bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of miR-210 and its significance in ischemic tissue damage
Authors: Zaccagnini G. , Maimone B. , Fuschi P. , Maselli D. , Spinetti G. , Gaetano C. , Martelli F.
Published: August 2017

Hypoxia-induced miR-210 displays a pro-survival, cytoprotective and pro-angiogenic role in severalin vitrosystems.In vivo, we previously found that miR-210 inhibition increases ischemic damage. Here we describe the generation of a versatile transgenic mouse model allowing the evaluation of miR-210 therapeutic potential in ischemic cardiovascular diseases. We generated a Tet-On miR-210 transgenic mouse strain (TG-210) by targeted transgenesis in the ROSA26 locus. To functionally validate miR-210 transgenic mice, hindlimb ischemia was induced by femoral artery dissection. Blood perfusion was evaluated by power Doppler while tissue damage and inflammation were assessed by histological evaluation. We found that miR-210 levels were rapidly increased in TG-210 mice upon doxycycline administration. miR-210 overexpression was maintained over time and remained within physiological levels in multiple tissues. When hindlimb ischemia was induced, miR-210 overexpression protected from both muscular and vascular ischemic damage, decreased inflammatory cells density and allowed to maintain a better calf perfusion. In conclusion, we generated and functionally validated a miR-210 transgenic mouse model. Albeit validated in the context of a specific cardiovascular ischemic disease, miR-210 transgenic mice may also represent a useful model to assess the function of miR-210 in other physio-pathological conditions.
GsCHX19.3, a member of cation/H+ exchanger superfamily from wild soybean contributes to high salinity and carbonate alkaline tolerance
Authors: Jia Bowei , Sun Mingzhe , DuanMu Huizi , Ding Xiaodong , Liu Beidong , Zhu Yanming , Sun Xiaoli
Published: August 2017

Cation/H+ exchangers (CHX) are characterized to be involved in plant growth, development and stress responses. Although soybean genome sequencing has been completed, the CHX family hasn’t yet been systematically analyzed, especially in wild soybean. Here, through Hidden Markov Model search against Glycine soja proteome, 34 GsCHXs were identified and phylogenetically clustered into five groups. Members within each group showed high conservation in motif architecture. Interestingly, according to our previous RNA-seq data, only Group IVa members exhibited highly induced expression under carbonate alkaline stress. Among them, GsCHX19.3 displayed the greatest up-regulation in response to carbonate alkaline stress, which was further confirmed by quantitative real-time PCR analysis. We also observed the ubiquitous expression of GsCHX19.3 in different tissues and its localization on plasma membrane. Moreover, we found that GsCHX19.3 expression in AXT4K, a yeast mutant lacking four ion transporters conferred resistance to low K+ at alkali pH, as well as carbonate stress. Consistently, in Arabidopsis, GsCHX19.3 overexpression increased plant tolerance both to high salt and carbonate alkaline stresses. Furthermore, we also confirmed that GsCHX19.3 transgenic lines showed lower Na+ concentration but higher K+/Na+ values under salt-alkaline stress. Taken together, our findings indicated that GsCHX19.3 contributed to high salinity and carbonate alkaline tolerance.
Bacterial Community Structure in the Asian Rice Gall Midge Reveals a Varied Microbiome Rich in Proteobacteria
Authors: Ojha Abhishek , Sinha Deepak Kumar , Padmakumari A. P. , Bentur J. S. , Nair Suresh
Published: August 2017

The Asian rice gall midge (ARGM) has emerged as a model gall forming pest of rice. The ARGM infestation of rice results in failure of panicle formation and economic loss. Understanding the molecular basis of ARGM-rice interactions is very crucial in order to control this devastating pest of rice. The current investigation was devised to identify bacterial communities present in the ARGM and in addition the bacterial diversity in the maggots during their interaction with susceptible or resistant rice varieties. Sequencing of 16S rRNA bacterial gene (V3-V4 region) revealed differences in the microflora of the ARGM maggots feeding on susceptible or resistant rice hosts. Results revealed that Wolbachia was the predominant bacterium in pupae and adults while Pseudomonas was predominant in maggots. Further, we observed that members of proteobacteria were predominant across all the samples. There was high species diversity in maggots isolated from susceptible rice and a high representation of unclassified bacteria in maggots isolated from resistant rice. This is the first study that reports variation of microbiome of the ARGM, based on host phenotype from which it was isolated, and results suggest that these variations could have an important role in host’s susceptibility.
Universal linear-temperature resistivity: possible quantum diffusion transport in strongly correlated superconductors
Authors: Hu Tao , Liu Yinshang , Xiao Hong , Mu Gang , Yang Yi-feng
Published: August 2017

The strongly correlated electron fluids in high temperature cuprate superconductors demonstrate an anomalous linear temperature (T) dependent resistivity behavior, which persists to a wide temperature range without exhibiting saturation. As cooling down, those electron fluids lose the resistivity and condense into the superfluid. However, the origin of the linear-T resistivity behavior and its relationship to the strongly correlated superconductivity remain a mystery. Here we report a universal relation $$d{\boldsymbol{\rho }}/{\boldsymbol{dT}}=({{\boldsymbol{\mu }}}_{{\bf{0}}}{{\boldsymbol{k}}}_{{\boldsymbol{B}}}/{\boldsymbol{\hslash }})\,{{\boldsymbol{\lambda }}}_{{\boldsymbol{L}}}^{{\bf{2}}}$$

d
ρ

/

dT

=
(

μ

0

k

B

/
ℏ

)

