bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-brain 3D mapping of human neural transplant innervation
Authors: Doerr Jonas , Schwarz Martin Karl , Wiedermann Dirk , Leinhaas Anke , Jakobs Alina , Schloen Florian , Schwarz Inna , Diedenhofen Michael , Braun Nils Christian , Koch Philipp , Peterson Daniel A. , Kubitscheck Ulrich , Hoehn Mathias , Brüstle Oliver
Published: January 2017

While transplantation represents a key tool for assessing in vivo functionality of neural stem cells and their suitability for neural repair, little is known about the integration of grafted neurons into the host brain circuitry. Rabies virus-based retrograde tracing has developed into a powerful approach for visualizing synaptically connected neurons. Here, we combine this technique with light sheet fluorescence microscopy (LSFM) to visualize transplanted cells and connected host neurons in whole-mouse brain preparations. Combined with co-registration of high-precision three-dimensional magnetic resonance imaging (3D MRI) reference data sets, this approach enables precise anatomical allocation of the host input neurons. Our data show that the same neural donor cell population grafted into different brain regions receives highly orthotopic input. These findings indicate that transplant connectivity is largely dictated by the circuitry of the target region and depict rabies-based transsynaptic tracing and LSFM as efficient tools for comprehensive assessment of host–donor cell innervation.
A broadly protective therapeutic antibody against influenza B virus with two mechanisms of action
Authors: Chai Ning , Swem Lee R. , Park Summer , Nakamura Gerald , Chiang Nancy , Estevez Alberto , Fong Rina , Kamen Lynn , Kho Elviza , Reichelt Mike , Lin Zhonghua , Chiu Henry , Skippington Elizabeth , Modrusan Zora , Stinson Jeremy , Xu Min , Lupardus Patrick , Ciferri Claudio , Tan Man-Wah
Published: January 2017

Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use anin vivoplasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs testedin vitroand protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion. After passage of the B/Brisbane/60/2008 virus in the presence of 46B8, we isolated three resistant clones, all harbouring the same mutation (Ser301Phe) in HA that abolishes 46B8 binding to HA at low pH. Interestingly, 46B8 is still able to protect mice against lethal challenge of the mutant viruses, possibly owing to its ability to mediate antibody-dependent cellular cytotoxicity (ADCC).
Identification, validation, and targeting of the mutant p53-PARP-MCM chromatin axis in triple negative breast cancer
Authors: Qiu Wei-Gang , Polotskaia Alla , Xiao Gu , Di Lia , Zhao Yuhan , Hu Wenwei , Philip John , Hendrickson Ronald C. , Bargonetti Jill
Published: January 2017

Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins. The present proteomics experiment corroborated our previous experiment-based results that poly ADP-ribose polymerase has a positive association with mutant p53 on the chromatin. Here, for the first time we report that the heterohexomeric minichromosome maintenance complex that participates in DNA replication initiation ranked as a high mutant p53-chromatin associated pathway. Enrichment analysis identified the minichromosome maintenance members 2–7. To validate this mutant p53- poly ADP-ribose polymerase-minichromosome maintenance functional axis, we experimentally depleted R273H mutant p53 and found a large reduction of the amount of minichromosome maintenance complex proteins on the chromatin. Furthermore a mutant p53-minichromosome maintenance 2 direct interaction was detected. Overexpressed mutant p53, but not wild type p53, showed a protein-protein interaction with minichromosome maintenance 2 and minichromosome maintenance 4. To target the mutant p53- poly ADP-ribose polymerase-minichromosome maintenance axis we treated cells with the poly ADP-ribose polymerase inhibitor talazoparib and the alkylating agent temozolomide and detected synergistic activation of apoptosis only in the presence of mutant p53. Furthermore when minichromosome maintenance 2–7 activity was inhibited the synergistic activation of apoptosis was blocked. This mutant p53- poly ADP-ribose polymerase -minichromosome maintenance axis may be useful for theranostics.
Comparison of efficacy of simo decoction and acupuncture or chewing gum alone on postoperative ileus in colorectal cancer resection: a randomized trial
Authors: Yang Yang , Zuo Hong-Qun , Li Zhao , Qin Yu-Zhou , Mo Xian-Wei , Huang Ming-Wei , Lai Hao , Wu Liu-Cheng , Chen Jian-Si
Published: January 2017

To compared the ability of chewing gum or simo decoction (SMD) and acupuncture to reduce incidence of postoperative ileus (POI) after colorectal cancer resection, patients with colorectal cancer undergoing open or laparoscopic resection were randomized to receive SMD and acupuncture (n = 196), chewing gum alone (n = 197) or no intervention (n = 197) starting on postoperative day 1 and continuing for 5 consecutive days. Patients treated with SMD and acupuncture experienced significantly shorter hospital stay, shorter time to first flatus and shorter time to defecation than patients in the other groups (all P < 0.05). Incidence of grade I and II complications was also significantly lower in patients treated with SMD and acupuncture. Patients who chewed gum were similar to those who received no intervention in terms of hospital stay, incidence of complications, and time to first bowel motion, flatus, and defecation (all P > 0.05). The combination of SMD and acupuncture may reduce the incidence of POI and shorten hospital stay for patients with colorectal cancer after resection. In contrast, chewing gum does not appear to affect recovery of bowel function or hospital stay, though it may benefit patients who undergo open resection. (Clinicaltrials.gov registration number: NCT02813278).
Surface reconstructions and related local properties of a BiFeO3 thin film
Authors: Jin L. , Xu P. X. , Zeng Y. , Lu L. , Barthel J. , Schulthess T. , Dunin-Borkowski R. E. , Wang H. , Jia C. L.
Published: January 2017

