bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting ornithine decarboxylase (ODC) inhibits esophageal squamous cell carcinoma progression
Authors: He Wei , Roh Eunmiri , Yao Ke , Liu Kangdong , Meng Xing , Liu Fangfang , Wang Penglei , Bode Ann M. , Dong Zigang
Published: April 2017

To explore the function of ornithine decarboxylase in esophageal squamous cell carcinoma progression and test the effectiveness of anti-ornithine decarboxylase therapy for esophageal squamous cell carcinoma. In this study, we examined the expression pattern of ornithine decarboxylase in esophageal squamous cell carcinoma cell lines and tissues using immunohistochemistry and Western blot analysis. Then we investigated the function of ornithine decarboxylase in ESCC cells by using shRNA and an irreversible inhibitor of ornithine decarboxylase, difluoromethylornithine. To gather more supporting pre-clinical data, a human esophageal squamous cell carcinoma patient-derived xenograft mouse model (C.B-17 severe combined immunodeficient mice) was used to determine the antitumor effects of difluoromethylornithine in vivo. Our data showed that the expression of the ornithine decarboxylase protein is increased in esophageal squamous cell carcinoma tissues compared with esophagitis or normal adjacent tissues. Polyamine depletion by ODC shRNA not only arrests esophageal squamous cell carcinoma cells in the G2/M phase, but also induces apoptosis, which further suppresses esophageal squamous cell carcinoma cell tumorigenesis. Difluoromethylornithine treatment decreases proliferation and also induces apoptosis of esophageal squamous cell carcinoma cells and implanted tumors, resulting in significant reduction in the size and weight of tumors. The results of this study indicate that ornithine decarboxylase is a promising target for esophageal squamous cell carcinoma therapy and difluoromethylornithine warrants further study in clinical trials to test its effectiveness against esophageal squamous cell carcinoma.
Restoring visual function to the blind retina with a potent, safe and long-lasting photoswitch
Authors: Tochitsky Ivan , Trautman Jay , Gallerani Nicholas , Malis Jonatan G. , Kramer Richard H.
Published: April 2017

Photoswitch compounds such as DENAQ confer light-sensitivity on endogenous neuronal ion channels, enabling photocontrol of neuronal activity without genetic manipulation. DENAQ treatment restores both retinal light responses and visual behaviors in rodent models of Retinitis pigmentosa. However, retinal photosensitization requires a high dose of DENAQ and disappears within several days after treatment. Here we report that BENAQ, an improved photoswitch, is 20-fold more potent than DENAQ and persists in restoring visual responses to the retina for almost 1 month after a single intraocular injection. Studies on mice and rabbits show that BENAQ is non-toxic at concentrations 10-fold higher than required to impart light-sensitivity. These favorable properties make BENAQ a potential drug candidate for vision restoration in patients with degenerative blinding diseases.
Role of Slow-Release Nanocomposite Fertilizers on Nitrogen and Phosphate Availability in Soil
Authors: Giroto Amanda S. , Guimarães Gelton G. F. , Foschini Milene , Ribeiro Caue
Published: April 2017

Developing efficient crop fertilization practices has become more and more important due to the ever-increasing global demand for food production. One approach to improving the efficiency of phosphate and urea fertilization is to improve their interaction through nanocomposites that are able to control the release of urea and P in the soil. Nanocomposites were produced from urea (Ur) or extruded thermoplastic starch/urea (TPSUr) blends as a matrix in which hydroxyapatite particles (Hap) were dispersed at ratios 50% and 20% Hap. Release tests and two incubation experiments were conducted in order to evaluate the role played by nanocomposites in controlling the availability of nitrogen and phosphate in the soil. Tests revealed an interaction between the fertilizer components and the morphological changes in the nanocomposites. TPSUr nanocomposites provided a controlled release of urea and increased the release of phosphorus from Hap in citric acid solution. The TPSUr nanocomposites also had lower NH3 volatilization compared to a control. The interaction resulting from dispersion of Hap within a urea matrix reduced the phosphorus adsorption and provided higher sustained P availability after 4 weeks of incubation in the soil.
Daily touchscreen use in infants and toddlers is associated with reduced sleep and delayed sleep onset
Authors: Cheung Celeste H. M. , Bedford Rachael , Saez De Urabain Irati R. , Karmiloff-Smith Annette , Smith Tim J.
Published: April 2017

Traditional screen time (e.g. TV and videogaming) has been linked to sleep problems and poorer developmental outcomes in children. With the advent of portable touchscreen devices, this association may be extending down in age to disrupt the sleep of infants and toddlers, an age when sleep is essential for cognitive development. However, this association has not been demonstrated empirically. This study aims to examine whether frequency of touchscreen use is associated with sleep in infants and toddlers between 6 and 36 months of age. An online survey was administered to 715 parents reporting on child media use (daily exposure to TV and use of touchscreens), sleep patterns (night-time and daytime sleep duration, sleep onset - time to fall asleep, and frequencies of night awakenings). Structural equation models controlling for age, sex, TV exposure and maternal education indicated a significant association between touchscreen use and night-time sleep, daytime sleep and sleep onset. No significant effect was observed for the number of night awakenings. To our knowledge, this is the first report linking the use of touchscreen with sleep problems in infants and toddlers. Future longitudinal studies are needed to clarify the direction of effects and the mechanisms underlying these associations using detailed sleep tracking.
Novel Heating-Induced Reversion during Crystallization of Al-based Glassy Alloys
Authors: Han F. F. , Inoue A. , Han Y. , Kong F. L. , Zhu S. L. , Shalaan E. , Al-Marzouki F. , Greer A. L.
Published: April 2017