λ

L

2

, which bridges the slope of the linear-T-dependent resistivity (dρ/dT) to the London penetration depth λ
L
at zero temperature among cuprate superconductor Bi2Sr2CaCu2O8+δ
and heavy fermion superconductors CeCoIn5, where μ0 is vacuum permeability, k
B
is the Boltzmann constant and ħ is the reduced Planck constant. We extend this scaling relation to different systems and found that it holds for other cuprate, pnictide and heavy fermion superconductors as well, regardless of the significant differences in the strength of electronic correlations, transport directions, and doping levels. Our analysis suggests that the scaling relation in strongly correlated superconductors could be described as a hydrodynamic diffusive transport, with the diffusion coefficient (D) approaching the quantum limit D ~ ħ/m*, where m* is the quasi-particle effective mass.
Exciton-polariton Josephson junctions at finite temperatures
Authors: Lebedev M. E. , Dolinina D. A. , Hong Kuo-Bin , Lu Tien-Chang , Kavokin A. V. , Alodjants A. P.
Published: August 2017

We consider finite temperature effects in a non-standard Bose-Hubbard model for an exciton- polariton Josephson junction (JJ) that is characterised by complicated potential energy landscapes (PEL) consisting of sets of barriers and wells. We show that the transition between thermal activation (classical) and tunneling (quantum) regimes exhibits universal features of the first and second order phase transition (PT) depending on the PEL for two polariton condensates that might be described as transition from the thermal to the quantum annealing regime. In the presence of dissipation the relative phase of two condensates exhibits non-equilibrium PT from the quantum regime characterized by efficient tunneling of polaritons to the regime of permanent Josephson or Rabi oscillations, where the tunneling is suppressed, respectively. This analysis paves the way for the application of coupled polariton condensates for the realisation of a quantum annealing algorithm in presently experimentally accessible semiconductor microcavities possessing high (105 and more) Q-factors.
Characterization and RNAi-mediated knockdown of Chitin Synthase A in the potato tuber moth, Phthorimaea operculella
Authors: Mohammed Ahmed M. A. , Diab Mervat R. , Abdelsattar Mohamed , khalil Sayed M. S.
Published: August 2017

Chitin is a major component of insect exoskeleton, tracheal system and gut where it is synthesized by chitin synthase (CHS) enzymes. In this paper, we report the isolation and RNAi of chitin synthase A (PhoCHSA) from the potato tuber moth Phthorimaea operculella. The full-length cDNA of PhoCHSA is 5,627 bp with 4,689 bp open reading frame coding for 1,563 amino acids. Structural analysis of conceptual amino acid translation showed three distinct regions found in all known insect CHS proteins; N-terminus region having 9 transmembrane helices, middle catalytic region containing several conserved domains identified in insect CHS enzymes, and C-terminus region containing seven transmembrane spans. Phylogenetic analysis showed that PhoCHSA protein clustered with CHSA enzymes identified from insects from different insect orders. RNAi targeting three different regions of the gene showed different efficacy against potato tuber moth larvae and dsRNA targeting the 5′ region has the highest efficacy. Results were verified by qRT-PCR which showed that dsRNA targeting the 5′ region caused the highest reduction in PhoCHSA mRNA level. Our results show the importance of selecting the RNAi target region and that chitin synthase A can be a suitable RNAi target for the potato tuber moth control.
SOCS1 regulates hepatic regenerative response and provides prognostic makers for acute obstructive cholangitis
Authors: Yu Jianhua , Zhang Weiguang , Qian Hongwei , Tang Haijun , Lin Weiguo , Lu Baochun
Published: August 2017

Acute obstructive cholangitis (AOC) is a common and severe infectious diseases that occurs in an obstructed biliary system. The suppressors of cytokine signaling (SOCS) family include well-known negative regulators of cytokine receptor signaling. However, few studies have been conducted to determine their function in AOC. In this study, we showed that SOCS1 expression aberrantly changed and was associated with AOC prognosis in rat models. Decreased SOCS1 expression enhances regenerative response after biliary drainage (BD) resulting from AOC by upregulating hepatocyte growth factor (HGF) signaling. To detect SOCS1 expression in the liver less invasively and to predict the prognosis for AOC after BD, miR-221 and miR-222 were investigated. Ectopic SOCS1 expression indirectly decreases miR-221/222 expression through Met in vitro. An inverse correlation between SOCS1 expression and miR-221/222 expression in liver tissue or in serum was verified in rats. Serum from AOC patients showed that lower expression of circulating miR-221/222 after endoscopic nasobiliary drainage was associated with delayed restoration of liver function. Our results showed that SOCS1 regulates hepatic regenerative response, and indirectly detecting downstream molecules, such as miR-221/222, may provide prognostic makers for AOC.
Bone marrow-derived cells and their conditioned medium induce microvascular repair in uremic rats by stimulation of endogenous repair mechanisms
Authors: Golle Lina , Gerth Hans U. , Beul Katrin , Heitplatz Barbara , Barth Peter , Fobker Manfred , Pavenstädt Hermann , Di Marco Giovana S. , Brand Marcus
Published: August 2017