Coupling between lattice and order parameters, such as polarization in ferroelectrics and/or polarity in polar structures, has a strong impact on surface relaxation and reconstruction. However, up to now, surface structures that involve the termination of both matrix polarization and polar atomic planes have received little attention, particularly on the atomic scale. Here, we study surface structures on a BiFeO3 thin film using atomic-resolution scanning transmission electron microscopy and spectroscopy. Two types of surface structure are found, depending on the polarization of the underlying ferroelectric domain. On domains that have an upward polarization component, a layer with an Aurivillius-Bi2O2-like structural unit is observed. Dramatic changes in local properties are measured directly below the surface layer. On domains that have a downward polarization component, no reconstructions are visible. Calculations based on ab initio density functional theory reproduce the results and are used to interpret the formation of the surface structures.
Correction: Corrigendum: Genomic Selection Improves Heat Tolerance in Dairy Cattle
Authors: Garner J. B. , Douglas M. L. , Williams S. R. O , Wales W. J. , Marett L. C. , Nguyen T. T. T. , Reich C. M. , Hayes B. J.
Published: January 2017

Scientific Reports 6: Article number: 34114; published online: 29 September 2016; updated: 19 January 2017. The original version of this Article omitted an affiliation for J. B. Garner. The correct affiliations are listed below: Agriculture Victoria, Department of Economic Development, Jobs, Transport and Resources, 1301 Hazeldean Road, Ellinbank, Victoria 3821, Australia.
Correction: Corrigendum: CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients
Authors: Su Shu , Hu Bian , Shao Jie , Shen Bin , Du Juan , Du Yinan , Zhou Jiankui , Yu Lixia , Zhang Lianru , Chen Fangjun , Sha Huizi , Cheng Lei , Meng Fanyan , Zou Zhengyun , Huang Xingxu , Liu Baorui
Published: January 2017

Scientific Reports 6: Article number: 20070; published online: 28 January 2016; updated: 19 January 2017. In figure 4d the micrograph for Patient 1 at 7 days was inadvertently duplicated for the Healthy Donor at day 7. The correct figure 4d appears below as Figure 1.
Correction: Corrigendum: Light-matter decoupling and A2 term detection in superconducting circuits
Authors: García-Ripoll J. J. , Peropadre B. , De Liberato S.
Published: January 2017

Scientific Reports 5: Article number: 16055; published online: 04 November 2015; updated: 19 January 2017. The original version of this Article contained a typographical error in Reference 24, which was incorrectly given as: T. Tufarelli, K. R. McEnery, S. A. Maier & M. S. Kim. Phys. Rev. A 89, 023817 (2014).
Improvement in the biochemical and chemical properties of badland soils by thorny bamboo
Authors: Shiau Yo-Jin , Wang Hsueh-Ching , Chen Tsai-Huei , Jien Shih-Hau , Tian Guanglong , Chiu Chih-Yu
Published: January 2017

Badland soils—which have high silt and clay contents, bulk density, and soil electric conductivity— cover a large area of Southern Taiwan. This study evaluated the amelioration of these poor soils by thorny bamboo, one of the few plant species that grows in badland soils. Soil physiochemical and biological parameters were measured from three thorny bamboo plantations and nearby bare lands. Results show that bamboo increased microbial C and N, soil acid-hydrolysable C, recalcitrant C, and soluble organic C of badland soils. High microbial biomass C to total organic C ratio indicates that soil organic matter was used more efficiently by microbes colonizing bamboo plantations than in bare land soils. High microbial respiration to biomass C ratio in bare land soils confirmed environmentally induced stress. Soil microbes in bare land soils also faced soil organic matter with the high ratio of recalcitrant C to total organic C. The high soil acid-hydrolysable C to total organic C ratio at bamboo plantations supported the hypothesis that decomposition of bamboo litter increased soil C in labile fractions. Overall, thorny bamboo improved soil quality, thus, this study demonstratesthat planting thorny bamboo is a successful practice for the amelioration of badland soils.
Wells provide a distorted view of life in the aquifer: implications for sampling, monitoring and assessment of groundwater ecosystems
Authors: Korbel Kathryn , Chariton Anthony , Stephenson Sarah , Greenfield Paul , Hose Grant C.
Published: January 2017