Thermal stability and crystallization of three multicomponent glassy alloys, Al86Y7Ni5Co1Fe0.5Pd0.5, Al85Y8Ni5Co1Fe0.5Pd0.5 and Al84Y9Ni4Co1.5Fe0.5Pd1, were examined to assess the ability to form the mixture of amorphous (am) and fcc-aluminum (α-Al) phases. On heating, the glass transition into the supercooled liquid is shown by the 85Al and 84Al glasses. The crystallization sequences are [am] → [am + α-Al] → [α-Al + compounds] for the 86Al and 85Al alloys, and [am] → [am + α-Al + cubic AlxMy (M = Y, Ni, Co, Fe, Pd)] → [am + α-Al] → [α-Al + Al3Y + Al9(Co, Ni)2 + unknown phase] for the 84Al alloy. The glass transition appears even for the 85Al alloy where the primary phase is α-Al. The heating-induced reversion from [am + α-Al + multicomponent AlxMy] to [am + α-Al] for the 84Al alloy is abnormal, not previously observed in crystallization of glassy alloys, and seems to originate from instability of the metastable AlxMy compound, in which significant inhomogeneous strain is caused by the mixture of solute elements. This novel reversion phenomenon is encouraging for obtaining the [am + α-Al] mixture over a wide range of high temperature effective for the formation of Al-based high-strength nanostructured bulk alloys by warm working.
Exploring the significance of morphological diversity for cerebellar granule cell excitability
Authors: Houston Catriona M. , Diamanti Efthymia , Diamantaki Maria , Kutsarova Elena , Cook Anna , Sultan Fahad , Brickley Stephen G.
Published: April 2017

The relatively simple and compact morphology of cerebellar granule cells (CGCs) has led to the view that heterogeneity in CGC shape has negligible impact upon the integration of mossy fibre (MF) information. Following electrophysiological recording, 3D models were constructed from high-resolution imaging data to identify morphological features that could influence the coding of MF input patterns by adult CGCs. Quantification of MF and CGC morphology provided evidence that CGCs could be connected to the multiple rosettes that arise from a single MF input. Predictions from our computational models propose that MF inputs could be more densely encoded within the CGC layer than previous models suggest. Moreover, those MF signals arriving onto the dendrite closest to the axon will generate greater CGC excitation. However, the impact of this morphological variability on MF input selectivity will be attenuated by high levels of CGC inhibition providing further flexibility to the MF → CGC pathway. These features could be particularly important when considering the integration of multimodal MF sensory input by individual CGCs.
Burstiness and tie activation strategies in time-varying social networks
Authors: Ubaldi Enrico , Vezzani Alessandro , Karsai Márton , Perra Nicola , Burioni Raffaella
Published: April 2017

The recent developments in the field of social networks shifted the focus from static to dynamical representations, calling for new methods for their analysis and modelling. Observations in real social systems identified two main mechanisms that play a primary role in networks’ evolution and influence ongoing spreading processes: the strategies individuals adopt when selecting between new or old social ties, and the bursty nature of the social activity setting the pace of these choices. We introduce a time-varying network model accounting both for ties selection and burstiness and we analytically study its phase diagram. The interplay of the two effects is non trivial and, interestingly, the effects of burstiness might be suppressed in regimes where individuals exhibit a strong preference towards previously activated ties. The results are tested against numerical simulations and compared with two empirical datasets with very good agreement. Consequently, the framework provides a principled method to classify the temporal features of real networks, and thus yields new insights to elucidate the effects of social dynamics on spreading processes.
The role of focal adhesion anchoring domains of CAS in mechanotransduction
Authors: Braniš Jaroslav , Pataki Csilla , Spörrer Marina , Gerum Richard C. , Mainka Astrid , Cermak Vladimir , Goldmann Wolfgang H. , Fabry Ben , Brabek Jan , Rosel Daniel
Published: April 2017

CAS is a docking protein, which was shown to act as a mechanosensor in focal adhesions. The unique assembly of structural domains in CAS is important for its function as a mechanosensor. The tension within focal adhesions is transmitted to a stretchable substrate domain of CAS by focal adhesion-targeting of SH3 and CCH domain of CAS, which anchor the CAS protein in focal adhesions. Mechanistic models of the stretching biosensor propose equal roles for both anchoring domains. Using deletion mutants and domain replacements, we have analyzed the relative importance of the focal adhesion anchoring domains on CAS localization and dynamics in focal adhesions as well as on CAS-mediated mechanotransduction. We confirmed the predicted prerequisite of the focal adhesion targeting for CAS-dependent mechanosensing and unraveled the critical importance of CAS SH3 domain in mechanosensing. We further show that CAS localizes to the force transduction layer of focal adhesions and that mechanical stress stabilizes CAS in focal adhesions.
Physicochemical characterizations of functional hybrid liposomal nanocarriers formed using photo-sensitive lipids
Authors: Kumar Pramanik Sumit , Losada-Pérez Patricia , Reekmans Gunter , Carleer Robert , D’Olieslaeger Marc , Vanderzande Dirk , Adriaensens Peter , Ethirajan Anitha
Published: April 2017