The reduced number of circulating stem/progenitor cells that is found in chronic kidney disease (CKD) patients may contribute to impaired angiogenic repair and decreased capillary density in the heart. Cell therapy with bone marrow-derived cells (BMDCs) has been shown to induce positive effects on the microvasculature and cardiac function, most likely due to secretion of growth factors and cytokines, all of which are present in the conditioned medium (CM); however, this is controversial. Here we showed that treatment with BMDC or CM restored vascular density and decreased the extent of fibrosis in a rat model of CKD, the 5/6 nephrectomy. Engraftment and differentiation of exogenous BMDCs could not be detected. Yet CM led to the mobilization and infiltration of endogenous circulating cells into the heart. Cell recruitment was facilitated by the local expression of pro-inflammatory factors such as the macrophage chemoattractant protein-1, interleukin-6, and endothelial adhesion molecules. Consistently, in vitro assays showed that CM increased endothelial adhesiveness to circulating cells by upregulating the expression of adhesion molecules, and stimulated angiogenesis/endothelial tube formation. Overall, our results suggest that both treatments exert vasculoprotective effects on the heart of uremic rats by stimulating endogenous repair mechanisms.
Accuracy of deep learning, a machine-learning technology, using ultra–wide-field fundus ophthalmoscopy for detecting rhegmatogenous retinal detachment
Authors: Ohsugi Hideharu , Tabuchi Hitoshi , Enno Hiroki , Ishitobi Naofumi
Published: August 2017

Rhegmatogenous retinal detachment (RRD) is a serious condition that can lead to blindness; however, it is highly treatable with timely and appropriate treatment. Thus, early diagnosis and treatment of RRD is crucial. In this study, we applied deep learning, a machine-learning technology, to detect RRD using ultra–wide-field fundus images and investigated its performance. In total, 411 images (329 for training and 82 for grading) from 407 RRD patients and 420 images (336 for training and 84 for grading) from 238 non-RRD patients were used in this study. The deep learning model demonstrated a high sensitivity of 97.6% [95% confidence interval (CI), 94.2–100%] and a high specificity of 96.5% (95% CI, 90.2–100%), and the area under the curve was 0.988 (95% CI, 0.981–0.995). This model can improve medical care in remote areas where eye clinics are not available by using ultra–wide-field fundus ophthalmoscopy for the accurate diagnosis of RRD. Early diagnosis of RRD can prevent blindness.
A missense MT-ND5 mutation in differentiated Parkinson Disease cytoplasmic hybrid induces ROS-dependent DNA Damage Response amplified by DROSHA
Authors: Pignataro Daniela , Francia Sofia , Zanetta Francesca , Brenna Giulia , Brandini Stefania , Olivieri Anna , Torroni Antonio , Biamonti Giuseppe , Montecucco Alessandra
Published: August 2017

Genome integrity is continuously threatened by endogenous sources of DNA damage including reactive oxygen species (ROS) produced by cell metabolism. Factors of the RNA interference (RNAi) machinery have been recently involved in the cellular response to DNA damage (DDR) in proliferating cells. To investigate the impact of component of RNAi machinery on DDR activation in terminally differentiated cells, we exploited cytoplasmic hybrid (cybrid) cell lines in which mitochondria of sporadic Parkinson’s disease patients repopulate neuroblastoma SH-SY5Y-Rho(0) cells. Upon differentiation into dopaminergic neuron-like cells, PD63 cybrid showed increased intracellular level of ROS and chronic DDR activation, compared to other cybrids with the same nuclear background. Importantly, DDR activation in these cells can be prevented by ROS scavenging treatment suggesting that ROS production is indeed causative of nuclear DNA damage. Sequence analysis of the mitogenomes identified a rare and heteroplasmic missense mutation affecting a highly conserved residue of the ND5-subunit of respiratory complex I, which accounts for ROS increase. We demonstrated that the assembly of nuclear DDR foci elicited by oxidative stress in these cells relies on DROSHA, providing the first evidence that components of RNAi machinery play a crucial role also in the mounting of ROS-induced DDR in non-replicating neuronal cells.
Work Function Modulation of Molybdenum Disulfide Nanosheets by Introducing Systematic Lattice Strain
Authors: Shakya Jyoti , Kumar Sanjeev , Kanjilal D. , Mohanty Tanuja
Published: August 2017

Tuning the surface electronic properties of 2D transition metal dichalcogenides such as Molebdenum disulfide (MoS2) nanosheets is worth exploring for their potential applications in strain sensitive flexible electronic devices. Here in, the correlation between tensile strain developed in MoS2 nanosheets during swift heavy ion irradiation and corresponding modifications in their surface electronic properties is investigated. With prior structural characterization by transmission electron microscopy, chemically exfoliated MoS2 nanosheets were exposed to 100 MeV Ag ion irradiation at varying fluence for creation of controlled defects. The presence of defect induced systematic tensile strain was verified by Raman spectroscopy and X-ray Diffraction analysis. The effect of ion irradiation on in–plane mode is observed to be significantly higher than that on out-of-plane mode. The contribution of irradiation induced in-plane strain on modification of the surface electronic properties of nanosheets was analyzed by work function measurement using scanning Kelvin probe microscopy. The work function value is observed to be linearly proportional to tensile strain along the basal plane indicating a systematic shifting of Fermi surface with fluence towards the valence band.
Dielectric collapse at the LaAlO3/SrTiO3 (001) heterointerface under applied electric field
Authors: Minohara M. , Hikita Y. , Bell C. , Inoue H. , Hosoda M. , Sato H. K. , Kumigashira H. , Oshima M. , Ikenaga E. , Hwang H. Y.
Published: August 2017