When compared to surface ecosystems, groundwater sampling has unique constraints, including limited access to ecosystems through wells. In order to monitor groundwater, a detailed understanding of groundwater biota and what biological sampling of wells truly reflects, is paramount. This study aims to address this uncertainty, comparing the composition of biota in groundwater wells prior to and after purging, with samples collected prior to purging reflecting a potentially artificial environment and samples collected after purging representing the surrounding aquifer. This study uses DNA community profiling (metabarcoding) of 16S rDNA and 18S rDNA, combined with traditional stygofauna sampling methods, to characterise groundwater biota from four catchments within eastern Australia. Aquifer waters were dominated by Archaea and bacteria (e.g. Nitrosopumilales) that are often associated with nitrification processes, and contained a greater proportion of bacteria (e.g. Anaerolineales) associated with fermenting processes compared to well waters. In contrast, unpurged wells contained greater proportions of pathogenic bacteria and bacteria often associated with denitrification processes. In terms of eukaryotes, the abundances of copepods, syncarids and oligochaetes and total abundances of stygofauna were greater in wells than aquifers. These findings highlight the need to consider sampling requirements when completing groundwater ecology surveys.
Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior
Authors: Mobley Aaron , Zhang Shizhen , Bondaruk Jolanta , Wang Yan , Majewski Tadeusz , Caraway Nancy P. , Huang Li , Shoshan Einav , Velazquez-Torres Guermarie , Nitti Giovanni , Lee Sangkyou , Lee June Goo , Fuentes-Mattei Enrique , Willis Daniel , Zhang Li , Guo Charles C. , Yao Hui , Baggerly Keith , Lotan Yair , Lerner Seth P. , Dinney Colin , McConkey David , Bar-Eli Menashe , Czerniak Bogdan
Published: January 2017

The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA. Chromatin immunoprecipitation and NNMT promoter luciferase assays revealed that AURKA’s effects on NNMT were caused by PAX3-mediated transcriptional repression and overexpression of NNMT blocked tumor cell invasion in vitro. Overexpression of AURKA and activation of its downstream pathway was enriched in the basal subtype in primary human tumors and was associated with poor clinical outcomes. We also show that the FISH test for the AURKA gene copy number in urine yielded a specificity of 79.7% (95% confidence interval [CI] = 74.2% to 84.1%), and a sensitivity of 79.6% (95% CI = 74.2% to 84.1%) with an AUC of 0.901 (95% CI = 0.872 to 0.928; P < 0.001). These results implicate AURKA as an effective biomarker for bladder cancer detection as well as therapeutic target especially for its basal type.
Cultivation and energy efficient harvesting of microalgae using thermoreversible sol-gel transition
Authors: Estime Bendy , Ren Dacheng , Sureshkumar Radhakrishna
Published: January 2017

Microalgae represent a promising source of renewable biomass for the production of biofuels and valuable chemicals. However, energy efficient cultivation and harvesting technologies are necessary to improve economic viability. A Tris-Acetate-Phosphate-Pluronic (TAPP) medium that undergoes a thermoreversible sol-gel transition is developed to efficiently culture and harvest microalgae without affecting the productivity as compared to that in traditional culture in a well-mixed suspension. After seeding microalgae in the TAPP medium in a solution phase at 15 °C, the temperature is increased by 7 °C to induce gelation. Within the gel, microalgae are observed to grow in large clusters rather than as isolated cells. The settling velocity of the microalgal clusters is approximately ten times larger than that of individual cells cultured in typical solution media. Such clusters are easily harvested gravimetrically by decreasing the temperature to bring the medium to a solution phase.
Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas
Authors: Peng DunFa , Guo Yan , Chen Heidi , Zhao Shilin , Washington Kay , Hu TianLing , Shyr Yu , El-Rifai Wael
Published: January 2017

The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the United States and Western countries. In this study, we carried out an integrative molecular analysis to identify interactions between genomic and epigenomic alterations in regulating gene expression networks in EAC. We detected significant alterations in DNA copy numbers (CN), gene expression levels, and DNA methylation profiles. The integrative analysis demonstrated that altered expression of 1,755 genes was associated with changes in CN or methylation. We found that expression alterations in 84 genes were associated with changes in both CN and methylation. These data suggest a strong interaction between genetic and epigenetic events to modulate gene expression in EAC. Of note, bioinformatics analysis detected a prominent K-RAS signature and predicted activation of several important transcription factor networks, including β-catenin, MYB, TWIST1, SOX7, GATA3 and GATA6. Notably, we detected hypomethylation and overexpression of several pro-inflammatory genes such as COX2, IL8 and IL23R, suggesting an important role of epigenetic regulation of these genes in the inflammatory cascade associated with EAC. In summary, this integrative analysis demonstrates a complex interaction between genetic and epigenetic mechanisms providing several novel insights for our understanding of molecular events in EAC.
Acetylcholine acts through M3 muscarinic receptor to activate the EGFR signaling and promotes gastric cancer cell proliferation
Authors: Yu Huangfei , Xia Hongwei , Tang Qiulin , Xu Huanji , Wei Guoqing , Chen Ying , Dai Xinyu , Gong Qiyong , Bi Feng
Published: January 2017

