bluuebunny/crossref_metadata_2025 huggingface dataset:
Aldehyde dehydrogenase 1a3 defines a subset of failing pancreatic β cells in diabetic mice
Authors: Kim-Muller Ja Young , Fan Jason , Kim Young Jung R. , Lee Seung-Ah , Ishida Emi , Blaner William S. , Accili Domenico
Published: August 2016

Insulin-producing β cells become dedifferentiated during diabetes progression. An impaired ability to select substrates for oxidative phosphorylation, or metabolic inflexibility, initiates progression from β-cell dysfunction to β-cell dedifferentiation. The identification of pathways involved in dedifferentiation may provide clues to its reversal. Here we isolate and functionally characterize failing β cells from various experimental models of diabetes and report a striking enrichment in the expression of aldehyde dehydrogenase 1 isoform A3 (ALDH+) as β cells become dedifferentiated. Flow-sorted ALDH+ islet cells demonstrate impaired glucose-induced insulin secretion, are depleted of Foxo1 and MafA, and include a Neurogenin3-positive subset. RNA sequencing analysis demonstrates that ALDH+ cells are characterized by: (i) impaired oxidative phosphorylation and mitochondrial complex I, IV and V; (ii) activated RICTOR; and (iii) progenitor cell markers. We propose that impaired mitochondrial function marks the progression from metabolic inflexibility to dedifferentiation in the natural history of β-cell failure.
Epoxide-functionalization of polyethyleneimine for synthesis of stable carbon dioxide adsorbent in temperature swing adsorption
Authors: Choi Woosung , Min Kyungmin , Kim Chaehoon , Ko Young Soo , Jeon Jae Wan , Seo Hwimin , Park Yong-Ki , Choi Minkee
Published: August 2016

Amine-containing adsorbents have been extensively investigated for post-combustion carbon dioxide capture due to their ability to chemisorb low-concentration carbon dioxide from a wet flue gas. However, earlier studies have focused primarily on the carbon dioxide uptake of adsorbents, and have not demonstrated effective adsorbent regeneration and long-term stability under such conditions. Here, we report the versatile and scalable synthesis of a functionalized-polyethyleneimine (PEI)/silica adsorbent which simultaneously exhibits a large working capacity (2.2 mmol g−1) and long-term stability in a practical temperature swing adsorption process (regeneration under 100% carbon dioxide at 120 °C), enabling the separation of concentrated carbon dioxide. We demonstrate that the functionalization of PEI with 1,2-epoxybutane reduces the heat of adsorption and facilitates carbon dioxide desorption (>99%) during regeneration compared with unmodified PEI (76%). Moreover, the functionalization significantly improves long-term adsorbent stability over repeated temperature swing adsorption cycles due to the suppression of urea formation and oxidative amine degradation.
Reprogramming metabolic pathways in vivo with CRISPR/Cas9 genome editing to treat hereditary tyrosinaemia
Authors: Pankowicz Francis P. , Barzi Mercedes , Legras Xavier , Hubert Leroy , Mi Tian , Tomolonis Julie A. , Ravishankar Milan , Sun Qin , Yang Diane , Borowiak Malgorzata , Sumazin Pavel , Elsea Sarah H. , Bissig-Choisat Beatrice , Bissig Karl-Dimiter
Published: August 2016

Many metabolic liver disorders are refractory to drug therapy and require orthotopic liver transplantation. Here we demonstrate a new strategy, which we call metabolic pathway reprogramming, to treat hereditary tyrosinaemia type I in mice; rather than edit the disease-causing gene, we delete a gene in a disease-associated pathway to render the phenotype benign. Using CRISPR/Cas9 in vivo, we convert hepatocytes from tyrosinaemia type I into the benign tyrosinaemia type III by deleting Hpd (hydroxyphenylpyruvate dioxigenase). Edited hepatocytes (Fah−/−/Hpd−/−) display a growth advantage over non-edited hepatocytes (Fah−/−/Hpd+/+) and, in some mice, almost completely replace them within 8 weeks. Hpd excision successfully reroutes tyrosine catabolism, leaving treated mice healthy and asymptomatic. Metabolic pathway reprogramming sidesteps potential difficulties associated with editing a critical disease-causing gene and can be explored as an option for treating other diseases.
Broadband giant-refractive-index material based on mesoscopic space-filling curves
Authors: Chang Taeyong , Kim Jong Uk , Kang Seung Kyu , Kim Hyowook , Kim Do Kyung , Lee Yong-Hee , Shin Jonghwa
Published: August 2016

The refractive index is the fundamental property of all optical materials and dictates Snell’s law, propagation speed, wavelength, diffraction, energy density, absorption and emission of light in materials. Experimentally realized broadband refractive indices remain <40, even with intricately designed artificial media. Herein, we demonstrate a measured index >1,800 resulting from a mesoscopic crystal with a dielectric constant greater than three million. This gigantic enhancement effect originates from the space-filling curve concept from mathematics. The principle is inherently very broad band, the enhancement being nearly constant from zero up to the frequency of interest. This broadband giant-refractive-index medium promises not only enhanced resolution in imaging and raised fundamental absorption limits in solar energy devices, but also compact, power-efficient components for optical communication and increased performance in many other applications.
Rapid evolutionary response to a transmissible cancer in Tasmanian devils
Authors: Epstein Brendan , Jones Menna , Hamede Rodrigo , Hendricks Sarah , McCallum Hamish , Murchison Elizabeth P. , Schönfeld Barbara , Wiench Cody , Hohenlohe Paul , Storfer Andrew
Published: August 2016