With recent advances in the field of diagnostics and theranostics, liposomal technology has secured a fortified position as a potential nanocarrier. Specifically, radiation/photo-sensitive liposomes containing photo-polymerizable cross-linking lipids are intriguing as they can impart the vesicles with highly interesting properties such as response to stimulus and improved shell stability. In this work, 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphoethanolamine (DTPE) is used as a photo-polymerizable lipid to form functional hybrid-liposomes as it can form intermolecular cross-linking through the diacetylenic groups. Hybrid-liposomes were formulated using mixtures of DTPE and saturated lipids of different chain lengths (dipalmitoylphosphatidylcholine (DPPC) and dimirystoilphosphatidylcholine (DMPC)) at different molar ratios. The physico-chemical characteristics of the liposomes has been studied before and after UV irradiation using a combination of techniques: DSC, QCM-D and solid-state NMR. The results signify the importance of a subtle modification in alkyl chain length on the phase behavior of the hybrid-liposomes and on the degree of crosslinking in the shell.
Decoupling of soil carbon and nitrogen turnover partly explains increased net ecosystem production in response to nitrogen fertilization
Authors: Ehtesham Emad , Bengtson Per
Published: April 2017

During the last decade there has been an ongoing controversy regarding the extent to which nitrogen fertilization can increase carbon sequestration and net ecosystem production in forest ecosystems. The debate is complicated by the fact that increased nitrogen availability caused by nitrogen deposition has coincided with increasing atmospheric carbon dioxide concentrations. The latter could further stimulate primary production but also result in increased allocation of carbon to root exudates, which could potentially ‘prime’ the decomposition of soil organic matter. Here we show that increased input of labile carbon to forest soil caused a decoupling of soil carbon and nitrogen cycling, which was manifested as a reduction in respiration of soil organic matter that coincided with a substantial increase in gross nitrogen mineralization. An estimate of the magnitude of the effect demonstrates that the decoupling could potentially result in an increase in net ecosystem production by up to 51 kg C ha−1 day−1 in nitrogen fertilized stands during peak summer. Even if the effect is several times lower on an annual basis, the results still suggest that nitrogen fertilization can have a much stronger influence on net ecosystem production than can be expected from a direct stimulation of primary production alone.
Preference for facial averageness: Evidence for a common mechanism in human and macaque infants
Authors: Damon Fabrice , Méary David , Quinn Paul C. , Lee Kang , Simpson Elizabeth A. , Paukner Annika , Suomi Stephen J. , Pascalis Olivier
Published: April 2017

Human adults and infants show a preference for average faces, which could stem from a general processing mechanism and may be shared among primates. However, little is known about preference for facial averageness in monkeys. We used a comparative developmental approach and eye-tracking methodology to assess visual attention in human and macaque infants to faces naturally varying in their distance from a prototypical face. In Experiment 1, we examined the preference for faces relatively close to or far from the prototype in 12-month-old human infants with human adult female faces. Infants preferred faces closer to the average than faces farther from it. In Experiment 2, we measured the looking time of 3-month-old rhesus macaques (Macaca mulatta) viewing macaque faces varying in their distance from the prototype. Like human infants, macaque infants looked longer to faces closer to the average. In Experiments 3 and 4, both species were presented with unfamiliar categories of faces (i.e., macaque infants tested with adult macaque faces; human infants and adults tested with infant macaque faces) and showed no prototype preferences, suggesting that the prototypicality effect is experience-dependent. Overall, the findings suggest a common processing mechanism across species, leading to averageness preferences in primates.
50-nm-resolution full-field X-ray microscope without chromatic aberration using total-reflection imaging mirrors
Authors: Matsuyama Satoshi , Yasuda Shuhei , Yamada Jumpei , Okada Hiromi , Kohmura Yoshiki , Yabashi Makina , Ishikawa Tetsuya , Yamauchi Kazuto
Published: April 2017

X-ray spectromicroscopy with a full-field imaging technique is a powerful method for chemical analysis of heterogeneous complex materials with a nano-scale spatial resolution. For imaging optics, an X-ray reflective optical system has excellent capabilities with highly efficient, achromatic, and long-working-distance properties. An advanced Kirkpatrick–Baez geometry that combines four independent mirrors with elliptic and hyperbolic shapes in both horizontal and vertical directions was developed for this purpose, although the complexity of the system has a limited applicable range. Here, we present an optical system consisting of two monolithic imaging mirrors. Elliptic and hyperbolic shapes were formed on a single substrate to achieve both high resolution and sufficient stability. The mirrors were finished with a ~1-nm shape accuracy using elastic emission machining. The performance was tested at SPring-8 with a photon energy of approximately 10 keV. We could clearly resolve 50-nm features in a Siemens star without chromatic aberration and with high stability over 20 h. We applied this system to X-ray absorption fine structure spectromicroscopy and identified elements and chemical states in specimens of zinc and tungsten micron-size particles.
Genetic visualization of protein interactions harnessing liquid phase transitions
Authors: Watanabe Taku , Seki Tatsuya , Fukano Takashi , Sakaue-Sawano Asako , Karasawa Satoshi , Kubota Misaki , Kurokawa Hiroshi , Inoue Ken , Akatsuka Junichi , Miyawaki Atsushi
Published: April 2017