Acetylcholine (ACh), known as a neurotransmitter, regulates the functions of numerous fundamental central and peripheral nervous system. Recently, emerging evidences indicate that ACh also plays an important role in tumorigenesis. However, little is known about the role of ACh in gastric cancer. Here, we reported that ACh could be auto-synthesized and released from MKN45 and BGC823 gastric cancer cells. Exogenous ACh promoted cell proliferation in a does-dependent manner. The M3R antagonist 4-DAMP, but not M1R antagonist trihexyphenidyl and M2/4 R antagonist AFDX-116, could reverse the ACh-induced cell proliferation. Moreover, ACh, via M3R, activated the EGFR signaling to induce the phosphorylation of ERK1/2 and AKT, and blocking EGFR pathway by specific inhibitor AG1478 suppressed the ACh induced cell proliferation. Furthermore, the M3R antagonist 4-DAMP and darifenacin could markedly inhibit gastric tumor formation in vivo. 4-DAMP could also significantly enhance the cytotoxic activity of 5-Fu against the MKN45 and BGC823 cells, and induce the expression of apoptosis-related proteins such as Bax and Caspase-3. Together, these findings indicated that the autocrine ACh could act through M3R and the EGFR signaling to promote gastric cancer cells proliferation, targeting M3R or EGFR may provide us a potential therapeutic strategy for gastric cancer treatment.
Crotalus atrox venom preconditioning increases plasma fibrinogen and reduces perioperative hemorrhage in a rat model of surgical brain injury
Authors: Kim Cherine H. , McBride Devin W. , Raval Ronak , Sherchan Prativa , Hay Karen L. , Gren Eric C. K. , Kelln Wayne , Lekic Tim , Hayes William K. , Bull Brian S. , Applegate Richard , Tang Jiping , Zhang John H.
Published: January 2017

Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries.
Erratum: Longitudinal modeling of ultrasensitive and traditional prostate-specific antigen and prediction of biochemical recurrence after radical prostatectomy
Authors: Laajala Teemu D. , Seikkula Heikki , Seyednasrollah Fatemeh , Mirtti Tuomas , Boström Peter J. , Elo Laura L.
Published: January 2017

Scientific Reports 6: Article number: 36161; published online: 02 November 2016; updated: 19 January 2017. The original version of this Article contained an error in the spelling of Fatemeh Seyednasrollah, which was incorrectly given as Fatemeh Seyednasrollah sadat. This has now been corrected in the HTML and PDF versions of this Article.
Correlations of charge neutrality level with electronic structure and p-d hybridization
Authors: Das Arkaprava , Gautam Subodh K. , Shukla D. K. , Singh Fouran
Published: January 2017

The formation of charge neutrality level (CNL) in highly conducting Cadmium oxide (CdO) thin films is demonstarted by the observed variation in the band gap upon annealing and doping. It may be explained by the observation that Tin (Sn) doping breaks the perfect periodicity of CdO cubic crystal structure and creates virtual gap states (ViGS). The level of local CNL resides at the branch point of ViGS, making the energy at which native defect’s character changes from predominantly donor-like below CNL to predominantly acceptor-like above the CNL and a schematic band diagram is developed to substantiate the same. Further investigations using soft x-ray absorption spectroscopy (SXAS) at Oxygen and Cadmium edges show the reduction of Sn4+ to Sn2+. The analysis of the spectral features has revealed an evidence of p-d interaction between O 2p and Cd 4d orbitals that pushes the valence band minima at higher energies which is symmetry forbidden at г point and causing a positive valance band dispersion away from the zone centre in the г ~ L, K direction. Thus, origin of the CNL is attributed to the high density of the Oxygen vacancies as confirmed by the change in the local electronic structure and p-d hybridization of orbitals.
Leads in Arctic pack ice enable early phytoplankton blooms below snow-covered sea ice
Authors: Assmy Philipp , Fernández-Méndez Mar , Duarte Pedro , Meyer Amelie , Randelhoff Achim , Mundy Christopher J. , Olsen Lasse M. , Kauko Hanna M. , Bailey Allison , Chierici Melissa , Cohen Lana , Doulgeris Anthony P. , Ehn Jens K. , Fransson Agneta , Gerland Sebastian , Hop Haakon , Hudson Stephen R. , Hughes Nick , Itkin Polona , Johnsen Geir , King Jennifer A. , Koch Boris P. , Koenig Zoe , Kwasniewski Slawomir , Laney Samuel R. , Nicolaus Marcel , Pavlov Alexey K. , Polashenski Christopher M. , Provost Christine , Rösel Anja , Sandbu Marthe , Spreen Gunnar , Smedsrud Lars H. , Sundfjord Arild , Taskjelle Torbjørn , Tatarek Agnieszka , Wiktor Jozef , Wagner Penelope M. , Wold Anette , Steen Harald , Granskog Mats A.
Published: January 2017

The Arctic icescape is rapidly transforming from a thicker multiyear ice cover to a thinner and largely seasonal first-year ice cover with significant consequences for Arctic primary production. One critical challenge is to understand how productivity will change within the next decades. Recent studies have reported extensive phytoplankton blooms beneath ponded sea ice during summer, indicating that satellite-based Arctic annual primary production estimates may be significantly underestimated. Here we present a unique time-series of a phytoplankton spring bloom observed beneath snow-covered Arctic pack ice. The bloom, dominated by the haptophyte algaePhaeocystis pouchetii, caused near depletion of the surface nitrate inventory and a decline in dissolved inorganic carbon by 16 ± 6 g C m−2. Ocean circulation characteristics in the area indicated that the bloom developedin situdespite the snow-covered sea ice. Leads in the dynamic ice cover provided added sunlight necessary to initiate and sustain the bloom. Phytoplankton blooms beneath snow-covered ice might become more common and widespread in the future Arctic Ocean with frequent lead formation due to thinner and more dynamic sea ice despite projected increases in high-Arctic snowfall. This could alter productivity, marine food webs and carbon sequestration in the Arctic Ocean.
PLIN2 is a Key Regulator of the Unfolded Protein Response and Endoplasmic Reticulum Stress Resolution in Pancreatic β Cells
Authors: Chen Elaine , Tsai Tsung Huang , Li Lan , Saha Pradip , Chan Lawrence , Chang Benny Hung-Junn
Published: January 2017