Although cancer rarely acts as an infectious disease, a recently emerged transmissible cancer in Tasmanian devils (Sarcophilus harrisii) is virtually 100% fatal. Devil facial tumour disease (DFTD) has swept across nearly the entire species’ range, resulting in localized declines exceeding 90% and an overall species decline of more than 80% in less than 20 years. Despite epidemiological models that predict extinction, populations in long-diseased sites persist. Here we report rare genomic evidence of a rapid, parallel evolutionary response to strong selection imposed by a wildlife disease. We identify two genomic regions that contain genes related to immune function or cancer risk in humans that exhibit concordant signatures of selection across three populations. DFTD spreads between hosts by suppressing and evading the immune system, and our results suggest that hosts are evolving immune-modulated resistance that could aid in species persistence in the face of this devastating disease.
Photon upconversion with directed emission
Authors: Börjesson K. , Rudquist P. , Gray V. , Moth-Poulsen K.
Published: August 2016

Photon upconversion has the potential to increase the efficiency of single bandgap solar cells beyond the Shockley Queisser limit. Efficient light management is an important point in this context. Here we demonstrate that the direction of upconverted emission can be controlled in a reversible way, by embedding anthracene derivatives together with palladium porphyrin in a liquid crystalline matrix. The system is employed in a triplet-triplet annihilation photon upconversion scheme demonstrating controlled switching of directional anti Stokes emission. Using this approach an emission ratio of 0.37 between the axial and longitudinal emission directions and a directivity of 1.52 is achieved, reasonably close to the theoretical maximal value of 2 obtained from a perfectly oriented sample. The system can be switched for multiple cycles without any visible degradation and the speed of switching is only limited by the intrinsic rate of alignment of the liquid crystalline matrix.
Tectonic collision and uplift of Wallacea triggered the global songbird radiation
Authors: Moyle Robert G. , Oliveros Carl H. , Andersen Michael J. , Hosner Peter A. , Benz Brett W. , Manthey Joseph D. , Travers Scott L. , Brown Rafe M. , Faircloth Brant C.
Published: August 2016

Songbirds (oscine passerines) are the most species-rich and cosmopolitan bird group, comprising almost half of global avian diversity. Songbirds originated in Australia, but the evolutionary trajectory from a single species in an isolated continent to worldwide proliferation is poorly understood. Here, we combine the first comprehensive genome-scale DNA sequence data set for songbirds, fossil-based time calibrations, and geologically informed biogeographic reconstructions to provide a well-supported evolutionary hypothesis for the group. We show that songbird diversification began in the Oligocene, but accelerated in the early Miocene, at approximately half the age of most previous estimates. This burst of diversification occurred coincident with extensive island formation in Wallacea, which provided the first dispersal corridor out of Australia, and resulted in independent waves of songbird expansion through Asia to the rest of the globe. Our results reconcile songbird evolution with Earth history and link a major radiation of terrestrial biodiversity to early diversification within an isolated Australian continent.
In Situ and Ex Situ TEM Study of Lithiation Behaviours of Porous Silicon Nanostructures
Authors: Shen Chenfei , Ge Mingyuan , Luo Langli , Fang Xin , Liu Yihang , Zhang Anyi , Rong Jiepeng , Wang Chongmin , Zhou Chongwu
Published: August 2016

In this work, we study the lithiation behaviours of both porous silicon (Si) nanoparticles and porous Si nanowires by in situ and ex situ transmission electron microscopy (TEM) and compare them with solid Si nanoparticles and nanowires. The in situ TEM observation reveals that the critical fracture diameter of porous Si particles reaches up to 1.52 μm, which is much larger than the previously reported 150 nm for crystalline Si nanoparticles and 870 nm for amorphous Si nanoparticles. After full lithiation, solid Si nanoparticles and nanowires transform to crystalline Li15Si4 phase while porous Si nanoparticles and nanowires transform to amorphous LixSi phase, which is due to the effect of domain size on the stability of Li15Si4 as revealed by the first-principle molecular dynamic simulation. Ex situ TEM characterization is conducted to further investigate the structural evolution of porous and solid Si nanoparticles during the cycling process, which confirms that the porous Si nanoparticles exhibit better capability to suppress pore evolution than solid Si nanoparticles. The investigation of structural evolution and phase transition of porous Si nanoparticles and nanowires during the lithiation process reveal that they are more desirable as lithium-ion battery anode materials than solid Si nanoparticles and nanowires.
The Association between Ideal Cardiovascular Health Metrics and Extracranial Carotid Artery Stenosis in a Northern Chinese Population: A Cross-Sectional Study
Authors: Hao Zhiru , Zhang Yong , Li Yongming , Zhao Jinbo , Zhou Yong , Qiu Jing , Zhao Ruiping , Hu Jiang
Published: August 2016