Protein-protein interactions (PPIs) are essential components of cellular function. Current fluorescence-based technologies to measure PPIs have limited dynamic range and quantitative reproducibility. Here, we describe a genetically-encoded PPI visualization system that harnesses the dynamics of condensed liquid-phase transitions to analyze protein interactions in living cells. The fluorescent protein Azami-Green and p62-PB1 domain when fused to PPI partners triggered a rapid concatenation/oligomerization process that drove the condensation of liquid-phase droplets for real-time analysis of the interaction with unlimited dynamic range in the fluorescence signal. Proof-of-principle studies revealed novel insights on the live cell dynamics of XIAP-Smac and ERK2-dimer interactions. A photoconvertible variant allowed time-resolved optical highlighting for PPI kinetic analysis. Our system, called Fluoppi, demonstrates the unique signal amplification properties of liquid-phase condensation to detect PPIs. The findings introduce a general method for discovery of novel PPIs and modulators of established PPIs.
Ribosomal background of the Bacillus cereus group thermotypes
Authors: Fiedoruk Krzysztof , Drewnowska Justyna M. , Daniluk Tamara , Leszczynska Katarzyna , Iwaniuk Piotr , Swiecicka Izabela
Published: April 2017

In this study we reconstructed the architecture of Bacillus cereus sensu lato population based on ribosomal proteins, and identified a link between the ribosomal proteins’ variants and thermal groups (thermotypes) of the bacilli. The in silico phyloproteomic analysis of 55 ribosomal proteins (34 large and 21 small subunit r-proteins) of 421 strains, representing 14 well-established or plausible B. cereus sensu lato species, revealed several ribosomal clusters (r-clusters), which in general were well correlated with the strains’ affiliation to phylogenetic/thermal groups I–VII. However, a conformity and possibly a thermal characteristic of certain phylogenetic groups, e.g. the group IV, were not supported by a distribution of the corresponding r-clusters, and consequently neither by the analysis of cold-shock proteins (CSPs) nor by a content of heat shock proteins (HSPs). Furthermore, a preference for isoleucine and serine over valine and alanine in r-proteins along with a lack of HSP16.4 were recognized in non-mesophilic thermotypes. In conclusion, we suggest that the observed divergence in ribosomal proteins may be connected with an adaptation of B. cereus sensu lato members to various thermal niches.
Fewer rainy days and more extreme rainfall by the end of the century in Southern Africa
Authors: Pohl Benjamin , Macron Clémence , Monerie Paul-Arthur
Published: April 2017

Future changes in the structure of daily rainfall, especially the number of rainy days and the intensity of extreme events, are likely to induce major impacts on rain-fed agriculture in the tropics. In Africa this issue is of primary importance, but the agreement between climate models to simulate such descriptors of rainfall is generally poor. Here, we show that the climate models used for the fifth assessment report of IPCC simulate a marked decrease in the number of rainy days, together with a strong increase in the rainfall amounts during the 1% wettest days, by the end of the 21st century over Southern Africa. These combined changes lead to an apparent stability of seasonal totals, but are likely to alter the quality of the rainy season. These evolutions are due to the superposition of slowly-changing moisture fluxes, mainly supported by increased hygrometric capacity associated with global warming, and unchanged short-term atmospheric configurations in which extreme events are embedded. This could cause enhanced floods or droughts, stronger soil erosion and nutriment loss, questioning the sustainability of food security for the 300 million people currently living in Africa south of the Equator.
Nanomechanics of the endothelial glycocalyx contribute to Na+-induced vascular inflammation
Authors: Schierke Florian , Wyrwoll Margot J. , Wisdorf Martin , Niedzielski Leon , Maase Martina , Ruck Tobias , Meuth Sven G. , Kusche-Vihrog Kristina
Published: April 2017

High dietary salt (NaCl) is a known risk factor for cardiovascular pathologies and inflammation. High plasma Na+ concentrations (high Na+) have been shown to stiffen the endothelial cortex and decrease nitric oxide (NO) release, a hallmark of endothelial dysfunction. Here we report that chronic high Na+ damages the endothelial glycocalyx (eGC), induces release of inflammatory cytokines from the endothelium and promotes monocyte adhesion. Single cell force spectroscopy reveals that high Na+ enhances vascular adhesion protein-1 (VCAM-1)-dependent adhesion forces between monocytes and endothelial surface, giving rise to increased numbers of adherent monocytes on the endothelial surface. Mineralocorticoid receptor antagonism with spironolactone prevents high Na+-induced eGC deterioration, decreases monocyte-endothelium interactions, and restores endothelial function, indicated by increased release of NO. Whereas high Na+ decreases NO release, it induces endothelial release of the pro-inflammatory cytokines IL-1ß and TNFα. However, in contrast to chronic salt load (hours), in vivo and in vitro, an acute salt challenge (minutes) does not impair eGC function. This study identifies the eGC as important mediator of inflammatory processes and might further explain how dietary salt contributes to endothelialitis and cardiovascular pathologies by linking endothelial nanomechanics with vascular inflammation.
Fast optoelectric printing of plasmonic nanoparticles into tailored circuits
Authors: Rodrigo José A.
Published: April 2017

Plasmonic nanoparticles are able to control light at nanometre-scale by coupling electromagnetic fields to the oscillations of free electrons in metals. Deposition of such nanoparticles onto substrates with tailored patterns is essential, for example, in fabricating plasmonic structures for enhanced sensing. This work presents an innovative micro-patterning technique, based on optoelectic printing, for fast and straightforward fabrication of curve-shaped circuits of plasmonic nanoparticles deposited onto a transparent electrode often used in optoelectronics, liquid crystal displays, touch screens, etc. We experimentally demonstrate that this kind of plasmonic structure, printed by using silver nanoparticles of 40 nm, works as a plasmonic enhanced optical device allowing for polarized-color-tunable light scattering in the visible. These findings have potential applications in biosensing and fabrication of future optoelectronic devices combining the benefits of plasmonic sensing and the functionality of transparent electrodes.
Electrokinetic instability in microchannel ferrofluid/water co-flows
Authors: Song Le , Yu Liandong , Zhou Yilong , Antao Asher Reginald , Prabhakaran Rama Aravind , Xuan Xiangchun
Published: April 2017