The fascinating interfacial transport properties at the LaAlO3/SrTiO3 heterointerface have led to intense investigations of this oxide system. Exploiting the large dielectric constant of SrTiO3 at low temperatures, tunability in the interfacial conductivity over a wide range has been demonstrated using a back-gate device geometry. In order to understand the effect of back-gating, it is crucial to assess the interface band structure and its evolution with external bias. In this study, we report measurements of the gate-bias dependent interface band alignment, especially the confining potential profile, at the conducting LaAlO3/SrTiO3 (001) heterointerface using soft and hard x-ray photoemission spectroscopy in conjunction with detailed model simulations. Depth-profiling analysis incorporating the electric field dependent dielectric constant in SrTiO3 reveals that a significant potential drop on the SrTiO3 side of the interface occurs within ~2 nm of the interface under negative gate-bias. These results demonstrate gate control of the collapse of the dielectric permittivity at the interface, and explain the dramatic loss of electron mobility with back-gate depletion.
Spatially destabilising effect of woody plant diversity on forest productivity in a subtropical mountain forest
Authors: Zhong Yonglin , Sun Yudan , Xu Mingfeng , Zhang Yi , Wang Yongqiang , Su Zhiyao
Published: August 2017

We used geographically weighted regression to investigate the relationship between biodiversity and the spatial stability of forest productivity (SSFP) in a subtropical mountain forest. We examined the effect of elevation on this relationship and on its spatial non-stationarity. We found that higher woody plant diversity reduced SSPF. Higher woody plant diversity strengthened the asynchrony of species responses to spatial heterogeneity of forest habitats, which contributed to SSFP, but reduced two factors that enhanced SSFP: species dominance and the spatial stability of the dominant species. The percentage of variation in SSFP explained by diversity measures was highest for the Shannon-Wiener index, lowest for functional dispersion, and intermediate for species richness. The correlations of woody plant diversity with SSFP became stronger with elevation and varied among plots, indicating that the spatial non-stationarity existed in the biodiversity-SSFP relationship. These correlations became weaker in most cases after controlling for elevation. Our results suggest that in the subtropical mountain forest higher woody plant diversity has a spatially destabilising effect on forest productivity, particularly at higher elevations.
Elucidation of Dietary Polyphenolics as Potential Inhibitor of Microtubule Affinity Regulating Kinase 4: In silico and In vitro Studies
Authors: Khan Parvez , Rahman Shafikur , Queen Aarfa , Manzoor Saaliqa , Naz Farha , Hasan Gulam Mustafa , Luqman Suaib , Kim Jihoe , Islam Asimul , Ahmad Faizan , Hassan Md. Imtaiyaz
Published: August 2017

Microtubule affinity regulating kinase 4 (MARK4) is a Ser/Thr kinase belonging to AMPK-like family, has recently become an important drug target against cancer and neurodegenerative disorders. In this study, we have evaluated different natural dietary polyphenolics including rutin, quercetin, ferulic acid, hesperidin, gallic acid and vanillin as MARK4 inhibitors. All compounds are primarily binds to the active site cavity of MARK4. In silico observations were further complemented by the fluorescence-binding studies and isothermal titration calorimetry (ITC) measurements. We found that rutin and vanillin bind to MARK4 with a reasonably high affinity. ATPase and tau-phosphorylation assay further suggesting that rutin and vanillin inhibit the enzyme activity of MARK4 to a great extent. Cell proliferation, ROS quantification and Annexin-V staining studies are clearly providing sufficient evidences for the apoptotic potential of rutin and vanillin. In conclusion, rutin and vanillin may be considered as potential inhibitors for MARK4 and further exploited to design novel therapeutic molecules against MARK4 associated diseases.
Plasmodium falciparum GPCR-like receptor SR25 mediates extracellular K+ sensing coupled to Ca2+ signaling and stress survival
Authors: Moraes Miriam S. , Budu Alexandre , Singh Maneesh K. , Borges-Pereira Lucas , Levano-Garcia Julio , Currà Chiara , Picci Leonardo , Pace Tomasino , Ponzi Marta , Pozzan Tullio , Garcia Célia R. S.
Published: August 2017

The malaria parasite Plasmodium falciparum is exposed, during its development, to major changes of ionic composition in its surrounding medium. We demonstrate that the P. falciparum serpentine-like receptor PfSR25 is a monovalent cation sensor capable of modulating Ca2+ signaling in the parasites. Changing from high (140 mM) to low (5.4 mM) KCl concentration triggers [Ca2+]cyt increase in isolated parasites and this Ca2+ rise is blocked either by phospholipase C (PLC) inhibition or by depleting the parasite’s internal Ca2+ pools. This response persists even in the absence of free extracellular Ca2+ and cannot be elicited by addition of Na+, Mg2+ or Ca2+. However, when the PfSR25 gene was deleted, no effect on [Ca2+]cyt was observed in response to changing KCl concentration in the knocked out (PfSR25−) parasite. Finally, we also demonstrate that: i) PfSR25 plays a role in parasite volume regulation, as hyperosmotic stress induces a significant decrease in parasite volume in wild type (wt), but not in PfSR25− parasites; ii) parasites lacking PfSR25 show decreased parasitemia and metacaspase gene expression on exposure to the nitric oxide donor sodium nitroprusside (SNP) and iii), compared to PfSR25− parasites, wt parasites showed a better survival in albumax-deprived condition.
Non-equilibrium plasma jet induced thermo-acoustic resistivity imaging for higher contrast and resolution
Authors: Guo Liang , Li Linbo , Dong Fanqing , Jiang Wencong
Published: August 2017