Past epidemiologic studies have indicated that the ideal cardiovascular health (CVH) metrics are associated with a lower risk of cardiovascular diseases (CVDs) and stroke. Carotid artery stenosis (CAS) causes approximately 10% of ischemic strokes. The association between ideal CVH and extracranial CAS has not yet been assessed. In the current study, extracranial CAS was assessed by carotid duplex ultrasonography. Logistic regression was used to analyze the association between ideal CVH metrics and extracranial CAS. A total of 3297 participants (52.2% women) aged 40 years and older were selected from the Jidong community in China. After adjusting for sex, age and other potential confounds, the odds ratios (95% confidence intervals) for extracranial CAS were 0.57 (0.39–0.84), 0.46 (0.26–0.80) and 0.29 (0.15–0.54) and for those quartiles, quartile 2 (9–10), quartile 3 (11) and quartile 4 (12–14), respectively, compared with quartile 1 (≤8). This negative correlation was particularly evident in women and the elderly (≥60 years). This cross-sectional study showed a negative correlation between the ideal CVH metrics and the prevalence of extracranial CAS in northern Chinese adults.
Response of aboveground biomass and diversity to nitrogen addition – a five-year experiment in semi-arid grassland of Inner Mongolia, China
Authors: He Kejian , Qi Yu , Huang Yongmei , Chen Huiying , Sheng Zhilu , Xu Xia , Duan Lei
Published: August 2016

Understanding the response of the plant community to increasing nitrogen (N) deposition is helpful for improving pasture management in semi-arid areas. We implemented a 5-year N addition experiment in aStipa kryloviisteppe of Inner Mongolia, northern China. The aboveground biomass (AGB) and species richness were measured annually. Along with the N addition levels, the species richness declined significantly, and the species composition changed noticeably. However, the total AGB did not exhibit a noticeable increase. We found that compensatory effects of the AGB occurred not only between the grasses and the forbs but also among Gramineae species. The plant responses to N addition, from the community to species level, lessened in dry years compared to wet or normal years. The N addition intensified the reduction of community productivity in dry years. Our study indicated that the compensatory effects of the AGB among the species sustained the stability of grassland productivity. However, biodiversity loss resulting from increasing N deposition might lead the semi-arid grassland ecosystem to be unsustainable, especially in dry years.
Suppression of c-Kit signaling induces adult neurogenesis in the mouse intestine after myenteric plexus ablation with benzalkonium chloride
Authors: Tamada Hiromi , Kiyama Hiroshi
Published: August 2016

Adult neurogenesis rarely occurs in the enteric nervous system (ENS). In this study, we demonstrated that, after intestinal myenteric plexus (MP) ablation with benzalkonium chloride (BAC), adult neurogenesis in the ENS was significantly induced in c-kit loss-of-function mutant mice (W/Wv). Almost all neurons and fibers in the MP disappeared after BAC treatment. However, 1 week after ablation, substantial penetration of nerve fibers from the non-damaged area was observed in the MP, longitudinal muscle and subserosal layers in both wildtype and W/Wv mice. Two weeks after BAC treatment, in addition to the penetrating fibers, a substantial number of ectopic neurons appeared in the subserosal and longitudinal muscle layers of W/Wv mice, whereas only a few ectopic neurons appeared in wildtype mice. Such ectopic neurons expressed either excitatory or inhibitory intrinsic motor neuron markers and formed ganglion-like structures, including glial cells, synaptic vesicles and basal lamina. Furthermore, oral administration of imatinib, an inhibitor of c-Kit and an anticancer agent for gastrointestinal stromal tumors, markedly induced appearance of ectopic neurons after BAC treatment, even in wildtype mice. These results suggest that adult neurogenesis in the ENS is negatively regulated by c-Kit signaling in vivo.
The critical role of phase difference in gamma oscillation within the temporoparietal network for binding visual working memory
Authors: Tseng Philip , Chang Yu-Ting , Chang Chi-Fu , Liang Wei-Kuang , Juan Chi-Hung
Published: August 2016

How does the brain enable us to remember two or more object representations in visual working memory (VWM) without confusing them? This “gluing” process, or feature binding, refers to the ability to join certain features together while keeping them segregated from others. Recent neuroimaging research has reported higher BOLD response in the left temporal and parietal cortex during a binding-VWM task. However, less is known about how the two regions work in synchrony to support such process. In this study, we applied transcranial alternating current stimulation (tACS) over the left temporal and parietal cortex in gamma and theta frequency, with a phase difference of either 0° (in-phase) or 180° (anti-phase) to account for the different ways through which neural synchronization may occur. We found no facilitatory or inhibitory effect from sham, theta and in-phase gamma stimulation. Importantly, there was an enhancement effect from anti-phase gamma tACS that was binding-specific and such effect was only apparent in low-performing individuals who had room for improvement. Together, these results demonstrate that binding-VWM is supported by a temporally-precise oscillatory mechanism within the gamma frequency range and that the advantageous 180°-apart phase relationship also implies a possible temporal driver-to-receiver time-lag between the temporal and parietal cortex.
Design a New Strategy Based on Nanoparticle-Enhanced Chemiluminescence Sensor Array for Biothiols Discrimination
Authors: Shahrajabian Maryam , Hormozi-Nezhad M. Reza
Published: August 2016

Array-based sensor is an interesting approach that suggests an alternative to expensive analytical methods. In this work, we introduce a novel, simple and sensitive nanoparticle-based chemiluminescence (CL) sensor array for discrimination of biothiols (e.g., cysteine, glutathione and glutathione disulfide). The proposed CL sensor array is based on the CL efficiencies of four types of enhanced nanoparticle-based CL systems. The intensity of CL was altered to varying degrees upon interaction with biothiols, producing unique CL response patterns. These distinct CL response patterns were collected as “fingerprints” and were then identified through chemometric methods, including linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA). The developed array was able to successfully differentiate between cysteine, glutathione and glutathione disulfide in a wide concentration range. Moreover, it was applied to distinguish among the above analytes in human plasma.
Effect of silver on the phase transition and wettability of titanium oxide films
Authors: Mosquera Adolfo A. , Albella Jose M. , Navarro Violeta , Bhattacharyya Debabrata , Endrino Jose L.
Published: August 2016