Progressive pancreatic β cell failure underlies the transition of impaired glucose tolerance to overt diabetes; endoplasmic reticulum (ER) stress expedites β cell failure in this situation. ER stress can be elicited by lipotoxicity and an increased demand for insulin in diabetes. We previously reported that the lipid droplet protein perilipin 2 (PLIN2) modulates lipid homeostasis in the liver. Here, we show that PLIN2 modulates the unfolded protein response (UPR) and ER stress in pancreatic β cells. PLIN2 expression goes up when β cells are exposed to a lipid load or to chemical ER stress inducers. Downregulation of PLIN2 ameliorates the effects of fatty acid- and chemical-induced ER stress, whereas PLIN2 overexpression exacerbates them. Diabetic Akita mice, which carry a heterozygous C96Y Ins2 mutation, exhibit elevated PLIN2 expression and ER stress in their β cells. Genetic ablation of Plin2 in Akita mice leads to mitigation of ER stress, forestalling β cell apoptosis, partially restoring β cell mass, and ameliorating diabetes. Mechanistic experiments showed that PLIN2 downregulation is associated with enhanced autophagic flux and accelerated ER stress resolution. In sum, we have identified a crucial role for PLIN2 in modulating autophagy, ER stress resolution, and β cell apoptosis and survival.
Methyl-Cytosine-Driven Structural Changes Enhance Adduction Kinetics of an Exon 7 fragment of the p53 Gene
Authors: Malla Spundana , Kadimisetty Karteek , Fu You-Jun , Choudhary Dharamainder , Schenkman John B. , Rusling James F.
Published: January 2017

Methylation of cytosine (C) at C-phosphate-guanine (CpG) sites enhances reactivity of DNA towards electrophiles. Mutations at CpG sites on the p53 tumor suppressor gene that can result from these adductions are in turn correlated with specific cancers. Here we describe the first restriction-enzyme-assisted LC-MS/MS sequencing study of the influence of methyl cytosines (MeC) on kinetics of p53 gene adduction by model metabolite benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), using methodology applicable to correlate gene damage sites for drug and pollutant metabolites with mutation sites. This method allows direct kinetic measurements by LC-MS/MS sequencing for oligonucleotides longer than 20 base pairs (bp). We used MeC and non-MeC (C) versions of a 32 bp exon 7 fragment of the p53 gene. Methylation of 19 cytosines increased the rate constant 3-fold for adduction on G at the major reactive CpG in codon 248 vs. the non-MeC fragment. Rate constants for non-CpG codons 244 and 243 were not influenced significantly by MeC. Conformational and hydrophobicity changes in the MeC-p53 exon 7 fragment revealed by CD spectra and molecular modeling increase the BPDE binding constant to G in codon 248 consistent with a pathway in which preceding reactant binding greatly facilitates the rate of covalent SN2 coupling.
A single identified glomerulus in the zebrafish olfactory bulb carries the high-affinity response to death-associated odor cadaverine
Authors: Dieris Milan , Ahuja Gaurav , Krishna Venkatesh , Korsching Sigrun I.
Published: January 2017

The death-associated odor cadaverine, generated by bacteria-mediated decarboxylation of lysine, has been described as the principal activator of a particular olfactory receptor in zebrafish, TAAR13c. Low concentrations of cadaverine activated mainly TAAR13c-expressing olfactory sensory neurons, suggesting TAAR13c as an important element of the neuronal processing pathway linking cadaverine stimulation to a strongly aversive innate behavioral response. Here, we characterized the initial steps of this neuronal pathway. First we identified TAAR13c-expressing cells as ciliated neurons, equivalent to the situation for mammalian taar genes, which shows a high degree of conservation despite the large evolutionary distance between teleost fishes and mammals. Next we identified the target area of cadaverine-responsive OSNs in the olfactory bulb. We report that cadaverine dose-dependently activates a group of dorsolateral glomeruli, at the lowest concentration down to a single invariant glomerulus, situated at the medial border of the dorsolateral cluster. This is the first demonstration of a single stereotyped target glomerulus in the fish olfactory system for a non-pheromone odor. A mix of different amines activates many glomeruli within the same dorsolateral cluster, suggesting this area to function as a general amine response region.
Correction: Corrigendum: Pre-amyloid oligomers budding:a metastatic mechanism of proteotoxicity
Authors: Bernini Fabrizio , Malferrari Daniele , Pignataro Marcello , Bortolotti Carlo Augusto , Di Rocco Giulia , Lancellotti Lidia , Brigatti Maria Franca , Kayed Rakez , Borsari Marco , del Monte Federica , Castellini Elena
Published: January 2017

Scientific Reports 6: Article number: 35865; published online: 24 October 2016; updated: 19 January 2017. The Author Contributions statement in this Article is incomplete: F.B., D.M., M.P., L.L., F.d.M. and E.C. acquired and analyzed the data; C.A.B., G.D.R., M.F.B. and M.B. provided critical input to the analyzed data and to the manuscript; R.
A signature of renal stress resistance induced by short-term dietary restriction, fasting, and protein restriction
Authors: Jongbloed F. , Saat T. C. , Verweij M. , Payan-Gomez C. , Hoeijmakers J. H. J. , van den Engel S. , van Oostrom C. T. , Ambagtsheer G. , Imholz S. , Pennings J. L. A. , van Steeg H. , IJzermans J. N. M. , Dollé M. E. T. , de Bruin R. W. F.
Published: January 2017