Electrokinetic instability refers to unstable electric field-driven disturbance to fluid flows, which can be harnessed to promote mixing for various electrokinetic microfluidic applications. This work presents a combined numerical and experimental study of electrokinetic ferrofluid/water co-flows in microchannels of various depths. Instability waves are observed at the ferrofluid and water interface when the applied DC electric field is beyond a threshold value. They are generated by the electric body force that acts on the free charge induced by the mismatch of ferrofluid and water electric conductivities. A nonlinear depth-averaged numerical model is developed to understand and simulate the interfacial electrokinetic behaviors. It considers the top and bottom channel walls’ stabilizing effects on electrokinetic flow through the depth averaging of three-dimensional transport equations in a second-order asymptotic analysis. This model is found accurate to predict both the observed electrokinetic instability patterns and the measured threshold electric fields for ferrofluids of different concentrations in shallow microchannels.
Influenza C in Lancaster, UK, in the winter of 2014–2015
Authors: Atkinson Kate V. , Bishop Lisa A. , Rhodes Glenn , Salez Nicolas , McEwan Neil R. , Hegarty Matthew J. , Robey Julie , Harding Nicola , Wetherell Simon , Lauder Robert M. , Pickup Roger W. , Wilkinson Mark , Gatherer Derek
Published: April 2017

Influenza C is not included in the annual seasonal influenza vaccine, and has historically been regarded as a minor respiratory pathogen. However, recent work has highlighted its potential role as a cause of pneumonia in infants. We performed nasopharyngeal or nasal swabbing and/or serum sampling (n = 148) in Lancaster, UK, over the winter of 2014–2015. Using enzyme-linked immunosorbent assay (ELISA), we obtain seropositivity of 77%. By contrast, only 2 individuals, both asymptomatic adults, were influenza C-positive by polymerase chain reaction (PCR). Deep sequencing of nasopharyngeal samples produced partial sequences for 4 genome segments in one of these patients. Bayesian phylogenetic analysis demonstrated that the influenza C genome from this individual is evolutionarily distant to those sampled in recent years and represents a novel genome constellation, indicating that it may be a product of a decades-old reassortment event. Although we find no evidence that influenza C was a significant respiratory pathogen during the winter of 2014–2015 in Lancaster, we confirm previous observations of seropositivity in the majority of the population. (170 words).
CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies
Authors: Ma Jie , Li Huan , Hu Xiangnan , Yang Lu , Chen Qi , Hu Congli , Chen Zhihao , Tian Xiaoyan , Yang Yang , Luo Ying , Gan Run , Yang Junqing
Published: April 2017

Dipeptidyl peptidase IV (DPP-IV) inhibitor has been expected to be a new class of anti-diabetic agent. The present study was designed to characterize the pharmacological profiles of CMD-05, a novel DPP-IV inhibitor discovered in our laboratory, in vitro and in vivo. The IC50 of CMD-05 on DPP-IV inhibitory activity was approximately 12 nM while vildagliptin was 3.5 nM in vitro. In diabetes rat model established by high fat diet/low dose streptozotocin, CMD-05 inhibited DPP-IV activity, significantly improved glucose tolerance, increased GLP-1 and insulin levels in plasma. Long-term administration of CMD-05 decreased HbA1c and TG levels and improved the islet function without significantly effect on body weight. Furthermore, CMD-05 reduced INS-1 cell apoptosis and increased GLP-1 secretion in NCI-H716. After oral administration, CMD-05 reached peak concentration at 30 min with half-life of 288 minutes and the inhibitory rate of DPP-IV greater than 50% lasted for 15 h. In fasted normal rats, CMD-05 didn’t cause significant hypoglycemia. CMD-05 had a lower cytotoxicity than vildagliptin in vitro and its maximum tolerance dose in mice is beyond 2000 mg/kg. These results indicated that CMD-05 has similar activity with vildagliptin in vivo and has a much longer half-life and lower cytotoxicity than vildagliptin.
Fabrication of large-area polymer microfilter membranes and their application for particle and cell enrichment
Authors: Hernández-Castro Javier Alejandro , Li Kebin , Meunier Anne , Juncker David , Veres Teodor
Published: April 2017

A vacuum assisted UV micro-molding (VAUM) process is proposed for the fabrication of freestanding and defect-free polymer membranes based on a UV-curable methacrylate polymer (MD 700).
Automatic concentration and reformulation of PET tracers via microfluidic membrane distillation
Authors: Chao Philip H. , Collins Jeffery , Argus Joseph P. , Tseng Wei-Yu , Lee Jason T. , Michael van Dam R.
Published: April 2017

We present an automated microfluidic platform relying on sweeping gas membrane distillation for rapid concentration and formulation of PET tracers for preclinical imaging applications.
Recent progress in the application of nanomaterials in the analysis of emerging chemical contaminants
Authors: Huang Xiu , Liu Qian , Yao Shouzhuo , Jiang Guibin
Published: April 2017