The effect of silver on the phase transition and microstructure of titanium oxide films grown by pulsed cathodic arc had been investigated by XRD, SEM and Raman spectroscopy. Following successive thermal annealing up to 1000 °C, microstructural analysis of annealed Ag-TiO2 films reveals that the incorporation of Ag nanoparticles strongly affects the transition temperature from the initial metastable amorphous phase to anatase and stable rutile phase. An increase of silver content into TiO2 matrix inhibits the amorphous to anatase phase transition, raising its temperature boundary and, simultaneously reduces the transition temperature to promote rutile structure at lower value of 600 °C. The results are interpreted in terms of the steric effects produced by agglomeration of Ag atoms into larger clusters following annealing which hinders diffusion of Ti and O ions for anatase formation and constrains the volume available for the anatase lattice, thus disrupting its structure to form rutile phase. The effect of silver on the optical and wetting properties of TiO2 was evaluated to demonstrate its improved photocatalytic performance.
Role of IL-17 Pathways in Immune Privilege: A RNA Deep Sequencing Analysis of the Mice Testis Exposure to Fluoride
Authors: Huo Meijun , Han Haijun , Sun Zilong , Lu Zhaojing , Yao Xinglei , Wang Shaolin , Wang Jundong
Published: August 2016

We sequenced RNA transcripts from the testicles of healthy male mice, divided into a control group with distilled water and two experimental groups with 50 and 100 mg/l NaF in drinking water for 56 days. Bowtie/Tophat were used to align 50-bp paired-end reads into transcripts, Cufflinks to measure the relative abundance of each transcript and IPA to analyze RNA-Sequencing data. In the 100 mg/l NaF-treated group, four pathways related to IL-17, TGF-β and other cellular growth factor pathways were overexpressed. The mRNA expression of IL-17RA, IL-17RC, MAP2K1, MAP2K2, MAP2K3 and MAPKAPK2, monitored by qRT-PCR, increased remarkably in the 100 mg/L NaF group and coincided with the result of RNA-Sequencing. Fluoride exposure could disrupt spermatogenesis and testicles in male mice by influencing many signaling pathways and genes, which work on the immune signal transduction and cellular metabolism. The high expression of the IL-17 signal pathway was a response to the invasion of the testicular immune system due to extracellular fluoride. The PI3-kinase/AKT, MAPKs and the cytokines in TGF-β family were contributed to control the IL-17 pathway activation and maintain the immune privilege and spermatogenesis. All the findings provided new ideas for further molecular researches of fluorosis on the reproduction and immune response mechanism.
Uncovering representations of sleep-associated hippocampal ensemble spike activity
Authors: Chen Zhe , Grosmark Andres D. , Penagos Hector , Wilson Matthew A.
Published: August 2016

Pyramidal neurons in the rodent hippocampus exhibit spatial tuning during spatial navigation and they are reactivated in specific temporal order during sharp-wave ripples observed in quiet wakefulness or slow wave sleep. However, analyzing representations of sleep-associated hippocampal ensemble spike activity remains a great challenge. In contrast to wake, during sleep there is a complete absence of animal behavior and the ensemble spike activity is sparse (low occurrence) and fragmental in time. To examine important issues encountered in sleep data analysis, we constructed synthetic sleep-like hippocampal spike data (short epochs, sparse and sporadic firing, compressed timescale) for detailed investigations. Based upon two Bayesian population-decoding methods (one receptive field-based and the other not), we systematically investigated their representation power and detection reliability. Notably, the receptive-field-free decoding method was found to be well-tuned for hippocampal ensemble spike data in slow wave sleep (SWS), even in the absence of prior behavioral measure or ground truth. Our results showed that in addition to the sample length, bin size and firing rate, number of active hippocampal pyramidal neurons are critical for reliable representation of the space as well as for detection of spatiotemporal reactivated patterns in SWS or quiet wakefulness.
Spiro[pyrrolidine-3, 3´-oxindole] as potent anti-breast cancer compounds: Their design, synthesis, biological evaluation and cellular target identification
Authors: Hati Santanu , Tripathy Sayantan , Dutta Pratip Kumar , Agarwal Rahul , Srinivasan Ramprasad , Singh Ashutosh , Singh Shailja , Sen Subhabrata
Published: August 2016

The spiro[pyrrolidine-3, 3´-oxindole] moiety is present as a core in number of alkaloids with substantial biological activities. Here in we report design and synthesis of a library of compounds bearing spiro[pyrrolidine-3, 3´-oxindole] motifs that demonstrated exceptional inhibitory activity against the proliferation of MCF-7 breast cancer cells. The synthesis involved a one pot Pictet Spengler-Oxidative ring contraction of tryptamine to the desired scaffolds and occurred in 1:1 THF and water with catalytic trifluoroacetic acid and stoichiometric N-bromosuccinimide as an oxidant. Phenotypic profiling indicated that these molecules induce apoptotic cell death in MCF-7 cells. Target deconvolution with most potent compound 5l from the library, using chemical proteomics indicated histone deacetylase 2 (HDAC2) and prohibitin 2 as the potential cellular binding partners. Molecular docking of 5l with HDAC2 provided insights pertinent to putative binding interactions.
Identification of microRNA-regulated pathways using an integration of microRNA-mRNA microarray and bioinformatics analysis in CD34+ cells of myelodysplastic syndromes
Authors: Xu Feng , Zhu Yang , He Qi , Wu Ling-Yun , Zhang Zheng , Shi Wen-Hui , Liu Li , Chang Chun-Kang , Li Xiao
Published: August 2016