During kidney transplantation, ischemia-reperfusion injury (IRI) induces oxidative stress. Short-term preoperative 30% dietary restriction (DR) and 3-day fasting protect against renal IRI. We investigated the contribution of macronutrients to this protection on both phenotypical and transcriptional levels. Male C57BL/6 mice were fed control food ad libitum, underwent two weeks of 30%DR, 3-day fasting, or received a protein-, carbohydrate- or fat-free diet for various periods of time. After completion of each diet, renal gene expression was investigated using microarrays. After induction of renal IRI by clamping the renal pedicles, animals were monitored seven days postoperatively for signs of IRI. In addition to 3-day fasting and two weeks 30%DR, three days of a protein-free diet protected against renal IRI as well, whereas the other diets did not. Gene expression patterns significantly overlapped between all diets except the fat-free diet. Detailed meta-analysis showed involvement of nuclear receptor signaling via transcription factors, including FOXO3, HNF4A and HMGA1. In conclusion, three days of a protein-free diet is sufficient to induce protection against renal IRI similar to 3-day fasting and two weeks of 30%DR. The elucidated network of common protective pathways and transcription factors further improves our mechanistic insight into the increased stress resistance induced by short-term DR.
Bacterial endophyte communities of three agricultural important grass species differ in their response towards management regimes
Authors: Wemheuer Franziska , Kaiser Kristin , Karlovsky Petr , Daniel Rolf , Vidal Stefan , Wemheuer Bernd
Published: January 2017

Endophytic bacteria are critical for plant growth and health. However, compositional and functional responses of bacterial endophyte communities towards agricultural practices are still poorly understood. Hence, we analyzed the influence of fertilizer application and mowing frequency on bacterial endophytes in three agriculturally important grass species. For this purpose, we examined bacterial endophytic communities in aerial plant parts of Dactylis glomerata L., Festuca rubra L., and Lolium perenne L. by pyrotag sequencing of bacterial 16S rRNA genes over two consecutive years. Although management regimes influenced endophyte communities, observed responses were grass species-specific. This might be attributed to several bacteria specifically associated with a single grass species. We further predicted functional profiles from obtained 16S rRNA data. These profiles revealed that predicted abundances of genes involved in plant growth promotion or nitrogen metabolism differed between grass species and between management regimes. Moreover, structural and functional community patterns showed no correlation to each other indicating that plant species-specific selection of endophytes is driven by functional rather than phylogenetic traits. The unique combination of 16S rRNA data and functional profiles provided a holistic picture of compositional and functional responses of bacterial endophytes in agricultural relevant grass species towards management practices.
High Speed Terahertz Modulator on the Chip Based on Tunable Terahertz Slot Waveguide
Authors: Singh P. K. , Sonkusale S.
Published: January 2017

This paper presents an on-chip device that can perform gigahertz-rate amplitude modulation and switching of broadband terahertz electromagnetic waves. The operation of the device is based on the interaction of confined THz waves in a novel slot waveguide with an electronically tunable two dimensional electron gas (2DEG) that controls the loss of the THz wave propagating through this waveguide. A prototype device is fabricated which shows THz intensity modulation of 96% at 0.25 THz carrier frequency with low insertion loss and device length as small as 100 microns. The demonstrated modulation cutoff frequency exceeds 14 GHz indicating potential for the high-speed modulation of terahertz waves. The entire device operates at room temperature with low drive voltage (<2 V) and zero DC power consumption. The device architecture has potential for realization of the next generation of on-chip modulators and switches at THz frequencies.
Size-selective separation and overall-amplification of cell-free fetal DNA fragments using PCR-based enrichment
Authors: Yang Qiwei , Du Zhenwu , Song Yang , Gao Sujie , Yu Shan , Zhu He , Ren Ming , Zhang Guizhen
Published: January 2017

This study aimed to establish a method for the selective amplification of cell-free fetal DNA (cffDNA) in maternal plasma and preserve the integrity of DNA fragments during amplification, thereby providing a sufficient amount of cffDNA to meet the requirement of routine non-invasive prenatal testing. We amplified DNA molecules in a one-reaction system without considering their particular sequences and lengths (overall amplification) by using PCR-based enrichment. We then modified PCR conditions to verify the effect of denaturation temperature on DNA amplification on various lengths of DNA (selective overall amplification). Finally, we used an optimum temperature range to amplify cffDNA selectively. Amplification results were validated by electrophoresis and real-time quantitative PCR. Our PCR-based enrichment efficiently amplified all DNA fragments with differing lengths within a single reaction system, as well as preserving the integrity of the DNA fragments. cffDNA was significantly amplified along with the selective amplification of small fragment maternal plasma DNA in an appropriate range of denaturation temperatures. We have established a PCR-based method for the simultaneous enrichment and amplification of cffDNA in order to meet the requirements of high cffDNA quantity for routine non-invasive prenatal testing.
Neural activity in the dorsal medial superior temporal area of monkeys represents retinal error during adaptive motor learning
Authors: Takemura Aya , Ofuji Tomoyo , Miura Kenichiro , Kawano Kenji
Published: January 2017