A thermo-acoustic imaging modality induced by non-equilibrium atmospheric pressure plasma jet is reported. A tiny plasma jet is generated by a fast-rising pulsed dielectric barrier discharge and applied to the surface of the biological tissues. The pulsed conductive current induced by the conductive plasma jet is injected into the biological tissues. The Joule heating inside the tissue stimulates the ultrasound signals effectively. The amplitude of the ultrasound is related to the resistivity of the biological tissues near the contact point and takes the maximum at the certain conductivity of the certain frequency. Accordingly the thermo-acoustic resistivity imaging modality of high contrast and resolution is demonstrated theoretically and experimentally.
High Serum Levels of Malondialdehyde and 8-OHdG are both Associated with Early Cognitive Impairment in Patients with Acute Ischaemic Stroke
Authors: Liu Zhihua , Liu Yuntao , Tu Xinjie , Shen Huiping , Qiu Huihua , Chen Huijun , He Jincai
Published: August 2017

Post-stroke cognitive impairment (PSCI) is an increasingly prevalent sequel after stroke that may associate with poor functional outcome and increased risk of recurrent stroke. We aimed to explore the relationship between oxidative stress biomarkers and the presence of PSCI. 193 first-ever acute ischaemic stroke patients were consecutively enrolled in the current study. The oxidative stress biomarkers malondialdehyde (MDA) and 8-hydroxydeoxyquanosine (8-OHdG) were measured within 24 h after admission. Cognition function was evaluated by the Mini-Mental State Examination (MMSE) at 1 month after stroke. Serum levels of 8-OHdG and MDA were both significantly higher in the PSCI (p < 0.001) compared with the non-PSCI group. Both the serum levels of both 8-OHdG and MDA were negatively correlated with the MMSE score. Receiver operating characteristic curve analysis was used to evaluate 8-OHdG and MDA as markers of a high risk of PSCI and produced area under curve values of 0.700 and 0.793. Adjusted logistic regression showed that serum 8-OHdG and MDA levels remained as independent markers of PSCI. High serum levels of malondialdehyde and 8-OHdG are associated with the presence of PSCI at 1 month after stroke.
Metabolomic Analysis Reveals Vitamin D-induced Decrease in Polyol Pathway and Subtle Modulation of Glycolysis in HEK293T Cells
Authors: Santos G. C. , Zeidler J. D. , Pérez-Valencia J. A. , Sant’Anna-Silva A. C. B. , Da Poian A. T. , El-Bacha T. , Almeida F. C. L.
Published: August 2017

We combined 1H NMR metabolomics with functional and molecular biochemical assays to describe the metabolic changes elicited by vitamin D in HEK293T, an embryonic proliferative cell line adapted to high-glucose concentrations. Activation of the polyol pathway, was the most important consequence of cell exposure to high glucose concentration, resembling cells exposed to hyperglycemia. Vitamin D induced alterations in HEK293T cells metabolism, including a decrease in sorbitol, glycine, glutamate, guanine. Vitamin D modulated glycolysis by increasing phosphoglycerate mutase and decreasing enolase activities, changing carbon fate without changing glucose consumption, lactate export and Krebs cycle. The decrease in sorbitol intracellular concentration seems to be related to vitamin D regulated redox homeostasis and protection against oxidative stress, and helped maintaining the high proliferative phenotype, supported by the decrease in glycine and guanine and orotate concentration and increase in choline and phosphocholine concentration. The decrease in orotate and guanine indicated an increased biosynthesis of purine and pyrimidines. Vitamin D elicited metabolic alteration without changing cellular proliferation and mitochondrial respiration, but reclaiming reductive power. Our study may contribute to the understanding of the metabolic mechanism of vitamin D upon exposure to hyperglycemia, suggesting a role of protection against oxidative stress.
Results from 11C-metformin-PET scans, tissue analysis and cellular drug-sensitivity assays questions the view that biguanides affects tumor respiration directly
Authors: Iversen Ane B. , Horsman Michael R. , Jakobsen Steen , Jensen Jonas B. , Garm Christian , Jessen Niels , Breining Peter , Frøkiær Jørgen , Busk Morten
Published: August 2017

The anti-diabetic biguanide drugs metformin (METF) and phenformin (PHEN) may have anti-cancer effects. Biguanides suppress plasma growth factors, but nonetheless, the view that these mitochondrial inhibitors accumulate in tumor tissue to an extent that leads to severe energetic stress or alleviation of hypoxia-induced radioresistance is gaining ground. Our cell studies confirm that biguanides inhibits cell proliferation by targeting respiration, but only at highly suprapharmacological concentrations due to low drug retention. Biodistribution/PET studies of 11C-labeled metformin (11C-METF) revealed that plasma bioavailability remained well below concentrations with metabolic/anti-proliferative in vitro effects, following a high oral dose. Intraperitoneal administration resulted in higher drug concentrations, which affected metabolism in normal organs with high METF uptake (e.g., kidneys), but tumor drug retention peaked at low levels comparable to plasma levels and hypoxia was unaffected. Prolonged intraperitoneal treatment reduced tumor growth in two tumor models, however, the response did not reflect in vitro drug sensitivity, and tumor metabolism and hypoxia was unaffected. Our results do not support that direct inhibition of tumor cell respiration is responsible for reduced tumor growth, but future studies using 11C-METF-PET are warranted, preferably in neoplasia’s originating from tissue with high drug transport capacity, to investigate the controversial idea of direct targeting.
Structure-based drug discovery for combating influenza virus by targeting the PA–PB1 interaction
Authors: Watanabe Ken , Ishikawa Takeshi , Otaki Hiroki , Mizuta Satoshi , Hamada Tsuyoshi , Nakagaki Takehiro , Ishibashi Daisuke , Urata Shuzo , Yasuda Jiro , Tanaka Yoshimasa , Nishida Noriyuki
Published: August 2017