The effect of microRNA (miRNA) and targeted mRNA on signal transduction is not fully understood in myelodysplastic syndromes (MDS). Here, we tried to identify the miRNAs-regulated pathways through a combination of miRNA and mRNA microarray in CD34+ cells from MDS patients. We identified 34 differentially expressed miRNAs and 1783 mRNAs in MDS. 25 dysregulated miRNAs and 394 targeted mRNAs were screened by a combination of Pearson’s correlation analysis and software prediction. Pathway analysis showed that several pathways such as Notch, PI3K/Akt might be regulated by those miRNA-mRNAs pairs. Through a combination of Pathway and miRNA-Gene or GO-Network analysis, miRNAs-regulated pathways, such as miR-195-5p/DLL1/Notch signaling pathway, were identified. Further qRT-PCR showed that miR-195-5p was up-regulated while DLL1 was down-regulated in patients with low-grade MDS compared with normal controls. Luciferase assay showed that DLL1 was a direct target of miR-195-5p. Overexpression of miR-195-5p led to increased cell apoptosis and reduced cell growth through inhibition of Notch signaling pathway. In conclusion, alteration expression of miRNAs and targeted mRNAs might have an important impact on cancer-related cellular pathways in MDS. Inhibition of Notch signaling pathway by miR-195-5p-DLL1 axis contributes to the excess apoptosis in low-grade MDS.
Role of Cathepsins in Mycobacterium tuberculosis Survival in Human Macrophages
Authors: Pires David , Marques Joana , Pombo João Palma , Carmo Nuno , Bettencourt Paulo , Neyrolles Olivier , Lugo-Villarino Geanncarlo , Anes Elsa
Published: August 2016

Cathepsins are proteolytic enzymes that function in the endocytic pathway, especially in lysosomes, where they contribute directly to pathogen killing or indirectly, by their involvement in the antigen presentation pathways. Mycobacterium tuberculosis (MTB) is a facultative intracellular pathogen that survives inside the macrophage phagosomes by inhibiting their maturation to phagolysosomes and thus avoiding a low pH and protease-rich environment. We previously showed that mycobacterial inhibition of the proinflammatory transcription factor NF-κB results in impaired delivery of lysosomal enzymes to phagosomes and reduced pathogen killing. Here, we elucidate how MTB also controls cathepsins and their inhibitors, cystatins, at the level of gene expression and proteolytic activity. MTB induced a general down-regulation of cathepsin expression in infected cells, and inhibited IFNγ-mediated increase of cathepsin mRNA. We further show that a decrease in cathepsins B, S and L favours bacterial survival within human primary macrophages. A siRNA knockdown screen of a large set of cathepsins revealed that almost half of these enzymes have a role in pathogen killing, while only cathepsin F coincided with MTB resilience. Overall, we show that cathepsins are important for the control of MTB infection, and as a response, it manipulates their expression and activity to favour its intracellular survival.
A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma
Authors: Kanzaki Hiroyuki , Shinohara Fumiaki , Suzuki Maiko , Wada Satoshi , Miyamoto Yutaka , Yamaguchi Yuuki , Katsumata Yuta , Makihira Seicho , Kawai Toshi , Taubman Martin A. , Nakamura Yoshiki
Published: August 2016

Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption. Peptidases of the a-disintegrin and metalloproteinase (ADAM) family are implicated in cancer cell proliferation and tumor progression. We hypothesized that the ADAM enzymes expressed by cancer cells degrades IFN-γ and attenuates IFN-γ-mediated anti-tumorigenic and anti-osteoclastogenic effects. Recombinant ADAM17 degraded IFN-γ into small fragments. The addition of ADAM17 to the culture supernatant of stimulated mouse splenocytes decreased IFN-γ concentration. However, ADAM17 inhibition in the stimulated mouse T-cells prevented IFN-γ degradation. ADAM17-expressing human breast cancer cell lines MCF-7 and MDA-MB-453 also degraded recombinant IFN-γ, but this was attenuated by ADAM17 inhibition. Degraded IFN-γ lost the functionality including the inhibititory effect on osteoclastogenesis. This is the first study to demonstrate the extracellular proteolytic degradation of IFN-γ by ADAM17. These results suggest that ADAM17-mediated degradation of IFN-γ may block the anti-tumorigenic and anti-osteoclastogenic effects of IFN-γ. ADAM17 inhibition may be useful for the treatment of attenuated cancer immune surveillance and/or bone metastases.
The Potential Role of Seaweeds in the Natural Manipulation of Rumen Fermentation and Methane Production
Authors: Maia Margarida R. G. , Fonseca António J. M. , Oliveira Hugo M. , Mendonça Carla , Cabrita Ana R. J.
Published: August 2016