To adapt to variable environments, humans regulate their behavior by modulating gains in sensory-to-motor processing. In this study, we measured a simple eye movement, the ocular following response (OFR), in monkeys to study the neuronal basis of adaptive motor learning in the visuomotor processing stream. The medial superior temporal (MST) area of the cerebral cortex is a critical site for contextual gain modulation of the OFR. However, the role of MST neurons in adaptive gain modulation of the OFR remains unknown. We adopted a velocity step-down sequence paradigm that was designed to promote adaptive gain modulation of the OFR to investigate the role of the dorsal MST (MSTd) in adaptive motor learning. In the initial learning stage, we observed a reduction in the OFR but no significant change in the “open-loop” responses for the majority of the MSTd neurons. However, in the late learning stage, some MSTd neurons exhibited significantly enhanced “closed-loop” responses in association with increases in retinal error velocity. These results indicate that the MSTd area primarily encodes visual motion, suggesting that MSTd neurons function upstream of the motor learning site to provide sensory signals to the downstream structures involved in adaptive motor learning.
Modification of distinct ion channels differentially modulates Ca2+ dynamics in primary cultured rat ventricular cardiomyocytes
Authors: Li Xichun , Shen Liping , Zhao Fang , Zou Xiaohan , He Yuwei , Zhang Fan , Zhang Chunlei , Yu Boyang , Cao Zhengyu
Published: January 2017

Primary cultured cardiomyocytes show spontaneous Ca2+ oscillations (SCOs) which not only govern contractile events, but undergo derangements that promote arrhythmogenesis through Ca2+ -dependent mechanism. We systematically examined influence on SCOs of an array of ion channel modifiers by recording intracellular Ca2+ dynamics in rat ventricular cardiomyocytes using Ca2+ specific fluorescence dye, Fluo-8/AM. Voltage-gated sodium channels (VGSCs) activation elongates SCO duration and reduces SCO frequency while inhibition of VGSCs decreases SCO frequency without affecting amplitude and duration. Inhibition of voltage-gated potassium channel increases SCO duration. Direct activation of L-type Ca2+ channels (LTCCs) induces SCO bursts while suppressing LTCCs decreases SCO amplitude and slightly increases SCO frequency. Activation of ryanodine receptors (RyRs) increases SCO duration and decreases both SCO amplitude and frequency while inhibiting RyRs decreases SCO frequency without affecting amplitude and duration. The potencies of these ion channel modifiers on SCO responses are generally consistent with their affinities in respective targets demonstrating that modification of distinct targets produces different SCO profiles. We further demonstrate that clinically-used drugs that produce Long-QT syndrome including cisapride, dofetilide, sotalol, and quinidine all induce SCO bursts while verapamil has no effect. Therefore, occurrence of SCO bursts may have a translational value to predict cardiotoxicants causing Long-QT syndrome.
Correction: Corrigendum: A comprehensive strategy for the analysis of acoustic compressibility and optical deformability on single cells
Authors: Yang Tie , Bragheri Francesca , Nava Giovanni , Chiodi Ilaria , Mondello Chiara , Osellame Roberto , Berg-Sørensen Kirstine , Cristiani Ilaria , Minzioni Paolo
Published: January 2017

Scientific Reports 6: Article number: 23946; published online: 04 April 2016; updated: 19 January 2017. This Article contains errors. In Figure 3c, the y-axis ‘Acoustic compressibility (10−10 Pa−1)’ is incorrectly given as ‘Acoustic compressibility (TPa−1)’. The correct Figure 3c appears below as Figure 1.
Correction: Corrigendum: Mesenchymal Stem Cells Reversed Morphine Tolerance and Opioid-induced Hyperalgesia
Authors: Hua Zhen , Liu LiPing , Shen Jun , Cheng Kathleen , Liu Aijun , Yang Jing , Wang Lina , Qu Tingyu , Yang HongNa , Li Yan , Wu Haiyan , Narouze John , Yin Yan , Cheng Jianguo
Published: January 2017

Scientific Reports 6: Article number: 32096; published online: 24 August 2016; updated: 19 January 2017. The original version of this Article contained a typographical error in the spelling of the author Kathleen Cheng, which was incorrectly given as Katherine Cheng. This has now been corrected in the PDF and HTML versions of the Article.
Strengthening of Ceramic-based Artificial Nacre via Synergistic Interactions of 1D Vanadium Pentoxide and 2D Graphene Oxide Building Blocks
Authors: Knöller Andrea , Lampa Christian P. , Cube Felix von , Zeng Tingying Helen , Bell David C. , Dresselhaus Mildred S. , Burghard Zaklina , Bill Joachim
Published: January 2017