Influenza virus infections are serious public health concerns throughout the world. The development of compounds with novel mechanisms of action is urgently required due to the emergence of viruses with resistance to the currently-approved anti-influenza viral drugs. We performed in silico screening using a structure-based drug discovery algorithm called Nagasaki University Docking Engine (NUDE), which is optimised for a GPU-based supercomputer (DEstination for Gpu Intensive MAchine; DEGIMA), by targeting influenza viral PA protein. The compounds selected by NUDE were tested for anti-influenza virus activity using a cell-based assay. The most potent compound, designated as PA-49, is a medium-sized quinolinone derivative bearing a tetrazole moiety, and it inhibited the replication of influenza virus A/WSN/33 at a half maximal inhibitory concentration of 0.47 μM. PA-49 has the ability to bind PA and its anti-influenza activity was promising against various influenza strains, including a clinical isolate of A(H1N1)pdm09 and type B viruses. The docking simulation suggested that PA-49 interrupts the PA–PB1 interface where important amino acids are mostly conserved in the virus strains tested, suggesting the strain independent utility. Because our NUDE/DEGIMA system is rapid and efficient, it may help effective drug discovery against the influenza virus and other emerging viruses.
Ultracompact bottom-up photonic crystal lasers on silicon-on-insulator
Authors: Lee Wook-Jae , Kim Hyunseok , You Jong-Bum , Huffaker Diana L.
Published: August 2017

Compact on-chip light sources lie at the heart of practical nanophotonic devices since chip-scale photonic circuits have been regarded as the next generation computing tools. In this work, we demonstrate room-temperature lasing in 7 × 7 InGaAs/InGaP core-shell nanopillar array photonic crystals with an ultracompact footprint of 2300 × 2300 nm2, which are monolithically grown on silicon-on-insulator substrates. A strong lateral confinement is achieved by a photonic band-edge mode, which is leading to a strong light-matter interaction in the 7 × 7 nanopillar array, and by choosing an appropriate thickness of a silicon-on-insulator layer the band-edge mode can be trapped vertically in the nanopillars. The nanopillar array band-edge lasers exhibit single-mode operation, where the mode frequency is sensitive to the diameter of the nanopillars. Our demonstration represents an important first step towards developing practical and monolithic III-V photonic components on a silicon platform.
Influence of synthesis parameters on CCVD growth of vertically aligned carbon nanotubes over aluminum substrate
Authors: Szabó Anna , Kecsenovity Egon , Pápa Zsuzsanna , Gyulavári Tamás , Németh Krisztián , Horvath Endre , Hernadi Klara
Published: August 2017

In the past two decades, important results have been achieved in the field of carbon nanotube (CNT) research, which revealed that carbon nanotubes have extremely good electrical and mechanical properties The range of applications widens more, if CNTs form a forest-like, vertically aligned structure (VACNT) Although, VACNT-conductive substrate structure could be very advantageous for various applications, to produce proper system without barrier films i.e. with good electrical contact is still a challenge. The aim of the current work is to develop a cheap and easy method for growing carbon nanotubes forests on conductive substrate with the CCVD (Catalytic Chemical Vapor Deposition) technique at 640 °C. The applied catalyst contained Fe and Co and was deposited via dip coating onto an aluminum substrate. In order to control the height of CNT forest several parameters were varied during the both catalyst layer fabrication (e.g. ink concentration, ink composition, dipping speed) and the CCVD synthesis (e.g. gas feeds, reaction time). As-prepared CNT forests were investigated with various methods such as scanning electron microscopy, Raman spectroscopy, and cyclic voltammetry. With such an easy process it was possible to tune both the height and the quality of carbon nanotube forests.
Evolutionary conserved role of eukaryotic translation factor eIF5A in the regulation of actin-nucleating formins
Authors: Muñoz-Soriano Verónica , Domingo-Muelas Ana , Li Tianlu , Gamero Esther , Bizy Alexandra , Fariñas Isabel , Alepuz Paula , Paricio Nuria
Published: August 2017

Elongation factor eIF5A is required for the translation of consecutive prolines, and was shown in yeast to translate polyproline-containing Bni1, an actin-nucleating formin required for polarized growth during mating. Here we show that Drosophila eIF5A can functionally replace yeast eIF5A and is required for actin-rich cable assembly during embryonic dorsal closure (DC). Furthermore, Diaphanous, the formin involved in actin dynamics during DC, is regulated by and mediates eIF5A effects. Finally, eIF5A controls cell migration and regulates Diaphanous levels also in mammalian cells. Our results uncover an evolutionary conserved role of eIF5A regulating cytoskeleton-dependent processes through translation of formins in eukaryotes.
A novel automatic quantification method for high-content screening analysis of DNA double strand-break response
Authors: Feng Jingwen , Lin Jie , Zhang Pengquan , Yang Songnan , Sa Yu , Feng Yuanming
Published: August 2017