We review the recent applications of nanomaterials in the analysis of emerging chemical contaminants (ECCs), which are defined as newly identified chemical contaminants with no regulatory status.
An internal magnetic field strategy to reuse pulverized active materials for high performance: a magnetic three-dimensional ordered macroporous TiO2/CoPt/α-Fe2O3nanocomposite anode
Authors: Tang Yiping , Hong Liang , Li Jiquan , Hou Guangya , Cao Huazhen , Wu Liankui , Zheng Guoqu , Wu Qingliu
Published: April 2017

An internally magnetic field was established by CoPt for attracting pulverized ferromagnetic α-Fe2O3. Combining with the unique porous structure for accommodating large volume change, the TiO2/CoPt/α-Fe2O3(3DOMTCF) anode demonstrated high reversible capacity and extremely promising cyclic stability.
Regioisomerically pure multiaryl coronene derivatives: highly efficient synthesis via bay-extended perylene tetrabutylester
Authors: Mao Wenxuan , Zhang Junji , Li Xin , Li Chen , Tian He
Published: April 2017

Regioisomerically pure multiaryl coronene bisimides (CBIs) are synthesized via a perylene tetraester precursor and IBr-mediated annelation with high yields.
Obtaining effective rate coefficients to describe the decomposition kinetics of the corannulene oxyradical at high temperatures
Authors: Wang Hongmiao , You Xiaoqing , Blitz Mark A. , Pilling Michael J. , Robertson Struan H.
Published: April 2017

This work analyzes the effect of overlapping eigenvalues on the high-temperature kinetics of a large oxyradical based on master equation solutions.
Structure and dynamics of [NH2(CH3)2]3Sb2Cl9 by means of 1H NMR relaxometry – quadrupolar relaxation enhancement effects
Authors: Florek-Wojciechowska M. , Jakubas R. , Kruk D.
Published: April 2017

NMR quadrupolar relaxation enhancement gives access to the structure and dynamics of solids.
Constructing a three-dimensionally ordered macroporous LaCrOδ composite oxide via cerium substitution for enhanced soot abatement
Authors: Feng Nengjie , Chen Chong , Meng Jie , Liu Geng , Fang Fan , Ding Jing , Wang Lei , Wan Hui , Guan Guofeng
Published: April 2017

The addition of Ce into Cr-based perovskite restrained the growth of the crystal size and delayed the transformation from LaCrO4 to LaCrO3, and thus, the 3DOM structure was maintained even after calcination at 800 °C.
A new method of Sn purification and isotopic determination with a double-spike technique for geological and cosmochemical samples
Authors: Wang Xueying , Fitoussi Caroline , Bourdon Bernard , Amet Quentin
Published: April 2017

This study aimed at developing a new methodology for measuring tin isotope compositions in geological and cosmochemical materials.
An intravascular bioartificial pancreas device (iBAP) with silicon nanopore membranes (SNM) for islet encapsulation under convective mass transport
Authors: Song Shang , Blaha Charles , Moses Willieford , Park Jaehyun , Wright Nathan , Groszek Joey , Fissell William , Vartanian Shant , Posselt Andrew M. , Roy Shuvo
Published: April 2017

The SNM-based iBAP demonstrates viability and functionality at clinically relevant cell density and hemocompatibility under convective transport in a porcine model.
Imidazoles as potential anticancer agents
Authors: Ali Imran , Lone Mohammad Nadeem , Aboul-Enein Haasan Y.
Published: April 2017

Cancer is a black spot on the face of humanity in this era of science and technology.
Pd nanocube decoration onto flexible nanofibrous mats of core–shell polymer–ZnO nanofibers for visible light photocatalysis
Authors: Arslan Osman , Topuz Fuat , Eren Hamit , Biyikli Necmi , Uyar Tamer
Published: April 2017

Plasmonic enhancement for electron–hole separation efficiency and visible light photocatalysis was achieved by Pd nanocube decoration on a ZnO nanolayer coated onto electrospun polymeric (polyacrylonitrile (PAN)) nanofibers.
Mechanistic insights into the selective cyclization of indolines with alkynes and alkenes to produce six- and seven-membered 1,7-fused indolines via Rh(iii) catalysis: a theoretical study
Authors: Han Lingli , Zhang Xinyu , Wang Xingdong , Zhao Fengyue , Liu Shaojing , Liu Tao
Published: April 2017

The origin of different partners for the coupling reaction determining the different products was rationalized.
A carbonyl reductase from Candida parapsilosis ATCC 7330: substrate selectivity and enantiospecificity
Authors: Sudhakara Sneha , Chadha Anju
Published: April 2017

A purified carbonyl reductase (SRED) asymmetrically reduces ketones and α-ketoesters to (S)-alcohols with a potential application in the synthesis of industrially important chiral molecules.
Fabrication of TiO2 coated porous CoMn2O4 submicrospheres for advanced lithium-ion anodes
Authors: Zhou Jun , Cheng Shuang , Jiang Yu , Zheng Fenghua , Ou Xing , Yang Lufeng , Wang Mengkun , Yao Minghai , Liu Meilin
Published: April 2017

Uniform CoMn2O4@TiO2 porous nanospheres have been developed with excellent electrochemical performance when evaluated as anode materials for lithium ion batteries.
Generation of radical species in CVD grown pristine and N-doped solid carbon spheres using H2 and Ar as carrier gases
Authors: Mutuma Bridget K. , Matsoso Boitumelo J. , Ranganathan Kamalakannan , Keartland Jonathan M. , Wamwangi Daniel , Coville Neil J.
Published: April 2017