Nature has evolved hierarchical structures of hybrid materials with excellent mechanical properties. Inspired by nacre’s architecture, a ternary nanostructured composite has been developed, wherein stacked lamellas of 1D vanadium pentoxide nanofibres, intercalated with water molecules, are complemented by 2D graphene oxide (GO) nanosheets. The components self-assemble at low temperature into hierarchically arranged, highly flexible ceramic-based papers. The papers’ mechanical properties are found to be strongly influenced by the amount of the integrated GO phase. Nanoindentation tests reveal an out-of-plane decrease in Young’s modulus with increasing GO content. Furthermore, nanotensile tests reveal that the ceramic-based papers with 0.5 wt% GO show superior in-plane mechanical performance, compared to papers with higher GO contents as well as to pristine V2O5and GO papers. Remarkably, the performance is preserved even after stretching the composite material for 100 nanotensile test cycles. The good mechanical stability and unique combination of stiffness and flexibility enable this material to memorize its micro- and macroscopic shape after repeated mechanical deformations. These findings provide useful guidelines for the development of bioinspired, multifunctional systems whose hierarchical structure imparts tailored mechanical properties and cycling stability, which is essential for applications such as actuators or flexible electrodes for advanced energy storage.
Unlocking the potential of SnS2: Transition metal catalyzed utilization of reversible conversion and alloying reactions
Authors: Huang Zhi Xiang , Wang Ye , Liu Bo , Kong Dezhi , Zhang Jun , Chen Tupei , Yang Hui Ying
Published: January 2017

The alloying-dealloying reactions of SnS2 proceeds with the initial conversion reaction of SnS2 with lithium that produces Li2S. Unfortunately, due to the electrochemical inactivity of Li2S, the conversion reaction of SnS2 is irreversible, which significantly limit its potential applications in lithium-ion batteries. Herein, a systematic understanding of transition metal molybdenum (Mo) as a catalyst in SnS2 anode is presented. It is found that Mo catalyst is able to efficiently promote the reversible conversion of Sn to SnS2. This leads to the utilization of both conversion and alloying reactions in SnS2 that greatly increases lithium storage capability of SnS2. Mo catalyst is introduced in the form of MoS2 grown directly onto self-assembled vertical SnS2 nanosheets that anchors on three-dimensional graphene (3DG) creating a hierarchal nanostructured named as SnS2/MoS2/3DG. The catalytic effect results in a significantly enhanced electrochemical properties of SnS2/MoS2/3DG; a high initial Coulombic efficiency (81.5%) and high discharge capacities of 960.5 and 495.6 mA h g−1 at current densities of 50 and 1000 mA g−1, respectively. Post cycling investigations using ex situ TEM and XPS analysis verifies the successful conversion reaction of SnS2 mediated by Mo. The successful integration of catalyst on alloying type metal sulfide anode creates a new avenue towards high energy density lithium anodes.
Evaluation of region selective bilirubin-induced brain damage as a basis for a pharmacological treatment
Authors: Dal Ben Matteo , Bottin Cristina , Zanconati Fabrizio , Tiribelli Claudio , Gazzin Silvia
Published: January 2017

The neurologic manifestations of neonatal hyperbilirubinemia in the central nervous system (CNS) exhibit high variations in the severity and appearance of motor, auditory and cognitive symptoms, which is suggestive of a still unexplained selective topography of bilirubin-induced damage. By applying the organotypic brain culture (OBC: preserving in vitro the cellular complexity, connection and architecture of the in vivo brain) technique to study hyperbilirubinemia, we mapped the regional target of bilirubin-induced damage, demonstrated a multifactorial toxic action of bilirubin, and used this information to evaluate the efficacy of drugs applicable to newborns to protect the brain. OBCs from 8-day-old rat pups showed a 2–13 fold higher sensitivity to bilirubin damage than 2-day-old preparations. The hippocampus, inferior colliculus and cerebral cortex were the only brain regions affected, presenting a mixed inflammatory-oxidative mechanism. Glutamate excitotoxicity was appreciable in only the hippocampus and inferior colliculus. Single drug treatment (indomethacin, curcumin, MgCl2) significantly improved cell viability in all regions, while the combined (cocktail) administration of the three drugs almost completely prevented damage in the most affected area (hippocampus). Our data may supports an innovative (complementary to phototherapy) approach for directly protecting the newborn brain from bilirubin neurotoxicity.
Deep brain stimulation for myoclonus-dystonia syndrome with double mutations in DYT1 and DYT11
Authors: Wang Jia-Wei , Li Ji-Ping , Wang Yun-Peng , Zhang Xiao-Hua , Zhang Yu-Qing
Published: January 2017

Myoclonus-dystonia syndrome (MDS) is a rare autosomal dominant inherited disorder characterized by the presentation of both myoclonic jerks and dystonia. Evidence is emerging that deep brain stimulation (DBS) may be a promising treatment for MDS. However, there are no studies reporting the effects of DBS on MDS with double mutations in DYT1 and DYT11. Two refractory MDS patients with double mutations were treated between 2011 and 2015 in our center. Genetic testing for DYT1 and DYT11 was performed through polymerase chain reaction amplification and direct sequencing of the specific exons of genes. For the first patient, initial bilateral ventral intermediate thalamus nucleus (Vim) DBS was performed. Because of worsening dystonia after initial improvement in symptoms, subsequent bilateral globus pallidus internus (GPi) DBS was offered at 43 months after initial surgery, which reversed the deterioration and restored the motor function. For the second patient, initial improvement in motor symptoms and quality of life was sustained at the follow-up 6 months after bilateral Vim DBS treatment. Thus, DBS may be an effective therapeutic option for MDS, even in patients with double mutations. Moreover, GPi DBS may be used as a supplementary treatment when initial Vim DBS fails to control MDS symptoms.