This study is the first to evaluate the effects of five seaweeds (Ulva sp., Laminaria ochroleuca, Saccharina latissima, Gigartina sp., and Gracilaria vermiculophylla) on gas and methane production and ruminal fermentation parameters when incubated in vitro with two substrates (meadow hay and corn silage) for 24 h. Seaweeds led to lower gas production, with Gigartina sp. presenting the lowest value. When incubated with meadow hay, Ulva sp., Gigartina sp. and G. vermiculophylla decreased methane production, but with corn silage, methane production was only decreased by G. vermiculophylla. With meadow hay, L. ochroleuca and S. latissima promoted similar methane production as the control, but with corn silage, L. ochroleuca increased it. With the exception of S. latissima, all seaweeds promoted similar levels of total volatile fatty acid production. The highest proportion of acetic acid was produced with Ulva sp., G. vermiculophylla, and S. latissima; the highest proportion of butyric acid with the control and L. ochroleuca; and the highest proportion of iso-valeric acid with Gigartina sp. These results reveal the potential of seaweeds to mitigate ruminal methane production and the importance of the basal diet. To efficiently use seaweeds as feed ingredients with nutritional and environmental benefits, more research is required to determine the mechanisms underlying seaweed and substrate interactions.
ZnO-nanorods/graphene heterostructure: a direct electron transfer glucose biosensor
Authors: Zhao Yu , Li Wenbo , Pan Lijia , Zhai Dongyuan , Wang Yu , Li Lanlan , Cheng Wen , Yin Wei , Wang Xinran , Xu Jian-Bin , Shi Yi
Published: August 2016

ZnO-nanorods/graphene heterostructure was synthesized by hydrothermal growth of ZnO nanorods on chemically reduced graphene (CRG) film. The hybrid structure was demonstrated as a biosensor, where direct electron transfer between glucose oxidase (GOD) and electrode was observed. The charge transfer was attributed to the ZnO nanorod wiring between the redox center of GOD and electrode and the ZnO/graphene heterostructure facilitated the transport of electrons on the hybride electrode. The glucose sensor based on the GOD-ZnO/CRG/Pt electrode had a high sensitivity of 17.64 μA mM−1, which is higher than most of the previously reported values for direct electron transfer based glucose biosensors. Moreover, this biosensor is linearly proportional to the concentration of glucose in the range of 0.2–1.6 mM. The study revealed that the band structure of electrode could affect the detection of direct electron transfer of GOD, which would be helpful for the design of the biosensor electrodes in the future.
In silico modelling of a cancer stem cell-targeting agent and its effects on tumour control during radiotherapy
Authors: Marcu Loredana G. , Marcu David
Published: August 2016

Head and neck cancers (HNC), like most solid tumours, contain a subpopulation of cancer stem cells (CSC) that are commonly responsible for treatment failure. Conventional therapies are unsuccessful in controlling CSCs, thus novel, targeting therapies are needed. A promising agent is ATRA (All-trans-retinoic acid) that was shown to induce CSC differentiation, cell cycle redistribution and CSCs radiosensitisation. To add to the limited data, this work simulated the effects of ATRA on a virtual HNC and evaluated tumour response to radiotherapy. A Monte Carlo technique was employed to grow a HNC consisting of all lineages of cancer cells. The biologically realistic input parameters led to a pre-treatment CSC population of 5.9%. The Linear Quadratic model was employed to simulate radiotherapy. ATRA-induced differentiation, cell arrest and apoptosis were modelled, based on literature data. While the effect of differentiation was marginal, the strongest influence on CSC subpopulation was displayed by ATRA’s cell arrest effect via an exponential behaviour of the dose-response curve. The apoptotic effect induced by ATRA shows linear correlation between the percentage of apoptotic cells and dose required to eradicate CSCs. In conclusion, ATRA is a potent CSC-targeting agent with viable impact on tumour control when combined with radiotherapy.
Prions efficiently cross the intestinal barrier after oral administration: Study of the bioavailability, and cellular and tissue distribution in vivo
Authors: Urayama Akihiko , Concha-Marambio Luis , Khan Uffaf , Bravo-Alegria Javiera , Kharat Vineetkumar , Soto Claudio
Published: August 2016

Natural forms of prion diseases frequently originate by oral (p.o.) infection. However, quantitative information on the gastro-intestinal (GI) absorption of prions (i.e. the bioavailability and subsequent biodistribution) is mostly unknown. The main goal of this study was to evaluate the fate of prions after oral administration, using highly purified radiolabeled PrPSc. The results showed a bi-phasic reduction of PrPSc with time in the GI, except for the ileum and colon which showed sustained increases peaking at 3–6 hr, respectively. Plasma and whole blood 125I-PrPSc reached maximal levels by 30 min and 3 hr, respectively, and blood levels were constantly higher than plasma. Upon crossing the GI-tract 125I-PrPSc became associated to blood cells, suggesting that binding to cells decreased the biological clearance of the agent. Size-exclusion chromatography revealed that oligomeric 125I-PrPSc were transported from the intestinal tract, and protein misfolding cyclic amplification showed that PrPSc in organs and blood retained the typical prion self-replicating ability. Pharmacokinetic analysis found the oral bioavailability of 125I-PrPSc to be 33.6%. Interestingly, 125I-PrPSc reached the brain in a quantity equivalent to the minimum amount needed to initiate prion disease. Our findings provide a comprehensive and quantitative study of the fate of prions upon oral infection.
Aromatase inhibition rapidly affects in a reversible manner distinct features of birdsong
Authors: Alward Beau A. , de Bournonville Catherine , Chan Trevor T. , Balthazart Jacques , Cornil Charlotte A. , Ball Gregory F.
Published: August 2016

