity that includes more variability in the target residues than previously believed. Based on all the available data, we generated an algorithm for identifying potential arginylation consensus motif and used this algorithm for global prediction of proteins arginylated in vivo on the N-terminal D and E. Our analysis reveals multiple proteins with potential ATE1 target sites and expand our understanding of the biological complexity of the intracellular arginylome.
An Innovated Application of Reutilize Copper Smelter Slag for Cement-based Electromagnetic Interference Composites
Authors: Fan Yong , Zhang Bo , Song Jianxun , Volski Vladimir , Vandenbosch Guy A. E. , Guo Muxing
Published: October 2018

In the present study, it has been attempted an innovated application, i.e., electromagnetic interference shielding material, to reutilize copper smelter slag, aiming at an alternative high value added product. Notably, a proof-of-concept experiment with an addition of a 45 wt.% of copper slag alone to the cement matrix boost the shielding effectiveness (SE) to approximately 7–8 dB in the 500 MHz–1.5 GHz frequency range, highlights the incident electromagnetic wave has been weakened by approximately 60 pct. This phenomenon is attributed to the iron silicate, fayalite, and magnetite embedded in the sample mixture serve as magnetic and dielectric loss absorbent, deriving from the copper slag. Copper slag with low value application, shows its competitive economic and social advantages as candidate infill for electromagnetic interference shielding materials.
Enoxacin and bis-enoxacin stimulate 4T1 murine breast cancer cells to release extracellular vesicles that inhibit osteoclastogenesis
Authors: Vracar Taylor C. , Zuo Jian , Park JeongSu , Azer Demyana , Mikhael Christy , Holliday Sophia A. , Holsey Dontreyl , Han Guanghong , VonMoss Lindsay , Neubert John K. , Rody Wellington J. , Chan Edward K. L. , Holliday L. Shannon
Published: October 2018

Enoxacin and its bone-seeking bisphosphonate derivative, bis-enoxacin, have recently captured attention as potential therapeutic agents for the treatment of cancer and bone disease. No differences in growth or survival of 4T1 murine breast cancer cells were detected at a concentration of 50 µM of enoxacin or bis-enoxacin. Growth was perturbed at higher concentrations. Both 50 µM enoxacin and bis-enoxacin stimulated increases in the number of GW/Processing bodies, but there were minimal changes in microRNA levels. Extracellular vesicles (EVs) released from 4T1 cells treated with 50 µM enoxacin or 50 µM bis-enoxacin stimulated proliferation of RAW 264.7 cells, and both significantly inhibited osteoclastogenesis in calcitriol-stimulated mouse marrow. EVs from 4T1 cells treated with enoxacin and bis-enoxacin displayed small reductions in the amount of microRNA (miR)-146a-5p and let-7b-5p. In marked contrast, miR-214-3p, which has been shown to regulate bone remodeling, was increased 22-fold and 30-fold respectively. We conclude that enoxacin and bis-enoxacin trigger the release of EVs from 4T1 cancer cells that inhibit osteoclastogenesis.
Author Correction: Electronic origin of hydrogen storage in MOF-covered palladium nanocubes investigated by synchrotron X-rays
Authors: Chen Yanna , Sakata Osami , Nanba Yusuke , Kumara Loku Singgappulige Rosantha , Yang Anli , Song Chulho , Koyama Michihisa , Li Guangqin , Kobayashi Hirokazu , Kitagawa Hiroshi
Published: October 2018

The previously published version of this Article contained an error in Fig. 1. In panel c, the thickness of the HKUST-1 layer (3 nm) was incorrectly labelled. This error has been corrected in both the PDF and HTML versions of the Article.
Nanomaterials for luminescent detection of water and humidity
Authors: Guo Yongming , Zhao Wei
Published: October 2018

Significant advances of typical nanomaterials in the luminescent detection of water and humidity are presented.
Preparation and evaluation of molecularly imprinted membrane of teicoplanin
Authors: Yao Ru , Yu Zhen , Wu Manman , Yu Haining
Published: October 2018

Synthesis of teicoplanin molecularly imprinted membranes and a novel enrichment method for rapid determination of teicoplanin.
Controllable preparation of a reverse-phase/hydrophilic interaction mixed-mode chromatographic stationary phase with adjustable selectivity
Authors: Bo Chunmiao , Dai Xiaojun , Chen Weimin , Cao Rui
Published: October 2018

A mixed-mode stationary phase prepared by grafting block copolymers via ATRP could adjust separation selectivity by simply tuning the ratios of copolymer chains.
Enzyme-free amplified DNA assay: five orders of linearity provided by metal stable isotope detection
Authors: Liu Yu , Ding Yonggang , Gao Ying , Liu Rui , Hu Xiaorong , Lv Yi
Published: October 2018

The metal stable isotope detection strategy demonstrates a wide linear range and a low detection limit, showing promising potential in clinical diagnosis.
Molecular design of high-temperature organic dielectric switches
Authors: Zhou Lin , Shi Ping-Ping , Zheng Xuan , Geng Fu-Juan , Ye Qiong , Fu Da-Wei
Published: October 2018

By reducing the molecular symmetry of tetramethylphosphonium cations, four high-temperature organic dielectric switches are successfully obtained.