High-content screening is commonly used in studies of the DNA damage response. The double-strand break (DSB) is one of the most harmful types of DNA damage lesions. The conventional method used to quantify DSBs is γH2AX foci counting, which requires manual adjustment and preset parameters and is usually regarded as imprecise, time-consuming, poorly reproducible, and inaccurate. Therefore, a robust automatic alternative method is highly desired. In this manuscript, we present a new method for quantifying DSBs which involves automatic image cropping, automatic foci-segmentation and fluorescent intensity measurement. Furthermore, an additional function was added for standardizing the measurement of DSB response inhibition based on co-localization analysis. We tested the method with a well-known inhibitor of DSB response. The new method requires only one preset parameter, which effectively minimizes operator-dependent variations. Compared with conventional methods, the new method detected a higher percentage difference of foci formation between different cells, which can improve measurement accuracy. The effects of the inhibitor on DSB response were successfully quantified with the new method (p = 0.000). The advantages of this method in terms of reliability, automation and simplicity show its potential in quantitative fluorescence imaging studies and high-content screening for compounds and factors involved in DSB response.
Correlations between Gray Matter and White Matter Degeneration in Pure Alzheimer’s Disease, Pure Subcortical Vascular Dementia, and Mixed Dementia
Authors: Jang Hyemin , Kwon Hunki , Yang Jin-Ju , Hong Jinwoo , Kim Yeshin , Kim Ko Woon , Lee Jin San , Jang Young Kyoung , Kim Sung Tae , Lee Kyung Han , Lee Jae Hong , Na Duk L. , Seo Sang Won , Kim Hee Jin , Lee Jong-Min
Published: August 2017

Alzheimer’s disease dementia (ADD) and subcortical vascular dementia (SVaD) both show cortical thinning and white matter (WM) microstructural changes. We evaluated different patterns of correlation between gray matter (GM) and WM microstructural changes in pure ADD, pure SVaD, and mixed dementia. We enrolled 40 Pittsburgh compound B (PiB) positive ADD patients without WM hyperintensities (pure ADD), 32 PiB negative SVaD patients (pure SVaD), 23 PiB positive SVaD patients (mixed dementia), and 56 normal controls. WM microstructural integrity was quantified using fractional anisotropy (FA), axial diffusivity (DA), and radial diffusivity (DR) values. We used sparse canonical correlation analysis to show correlated regions of cortical thinning and WM microstructural changes. In pure ADD patients, lower FA in the frontoparietal area correlated with cortical thinning in the left inferior parietal lobule and bilateral paracentral lobules. In pure SVaD patients, lower FA and higher DR across extensive WM regions correlated with cortical thinning in bilateral fronto-temporo-parietal regions. In mixed dementia patients, DR and DA changes across extensive WM regions correlated with cortical thinning in the bilateral fronto-temporo-parietal regions. Our findings showed that the relationships between GM and WM degeneration are distinct in pure ADD, pure SVaD, and mixed dementia, suggesting that different pathomechanisms underlie their correlations.
The E-cadherin/AmotL2 complex organizes actin filaments required for epithelial hexagonal packing and blastocyst hatching
Authors: Hildebrand Sebastian , Hultin Sara , Subramani Aravindh , Petropoulos Sophie , Zhang Yuanyuan , Cao Xiaofang , Mpindi John , Kalloniemi Olli , Johansson Staffan , Majumdar Arindam , Lanner Fredrik , Holmgren Lars
Published: August 2017

Epithelial cells connect via cell-cell junctions to form sheets of cells with separate cellular compartments. These cellular connections are essential for the generation of cellular forms and shapes consistent with organ function. Tissue modulation is dependent on the fine-tuning of mechanical forces that are transmitted in part through the actin connection to E-cadherin as well as other components in the adherens junctions. In this report we show that p100 amotL2 forms a complex with E-cadherin that associates with radial actin filaments connecting cells over multiple layers. Genetic inactivation or depletion of amotL2 in epithelial cells in vitro or zebrafish and mouse in vivo, resulted in the loss of contractile actin filaments and perturbed epithelial packing geometry. We further showed that AMOTL2 mRNA and protein was expressed in the trophectoderm of human and mouse blastocysts. Genetic inactivation of amotL2 did not affect cellular differentiation but blocked hatching of the blastocysts from the zona pellucida. These results were mimicked by treatment with the myosin II inhibitor blebbistatin. We propose that the tension generated by the E-cadherin/AmotL2/actin filaments plays a crucial role in developmental processes such as epithelial geometrical packing as well as generation of forces required for blastocyst hatching.
Evaluation of the Elecsys syphilis immunoassay for routine screening of serum samples in China
Authors: Tao Chuanmin , Hao Xiaoke , Xu Wei , Zhang Jie , Pan Shiyang , Tao Zhihua , Li Xiaofei , Chen Junmei , Zhang Bingchang , Qiu Yurong , Wu Yanan , Ou Qishui , Huang Xianzhang , Wang Lanlan
Published: August 2017

We compared the performance of the Roche Diagnostics Elecsys immunoassay for the detection of Treponema pallidum specific antibodies in patient serum samples with that of the Abbott Laboratories Architect chemiluminescent microparticle immunoassay and the InTec and KHB enzyme-linked immunosorbent assays, which are commonly used in China. We tested 13,767 serum samples collected from 13 independent laboratories throughout China, which included samples from 999 previously confirmed syphilis cases and 158 ‘borderline’ samples previously identified using the Architect, InTec, and KHB tests. The Mikrogen Syphilis Immunoblot was used to confirm positive test results. The consistency between the four different assays was 100%. The sensitivity of Elecsys immunoassay was 100% versus 98.26% for Architect, 99.11% for InTec; and 98.56% for KHB. The specificity of the Elecsys immunoassay was 99.81% versus 99.74% for Architect; 99.93% versus 99.80% for InTec; and 99.85% versus 99.77% for KHB. For borderline samples, the Elecsys immunoassay yielded no false-negative results and fewer false-positive results, compared to the other tests. Considering the ease-of-use, automation, high speed, and high throughput capacity of the Elecsys assay, the higher sensitivity and specificity indicate it is superior for routine screening of serum samples for syphilis diagnosis.
Prevalence of hyperuricemia and its related risk factors among preschool children from China
Authors: Li Nan , Zhang Shuang , Li Weiqin , Wang Leishen , Liu Huikun , Li Wei , Zhang Tao , Liu Gongshu , Du Yuexin , Leng Junhong
Published: August 2017