Recent evidence has implicated steroid hormones, specifically estrogens, in the rapid modulation of cognitive processes. Songbirds have been a useful model system in the study of complex cognitive processes including birdsong, a naturally learned vocal behavior regulated by a discrete steroid-sensitive telencephalic circuitry. Singing behavior is known to be regulated by long-term actions of estrogens but rapid steroid modulation of this behavior has never been examined. We investigated if acute actions of estrogens regulate birdsong in canaries (Serinus canaria). In the morning, male canaries sing within minutes after light onset. Birds were injected with fadrozole, a potent aromatase inhibitor, or vehicle within 2–5 minutes after lights on to implement a within-subjects experimental design. This single injection of fadrozole reduced the motivation to sing as well as song acoustic stereotypy, a measure of consistency over song renditions, on the same day. By the next day, however, all song measures that were affected had returned to baseline. This study indicates that estrogens also act in a rapid fashion to regulate two distinct features of song, a learned vocal behavior.
The use of Haemostatic Agents does not impact the rate of hemorrhagic complications in patients undergoing partial nephrectomy for renal masses
Authors: Abu-Ghanem Yasmin , Dotan Zohar , Kaver Issac , Zilberman Dorit E. , Ramon Jacob
Published: August 2016

Hemostatic agents(HAs) have gained increasing popularity as interventions to improve perioperative haemostasis and diminish the need for allogeneic red cell transfusion(PBT) despite a paucity of data supporting the practice. The aim of the current study is to examine the efficacy of HAs in reducing the rate of hemorrhagic complications during partial nephrectomy(PN). Data on 657 patients, who underwent elective PN between 2004–2013, were analyzed. The impact of HAs and SURGICEL was evaluated by comparing four sequential groups of patients: Group1 = Sutures alone, Group2 = sutures and HA, Group3 = sutures and SURGICEL, Group4 = both HA and SURGICEL. Complications included post-operative urinary leak(UL), PBT rate, delayed bleeding and post-operative renal failure. Results showed that the use of HAs did not engender a statistically significant difference in overall complications rate. Specifically, the addition of HAs did not reduce the rate of PBT, delayed bleeding or UL. Further analysis revealed that patients who received SURGICEL had significantly higher PBT rate and higher prevalence of UL cases. Addition of HAs to SURGICEL had no effect on the rate of these complications. In the current study, the use of HAs during open and laparoscopic PN did not reduce the rate of negative outcomes. Adequate suture renorrhaphy may be sufficient to prevent hemorrhagic complications.
Universal optical conductivity of a disordered Weyl semimetal
Authors: Roy Bitan , Juričić Vladimir , Das Sarma Sankar
Published: August 2016

Topological Weyl semimetals, besides manifesting chiral anomaly, can also accommodate a disorder-driven unconventional quantum phase transition into a metallic phase. A fundamentally and practically important question in this regard concerns an experimentally measurable quantity that can clearly distinguish these two phases. We show that the optical conductivity while serving this purpose can also play the role of a bonafide order parameter across such disorder-driven semimetal-metal quantum phase transition by virtue of displaying distinct scaling behavior in the semimetallic and metallic phases, as well as inside the quantum critical fan supporting a non-Fermi liquid. We demonstrate that the correction to the dielectric constant and optical conductivity in a dirty Weyl semimetal due to weak disorder is independent of the actual nature of point-like impurity scatterers. Therefore, optical conductivity can be used as an experimentally measurable quantity to study the critical properties and to pin the universality class of the disorder-driven quantum phase transition in Weyl semimetals.
Rising Mediterranean Sea Surface Temperatures Amplify Extreme Summer Precipitation in Central Europe
Authors: Volosciuk Claudia , Maraun Douglas , Semenov Vladimir A. , Tilinina Natalia , Gulev Sergey K. , Latif Mojib
Published: August 2016

The beginning of the 21st century was marked by a number of severe summer floods in Central Europe associated with extreme precipitation (e.g., Elbe 2002, Oder 2010 and Danube 2013). Extratropical storms, known as Vb-cyclones, cause summer extreme precipitation events over Central Europe and can thus lead to such floodings. Vb-cyclones develop over the Mediterranean Sea, which itself strongly warmed during recent decades. Here we investigate the influence of increased Mediterranean Sea surface temperature (SST) on extreme precipitation events in Central Europe. To this end, we carry out atmosphere model simulations forced by average Mediterranean SSTs during 1970–1999 and 2000–2012. Extreme precipitation events occurring on average every 20 summers in the warmer-SST-simulation (2000–2012) amplify along the Vb-cyclone track compared to those in the colder-SST-simulation (1970–1999), on average by 17% in Central Europe. The largest increase is located southeast of maximum precipitation for both simulated heavy events and historical Vb-events. The responsible physical mechanism is increased evaporation from and enhanced atmospheric moisture content over the Mediterranean Sea. The excess in precipitable water is transported from the Mediterranean Sea to Central Europe causing stronger precipitation extremes over that region. Our findings suggest that Mediterranean Sea surface warming amplifies Central European precipitation extremes.
Open System Tribology and Influence of Weather Condition
Authors: Lyu Yezhe , Bergseth Ellen , Olofsson Ulf
Published: August 2016

The tribology of an open system at temperatures ranging between 3 °C and −35 °C, with and without snow, was investigated using a pin-on-disc tribometer mounted in a temperature-controlled environmental chamber. The relationship between the microstructure and ductility of the materials and the tribology at the contacting surfaces was investigated. The study shows that during continuous sliding, pressure causes snow particles to melt into a liquid-like layer, encouraging the generation of oxide flakes on the contact path. The friction coefficient and wear rate are dramatically reduced through an oxidative friction and wear mechanism. In the absence of snow, the tribological process is controlled by the low temperature brittleness of steel in the temperature range from 3 °C to −15 °C. At these temperatures, cracks are prone to form and extend on the worn surfaces, resulting in the spalling of bulk scraps, which are crushed into debris that increases the friction coefficient and wear rate due to strong abrasion. When the temperature falls to −25 °C, an ice layer condenses on the metal surfaces and relaxes the tribological process in the same way as the added snow particles, which significantly decreases the friction and wear.
Eye blinking in an avian species is associated with gaze shifts
Authors: Yorzinski Jessica L.
Published: August 2016