A mechanism showing the role of carrier gas on the N-configuration of the post-N-doped CSs synthesized in the presence of (a) H2 and (b) Ar, respectively.
Ladder-type oligo(p-phenylene)s with D–π–A architectures: design, synthesis, optical gain properties, and stabilized amplified spontaneous emission
Authors: Fang Mei , Huang Jinjin , Chang Si-Ju , Jiang Yi , Lai Wen-Yong , Huang Wei
Published: April 2017

A novel family of D–π–A ladder-type oligo(p-phenylene)s with promising optoelectronic properties have been explored as gain media for organic lasers.
Tspan2: a tetraspanin protein involved in oligodendrogenesis and cancer metastasis
Authors: Yaseen Ibrahim H. , Monk Peter N. , Partridge Lynda J.
Published: April 2017

Tetraspanin 2 (Tspan2) is one of the less well-characterised members of the tetraspanin superfamily, and its precise function in different human tissue types remains to be explored. Initial studies have highlighted its possible association in neuroinflammation and carcinogenesis. In the central nervous system, Tspan2 may contribute to the early stages of the oligodendrocyte differentiation into myelin-forming glia. Furthermore, in human lung cancer, Tspan2 could be involved in the progression of the tumour metastasis by modulating cancer cell motility and invasion functions. In this review, we discuss the available evidence for the potential role of Tspan2 and introduce possible strategies for disease targeting.
Mitochondrial DNA replication: a PrimPol perspective
Authors: Bailey Laura J. , Doherty Aidan J.
Published: April 2017

PrimPol, (primase–polymerase), the most recently identified eukaryotic polymerase, has roles in both nuclear and mitochondrial DNA maintenance. PrimPol is capable of acting as a DNA polymerase, with the ability to extend primers and also bypass a variety of oxidative and photolesions. In addition, PrimPol also functions as a primase, catalysing the preferential formation of DNA primers in a zinc finger-dependent manner. Although PrimPol's catalytic activities have been uncovered in vitro, we still know little about how and why it is targeted to the mitochondrion and what its key roles are in the maintenance of this multicopy DNA molecule. Unlike nuclear DNA, the mammalian mitochondrial genome is circular and the organelle has many unique proteins essential for its maintenance, presenting a differing environment within which PrimPol must function. Here, we discuss what is currently known about the mechanisms of DNA replication in the mitochondrion, the proteins that carry out these processes and how PrimPol is likely to be involved in assisting this vital cellular process.
O-GlcNAc cycling and the regulation of nucleocytoplasmic dynamics
Authors: Eustice Moriah , Bond Michelle R. , Hanover John A.
Published: April 2017

The dynamic carbohydrate post-translational modification (PTM) O-linked β-N-acetyl glucosamine (O-GlcNAc) is found on thousands of proteins throughout the nucleus and cytoplasm, and rivals phosphorylation in terms of the number of substrates and pathways influenced. O-GlcNAc is highly conserved and essential in most organisms, with disruption of O-GlcNAc cycling linked to diseases ranging from cancer to neurodegeneration. Nuclear pore proteins were the first identified O-GlcNAc-modified substrates, generating intense and ongoing interest in understanding the role of O-GlcNAc cycling in nuclear pore complex structure and function. Recent advances in detecting and altering O-GlcNAcylation levels have provided insights into many mechanisms by which O-GlcNAcylation influences the nucleocytoplasmic localization and stability of protein targets. The emerging view is that the multifunctional enzymes of O-GlcNAc cycling are critical nutrient-sensing components of a complex network of signaling cascades involving multiple PTMs. Furthermore, O-GlcNAc plays a role in maintaining the structural integrity of the nuclear pore and regulating its function as the gatekeeper of nucleocytoplasmic trafficking.
When mRNA translation meets decay
Authors: Bicknell Alicia A. , Ricci Emiliano P.
Published: April 2017

Messenger RNA (mRNA) translation and mRNA degradation are important determinants of protein output, and they are interconnected. Previously, it was thought that translation of an mRNA, as a rule, prevents its degradation. mRNA surveillance mechanisms, which degrade mRNAs as a consequence of their translation, were considered to be exceptions to this rule. Recently, however, it has become clear that many mRNAs are degraded co-translationally, and it has emerged that codon choice, by influencing the rate of ribosome elongation, affects the rate of mRNA decay. In this review, we discuss the links between translation and mRNA stability, with an emphasis on emerging data suggesting that codon optimality may regulate mRNA degradation.
Antagonistic roles for STYX pseudophosphatases in neurite outgrowth
Authors: Dahal Arya , Hinton Shantá D.
Published: April 2017

Mitogen-activated protein kinases (MAPKs) are essential players in important neuronal signaling pathways including neuronal development, plasticity, survival, learning, and memory. The inactivation of MAPKs is tightly controlled by MAPK phosphatases (MKPs), which also are important regulators of these neuronal processes. Considering that MAPKs and MKPs are major players in neuronal signaling, it follows that their misregulation is pivotal in neurodegenerative diseases such as Alzheimer's, Huntington's, Parkinson's, and amyotrophic lateral sclerosis. In contrast, the actions of their noncatalytic homologs, or pseudoenzymes, have received minimal attention as important regulators in neuronal signaling pathways and relevant diseases. There is compelling evidence, however, that pseudophosphatases, such as STYX (phospho-serine–threonine/tyrosine-binding protein) and MAPK-STYX (MK-STYX), are integral signaling molecules in regulating pathways involved in neuronal developmental processes such as neurite outgrowth. Here, we discuss how the dynamics of MK-STYX in the stress response pathway imply that this unique member of the MKP subfamily has the potential to have a major role in neuronal signaling. We further compare the actions of STYX in preventing neurite-like outgrowths and MK-STYX in inducing neurite outgrowths. The roles of these pseudophosphatases in neurite outgrowth highlight their emergence as important candidates to investigate in neurodegenerative disorders and diseases.
Small regulatory bacterial RNAs regulating the envelope stress response
Authors: Klein Gracjana , Raina Satish
Published: April 2017