To estimate the prevalence of hyperuricemia and its major risk factors among Chinese preschool children. A cross-sectional survey was carried out in six central urban districts of Tianjin from March to June 2015. A cluster sampling was employed to obtain a random sample of preschool children. A total of 4073 children aged from 3 to 6 years participated in this survey. Logistic regression was used to obtain odds ratios and 95% confidence intervals. The overall mean serum uric acid concentrations was 243.0 ± 53.2 μmol/L, corresponding to a mean concentrations of 247.3 ± 53.7 μmol/L among boys and 238.3 ± 52.4 μmol/L among girls. The overall prevalence of serum uric acid ≥ 310 μmol/L among children was 10.1%. Boys, obesity, diastolic blood pressure, and serum triglyceride concentrations were associated with the increased risk of hyperuricemia in univariable models, although the statistically significant association between diastolic blood pressure, serum triglyceride concentrations and hyperuricemia disappeared in multivariable models. The prevalence of hyperuricemia among children aged from 3 to 6 years was relatively high. Several metabolic syndrome components were associated with the risk of hyperuricemia.
Probing the Hydrogen Enhanced Near-Field Emission of ITO without a Vacuum-Gap
Authors: Poole Jacob L. , Yu Yang , Ohodnicki Paul R.
Published: August 2017

Electromagnetic fields produced by thermal fluctuation can excite the near-field optical states, creating the potential for thermal radiation orders of magnitude greater than what is predicted by Plank’s blackbody theory. The typical schemes employed to probe the trapped electromagnetic energy of the near-field are with considerable technical challenges, suffering from scalability and high costs, hindering widespread use. A waveguide-based scheme relying on photon tunneling is presented as an alternate approach, as waveguides inherently provide a large density of channels for photons to tunnel to with the required k-vector matching and probability density overlap. The conducted experiments with a 10 nm indium tin oxide film, having plasmonic resonance in the 1500 nm wavelength range, show that the near-field EM radiation can be extracted to the far-field by establishing the mode of de-excitation to be that of photon tunneling to a nearby waveguide. Furthermore, it is also demonstrated that the thermally emitted energy is very sensitive to changes in the surface free electron density, a property that is unique to the near-field. In addition to the ease of implementation and scalability, the proposed waveguide-based extraction method does not require a vacuum-gap, which is a significant reduction in the required complexity.
Procedural complication and long term outcomes after alcohol septal ablation in patients with obstructive hypertrophic cardiomyopathy: data from China
Authors: An Shuo-yan , Yang Yin-jian , Hang Fei , Wang Zhi-min , Fan Chao-mei
Published: August 2017

Data on procedural complications and long term survival after alcohol septal ablation (ASA) in Chinese patients with obstructive hypertrophic cardiomyopathy (HOCM) are lacking. We aimed to investigate long-term survival of HOCM patients after ASA and compared to the non-obstructive hypertrophic cardiomyopathy(NOHCM). A total of 233 patients with HOCM and a peak pressure gradient of ≥50 mm Hg at rest or with provocation were consecutively enrolled from Fuwai Hospital in China between 2000 and 2012. Another 297 patients without left ventricular outflow tract obstruction were regarded as control group. Periprocedural mortality of ASA were low (0.89%). Periprocedural lethal ventricular arrhythmia occurred in 9 patients (4.0%). Alcohol volume (RR 1.44, 95% CI: 1.03–2.03, P = 0.034) and age ≤40 years old (RR 4.63, 95% CI: 1.07–20.0, P = 0.040) were independent predictors for periprocedural lethal ventricular arrhythmia. The 10- year overall survival was 94.6% in the ASA group, similar with 92.9% in the NOHCM group (P = 0.930). In conclusion, periprocedural mortality and complications were rare in ASA. Long term survival after ASA were satisfactory and comparable to NOHCM. Patients under 40 years old should be more cautious undergoing ASA, for these patients were more likely to endure lethal ventricular arrhythmia during periprocedural period of ASA.
Potential therapeutic targets for ALS: MIR206, MIR208b and MIR499 are modulated during disease progression in the skeletal muscle of patients
Authors: Di Pietro Lorena , Baranzini Mirko , Berardinelli Maria Grazia , Lattanzi Wanda , Monforte Mauro , Tasca Giorgio , Conte Amelia , Logroscino Giandomenico , Michetti Fabrizio , Ricci Enzo , Sabatelli Mario , Bernardini Camilla
Published: August 2017

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motor neurons followed by muscle weakness, paralysis and death. The disease progression is extremely variable among patients, and reliable prognostic markers have not been identified. The aim of the study was to functionally characterize selected genes and microRNAs acting in the skeletal muscle of ALS patients, taking into account the duration and evolution of the disease, in order to obtain information regarding the muscle response to ALS progression. This prospective, longitudinal study enrolled 14 ALS patients and 24 age- and sex-matched healthy controls. Gene expression and histological analysis indicated an increase of MIR208B and MIR499 levels and the predominance of slow fibres, respectively, in the muscles of patients with a slower disease progression. A decreased expression of MIR206 and increased levels of HDAC4, during the progression of the disease were also observed. Taken together, our data suggest that the molecular signalling that regulates re-innervation and muscle regeneration is hampered during the progression of skeletal muscle impairment in ALS. This could provide precious hints towards defining prognostic protocols, and designing novel tailored therapeutic approaches, to improve ALS patients’ care and delay disease progression.