Even when animals are actively monitoring their environment, they lose access to visual information whenever they blink. They can strategically time their blinks to minimize information loss and improve visual functioning but we have little understanding of how this process operates in birds. This study therefore examined blinking in freely-moving peacocks (Pavo cristatus) to determine the relationship between their blinks, gaze shifts and context. Peacocks wearing a telemetric eye-tracker were exposed to a taxidermy predator (Vulpes vulpes) and their blinks and gaze shifts were recorded. Peacocks blinked during the majority of their gaze shifts, especially when gaze shifts were large, thereby timing their blinks to coincide with periods when visual information is already suppressed. They inhibited their blinks the most when they exhibited high rates of gaze shifts and were thus highly alert. Alternative hypotheses explaining the link between blinks and gaze shifts are discussed.
Synergistic effects of dissolved organic carbon and inorganic nitrogen on methane uptake in forest soils without and with freezing treatment
Authors: Wu Haohao , Xu Xingkai , Duan Cuntao , Li Tuansheng , Cheng Weiguo
Published: August 2016

There is limited knowledge about how the interaction of dissolved organic carbon (DOC) and inorganic nitrogen (N) released into the soil just after freezing can affect methane (CH4) uptake in forest soils. Here, we present how freezing treatment and glucose, as a DOC source, can affect the roles of NH4+-N and NO3−-N in inhibiting soil CH4 uptake, by using soil-core incubation experiments. A long-term freezing at low temperature reduced cumulative CH4 uptake in the soils sampled from two temperate forest stands without carbon (C) and N addition. The inhibition effects of N addition as NH4Cl and KNO3 on the soil CH4 uptake were much larger than C addition. Freezing treatment eliminated the inhibition effect of NH4Cl and KNO3 addition on CH4 uptake, and this response was affected by glucose addition and forest types. The addition of glucose eliminated the inhibition effect of NO3−-N on CH4 uptake in the forest soils without and with freezing treatment, while the addition of NH4+-N and glucose inhibited synergistically the soil CH4 uptake. The results highlight the importance of synergistic effects of DOC and N inputs on the soil CH4 uptake under forest stands during soil wetting and thawing periods.
Preliminary evidence for association of genetic variants in pri-miR-34b/c and abnormal miR-34c expression with attention deficit and hyperactivity disorder
Authors: Garcia-Martínez I , Sánchez-Mora C , Pagerols M , Richarte V , Corrales M , Fadeuilhe C , Cormand B , Casas M , Ramos-Quiroga J A , Ribasés M
Published: August 2016

Attention deficit and hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by impairment to sustain attention and inability to control impulses and activity level. The etiology of ADHD is complex, with an estimated heritability of 70–80%. Under the hypothesis that alterations in the processing or target binding of microRNAs (miRNAs) may result in functional alterations predisposing to ADHD, we explored whether common polymorphisms potentially affecting miRNA-mediated regulation are involved in this psychiatric disorder. We performed a comprehensive association study focused on 134 miRNAs in 754 ADHD subjects and 766 controls and found association between the miR-34b/c locus and ADHD. Subsequently, we provided preliminary evidence for overexpression of the miR-34c-3p mature form in peripheral blood mononuclear cells of ADHD subjects. Next, we tested the effect on gene expression of single-nucleotide polymorphisms within the ADHD-associated region and found that rs4938923 in the promoter of the pri-miR-34b/c tags cis expression quantitative trait loci for both miR-34b and miR-34c and has an impact on the expression levels of 681 transcripts in trans, including genes previously associated with ADHD. This gene set was enriched for miR-34b/c binding sites, functional categories related to the central nervous system, such as axon guidance or neuron differentiation, and serotonin biosynthesis and signaling canonical pathways. Our results provide preliminary evidence for the contribution to ADHD of a functional variant in the pri-miR-34b/c promoter, possibly through dysregulation of the expression of mature forms of miR-34b and miR-34c and some target genes. These data highlight the importance of abnormal miRNA function as a potential epigenetic mechanism contributing to ADHD.
Host–guest chemistry in two-dimensional supramolecular networks
Authors: Teyssandier Joan , Feyter Steven De , Mali Kunal S.
Published: August 2016

In this feature article, we survey recent developments in host–guest chemistry studied in surface-adsorbed physisorbed supramolecular networks.
Microfluidics in microbiology: putting a magnifying glass on microbes
Authors: Siddiqui Sanya , Tufenkji Nathalie , Moraes Christopher
Published: August 2016

In this Research Highlight, we describe recently developed tools for diagnostic assays, high-throughput mutant screening, and the study of human disease development as well as a future outlook on microbes for renewable energy.
A reconfigurable stick-n-play modular microfluidic system using magnetic interconnects
Authors: Yuen Po Ki
Published: August 2016

A reconfigurable “stick-n-play” modular microfluidic system that can be assembled, disassembled, reconfigured and assembled again for building different integrated microfluidic systems is presented.
Microfluidic technique for measuring wax appearance temperature of reservoir fluids
Authors: Molla Shahnawaz , Magro Laura , Mostowfi Farshid
Published: August 2016

We present a powerful technique for measuring wax appearance temperature (WAT) of crude oils using a simple microfluidic device.