Most bacteria encode a large repertoire of RNA-based regulatory mechanisms. Recent discoveries have revealed that the expression of many genes is controlled by a plethora of base-pairing noncoding small regulatory RNAs (sRNAs), regulatory RNA-binding proteins and RNA-degrading enzymes. Some of these RNA-based regulated processes respond to stress conditions and are involved in the maintenance of cellular homeostasis. They achieve it by either direct posttranscriptional repression of several mRNAs, including blocking access to ribosome and/or directing them to RNA degradation when the synthesis of their cognate proteins is unwanted, or by enhanced translation of some key stress-regulated transcriptional factors. Noncoding RNAs that regulate the gene expression by binding to regulatory proteins/transcriptional factors often act negatively by sequestration, preventing target recognition. Expression of many sRNAs is positively regulated by stress-responsive sigma factors like RpoE and RpoS, and two-component systems like PhoP/Q, Cpx and Rcs. Some of these regulatory RNAs act via a feedback mechanism on their own regulators, which is best reflected by recent discoveries, concerning the regulation of cell membrane composition by sRNAs in Escherichia coli and Salmonella, which are highlighted here.
Genomes, structural biology and drug discovery: combating the impacts of mutations in genetic disease and antibiotic resistance
Authors: Pandurangan Arun Prasad , Ascher David B. , Thomas Sherine E. , Blundell Tom L.
Published: April 2017

For over four decades structural biology has been used to understand the mechanisms of disease, and structure-guided approaches have demonstrated clearly that they can contribute to many aspects of early drug discovery, both computationally and experimentally. Structure can also inform our understanding of impacts of mutations in human genetic diseases and drug resistance in cancers and infectious diseases. We discuss the ways that structural insights might be useful in both repurposing off-licence drugs and guide the design of new molecules that might be less susceptible to drug resistance in the future.
DJ-1 overexpression restores ischaemic post-conditioning-mediated cardioprotection in diabetic rats: role of autophagy
Authors: Zhou Bin , Lei Shaoqing , Xue Rui , Leng Yan , Xia Zhengyuan , Xia Zhong-Yuan
Published: April 2017

IPO (ischaemic post-conditioning) is a promising method of alleviating myocardial IR (ischaemia-reperfusion) injury; however, IPO-mediated cardioprotection is lost in diabetic hearts via mechanisms that remain largely unclear. We hypothesized that decreased cardiac expression of DJ-1, a positive modulator of autophagy, compromises the effectiveness of IPO-induced cardioprotection in diabetic rats. Diabetic rats subjected to myocardial IR (30 min of coronary artery occlusion followed by 120 min of reperfusion) exhibited more severe myocardial injury, less cardiac autophagy, lower DJ-1 expression and AMPK (adenosine monophosphate-activated protein kinase)/mTOR (mammalian target of rapamycin) pathway activity than non-diabetic rats. IPO significantly attenuated myocardial injury and up-regulated cardiac DJ-1 expression, AMPK/mTOR activity and autophagy in non-diabetic rats but not in diabetic rats. AAV9 (adeno-associated virus 9)-mediated cardiac DJ-1 overexpression as well as pretreatment with the autophagy inducer rapamycin restored IPO-induced cardioprotection in diabetic rats, an effect accompanied by AMPK/mTOR activation and autophagy up-regulation. Combining HPO (hypoxic post-conditioning) with DJ-1 overexpression markedly attenuated HR (hypoxia-reoxygenation) injury in H9c2 cells with high glucose (HG, 30 mM) exposure, accompanied by AMPK/mTOR signalling activation and autophagy up-regulation. The DJ-1 overexpression-mediated preservation of HPO-induced cardioprotection was completely inhibited by the AMPK inhibitor compound C (CC) and the autophagy inhibitor 3-MA (3-methyladenine). Thus, decreased cardiac DJ-1 expression, which results in impaired AMPK/mTOR signalling and decreased autophagy, could be a major mechanism underlying the loss of IPO-induced cardioprotection in diabetes.
Multi‐megahertz quasi‐square‐wave flyback converter using eGaN FETs
Authors: Zhang Zhemin , Ngo Khai D.T.
Published: April 2017

As the fast development of the better figure‐of‐merits gallium nitride (GaN) devices, the switching frequency of isolated flyback converter could be pushed to multi‐megahertz to evaluate the improvement of the power density. A constant frequency zero‐voltage switching (ZVS) quasi‐square‐wave (QSW) mode is applied to the 30 W flyback in telecommunication application, and a charge conservation method including capacitor non‐linearity is proposed to design the coupled inductors for soft switching over entire input and load range. Leakage inductance, eddy losses and parasitic capacitance were quantified and optimised in the design of high‐frequency PCB windings. A 98% coupling planar‐coupled inductors by utilising nickel‐zinc ferrite material with EI‐shaped core were designed by finite‐element simulation. To validate all the analysis, a 30 W flyback converter was fabricated and measured with peak efficiency of 90.6% operating at 5 MHz. The coupled inductors consumed almost 2.5% of the output power with the area of 180 mm2 occupied 30% of the power stage.